Study on Coagulant Dosing Control System of Micro Vortex Water Treatment

NASA Astrophysics Data System (ADS)

Fengping, Hu; Qi, Fan; Wenjie, Hu; Xizhen, He; Hongling, Dai

2018-03-01

In view of the characteristics of nonlinearity, large time delay and multi disturbance in the process of coagulant dosing in water treatment, it is difficult to control the dosage of coagulant. According to the four indexes of raw water quality parameters (raw water flow, turbidity, pH value) and turbidity of sedimentation tank, the micro vortex coagulation dosing control model is constructed based on BP neural network and GA. The forecast results of BP neural network model are ideal, and after the optimization of GA, the prediction accuracy of the model is partly improved. The prediction error of the optimized network is ±0.5 mg/L, and has a better performance than non-optimized network.

A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy.

PubMed

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2017-01-07

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy

NASA Astrophysics Data System (ADS)

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2017-01-01

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

A New Approach to Integrate GPU-based Monte Carlo Simulation into Inverse Treatment Plan Optimization for Proton Therapy

PubMed Central

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2016-01-01

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6±15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size. PMID:27991456

Image quality and dose differences caused by vendor-specific image processing of neonatal radiographs.

PubMed

Sensakovic, William F; O'Dell, M Cody; Letter, Haley; Kohler, Nathan; Rop, Baiywo; Cook, Jane; Logsdon, Gregory; Varich, Laura

2016-10-01

Image processing plays an important role in optimizing image quality and radiation dose in projection radiography. Unfortunately commercial algorithms are black boxes that are often left at or near vendor default settings rather than being optimized. We hypothesize that different commercial image-processing systems, when left at or near default settings, create significant differences in image quality. We further hypothesize that image-quality differences can be exploited to produce images of equivalent quality but lower radiation dose. We used a portable radiography system to acquire images on a neonatal chest phantom and recorded the entrance surface air kerma (ESAK). We applied two image-processing systems (Optima XR220amx, by GE Healthcare, Waukesha, WI; and MUSICA(2) by Agfa HealthCare, Mortsel, Belgium) to the images. Seven observers (attending pediatric radiologists and radiology residents) independently assessed image quality using two methods: rating and matching. Image-quality ratings were independently assessed by each observer on a 10-point scale. Matching consisted of each observer matching GE-processed images and Agfa-processed images with equivalent image quality. A total of 210 rating tasks and 42 matching tasks were performed and effective dose was estimated. Median Agfa-processed image-quality ratings were higher than GE-processed ratings. Non-diagnostic ratings were seen over a wider range of doses for GE-processed images than for Agfa-processed images. During matching tasks, observers matched image quality between GE-processed images and Agfa-processed images acquired at a lower effective dose (11 ± 9 μSv; P < 0.0001). Image-processing methods significantly impact perceived image quality. These image-quality differences can be exploited to alter protocols and produce images of equivalent image quality but lower doses. Those purchasing projection radiography systems or third-party image-processing software should be aware that image processing can significantly impact image quality when settings are left near default values.

Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

PubMed

Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

2016-08-01

Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

PubMed Central

Day, Troy; Read, Andrew F.

2016-01-01

High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

PubMed

Day, Troy; Read, Andrew F

2016-01-01

High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients.

Fluence map optimization (FMO) with dose-volume constraints in IMRT using the geometric distance sorting method.

PubMed

Lan, Yihua; Li, Cunhua; Ren, Haozheng; Zhang, Yong; Min, Zhifang

2012-10-21

A new heuristic algorithm based on the so-called geometric distance sorting technique is proposed for solving the fluence map optimization with dose-volume constraints which is one of the most essential tasks for inverse planning in IMRT. The framework of the proposed method is basically an iterative process which begins with a simple linear constrained quadratic optimization model without considering any dose-volume constraints, and then the dose constraints for the voxels violating the dose-volume constraints are gradually added into the quadratic optimization model step by step until all the dose-volume constraints are satisfied. In each iteration step, an interior point method is adopted to solve each new linear constrained quadratic programming. For choosing the proper candidate voxels for the current dose constraint adding, a so-called geometric distance defined in the transformed standard quadratic form of the fluence map optimization model was used to guide the selection of the voxels. The new geometric distance sorting technique can mostly reduce the unexpected increase of the objective function value caused inevitably by the constraint adding. It can be regarded as an upgrading to the traditional dose sorting technique. The geometry explanation for the proposed method is also given and a proposition is proved to support our heuristic idea. In addition, a smart constraint adding/deleting strategy is designed to ensure a stable iteration convergence. The new algorithm is tested on four cases including head-neck, a prostate, a lung and an oropharyngeal, and compared with the algorithm based on the traditional dose sorting technique. Experimental results showed that the proposed method is more suitable for guiding the selection of new constraints than the traditional dose sorting method, especially for the cases whose target regions are in non-convex shapes. It is a more efficient optimization technique to some extent for choosing constraints than the dose sorting method. By integrating a smart constraint adding/deleting scheme within the iteration framework, the new technique builds up an improved algorithm for solving the fluence map optimization with dose-volume constraints.

SU-E-T-488: An Iso-Dose Curve Based Interactive IMRT Optimization System for Physician-Driven Plan Tuning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, F; Tian, Z; Jia, X

Purpose: In treatment plan optimization for Intensity Modulated Radiation Therapy (IMRT), after a plan is initially developed by a dosimetrist, the attending physician evaluates its quality and often would like to improve it. As opposed to having the dosimetrist implement the improvements, it is desirable to have the physician directly and efficiently modify the plan for a more streamlined and effective workflow. In this project, we developed an interactive optimization system for physicians to conveniently and efficiently fine-tune iso-dose curves. Methods: An interactive interface is developed under C++/Qt. The physician first examines iso-dose lines. S/he then picks an iso-dose curvemore » to be improved and drags it to a more desired configuration using a computer mouse or touchpad. Once the mouse is released, a voxel-based optimization engine is launched. The weighting factors corresponding to voxels between the iso-dose lines before and after the dragging are modified. The underlying algorithm then takes these factors as input to re-optimize the plan in near real-time on a GPU platform, yielding a new plan best matching the physician's desire. The re-optimized DVHs and iso-dose curves are then updated for the next iteration of modifications. This process is repeated until a physician satisfactory plan is achieved. Results: We have tested this system for a series of IMRT plans. Results indicate that our system provides the physicians an intuitive and efficient tool to edit the iso-dose curves according to their preference. The input information is used to guide plan re-optimization, which is achieved in near real-time using our GPU-based optimization engine. Typically, a satisfactory plan can be developed by a physician in a few minutes using this tool. Conclusion: With our system, physicians are able to manipulate iso-dose curves according to their preferences. Preliminary results demonstrate the feasibility and effectiveness of this tool.« less

Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction.

PubMed

Benowitz, N L

1991-05-01

Rational treatment of the pharmacologic aspects of tobacco addiction includes nicotine substitution therapy. Understanding the pharmacodynamics of nicotine and its role in the addiction process provides a basis for rational therapeutic intervention. Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks.

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

Optimization of composite coagulant made from polyferric chloride and tapioca starch in landfill leachate treatment

NASA Astrophysics Data System (ADS)

Shaylinda, M. Z. N.; Hamidi, A. A.; Mohd, N. A.; Ariffin, A.; Irvan, D.; Hazreek, Z. A. M.; Nizam, Z. M.

2018-04-01

In this research, the performance of polyferric chloride and tapioca flour as composite coagulants for partially stabilized leachate was investigated. Response surface methodology (RSM) was used to optimize the coagulation and flocculation process of partially stabilized leachate. Central composite design a standard design tool in RSM was applied to evaluate the interactions and effects of dose and pH. Dose 0.2 g/L Fe and pH 4.71 were the optimum value suggested by RSM. Experimental test based on the optimum condition, resulted in 95.9%, 94.6% and 50.4% of SS, color and COD removals, respectively. The percentage difference recorded between experimental and model responses was <5%. Therefore, it can be concluded that RSM was an appropriate optimization tool for coagulation and flocculation process.

Intensity modulated neutron radiotherapy optimization by photon proxy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snyder, Michael; Hammoud, Ahmad; Bossenberger, Todd

2012-08-15

Purpose: Introducing intensity modulation into neutron radiotherapy (IMNRT) planning has the potential to mitigate some normal tissue complications seen in past neutron trials. While the hardware to deliver IMNRT plans has been in use for several years, until recently the IMNRT planning process has been cumbersome and of lower fidelity than conventional photon plans. Our in-house planning system used to calculate neutron therapy plans allows beam weight optimization of forward planned segments, but does not provide inverse optimization capabilities. Commercial treatment planning systems provide inverse optimization capabilities, but currently cannot model our neutron beam. Methods: We have developed a methodologymore » and software suite to make use of the robust optimization in our commercial planning system while still using our in-house planning system to calculate final neutron dose distributions. Optimized multileaf collimator (MLC) leaf positions for segments designed in the commercial system using a 4 MV photon proxy beam are translated into static neutron ports that can be represented within our in-house treatment planning system. The true neutron dose distribution is calculated in the in-house system and then exported back through the MATLAB software into the commercial treatment planning system for evaluation. Results: The planning process produces optimized IMNRT plans that reduce dose to normal tissue structures as compared to 3D conformal plans using static MLC apertures. The process involves standard planning techniques using a commercially available treatment planning system, and is not significantly more complex than conventional IMRT planning. Using a photon proxy in a commercial optimization algorithm produces IMNRT plans that are more conformal than those previously designed at our center and take much less time to create. Conclusions: The planning process presented here allows for the optimization of IMNRT plans by a commercial treatment planning optimization algorithm, potentially allowing IMNRT to achieve similar conformality in treatment as photon IMRT. The only remaining requirements for the delivery of very highly modulated neutron treatments are incremental improvements upon already implemented hardware systems that should be readily achievable.« less

A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.

PubMed

Ma, Jiasen; Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G

2014-12-01

Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. For relatively large and complex three-field head and neck cases, i.e., >100,000 spots with a target volume of ∼ 1000 cm(3) and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45,000 dollars. The fast calculation and optimization make the system easily expandable to robust and multicriteria optimization.

A photon source model based on particle transport in a parameterized accelerator structure for Monte Carlo dose calculations.

PubMed

Ishizawa, Yoshiki; Dobashi, Suguru; Kadoya, Noriyuki; Ito, Kengo; Chiba, Takahito; Takayama, Yoshiki; Sato, Kiyokazu; Takeda, Ken

2018-05-17

An accurate source model of a medical linear accelerator is essential for Monte Carlo (MC) dose calculations. This study aims to propose an analytical photon source model based on particle transport in parameterized accelerator structures, focusing on a more realistic determination of linac photon spectra compared to existing approaches. We designed the primary and secondary photon sources based on the photons attenuated and scattered by a parameterized flattening filter. The primary photons were derived by attenuating bremsstrahlung photons based on the path length in the filter. Conversely, the secondary photons were derived from the decrement of the primary photons in the attenuation process. This design facilitates these sources to share the free parameters of the filter shape and be related to each other through the photon interaction in the filter. We introduced two other parameters of the primary photon source to describe the particle fluence in penumbral regions. All the parameters are optimized based on calculated dose curves in water using the pencil-beam-based algorithm. To verify the modeling accuracy, we compared the proposed model with the phase space data (PSD) of the Varian TrueBeam 6 and 15 MV accelerators in terms of the beam characteristics and the dose distributions. The EGS5 Monte Carlo code was used to calculate the dose distributions associated with the optimized model and reference PSD in a homogeneous water phantom and a heterogeneous lung phantom. We calculated the percentage of points passing 1D and 2D gamma analysis with 1%/1 mm criteria for the dose curves and lateral dose distributions, respectively. The optimized model accurately reproduced the spectral curves of the reference PSD both on- and off-axis. The depth dose and lateral dose profiles of the optimized model also showed good agreement with those of the reference PSD. The passing rates of the 1D gamma analysis with 1%/1 mm criteria between the model and PSD were 100% for 4 × 4, 10 × 10, and 20 × 20 cm 2 fields at multiple depths. For the 2D dose distributions calculated in the heterogeneous lung phantom, the 2D gamma pass rate was 100% for 6 and 15 MV beams. The model optimization time was less than 4 min. The proposed source model optimization process accurately produces photon fluence spectra from a linac using valid physical properties, without detailed knowledge of the geometry of the linac head, and with minimal optimization time. © 2018 American Association of Physicists in Medicine.

A quantitative study of IMRT delivery effects in commercial planning systems for the case of oesophagus and prostate tumours.

PubMed

Seco, J; Clark, C H; Evans, P M; Webb, S

2006-05-01

This study focuses on understanding the impact of intensity-modulated radiotherapy (IMRT) delivery effects when applied to plans generated by commercial treatment-planning systems such as Pinnacle (ADAC Laboratories Inc.) and CadPlan/Helios (Varian Medical Systems). These commercial planning systems have had several version upgrades (with improvements in the optimization algorithm), but the IMRT delivery effects have not been incorporated into the optimization process. IMRT delivery effects include head-scatter fluence from IMRT fields, transmission through leaves and the effect of the rounded shape of the leaf ends. They are usually accounted for after optimization when leaf sequencing the "optimal" fluence profiles, to derive the delivered fluence profile. The study was divided into two main parts: (a) analysing the dose distribution within the planning-target volume (PTV), produced by each of the commercial treatment-planning systems, after the delivered fluence had been renormalized to deliver the correct dose to the PTV; and (b) studying the impact of the IMRT delivery technique on the surrounding critical organs such as the spinal cord, lungs, rectum, bladder etc. The study was performed for tumours of (i) the oesophagus and (ii) the prostate and pelvic nodes. An oesophagus case was planned with the Pinnacle planning system for IMRT delivery, via multiple-static fields (MSF) and compensators, using the Elekta SL25 with a multileaf collimator (MLC) component. A prostate and pelvic nodes IMRT plan was performed with the Cadplan/Helios system for a dynamic delivery (DMLC) using the Varian 120-leaf Millennium MLC. In these commercial planning systems, since IMRT delivery effects are not included into the optimization process, fluence renormalization is required such that the median delivered PTV dose equals the initial prescribed PTV dose. In preparing the optimum fluence profile for delivery, the PTV dose has been "smeared" by the IMRT delivery techniques. In the case of the oesophagus, the critical organ, spinal cord, received a greater dose than initially planned, due to the delivery effects. The increase in the spinal cord dose is of the order of 2-3 Gy. In the case of the prostate and pelvic nodes, the IMRT delivery effects led to an increase of approximately 2 Gy in the dose delivered to the secondary PTV, the pelvic nodes. In addition to this, the small bowel, rectum and bladder received an increased dose of the order of 2-3 Gy to 50% of their total volume. IMRT delivery techniques strongly influence the delivered dose distributions for the oesophagus and prostate/pelvic nodes tumour sites and these effects are not yet accounted for in the Pinnacle and the CadPlan/Helios planning systems. Currently, they must be taken into account during the optimization stage by altering the dose limits accepted during optimization so that the final (sequenced) dose is within the constraints.

Optimized Dose Distribution of Gammamed Plus Vaginal Cylinders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Supe, Sanjay S.; Bijina, T.K.; Varatharaj, C.

2009-04-01

Endometrial carcinoma is the most common malignancy arising in the female genital tract. Intracavitary vaginal cuff irradiation may be given alone or with external beam irradiation in patients determined to be at risk for locoregional recurrence. Vaginal cylinders are often used to deliver a brachytherapy dose to the vaginal apex and upper vagina or the entire vaginal surface in the management of postoperative endometrial cancer or cervical cancer. The dose distributions of HDR vaginal cylinders must be evaluated carefully, so that clinical experiences with LDR techniques can be used in guiding optimal use of HDR techniques. The aim of thismore » study was to optimize dose distribution for Gammamed plus vaginal cylinders. Placement of dose optimization points was evaluated for its effect on optimized dose distributions. Two different dose optimization point models were used in this study, namely non-apex (dose optimization points only on periphery of cylinder) and apex (dose optimization points on periphery and along the curvature including the apex points). Thirteen dwell positions were used for the HDR dosimetry to obtain a 6-cm active length. Thus 13 optimization points were available at the periphery of the cylinder. The coordinates of the points along the curvature depended on the cylinder diameters and were chosen for each cylinder so that four points were distributed evenly in the curvature portion of the cylinder. Diameter of vaginal cylinders varied from 2.0 to 4.0 cm. Iterative optimization routine was utilized for all optimizations. The effects of various optimization routines (iterative, geometric, equal times) was studied for the 3.0-cm diameter vaginal cylinder. The effect of source travel step size on the optimized dose distributions for vaginal cylinders was also evaluated. All optimizations in this study were carried for dose of 6 Gy at dose optimization points. For both non-apex and apex models of vaginal cylinders, doses for apex point and three dome points were higher for the apex model compared with the non-apex model. Mean doses to the optimization points for both the cylinder models and all the cylinder diameters were 6 Gy, matching with the prescription dose of 6 Gy. Iterative optimization routine resulted in the highest dose to apex point and dome points. The mean dose for optimization point was 6.01 Gy for iterative optimization and was much higher than 5.74 Gy for geometric and equal times routines. Step size of 1 cm gave the highest dose to the apex point. This step size was superior in terms of mean dose to optimization points. Selection of dose optimization points for the derivation of optimized dose distributions for vaginal cylinders affects the dose distributions.« less

Dosimetric evaluation of total marrow irradiation using 2 different planning systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nalichowski, Adrian, E-mail: nalichoa@karmanos.org; Eagle, Don G.; Burmeister, Jay

This study compared 2 different treatment planning systems (TPSs) for quality and efficiency of total marrow irradiation (TMI) plans. The TPSs used in this study were VOxel-Less Optimization (VoLO) (Accuray Inc, Sunnyvale, CA) using helical dose delivery on a Tomotherapy Hi-Art treatment unit and Eclipse (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) dose delivery on a Varian iX treatment unit. A total dose of 1200 cGy was prescribed to cover 95% of the planning target volume (PTV). The plans were optimized and calculated based on a single CT data and structure set using themore » Alderson Rando phantom (The Phantom Laboratory, Salem, NY) and physician contoured target and organ at risk (OAR) volumes. The OARs were lungs, heart, liver, kidneys, brain, and small bowel. The plans were evaluated based on plan quality, time to optimize the plan and calculate the dose, and beam on time. The resulting mean and maximum doses to the PTV were 1268 and 1465 cGy for VoLO and 1284 and 1541 cGy for Eclipse, respectively. For 5 of 6 OAR structures the VoLO system achieved lower mean and D10 doses ranging from 22% to 52% and 3% to 44%, respectively. Total computational time including only optimization and dose calculation were 0.9 hours for VoLO and 3.8 hours for Eclipse. These times do not include user-dependent target delineation and field setup. Both planning systems are capable of creating high-quality plans for total marrow irradiation. The VoLO planning system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing. VoLO's graphics processing unit (GPU)–based optimization and dose calculation algorithm also allowed much faster creation of TMI plans.« less

Interactive Dose Shaping - efficient strategies for CPU-based real-time treatment planning

NASA Astrophysics Data System (ADS)

Ziegenhein, P.; Kamerling, C. P.; Oelfke, U.

2014-03-01

Conventional intensity modulated radiation therapy (IMRT) treatment planning is based on the traditional concept of iterative optimization using an objective function specified by dose volume histogram constraints for pre-segmented VOIs. This indirect approach suffers from unavoidable shortcomings: i) The control of local dose features is limited to segmented VOIs. ii) Any objective function is a mathematical measure of the plan quality, i.e., is not able to define the clinically optimal treatment plan. iii) Adapting an existing plan to changed patient anatomy as detected by IGRT procedures is difficult. To overcome these shortcomings, we introduce the method of Interactive Dose Shaping (IDS) as a new paradigm for IMRT treatment planning. IDS allows for a direct and interactive manipulation of local dose features in real-time. The key element driving the IDS process is a two-step Dose Modification and Recovery (DMR) strategy: A local dose modification is initiated by the user which translates into modified fluence patterns. This also affects existing desired dose features elsewhere which is compensated by a heuristic recovery process. The IDS paradigm was implemented together with a CPU-based ultra-fast dose calculation and a 3D GUI for dose manipulation and visualization. A local dose feature can be implemented via the DMR strategy within 1-2 seconds. By imposing a series of local dose features, equal plan qualities could be achieved compared to conventional planning for prostate and head and neck cases within 1-2 minutes. The idea of Interactive Dose Shaping for treatment planning has been introduced and first applications of this concept have been realized.

TU-AB-303-12: Towards Inter and Intra Fraction Plan Adaptation for the MR-Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kontaxis, C; Bol, G; Lagendijk, J

Purpose: To develop a new sequencer for IMRT that during treatment can account for anatomy changes provided by online and real-time MRI. This sequencer employs a novel inter and intra fraction scheme that converges to the prescribed dose without a final segment weight optimization (SWO) and enables immediate optimization and delivery of radiation adapted to the deformed anatomy. Methods: The sequencer is initially supplied with a voxel-based dose prescription and during the optimization iteratively generates segments that provide this prescribed dose. Every iteration selects the best segment for the current anatomy state, calculates the dose it will deliver, warps itmore » back to the reference prescription grid and subtracts it from the remaining prescribed dose. This process continues until a certain percentage of dose or a number of segments has been delivered. The anatomy changes that occur during treatment require that convergence is achieved without a final SWO. This is resolved by adding the difference between the prescribed and delivered dose up to this fraction to the prescription of the subsequent fraction. This process is repeated for all fractions of the treatment. Results: Two breast cases were selected to stress test the pipeline by producing artificial inter and intra fraction anatomy deformations using a combination of incrementally applied rigid transformations. The dose convergence of the adaptive scheme over the entire treatment, relative to the prescribed dose, was on average 8.6% higher than the static plans delivered to the respective deformed anatomies and only 1.6% less than the static segment weighted plans on the static anatomy. Conclusion: This new adaptive sequencing strategy enables dose convergence without the need of SWO while adapting the plan to intermediate anatomies, which is a prerequisite for online plan adaptation. We are now testing our pipeline on prostate cases using clinical anatomy deformation data from our department. This work is financially supported by Elekta AB, Stockholm, Sweden.« less

GPU computing in medical physics: a review.

PubMed

Pratx, Guillem; Xing, Lei

2011-05-01

The graphics processing unit (GPU) has emerged as a competitive platform for computing massively parallel problems. Many computing applications in medical physics can be formulated as data-parallel tasks that exploit the capabilities of the GPU for reducing processing times. The authors review the basic principles of GPU computing as well as the main performance optimization techniques, and survey existing applications in three areas of medical physics, namely image reconstruction, dose calculation and treatment plan optimization, and image processing.

Lean methodology in i.v. medication processes in a children's hospital.

PubMed

L'Hommedieu, Timothy; Kappeler, Karl

2010-12-15

The impact of lean methodology in i.v. medication processes in a children's hospital was studied. Medication orders at a children's hospital were analyzed for 30 days to identify the specific times when most medications were changed or discontinued. Value-stream mapping was used to define the current state of preparation and identify non-value-added tasks in the i.v. medication preparation and dispensing processes. An optimization model was created using specific measurements to establish the optimal number of batches and batch preparation times of batches. Returned i.v. medications were collected for 7 days before and after implementation of the lean process to determine the impact of the lean process changes. Patient-days increased from 1,836 during the first collection period to 2,017 during the second, and the total number of i.v. doses dispensed increased from 8,054 to 9,907. Wasted i.v. doses decreased from 1,339 (16.6% of the total doses dispensed) to 853 (8.6%). With the new process, Nationwide Children's Hospital was projected to realize a weekly savings of $8,197 ($426,244 annually), resulting in a 2.6% reduction in annual drug expenditure. The annual savings is a conservative estimate, due to the 10% increase in patient-days after the lean collection period compared with baseline. The differences in wasted doses and their costs were significant (p < 0.05). Implementing lean concepts in the i.v. medication preparation process had a positive effect on efficiency and drug cost.

Dosimetric comparison of helical tomotherapy treatment plans for total marrow irradiation created using GPU and CPU dose calculation engines.

PubMed

Nalichowski, Adrian; Burmeister, Jay

2013-07-01

To compare optimization characteristics, plan quality, and treatment delivery efficiency between total marrow irradiation (TMI) plans using the new TomoTherapy graphic processing unit (GPU) based dose engine and CPU/cluster based dose engine. Five TMI plans created on an anthropomorphic phantom were optimized and calculated with both dose engines. The planning treatment volume (PTV) included all the bones from head to mid femur except for upper extremities. Evaluated organs at risk (OAR) consisted of lung, liver, heart, kidneys, and brain. The following treatment parameters were used to generate the TMI plans: field widths of 2.5 and 5 cm, modulation factors of 2 and 2.5, and pitch of either 0.287 or 0.43. The optimization parameters were chosen based on the PTV and OAR priorities and the plans were optimized with a fixed number of iterations. The PTV constraint was selected to ensure that at least 95% of the PTV received the prescription dose. The plans were evaluated based on D80 and D50 (dose to 80% and 50% of the OAR volume, respectively) and hotspot volumes within the PTVs. Gamma indices (Γ) were also used to compare planar dose distributions between the two modalities. The optimization and dose calculation times were compared between the two systems. The treatment delivery times were also evaluated. The results showed very good dosimetric agreement between the GPU and CPU calculated plans for any of the evaluated planning parameters indicating that both systems converge on nearly identical plans. All D80 and D50 parameters varied by less than 3% of the prescription dose with an average difference of 0.8%. A gamma analysis Γ(3%, 3 mm) < 1 of the GPU plan resulted in over 90% of calculated voxels satisfying Γ < 1 criterion as compared to baseline CPU plan. The average number of voxels meeting the Γ < 1 criterion for all the plans was 97%. In terms of dose optimization/calculation efficiency, there was a 20-fold reduction in planning time with the new GPU system. The average optimization/dose calculation time utilizing the traditional CPU/cluster based system was 579 vs 26.8 min for the GPU based system. There was no difference in the calculated treatment delivery time per fraction. Beam-on time varied based on field width and pitch and ranged between 15 and 28 min. The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation.

Optimization of image quality and dose for Varian aS500 electronic portal imaging devices (EPIDs).

PubMed

McGarry, C K; Grattan, M W D; Cosgrove, V P

2007-12-07

This study was carried out to investigate whether the electronic portal imaging (EPI) acquisition process could be optimized, and as a result tolerance and action levels be set for the PIPSPro QC-3V phantom image quality assessment. The aim of the optimization process was to reduce the dose delivered to the patient while maintaining a clinically acceptable image quality. This is of interest when images are acquired in addition to the planned patient treatment, rather than images being acquired using the treatment field during a patient's treatment. A series of phantoms were used to assess image quality for different acquisition settings relative to the baseline values obtained following acceptance testing. Eight Varian aS500 EPID systems on four matched Varian 600C/D linacs and four matched Varian 2100C/D linacs were compared for consistency of performance and images were acquired at the four main orthogonal gantry angles. Images were acquired using a 6 MV beam operating at 100 MU min(-1) and the low-dose acquisition mode. Doses used in the comparison were measured using a Farmer ionization chamber placed at d(max) in solid water. The results demonstrated that the number of reset frames did not have any influence on the image contrast, but the number of frame averages did. The expected increase in noise with corresponding decrease in contrast was also observed when reducing the number of frame averages. The optimal settings for the low-dose acquisition mode with respect to image quality and dose were found to be one reset frame and three frame averages. All patients at the Northern Ireland Cancer Centre are now imaged using one reset frame and three frame averages in the 6 MV 100 MU min(-1) low-dose acquisition mode. Routine EPID QC contrast tolerance (+/-10) and action (+/-20) levels using the PIPSPro phantom based around expected values of 190 (Varian 600C/D) and 225 (Varian 2100C/D) have been introduced. The dose at dmax from electronic portal imaging has been reduced by approximately 28%, and while the image quality has been reduced, the images produced are still clinically acceptable.

Optimization of dual-energy subtraction chest radiography by use of a direct-conversion flat-panel detector system.

PubMed

Fukao, Mari; Kawamoto, Kiyosumi; Matsuzawa, Hiroaki; Honda, Osamu; Iwaki, Takeshi; Doi, Tsukasa

2015-01-01

We aimed to optimize the exposure conditions in the acquisition of soft-tissue images using dual-energy subtraction chest radiography with a direct-conversion flat-panel detector system. Two separate chest images were acquired at high- and low-energy exposures with standard or thick chest phantoms. The high-energy exposure was fixed at 120 kVp with the use of an auto-exposure control technique. For the low-energy exposure, the tube voltages and entrance surface doses ranged 40-80 kVp and 20-100 % of the dose required for high-energy exposure, respectively. Further, a repetitive processing algorithm was used for reduction of the image noise generated by the subtraction process. Seven radiology technicians ranked soft-tissue images, and these results were analyzed using the normalized-rank method. Images acquired at 60 kVp were of acceptable quality regardless of the entrance surface dose and phantom size. Using a repetitive processing algorithm, the minimum acceptable doses were reduced from 75 to 40 % for the standard phantom and to 50 % for the thick phantom. We determined that the optimum low-energy exposure was 60 kVp at 50 % of the dose required for the high-energy exposure. This allowed the simultaneous acquisition of standard radiographs and soft-tissue images at 1.5 times the dose required for a standard radiograph, which is significantly lower than the values reported previously.

Simultaneous optimization of photons and electrons for mixed beam radiotherapy

NASA Astrophysics Data System (ADS)

Mueller, S.; Fix, M. K.; Joosten, A.; Henzen, D.; Frei, D.; Volken, W.; Kueng, R.; Aebersold, D. M.; Stampanoni, M. F. M.; Manser, P.

2017-07-01

The aim of this work is to develop and investigate an inverse treatment planning process (TPP) for mixed beam radiotherapy (MBRT) capable of performing simultaneous optimization of photon and electron apertures. A simulated annealing based direct aperture optimization (DAO) is implemented to perform simultaneous optimization of photon and electron apertures, both shaped with the photon multileaf collimator (pMLC). Validated beam models are used as input for Monte Carlo dose calculations. Consideration of photon pMLC transmission during DAO and a weight re-optimization of the apertures after deliverable dose calculation are utilized to efficiently reduce the differences between optimized and deliverable dose distributions. The TPP for MBRT is evaluated for an academic situation with a superficial and an enlarged PTV in the depth, a left chest wall case including the internal mammary chain and a squamous cell carcinoma case. Deliverable dose distributions of MBRT plans are compared to those of modulated electron radiotherapy (MERT), photon IMRT and if available to those of clinical VMAT plans. The generated MBRT plans dosimetrically outperform the MERT, photon IMRT and VMAT plans for all investigated situations. For the clinical cases of the left chest wall and the squamous cell carcinoma, the MBRT plans cover the PTV similarly or more homogeneously than the VMAT plans, while OARs are spared considerably better with average reductions of the mean dose to parallel OARs and D 2% to serial OARs by 54% and 26%, respectively. Moreover, the low dose bath expressed as V 10% to normal tissue is substantially reduced by up to 45% compared to the VMAT plans. A TPP for MBRT including simultaneous optimization is successfully implemented and the dosimetric superiority of MBRT plans over MERT, photon IMRT and VMAT plans is demonstrated for academic and clinical situations including superficial targets with and without deep-seated part.

Simultaneous optimization of photons and electrons for mixed beam radiotherapy.

PubMed

Mueller, S; Fix, M K; Joosten, A; Henzen, D; Frei, D; Volken, W; Kueng, R; Aebersold, D M; Stampanoni, M F M; Manser, P

2017-06-26

The aim of this work is to develop and investigate an inverse treatment planning process (TPP) for mixed beam radiotherapy (MBRT) capable of performing simultaneous optimization of photon and electron apertures. A simulated annealing based direct aperture optimization (DAO) is implemented to perform simultaneous optimization of photon and electron apertures, both shaped with the photon multileaf collimator (pMLC). Validated beam models are used as input for Monte Carlo dose calculations. Consideration of photon pMLC transmission during DAO and a weight re-optimization of the apertures after deliverable dose calculation are utilized to efficiently reduce the differences between optimized and deliverable dose distributions. The TPP for MBRT is evaluated for an academic situation with a superficial and an enlarged PTV in the depth, a left chest wall case including the internal mammary chain and a squamous cell carcinoma case. Deliverable dose distributions of MBRT plans are compared to those of modulated electron radiotherapy (MERT), photon IMRT and if available to those of clinical VMAT plans. The generated MBRT plans dosimetrically outperform the MERT, photon IMRT and VMAT plans for all investigated situations. For the clinical cases of the left chest wall and the squamous cell carcinoma, the MBRT plans cover the PTV similarly or more homogeneously than the VMAT plans, while OARs are spared considerably better with average reductions of the mean dose to parallel OARs and D 2% to serial OARs by 54% and 26%, respectively. Moreover, the low dose bath expressed as V 10% to normal tissue is substantially reduced by up to 45% compared to the VMAT plans. A TPP for MBRT including simultaneous optimization is successfully implemented and the dosimetric superiority of MBRT plans over MERT, photon IMRT and VMAT plans is demonstrated for academic and clinical situations including superficial targets with and without deep-seated part.

SU-F-19A-03: Dosimetric Advantages in Critical Structure Dose Sparing by Using a Multichannel Cylinder in High Dose Rate Brachytherapy to Treat Vaginal Cuff Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syh, J; Syh, J; Patel, B

2014-06-15

Purpose: The multichannel cylindrical vaginal applicator is a variation of traditional single channel cylindrical vaginal applicator. The multichannel applicator has additional peripheral channels that provide more flexibility in the planning process. The dosimetric advantage is to reduce dose to adjacent organ at risk (OAR) such as bladder and rectum while maintaining target coverage with the dose optimization from additional channels. Methods: Vaginal HDR brachytherapy plans are all CT based. CT images were acquired in 2 mm thickness to keep integrity of cylinder contouring. The CTV of 5mm Rind with prescribed treatment length was reconstructed from 5mm expansion of inserted cylinder.more » The goal was 95% of CTV covered by 95% of prescribed dose in both single channel planning (SCP)and multichannel planning (MCP) before proceeding any further optimization for dose reduction to critical structures with emphasis on D2cc and V2Gy . Results: This study demonstrated noticeable dose reduction to OAR was apparent in multichannel plans. The D2cc of the rectum and bladder were showing the reduced dose for multichannel versus single channel. The V2Gy of the rectum was 93.72% and 83.79% (p=0.007) for single channel and multichannel respectively (Figure 1 and Table 1). To assure adequate coverage to target while reducing the dose to the OAR without any compromise is the main goal in using multichannel vaginal applicator in HDR brachytherapy. Conclusion: Multichannel plans were optimized using anatomical based inverse optimization algorithm of inverse planning simulation annealing. The optimization solution of the algorithm was to improve the clinical target volume dose coverage while reducing the dose to critical organs such as bladder, rectum and bowels. The comparison between SCP and MCP demonstrated MCP is superior to SCP where the dwell positions were based on geometric array only. It concluded that MCP is preferable and is able to provide certain features superior to SCP.« less

Statistical optimization of process parameters for the simultaneous adsorption of Cr(VI) and phenol onto Fe-treated tea waste biomass

NASA Astrophysics Data System (ADS)

Gupta, Ankur; Balomajumder, Chandrajit

2017-12-01

In this study, simultaneous removal of Cr(VI) and phenol from binary solution was carried out using Fe-treated tea waste biomass. The effect of process parameters such as adsorbent dose, pH, initial concentration of Cr(VI) (mg/L), and initial concentration of phenol (mg/L) was optimized. The analysis of variance of the quadratic model demonstrates that the experimental results are in good agreement with the predicted values. Based on experimental design at an initial concentration of 55 mg/L of Cr(VI), 27.50 mg/L of phenol, pH 2.0, 15 g/L adsorbent dose, 99.99% removal of Cr(VI), and phenol was achieved.

Clinical implementation of a knowledge based planning tool for prostate VMAT.

PubMed

Powis, Richard; Bird, Andrew; Brennan, Matthew; Hinks, Susan; Newman, Hannah; Reed, Katie; Sage, John; Webster, Gareth

2017-05-08

A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.

WE-AB-207B-07: Dose Cloud: Generating “Big Data” for Radiation Therapy Treatment Plan Optimization Research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Folkerts, MM; University of California San Diego, La Jolla, California; Long, T

Purpose: To provide a tool to generate large sets of realistic virtual patient geometries and beamlet doses for treatment optimization research. This tool enables countless studies exploring the fundamental interplay between patient geometry, objective functions, weight selections, and achievable dose distributions for various algorithms and modalities. Methods: Generating realistic virtual patient geometries requires a small set of real patient data. We developed a normalized patient shape model (PSM) which captures organ and target contours in a correspondence-preserving manner. Using PSM-processed data, we perform principal component analysis (PCA) to extract major modes of variation from the population. These PCA modes canmore » be shared without exposing patient information. The modes are re-combined with different weights to produce sets of realistic virtual patient contours. Because virtual patients lack imaging information, we developed a shape-based dose calculation (SBD) relying on the assumption that the region inside the body contour is water. SBD utilizes a 2D fluence-convolved scatter kernel, derived from Monte Carlo simulations, and can compute both full dose for a given set of fluence maps, or produce a dose matrix (dose per fluence pixel) for many modalities. Combining the shape model with SBD provides the data needed for treatment plan optimization research. Results: We used PSM to capture organ and target contours for 96 prostate cases, extracted the first 20 PCA modes, and generated 2048 virtual patient shapes by randomly sampling mode scores. Nearly half of the shapes were thrown out for failing anatomical checks, the remaining 1124 were used in computing dose matrices via SBD and a standard 7-beam protocol. As a proof of concept, and to generate data for later study, we performed fluence map optimization emphasizing PTV coverage. Conclusions: We successfully developed and tested a tool for creating customizable sets of virtual patients suitable for large-scale radiation therapy optimization research.« less

A dose optimization method for electron radiotherapy using randomized aperture beams

NASA Astrophysics Data System (ADS)

Engel, Konrad; Gauer, Tobias

2009-09-01

The present paper describes the entire optimization process of creating a radiotherapy treatment plan for advanced electron irradiation. Special emphasis is devoted to the selection of beam incidence angles and beam energies as well as to the choice of appropriate subfields generated by a refined version of intensity segmentation and a novel random aperture approach. The algorithms have been implemented in a stand-alone programme using dose calculations from a commercial treatment planning system. For this study, the treatment planning system Pinnacle from Philips has been used and connected to the optimization programme using an ASCII interface. Dose calculations in Pinnacle were performed by Monte Carlo simulations for a remote-controlled electron multileaf collimator (MLC) from Euromechanics. As a result, treatment plans for breast cancer patients could be significantly improved when using randomly generated aperture beams. The combination of beams generated through segmentation and randomization achieved the best results in terms of target coverage and sparing of critical organs. The treatment plans could be further improved by use of a field reduction algorithm. Without a relevant loss in dose distribution, the total number of MLC fields and monitor units could be reduced by up to 20%. In conclusion, using randomized aperture beams is a promising new approach in radiotherapy and exhibits potential for further improvements in dose optimization through a combination of randomized electron and photon aperture beams.

Automated IMRT planning with regional optimization using planning scripts

PubMed Central

Wong, Eugene; Bzdusek, Karl; Lock, Michael; Chen, Jeff Z.

2013-01-01

Intensity‐modulated radiation therapy (IMRT) has become a standard technique in radiation therapy for treating different types of cancers. Various class solutions have been developed for simple cases (e.g., localized prostate, whole breast) to generate IMRT plans efficiently. However, for more complex cases (e.g., head and neck, pelvic nodes), it can be time‐consuming for a planner to generate optimized IMRT plans. To generate optimal plans in these more complex cases which generally have multiple target volumes and organs at risk, it is often required to have additional IMRT optimization structures such as dose limiting ring structures, adjust beam geometry, select inverse planning objectives and associated weights, and additional IMRT objectives to reduce cold and hot spots in the dose distribution. These parameters are generally manually adjusted with a repeated trial and error approach during the optimization process. To improve IMRT planning efficiency in these more complex cases, an iterative method that incorporates some of these adjustment processes automatically in a planning script is designed, implemented, and validated. In particular, regional optimization has been implemented in an iterative way to reduce various hot or cold spots during the optimization process that begins with defining and automatic segmentation of hot and cold spots, introducing new objectives and their relative weights into inverse planning, and turn this into an iterative process with termination criteria. The method has been applied to three clinical sites: prostate with pelvic nodes, head and neck, and anal canal cancers, and has shown to reduce IMRT planning time significantly for clinical applications with improved plan quality. The IMRT planning scripts have been used for more than 500 clinical cases. PACS numbers: 87.55.D, 87.55.de PMID:23318393

Automatic treatment plan re-optimization for adaptive radiotherapy guided with the initial plan DVHs.

PubMed

Li, Nan; Zarepisheh, Masoud; Uribe-Sanchez, Andres; Moore, Kevin; Tian, Zhen; Zhen, Xin; Graves, Yan Jiang; Gautier, Quentin; Mell, Loren; Zhou, Linghong; Jia, Xun; Jiang, Steve

2013-12-21

Adaptive radiation therapy (ART) can reduce normal tissue toxicity and/or improve tumor control through treatment adaptations based on the current patient anatomy. Developing an efficient and effective re-planning algorithm is an important step toward the clinical realization of ART. For the re-planning process, manual trial-and-error approach to fine-tune planning parameters is time-consuming and is usually considered unpractical, especially for online ART. It is desirable to automate this step to yield a plan of acceptable quality with minimal interventions. In ART, prior information in the original plan is available, such as dose-volume histogram (DVH), which can be employed to facilitate the automatic re-planning process. The goal of this work is to develop an automatic re-planning algorithm to generate a plan with similar, or possibly better, DVH curves compared with the clinically delivered original plan. Specifically, our algorithm iterates the following two loops. An inner loop is the traditional fluence map optimization, in which we optimize a quadratic objective function penalizing the deviation of the dose received by each voxel from its prescribed or threshold dose with a set of fixed voxel weighting factors. In outer loop, the voxel weighting factors in the objective function are adjusted according to the deviation of the current DVH curves from those in the original plan. The process is repeated until the DVH curves are acceptable or maximum iteration step is reached. The whole algorithm is implemented on GPU for high efficiency. The feasibility of our algorithm has been demonstrated with three head-and-neck cancer IMRT cases, each having an initial planning CT scan and another treatment CT scan acquired in the middle of treatment course. Compared with the DVH curves in the original plan, the DVH curves in the resulting plan using our algorithm with 30 iterations are better for almost all structures. The re-optimization process takes about 30 s using our in-house optimization engine.

Towards more reliable automated multi-dose dispensing: retrospective follow-up study on medication dose errors and product defects.

PubMed

Palttala, Iida; Heinämäki, Jyrki; Honkanen, Outi; Suominen, Risto; Antikainen, Osmo; Hirvonen, Jouni; Yliruusi, Jouko

2013-03-01

To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product defects and dose dispensing errors in automated multi-dose dispensing were retrospectively investigated during a 6-months follow-up period. The study was based on the analysis of process data of totally nine automated high-speed multi-dose dispensing systems. Special attention was paid to the dependence of multi-dose dispensing errors/product defects and pharmaceutical tablet properties (such as shape, dimensions, weight, scored lines, coatings, etc.) to profile the most suitable forms of tablets for automated dose dispensing systems. The relationship between the risk of errors in dose dispensing and tablet characteristics were visualized by creating a principal component analysis (PCA) model for the outcome of dispensed tablets. The two most common process-induced failures identified in the multi-dose dispensing are predisposal of tablet defects and unexpected product transitions in the medication cassette (dose dispensing error). The tablet defects are product-dependent failures, while the tablet transitions are dependent on automated multi-dose dispensing systems used. The occurrence of tablet defects is approximately twice as common as tablet transitions. Optimal tablet preparation for the high-speed multi-dose dispensing would be a round-shaped, relatively small/middle-sized, film-coated tablet without any scored line. Commercial tablet products can be profiled and classified based on their suitability to a high-speed multi-dose dispensing process.

Dose to mass for evaluation and optimization of lung cancer radiation therapy.

PubMed

Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V

2017-11-01

To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Modeling and optimization aspects of radiation induced grafting of 4-vinylpyridene onto partially fluorinated films

NASA Astrophysics Data System (ADS)

Nasef, Mohamed Mahmoud; Ahmad Ali, Amgad; Saidi, Hamdani; Ahmad, Arshad

2014-01-01

Modeling and optimization aspects of radiation induced grafting (RIG) of 4-vinylpyridine (4-VP) onto partially fluorinated polymers such as poly(ethylene-co-tetrafluoroethene) (ETFE) and poly(vinylidene fluoride) (PVDF) films were comparatively investigated using response surface method (RSM). The effects of independent parameters: absorbed dose, monomer concentration, grafting time and reaction temperature on the response, grafting yield (GY) were correlated through two quadratic models. The results of this work confirm that RSM is a reliable tool not only for optimization of the reaction parameters and prediction of GY in RIG processes, but also for the reduction of the number of the experiments, monomer consumption and absorbed dose leading to an improvement of the overall reaction cost.

Emerging Techniques for Dose Optimization in Abdominal CT

PubMed Central

Platt, Joel F.; Goodsitt, Mitchell M.; Al-Hawary, Mahmoud M.; Maturen, Katherine E.; Wasnik, Ashish P.; Pandya, Amit

2014-01-01

Recent advances in computed tomographic (CT) scanning technique such as automated tube current modulation (ATCM), optimized x-ray tube voltage, and better use of iterative image reconstruction have allowed maintenance of good CT image quality with reduced radiation dose. ATCM varies the tube current during scanning to account for differences in patient attenuation, ensuring a more homogeneous image quality, although selection of the appropriate image quality parameter is essential for achieving optimal dose reduction. Reducing the x-ray tube voltage is best suited for evaluating iodinated structures, since the effective energy of the x-ray beam will be closer to the k-edge of iodine, resulting in a higher attenuation for the iodine. The optimal kilovoltage for a CT study should be chosen on the basis of imaging task and patient habitus. The aim of iterative image reconstruction is to identify factors that contribute to noise on CT images with use of statistical models of noise (statistical iterative reconstruction) and selective removal of noise to improve image quality. The degree of noise suppression achieved with statistical iterative reconstruction can be customized to minimize the effect of altered image quality on CT images. Unlike with statistical iterative reconstruction, model-based iterative reconstruction algorithms model both the statistical noise and the physical acquisition process, allowing CT to be performed with further reduction in radiation dose without an increase in image noise or loss of spatial resolution. Understanding these recently developed scanning techniques is essential for optimization of imaging protocols designed to achieve the desired image quality with a reduced dose. © RSNA, 2014 PMID:24428277

Optimization of Methylphenidate Extended-Release Chewable Tablet Dose in Children with ADHD: Open-Label Dose Optimization in a Laboratory Classroom Study.

PubMed

Wigal, Sharon B; Childress, Ann; Berry, Sally A; Belden, Heidi W; Chappell, Phillip; Wajsbrot, Dalia B; Nagraj, Praneeta; Abbas, Richat; Palumbo, Donna

2018-06-01

To examine methylphenidate extended-release chewable tablets (MPH ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom scores, and safety during the 6-week, open-label (OL) dose-optimization period of a phase 3, laboratory classroom study. Boys and girls (6-12 years) diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20 mg/day; participants were titrated in 10-20 mg/day increments weekly based on efficacy and tolerability (maximum dose, 60 mg/day). Dose-optimization period efficacy assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a post hoc analysis using a mixed-effects model for repeated measures with final optimized dose (20, 30/40, or 50/60 mg), visit, final optimized dose and visit interaction, and baseline score as terms. Adverse events (AEs) and concomitant medications were collected throughout the study. Mean MPH ERCT daily dose increased weekly from 29.4 mg/day after the first dose adjustment at week 1 (n = 90) to 42.8 mg/day after the final adjustment at week 5 (n = 86). Final optimized MPH ERCT dose ranged from 20 to 60 mg/day. Mean final optimized MPH ERCT dose ranged from 40.0 mg/day in 6-8 year-old participants to 44.8 mg/day for 11-12 year-old participants. There was a progressive decrease in mean (standard deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at OL week 5, with similar improvement patterns for hyperactivity/impulsivity and inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60 mg/day had a significantly higher mean (standard error) ADHD-RS-IV score at baseline compared with participants optimized to MPH ERCT 20 mg/day (42.4 [1.34] vs. 35.1 [2.55]; p = 0.013). Treatment-emergent AEs were reported by 65/90 (72.2%) participants in the dose-optimization period. Dose-optimization period results describing relationships between change in ADHD symptom scores and final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT dose.

Development of a standardized, citywide process for managing smart-pump drug libraries.

PubMed

Walroth, Todd A; Smallwood, Shannon; Arthur, Karen; Vance, Betsy; Washington, Alana; Staublin, Therese; Haslar, Tammy; Reddan, Jennifer G; Fuller, James

2018-06-15

Development and implementation of an interprofessional consensus-driven process for review and optimization of smart-pump drug libraries and dosing limits are described. The Indianapolis Coalition for Patient Safety (ICPS), which represents 6 Indianapolis-area health systems, identified an opportunity to reduce clinically insignificant alerts that smart infusion pumps present to end users. Through a consensus-driven process, ICPS aimed to identify best practices to implement at individual hospitals in order to establish specific action items for smart-pump drug library optimization. A work group of pharmacists, nurses, and industrial engineers met to evaluate variability within and lack of scrutiny of smart-pump drug libraries. The work group used Lean Six Sigma methodologies to generate a list of key needs and barriers to be addressed in process standardization. The group reviewed targets for smart-pump drug library optimization, including dosing limits, types of alerts reviewed, policies, and safety best practices. The work group also analyzed existing processes at each site to develop a final consensus statement outlining a model process for reviewing alerts and managing smart-pump data. Analysis of the total number of alerts per device across ICPS-affiliated health systems over a 4-year period indicated a 50% decrease (from 7.2 to 3.6 alerts per device per month) after implementation of the model by ICPS member organizations. Through implementation of a standardized, consensus-driven process for smart-pump drug library optimization, ICPS member health systems reduced clinically insignificant smart-pump alerts. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

GPU-based ultra-fast dose calculation using a finite size pencil beam model.

PubMed

Gu, Xuejun; Choi, Dongju; Men, Chunhua; Pan, Hubert; Majumdar, Amitava; Jiang, Steve B

2009-10-21

Online adaptive radiation therapy (ART) is an attractive concept that promises the ability to deliver an optimal treatment in response to the inter-fraction variability in patient anatomy. However, it has yet to be realized due to technical limitations. Fast dose deposit coefficient calculation is a critical component of the online planning process that is required for plan optimization of intensity-modulated radiation therapy (IMRT). Computer graphics processing units (GPUs) are well suited to provide the requisite fast performance for the data-parallel nature of dose calculation. In this work, we develop a dose calculation engine based on a finite-size pencil beam (FSPB) algorithm and a GPU parallel computing framework. The developed framework can accommodate any FSPB model. We test our implementation in the case of a water phantom and the case of a prostate cancer patient with varying beamlet and voxel sizes. All testing scenarios achieved speedup ranging from 200 to 400 times when using a NVIDIA Tesla C1060 card in comparison with a 2.27 GHz Intel Xeon CPU. The computational time for calculating dose deposition coefficients for a nine-field prostate IMRT plan with this new framework is less than 1 s. This indicates that the GPU-based FSPB algorithm is well suited for online re-planning for adaptive radiotherapy.

Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

PubMed Central

Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

2017-01-01

Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164

TU-AB-303-01: A Feasibility Study for Dynamic Adaptive Therapy of Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M; Phillips, M

2015-06-15

Purpose: To compare plans for NSCLC optimized using Dynamic Adaptive Therapy (DAT) with conventional IMRT optimization. DAT adapts plans based on changes in the target volume by using dynamic programing techniques to consider expected changes into the optimization process. Information gathered during treatment, e.g. from CBCT, is incorporated into the optimization. Methods and materials: DAT is formulated using stochastic control formalism, which minimizes the total expected number of tumor cells at the end of a treatment course subject to uncertainty inherent in the tumor response and organs-at-risk (OAR) dose constraints. This formulation allows for non-stationary dose distribution as well asmore » non-stationary fractional dose as needed to achieve a series of optimal plans that are conformal to tumor over time. Sixteen phantom cases with various sizes and locations of tumors, and OAR geometries were generated. Each case was planned with DAT and conventional IMRT (60Gy/30fx). Tumor volume change over time was obtained by using, daily MVCT-based, two-level cell population model. Monte Carlo simulations have been performed for each treatment course to account for uncertainty in tumor response. Same OAR dose constraints were applied for both methods. The frequency of plan modification was varied to 1, 2, 5 (weekly), and 29 (daily). The final average tumor dose and OAR doses have been compared to quantify the potential benefit of DAT. Results: The average tumor max, min, mean, and D95 resulted from DAT were 124.0–125.2%, 102.1–114.7%, 113.7–123.4%, and 102.0–115.9% (range dependent on the frequency of plan modification) of those from conventional IMRT. Cord max, esophagus max, lung mean, heart mean, and unspecified tissue D05 resulted from AT were 84–102.4%, 99.8–106.9%, 66.9–85.6%, 58.2–78.8%, and 85.2–94.0% of those from conventional IMRT. Conclusions: Significant tumor dose increase and OAR dose reduction, especially with parallel OAR with mean or dose-volume constraints, can be achieved using DAT.« less

Determination of MLC model parameters for Monaco using commercial diode arrays.

PubMed

Kinsella, Paul; Shields, Laura; McCavana, Patrick; McClean, Brendan; Langan, Brian

2016-07-08

Multileaf collimators (MLCs) need to be characterized accurately in treatment planning systems to facilitate accurate intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). The aim of this study was to examine the use of MapCHECK 2 and ArcCHECK diode arrays for optimizing MLC parameters in Monaco X-ray voxel Monte Carlo (XVMC) dose calculation algorithm. A series of radiation test beams designed to evaluate MLC model parameters were delivered to MapCHECK 2, ArcCHECK, and EBT3 Gafchromic film for comparison. Initial comparison of the calculated and ArcCHECK-measured dose distributions revealed it was unclear how to change the MLC parameters to gain agreement. This ambiguity arose due to an insufficient sampling of the test field dose distributions and unexpected discrepancies in the open parts of some test fields. Consequently, the XVMC MLC parameters were optimized based on MapCHECK 2 measurements. Gafchromic EBT3 film was used to verify the accuracy of MapCHECK 2 measured dose distributions. It was found that adjustment of the MLC parameters from their default values resulted in improved global gamma analysis pass rates for MapCHECK 2 measurements versus calculated dose. The lowest pass rate of any MLC-modulated test beam improved from 68.5% to 93.5% with 3% and 2 mm gamma criteria. Given the close agreement of the optimized model to both MapCHECK 2 and film, the optimized model was used as a benchmark to highlight the relatively large discrepancies in some of the test field dose distributions found with ArcCHECK. Comparison between the optimized model-calculated dose and ArcCHECK-measured dose resulted in global gamma pass rates which ranged from 70.0%-97.9% for gamma criteria of 3% and 2 mm. The simple square fields yielded high pass rates. The lower gamma pass rates were attributed to the ArcCHECK overestimating the dose in-field for the rectangular test fields whose long axis was parallel to the long axis of the ArcCHECK. Considering ArcCHECK measurement issues and the lower gamma pass rates for the MLC-modulated test beams, it was concluded that MapCHECK 2 was a more suitable detector than ArcCHECK for the optimization process. © 2016 The Authors

An online replanning method using warm start optimization and aperture morphing for flattening-filter-free beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahunbay, Ergun E., E-mail: eahunbay@mcw.edu; Ates,

Purpose: In a situation where a couch shift for patient positioning is not preferred or prohibited (e.g., MR-linac), segment aperture morphing (SAM) can address target dislocation and deformation. For IMRT/VMAT with flattening-filter-free (FFF) beams, however, SAM method would lead to an adverse translational dose effect due to the beam unflattening. Here the authors propose a new two-step process to address both the translational effect of FFF beams and the target deformation. Methods: The replanning method consists of an offline and an online step. The offline step is to create a series of preshifted-plans (PSPs) obtained by a so-called “warm start”more » optimization (starting optimization from the original plan, rather than from scratch) at a series of isocenter shifts. The PSPs all have the same number of segments with very similar shapes, since the warm start optimization only adjusts the MLC positions instead of regenerating them. In the online step, a new plan is obtained by picking the closest PSP or linearly interpolating the MLC positions and the monitor units of the closest PSPs for the shift determined from the image of the day. This two-step process is completely automated and almost instantaneous (no optimization or dose calculation needed). The previously developed SAM algorithm is then applied for daily deformation. The authors tested the method on sample prostate and pancreas cases. Results: The two-step interpolation method can account for the adverse dose effects from FFF beams, while SAM corrects for the target deformation. Plan interpolation method is effective in diminishing the unflat beam effect and may allow reducing the required number of PSPs. The whole process takes the same time as the previously reported SAM process (5–10 min). Conclusions: The new two-step method plus SAM can address both the translation effects of FFF beams and target deformation, and can be executed in full automation except the delineation of target contour required by the SAM process.« less

Prospective estimation of organ dose in CT under tube current modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Xiaoyu, E-mail: xt3@duke.edu; Li, Xiang; Segars, W. Paul

Purpose: Computed tomography (CT) has been widely used worldwide as a tool for medical diagnosis and imaging. However, despite its significant clinical benefits, CT radiation dose at the population level has become a subject of public attention and concern. In this light, optimizing radiation dose has become a core responsibility for the CT community. As a fundamental step to manage and optimize dose, it may be beneficial to have accurate and prospective knowledge about the radiation dose for an individual patient. In this study, the authors developed a framework to prospectively estimate organ dose for chest and abdominopelvic CT examsmore » under tube current modulation (TCM). Methods: The organ dose is mainly dependent on two key factors: patient anatomy and irradiation field. A prediction process was developed to accurately model both factors. To model the anatomical diversity and complexity in the patient population, the authors used a previously developed library of computational phantoms with broad distributions of sizes, ages, and genders. A selected clinical patient, represented by a computational phantom in the study, was optimally matched with another computational phantom in the library to obtain a representation of the patient’s anatomy. To model the irradiation field, a previously validated Monte Carlo program was used to model CT scanner systems. The tube current profiles were modeled using a ray-tracing program as previously reported that theoretically emulated the variability of modulation profiles from major CT machine manufacturers Li et al., [Phys. Med. Biol. 59, 4525–4548 (2014)]. The prediction of organ dose was achieved using the following process: (1) CTDI{sub vol}-normalized-organ dose coefficients (h{sub organ}) for fixed tube current were first estimated as the prediction basis for the computational phantoms; (2) each computation phantom, regarded as a clinical patient, was optimally matched with one computational phantom in the library; (3) to account for the effect of the TCM scheme, a weighted organ-specific CTDI{sub vol} [denoted as (CTDI{sub vol}){sub organ,weighted}] was computed for each organ based on the TCM profile and the anatomy of the “matched” phantom; (4) the organ dose was predicted by multiplying the weighted organ-specific CTDI{sub vol} with the organ dose coefficients (h{sub organ}). To quantify the prediction accuracy, each predicted organ dose was compared with the corresponding organ dose simulated from the Monte Carlo program with the TCM profile explicitly modeled. Results: The predicted organ dose showed good agreements with the simulated organ dose across all organs and modulation profiles. The average percentage error in organ dose estimation was generally within 20% across all organs and modulation profiles, except for organs located in the pelvic and shoulder regions. For an average CTDI{sub vol} of a CT exam of 10 mGy, the average error at full modulation strength (α = 1) across all organs was 0.91 mGy for chest exams, and 0.82 mGy for abdominopelvic exams. Conclusions: This study developed a quantitative model to predict organ dose for clinical chest and abdominopelvic scans. Such information may aid in the design of optimized CT protocols in relation to a targeted level of image quality.« less

Optimization of the synthesis process of an iron oxide nanocatalyst supported on activated carbon for the inactivation of Ascaris eggs in water using the heterogeneous Fenton-like reaction.

PubMed

Morales-Pérez, Ariadna A; Maravilla, Pablo; Solís-López, Myriam; Schouwenaars, Rafael; Durán-Moreno, Alfonso; Ramírez-Zamora, Rosa-María

2016-01-01

An experimental design methodology was used to optimize the synthesis of an iron-supported nanocatalyst as well as the inactivation process of Ascaris eggs (Ae) using this material. A factor screening design was used for identifying the significant experimental factors for nanocatalyst support (supported %Fe, (w/w), temperature and time of calcination) and for the inactivation process called the heterogeneous Fenton-like reaction (H2O2 dose, mass ratio Fe/H2O2, pH and reaction time). The optimization of the significant factors was carried out using a face-centered central composite design. The optimal operating conditions for both processes were estimated with a statistical model and implemented experimentally with five replicates. The predicted value of the Ae inactivation rate was close to the laboratory results. At the optimal operating conditions of the nanocatalyst production and Ae inactivation process, the Ascaris ova showed genomic damage to the point that no cell reparation was possible showing that this advanced oxidation process was highly efficient for inactivating this pathogen.

Influence of ion-implanted profiles on the performance of GaAs MESFET's and MMIC amplifiers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavlidis, D.; Cazaux, J.L.; Graffeuil, J.

1988-04-01

The RF small-signal performance of GaAs MESFET's and MMIC amplifiers as a function of various ion-implanted profiles is theoretically and experimentally investigated. Implantation energy, dose, and recess depth influence are theoretically analyzed with the help of a specially developed device simulator. The performance of MMIC amplifiers processed with various energies, doses, recess depths, and bias conditions is discussed and compared to experimental characteristics. Some criteria are finally proposed for the choice of implantation conditions and process in order to optimize the characteristics of ion-implanted FET's and to realize process-tolerant MMIC amplifiers.

Acceleration of intensity-modulated radiotherapy dose calculation by importance sampling of the calculation matrices.

PubMed

Thieke, Christian; Nill, Simeon; Oelfke, Uwe; Bortfeld, Thomas

2002-05-01

In inverse planning for intensity-modulated radiotherapy, the dose calculation is a crucial element limiting both the maximum achievable plan quality and the speed of the optimization process. One way to integrate accurate dose calculation algorithms into inverse planning is to precalculate the dose contribution of each beam element to each voxel for unit fluence. These precalculated values are stored in a big dose calculation matrix. Then the dose calculation during the iterative optimization process consists merely of matrix look-up and multiplication with the actual fluence values. However, because the dose calculation matrix can become very large, this ansatz requires a lot of computer memory and is still very time consuming, making it not practical for clinical routine without further modifications. In this work we present a new method to significantly reduce the number of entries in the dose calculation matrix. The method utilizes the fact that a photon pencil beam has a rapid radial dose falloff, and has very small dose values for the most part. In this low-dose part of the pencil beam, the dose contribution to a voxel is only integrated into the dose calculation matrix with a certain probability. Normalization with the reciprocal of this probability preserves the total energy, even though many matrix elements are omitted. Three probability distributions were tested to find the most accurate one for a given memory size. The sampling method is compared with the use of a fully filled matrix and with the well-known method of just cutting off the pencil beam at a certain lateral distance. A clinical example of a head and neck case is presented. It turns out that a sampled dose calculation matrix with only 1/3 of the entries of the fully filled matrix does not sacrifice the quality of the resulting plans, whereby the cutoff method results in a suboptimal treatment plan.

Analytical modeling and feasibility study of a multi-GPU cloud-based server (MGCS) framework for non-voxel-based dose calculations.

PubMed

Neylon, J; Min, Y; Kupelian, P; Low, D A; Santhanam, A

2017-04-01

In this paper, a multi-GPU cloud-based server (MGCS) framework is presented for dose calculations, exploring the feasibility of remote computing power for parallelization and acceleration of computationally and time intensive radiotherapy tasks in moving toward online adaptive therapies. An analytical model was developed to estimate theoretical MGCS performance acceleration and intelligently determine workload distribution. Numerical studies were performed with a computing setup of 14 GPUs distributed over 4 servers interconnected by a 1 Gigabits per second (Gbps) network. Inter-process communication methods were optimized to facilitate resource distribution and minimize data transfers over the server interconnect. The analytically predicted computation time predicted matched experimentally observations within 1-5 %. MGCS performance approached a theoretical limit of acceleration proportional to the number of GPUs utilized when computational tasks far outweighed memory operations. The MGCS implementation reproduced ground-truth dose computations with negligible differences, by distributing the work among several processes and implemented optimization strategies. The results showed that a cloud-based computation engine was a feasible solution for enabling clinics to make use of fast dose calculations for advanced treatment planning and adaptive radiotherapy. The cloud-based system was able to exceed the performance of a local machine even for optimized calculations, and provided significant acceleration for computationally intensive tasks. Such a framework can provide access to advanced technology and computational methods to many clinics, providing an avenue for standardization across institutions without the requirements of purchasing, maintaining, and continually updating hardware.

Panthere V2: Multipurpose Simulation Software for 3D Dose Rate Calculations

NASA Astrophysics Data System (ADS)

Penessot, Gaël; Bavoil, Éléonore; Wertz, Laurent; Malouch, Fadhel; Visonneau, Thierry; Dubost, Julien

2017-09-01

PANTHERE is a multipurpose radiation protection software developed by EDF to calculate gamma dose rates in complex 3D environments. PANTHERE takes a key role in the EDF ALARA process, enabling to predict dose rates and to organize and optimize operations in high radiation environments. PANTHERE is also used for nuclear waste characterization, transport of nuclear materials, etc. It is used in most of the EDF engineering units and their design service providers and industrial partners.

MO-C-18A-01: Advances in Model-Based 3D Image Reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, G; Pan, X; Stayman, J

2014-06-15

Recent years have seen the emergence of CT image reconstruction techniques that exploit physical models of the imaging system, photon statistics, and even the patient to achieve improved 3D image quality and/or reduction of radiation dose. With numerous advantages in comparison to conventional 3D filtered backprojection, such techniques bring a variety of challenges as well, including: a demanding computational load associated with sophisticated forward models and iterative optimization methods; nonlinearity and nonstationarity in image quality characteristics; a complex dependency on multiple free parameters; and the need to understand how best to incorporate prior information (including patient-specific prior images) within themore » reconstruction process. The advantages, however, are even greater – for example: improved image quality; reduced dose; robustness to noise and artifacts; task-specific reconstruction protocols; suitability to novel CT imaging platforms and noncircular orbits; and incorporation of known characteristics of the imager and patient that are conventionally discarded. This symposium features experts in 3D image reconstruction, image quality assessment, and the translation of such methods to emerging clinical applications. Dr. Chen will address novel methods for the incorporation of prior information in 3D and 4D CT reconstruction techniques. Dr. Pan will show recent advances in optimization-based reconstruction that enable potential reduction of dose and sampling requirements. Dr. Stayman will describe a “task-based imaging” approach that leverages models of the imaging system and patient in combination with a specification of the imaging task to optimize both the acquisition and reconstruction process. Dr. Samei will describe the development of methods for image quality assessment in such nonlinear reconstruction techniques and the use of these methods to characterize and optimize image quality and dose in a spectrum of clinical applications. Learning Objectives: Learn the general methodologies associated with model-based 3D image reconstruction. Learn the potential advantages in image quality and dose associated with model-based image reconstruction. Learn the challenges associated with computational load and image quality assessment for such reconstruction methods. Learn how imaging task can be incorporated as a means to drive optimal image acquisition and reconstruction techniques. Learn how model-based reconstruction methods can incorporate prior information to improve image quality, ease sampling requirements, and reduce dose.« less

Optimization of Refining Craft for Vegetable Insulating Oil

NASA Astrophysics Data System (ADS)

Zhou, Zhu-Jun; Hu, Ting; Cheng, Lin; Tian, Kai; Wang, Xuan; Yang, Jun; Kong, Hai-Yang; Fang, Fu-Xin; Qian, Hang; Fu, Guang-Pan

2016-05-01

Vegetable insulating oil because of its environmental friendliness are considered as ideal material instead of mineral oil used for the insulation and the cooling of the transformer. The main steps of traditional refining process included alkali refining, bleaching and distillation. This kind of refining process used in small doses of insulating oil refining can get satisfactory effect, but can't be applied to the large capacity reaction kettle. This paper using rapeseed oil as crude oil, and the refining process has been optimized for large capacity reaction kettle. The optimized refining process increases the acid degumming process. The alkali compound adds the sodium silicate composition in the alkali refining process, and the ratio of each component is optimized. Add the amount of activated clay and activated carbon according to 10:1 proportion in the de-colorization process, which can effectively reduce the oil acid value and dielectric loss. Using vacuum pumping gas instead of distillation process can further reduce the acid value. Compared some part of the performance parameters of refined oil products with mineral insulating oil, the dielectric loss of vegetable insulating oil is still high and some measures are needed to take to further optimize in the future.

Optimization strategies with resource scarcity: From immunization of networks to the traveling salesman problem

NASA Astrophysics Data System (ADS)

Bellingeri, Michele; Agliari, Elena; Cassi, Davide

2015-10-01

The best strategy to immunize a complex network is usually evaluated in terms of the percolation threshold, i.e. the number of vaccine doses which make the largest connected cluster (LCC) vanish. The strategy inducing the minimum percolation threshold represents the optimal way to immunize the network. Here we show that the efficacy of the immunization strategies can change during the immunization process. This means that, if the number of doses is limited, the best strategy is not necessarily the one leading to the smallest percolation threshold. This outcome should warn about the adoption of global measures in order to evaluate the best immunization strategy.

Application of mathematical models to metronomic chemotherapy: What can be inferred from minimal parameterized models?

PubMed

Ledzewicz, Urszula; Schättler, Heinz

2017-08-10

Metronomic chemotherapy refers to the frequent administration of chemotherapy at relatively low, minimally toxic doses without prolonged treatment interruptions. Different from conventional or maximum-tolerated-dose chemotherapy which aims at an eradication of all malignant cells, in a metronomic dosing the goal often lies in the long-term management of the disease when eradication proves elusive. Mathematical modeling and subsequent analysis (theoretical as well as numerical) have become an increasingly more valuable tool (in silico) both for determining conditions under which specific treatment strategies should be preferred and for numerically optimizing treatment regimens. While elaborate, computationally-driven patient specific schemes that would optimize the timing and drug dose levels are still a part of the future, such procedures may become instrumental in making chemotherapy effective in situations where it currently fails. Ideally, mathematical modeling and analysis will develop into an additional decision making tool in the complicated process that is the determination of efficient chemotherapy regimens. In this article, we review some of the results that have been obtained about metronomic chemotherapy from mathematical models and what they infer about the structure of optimal treatment regimens. Copyright © 2017 Elsevier B.V. All rights reserved.

Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

PubMed Central

Giżyńska, Marta K.; Kukołowicz, Paweł F.; Kordowski, Paweł

2014-01-01

Aim The aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer. Background 3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use. Materials and methods Optimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed. Results The quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed. Conclusions Optimization shortens very much time planning. The average planning time was 5 min and less than a minute for forward and computer optimization, respectively. PMID:25337411

Evaluation of hybrid inverse planning and optimization (HIPO) algorithm for optimization in real-time, high-dose-rate (HDR) brachytherapy for prostate.

PubMed

Pokharel, Shyam; Rana, Suresh; Blikenstaff, Joseph; Sadeghi, Amir; Prestidge, Bradley

2013-07-08

The purpose of this study is to investigate the effectiveness of the HIPO planning and optimization algorithm for real-time prostate HDR brachytherapy. This study consists of 20 patients who underwent ultrasound-based real-time HDR brachytherapy of the prostate using the treatment planning system called Oncentra Prostate (SWIFT version 3.0). The treatment plans for all patients were optimized using inverse dose-volume histogram-based optimization followed by graphical optimization (GRO) in real time. The GRO is manual manipulation of isodose lines slice by slice. The quality of the plan heavily depends on planner expertise and experience. The data for all patients were retrieved later, and treatment plans were created and optimized using HIPO algorithm with the same set of dose constraints, number of catheters, and set of contours as in the real-time optimization algorithm. The HIPO algorithm is a hybrid because it combines both stochastic and deterministic algorithms. The stochastic algorithm, called simulated annealing, searches the optimal catheter distributions for a given set of dose objectives. The deterministic algorithm, called dose-volume histogram-based optimization (DVHO), optimizes three-dimensional dose distribution quickly by moving straight downhill once it is in the advantageous region of the search space given by the stochastic algorithm. The PTV receiving 100% of the prescription dose (V100) was 97.56% and 95.38% with GRO and HIPO, respectively. The mean dose (D(mean)) and minimum dose to 10% volume (D10) for the urethra, rectum, and bladder were all statistically lower with HIPO compared to GRO using the student pair t-test at 5% significance level. HIPO can provide treatment plans with comparable target coverage to that of GRO with a reduction in dose to the critical structures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pantelis, Evaggelos, E-mail: vpantelis@phys.uoa.g; Medical Physics Laboratory, Medical School, University of Athens, Athens; Papadakis, Nikolaos

Purpose: To study the efficacy of the integration of functional magnetic resonance imaging (fMRI) and diffusion tensor imaging tractography data into stereotactic radiosurgery clinical practice. Methods and Materials: fMRI and tractography data sets were acquired and fused with corresponding anatomical MR and computed tomography images of patients with arteriovenous malformation (AVM), astrocytoma, brain metastasis, or hemangioma and referred for stereotactic radiosurgery. The acquired data sets were imported into a CyberKnife stereotactic radiosurgery system and used to delineate the target, organs at risk, and nearby functional structures and fiber tracts. Treatment plans with and without the incorporation of the functional structuresmore » and the fiber tracts into the optimization process were developed and compared. Results: The nearby functional structures and fiber tracts could receive doses of >50% of the maximum dose if they were excluded from the planning process. In the AVM case, the doses received by the Broadmann-17 structure and the optic tract were reduced to 700 cGy from 1,400 cGy and to 1,200 cGy from 2,000 cGy, respectively, upon inclusion into the optimization process. In the metastasis case, the motor cortex received 850 cGy instead of 1,400 cGy; and in the hemangioma case, the pyramidal tracts received 780 cGy instead of 990 cGy. In the astrocytoma case, the dose to the motor cortex bordering the lesion was reduced to 1,900 cGy from 2,100 cGy, and therefore, the biologically equivalent dose in three fractions was delivered instead. Conclusions: Functional structures and fiber tracts could receive high doses if they were not considered during treatment planning. With the aid of fMRI and tractography images, they can be delineated and spared.« less

Development of a pharmacokinetic-guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia.

PubMed

Dong, Min; McGann, Patrick T; Mizuno, Tomoyuki; Ware, Russell E; Vinks, Alexander A

2016-04-01

Hydroxyurea has emerged as the primary disease-modifying therapy for patients with sickle cell anaemia (SCA). The laboratory and clinical benefits of hydroxyurea are optimal at maximum tolerated dose (MTD), but the current empirical dose escalation process often takes up to 12 months. The purpose of this study was to develop a pharmacokinetic-guided dosing strategy to reduce the time required to reach hydroxyurea MTD in children with SCA. Pharmacokinetic (PK) data from the HUSTLE trial (NCT00305175) were used to develop a population PK model using non-linear mixed effects modelling (nonmem 7.2). A D-optimal sampling strategy was developed to estimate individual PK and hydroxyurea exposure (area under the concentration-time curve (AUC)). The initial AUC target was derived from HUSTLE clinical data and defined as the mean AUC at MTD. PK profiles were best described by a one compartment with Michaelis-Menten elimination and a transit absorption model. Body weight and cystatin C were identified as significant predictors of hydroxyurea clearance. The following clinically feasible sampling times are included in a new prospective protocol: pre-dose (baseline), 15-20 min, 50-60 min and 3 h after an initial 20 mg kg(-1) oral dose. The mean target AUC(0,∞) for initial dose titration was 115 mg l(-1)  h. We developed a PK model-based individualized dosing strategy for the prospective Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154). This approach has the potential to optimize the dose titration of hydroxyurea therapy for children with SCA, such that the clinical benefits at MTD are achieved more quickly. © 2015 The British Pharmacological Society.

Development of a pharmacokinetic‐guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia

PubMed Central

Dong, Min; McGann, Patrick T.; Mizuno, Tomoyuki; Ware, Russell E.

2016-01-01

AIMS Hydroxyurea has emerged as the primary disease‐modifying therapy for patients with sickle cell anaemia (SCA). The laboratory and clinical benefits of hydroxyurea are optimal at maximum tolerated dose (MTD), but the current empirical dose escalation process often takes up to 12 months. The purpose of this study was to develop a pharmacokinetic‐guided dosing strategy to reduce the time required to reach hydroxyurea MTD in children with SCA. Methods Pharmacokinetic (PK) data from the HUSTLE trial (NCT00305175) were used to develop a population PK model using non‐linear mixed effects modelling (nonmem 7.2). A D‐optimal sampling strategy was developed to estimate individual PK and hydroxyurea exposure (area under the concentration–time curve (AUC)). The initial AUC target was derived from HUSTLE clinical data and defined as the mean AUC at MTD. Results PK profiles were best described by a one compartment with Michaelis–Menten elimination and a transit absorption model. Body weight and cystatin C were identified as significant predictors of hydroxyurea clearance. The following clinically feasible sampling times are included in a new prospective protocol: pre‐dose (baseline), 15–20 min, 50–60 min and 3 h after an initial 20 mg kg–1 oral dose. The mean target AUC(0,∞) for initial dose titration was 115 mg l–1 h. Conclusion We developed a PK model‐based individualized dosing strategy for the prospective Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154). This approach has the potential to optimize the dose titration of hydroxyurea therapy for children with SCA, such that the clinical benefits at MTD are achieved more quickly. PMID:26615061

Generation of a novel phase-space-based cylindrical dose kernel for IMRT optimization.

PubMed

Zhong, Hualiang; Chetty, Indrin J

2012-05-01

Improving dose calculation accuracy is crucial in intensity-modulated radiation therapy (IMRT). We have developed a method for generating a phase-space-based dose kernel for IMRT planning of lung cancer patients. Particle transport in the linear accelerator treatment head of a 21EX, 6 MV photon beam (Varian Medical Systems, Palo Alto, CA) was simulated using the EGSnrc/BEAMnrc code system. The phase space information was recorded under the secondary jaws. Each particle in the phase space file was associated with a beamlet whose index was calculated and saved in the particle's LATCH variable. The DOSXYZnrc code was modified to accumulate the energy deposited by each particle based on its beamlet index. Furthermore, the central axis of each beamlet was calculated from the orientation of all the particles in this beamlet. A cylinder was then defined around the central axis so that only the energy deposited within the cylinder was counted. A look-up table was established for each cylinder during the tallying process. The efficiency and accuracy of the cylindrical beamlet energy deposition approach was evaluated using a treatment plan developed on a simulated lung phantom. Profile and percentage depth doses computed in a water phantom for an open, square field size were within 1.5% of measurements. Dose optimized with the cylindrical dose kernel was found to be within 0.6% of that computed with the nontruncated 3D kernel. The cylindrical truncation reduced optimization time by approximately 80%. A method for generating a phase-space-based dose kernel, using a truncated cylinder for scoring dose, in beamlet-based optimization of lung treatment planning was developed and found to be in good agreement with the standard, nontruncated scoring approach. Compared to previous techniques, our method significantly reduces computational time and memory requirements, which may be useful for Monte-Carlo-based 4D IMRT or IMAT treatment planning.

SU-E-T-109: An Investigation of Including Variable Relative Biological Effectiveness in Intensity Modulated Proton Therapy Planning Optimization for Head and Neck Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, W; Zaghian, M; Lim, G

2015-06-15

Purpose: The current practice of considering the relative biological effectiveness (RBE) of protons in intensity modulated proton therapy (IMPT) planning is to use a generic RBE value of 1.1. However, RBE is indeed a variable depending on the dose per fraction, the linear energy transfer, tissue parameters, etc. In this study, we investigate the impact of using variable RBE based optimization (vRBE-OPT) on IMPT dose distributions compared by conventional fixed RBE based optimization (fRBE-OPT). Methods: Proton plans of three head and neck cancer patients were included for our study. In order to calculate variable RBE, tissue specific parameters were obtainedmore » from the literature and dose averaged LET values were calculated by Monte Carlo simulations. Biological effects were calculated using the linear quadratic model and they were utilized in the variable RBE based optimization. We used a Polak-Ribiere conjugate gradient algorithm to solve the model. In fixed RBE based optimization, we used conventional physical dose optimization to optimize doses weighted by 1.1. IMPT plans for each patient were optimized by both methods (vRBE-OPT and fRBE-OPT). Both variable and fixed RBE weighted dose distributions were calculated for both methods and compared by dosimetric measures. Results: The variable RBE weighted dose distributions were more homogenous within the targets, compared with the fixed RBE weighted dose distributions for the plans created by vRBE-OPT. We observed that there were noticeable deviations between variable and fixed RBE weighted dose distributions if the plan were optimized by fRBE-OPT. For organs at risk sparing, dose distributions from both methods were comparable. Conclusion: Biological dose based optimization rather than conventional physical dose based optimization in IMPT planning may bring benefit in improved tumor control when evaluating biologically equivalent dose, without sacrificing OAR sparing, for head and neck cancer patients. The research is supported in part by National Institutes of Health Grant No. 2U19CA021239-35.« less

Robust optimization based upon statistical theory.

PubMed

Sobotta, B; Söhn, M; Alber, M

2010-08-01

Organ movement is still the biggest challenge in cancer treatment despite advances in online imaging. Due to the resulting geometric uncertainties, the delivered dose cannot be predicted precisely at treatment planning time. Consequently, all associated dose metrics (e.g., EUD and maxDose) are random variables with a patient-specific probability distribution. The method that the authors propose makes these distributions the basis of the optimization and evaluation process. The authors start from a model of motion derived from patient-specific imaging. On a multitude of geometry instances sampled from this model, a dose metric is evaluated. The resulting pdf of this dose metric is termed outcome distribution. The approach optimizes the shape of the outcome distribution based on its mean and variance. This is in contrast to the conventional optimization of a nominal value (e.g., PTV EUD) computed on a single geometry instance. The mean and variance allow for an estimate of the expected treatment outcome along with the residual uncertainty. Besides being applicable to the target, the proposed method also seamlessly includes the organs at risk (OARs). The likelihood that a given value of a metric is reached in the treatment is predicted quantitatively. This information reveals potential hazards that may occur during the course of the treatment, thus helping the expert to find the right balance between the risk of insufficient normal tissue sparing and the risk of insufficient tumor control. By feeding this information to the optimizer, outcome distributions can be obtained where the probability of exceeding a given OAR maximum and that of falling short of a given target goal can be minimized simultaneously. The method is applicable to any source of residual motion uncertainty in treatment delivery. Any model that quantifies organ movement and deformation in terms of probability distributions can be used as basis for the algorithm. Thus, it can generate dose distributions that are robust against interfraction and intrafraction motion alike, effectively removing the need for indiscriminate safety margins.

Voxel-based dose prediction with multi-patient atlas selection for automated radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

McIntosh, Chris; Purdie, Thomas G.

2017-01-01

Automating the radiotherapy treatment planning process is a technically challenging problem. The majority of automated approaches have focused on customizing and inferring dose volume objectives to be used in plan optimization. In this work we outline a multi-patient atlas-based dose prediction approach that learns to predict the dose-per-voxel for a novel patient directly from the computed tomography planning scan without the requirement of specifying any objectives. Our method learns to automatically select the most effective atlases for a novel patient, and then map the dose from those atlases onto the novel patient. We extend our previous work to include a conditional random field for the optimization of a joint distribution prior that matches the complementary goals of an accurately spatially distributed dose distribution while still adhering to the desired dose volume histograms. The resulting distribution can then be used for inverse-planning with a new spatial dose objective, or to create typical dose volume objectives for the canonical optimization pipeline. We investigated six treatment sites (633 patients for training and 113 patients for testing) and evaluated the mean absolute difference in all DVHs for the clinical and predicted dose distribution. The results on average are favorable in comparison to our previous approach (1.91 versus 2.57). Comparing our method with and without atlas-selection further validates that atlas-selection improved dose prediction on average in whole breast (0.64 versus 1.59), prostate (2.13 versus 4.07), and rectum (1.46 versus 3.29) while it is less important in breast cavity (0.79 versus 0.92) and lung (1.33 versus 1.27) for which there is high conformity and minimal dose shaping. In CNS brain, atlas-selection has the potential to be impactful (3.65 versus 5.09), but selecting the ideal atlas is the most challenging.

Penalization of aperture complexity in inversely planned volumetric modulated arc therapy

PubMed Central

Younge, Kelly C.; Matuszak, Martha M.; Moran, Jean M.; McShan, Daniel L.; Fraass, Benedick A.; Roberts, Donald A.

2012-01-01

Purpose: Apertures obtained during volumetric modulated arc therapy (VMAT) planning can be small and irregular, resulting in dosimetric inaccuracies during delivery. Our purpose is to develop and integrate an aperture-regularization objective function into the optimization process for VMAT, and to quantify the impact of using this objective function on dose delivery accuracy and optimized dose distributions. Methods: An aperture-based metric (“edge penalty”) was developed that penalizes complex aperture shapes based on the ratio of MLC side edge length and aperture area. To assess the utility of the metric, VMAT plans were created for example paraspinal, brain, and liver SBRT cases with and without incorporating the edge penalty in the cost function. To investigate the dose calculation accuracy, Gafchromic EBT2 film was used to measure the 15 highest weighted apertures individually and as a composite from each of two paraspinal plans: one with and one without the edge penalty applied. Films were analyzed using a triple-channel nonuniformity correction and measurements were compared directly to calculations. Results: Apertures generated with the edge penalty were larger, more regularly shaped and required up to 30% fewer monitor units than those created without the edge penalty. Dose volume histogram analysis showed that the changes in doses to targets, organs at risk, and normal tissues were negligible. Edge penalty apertures that were measured with film for the paraspinal plan showed a notable decrease in the number of pixels disagreeing with calculation by more than 10%. For a 5% dose passing criterion, the number of pixels passing in the composite dose distributions for the non-edge penalty and edge penalty plans were 52% and 96%, respectively. Employing gamma with 3% dose/1 mm distance criteria resulted in a 79.5% (without penalty)/95.4% (with penalty) pass rate for the two plans. Gradient compensation of 3%/1 mm resulted in 83.3%/96.2% pass rates. Conclusions: The use of the edge penalty during optimization has the potential to markedly improve dose delivery accuracy for VMAT plans while still maintaining high quality optimized dose distributions. The penalty regularizes aperture shape and improves delivery efficiency. PMID:23127107

Automatic treatment plan re-optimization for adaptive radiotherapy guided with the initial plan DVHs

NASA Astrophysics Data System (ADS)

Li, Nan; Zarepisheh, Masoud; Uribe-Sanchez, Andres; Moore, Kevin; Tian, Zhen; Zhen, Xin; Jiang Graves, Yan; Gautier, Quentin; Mell, Loren; Zhou, Linghong; Jia, Xun; Jiang, Steve

2013-12-01

Adaptive radiation therapy (ART) can reduce normal tissue toxicity and/or improve tumor control through treatment adaptations based on the current patient anatomy. Developing an efficient and effective re-planning algorithm is an important step toward the clinical realization of ART. For the re-planning process, manual trial-and-error approach to fine-tune planning parameters is time-consuming and is usually considered unpractical, especially for online ART. It is desirable to automate this step to yield a plan of acceptable quality with minimal interventions. In ART, prior information in the original plan is available, such as dose-volume histogram (DVH), which can be employed to facilitate the automatic re-planning process. The goal of this work is to develop an automatic re-planning algorithm to generate a plan with similar, or possibly better, DVH curves compared with the clinically delivered original plan. Specifically, our algorithm iterates the following two loops. An inner loop is the traditional fluence map optimization, in which we optimize a quadratic objective function penalizing the deviation of the dose received by each voxel from its prescribed or threshold dose with a set of fixed voxel weighting factors. In outer loop, the voxel weighting factors in the objective function are adjusted according to the deviation of the current DVH curves from those in the original plan. The process is repeated until the DVH curves are acceptable or maximum iteration step is reached. The whole algorithm is implemented on GPU for high efficiency. The feasibility of our algorithm has been demonstrated with three head-and-neck cancer IMRT cases, each having an initial planning CT scan and another treatment CT scan acquired in the middle of treatment course. Compared with the DVH curves in the original plan, the DVH curves in the resulting plan using our algorithm with 30 iterations are better for almost all structures. The re-optimization process takes about 30 s using our in-house optimization engine. This work was originally presented at the 54th AAPM annual meeting in Charlotte, NC, July 29-August 2, 2012.

On the role of the optimization algorithm of RapidArc(®) volumetric modulated arc therapy on plan quality and efficiency.

PubMed

Vanetti, Eugenio; Nicolini, Giorgia; Nord, Janne; Peltola, Jarkko; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca

2011-11-01

The RapidArc volumetric modulated arc therapy (VMAT) planning process is based on a core engine, the so-called progressive resolution optimizer (PRO). This is the optimization algorithm used to determine the combination of field shapes, segment weights (with dose rate and gantry speed variations), which best approximate the desired dose distribution in the inverse planning problem. A study was performed to assess the behavior of two versions of PRO. These two versions mostly differ in the way continuous variables describing the modulated arc are sampled into discrete control points, in the planning efficiency and in the presence of some new features. The analysis aimed to assess (i) plan quality, (ii) technical delivery aspects, (iii) agreement between delivery and calculations, and (iv) planning efficiency of the two versions. RapidArc plans were generated for four groups of patients (five patients each): anal canal, advanced lung, head and neck, and multiple brain metastases and were designed to test different levels of planning complexity and anatomical features. Plans from optimization with PRO2 (first generation of RapidArc optimizer) were compared against PRO3 (second generation of the algorithm). Additional plans were optimized with PRO3 using new features: the jaw tracking, the intermediate dose and the air cavity correction options. Results showed that (i) plan quality was generally improved with PRO3 and, although not for all parameters, some of the scored indices showed a macroscopic improvement with PRO3. (ii) PRO3 optimization leads to simpler patterns of the dynamic parameters particularly for dose rate. (iii) No differences were observed between the two algorithms in terms of pretreatment quality assurance measurements and (iv) PRO3 optimization was generally faster, with a time reduction of a factor approximately 3.5 with respect to PRO2. These results indicate that PRO3 is either clinically beneficial or neutral in terms of dosimetric quality while it showed significant advantages in speed and technical aspects.

Reliability Methods for Shield Design Process

NASA Technical Reports Server (NTRS)

Tripathi, R. K.; Wilson, J. W.

2002-01-01

Providing protection against the hazards of space radiation is a major challenge to the exploration and development of space. The great cost of added radiation shielding is a potential limiting factor in deep space operations. In this enabling technology, we have developed methods for optimized shield design over multi-segmented missions involving multiple work and living areas in the transport and duty phase of space missions. The total shield mass over all pieces of equipment and habitats is optimized subject to career dose and dose rate constraints. An important component of this technology is the estimation of two most commonly identified uncertainties in radiation shield design, the shielding properties of materials used and the understanding of the biological response of the astronaut to the radiation leaking through the materials into the living space. The largest uncertainty, of course, is in the biological response to especially high charge and energy (HZE) ions of the galactic cosmic rays. These uncertainties are blended with the optimization design procedure to formulate reliability-based methods for shield design processes. The details of the methods will be discussed.

Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

NASA Astrophysics Data System (ADS)

Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

2013-06-01

In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less smoothing at early time points post-radiopharmaceutical administration but more smoothing and fewer iterations at later time points when the total organ activity was lower. The results of this study demonstrate the importance of using optimal reconstruction and regularization parameters. Optimal results were obtained with different parameters at each time point, but using a single set of parameters for all time points produced near-optimal dose-volume histograms.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-01-01

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

PubMed

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

PubMed Central

Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. PMID:28740389

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity.

PubMed

Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD.

Pharmacometric Approaches to Personalize Use of Primarily Renally Eliminated Antibiotics in Preterm and Term Neonates.

PubMed

Wilbaux, Mélanie; Fuchs, Aline; Samardzic, Janko; Rodieux, Frédérique; Csajka, Chantal; Allegaert, Karel; van den Anker, Johannes N; Pfister, Marc

2016-08-01

Sepsis remains a major cause of mortality and morbidity in neonates, and, as a consequence, antibiotics are the most frequently prescribed drugs in this vulnerable patient population. Growth and dynamic maturation processes during the first weeks of life result in large inter- and intrasubject variability in the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics. In this review we (1) summarize the available population PK data and models for primarily renally eliminated antibiotics, (2) discuss quantitative approaches to account for effects of growth and maturation processes on drug exposure and response, (3) evaluate current dose recommendations, and (4) identify opportunities to further optimize and personalize dosing strategies of these antibiotics in preterm and term neonates. Although population PK models have been developed for several of these drugs, exposure-response relationships of primarily renally eliminated antibiotics in these fragile infants are not well understood, monitoring strategies remain inconsistent, and consensus on optimal, personalized dosing of these drugs in these patients is absent. Tailored PK/PD studies and models are useful to better understand relationships between drug exposures and microbiological or clinical outcomes. Pharmacometric modeling and simulation approaches facilitate quantitative evaluation and optimization of treatment strategies. National and international collaborations and platforms are essential to standardize and harmonize not only studies and models but also monitoring and dosing strategies. Simple bedside decision tools assist clinical pharmacologists and neonatologists in their efforts to fine-tune and personalize the use of primarily renally eliminated antibiotics in term and preterm neonates. © 2016, The American College of Clinical Pharmacology.

Optimization of the sensitivity/doses relationship for a bench-top EDXRF system used for in vivo quantification of gold nanoparticles.

PubMed

Santibáñez, M; Saavedra, R; Vásquez, M; Malano, F; Pérez, P; Valente, M; Figueroa, R G

2017-11-01

The present work is devoted to optimizing the sensitivity-doses relationship of a bench-top EDXRF system, with the aim of achieving a detection limit of 0.010mg/ml of gold nanoparticles in tumor tissue (clinical values expected), for doses below 10mGy (value fixed for in vivo application). Tumor phantoms of 0.3cm 3 made of a suspension of gold nanoparticles (15nm AurovistTM, Nanoprobes Inc.) were studied at depths of 0-4mm in a tissue equivalent cylindrical phantom. The optimization process was implemented configuring several tube voltages and aluminum filters, to obtain non-symmetrical narrow spectra with fixed FWHM of 5keV and centered among the 11.2-20.3keV. The used statistical figure of merit was the obtained sensitivity (with each spectrum at each depth) weighted by the delivered surface doses. The detection limit of the system was determined measuring several gold nanoparticles concentrations ranging from 0.0010 to 5.0mg/ml and a blank sample into tumor phantoms, considering a statistical fluctuation within 95% of confidence. The results show the possibility of obtaining a detection limit for gold nanoparticles concentrations around 0.010mg/ml for surface tumor phantoms requiring doses around 2mGy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spatial frequency performance limitations of radiation dose optimization and beam positioning

NASA Astrophysics Data System (ADS)

Stewart, James M. P.; Stapleton, Shawn; Chaudary, Naz; Lindsay, Patricia E.; Jaffray, David A.

2018-06-01

The flexibility and sophistication of modern radiotherapy treatment planning and delivery methods have advanced techniques to improve the therapeutic ratio. Contemporary dose optimization and calculation algorithms facilitate radiotherapy plans which closely conform the three-dimensional dose distribution to the target, with beam shaping devices and image guided field targeting ensuring the fidelity and accuracy of treatment delivery. Ultimately, dose distribution conformity is limited by the maximum deliverable dose gradient; shallow dose gradients challenge techniques to deliver a tumoricidal radiation dose while minimizing dose to surrounding tissue. In this work, this ‘dose delivery resolution’ observation is rigorously formalized for a general dose delivery model based on the superposition of dose kernel primitives. It is proven that the spatial resolution of a delivered dose is bounded by the spatial frequency content of the underlying dose kernel, which in turn defines a lower bound in the minimization of a dose optimization objective function. In addition, it is shown that this optimization is penalized by a dose deposition strategy which enforces a constant relative phase (or constant spacing) between individual radiation beams. These results are further refined to provide a direct, analytic method to estimate the dose distribution arising from the minimization of such an optimization function. The efficacy of the overall framework is demonstrated on an image guided small animal microirradiator for a set of two-dimensional hypoxia guided dose prescriptions.

SU-C-BRB-02: Symmetric and Asymmetric MLC Based Lung Shielding and Dose Optimization During Translating Bed TBI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, S; Kakakhel, MB; Ahmed, SBS

2015-06-15

Purpose: The primary aim was to introduce a dose optimization method for translating bed total body irradiation technique that ensures lung shielding dynamically. Symmetric and asymmetric dynamic MLC apertures were employed for this purpose. Methods: The MLC aperture sizes were defined based on the radiological depth values along the divergent ray lines passing through the individual CT slices. Based on these RD values, asymmetrically shaped MLC apertures were defined every 9 mm of the phantom in superior-inferior direction. Individual MLC files were created with MATLAB™ and were imported into Eclipse™ treatment planning system for dose calculations. Lungs can be shieldedmore » to an optimum level by reducing the MLC aperture width over the lungs. The process was repeated with symmetrically shaped apertures. Results: Dose-volume histogram (DVH) analysis shows that the asymmetric MLC based technique provides better dose coverage to the body and optimum shielding of the lungs compared to symmetrically shaped beam apertures. Midline dose homogeneity is within ±3% with asymmetric MLC apertures whereas it remains within ±4.5% with symmetric ones (except head region where it drops down to −7%). The substantial over and under dosage of ±5% at tissue interfaces has been reduced to ±2% with asymmetric MLC technique. Lungs dose can be reduced to any desired limit. In this experiment lungs dose was reduced to 80% of the prescribed dose, as was desired. Conclusion: The novel asymmetric MLC based technique assures optimum shielding of OARs (e.g. lungs) and better 3-D dose homogeneity and body-dose coverage in comparison with the symmetric MLC aperture optimization. The authors acknowledge the financial and infrastructural support provided by Pakistan Institute of Engineering & Applied Sciences (PIEAS), Islamabad and Aga Khan University Hospital (AKUH), Karachi during the course of this research project. Authors have no conflict of interest with any national / international body for the presented work.« less

SU-F-T-380: Comparing the Effect of Respiration On Dose Distribution Between Conventional Tangent Pair and IMRT Techniques for Adjuvant Radiotherapy in Early Stage Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, M; Ramaseshan, R

2016-06-15

Purpose: In this project, we compared the conventional tangent pair technique to IMRT technique by analyzing the dose distribution. We also investigated the effect of respiration on planning target volume (PTV) dose coverage in both techniques. Methods: In order to implement IMRT technique a template based planning protocol, dose constrains and treatment process was developed. Two open fields with optimized field weights were combined with two beamlet optimization fields in IMRT plans. We compared the dose distribution between standard tangential pair and IMRT. The improvement in dose distribution was measured by parameters such as conformity index, homogeneity index and coveragemore » index. Another end point was the IMRT technique will reduce the planning time for staff. The effect of patient’s respiration on dose distribution was also estimated. The four dimensional computed tomography (4DCT) for different phase of breathing cycle was used to evaluate the effect of respiration on IMRT planned dose distribution. Results: We have accumulated 10 patients that acquired 4DCT and planned by both techniques. Based on the preliminary analysis, the dose distribution in IMRT technique was better than conventional tangent pair technique. Furthermore, the effect of respiration in IMRT plan was not significant as evident from the 95% isodose line coverage of PTV drawn on all phases of 4DCT. Conclusion: Based on the 4DCT images, the breathing effect on dose distribution was smaller than what we expected. We suspect that there are two reasons. First, the PTV movement due to respiration was not significant. It might be because we used a tilted breast board to setup patients. Second, the open fields with optimized field weights in IMRT technique might reduce the breathing effect on dose distribution. A further investigation is necessary.« less

Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort.

PubMed

Gaujoux-Viala, Cécile; Rincheval, Nathalie; Dougados, Maxime; Combe, Bernard; Fautrel, Bruno

2017-12-01

Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

SU-F-T-195: Systematic Constraining of Contralateral Parotid Gland Led to Improved Dosimetric Outcomes for Multi-Field Optimization with Scanning Beam Proton Therapy: Promising Results From a Pilot Study in Patients with Base of Tongue Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, R; Liu, A; Poenisch, F

Purpose: Treatment planning for Intensity Modulated Proton Therapy (IMPT) for head and neck cancer is time-consuming due to the large number of organs-at-risk (OAR) to be considered. As there are many competing objectives and also wide range of acceptable OAR constraints, the final approved plan may not be most optimal for the given structures. We evaluated the dose reduction to the contralateral parotid by implementing standardized constraints during optimization for scanning beam proton therapy planning. Methods: Twenty-four (24) consecutive patients previously treated for base of tongue carcinoma were retrospectively selected. The doses were 70Gy, 63Gy and 57Gy (SIB in 33more » fractions) for high-, intermediate-, and standard-risk clinical target volumes (CTV), respectively; the treatment included bilateral neck. Scanning beams using MFO with standardized bilateral anterior oblique and PA fields were applied. New plans where then developed and optimized by employing additional contralateral parotid constraints at multiple defined dose levels. Using a step-wise iterative process, the volume-based constraints at each level were then further reduced until known target coverages were compromised. The newly developed plans were then compared to the original clinically approved plans using paired student t-testing. Results: All 24 newly optimized treatment plans maintained initial plan quality as compared to the approved plans, and the 98% prescription dose coverage to the CTV’s were not compromised. Representative DVH comparison is shown in FIGURE 1. The contralateral parotid doses were reduced at all levels of interest when systematic constraints were applied to V10, V20, V30 and V40Gy (All P<0.0001; TABLE 1). Overall, the mean contralateral parotid doses were reduced by 2.26 Gy on average, a ∼13% relative improvement. Conclusion: Applying systematic and volume-based contralateral parotid constraints for IMPT planning significantly reduced the dose at all dosimetric levels for patients with base of tongue cancer.« less

SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul; Park, H

Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from themore » whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP) (Grant No. 200900420)« less

Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions.

PubMed

Hassan, Sally; Simaria, Ana S; Varadaraju, Hemanthram; Gupta, Siddharth; Warren, Kim; Farid, Suzanne S

2015-01-01

To develop a decisional tool to identify the most cost effective process flowsheets for allogeneic cell therapies across a range of production scales. A bioprocess economics and optimization tool was built to assess competing cell expansion and downstream processing (DSP) technologies. Tangential flow filtration was generally more cost-effective for the lower cells/lot achieved in planar technologies and fluidized bed centrifugation became the only feasible option for handling large bioreactor outputs. DSP bottlenecks were observed at large commercial lot sizes requiring multiple large bioreactors. The DSP contribution to the cost of goods/dose ranged between 20-55%, and 50-80% for planar and bioreactor flowsheets, respectively. This analysis can facilitate early decision-making during process development.

Open-label dose optimization of methylphenidate modified release long acting (MPH-LA): a post hoc analysis of real-life titration from a 40-week randomized trial.

PubMed

Huss, Michael; Ginsberg, Ylva; Arngrim, Torben; Philipsen, Alexandra; Carter, Katherine; Chen, Chien-Wei; Gandhi, Preetam; Kumar, Vinod

2014-09-01

In the management of attention-deficit hyperactivity disorder (ADHD) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses. Studies with methylphenidate modified release long acting (MPH-LA) in children have reported the need for treatment optimization for improved outcomes. We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized, placebo-controlled, multicenter 40-week study (9-week double-blind dose confirmation phase, 5-week open-label dose optimization phase, and 26-week double-blind maintenance of effect phase). Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day; up/down titrated to their optimal dose (at which there was balance between control of symptoms and side effects) of 40, 60, or 80 mg/day in increments of 20 mg/week by week 12 or 13. Safety was assessed by monitoring the adverse events (AEs) and serious AEs. Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Attention-Deficit Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores. At the end of the dose confirmation phase, similar numbers of patients were treated optimally with each of the 40, 60, and 80 mg/day doses (152, 177, and 160, respectively) for MPH-LA. Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 ± 9.90 and 9.7 ± 7.36, respectively. Dose optimization with MPH-LA (40, 60, or 80 mg/day) improved treatment outcomes and was well-tolerated in adult ADHD patients.

Optimization of light source parameters in the photodynamic therapy of heterogeneous prostate

NASA Astrophysics Data System (ADS)

Li, Jun; Altschuler, Martin D.; Hahn, Stephen M.; Zhu, Timothy C.

2008-08-01

The three-dimensional (3D) heterogeneous distributions of optical properties in a patient prostate can now be measured in vivo. Such data can be used to obtain a more accurate light-fluence kernel. (For specified sources and points, the kernel gives the fluence delivered to a point by a source of unit strength.) In turn, the kernel can be used to solve the inverse problem that determines the source strengths needed to deliver a prescribed photodynamic therapy (PDT) dose (or light-fluence) distribution within the prostate (assuming uniform drug concentration). We have developed and tested computational procedures to use the new heterogeneous data to optimize delivered light-fluence. New problems arise, however, in quickly obtaining an accurate kernel following the insertion of interstitial light sources and data acquisition. (1) The light-fluence kernel must be calculated in 3D and separately for each light source, which increases kernel size. (2) An accurate kernel for light scattering in a heterogeneous medium requires ray tracing and volume partitioning, thus significant calculation time. To address these problems, two different kernels were examined and compared for speed of creation and accuracy of dose. Kernels derived more quickly involve simpler algorithms. Our goal is to achieve optimal dose planning with patient-specific heterogeneous optical data applied through accurate kernels, all within clinical times. The optimization process is restricted to accepting the given (interstitially inserted) sources, and determining the best source strengths with which to obtain a prescribed dose. The Cimmino feasibility algorithm is used for this purpose. The dose distribution and source weights obtained for each kernel are analyzed. In clinical use, optimization will also be performed prior to source insertion to obtain initial source positions, source lengths and source weights, but with the assumption of homogeneous optical properties. For this reason, we compare the results from heterogeneous optical data with those obtained from average homogeneous optical properties. The optimized treatment plans are also compared with the reference clinical plan, defined as the plan with sources of equal strength, distributed regularly in space, which delivers a mean value of prescribed fluence at detector locations within the treatment region. The study suggests that comprehensive optimization of source parameters (i.e. strengths, lengths and locations) is feasible, thus allowing acceptable dose coverage in a heterogeneous prostate PDT within the time constraints of the PDT procedure.

Evaluation of an artificial intelligence guided inverse planning system: clinical case study.

PubMed

Yan, Hui; Yin, Fang-Fang; Willett, Christopher

2007-04-01

An artificial intelligence (AI) guided method for parameter adjustment of inverse planning was implemented on a commercial inverse treatment planning system. For evaluation purpose, four typical clinical cases were tested and the results from both plans achieved by automated and manual methods were compared. The procedure of parameter adjustment mainly consists of three major loops. Each loop is in charge of modifying parameters of one category, which is carried out by a specially customized fuzzy inference system. A physician prescribed multiple constraints for a selected volume were adopted to account for the tradeoff between prescription dose to the PTV and dose-volume constraints for critical organs. The searching process for an optimal parameter combination began with the first constraint, and proceeds to the next until a plan with acceptable dose was achieved. The initial setup of the plan parameters was the same for each case and was adjusted independently by both manual and automated methods. After the parameters of one category were updated, the intensity maps of all fields were re-optimized and the plan dose was subsequently re-calculated. When final plan arrived, the dose statistics were calculated from both plans and compared. For planned target volume (PTV), the dose for 95% volume is up to 10% higher in plans using the automated method than those using the manual method. For critical organs, an average decrease of the plan dose was achieved. However, the automated method cannot improve the plan dose for some critical organs due to limitations of the inference rules currently employed. For normal tissue, there was no significant difference between plan doses achieved by either automated or manual method. With the application of AI-guided method, the basic parameter adjustment task can be accomplished automatically and a comparable plan dose was achieved in comparison with that achieved by the manual method. Future improvements to incorporate case-specific inference rules are essential to fully automate the inverse planning process.

SU-E-J-126: An Online Replanning Method for FFF Beams Without Couch Shift

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahunbay, E; Ates, O; Li, X

2015-06-15

Purpose: In a situation that couch shift for patient positioning is not preferred or prohibited (e.g., MR-Linac), segment aperture morphing (SAM) can address target dislocation and deformation. For IMRT/VMAT with flattening filter free (FFF) beams, however, SAM method would lead to an adverse translational dose effect due to the beam unflattening. Here we propose a new 2-step process to address both the translational effect of FFF beams and the target deformation. Methods: The replanning method consists of an offline and an online steps. The offline step is to create a series of pre-shifted plans (PSP) obtained by a so calledmore » “warm start” optimization (starting optimization from the original plan, rather from scratch) at a series of isocenter shifts with fixed distance (e.g. 2 cm, at x,y,z = 2,0,0 ; 2,2,0 ; 0,2,0; …;− 2,0,0). The PSPs all have the same number of segments with very similar shapes, since the warm-start optimization only adjusts the MLC positions instead of regenerating them. In the online step, a new plan is obtained by linearly interpolating the MLC positions and the monitor units of the closest PSPs for the shift determined from the image of the day. This two-step process is completely automated, and instantaneously fast (no optimization or dose calculation needed). The previously-developed SAM algorithm is then applied for daily deformation. We tested the method on sample prostate and pancreas cases. Results: The two-step interpolation method can account for the adverse dose effects from FFF beams, while SAM corrects for the target deformation. The whole process takes the same time as the previously reported SAM process (5–10 min). Conclusion: The new two-step method plus SAM can address both the translation effects of FFF beams and target deformation, and can be executed in full automation requiring no additional time from the SAM process. This research was supported by Elekta inc. (Crawley, UK)« less

Multi-GPU configuration of 4D intensity modulated radiation therapy inverse planning using global optimization

NASA Astrophysics Data System (ADS)

Hagan, Aaron; Sawant, Amit; Folkerts, Michael; Modiri, Arezoo

2018-01-01

We report on the design, implementation and characterization of a multi-graphic processing unit (GPU) computational platform for higher-order optimization in radiotherapy treatment planning. In collaboration with a commercial vendor (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We demonstrate the utility of this platform for large radiotherapy optimization problems through the development and characterization of a parallelized particle swarm optimization (PSO) four dimensional (4D) intensity modulated radiation therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment planning system via a vendor-provided scripting interface. Specific challenges addressed in this implementation were (i) data management and (ii) non-uniform memory access (NUMA). For the former, we alternated between parameters over which the computation process was parallelized. For the latter, we reduced the amount of data required to be transferred over the NUMA bridge. The datasets examined in this study were approximately 300 GB in size, including 4D computed tomography images, anatomical structure contours and dose deposition matrices. For evaluation, we created a 4D-IMRT treatment plan for one lung cancer patient and analyzed computation speed while varying several parameters (number of respiratory phases, GPUs, PSO particles, and data matrix sizes). The optimized 4D-IMRT plan enhanced sparing of organs at risk by an average reduction of 26% in maximum dose, compared to the clinical optimized IMRT plan, where the internal target volume was used. We validated our computation time analyses in two additional cases. The computation speed in our implementation did not monotonically increase with the number of GPUs. The optimal number of GPUs (five, in our study) is directly related to the hardware specifications. The optimization process took 35 min using 50 PSO particles, 25 iterations and 5 GPUs.

Multi-GPU configuration of 4D intensity modulated radiation therapy inverse planning using global optimization.

PubMed

Hagan, Aaron; Sawant, Amit; Folkerts, Michael; Modiri, Arezoo

2018-01-16

We report on the design, implementation and characterization of a multi-graphic processing unit (GPU) computational platform for higher-order optimization in radiotherapy treatment planning. In collaboration with a commercial vendor (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We demonstrate the utility of this platform for large radiotherapy optimization problems through the development and characterization of a parallelized particle swarm optimization (PSO) four dimensional (4D) intensity modulated radiation therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment planning system via a vendor-provided scripting interface. Specific challenges addressed in this implementation were (i) data management and (ii) non-uniform memory access (NUMA). For the former, we alternated between parameters over which the computation process was parallelized. For the latter, we reduced the amount of data required to be transferred over the NUMA bridge. The datasets examined in this study were approximately 300 GB in size, including 4D computed tomography images, anatomical structure contours and dose deposition matrices. For evaluation, we created a 4D-IMRT treatment plan for one lung cancer patient and analyzed computation speed while varying several parameters (number of respiratory phases, GPUs, PSO particles, and data matrix sizes). The optimized 4D-IMRT plan enhanced sparing of organs at risk by an average reduction of [Formula: see text] in maximum dose, compared to the clinical optimized IMRT plan, where the internal target volume was used. We validated our computation time analyses in two additional cases. The computation speed in our implementation did not monotonically increase with the number of GPUs. The optimal number of GPUs (five, in our study) is directly related to the hardware specifications. The optimization process took 35 min using 50 PSO particles, 25 iterations and 5 GPUs.

Optimal design of clinical trials with biologics using dose-time-response models.

PubMed

Lange, Markus R; Schmidli, Heinz

2014-12-30

Biologics, in particular monoclonal antibodies, are important therapies in serious diseases such as cancer, psoriasis, multiple sclerosis, or rheumatoid arthritis. While most conventional drugs are given daily, the effect of monoclonal antibodies often lasts for months, and hence, these biologics require less frequent dosing. A good understanding of the time-changing effect of the biologic for different doses is needed to determine both an adequate dose and an appropriate time-interval between doses. Clinical trials provide data to estimate the dose-time-response relationship with semi-mechanistic nonlinear regression models. We investigate how to best choose the doses and corresponding sample size allocations in such clinical trials, so that the nonlinear dose-time-response model can be precisely estimated. We consider both local and conservative Bayesian D-optimality criteria for the design of clinical trials with biologics. For determining the optimal designs, computer-intensive numerical methods are needed, and we focus here on the particle swarm optimization algorithm. This metaheuristic optimizer has been successfully used in various areas but has only recently been applied in the optimal design context. The equivalence theorem is used to verify the optimality of the designs. The methodology is illustrated based on results from a clinical study in patients with gout, treated by a monoclonal antibody. Copyright © 2014 John Wiley & Sons, Ltd.

Nano-SiC region formation in (100) Si-on-insulator substrate: Optimization of hot-C+-ion implantation process to improve photoluminescence intensity

NASA Astrophysics Data System (ADS)

Mizuno, Tomohisa; Omata, Yuhsuke; Kanazawa, Rikito; Iguchi, Yusuke; Nakada, Shinji; Aoki, Takashi; Sasaki, Tomokazu

2018-04-01

We experimentally studied the optimization of the hot-C+-ion implantation process for forming nano-SiC (silicon carbide) regions in a (100) Si-on-insulator substrate at various hot-C+-ion implantation temperatures and C+ ion doses to improve photoluminescence (PL) intensity for future Si-based photonic devices. We successfully optimized the process by hot-C+-ion implantation at a temperature of about 700 °C and a C+ ion dose of approximately 4 × 1016 cm-2 to realize a high intensity of PL emitted from an approximately 1.5-nm-thick C atom segregation layer near the surface-oxide/Si interface. Moreover, atom probe tomography showed that implanted C atoms cluster in the Si layer and near the oxide/Si interface; thus, the C content locally condenses even in the C atom segregation layer, which leads to SiC formation. Corrector-spherical aberration transmission electron microscopy also showed that both 4H-SiC and 3C-SiC nanoareas near both the surface-oxide/Si and buried-oxide/Si interfaces partially grow into the oxide layer, and the observed PL photons are mainly emitted from the surface SiC nano areas.

Kinetic modeling of simultaneous saccharification and fermentation of corn starch for ethanol production.

PubMed

Białas, Wojciech; Czerniak, Adrian; Szymanowska-Powałowska, Daria

2014-01-01

Fuel ethanol production, using a simultaneous saccharification and fermentation process (SSF) of native starch from corn flour, has been performed using Saccharomyces cerevisiae and a granular starch hydrolyzing enzyme. The quantitative effects of mash concentration, enzyme dose and pH were investigated with the use of a Box-Wilson central composite design protocol. Proceeding from results obtained in optimal fermentation conditions, a kinetics model relating the utilization rates of starch and glucose as well as the production rates of ethanol and biomass was tested. Moreover, scanning electron microscopy (SEM) was applied to investigate corn starch granule surface after the SFF process. A maximum ethanol concentration of 110.36 g/l was obtained for native corn starch using a mash concentration of 25%, which resulted in ethanol yield of 85.71%. The optimal conditions for the above yield were found with an enzyme dose of 2.05 ml/kg and pH of 5.0. These results indicate that by using a central composite design, it is possible to determine optimal values of the fermentation parameters for maximum ethanol production. The investigated kinetics model can be used to describe SSF process conducted with granular starch hydrolyzing enzymes. The SEM micrographs reveal randomly distributed holes on the surface of granules.

Multiple-Objective Optimal Designs for Studying the Dose Response Function and Interesting Dose Levels

PubMed Central

Hyun, Seung Won; Wong, Weng Kee

2016-01-01

We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs. PMID:26565557

Multiple-Objective Optimal Designs for Studying the Dose Response Function and Interesting Dose Levels.

PubMed

Hyun, Seung Won; Wong, Weng Kee

2015-11-01

We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs.

WE-AB-303-06: Combining DAO with MV + KV Optimization to Improve Skin Dose Sparing with Real-Time Fluoroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grelewicz, Z; Wiersma, R

Purpose: Real-time fluoroscopy may allow for improved patient positioning and tumor tracking, particularly in the treatment of lung tumors. In order to mitigate the effects of the imaging dose, previous studies have demonstrated the effect of including both imaging dose and imaging constraints into the inverse treatment planning object function. That method of combined MV+kV optimization may Result in plans with treatment beams chosen to allow for more gentle imaging beam-on times. Direct-aperture optimization (DAO) is also known to produce treatment plans with fluence maps more conducive to lower beam-on times. Therefore, in this work we demonstrate the feasibility ofmore » a combination of DAO and MV+kV optimization for further optimized real-time kV imaging. Methods: Therapeutic and imaging beams were modeled in the EGSnrc Monte Carlo environment, and applied to a patient model for a previously treated lung patient to provide dose influence matrices from DOSXYZnrc. An MV + kV IMRT DAO treatment planning system was developed to compare DAO treatment plans with and without MV+kV optimization. The objective function was optimized using simulated annealing. In order to allow for comparisons between different cases of the stochastically optimized plans, the optimization was repeated twenty times. Results: Across twenty optimizations, combined MV+kV IMRT resulted in an average of 12.8% reduction in peak skin dose. Both non-optimized and MV+kV optimized imaging beams delivered, on average, mean dose of approximately 1 cGy per fraction to the target, with peak doses to target of approximately 6 cGy per fraction. Conclusion: When using DAO, MV+kV optimization is shown to Result in improvements to plan quality in terms of skin dose, when compared to the case of MV optimization with non-optimized kV imaging. The combination of DAO and MV+kV optimization may allow for real-time imaging without excessive imaging dose. Financial support for the work has been provided in part by NIH Grant T32 EB002103, ACS RSG-13-313-01-CCE, and NIH S10 RR021039 and P30 CA14599 grants. The contents of this submission do not necessarily represent the official views of any of the supporting organizations.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X; Wang, J; Hu, W

Purpose: The Varian RapidPlan™ is a commercial knowledge-based optimization process which uses a set of clinically used treatment plans to train a model that can predict individualized dose-volume objectives. The purpose of this study is to evaluate the performance of RapidPlan to generate intensity modulated radiation therapy (IMRT) plans for cervical cancer. Methods: Totally 70 IMRT plans for cervical cancer with varying clinical and physiological indications were enrolled in this study. These patients were all previously treated in our institution. There were two prescription levels usually used in our institution: 45Gy/25 fractions and 50.4Gy/28 fractions. 50 of these plans weremore » selected to train the RapidPlan model for predicting dose-volume constraints. After model training, this model was validated with 10 plans from training pool(internal validation) and additional other 20 new plans(external validation). All plans used for the validation were re-optimized with the original beam configuration and the generated priorities from RapidPlan were manually adjusted to ensure that re-optimized DVH located in the range of the model prediction. DVH quantitative analysis was performed to compare the RapidPlan generated and the original manual optimized plans. Results: For all the validation cases, RapidPlan based plans (RapidPlan) showed similar or superior results compared to the manual optimized ones. RapidPlan increased the result of D98% and homogeneity in both two validations. For organs at risk, the RapidPlan decreased mean doses of bladder by 1.25Gy/1.13Gy (internal/external validation) on average, with p=0.12/p<0.01. The mean dose of rectum and bowel were also decreased by an average of 2.64Gy/0.83Gy and 0.66Gy/1.05Gy,with p<0.01/ p<0.01and p=0.04/<0.01 for the internal/external validation, respectively. Conclusion: The RapidPlan model based cervical cancer plans shows ability to systematically improve the IMRT plan quality. It suggests that RapidPlan has great potential to make the treatment planning process more efficient.« less

Optimization for high-dose-rate brachytherapy of cervical cancer with adaptive simulated annealing and gradient descent.

PubMed

Yao, Rui; Templeton, Alistair K; Liao, Yixiang; Turian, Julius V; Kiel, Krystyna D; Chu, James C H

2014-01-01

To validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)-based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer. Eight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose-volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program. The ASA plans are higher on bladder V75% and D2cc (p=0.034) and lower on rectum V75% and D2cc (p=0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p=0.034), lower overdose index (p=0.005), and lower rectum gEUD and normal tissue complication probability (p=0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose-volume histogram could have different dose distributions. Our optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Automated medial axis seeding and guided evolutionary simulated annealing for optimization of gamma knife radiosurgery treatment plans

NASA Astrophysics Data System (ADS)

Zhang, Pengpeng

The Leksell Gamma KnifeRTM (LGK) is a tool for providing accurate stereotactic radiosurgical treatment of brain lesions, especially tumors. Currently, the treatment planning team "forward" plans radiation treatment parameters while viewing a series of 2D MR scans. This primarily manual process is cumbersome and time consuming because the difficulty in visualizing the large search space for the radiation parameters (i.e., shot overlap, number, location, size, and weight). I hypothesize that a computer-aided "inverse" planning procedure that utilizes tumor geometry and treatment goals could significantly improve the planning process and therapeutic outcome of LGK radiosurgery. My basic observation is that the treatment team is best at identification of the location of the lesion and prescribing a lethal, yet safe, radiation dose. The treatment planning computer is best at determining both the 3D tumor geometry and optimal LGK shot parameters necessary to deliver a desirable dose pattern to the tumor while sparing adjacent normal tissue. My treatment planning procedure asks the neurosurgeon to identify the tumor and critical structures in MR images and the oncologist to prescribe a tumoricidal radiation dose. Computer-assistance begins with geometric modeling of the 3D tumor's medial axis properties. This begins with a new algorithm, a Gradient-Phase Plot (G-P Plot) decomposition of the tumor object's medial axis. I have found that medial axis seeding, while insufficient in most cases to produce an acceptable treatment plan, greatly reduces the solution space for Guided Evolutionary Simulated Annealing (GESA) treatment plan optimization by specifying an initial estimate for shot number, size, and location, but not weight. They are used to generate multiple initial plans which become initial seed plans for GESA. The shot location and weight parameters evolve and compete in the GESA procedure. The GESA objective function optimizes tumor irradiation (i.e., as close to the prescribed dose as possible) and minimizes normal tissue and critical structure damage. In tests of five patient data sets (4 acoustic neuromas and 1 meningioma), the G-P Plot/GESA-generated treatment plans improved conformality of the lethal dose to the tumor, required no human interaction, improved dose homogeneity, suggested use of fewer shots, and reduced treatment administration time.

TU-EF-204-09: A Preliminary Method of Risk-Informed Optimization of Tube Current Modulation for Dose Reduction in CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Y; Liu, B; Kalra, M

Purpose: X-rays from CT scans can increase cancer risk to patients. Lifetime Attributable Risk of Cancer Incidence for adult patients has been investigated and shown to decrease as patient age. However, a new risk model shows an increasing risk trend for several radiosensitive organs for middle age patients. This study investigates the feasibility of a general method for optimizing tube current modulation (TCM) functions to minimize risk by reducing radiation dose to radiosensitive organs of patients. Methods: Organ-based TCM has been investigated in literature for eye lens dose and breast dose. Adopting the concept in organ-based TCM, this study seeksmore » to find an optimized tube current for minimal total risk to breasts and lungs by reducing dose to these organs. The contributions of each CT view to organ dose are determined through simulations of CT scan view-by-view using a GPU-based fast Monte Carlo code, ARCHER. A Linear Programming problem is established for tube current optimization, with Monte Carlo results as weighting factors at each view. A pre-determined dose is used as upper dose boundary, and tube current of each view is optimized to minimize the total risk. Results: An optimized tube current is found to minimize the total risk of lungs and breasts: compared to fixed current, the risk is reduced by 13%, with breast dose reduced by 38% and lung dose reduced by 7%. The average tube current is maintained during optimization to maintain image quality. In addition, dose to other organs in chest region is slightly affected, with relative change in dose smaller than 10%. Conclusion: Optimized tube current plans can be generated to minimize cancer risk to lungs and breasts while maintaining image quality. In the future, various risk models and greater number of projections per rotation will be simulated on phantoms of different gender and age. National Institutes of Health R01EB015478.« less

Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy.

PubMed

Svensson, Elin M; Yngman, Gunnar; Denti, Paolo; McIlleron, Helen; Kjellsson, Maria C; Karlsson, Mats O

2018-05-01

Fixed-dose combination formulations where several drugs are included in one tablet are important for the implementation of many long-term multidrug therapies. The selection of optimal dose ratios and tablet content of a fixed-dose combination and the design of individualized dosing regimens is a complex task, requiring multiple simultaneous considerations. In this work, a methodology for the rational design of a fixed-dose combination was developed and applied to the case of a three-drug pediatric anti-tuberculosis formulation individualized on body weight. The optimization methodology synthesizes information about the intended use population, the pharmacokinetic properties of the drugs, therapeutic targets, and practical constraints. A utility function is included to penalize deviations from the targets; a sequential estimation procedure was developed for stable estimation of break-points for individualized dosing. The suggested optimized pediatric anti-tuberculosis fixed-dose combination was compared with the recently launched World Health Organization-endorsed formulation. The optimized fixed-dose combination included 15, 36, and 16% higher amounts of rifampicin, isoniazid, and pyrazinamide, respectively. The optimized fixed-dose combination is expected to result in overall less deviation from the therapeutic targets based on adult exposure and substantially fewer children with underexposure (below half the target). The development of this design tool can aid the implementation of evidence-based formulations, integrating available knowledge and practical considerations, to optimize drug exposures and thereby treatment outcomes.

MO-G-18A-01: Radiation Dose Reducing Strategies in CT, Fluoroscopy and Radiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahesh, M; Gingold, E; Jones, A

2014-06-15

Advances in medical x-ray imaging have provided significant benefits to patient care. According to NCRP 160, there are more than 400 million x-ray procedures performed annually in the United States alone that contributes to nearly half of all the radiation exposure to the US population. Similar growth trends in medical x-ray imaging are observed worldwide. Apparent increase in number of medical x-ray imaging procedures, new protocols and the associated radiation dose and risk has drawn considerable attention. This has led to a number of technological innovations such as tube current modulation, iterative reconstruction algorithms, dose alerts, dose displays, flat panelmore » digital detectors, high efficient digital detectors, storage phosphor radiography, variable filters, etc. that are enabling users to acquire medical x-ray images at a much lower radiation dose. Along with these, there are number of radiation dose optimization strategies that users can adapt to effectively lower radiation dose in medical x-ray procedures. The main objectives of this SAM course are to provide information and how to implement the various radiation dose optimization strategies in CT, Fluoroscopy and Radiography. Learning Objectives: To update impact of technological advances on dose optimization in medical imaging. To identify radiation optimization strategies in computed tomography. To describe strategies for configuring fluoroscopic equipment that yields optimal images at reasonable radiation dose. To assess ways to configure digital radiography systems and recommend ways to improve image quality at optimal dose.« less

Robust resolution enhancement optimization methods to process variations based on vector imaging model

NASA Astrophysics Data System (ADS)

Ma, Xu; Li, Yanqiu; Guo, Xuejia; Dong, Lisong

2012-03-01

Optical proximity correction (OPC) and phase shifting mask (PSM) are the most widely used resolution enhancement techniques (RET) in the semiconductor industry. Recently, a set of OPC and PSM optimization algorithms have been developed to solve for the inverse lithography problem, which are only designed for the nominal imaging parameters without giving sufficient attention to the process variations due to the aberrations, defocus and dose variation. However, the effects of process variations existing in the practical optical lithography systems become more pronounced as the critical dimension (CD) continuously shrinks. On the other hand, the lithography systems with larger NA (NA>0.6) are now extensively used, rendering the scalar imaging models inadequate to describe the vector nature of the electromagnetic field in the current optical lithography systems. In order to tackle the above problems, this paper focuses on developing robust gradient-based OPC and PSM optimization algorithms to the process variations under a vector imaging model. To achieve this goal, an integrative and analytic vector imaging model is applied to formulate the optimization problem, where the effects of process variations are explicitly incorporated in the optimization framework. The steepest descent algorithm is used to optimize the mask iteratively. In order to improve the efficiency of the proposed algorithms, a set of algorithm acceleration techniques (AAT) are exploited during the optimization procedure.

Identifying optimal agricultural countermeasure strategies for a hypothetical contamination scenario using the strategy model.

PubMed

Cox, G; Beresford, N A; Alvarez-Farizo, B; Oughton, D; Kis, Z; Eged, K; Thørring, H; Hunt, J; Wright, S; Barnett, C L; Gil, J M; Howard, B J; Crout, N M J

2005-01-01

A spatially implemented model designed to assist the identification of optimal countermeasure strategies for radioactively contaminated regions is described. Collective and individual ingestion doses for people within the affected area are estimated together with collective exported ingestion dose. A range of countermeasures are incorporated within the model, and environmental restrictions have been included as appropriate. The model evaluates the effectiveness of a given combination of countermeasures through a cost function which balances the benefit obtained through the reduction in dose with the cost of implementation. The optimal countermeasure strategy is the combination of individual countermeasures (and when and where they are implemented) which gives the lowest value of the cost function. The model outputs should not be considered as definitive solutions, rather as interactive inputs to the decision making process. As a demonstration the model has been applied to a hypothetical scenario in Cumbria (UK). This scenario considered a published nuclear power plant accident scenario with a total deposition of 1.7x10(14), 1.2x10(13), 2.8x10(10) and 5.3x10(9)Bq for Cs-137, Sr-90, Pu-239/240 and Am-241, respectively. The model predicts that if no remediation measures were implemented the resulting collective dose would be approximately 36 000 person-Sv (predominantly from 137Cs) over a 10-year period post-deposition. The optimal countermeasure strategy is predicted to avert approximately 33 000 person-Sv at a cost of approximately 160 million pounds. The optimal strategy comprises a mixture of ploughing, AFCF (ammonium-ferric hexacyano-ferrate) administration, potassium fertiliser application, clean feeding of livestock and food restrictions. The model recommends specific areas within the contaminated area and time periods where these measures should be implemented.

Influence of scatter reduction method and monochromatic beams on image quality and dose in mammography.

PubMed

Moeckli, Raphaël; Verdun, Francis R; Fiedler, Stefan; Pachoud, Marc; Bulling, Shelley; Schnyder, Pierre; Valley, Jean-François

2003-12-01

In mammography, the image contrast and dose delivered to the patient are determined by the x-ray spectrum and the scatter to primary ratio S/P. Thus the quality of the mammographic procedure is highly dependent on the choice of anode and filter material and on the method used to reduce the amount of scattered radiation reaching the detector. Synchrotron radiation is a useful tool to study the effect of beam energy on the optimization of the mammographic process because it delivers a high flux of monochromatic photons. Moreover, because the beam is naturally flat collimated in one direction, a slot can be used instead of a grid for scatter reduction. We have measured the ratio S/P and the transmission factors for grids and slots for monoenergetic synchrotron radiation. In this way the effect of beam energy and scatter rejection method were separated, and their respective importance for image quality and dose analyzed. Our results show that conventional mammographic spectra are not far from optimum and that the use of a slot instead of a grid has an important effect on the optimization of the mammographic process. We propose a simple numerical model to quantify this effect.

Inactivation disinfection property of Moringa Oleifera seed extract: optimization and kinetic studies

NASA Astrophysics Data System (ADS)

Idris, M. A.; Jami, M. S.; Hammed, A. M.

2017-05-01

This paper presents the statistical optimization study of disinfection inactivation parameters of defatted Moringa oleifera seed extract on Pseudomonas aeruginosa bacterial cells. Three level factorial design was used to estimate the optimum range and the kinetics of the inactivation process was also carried. The inactivation process involved comparing different disinfection models of Chicks-Watson, Collins-Selleck and Homs models. The results from analysis of variance (ANOVA) of the statistical optimization process revealed that only contact time was significant. The optimum disinfection range of the seed extract was 125 mg/L, 30 minutes and 120rpm agitation. At the optimum dose, the inactivation kinetics followed the Collin-Selleck model with coefficient of determination (R2) of 0.6320. This study is the first of its kind in determining the inactivation kinetics of pseudomonas aeruginosa using the defatted seed extract.

Real-time inverse planning for Gamma Knife radiosurgery.

PubMed

Wu, Q Jackie; Chankong, Vira; Jitprapaikulsarn, Suradet; Wessels, Barry W; Einstein, Douglas B; Mathayomchan, Boonyanit; Kinsella, Timothy J

2003-11-01

The challenges of real-time Gamma Knife inverse planning are the large number of variables involved and the unknown search space a priori. With limited collimator sizes, shots have to be heavily overlapped to form a smooth prescription isodose line that conforms to the irregular target shape. Such overlaps greatly influence the total number of shots per plan, making pre-determination of the total number of shots impractical. However, this total number of shots usually defines the search space, a pre-requisite for most of the optimization methods. Since each shot only covers part of the target, a collection of shots in different locations and various collimator sizes selected makes up the global dose distribution that conforms to the target. Hence, planning or placing these shots is a combinatorial optimization process that is computationally expensive by nature. We have previously developed a theory of shot placement and optimization based on skeletonization. The real-time inverse planning process, reported in this paper, is an expansion and the clinical implementation of this theory. The complete planning process consists of two steps. The first step is to determine an optimal number of shots including locations and sizes and to assign initial collimator size to each of the shots. The second step is to fine-tune the weights using a linear-programming technique. The objective function is to minimize the total dose to the target boundary (i.e., maximize the dose conformity). Results of an ellipsoid test target and ten clinical cases are presented. The clinical cases are also compared with physician's manual plans. The target coverage is more than 99% for manual plans and 97% for all the inverse plans. The RTOG PITV conformity indices for the manual plans are between 1.16 and 3.46, compared to 1.36 to 2.4 for the inverse plans. All the inverse plans are generated in less than 2 min, making real-time inverse planning a reality.

SU-E-T-503: IMRT Optimization Using Monte Carlo Dose Engine: The Effect of Statistical Uncertainty.

PubMed

Tian, Z; Jia, X; Graves, Y; Uribe-Sanchez, A; Jiang, S

2012-06-01

With the development of ultra-fast GPU-based Monte Carlo (MC) dose engine, it becomes clinically realistic to compute the dose-deposition coefficients (DDC) for IMRT optimization using MC simulation. However, it is still time-consuming if we want to compute DDC with small statistical uncertainty. This work studies the effects of the statistical error in DDC matrix on IMRT optimization. The MC-computed DDC matrices are simulated here by adding statistical uncertainties at a desired level to the ones generated with a finite-size pencil beam algorithm. A statistical uncertainty model for MC dose calculation is employed. We adopt a penalty-based quadratic optimization model and gradient descent method to optimize fluence map and then recalculate the corresponding actual dose distribution using the noise-free DDC matrix. The impacts of DDC noise are assessed in terms of the deviation of the resulted dose distributions. We have also used a stochastic perturbation theory to theoretically estimate the statistical errors of dose distributions on a simplified optimization model. A head-and-neck case is used to investigate the perturbation to IMRT plan due to MC's statistical uncertainty. The relative errors of the final dose distributions of the optimized IMRT are found to be much smaller than those in the DDC matrix, which is consistent with our theoretical estimation. When history number is decreased from 108 to 106, the dose-volume-histograms are still very similar to the error-free DVHs while the error in DDC is about 3.8%. The results illustrate that the statistical errors in the DDC matrix have a relatively small effect on IMRT optimization in dose domain. This indicates we can use relatively small number of histories to obtain the DDC matrix with MC simulation within a reasonable amount of time, without considerably compromising the accuracy of the optimized treatment plan. This work is supported by Varian Medical Systems through a Master Research Agreement. © 2012 American Association of Physicists in Medicine.

4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors

PubMed Central

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-01-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking. PMID:24889215

4D optimization of scanned ion beam tracking therapy for moving tumors

NASA Astrophysics Data System (ADS)

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-07-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

PubMed

Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M

2011-01-01

The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

Optimization of equivalent uniform dose using the L-curve criterion.

PubMed

Chvetsov, Alexei V; Dempsey, James F; Palta, Jatinder R

2007-10-07

Optimization of equivalent uniform dose (EUD) in inverse planning for intensity-modulated radiation therapy (IMRT) prevents variation in radiobiological effect between different radiotherapy treatment plans, which is due to variation in the pattern of dose nonuniformity. For instance, the survival fraction of clonogens would be consistent with the prescription when the optimized EUD is equal to the prescribed EUD. One of the problems in the practical implementation of this approach is that the spatial dose distribution in EUD-based inverse planning would be underdetermined because an unlimited number of nonuniform dose distributions can be computed for a prescribed value of EUD. Together with ill-posedness of the underlying integral equation, this may significantly increase the dose nonuniformity. To optimize EUD and keep dose nonuniformity within reasonable limits, we implemented into an EUD-based objective function an additional criterion which ensures the smoothness of beam intensity functions. This approach is similar to the variational regularization technique which was previously studied for the dose-based least-squares optimization. We show that the variational regularization together with the L-curve criterion for the regularization parameter can significantly reduce dose nonuniformity in EUD-based inverse planning.

SU-F-BRD-07: Fast Monte Carlo-Based Biological Optimization of Proton Therapy Treatment Plans for Thyroid Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Chan Tseung, H; Ma, J; Ma, D

2015-06-15

Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based biological planning for the treatment of thyroid tumors in spot-scanning proton therapy. Methods: Recently, we developed a fast and accurate GPU-based MC simulation of proton transport that was benchmarked against Geant4.9.6 and used as the dose calculation engine in a clinically-applicable GPU-accelerated IMPT optimizer. Besides dose, it can simultaneously score the dose-averaged LET (LETd), which makes fast biological dose (BD) estimates possible. To convert from LETd to BD, we used a linear relation based on cellular irradiation data. Given a thyroid patient with a 93cc tumor volume, we createdmore » a 2-field IMPT plan in Eclipse (Varian Medical Systems). This plan was re-calculated with our MC to obtain the BD distribution. A second 5-field plan was made with our in-house optimizer, using pre-generated MC dose and LETd maps. Constraints were placed to maintain the target dose to within 25% of the prescription, while maximizing the BD. The plan optimization and calculation of dose and LETd maps were performed on a GPU cluster. The conventional IMPT and biologically-optimized plans were compared. Results: The mean target physical and biological doses from our biologically-optimized plan were, respectively, 5% and 14% higher than those from the MC re-calculation of the IMPT plan. Dose sparing to critical structures in our plan was also improved. The biological optimization, including the initial dose and LETd map calculations, can be completed in a clinically viable time (∼30 minutes) on a cluster of 25 GPUs. Conclusion: Taking advantage of GPU acceleration, we created a MC-based, biologically optimized treatment plan for a thyroid patient. Compared to a standard IMPT plan, a 5% increase in the target’s physical dose resulted in ∼3 times as much increase in the BD. Biological planning was thus effective in escalating the target BD.« less

SU-F-T-89: Investigation of Simultaneous Optimization of Photon and Electron Apertures for Mixed Beam Radiotherapy Based On An Academic Case

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, S; Joosten, A; Fix, MK

Purpose: To estimate the dosimetric potential of mixed beam radiotherapy (MBRT) by using a single process optimizing the shape and weight of photon and electron apertures simultaneously based on Monte Carlo beamlet dose distributions. Methods: A simulated annealing based direct aperture optimization capable to perform simultaneous optimization was developed to generate treatment plans for MERT, photon-IMRT and MBRT. Both photon and electron apertures are collimated with the photon-MLC and are delivered in a segmented manner. For dosimetric comparison and for investigating the dependency on the number of apertures, photon-IMRT, MERT and MBRT plans were generated for an academic case consistingmore » of a water phantom containing two shallow PTVs differing in the maximal depth of 5 and 7 cm, respectively and two OARs in distal and lateral direction to the PTVs. Results: For the superficial PTV, the dose homogeneity (V95%–V107%) and the mean dose (in percent of the prescribed dose) to the distal and the lateral OARs of the MBRT plan (94.9%, 16.9%, 17.8%) are superior or comparable to those for the MERT (74%, 18.4%, 15.4%) and the photon-IMRT plan (89.4%, 20.8%, 24.7%). For the enlarged PTV, the dosimetric superiority of MBRT compared to MERT and photon-IMRT is even more pronounced. Furthermore, an MBRT plan with 12 electron and 10 photon apertures lead to an objective function value 38% lower than that of a photon-IMRT plan with 40 apertures. Conclusion: The results of simultaneous optimization for MBRT are promising with regards to further OAR sparing and improved dose coverage to the PTV compared to photon-IMRT and MERT. Especially superficial targets with deeper subparts (>5 cm) could substantially benefit. Moreover, MBRT seems to be a possible solution of two downsides of photon-IMRT, namely the extended low dose bath and the requirement of numerous apertures. This work was supported by Varian Medical Systems. This work was supported by Varian Medical Systems.« less

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, Edward T.

Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when comparedmore » the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.« less

On the calibration process of film dosimetry: OLS inverse regression versus WLS inverse prediction.

PubMed

Crop, F; Van Rompaye, B; Paelinck, L; Vakaet, L; Thierens, H; De Wagter, C

2008-07-21

The purpose of this study was both putting forward a statistically correct model for film calibration and the optimization of this process. A reliable calibration is needed in order to perform accurate reference dosimetry with radiographic (Gafchromic) film. Sometimes, an ordinary least squares simple linear (in the parameters) regression is applied to the dose-optical-density (OD) curve with the dose as a function of OD (inverse regression) or sometimes OD as a function of dose (inverse prediction). The application of a simple linear regression fit is an invalid method because heteroscedasticity of the data is not taken into account. This could lead to erroneous results originating from the calibration process itself and thus to a lower accuracy. In this work, we compare the ordinary least squares (OLS) inverse regression method with the correct weighted least squares (WLS) inverse prediction method to create calibration curves. We found that the OLS inverse regression method could lead to a prediction bias of up to 7.3 cGy at 300 cGy and total prediction errors of 3% or more for Gafchromic EBT film. Application of the WLS inverse prediction method resulted in a maximum prediction bias of 1.4 cGy and total prediction errors below 2% in a 0-400 cGy range. We developed a Monte-Carlo-based process to optimize calibrations, depending on the needs of the experiment. This type of thorough analysis can lead to a higher accuracy for film dosimetry.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Robust optimization in lung treatment plans accounting for geometric uncertainty.

PubMed

Zhang, Xin; Rong, Yi; Morrill, Steven; Fang, Jian; Narayanasamy, Ganesh; Galhardo, Edvaldo; Maraboyina, Sanjay; Croft, Christopher; Xia, Fen; Penagaricano, Jose

2018-05-01

Robust optimization generates scenario-based plans by a minimax optimization method to find optimal scenario for the trade-off between target coverage robustness and organ-at-risk (OAR) sparing. In this study, 20 lung cancer patients with tumors located at various anatomical regions within the lungs were selected and robust optimization photon treatment plans including intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. The plan robustness was analyzed using perturbed doses with setup error boundary of ±3 mm in anterior/posterior (AP), ±3 mm in left/right (LR), and ±5 mm in inferior/superior (IS) directions from isocenter. Perturbed doses for D 99 , D 98 , and D 95 were computed from six shifted isocenter plans to evaluate plan robustness. Dosimetric study was performed to compare the internal target volume-based robust optimization plans (ITV-IMRT and ITV-VMAT) and conventional PTV margin-based plans (PTV-IMRT and PTV-VMAT). The dosimetric comparison parameters were: ITV target mean dose (D mean ), R 95 (D 95 /D prescription ), Paddick's conformity index (CI), homogeneity index (HI), monitor unit (MU), and OAR doses including lung (D mean , V 20 Gy and V 15 Gy ), chest wall, heart, esophagus, and maximum cord doses. A comparison of optimization results showed the robust optimization plan had better ITV dose coverage, better CI, worse HI, and lower OAR doses than conventional PTV margin-based plans. Plan robustness evaluation showed that the perturbed doses of D 99 , D 98 , and D 95 were all satisfied at least 99% of the ITV to received 95% of prescription doses. It was also observed that PTV margin-based plans had higher MU than robust optimization plans. The results also showed robust optimization can generate plans that offer increased OAR sparing, especially for normal lungs and OARs near or abutting the target. Weak correlation was found between normal lung dose and target size, and no other correlation was observed in this study. © 2018 University of Arkansas for Medical Sciences. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Expected treatment dose construction and adaptive inverse planning optimization: Implementation for offline head and neck cancer adaptive radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan Di; Liang Jian

Purpose: To construct expected treatment dose for adaptive inverse planning optimization, and evaluate it on head and neck (h and n) cancer adaptive treatment modification. Methods: Adaptive inverse planning engine was developed and integrated in our in-house adaptive treatment control system. The adaptive inverse planning engine includes an expected treatment dose constructed using the daily cone beam (CB) CT images in its objective and constrains. Feasibility of the adaptive inverse planning optimization was evaluated retrospectively using daily CBCT images obtained from the image guided IMRT treatment of 19 h and n cancer patients. Adaptive treatment modification strategies with respect tomore » the time and the number of adaptive inverse planning optimization during the treatment course were evaluated using the cumulative treatment dose in organs of interest constructed using all daily CBCT images. Results: Expected treatment dose was constructed to include both the delivered dose, to date, and the estimated dose for the remaining treatment during the adaptive treatment course. It was used in treatment evaluation, as well as in constructing the objective and constraints for adaptive inverse planning optimization. The optimization engine is feasible to perform planning optimization based on preassigned treatment modification schedule. Compared to the conventional IMRT, the adaptive treatment for h and n cancer illustrated clear dose-volume improvement for all critical normal organs. The dose-volume reductions of right and left parotid glands, spine cord, brain stem and mandible were (17 {+-} 6)%, (14 {+-} 6)%, (11 {+-} 6)%, (12 {+-} 8)%, and (5 {+-} 3)% respectively with the single adaptive modification performed after the second treatment week; (24 {+-} 6)%, (22 {+-} 8)%, (21 {+-} 5)%, (19 {+-} 8)%, and (10 {+-} 6)% with three weekly modifications; and (28 {+-} 5)%, (25 {+-} 9)%, (26 {+-} 5)%, (24 {+-} 8)%, and (15 {+-} 9)% with five weekly modifications. Conclusions: Adaptive treatment modification can be implemented including the expected treatment dose in the adaptive inverse planning optimization. The retrospective evaluation results demonstrate that utilizing the weekly adaptive inverse planning optimization, the dose distribution of h and n cancer treatment can be largely improved.« less

Occupational dose constraints for the lens of the eye for interventional radiologists and interventional cardiologists in the UK.

PubMed

Mairs, William DA

2016-06-01

The International Commission on Radiological Protection (ICRP) has recommended a 20 mSv year(-1) dose limit for the lens of the eye, which has been adopted in the European Union Basic Safety Standards. Interventional radiologists (IRs) and interventional cardiologists (ICs) are likely to be affected by this. The effects of radiation in the lens are somewhat uncertain, and the ICRP explicitly recommend optimization. Occupational dose constraints are part of the optimization process and define a level of dose which ought to be achievable in a well-managed practice. This commentary calls on the professional bodies to review a need for national constraints to guide local decisions. Consideration is given to developing such constraints using maximum expected doses in high-workload facilities with good radiation protection practices and application of a factor allowing for attenuation by lead glasses (LG). Doses are based on a Public Health England survey of eye dose in the UK. Maximum expected doses for ICs are approximately 21 mSv year(-1), neglecting LG. However, the extent of IR exposure is not yet fully known, and further evidence is required before conclusions are drawn. A Health and Safety Laboratory review of LG established a conservative dose reduction factor of 3 for models available in 2012. Application of this factor provides a dose constraint of 7 mSv year(-1) to the eye for ICs. To achieve this constraint, those employers with the most exposed ICs will have to provide and ensure the correct use of a ceiling-suspended eye shield and LG.

SU-E-T-368: Evaluating Dosimetric Outcome of Modulated Photon Radiotherapy (XMRT) Optimization for Head and Neck Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGeachy, P; Villarreal-Barajas, JE; Khan, R

2015-06-15

Purpose: The dosimetric outcome of optimized treatment plans obtained by modulating the photon beamlet energy and fluence on a small cohort of four Head and Neck (H and N) patients was investigated. This novel optimization technique is denoted XMRT for modulated photon radiotherapy. The dosimetric plans from XMRT for H and N treatment were compared to conventional, 6 MV intensity modulated radiotherapy (IMRT) optimization plans. Methods: An arrangement of two non-coplanar and five coplanar beams was used for all four H and N patients. Both XMRT and IMRT were subject to the same optimization algorithm, with XMRT optimization allowing bothmore » 6 and 18 MV beamlets while IMRT was restricted to 6 MV only. The optimization algorithm was based on a linear programming approach with partial-volume constraints implemented via the conditional value-at-risk method. H and N constraints were based off of those mentioned in the Radiation Therapy Oncology Group 1016 protocol. XMRT and IMRT solutions were assessed using metrics suggested by International Commission on Radiation Units and Measurements report 83. The Gurobi solver was used in conjunction with the CVX package to solve each optimization problem. Dose calculations and analysis were done in CERR using Monte Carlo dose calculation with VMC{sub ++}. Results: Both XMRT and IMRT solutions met all clinical criteria. Trade-offs were observed between improved dose uniformity to the primary target volume (PTV1) and increased dose to some of the surrounding healthy organs for XMRT compared to IMRT. On average, IMRT improved dose to the contralateral parotid gland and spinal cord while XMRT improved dose to the brainstem and mandible. Conclusion: Bi-energy XMRT optimization for H and N patients provides benefits in terms of improved dose uniformity to the primary target and reduced dose to some healthy structures, at the expense of increased dose to other healthy structures when compared with IMRT.« less

Contrast-enhanced digital mammography (CEDM): imaging modeling, computer simulations, and phantom study

NASA Astrophysics Data System (ADS)

Chen, Biao; Jing, Zhenxue; Smith, Andrew

2005-04-01

Contrast enhanced digital mammography (CEDM), which is based upon the analysis of a series of x-ray projection images acquired before/after the administration of contrast agents, may provide physicians critical physiologic and morphologic information of breast lesions to determine the malignancy of lesions. This paper proposes to combine the kinetic analysis (KA) of contrast agent uptake/washout process and the dual-energy (DE) contrast enhancement together to formulate a hybrid contrast enhanced breast-imaging framework. The quantitative characteristics of materials and imaging components in the x-ray imaging chain, including x-ray tube (tungsten) spectrum, filter, breast tissues/lesions, contrast agents (non-ionized iodine solution), and selenium detector, were systematically modeled. The contrast-noise-ration (CNR) of iodinated lesions and mean absorbed glandular dose were estimated mathematically. The x-ray techniques optimization was conducted through a series of computer simulations to find the optimal tube voltage, filter thickness, and exposure levels for various breast thicknesses, breast density, and detectable contrast agent concentration levels in terms of detection efficiency (CNR2/dose). A phantom study was performed on a modified Selenia full field digital mammography system to verify the simulated results. The dose level was comparable to the dose in diagnostic mode (less than 4 mGy for an average 4.2 cm compressed breast). The results from the computer simulations and phantom study are being used to optimize an ongoing clinical study.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, J; Lindsay, P; University of Toronto, Toronto

Purpose: Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x-ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x-ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions. Methods: Two-dimensional dose kernels were measured for a 1 mmmore » circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x-ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low- and high-spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam-on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy. Results: Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery. Conclusion: The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations. Funding Support: this work is supported by funding the National Sciences and Engineering Research Council of Canada, and a Mitacs-accelerate fellowship. Conflict of Interest: Dr. Lindsay and Dr. Jaffray are listed as inventors of the small animal microirradiator described herein. This system has been licensed for commercial development.« less

Impact of a phenytoin loading dose program in the emergency department.

PubMed

Brancaccio, Adam; Giuliano, Christopher; McNorton, Kelly; Delgado, George

2014-11-01

The use of a combined physician-and pharmacist-directed phenytoin loading dose program in an emergency department (ED) was evaluated. This single-center, observational, preimplementation-postimplementation study evaluated adult patients who received a phenytoin loading dose in the ED. The primary outcome compared the proportion of optimal phenytoin loading doses in the preimplementation and postimplementation groups. The postimplementation group was further stratified into pharmacist- and prescriber-dosing groups. Other outcomes evaluated included the numbers of appropriate serum phenytoin concentrations measured, adverse drug reactions (ADRs), and recurrence of seizures within 24 hours of loading dose administration in the preimplementation and postimplementation groups. There was no difference in the proportion of optimal phenytoin loading doses between the preimplementation and postimplementation groups (50% versus 62%, respectively; p=0.19). When stratified by individual groups, the rate of optimal phenytoin loading doses increased by 64% in the postimplementation pharmacist group (50% versus 82%, p=0.007), while the rate in the prescriber-dosing group remained relatively unchanged (50% versus 49%, p=0.91). The number of appropriate serum phenytoin concentrations significantly improved in the postimplementation versus preimplementation group (65% versus 40%, p=0.025). Rates of ADRs and recurrence of seizures did not differ across the study groups. No change in the percentage of optimal phenytoin loading doses in the ED was observed after implementation of a combined pharmacist- and physician- dosing program. When stratified into pharmacist or prescriber dosing, the pharmacist-led dosing program significantly improved the proportion of patients who received optimal phenytoin loading doses. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

SU-E-T-549: A Combinatorial Optimization Approach to Treatment Planning with Non-Uniform Fractions in Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papp, D; Unkelbach, J

2014-06-01

Purpose: Non-uniform fractionation, i.e. delivering distinct dose distributions in two subsequent fractions, can potentially improve outcomes by increasing biological dose to the target without increasing dose to healthy tissues. This is possible if both fractions deliver a similar dose to normal tissues (exploit the fractionation effect) but high single fraction doses to subvolumes of the target (hypofractionation). Optimization of such treatment plans can be formulated using biological equivalent dose (BED), but leads to intractable nonconvex optimization problems. We introduce a novel optimization approach to address this challenge. Methods: We first optimize a reference IMPT plan using standard techniques that deliversmore » a homogeneous target dose in both fractions. The method then divides the pencil beams into two sets, which are assigned to either fraction one or fraction two. The total intensity of each pencil beam, and therefore the physical dose, remains unchanged compared to the reference plan. The objectives are to maximize the mean BED in the target and to minimize the mean BED in normal tissues, which is a quadratic function of the pencil beam weights. The optimal reassignment of pencil beams to one of the two fractions is formulated as a binary quadratic optimization problem. A near-optimal solution to this problem can be obtained by convex relaxation and randomized rounding. Results: The method is demonstrated for a large arteriovenous malformation (AVM) case treated in two fractions. The algorithm yields a treatment plan, which delivers a high dose to parts of the AVM in one of the fractions, but similar doses in both fractions to the normal brain tissue adjacent to the AVM. Using the approach, the mean BED in the target was increased by approximately 10% compared to what would have been possible with a uniform reference plan for the same normal tissue mean BED.« less

Obtaining the Optimal Dose in Alcohol Dependence Studies

PubMed Central

Wages, Nolan A.; Liu, Lei; O’Quigley, John; Johnson, Bankole A.

2012-01-01

In alcohol dependence studies, the treatment effect at different dose levels remains to be ascertained. Establishing this effect would aid us in identifying the best dose that has satisfactory efficacy while minimizing the rate of adverse events. We advocate the use of dose-finding methodology that has been successfully implemented in the cancer and HIV settings to identify the optimal dose in a cost-effective way. Specifically, we describe the continual reassessment method (CRM), an adaptive design proposed for cancer trials to reconcile the needs of dose-finding experiments with the ethical demands of established medical practice. We are applying adaptive designs for identifying the optimal dose of medications for the first time in the context of pharmacotherapy research in alcoholism. We provide an example of a topiramate trial as an illustration of how adaptive designs can be used to locate the optimal dose in alcohol treatment trials. It is believed that the introduction of adaptive design methods will enable the development of medications for the treatment of alcohol dependence to be accelerated. PMID:23189064

SU-E-J-42: Motion Adaptive Image Filter for Low Dose X-Ray Fluoroscopy in the Real-Time Tumor-Tracking Radiotherapy System.

PubMed

Miyamoto, N; Ishikawa, M; Sutherland, K; Suzuki, R; Matsuura, T; Takao, S; Toramatsu, C; Nihongi, H; Shimizu, S; Onimaru, R; Umegaki, K; Shirato, H

2012-06-01

In the real-time tumor-tracking radiotherapy system, fiducial markers are detected by X-ray fluoroscopy. The fluoroscopic parameters should be optimized as low as possible in order to reduce unnecessary imaging dose. However, the fiducial markers could not be recognized due to effect of statistical noise in low dose imaging. Image processing is envisioned to be a solution to improve image quality and to maintain tracking accuracy. In this study, a recursive image filter adapted to target motion is proposed. A fluoroscopy system was used for the experiment. A spherical gold marker was used as a fiducial marker. About 450 fluoroscopic images of the marker were recorded. In order to mimic respiratory motion of the marker, the images were shifted sequentially. The tube voltage, current and exposure duration were fixed at 65 kV, 50 mA and 2.5 msec as low dose imaging condition, respectively. The tube current was 100 mA as high dose imaging. A pattern recognition score (PRS) ranging from 0 to 100 and image registration error were investigated by performing template pattern matching to each sequential image. The results with and without image processing were compared. In low dose imaging, theimage registration error and the PRS without the image processing were 2.15±1.21 pixel and 46.67±6.40, respectively. Those with the image processing were 1.48±0.82 pixel and 67.80±4.51, respectively. There was nosignificant difference in the image registration error and the PRS between the results of low dose imaging with the image processing and that of high dose imaging without the image processing. The results showed that the recursive filter was effective in order to maintain marker tracking stability and accuracy in low dose fluoroscopy. © 2012 American Association of Physicists in Medicine.

SU-E-T-10: A Clinical Implementation and the Dosimetric Evidence in High Dose Rate Vaginal Multichannel Applicator Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syh, J; Syh, J; Patel, B

2015-06-15

Purpose: The multichannel cylindrical applicator has a distinctive modification of the traditional single channel cylindrical applicator. The novel multichannel applicator has additional peripheral channels that provide more flexibility both in treatment planning process and outcomes. To protect by reducing doses to adjacent organ at risk (OAR) while maintaining target coverage with inverse plan optimization are the goals for such novel Brachytherapy device. Through a series of comparison and analysis of reults in more than forty patients who received HDR Brachytherapy using multichannel vaginal applicator, this procedure has been implemented in our institution. Methods: Multichannel planning was CT image based. Themore » CTV of 5mm vaginal cuff rind with prescribed length was well reconstructed as well as bladder and rectum. At least D95 of CTV coverage is 95% of prescribed dose. Multichannel inverse plan optimization algorithm not only shapes target dose cloud but set dose avoids to OAR’s exclusively. The doses of D2cc, D5cc and D5; volume of V2Gy in OAR’s were selected to compare with single channel results when sole central channel is only possibility. Results: Study demonstrates plan superiorly in OAR’s doe reduction in multi-channel plan. The D2cc of the rectum and bladder were showing a little lower for multichannel vs. single channel. The V2Gy of the rectum was 93.72% vs. 83.79% (p=0.007) for single channel vs. multichannel respectively. Absolute reduced mean dose of D5 by multichannel was 17 cGy (s.d.=6.4) and 44 cGy (s.d.=15.2) in bladder and rectum respectively. Conclusion: The optimization solution in multichannel was to maintain D95 CTV coverage while reducing the dose to OAR’s. Dosimetric advantage in sparing critical organs by using a multichannel applicator in HDR Brachytherapy treatment of the vaginal cuff is so promising and has been implemented clinically.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demirag, N

Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 andmore » 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics.« less

Coagulation-flocculation sequential with Fenton or Photo-Fenton processes as an alternative for the industrial textile wastewater treatment.

PubMed

GilPavas, Edison; Dobrosz-Gómez, Izabela; Gómez-García, Miguel Ángel

2017-04-15

In this study, the industrial textile wastewater was treated using a chemical-based technique (coagulation-flocculation, C-F) sequential with an advanced oxidation process (AOP: Fenton or Photo-Fenton). During the C-F, Al 2 (SO 4 ) 3 was used as coagulant and its optimal dose was determined using the jar test. The following operational conditions of C-F, maximizing the organic matter removal, were determined: 700 mg/L of Al 2 (SO 4 ) 3  at pH = 9.96. Thus, the C-F allowed to remove 98% of turbidity, 48% of Chemical Oxygen Demand (COD), and let to increase in the BOD 5 /COD ratio from 0.137 to 0.212. Subsequently, the C-F effluent was treated using each of AOPs. Their performances were optimized by the Response Surface Methodology (RSM) coupled with a Box-Behnken experimental design (BBD). The following optimal conditions of both Fenton (Fe 2+ /H 2 O 2 ) and Photo-Fenton (Fe 2+ /H 2 O 2 /UV) processes were found: Fe 2+ concentration = 1 mM, H 2 O 2 dose = 2 mL/L (19.6 mM), and pH = 3. The combination of C-F pre-treatment with the Fenton reagent, at optimized conditions, let to remove 74% of COD during 90 min of the process. The C-F sequential with Photo-Fenton process let to reach 87% of COD removal, in the same time. Moreover, the BOD 5 /COD ratio increased from 0.212 to 0.68 and from 0.212 to 0.74 using Fenton and Photo-Fenton processes, respectively. Thus, the enhancement of biodegradability with the physico-chemical treatment was proved. The depletion of H 2 O 2 was monitored during kinetic study. Strategies for improving the reaction efficiency, based on the H 2 O 2 evolution, were also tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-E-T-422: Fast Analytical Beamlet Optimization for Volumetric Intensity-Modulated Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Kenny S K; Lee, Louis K Y; Xing, L

2015-06-15

Purpose: To implement a fast optimization algorithm on CPU/GPU heterogeneous computing platform and to obtain an optimal fluence for a given target dose distribution from the pre-calculated beamlets in an analytical approach. Methods: The 2D target dose distribution was modeled as an n-dimensional vector and estimated by a linear combination of independent basis vectors. The basis set was composed of the pre-calculated beamlet dose distributions at every 6 degrees of gantry angle and the cost function was set as the magnitude square of the vector difference between the target and the estimated dose distribution. The optimal weighting of the basis,more » which corresponds to the optimal fluence, was obtained analytically by the least square method. Those basis vectors with a positive weighting were selected for entering into the next level of optimization. Totally, 7 levels of optimization were implemented in the study.Ten head-and-neck and ten prostate carcinoma cases were selected for the study and mapped to a round water phantom with a diameter of 20cm. The Matlab computation was performed in a heterogeneous programming environment with Intel i7 CPU and NVIDIA Geforce 840M GPU. Results: In all selected cases, the estimated dose distribution was in a good agreement with the given target dose distribution and their correlation coefficients were found to be in the range of 0.9992 to 0.9997. Their root-mean-square error was monotonically decreasing and converging after 7 cycles of optimization. The computation took only about 10 seconds and the optimal fluence maps at each gantry angle throughout an arc were quickly obtained. Conclusion: An analytical approach is derived for finding the optimal fluence for a given target dose distribution and a fast optimization algorithm implemented on the CPU/GPU heterogeneous computing environment greatly reduces the optimization time.« less

Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies

NASA Astrophysics Data System (ADS)

van de Water, Steven; Albertini, Francesca; Weber, Damien C.; Heijmen, Ben J. M.; Hoogeman, Mischa S.; Lomax, Antony J.

2018-01-01

The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 ‘synthetic’ CTs with varying nasal cavity filling. The robust optimization method available in our treatment planning system ‘Erasmus-iCycle’ was extended to also account for anatomical uncertainties by including (synthetic) CTs with varying patient anatomy as error scenarios in the inverse optimization. For each patient, we generated treatment plans using anatomical robust optimization and, for benchmarking, using SFUD optimization and online plan adaptation. Clinical target volume (CTV) and organ-at-risk (OAR) doses were assessed by recalculating the treatment plans on the synthetic CTs, evaluating dose distributions individually and accumulated over an entire fractionated 50 GyRBE treatment, assuming each synthetic CT to correspond to a 2 GyRBE fraction. Treatment plans were also evaluated using actual repeat CTs. Anatomical robust optimization resulted in adequate CTV doses (V95%  ⩾  98% and V107%  ⩽  2%) if at least three synthetic CTs were included in addition to the planning CT. These CTV requirements were also fulfilled for online plan adaptation, but not for the SFUD approach, even when applying a margin of 5 mm. Compared with anatomical robust optimization, OAR dose parameters for the accumulated dose distributions were on average 5.9 GyRBE (20%) higher when using SFUD optimization and on average 3.6 GyRBE (18%) lower for online plan adaptation. In conclusion, anatomical robust optimization effectively accounted for changes in nasal cavity filling during IMPT, providing substantially improved CTV and OAR doses compared with conventional SFUD optimization. OAR doses can be further reduced by using online plan adaptation.

A gEUD-based inverse planning technique for HDR prostate brachytherapy: Feasibility study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giantsoudi, D.; Department of Radiation Oncology, Francis H. Burr Proton Therapy Center, Boston, Massachusetts 02114; Baltas, D.

2013-04-15

Purpose: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. Methods: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the differentmore » dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. Results: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D{sub 10} or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. Conclusions: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.« less

Process optimization of solid rad waste management at the Shelter object transformation to the ecologically safety system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batiy, V.G.; Stojanov, A.I.; Schmieman, E.

2007-07-01

Methodological approach of optimization of schemes of solid radwaste management of the Object Shelter (Shelter) and ChNPP industrial site during transformation to the ecologically safe system was developed. On the basis of the conducted models researches the ALARA-analysis was carried out for the choice of optimum variant of schemes and technologies of solid radwaste management. The criteria of choice of optimum schemes, which are directed on optimization of doses and financial expenses, minimization of amount of the formed radwaste etc, were developed for realization of this ALARA-analysis. (authors)

Failure-probability driven dose painting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vogelius, Ivan R.; Håkansson, Katrin; Due, Anne K.

Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). Themore » total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose–response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%–91%) as compared to the observed TCP of 70%.Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of toxicity.« less

Clinical knowledge-based inverse treatment planning

NASA Astrophysics Data System (ADS)

Yang, Yong; Xing, Lei

2004-11-01

Clinical IMRT treatment plans are currently made using dose-based optimization algorithms, which do not consider the nonlinear dose-volume effects for tumours and normal structures. The choice of structure specific importance factors represents an additional degree of freedom of the system and makes rigorous optimization intractable. The purpose of this work is to circumvent the two problems by developing a biologically more sensible yet clinically practical inverse planning framework. To implement this, the dose-volume status of a structure was characterized by using the effective volume in the voxel domain. A new objective function was constructed with the incorporation of the volumetric information of the system so that the figure of merit of a given IMRT plan depends not only on the dose deviation from the desired distribution but also the dose-volume status of the involved organs. The conventional importance factor of an organ was written into a product of two components: (i) a generic importance that parametrizes the relative importance of the organs in the ideal situation when the goals for all the organs are met; (ii) a dose-dependent factor that quantifies our level of clinical/dosimetric satisfaction for a given plan. The generic importance can be determined a priori, and in most circumstances, does not need adjustment, whereas the second one, which is responsible for the intractable behaviour of the trade-off seen in conventional inverse planning, was determined automatically. An inverse planning module based on the proposed formalism was implemented and applied to a prostate case and a head-neck case. A comparison with the conventional inverse planning technique indicated that, for the same target dose coverage, the critical structure sparing was substantially improved for both cases. The incorporation of clinical knowledge allows us to obtain better IMRT plans and makes it possible to auto-select the importance factors, greatly facilitating the inverse planning process. The new formalism proposed also reveals the relationship between different inverse planning schemes and gives important insight into the problem of therapeutic plan optimization. In particular, we show that the EUD-based optimization is a special case of the general inverse planning formalism described in this paper.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beltran, C; Kamal, H

Purpose: To provide a multicriteria optimization algorithm for intensity modulated radiation therapy using pencil proton beam scanning. Methods: Intensity modulated radiation therapy using pencil proton beam scanning requires efficient optimization algorithms to overcome the uncertainties in the Bragg peaks locations. This work is focused on optimization algorithms that are based on Monte Carlo simulation of the treatment planning and use the weights and the dose volume histogram (DVH) control points to steer toward desired plans. The proton beam treatment planning process based on single objective optimization (representing a weighted sum of multiple objectives) usually leads to time-consuming iterations involving treatmentmore » planning team members. We proved a time efficient multicriteria optimization algorithm that is developed to run on NVIDIA GPU (Graphical Processing Units) cluster. The multicriteria optimization algorithm running time benefits from up-sampling of the CT voxel size of the calculations without loss of fidelity. Results: We will present preliminary results of Multicriteria optimization for intensity modulated proton therapy based on DVH control points. The results will show optimization results of a phantom case and a brain tumor case. Conclusion: The multicriteria optimization of the intensity modulated radiation therapy using pencil proton beam scanning provides a novel tool for treatment planning. Work support by a grant from Varian Inc.« less

Growth process optimization of ZnO thin film using atomic layer deposition

NASA Astrophysics Data System (ADS)

Weng, Binbin; Wang, Jingyu; Larson, Preston; Liu, Yingtao

2016-12-01

The work reports experimental studies of ZnO thin films grown on Si(100) wafers using a customized thermal atomic layer deposition. The impact of growth parameters including H2O/DiethylZinc (DEZn) dose ratio, background pressure, and temperature are investigated. The imaging results of scanning electron microscopy and atomic force microscopy reveal that the dose ratio is critical to the surface morphology. To achieve high uniformity, the H2O dose amount needs to be at least twice that of DEZn per each cycle. If the background pressure drops below 400 mTorr, a large amount of nanoflower-like ZnO grains would emerge and increase surface roughness significantly. In addition, the growth temperature range between 200 °C and 250 °C is found to be the optimal growth window. And the crystal structures and orientations are also strongly correlated to the temperature as proved by electron back-scattering diffraction and x-ray diffraction results.

A normal tissue dose response model of dynamic repair processes.

PubMed

Alber, Markus; Belka, Claus

2006-01-07

A model is presented for serial, critical element complication mechanisms for irradiated volumes from length scales of a few millimetres up to the entire organ. The central element of the model is the description of radiation complication as the failure of a dynamic repair process. The nature of the repair process is seen as reestablishing the structural organization of the tissue, rather than mere replenishment of lost cells. The interactions between the cells, such as migration, involved in the repair process are assumed to have finite ranges, which limits the repair capacity and is the defining property of a finite-sized reconstruction unit. Since the details of the repair processes are largely unknown, the development aims to make the most general assumptions about them. The model employs analogies and methods from thermodynamics and statistical physics. An explicit analytical form of the dose response of the reconstruction unit for total, partial and inhomogeneous irradiation is derived. The use of the model is demonstrated with data from animal spinal cord experiments and clinical data about heart, lung and rectum. The three-parameter model lends a new perspective to the equivalent uniform dose formalism and the established serial and parallel complication models. Its implications for dose optimization are discussed.

Universal field matching in craniospinal irradiation by a background-dose gradient-optimized method.

PubMed

Traneus, Erik; Bizzocchi, Nicola; Fellin, Francesco; Rombi, Barbara; Farace, Paolo

2018-01-01

The gradient-optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient-optimized technique, based on the use of a background dose, is described. Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An 'in silico' ideal background dose was created first to cover the upper-spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower-spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper-spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on. In both proton and photon plans, the optimized cranial and the lower-spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper-spinal beam. The final dose distributions showed a homogeneous coverage of the targets. Our simple technique allowed to obtain high-quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Efficacy of robust optimization plan with partial-arc VMAT for photon volumetric-modulated arc therapy: A phantom study.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Nagata, Yasushi

2017-09-01

This study investigated position dependence in planning target volume (PTV)-based and robust optimization plans using full-arc and partial-arc volumetric modulated arc therapy (VMAT). The gantry angles at the periphery, intermediate, and center CTV positions were 181°-180° (full-arc VMAT) and 181°-360° (partial-arc VMAT). A PTV-based optimization plan was defined by 5 mm margin expansion of the CTV to a PTV volume, on which the dose constraints were applied. The robust optimization plan consisted of a directly optimized dose to the CTV under a maximum-uncertainties setup of 5 mm. The prescription dose was normalized to the CTV D 99% (the minimum relative dose that covers 99% of the volume of the CTV) as an original plan. The isocenter was rigidly shifted at 1 mm intervals in the anterior-posterior (A-P), superior-inferior (S-I), and right-left (R-L) directions from the original position to the maximum-uncertainties setup of 5 mm in the original plan, yielding recalculated dose distributions. It was found that for the intermediate and center positions, the uncertainties in the D 99% doses to the CTV for all directions did not significantly differ when comparing the PTV-based and robust optimization plans (P > 0.05). For the periphery position, uncertainties in the D 99% doses to the CTV in the R-L direction for the robust optimization plan were found to be lower than those in the PTV-based optimization plan (P < 0.05). Our study demonstrated that a robust optimization plan's efficacy using partial-arc VMAT depends on the periphery CTV position. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

TU-EF-304-07: Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y; UT Southwestern Medical Center, Dallas, TX; Tian, Z

2015-06-15

Purpose: Intensity-modulated proton therapy (IMPT) is increasingly used in proton therapy. For IMPT optimization, Monte Carlo (MC) is desired for spots dose calculations because of its high accuracy, especially in cases with a high level of heterogeneity. It is also preferred in biological optimization problems due to the capability of computing quantities related to biological effects. However, MC simulation is typically too slow to be used for this purpose. Although GPU-based MC engines have become available, the achieved efficiency is still not ideal. The purpose of this work is to develop a new optimization scheme to include GPU-based MC intomore » IMPT. Methods: A conventional approach using MC in IMPT simply calls the MC dose engine repeatedly for each spot dose calculations. However, this is not the optimal approach, because of the unnecessary computations on some spots that turned out to have very small weights after solving the optimization problem. GPU-memory writing conflict occurring at a small beam size also reduces computational efficiency. To solve these problems, we developed a new framework that iteratively performs MC dose calculations and plan optimizations. At each dose calculation step, the particles were sampled from different spots altogether with Metropolis algorithm, such that the particle number is proportional to the latest optimized spot intensity. Simultaneously transporting particles from multiple spots also mitigated the memory writing conflict problem. Results: We have validated the proposed MC-based optimization schemes in one prostate case. The total computation time of our method was ∼5–6 min on one NVIDIA GPU card, including both spot dose calculation and plan optimization, whereas a conventional method naively using the same GPU-based MC engine were ∼3 times slower. Conclusion: A fast GPU-based MC dose calculation method along with a novel optimization workflow is developed. The high efficiency makes it attractive for clinical usages.« less

SU-F-T-428: An Optimization-Based Commissioning Tool for Finite Size Pencil Beam Dose Calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y; Tian, Z; Song, T

Purpose: Finite size pencil beam (FSPB) algorithms are commonly used to pre-calculate the beamlet dose distribution for IMRT treatment planning. FSPB commissioning, which usually requires fine tuning of the FSPB kernel parameters, is crucial to the dose calculation accuracy and hence the plan quality. Yet due to the large number of beamlets, FSPB commissioning could be very tedious. This abstract reports an optimization-based FSPB commissioning tool we have developed in MatLab to facilitate the commissioning. Methods: A FSPB dose kernel generally contains two types of parameters: the profile parameters determining the dose kernel shape, and a 2D scaling factors accountingmore » for the longitudinal and off-axis corrections. The former were fitted using the penumbra of a reference broad beam’s dose profile with Levenberg-Marquardt algorithm. Since the dose distribution of a broad beam is simply a linear superposition of the dose kernel of each beamlet calculated with the fitted profile parameters and scaled using the scaling factors, these factors could be determined by solving an optimization problem which minimizes the discrepancies between the calculated dose of broad beams and the reference dose. Results: We have commissioned a FSPB algorithm for three linac photon beams (6MV, 15MV and 6MVFFF). Dose of four field sizes (6*6cm2, 10*10cm2, 15*15cm2 and 20*20cm2) were calculated and compared with the reference dose exported from Eclipse TPS system. For depth dose curves, the differences are less than 1% of maximum dose after maximum dose depth for most cases. For lateral dose profiles, the differences are less than 2% of central dose at inner-beam regions. The differences of the output factors are within 1% for all the three beams. Conclusion: We have developed an optimization-based commissioning tool for FSPB algorithms to facilitate the commissioning, providing sufficient accuracy of beamlet dose calculation for IMRT optimization.« less

A method to incorporate leakage and head scatter corrections into a tomotherapy inverse treatment planning algorithm

NASA Astrophysics Data System (ADS)

Holmes, Timothy W.

2001-01-01

A detailed tomotherapy inverse treatment planning method is described which incorporates leakage and head scatter corrections during each iteration of the optimization process, allowing these effects to be directly accounted for in the optimized dose distribution. It is shown that the conventional inverse planning method for optimizing incident intensity can be extended to include a `concurrent' leaf sequencing operation from which the leakage and head scatter corrections are determined. The method is demonstrated using the steepest-descent optimization technique with constant step size and a least-squared error objective. The method was implemented using the MATLAB scientific programming environment and its feasibility demonstrated for 2D test cases simulating treatment delivery using a single coplanar rotation. The results indicate that this modification does not significantly affect convergence of the intensity optimization method when exposure times of individual leaves are stratified to a large number of levels (>100) during leaf sequencing. In general, the addition of aperture dependent corrections, especially `head scatter', reduces incident fluence in local regions of the modulated fan beam, resulting in increased exposure times for individual collimator leaves. These local variations can result in 5% or greater local variation in the optimized dose distribution compared to the uncorrected case. The overall efficiency of the modified intensity optimization algorithm is comparable to that of the original unmodified case.

SU-E-T-367: Optimization of DLG Using TG-119 Test Cases and a Weighted Mean Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sintay, B; Vanderstraeten, C; Terrell, J

2014-06-01

Purpose: Optimization of the dosimetric leaf gap (DLG) is an important step in commissioning the Eclipse treatment planning system for sliding window intensity-modulated radiation therapy (SW-IMRT) and RapidArc. Often the values needed for optimal dose delivery differ markedly from those measured at commissioning. We present a method to optimize this value using the AAPM TG-119 test cases. Methods: For SW-IMRT and RapidArc, TG-119 based test plans were created using a water-equivalent phantom. Dose distributions measured on film and ion chamber (IC) readings taken in low-gradient regions within the targets were analyzed separately. Since DLG is a single value per energy,more » SW-IMRT and RapidArc must be considered simultaneously. Plans were recalculated using a linear sweep from 0.02cm (the minimum DLG) to 0.3 cm. The calculated point doses were compared to the measured doses for each plan, and based on these comparisons an optimal DLG value was computed for each plan. TG-119 cases are designed to push the system in various ways, thus, a weighted mean of the DLG was computed where the relative importance of each type of plan was given a score from 0.0 to 1.0. Finally, SW-IMRT and RapidArc are assigned an overall weight based on clinical utilization. Our routine patient-QA (PQA) process was performed as independent validation. Results: For a Varian TrueBeam, the optimized DLG varied with σ = 0.044cm for SW-IMRT and σ = 0.035cm for RapidArc. The difference between the weighted mean SW-IMRT and RapidArc value was 0.038cm. We predicted utilization of 25% SW-IMRT and 75% RapidArc. The resulting DLG was ~1mm different than that found by commissioning and produced an average error of <1% for SW-IMRT and RapidArc PQA test cases separately. Conclusion: The weighted mean method presented is a useful tool for determining an optimal DLG value for commissioning Eclipse.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugano, Yasutaka; Mizuta, Masahiro; Takao, Seishin

Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of themore » tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.« less

Design of experiments confirms optimization of lithium administration parameters for enhanced fracture healing.

PubMed

Vachhani, Kathak; Pagotto, Andrea; Wang, Yufa; Whyne, Cari; Nam, Diane

2018-01-03

Fracture healing is a lengthy process which fails in 5-10% of cases. Lithium, a low-cost therapeutic used in psychiatric medicine, up-regulates the canonical Wingless pathway crucial for osteoblastic mineralization in fracture healing. A design-of-experiments (DOE) methodology was used to optimize lithium administration parameters (dose, onset time and treatment duration) to enhance healing in a rat femoral fracture model. In the previously completed first stage (screening), onset time was found to significantly impact healing, with later (day 7 vs. day 3 post-fracture) treatment yielding improved maximum yield torque. The greatest strength was found in healing femurs treated at day 7 post fracture, with a low lithium dose (20 mg/kg) for 2 weeks duration. This paper describes the findings of the second (optimization) and third (verification) stages of the DOE investigation. Closed traumatic diaphyseal femur fractures were induced in 3-month old rats. Healing was evaluated on day 28 post fracture by CT-based morphometry and torsional loading. In optimization, later onset times of day 10 and 14 did not perform as well as day 7 onset. As such, efficacy of the best regimen (20 mg/kg dose given at day 7 onset for 2 weeks duration) was reassessed in a distinct cohort of animals to complete the DOE verification. A significant 44% higher maximum yield torque (primary outcome) was seen with optimized lithium treatment vs. controls, which paralleled the 46% improvement seen in the screening stage. Successful completion of this robustly designed preclinical DOE study delineates the optimal lithium regimen for enhancing preclinical long-bone fracture healing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quality assurance for high dose rate brachytherapy treatment planning optimization: using a simple optimization to verify a complex optimization

NASA Astrophysics Data System (ADS)

Deufel, Christopher L.; Furutani, Keith M.

2014-02-01

As dose optimization for high dose rate brachytherapy becomes more complex, it becomes increasingly important to have a means of verifying that optimization results are reasonable. A method is presented for using a simple optimization as quality assurance for the more complex optimization algorithms typically found in commercial brachytherapy treatment planning systems. Quality assurance tests may be performed during commissioning, at regular intervals, and/or on a patient specific basis. A simple optimization method is provided that optimizes conformal target coverage using an exact, variance-based, algebraic approach. Metrics such as dose volume histogram, conformality index, and total reference air kerma agree closely between simple and complex optimizations for breast, cervix, prostate, and planar applicators. The simple optimization is shown to be a sensitive measure for identifying failures in a commercial treatment planning system that are possibly due to operator error or weaknesses in planning system optimization algorithms. Results from the simple optimization are surprisingly similar to the results from a more complex, commercial optimization for several clinical applications. This suggests that there are only modest gains to be made from making brachytherapy optimization more complex. The improvements expected from sophisticated linear optimizations, such as PARETO methods, will largely be in making systems more user friendly and efficient, rather than in finding dramatically better source strength distributions.

General equations for optimal selection of diagnostic image acquisition parameters in clinical X-ray imaging.

PubMed

Zheng, Xiaoming

2017-12-01

The purpose of this work was to examine the effects of relationship functions between diagnostic image quality and radiation dose on the governing equations for image acquisition parameter variations in X-ray imaging. Various equations were derived for the optimal selection of peak kilovoltage (kVp) and exposure parameter (milliAmpere second, mAs) in computed tomography (CT), computed radiography (CR), and direct digital radiography. Logistic, logarithmic, and linear functions were employed to establish the relationship between radiation dose and diagnostic image quality. The radiation dose to the patient, as a function of image acquisition parameters (kVp, mAs) and patient size (d), was used in radiation dose and image quality optimization. Both logistic and logarithmic functions resulted in the same governing equation for optimal selection of image acquisition parameters using a dose efficiency index. For image quality as a linear function of radiation dose, the same governing equation was derived from the linear relationship. The general equations should be used in guiding clinical X-ray imaging through optimal selection of image acquisition parameters. The radiation dose to the patient could be reduced from current levels in medical X-ray imaging.

A comprehensive formulation for volumetric modulated arc therapy planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Dan; Lyu, Qihui; Ruan, Dan

2016-07-15

Purpose: Volumetric modulated arc therapy (VMAT) is a widely employed radiation therapy technique, showing comparable dosimetry to static beam intensity modulated radiation therapy (IMRT) with reduced monitor units and treatment time. However, the current VMAT optimization has various greedy heuristics employed for an empirical solution, which jeopardizes plan consistency and quality. The authors introduce a novel direct aperture optimization method for VMAT to overcome these limitations. Methods: The comprehensive VMAT (comVMAT) planning was formulated as an optimization problem with an L2-norm fidelity term to penalize the difference between the optimized dose and the prescribed dose, as well as an anisotropicmore » total variation term to promote piecewise continuity in the fluence maps, preparing it for direct aperture optimization. A level set function was used to describe the aperture shapes and the difference between aperture shapes at adjacent angles was penalized to control MLC motion range. A proximal-class optimization solver was adopted to solve the large scale optimization problem, and an alternating optimization strategy was implemented to solve the fluence intensity and aperture shapes simultaneously. Single arc comVMAT plans, utilizing 180 beams with 2° angular resolution, were generated for a glioblastoma multiforme case, a lung (LNG) case, and two head and neck cases—one with three PTVs (H&N{sub 3PTV}) and one with foue PTVs (H&N{sub 4PTV})—to test the efficacy. The plans were optimized using an alternating optimization strategy. The plans were compared against the clinical VMAT (clnVMAT) plans utilizing two overlapping coplanar arcs for treatment. Results: The optimization of the comVMAT plans had converged within 600 iterations of the block minimization algorithm. comVMAT plans were able to consistently reduce the dose to all organs-at-risk (OARs) as compared to the clnVMAT plans. On average, comVMAT plans reduced the max and mean OAR dose by 6.59% and 7.45%, respectively, of the prescription dose. Reductions in max dose and mean dose were as high as 14.5 Gy in the LNG case and 15.3 Gy in the H&N{sub 3PTV} case. PTV coverages measured by D95, D98, and D99 were within 0.25% of the prescription dose. By comprehensively optimizing all beams, the comVMAT optimizer gained the freedom to allow some selected beams to deliver higher intensities, yielding a dose distribution that resembles a static beam IMRT plan with beam orientation optimization. Conclusions: The novel nongreedy VMAT approach simultaneously optimizes all beams in an arc and then directly generates deliverable apertures. The single arc VMAT approach thus fully utilizes the digital Linac’s capability in dose rate and gantry rotation speed modulation. In practice, the new single VMAT algorithm generates plans superior to existing VMAT algorithms utilizing two arcs.« less

SU-E-J-07: IGRT Gently: Evaluating Imaging Dose in Phantoms of Different Sizes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, B; Duggar, W; Stanford, J

Purpose: IGRT imaging procedures have emerged as a common method of patient position verification in radiotherapy, though imaging dose is generally neglected in the treatment plan. Consequently, evaluating and optimizing the dose from these procedures is worthwhile. This process is especially important for children, who are more radiosensitive than adults. The aim of this work was to gain some understanding of the relative doses involved with various XVI-preset parameters for an “adult” and “child” phantom set, with the hopes that imaging dose for a child can be reduced. Methods: 32 and 16cm CTDI-phantoms were used as surrogates for adult andmore » child torsos, respectively. Dose was measured in the central and peripheral chamber positions of the phantoms. CBCT scans were made for both phantoms using Elekta’s Chest-preset to establish a dose baseline. The child-phantom was then scanned using the Elekta Head and Neck (HN) preset. A modified HN-preset (named Peds Abd-pelvis) was also created with a doubled mAs to maintain a reduction in dose to the child-phantom (relative to the baseline), while providing clinically-usable image quality. Results: The baseline dose to the child-phantom from the Chest-preset was 310% that of the adult-phantom for the center chamber position and 150% at the periphery. An average dose reduction of 97% was obtained in the childphantom by switching from the Chest-preset to the HN-preset, while the Peds Abd-pelvis-preset similarly reduced the dose by an average of 92%. Conclusion: XVI-preset parameters significantly affect dose, and should be optimized to reduce dose, while ensuring clinically-usable image quality. Using a modified imaging preset (Peds Abd-pelvis-preset) greatly reduced the dose to the child-phantom compared to the dose for the Chest-preset for both the child and adult-phantoms. This outcome provides support for the development of child-specific protocols for IGRT imaging in pediatric patients.« less

Use of a channelized Hotelling observer to assess CT image quality and optimize dose reduction for iteratively reconstructed images.

PubMed

Favazza, Christopher P; Ferrero, Andrea; Yu, Lifeng; Leng, Shuai; McMillan, Kyle L; McCollough, Cynthia H

2017-07-01

The use of iterative reconstruction (IR) algorithms in CT generally decreases image noise and enables dose reduction. However, the amount of dose reduction possible using IR without sacrificing diagnostic performance is difficult to assess with conventional image quality metrics. Through this investigation, achievable dose reduction using a commercially available IR algorithm without loss of low contrast spatial resolution was determined with a channelized Hotelling observer (CHO) model and used to optimize a clinical abdomen/pelvis exam protocol. A phantom containing 21 low contrast disks-three different contrast levels and seven different diameters-was imaged at different dose levels. Images were created with filtered backprojection (FBP) and IR. The CHO was tasked with detecting the low contrast disks. CHO performance indicated dose could be reduced by 22% to 25% without compromising low contrast detectability (as compared to full-dose FBP images) whereas 50% or more dose reduction significantly reduced detection performance. Importantly, default settings for the scanner and protocol investigated reduced dose by upward of 75%. Subsequently, CHO-based protocol changes to the default protocol yielded images of higher quality and doses more consistent with values from a larger, dose-optimized scanner fleet. CHO assessment provided objective data to successfully optimize a clinical CT acquisition protocol.

Harmony search optimization for HDR prostate brachytherapy

NASA Astrophysics Data System (ADS)

Panchal, Aditya

In high dose-rate (HDR) prostate brachytherapy, multiple catheters are inserted interstitially into the target volume. The process of treating the prostate involves calculating and determining the best dose distribution to the target and organs-at-risk by means of optimizing the time that the radioactive source dwells at specified positions within the catheters. It is the goal of this work to investigate the use of a new optimization algorithm, known as Harmony Search, in order to optimize dwell times for HDR prostate brachytherapy. The new algorithm was tested on 9 different patients and also compared with the genetic algorithm. Simulations were performed to determine the optimal value of the Harmony Search parameters. Finally, multithreading of the simulation was examined to determine potential benefits. First, a simulation environment was created using the Python programming language and the wxPython graphical interface toolkit, which was necessary to run repeated optimizations. DICOM RT data from Varian BrachyVision was parsed and used to obtain patient anatomy and HDR catheter information. Once the structures were indexed, the volume of each structure was determined and compared to the original volume calculated in BrachyVision for validation. Dose was calculated using the AAPM TG-43 point source model of the GammaMed 192Ir HDR source and was validated against Varian BrachyVision. A DVH-based objective function was created and used for the optimization simulation. Harmony Search and the genetic algorithm were implemented as optimization algorithms for the simulation and were compared against each other. The optimal values for Harmony Search parameters (Harmony Memory Size [HMS], Harmony Memory Considering Rate [HMCR], and Pitch Adjusting Rate [PAR]) were also determined. Lastly, the simulation was modified to use multiple threads of execution in order to achieve faster computational times. Experimental results show that the volume calculation that was implemented in this thesis was within 2% of the values computed by Varian BrachyVision for the prostate, within 3% for the rectum and bladder and 6% for the urethra. The calculation of dose compared to BrachyVision was determined to be different by only 0.38%. Isodose curves were also generated and were found to be similar to BrachyVision. The comparison between Harmony Search and genetic algorithm showed that Harmony Search was over 4 times faster when compared over multiple data sets. The optimal Harmony Memory Size was found to be 5 or lower; the Harmony Memory Considering Rate was determined to be 0.95, and the Pitch Adjusting Rate was found to be 0.9. Ultimately, the effect of multithreading showed that as intensive computations such as optimization and dose calculation are involved, the threads of execution scale with the number of processors, achieving a speed increase proportional to the number of processor cores. In conclusion, this work showed that Harmony Search is a viable alternative to existing algorithms for use in HDR prostate brachytherapy optimization. Coupled with the optimal parameters for the algorithm and a multithreaded simulation, this combination has the capability to significantly decrease the time spent on minimizing optimization problems in the clinic that are time intensive, such as brachytherapy, IMRT and beam angle optimization.

SU-E-T-618: Dosimetric Comparison of Manual and Beam Angle Optimization of Gantry Angles in IMRT for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, X; Sun, T; Liu, T

2014-06-01

Purpose: To evaluate the dosimetric characteristics of intensity-modulated radiotherapy (IMRT) treatment plan with beam angle optimization. Methods: Ten post-operation patients with cervical cancer were included in this analysis. Two IMRT plans using seven beams were designed in each patient. A standard coplanar equi-space beam angles were used in the first plan (plan 1), whereas the selection of beam angle was optimized by beam angle optimization algorithm in Varian Eclipse treatment planning system for the same number of beams in the second plan (plan 2). Two plans were designed for each patient with the same dose-volume constraints and prescription dose. Allmore » plans were normalized to the mean dose to PTV. The dose distribution in the target, the dose to the organs at risk and total MU were compared. Results: For conformity and homogeneity in PTV, no statistically differences were observed in the two plans. For the mean dose in bladder, plan 2 were significantly lower than plan 1(p<0.05). No statistically significant differences were observed between two plans for the mean doses in rectum, left and right femur heads. Compared with plan1, the average monitor units reduced 16% in plan 2. Conclusion: The IMRT plan based on beam angle optimization for cervical cancer could reduce the dose delivered to bladder and also reduce MU. Therefore there were some dosimetric advantages in the IMRT plan with beam angle optimization for cervical cancer.« less

Optimal sensitometric curves of Kodak EDR2 film for dynamic intensity modulated radiation therapy verification

PubMed Central

Suriyapee, S; Pitaxtarnin, N; Oonsiri, S; Jumpangern, C; Israngkul Na Ayuthaya, I

2008-01-01

Purpose: To investigate the optimal sensitometric curves of extended dose range (EDR2) radiographic film in terms of depth, field size, dose range and processing conditions for dynamic intensity modulated radiation therapy (IMRT) dosimetry verification with 6 MV X-ray beams. Materials and methods: A Varian Clinac 23 EX linear accelerator with 6 MV X-ray beam was used to study the response of Kodak EDR2 film. Measurements were performed at depths of 5, 10 and 15 cm in MedTec virtual water phantom and with field sizes of 2x2, 3x3, 10x10 and 15x15 cm2. Doses ranging from 20 to 450 cGy were used. The film was developed with the Kodak RP X-OMAT Model M6B automatic film processor. Film response was measured with the Vidar model VXR-16 scanner. Sensitometric curves were applied to the dose profiles measured with film at 5 cm in the virtual water phantom with field sizes of 2x2 and 10x10 cm2 and compared with ion chamber data. Scanditronix/Wellhofer OmniProTM IMRT software was used for the evaluation of the IMRT plan calculated by Eclipse treatment planning. Results: Investigation of the reproducibility and accuracy of the film responses, which depend mainly on the film processor, was carried out by irradiating one film nine times with doses of 20 to 450 cGy. A maximum standard deviation of 4.9% was found which decreased to 1.9% for doses between 20 and 200 cGy. The sensitometric curves for various field sizes at fixed depth showed a maximum difference of 4.2% between 2x2 and 15x15 cm2 at 5 cm depth with a dose of 450 cGy. The shallow depth tended to show a greater effect of field size responses than the deeper depths. The sensitometric curves for various depths at fixed field size showed slightly different film responses; the difference due to depth was within 1.8% for all field sizes studied. Both field size and depth effect were reduced when the doses were lower than 450 cGy. The difference was within 2.5% in the dose range from 20 to 300 cGy for all field sizes and depths studied. Dose profiles measured with EDR2 film were consistent with those measured with an ion chamber. The optimal sensitometric curve was acquired by irradiating film at a depth of 5 cm with doses ranging from 20 to 450 cGy with a 3×3 cm2 multileaf collimator. The optimal sensitometric curve allowed accurate determination of the absolute dose distribution. In almost 200 cases of dynamic IMRT plan verification with EDR2 film, the difference between measured and calculated dose was generally less than 3% and with 3 mm distance to agreement when using gamma value verification. Conclusion: EDR2 film can be used for accurate verification of composite isodose distributions of dynamic IMRT when the optimal sensitometric curve has been established. PMID:21614315

Optimal sensitometric curves of Kodak EDR2 film for dynamic intensity modulated radiation therapy verification.

PubMed

Suriyapee, S; Pitaxtarnin, N; Oonsiri, S; Jumpangern, C; Israngkul Na Ayuthaya, I

2008-01-01

To investigate the optimal sensitometric curves of extended dose range (EDR2) radiographic film in terms of depth, field size, dose range and processing conditions for dynamic intensity modulated radiation therapy (IMRT) dosimetry verification with 6 MV X-ray beams. A Varian Clinac 23 EX linear accelerator with 6 MV X-ray beam was used to study the response of Kodak EDR2 film. Measurements were performed at depths of 5, 10 and 15 cm in MedTec virtual water phantom and with field sizes of 2x2, 3x3, 10x10 and 15x15 cm(2). Doses ranging from 20 to 450 cGy were used. The film was developed with the Kodak RP X-OMAT Model M6B automatic film processor. Film response was measured with the Vidar model VXR-16 scanner. Sensitometric curves were applied to the dose profiles measured with film at 5 cm in the virtual water phantom with field sizes of 2x2 and 10x10 cm(2) and compared with ion chamber data. Scanditronix/Wellhofer OmniPro(TM) IMRT software was used for the evaluation of the IMRT plan calculated by Eclipse treatment planning. Investigation of the reproducibility and accuracy of the film responses, which depend mainly on the film processor, was carried out by irradiating one film nine times with doses of 20 to 450 cGy. A maximum standard deviation of 4.9% was found which decreased to 1.9% for doses between 20 and 200 cGy. The sensitometric curves for various field sizes at fixed depth showed a maximum difference of 4.2% between 2x2 and 15x15 cm(2) at 5 cm depth with a dose of 450 cGy. The shallow depth tended to show a greater effect of field size responses than the deeper depths. The sensitometric curves for various depths at fixed field size showed slightly different film responses; the difference due to depth was within 1.8% for all field sizes studied. Both field size and depth effect were reduced when the doses were lower than 450 cGy. The difference was within 2.5% in the dose range from 20 to 300 cGy for all field sizes and depths studied. Dose profiles measured with EDR2 film were consistent with those measured with an ion chamber. The optimal sensitometric curve was acquired by irradiating film at a depth of 5 cm with doses ranging from 20 to 450 cGy with a 3×3 cm(2) multileaf collimator. The optimal sensitometric curve allowed accurate determination of the absolute dose distribution. In almost 200 cases of dynamic IMRT plan verification with EDR2 film, the difference between measured and calculated dose was generally less than 3% and with 3 mm distance to agreement when using gamma value verification. EDR2 film can be used for accurate verification of composite isodose distributions of dynamic IMRT when the optimal sensitometric curve has been established.

Development of light ion therapy at the Karolinska Hospital and Institute.

PubMed

Svensson, Hans; Ringborg, Ulrik; Näslund, Ingemar; Brahme, Anders

2004-12-01

Recent developments in radiation therapy have made it possible to optimize the high dose region to cover almost any target volume and shape at the same time as the dose level to adjacent organs at risk is acceptable. Further implementations of IMRT (Intensity Modulated Radiation Therapy), and inverse treatment planning using already available technologies but also foreseeable improved design of therapy accelerators delivering electron- and photon beams, will bring these advances to the benefit of a broad population of cancer patients. Protons will therefore generally not be needed since in most situations the improvement will be insignificant or moderate due to the large lateral penumbra with deep proton therapy. A further step would be to use He-ions, which have only half the penumbra width of protons and still a fairly low-LET in the spread-out Bragg peak. There is however still a group of patients that cannot be helped by these advances as the tumor might be radioresistant for the presently utilized low ionization density beam qualities. The ultimate step in the therapy development process should therefore be to optimize the beam quality for each tumor-normal tissue situation. To facilitate beam quality optimization light ions are needed. It is argued that in many radioresistant tumors a dose-mean LET of 25-50 eV/nm in the target would be optimum as then tumor cells will be lost in the highest proportion through apoptotic cell kill and the superficial tissues will still be irradiated with a fairly low LET. Light ions using Li, Be, B, and C would then be the ideal choice. In this paper a light ion facility is outlined for the Karolinska University Hospital facilitating both dose distribution and beam quality optimization.

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

Multiple anatomy optimization of accumulated dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V.; Moore, Joseph A.

Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dosemore » variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.« less

SU-E-T-502: Initial Results of a Comparison of Treatment Plans Produced From Automated Prioritized Planning Method and a Commercial Treatment Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tiwari, P; Chen, Y; Hong, L

2015-06-15

Purpose We developed an automated treatment planning system based on a hierarchical goal programming approach. To demonstrate the feasibility of our method, we report the comparison of prostate treatment plans produced from the automated treatment planning system with those produced by a commercial treatment planning system. Methods In our approach, we prioritized the goals of the optimization, and solved one goal at a time. The purpose of prioritization is to ensure that higher priority dose-volume planning goals are not sacrificed to improve lower priority goals. The algorithm has four steps. The first step optimizes dose to the target structures, whilemore » sparing key sensitive organs from radiation. In the second step, the algorithm finds the best beamlet weight to reduce toxicity risks to normal tissue while holding the objective function achieved in the first step as a constraint, with a small amount of allowed slip. Likewise, the third and fourth steps introduce lower priority normal tissue goals and beam smoothing. We compared with prostate treatment plans from Memorial Sloan Kettering Cancer Center developed using Eclipse, with a prescription dose of 72 Gy. A combination of liear, quadratic, and gEUD objective functions were used with a modified open source solver code (IPOPT). Results Initial plan results on 3 different cases show that the automated planning system is capable of competing or improving on expert-driven eclipse plans. Compared to the Eclipse planning system, the automated system produced up to 26% less mean dose to rectum and 24% less mean dose to bladder while having the same D95 (after matching) to the target. Conclusion We have demonstrated that Pareto optimal treatment plans can be generated automatically without a trial-and-error process. The solver finds an optimal plan for the given patient, as opposed to database-driven approaches that set parameters based on geometry and population modeling.« less

An investigation of flat panel equipment variables on image quality with a dedicated cardiac phantom

NASA Astrophysics Data System (ADS)

Dragusin, O.; Bosmans, H.; Pappas, C.; Desmet, W.

2008-09-01

Image quality (IQ) evaluation plays a key role in the process of optimization of new x-ray systems. Ideally, this process should be supported by real clinical images, but ethical issues and differences in anatomy and pathology of patients make it impossible. Phantom studies might overcome these issues. This paper presents the IQ evaluation of 30 cineangiographic films acquired with a cardiac flat panel system. The phantom used simulates the anatomy of the heart and allows the circulation of contrast agent boluses through coronary arteries. Variables investigated with influence on IQ and radiation dose are: tube potential, detector dose, added Copper filters, dynamic density optimization (DDO) and viewing angle. The IQ evaluation consisted of scoring 4 simulated calcified lesions located on different coronary artery segments in terms of degree of visualization. Eight cardiologists rated the lesions using a five-point scale ((1) lesion not visible to (5) very good visibility). Radiation doses associated to the angiograms are expressed in terms of incident air kerma (IAK) and effective dose that has been calculated with PCXMX software (STUK, Finland) from the exposure settings assuming a standard sized patient of 70 Kg. Mean IQ scores ranged from 1.68 to 4.88. The highest IQ scores were obtained for the angiograms acquired with tube potential 80 kVp, no added Cu filters, DDO 60%, RAO and LAO views and the highest entrance detector dose that has been used in the present study, namely 0.17 μGy/im. Radiation doses (IAK ~40 mGy and effective dose of 1 mSv) were estimated for angiograms acquired at 15 frames s-1, detector field-of-view 20 cm, and a length of 5 s. The following parameters improved the IQ factor significantly: a change in tube potential from 96 to 80 kVp, detector dose from 0.10 μGy/im to 0.17 μGy/im, the absence of Copper filtration. DDO variable which is a post-processing parameter should be carefully evaluated because it alters the quality of the images independently of radiation exposure settings. The SAM anthropomorphic phantom has the advantage of visualization of stenotic lesions during the injection of a contrast agent and using an anatomical background. In the future, this phantom could potentially bridge the gap between physics tests and the clinical reality in the catheterization laboratory.

SU-F-T-453: Improved Head and Neck SBRT Treatment Planning Using PlanIQ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, H; Wang, C; Phan, J

Purpose: Treatment planning for Head and Neck(HN) re-irradiation is a challenge because of ablative doses to target volume and strict critical structure constraints. PlanIQ(Sun Nuclear Corporation) can assess the feasibility of clinical goals and quantitatively measure plan quality. Here, we assess whether incorporation of PlanIQ in our SBRT treatment planning process can improve plan quality and planning efficiency. Methods: From 2013–2015, 35 patients (29 retrospective, 6 prospective) with recurrent HN tumors were treated with SBRT using VMAT treatment plans. The median prescription dose was 45 Gy in 5 fractions. We retrospectively reviewed the treatment plans and physician directives of ourmore » first 29 patients and generated score functions of the dosimetric goals used in our practice and obtained a baseline histogram. We then re-optimized 12 plans that had potential to further reduce organs-at-risk (OAR) doses according to PlanIQ feasibility DVH and plan quality analysis and compared them to the original plans. We applied our new PlanIQ-assisted planning process for our 6 most recently treated patients and evaluated the plan quality and planning efficiency. Results: The mean plan quality metric(PQM) and feasibility adjusted PQM(APQM) scores of our initial 29 treatment plans were 77.1±13.1 and 88.7±11.9, respectively (0–100 scale). The PQM and APQM scores for the 12 optimized plans improved from 75.9±11.0 and 85.1±10.2 to 80.7±9.3 and 90.2±8.0, respectively (p<0.005). Using our newly developed PlanIQ-assisted planning process, the PQM and APQM scores for the 6 most recently treated patients were 93.6±6.5 and 99.1±0.6, respectively. The planning goals were more straightforward to minimize OAR doses during optimization, thus less planning and revision time were used than before. Conclusion: PlanIQ has the potential to provide achievable planning goals and also improve plan quality and planning efficiency.« less

Comparison of linear and nonlinear programming approaches for "worst case dose" and "minmax" robust optimization of intensity-modulated proton therapy dose distributions.

PubMed

Zaghian, Maryam; Cao, Wenhua; Liu, Wei; Kardar, Laleh; Randeniya, Sharmalee; Mohan, Radhe; Lim, Gino

2017-03-01

Robust optimization of intensity-modulated proton therapy (IMPT) takes uncertainties into account during spot weight optimization and leads to dose distributions that are resilient to uncertainties. Previous studies demonstrated benefits of linear programming (LP) for IMPT in terms of delivery efficiency by considerably reducing the number of spots required for the same quality of plans. However, a reduction in the number of spots may lead to loss of robustness. The purpose of this study was to evaluate and compare the performance in terms of plan quality and robustness of two robust optimization approaches using LP and nonlinear programming (NLP) models. The so-called "worst case dose" and "minmax" robust optimization approaches and conventional planning target volume (PTV)-based optimization approach were applied to designing IMPT plans for five patients: two with prostate cancer, one with skull-based cancer, and two with head and neck cancer. For each approach, both LP and NLP models were used. Thus, for each case, six sets of IMPT plans were generated and assessed: LP-PTV-based, NLP-PTV-based, LP-worst case dose, NLP-worst case dose, LP-minmax, and NLP-minmax. The four robust optimization methods behaved differently from patient to patient, and no method emerged as superior to the others in terms of nominal plan quality and robustness against uncertainties. The plans generated using LP-based robust optimization were more robust regarding patient setup and range uncertainties than were those generated using NLP-based robust optimization for the prostate cancer patients. However, the robustness of plans generated using NLP-based methods was superior for the skull-based and head and neck cancer patients. Overall, LP-based methods were suitable for the less challenging cancer cases in which all uncertainty scenarios were able to satisfy tight dose constraints, while NLP performed better in more difficult cases in which most uncertainty scenarios were hard to meet tight dose limits. For robust optimization, the worst case dose approach was less sensitive to uncertainties than was the minmax approach for the prostate and skull-based cancer patients, whereas the minmax approach was superior for the head and neck cancer patients. The robustness of the IMPT plans was remarkably better after robust optimization than after PTV-based optimization, and the NLP-PTV-based optimization outperformed the LP-PTV-based optimization regarding robustness of clinical target volume coverage. In addition, plans generated using LP-based methods had notably fewer scanning spots than did those generated using NLP-based methods. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Vectorial mask optimization methods for robust optical lithography

NASA Astrophysics Data System (ADS)

Ma, Xu; Li, Yanqiu; Guo, Xuejia; Dong, Lisong; Arce, Gonzalo R.

2012-10-01

Continuous shrinkage of critical dimension in an integrated circuit impels the development of resolution enhancement techniques for low k1 lithography. Recently, several pixelated optical proximity correction (OPC) and phase-shifting mask (PSM) approaches were developed under scalar imaging models to account for the process variations. However, the lithography systems with larger-NA (NA>0.6) are predominant for current technology nodes, rendering the scalar models inadequate to describe the vector nature of the electromagnetic field that propagates through the optical lithography system. In addition, OPC and PSM algorithms based on scalar models can compensate for wavefront aberrations, but are incapable of mitigating polarization aberrations in practical lithography systems, which can only be dealt with under the vector model. To this end, we focus on developing robust pixelated gradient-based OPC and PSM optimization algorithms aimed at canceling defocus, dose variation, wavefront and polarization aberrations under a vector model. First, an integrative and analytic vector imaging model is applied to formulate the optimization problem, where the effects of process variations are explicitly incorporated in the optimization framework. A steepest descent algorithm is then used to iteratively optimize the mask patterns. Simulations show that the proposed algorithms can effectively improve the process windows of the optical lithography systems.

Optimization of methylene blue using Ca(2+) and Zn(2+) bio-polymer hydrogel beads: A comparative study.

PubMed

Kumar, M; Tamilarasan, R; Arthanareeswaran, G; Ismail, A F

2015-11-01

Recently noted that the methylene blue cause severe central nervous system toxicity. It is essential to optimize the methylene blue from aqueous environment. In this study, a comparison of an optimization of methylene blue was investigated by using modified Ca(2+) and Zn(2+) bio-polymer hydrogel beads. A batch mode study was conducted using various parameters like time, dye concentration, bio-polymer dose, pH and process temperature. The isotherms, kinetics, diffusion and thermodynamic studies were performed for feasibility of the optimization process. Freundlich and Langmuir isotherm equations were used for the prediction of isotherm parameters and correlated with dimensionless separation factor (RL). Pseudo-first order and pseudo-second order Lagegren's kinetic equations were used for the correlation of kinetic parameters. Intraparticle diffusion model was employed for diffusion of the optimization process. The Fourier Transform Infrared Spectroscopy (FTIR) shows different absorbent peaks of Ca(2+) and Zn(2+) beads and the morphology of the bio-polymer material analyzed with Scanning Electron Microscope (SEM). The TG & DTA studies show that good thermal stability with less humidity without production of any non-degraded products. Copyright © 2015 Elsevier Inc. All rights reserved.

Challenges and Potential Solutions – Individualised Antibiotic Dosing at the Bedside for Critically Ill Patients: a structured review

PubMed Central

Roberts, Jason A.; Aziz, Mohd Hafiz Abdul; Lipman, Jeffrey; Mouton, Johan W.; Vinks, Alexander A.; Felton, Timothy W.; Hope, William W.; Farkas, Andras; Neely, Michael N.; Schentag, Jerome J.; Drusano, George; Frey, Otto R.; Theuretzbacher, Ursula; Kuti, Joseph L.

2014-01-01

Summary Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in sub-optimal outcomes. In this paper, we review the patient- and pathogen-related challenges that contribute to inadequate antibiotic dosing and discuss how a process for individualised antibiotic therapy, that increases the accuracy of dosing, can be implemented to further optimise care for the critically ill patient. The process for optimised antibiotic dosing firstly requires determination of the physiological derangements in the patient that can alter antibiotic concentrations including altered fluid status, microvascular failure, serum albumin concentrations as well as altered renal and hepatic function. Secondly, knowledge of the susceptibility of the infecting pathogen should be determined through liaison with the microbiology laboratory. The patient and pathogen challenges can then be solved by combining susceptibility data with measured antibiotic concentration data (where possible) into a clinical dosing software. Such software uses pharmacokinetic-pharmacodynamic (PK/PD) models from critically ill patients to accurately predict the dosing requirements for the individual patient with the aim of optimising antibiotic exposure and maximising effectiveness. PMID:24768475

Optimization of beam shaping assembly based on D-T neutron generator and dose evaluation for BNCT

NASA Astrophysics Data System (ADS)

Naeem, Hamza; Chen, Chaobin; Zheng, Huaqing; Song, Jing

2017-04-01

The feasibility of developing an epithermal neutron beam for a boron neutron capture therapy (BNCT) facility based on a high intensity D-T fusion neutron generator (HINEG) and using the Monte Carlo code SuperMC (Super Monte Carlo simulation program for nuclear and radiation process) is proposed in this study. The Monte Carlo code SuperMC is used to determine and optimize the final configuration of the beam shaping assembly (BSA). The optimal BSA design in a cylindrical geometry which consists of a natural uranium sphere (14 cm) as a neutron multiplier, AlF3 and TiF3 as moderators (20 cm each), Cd (1 mm) as a thermal neutron filter, Bi (5 cm) as a gamma shield, and Pb as a reflector and collimator to guide neutrons towards the exit window. The epithermal neutron beam flux of the proposed model is 5.73 × 109 n/cm2s, and other dosimetric parameters for the BNCT reported by IAEA-TECDOC-1223 have been verified. The phantom dose analysis shows that the designed BSA is accurate, efficient and suitable for BNCT applications. Thus, the Monte Carlo code SuperMC is concluded to be capable of simulating the BSA and the dose calculation for BNCT, and high epithermal flux can be achieved using proposed BSA.

SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT

PubMed Central

Halliburton, Sandra S.; Abbara, Suhny; Chen, Marcus Y.; Gentry, Ralph; Mahesh, Mahadevappa; Raff, Gilbert L.; Shaw, Leslee J.; Hausleiter, Jörg

2012-01-01

Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring. PMID:21723512

Process optimization for the preparation of straw feedstuff for rearing yellow mealworms (Tenebrio molitor L.) in BLSS

NASA Astrophysics Data System (ADS)

Li, Leyuan; Liu, lh64. Hong

2012-07-01

It has been confirmed in our previous work that in bioregenerative life support systems, feeding yellow mealworms (Tenebrio molitor L.) using fermented straw has the potential to provide good animal protein for astronauts, meanwhile treating with plant wastes. However, since the nitrogen content in straw is very low, T. molitor larvae can not obtain sufficient nitrogen, which results in a relatively low growth efficiency. In this study, wheat straw powder was mixed with simulated human urine before fermentation. Condition parameters, e.g. urine:straw ratio, moisture content, inoculation dose, fermentation time, fermentation temperature and pH were optimized using Taguchi method. Larval growth rate and average individual mass of mature larva increased significantly in the group of T. molitor larvae fed with feedstuff prepared with the optimized process.

SU-E-T-500: Initial Implementation of GPU-Based Particle Swarm Optimization for 4D IMRT Planning in Lung SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Modiri, A; Hagan, A; Gu, X

Purpose 4D-IMRT planning, combined with dynamic MLC tracking delivery, utilizes the temporal dimension as an additional degree of freedom to achieve improved OAR-sparing. The computational complexity for such optimization increases exponentially with increase in dimensionality. In order to accomplish this task in a clinically-feasible time frame, we present an initial implementation of GPU-based 4D-IMRT planning based on particle swarm optimization (PSO). Methods The target and normal structures were manually contoured on ten phases of a 4DCT scan of a NSCLC patient with a 54cm3 right-lower-lobe tumor (1.5cm motion). Corresponding ten 3D-IMRT plans were created in the Eclipse treatment planning systemmore » (Ver-13.6). A vendor-provided scripting interface was used to export 3D-dose matrices corresponding to each control point (10 phases × 9 beams × 166 control points = 14,940), which served as input to PSO. The optimization task was to iteratively adjust the weights of each control point and scale the corresponding dose matrices. In order to handle the large amount of data in GPU memory, dose matrices were sparsified and placed in contiguous memory blocks with the 14,940 weight-variables. PSO was implemented on CPU (dual-Xeon, 3.1GHz) and GPU (dual-K20 Tesla, 2496 cores, 3.52Tflops, each) platforms. NiftyReg, an open-source deformable image registration package, was used to calculate the summed dose. Results The 4D-PSO plan yielded PTV coverage comparable to the clinical ITV-based plan and significantly higher OAR-sparing, as follows: lung Dmean=33%; lung V20=27%; spinal cord Dmax=26%; esophagus Dmax=42%; heart Dmax=0%; heart Dmean=47%. The GPU-PSO processing time for 14940 variables and 7 PSO-particles was 41% that of CPU-PSO (199 vs. 488 minutes). Conclusion Truly 4D-IMRT planning can yield significant OAR dose-sparing while preserving PTV coverage. The corresponding optimization problem is large-scale, non-convex and computationally rigorous. Our initial results indicate that GPU-based PSO with further software optimization can make such planning clinically feasible. This work was supported through funding from the National Institutes of Health and Varian Medical Systems.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorissen, BL; Giantsoudi, D; Unkelbach, J

Purpose: Cell survival experiments suggest that the relative biological effectiveness (RBE) of proton beams depends on linear energy transfer (LET), leading to higher RBE near the end of range. With intensity-modulated proton therapy (IMPT), multiple treatment plans that differ in the dose contribution per field may yield a similar physical dose distribution, but the RBE-weighted dose distribution may be disparate. RBE models currently do not have the required predictive power to be included in an optimization model due to the variations in experimental data. We propose an LET-based planning method that guides IMPT optimization models towards plans with reduced RBE-weightedmore » dose in surrounding organs at risk (OARs) compared to inverse planning based on physical dose alone. Methods: Optimization models for physical dose are extended with a term for dose times LET (doseLET). Monte Carlo code is used to generate the physical dose and doseLET distribution of each individual pencil beam. The method is demonstrated for an atypical meningioma patient where the target volume abuts the brainstem and partially overlaps with the optic nerve. Results: A reference plan optimized based on physical dose alone yields high doseLET values in parts of the brainstem and optic nerve. Minimizing doseLET in these critical structures as an additional planning goal reduces the risk of high RBE-weighted dose. The resulting treatment plan avoids the distal fall-off of the Bragg peaks for shaping the dose distribution in front of critical stuctures. The maximum dose in the OARs evaluated with RBE models from literature is reduced by 8–14\\% with our method compared to conventional planning. Conclusion: LET-based inverse planning for IMPT offers the ability to reduce the RBE-weighted dose in OARs without sacrificing target dose. This project was in part supported by NCI - U19 CA 21239.« less

Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements.

PubMed

Mantel, Irmela

2015-06-01

This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which- although not the classical interpretation of translation from fundamental to clinical research, but a subsequent process after the pivotal clinical trials - represents an important translational step from the clinical proof of efficacy to optimization in terms of patients' and clinics' needs. The related scientific procedure includes the exploration of the concept, evaluation of security, and finally proof of efficacy.

SU-F-P-61: Does It Matter Not to Use Optimization Points at the Apex for Vaginal Cylinder HDR Brachytherapy Planning?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Y

2016-06-15

Purpose: To test the impact of the use of apex optimization points for new vaginal cylinder (VC) applicators. Methods: New “ClickFit” single channel VC applicators (Varian) that have a different top thicknesses but the same diameters as the old VC applicators (2.3 cm diameter, 2.6 cm, 3.0 cm, and 3.5 cm) were compared using phantom studies. Old VC applicator plans without apex optimization points were also compared to the plans with the optimization points. The apex doses were monitored at 5 mm depth doses (8 points) where a prescription dose (Rx) of 6Gy was prescribed. VC surface doses (8 points)more » were also analyzed. Results: The new VC applicator plans without apex optimization points presented significantly lower 5mm depth doses than Rx (on average −31 ± 7%, p <0.00001) due to their thicker VC tops (3.4 ± 1.1 mm thicker with the range of 1.2 to 4.4 mm) than the old VC applicators. Old VC applicator plans also showed a statistically significant reduction (p <0.00001) due to Ir-192 source anisotropic effect at the apex region but the % reduction over Rx was only −7 ± 9%. However, by adding apex optimization points to the new VC applicator plans, the plans improved 5 mm depth doses (−7 ± 9% over Rx) that were not statistically different from old VC plans (p = 0.923), along with apex VC surface doses (−22 ± 10% over old VC versus −46 ± 7% without using apex optimization points). Conclusion: The use of apex optimization points are important in order to avoid significant additional cold doses (−24 ± 2%) at the prescription depth (5 mm) of apex, especially for the new VC applicators that have thicker tops.« less

Rare-Earth Ions in Niobium-Based Devices as a Quantum Memory: Magneto-Optical Effects on Room Temperature Electrical Transport

DTIC Science & Technology

2016-09-01

rare-earth neodymium by ion implantation in thin films of niobium and niobium-based heterostructure devices. We model the ion implantation process...the films and devices so they can properly designed and optimized for utility as quantum memory. We find that the magnetic field has a strong effect...thin films of niobium. Simulations are made at low 1013 cm-2 and high 1014 cm-2 dose at 60 keV. At high dose, disorder induced is significantly

Optimization of radiation treatment of ginger ( Zingiber officinale) rhizomes using response surface methodology

NASA Astrophysics Data System (ADS)

Nketsia-Tabiri, Josephine

1998-06-01

The effects of pre-irradiation storage time (7-21 days), radiation dose (0-75 Gy) and post-irradiation storage time (2-20 weeks) on sprouting, wrinkling and weight loss of ginger was investigated using a central composite rotatable design. Predictive models developed for all three responses were highly significant. Weight loss and wrinkling decreased as pre-irradiation storage time increased. Dose and post-irradiation storage time had significant interactive effects on weight loss and sprouting. Processing conditions for achieving minimal sprouting resulted in maximum weight loss and wrinkling.

Effect of electron beam radiation processing on mechanical and thermal properties of fully biodegradable crops straw/poly (vinyl alcohol) biocomposites

NASA Astrophysics Data System (ADS)

Guo, Dan

2017-01-01

Fully biodegradable biocomposites based on crops straw and poly(vinyl alcohol) was prepared through thermal processing, and the effect of electron beam radiation processing with N,N-methylene double acrylamide as radiation sensitizer on mechanical and thermal properties of the biocomposites were investigated. The results showed that, when the radiation dose were in the range of 0-50 kGy, the mechanical and thermal properties of the biocomposites could be improved significantly through the electron beam radiation processing, and the interface compatibility was also improved because of the formation of stable cross-linked network structure, when the radiation dose were above the optimal value (50 kGy), the comprehensive properties of the biocomposites were gradually destroyed. EB radiation processing could be used as an effective technology to improve the comprehensive performance of the biocomposites, and as a green and efficient processing technology, radiation processing takes place at room temperature, and no contamination and by-product are possible.

TU-EF-204-03: Task-Based KV and MAs Optimization for Radiation Dose Reduction in CT: From FBP to Statistical Model-Based Iterative Reconstruction (MBIR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomez-Cardona, D; Li, K; Lubner, M G

Purpose: The introduction of the highly nonlinear MBIR algorithm to clinical CT systems has made CNR an invalid metric for kV optimization. The purpose of this work was to develop a task-based framework to unify kV and mAs optimization for both FBP- and MBIR-based CT systems. Methods: The kV-mAs optimization was formulated as a constrained minimization problem: to select kV and mAs to minimize dose under the constraint of maintaining the detection performance as clinically prescribed. To experimentally solve this optimization problem, exhaustive measurements of detectability index (d’) for a hepatic lesion detection task were performed at 15 different mAmore » levels and 4 kV levels using an anthropomorphic phantom. The measured d’ values were used to generate an iso-detectability map; similarly, dose levels recorded at different kV-mAs combinations were used to generate an iso-dose map. The iso-detectability map was overlaid on top of the iso-dose map so that for a prescribed detectability level d’, the optimal kV-mA can be determined from the crossing between the d’ contour and the dose contour that corresponds to the minimum dose. Results: Taking d’=16 as an example: the kV-mAs combinations on the measured iso-d’ line of MBIR are 80–150 (3.8), 100–140 (6.6), 120–150 (11.3), and 140–160 (17.2), where values in the parentheses are measured dose values. As a Result, the optimal kV was 80 and optimal mA was 150. In comparison, the optimal kV and mA for FBP were 100 and 500, which corresponded to a dose level of 24 mGy. Results of in vivo animal experiments were consistent with the phantom results. Conclusion: A new method to optimize kV and mAs selection has been developed. This method is applicable to both linear and nonlinear CT systems such as those using MBIR. Additional dose savings can be achieved by combining MBIR with this method. This work was partially supported by an NIH grant R01CA169331 and GE Healthcare. K. Li, D. Gomez-Cardona, M. G. Lubner: Nothing to disclose. P. J. Pickhardt: Co-founder, VirtuoCTC, LLC Stockholder, Cellectar Biosciences, Inc. G.-H. Chen: Research funded, GE Healthcare; Research funded, Siemens AX.« less

TH-AB-202-09: Direct-Aperture Optimization for Combined MV+kV Dose Planning in Fluoroscopic Real-Time Tumor-Tracking Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, X; Belcher, AH; Grelewicz, Z

Purpose: Real-time kV fluoroscopic tumor tracking has the benefit of direct tumor position monitoring. However, there is clinical concern over the excess kV imaging dose cost to the patient when imaging in continuous fluoroscopic mode. This work addresses this specific issue by proposing a combined MV+kV direct-aperture optimization (DAO) approach to integrate the kV imaging beam into a treatment planning such that the kV radiation is considered as a contributor to the overall dose delivery. Methods: The combined MV+kV DAO approach includes three algorithms. First, a projected Quasi-Newton algorithm (L-BFGS) is used to find optimized fluence with MV+kV dose formore » the best possible dose distribution. Then, Engel’s algorithm is applied to optimize the total number of monitor units and heuristically optimize the number of apertures. Finally, an aperture shape optimization (ASO) algorithm is applied to locally optimize the leaf positions of MLC. Results: Compared to conventional DAO MV plans with continuous kV fluoroscopic tracking, combined MV+kV DAO plan leads to a reduction in the total number of MV monitor units due to inclusion of kV dose as part of the PTV, and was also found to reduce the mean and maximum doses on the organs at risk (OAR). Compared to conventional DAO MV plan without kV tracking, the OAR dose in the combined MV+kV DAO plan was only slightly higher. DVH curves show that combined MV+kV DAO plan provided about the same PTV coverage as that in the conventional DAO plans without kV imaging. Conclusion: We report a combined MV+kV DAO approach that allows real time kV imager tumor tracking with only a trivial increasing on the OAR doses while providing the same coverage to PTV. The approach is suitable for clinic implementation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Botas, Pablo; Faculty of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg

Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dosemore » objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.« less

Statistical model based iterative reconstruction in clinical CT systems. Part III. Task-based kV/mAs optimization for radiation dose reduction

PubMed Central

Li, Ke; Gomez-Cardona, Daniel; Hsieh, Jiang; Lubner, Meghan G.; Pickhardt, Perry J.; Chen, Guang-Hong

2015-01-01

Purpose: For a given imaging task and patient size, the optimal selection of x-ray tube potential (kV) and tube current-rotation time product (mAs) is pivotal in achieving the maximal radiation dose reduction while maintaining the needed diagnostic performance. Although contrast-to-noise (CNR)-based strategies can be used to optimize kV/mAs for computed tomography (CT) imaging systems employing the linear filtered backprojection (FBP) reconstruction method, a more general framework needs to be developed for systems using the nonlinear statistical model-based iterative reconstruction (MBIR) method. The purpose of this paper is to present such a unified framework for the optimization of kV/mAs selection for both FBP- and MBIR-based CT systems. Methods: The optimal selection of kV and mAs was formulated as a constrained optimization problem to minimize the objective function, Dose(kV,mAs), under the constraint that the achievable detectability index d′(kV,mAs) is not lower than the prescribed value of d℞′ for a given imaging task. Since it is difficult to analytically model the dependence of d′ on kV and mAs for the highly nonlinear MBIR method, this constrained optimization problem is solved with comprehensive measurements of Dose(kV,mAs) and d′(kV,mAs) at a variety of kV–mAs combinations, after which the overlay of the dose contours and d′ contours is used to graphically determine the optimal kV–mAs combination to achieve the lowest dose while maintaining the needed detectability for the given imaging task. As an example, d′ for a 17 mm hypoattenuating liver lesion detection task was experimentally measured with an anthropomorphic abdominal phantom at four tube potentials (80, 100, 120, and 140 kV) and fifteen mA levels (25 and 50–700) with a sampling interval of 50 mA at a fixed rotation time of 0.5 s, which corresponded to a dose (CTDIvol) range of [0.6, 70] mGy. Using the proposed method, the optimal kV and mA that minimized dose for the prescribed detectability level of d℞′=16 were determined. As another example, the optimal kV and mA for an 8 mm hyperattenuating liver lesion detection task were also measured using the developed framework. Both an in vivo animal and human subject study were used as demonstrations of how the developed framework can be applied to the clinical work flow. Results: For the first task, the optimal kV and mAs were measured to be 100 and 500, respectively, for FBP, which corresponded to a dose level of 24 mGy. In comparison, the optimal kV and mAs for MBIR were 80 and 150, respectively, which corresponded to a dose level of 4 mGy. The topographies of the iso-d′ map and the iso-CNR map were the same for FBP; thus, the use of d′- and CNR-based optimization methods generated the same results for FBP. However, the topographies of the iso-d′ and iso-CNR map were significantly different in MBIR; the CNR-based method overestimated the performance of MBIR, predicting an overly aggressive dose reduction factor. For the second task, the developed framework generated the following optimization results: for FBP, kV = 140, mA = 350, dose = 37.5 mGy; for MBIR, kV = 120, mA = 250, dose = 18.8 mGy. Again, the CNR-based method overestimated the performance of MBIR. Results of the preliminary in vivo studies were consistent with those of the phantom experiments. Conclusions: A unified and task-driven kV/mAs optimization framework has been developed in this work. The framework is applicable to both linear and nonlinear CT systems such as those using the MBIR method. As expected, the developed framework can be reduced to the conventional CNR-based kV/mAs optimization frameworks if the system is linear. For MBIR-based nonlinear CT systems, however, the developed task-based kV/mAs optimization framework is needed to achieve the maximal dose reduction while maintaining the desired diagnostic performance. PMID:26328971

Dose-Related Effects of Alcohol on Cognitive Functioning

PubMed Central

Dry, Matthew J.; Burns, Nicholas R.; Nettelbeck, Ted; Farquharson, Aaron L.; White, Jason M.

2012-01-01

We assessed the suitability of six applied tests of cognitive functioning to provide a single marker for dose-related alcohol intoxication. Numerous studies have demonstrated that alcohol has a deleterious effect on specific areas of cognitive processing but few have compared the effects of alcohol across a wide range of different cognitive processes. Adult participants (N = 56, 32 males, 24 females aged 18–45 years) were randomized to control or alcohol treatments within a mixed design experiment involving multiple-dosages at approximately one hour intervals (attained mean blood alcohol concentrations (BACs) of 0.00, 0.048, 0.082 and 0.10%), employing a battery of six psychometric tests; the Useful Field of View test (UFOV; processing speed together with directed attention); the Self-Ordered Pointing Task (SOPT; working memory); Inspection Time (IT; speed of processing independent from motor responding); the Traveling Salesperson Problem (TSP; strategic optimization); the Sustained Attention to Response Task (SART; vigilance, response inhibition and psychomotor function); and the Trail-Making Test (TMT; cognitive flexibility and psychomotor function). Results demonstrated that impairment is not uniform across different domains of cognitive processing and that both the size of the alcohol effect and the magnitude of effect change across different dose levels are quantitatively different for different cognitive processes. Only IT met the criteria for a marker for wide-spread application: reliable dose-related decline in a basic process as a function of rising BAC level and easy to use non-invasive task properties. PMID:23209840

Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

PubMed Central

Zhang, Rongxiao; Gladstone, David J.; Williams, Benjamin B.; Glaser, Adam K.; Pogue, Brian W.; Jarvis, Lesley A.

2016-01-01

Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R2 = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R2 = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. Conclusions: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments. PMID:26843259

Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andreozzi, Jacqueline M., E-mail: Jacqueline.M.Andreozzi.th@dartmouth.edu, E-mail: Lesley.A.Jarvis@hitchcock.org; Glaser, Adam K.; Zhang, Rongxiao

2016-02-15

Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, compositemore » images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R{sup 2} = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R{sup 2} = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. Conclusions: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments.« less

Process Performance of Optima XEx Single Wafer High Energy Implanter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, J. H.; Yoon, Jongyoon; Kondratenko, S.

2011-01-07

To meet the process requirements for well formation in future CMOS memory production, high energy implanters require more robust angle, dose, and energy control while maintaining high productivity. The Optima XEx high energy implanter meets these requirements by integrating a traditional LINAC beamline with a robust single wafer handling system. To achieve beam angle control, Optima XEx can control both the horizontal and vertical beam angles to within 0.1 degrees using advanced beam angle measurement and correction. Accurate energy calibration and energy trim functions accelerate process matching by eliminating energy calibration errors. The large volume process chamber and UDC (upstreammore » dose control) using faraday cups outside of the process chamber precisely control implant dose regardless of any chamber pressure increase due to PR (photoresist) outgassing. An optimized RF LINAC accelerator improves reliability and enables singly charged phosphorus and boron energies up to 1200 keV and 1500 keV respectively with higher beam currents. A new single wafer endstation combined with increased beam performance leads to overall increased productivity. We report on the advanced performance of Optima XEx observed during tool installation and volume production at an advanced memory fab.« less

Use of old antibiotics now and in the future from a pharmacokinetic/pharmacodynamic perspective.

PubMed

Muller, A E; Theuretzbacher, U; Mouton, J W

2015-10-01

Because of the increase in bacterial resistance to commonly used antibacterial drugs, old antibiotics are being 'revived' and, once again, are attracting interest. Many of these old antibiotics were approved long ago, in an era when there was no clear process for development, and requirements for efficacy to be demonstrated in rigorous clinical trials did not exist. At the time of these approvals, pharmacokinetic and pharmacodynamic principles were largely unknown, and did not inform the dose-finding process or recommendations for optimal usage. Indeed, the task of generating basic vital information for these old antibiotics remains to be performed. In this review, we provide a brief overview of the most essential data needed for dose justification and optimization. An overview of the shortage of data for selected old antibiotics illustrates the scope of the problem. In order to prevent harming patients with clinical decisions based on inadequate evidence, a redevelopment procedure for old antibiotics is urgently needed, including a regulatory framework. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Feasibility study of using statistical process control to customized quality assurance in proton therapy.

PubMed

Rah, Jeong-Eun; Shin, Dongho; Oh, Do Hoon; Kim, Tae Hyun; Kim, Gwe-Ya

2014-09-01

To evaluate and improve the reliability of proton quality assurance (QA) processes and, to provide an optimal customized tolerance level using the statistical process control (SPC) methodology. The authors investigated the consistency check of dose per monitor unit (D/MU) and range in proton beams to see whether it was within the tolerance level of the daily QA process. This study analyzed the difference between the measured and calculated ranges along the central axis to improve the patient-specific QA process in proton beams by using process capability indices. The authors established a customized tolerance level of ±2% for D/MU and ±0.5 mm for beam range in the daily proton QA process. In the authors' analysis of the process capability indices, the patient-specific range measurements were capable of a specification limit of ±2% in clinical plans. SPC methodology is a useful tool for customizing the optimal QA tolerance levels and improving the quality of proton machine maintenance, treatment delivery, and ultimately patient safety.

SU-E-T-625: Robustness Evaluation and Robust Optimization of IMPT Plans Based on Per-Voxel Standard Deviation of Dose Distributions.

PubMed

Liu, W; Mohan, R

2012-06-01

Proton dose distributions, IMPT in particular, are highly sensitive to setup and range uncertainties. We report a novel method, based on per-voxel standard deviation (SD) of dose distributions, to evaluate the robustness of proton plans and to robustly optimize IMPT plans to render them less sensitive to uncertainties. For each optimization iteration, nine dose distributions are computed - the nominal one, and one each for ± setup uncertainties along x, y and z axes and for ± range uncertainty. SD of dose in each voxel is used to create SD-volume histogram (SVH) for each structure. SVH may be considered a quantitative representation of the robustness of the dose distribution. For optimization, the desired robustness may be specified in terms of an SD-volume (SV) constraint on the CTV and incorporated as a term in the objective function. Results of optimization with and without this constraint were compared in terms of plan optimality and robustness using the so called'worst case' dose distributions; which are obtained by assigning the lowest among the nine doses to each voxel in the clinical target volume (CTV) and the highest to normal tissue voxels outside the CTV. The SVH curve and the area under it for each structure were used as quantitative measures of robustness. Penalty parameter of SV constraint may be varied to control the tradeoff between robustness and plan optimality. We applied these methods to one case each of H&N and lung. In both cases, we found that imposing SV constraint improved plan robustness but at the cost of normal tissue sparing. SVH-based optimization and evaluation is an effective tool for robustness evaluation and robust optimization of IMPT plans. Studies need to be conducted to test the methods for larger cohorts of patients and for other sites. This research is supported by National Cancer Institute (NCI) grant P01CA021239, the University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center, and MD Anderson’s cancer center support grant CA016672. © 2012 American Association of Physicists in Medicine.

Robust plan optimization for electromagnetic transponder guided hypo-fractionated prostate treatment using volumetric modulated arc therapy

NASA Astrophysics Data System (ADS)

Zhang, Pengpeng; Hunt, Margie; Happersett, Laura; Yang, Jie; Zelefsky, Michael; Mageras, Gig

2013-11-01

To develop an optimization algorithm for volumetric modulated arc therapy which incorporates an electromagnetic tracking (EMT) guided gating strategy and is robust to residual intra-fractional motion uncertainties. In a computer simulation, intra-fractional motion traces from prior treatments with EMT were converted to a probability distribution function (PDF), truncated using a patient specific action volume that encloses allowed deviations from the planned position, and renormalized to yield a new PDF with EMT-gated interventions. In lieu of a conventional planning target volume (PTV), multiple instances of clinical target volume (CTV) and organs at risk (OARs) were replicated and displaced to extreme positions inside the action volume representing possible delivery scenarios. When optimizing the volumetric modulated arc therapy plan, doses to the CTV and OARs were calculated as a sum of doses to the replicas weighted by the PDF to account for motion. A treatment plan meeting the clinical constraints was produced and compared to the counterpart conventional margin (PTV) plan. EMT traces from a separate testing database served to simulate motion during gated delivery. Dosimetric end points extracted from dose accumulations for each motion trace were utilized to evaluate potential clinical benefit. Five prostate cases from a hypofractionated protocol (42.5 Gy in 5 fractions) were retrospectively investigated. The patient specific gating window resulted in tight anterior and inferior action levels (∼1 mm) to protect rectal wall and bladder wall, and resulted in an average of four beam interruptions per fraction in the simulation. The robust-optimized plans achieved the same average CTV D95 coverage of 40.5 Gy as the PTV-optimized plans, but with reduced patient-averaged rectum wall D1cc by 2.2 Gy (range 0.7 to 4.7 Gy) and bladder wall mean dose by 2.9 Gy (range 2.0 to 3.4 Gy). Integration of an intra-fractional motion management strategy into the robust optimization process is feasible and may yield improved OAR sparing compared to the standard margin approach.

SU-F-19A-08: Optimal Time Release Schedule of In-Situ Drug Release During Permanent Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cormack, R; Ngwa, W; Makrigiorgos, G

Purpose: Permanent prostate brachytherapy spacers can be used to deliver sustained doses of radiosentitizing drug directly to the target, in order to enhance the radiation effect. Implantable nanoplatforms for chemo-radiation therapy (INCeRTs) have a maximum drug capacity and can be engineered to control the drug release schedule. The optimal schedule for sensitization during continuous low dose rate irradiation is unknown. This work studies the optimal release schedule of drug for both traditional sensitizers, and those that work by suppressing DNA repair processes. Methods: Six brachytherapy treatment plans were used to model the anatomy, implant geometry and calculate the spatial distributionmore » of radiation dose and drug concentrations for a range of drug diffusion parameters. Three state partial differential equations (cells healthy, damaged or dead) modeled the effect of continuous radiation (radiosensitivities α,β) and cellular repair (time tr) on a cell population. Radiosensitization was modeled as concentration dependent change in α,β or tr which with variable duration under the constraint of fixed total drug release. Average cell kill was used to measure effectiveness. Sensitization by means of both enhanced damage and reduced repair were studied. Results: Optimal release duration is dependent on the concentration of radiosensitizer compared to the saturation concentration (csat) above which additional sensitization does not occur. Long duration drug release when enhancing α or β maximizes cell death when drug concentrations are generally over csat. Short term release is optimal for concentrations below saturation. Sensitization by suppressing repair has a similar though less distinct trend that is more affected by the radiation dose distribution. Conclusion: Models of sustained local radiosensitization show potential to increase the effectiveness of radiation in permanent prostate brachytherapy. INCeRTs with high drug capacity produce the greatest benefit with drug release over weeks. If in-vivo drug concentrations are not able to approach saturation concentration, durations of days is optimal. DOD 1R21CA16977501; A. David Mazzone Awards Program 2012PD164.« less

Robust plan optimization for electromagnetic transponder guided hypo-fractionated prostate treatment using volumetric modulated arc therapy.

PubMed

Zhang, Pengpeng; Hunt, Margie; Happersett, Laura; Yang, Jie; Zelefsky, Michael; Mageras, Gig

2013-11-07

To develop an optimization algorithm for volumetric modulated arc therapy which incorporates an electromagnetic tracking (EMT) guided gating strategy and is robust to residual intra-fractional motion uncertainties. In a computer simulation, intra-fractional motion traces from prior treatments with EMT were converted to a probability distribution function (PDF), truncated using a patient specific action volume that encloses allowed deviations from the planned position, and renormalized to yield a new PDF with EMT-gated interventions. In lieu of a conventional planning target volume (PTV), multiple instances of clinical target volume (CTV) and organs at risk (OARs) were replicated and displaced to extreme positions inside the action volume representing possible delivery scenarios. When optimizing the volumetric modulated arc therapy plan, doses to the CTV and OARs were calculated as a sum of doses to the replicas weighted by the PDF to account for motion. A treatment plan meeting the clinical constraints was produced and compared to the counterpart conventional margin (PTV) plan. EMT traces from a separate testing database served to simulate motion during gated delivery. Dosimetric end points extracted from dose accumulations for each motion trace were utilized to evaluate potential clinical benefit. Five prostate cases from a hypofractionated protocol (42.5 Gy in 5 fractions) were retrospectively investigated. The patient specific gating window resulted in tight anterior and inferior action levels (~1 mm) to protect rectal wall and bladder wall, and resulted in an average of four beam interruptions per fraction in the simulation. The robust-optimized plans achieved the same average CTV D95 coverage of 40.5 Gy as the PTV-optimized plans, but with reduced patient-averaged rectum wall D1cc by 2.2 Gy (range 0.7 to 4.7 Gy) and bladder wall mean dose by 2.9 Gy (range 2.0 to 3.4 Gy). Integration of an intra-fractional motion management strategy into the robust optimization process is feasible and may yield improved OAR sparing compared to the standard margin approach.

Robust optimization methods for cardiac sparing in tangential breast IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahmoudzadeh, Houra, E-mail: houra@mie.utoronto.ca; Lee, Jenny; Chan, Timothy C. Y.

Purpose: In left-sided tangential breast intensity modulated radiation therapy (IMRT), the heart may enter the radiation field and receive excessive radiation while the patient is breathing. The patient’s breathing pattern is often irregular and unpredictable. We verify the clinical applicability of a heart-sparing robust optimization approach for breast IMRT. We compare robust optimized plans with clinical plans at free-breathing and clinical plans at deep inspiration breath-hold (DIBH) using active breathing control (ABC). Methods: Eight patients were included in the study with each patient simulated using 4D-CT. The 4D-CT image acquisition generated ten breathing phase datasets. An average scan was constructedmore » using all the phase datasets. Two of the eight patients were also imaged at breath-hold using ABC. The 4D-CT datasets were used to calculate the accumulated dose for robust optimized and clinical plans based on deformable registration. We generated a set of simulated breathing probability mass functions, which represent the fraction of time patients spend in different breathing phases. The robust optimization method was applied to each patient using a set of dose-influence matrices extracted from the 4D-CT data and a model of the breathing motion uncertainty. The goal of the optimization models was to minimize the dose to the heart while ensuring dose constraints on the target were achieved under breathing motion uncertainty. Results: Robust optimized plans were improved or equivalent to the clinical plans in terms of heart sparing for all patients studied. The robust method reduced the accumulated heart dose (D10cc) by up to 801 cGy compared to the clinical method while also improving the coverage of the accumulated whole breast target volume. On average, the robust method reduced the heart dose (D10cc) by 364 cGy and improved the optBreast dose (D99%) by 477 cGy. In addition, the robust method had smaller deviations from the planned dose to the accumulated dose. The deviation of the accumulated dose from the planned dose for the optBreast (D99%) was 12 cGy for robust versus 445 cGy for clinical. The deviation for the heart (D10cc) was 41 cGy for robust and 320 cGy for clinical. Conclusions: The robust optimization approach can reduce heart dose compared to the clinical method at free-breathing and can potentially reduce the need for breath-hold techniques.« less

Algorithms for the optimization of RBE-weighted dose in particle therapy.

PubMed

Horcicka, M; Meyer, C; Buschbacher, A; Durante, M; Krämer, M

2013-01-21

We report on various algorithms used for the nonlinear optimization of RBE-weighted dose in particle therapy. Concerning the dose calculation carbon ions are considered and biological effects are calculated by the Local Effect Model. Taking biological effects fully into account requires iterative methods to solve the optimization problem. We implemented several additional algorithms into GSI's treatment planning system TRiP98, like the BFGS-algorithm and the method of conjugated gradients, in order to investigate their computational performance. We modified textbook iteration procedures to improve the convergence speed. The performance of the algorithms is presented by convergence in terms of iterations and computation time. We found that the Fletcher-Reeves variant of the method of conjugated gradients is the algorithm with the best computational performance. With this algorithm we could speed up computation times by a factor of 4 compared to the method of steepest descent, which was used before. With our new methods it is possible to optimize complex treatment plans in a few minutes leading to good dose distributions. At the end we discuss future goals concerning dose optimization issues in particle therapy which might benefit from fast optimization solvers.

Algorithms for the optimization of RBE-weighted dose in particle therapy

NASA Astrophysics Data System (ADS)

Horcicka, M.; Meyer, C.; Buschbacher, A.; Durante, M.; Krämer, M.

2013-01-01

We report on various algorithms used for the nonlinear optimization of RBE-weighted dose in particle therapy. Concerning the dose calculation carbon ions are considered and biological effects are calculated by the Local Effect Model. Taking biological effects fully into account requires iterative methods to solve the optimization problem. We implemented several additional algorithms into GSI's treatment planning system TRiP98, like the BFGS-algorithm and the method of conjugated gradients, in order to investigate their computational performance. We modified textbook iteration procedures to improve the convergence speed. The performance of the algorithms is presented by convergence in terms of iterations and computation time. We found that the Fletcher-Reeves variant of the method of conjugated gradients is the algorithm with the best computational performance. With this algorithm we could speed up computation times by a factor of 4 compared to the method of steepest descent, which was used before. With our new methods it is possible to optimize complex treatment plans in a few minutes leading to good dose distributions. At the end we discuss future goals concerning dose optimization issues in particle therapy which might benefit from fast optimization solvers.

SU-F-BRD-13: Quantum Annealing Applied to IMRT Beamlet Intensity Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nazareth, D; Spaans, J

Purpose: We report on the first application of quantum annealing (QA) to the process of beamlet intensity optimization for IMRT. QA is a new technology, which employs novel hardware and software techniques to address various discrete optimization problems in many fields. Methods: We apply the D-Wave Inc. proprietary hardware, which natively exploits quantum mechanical effects for improved optimization. The new QA algorithm, running on this hardware, is most similar to simulated annealing, but relies on natural processes to directly minimize the free energy of a system. A simple quantum system is slowly evolved into a classical system, representing the objectivemore » function. To apply QA to IMRT-type optimization, two prostate cases were considered. A reduced number of beamlets were employed, due to the current QA hardware limitation of ∼500 binary variables. The beamlet dose matrices were computed using CERR, and an objective function was defined based on typical clinical constraints, including dose-volume objectives. The objective function was discretized, and the QA method was compared to two standard optimization Methods: simulated annealing and Tabu search, run on a conventional computing cluster. Results: Based on several runs, the average final objective function value achieved by the QA was 16.9 for the first patient, compared with 10.0 for Tabu and 6.7 for the SA. For the second patient, the values were 70.7 for the QA, 120.0 for Tabu, and 22.9 for the SA. The QA algorithm required 27–38% of the time required by the other two methods. Conclusion: In terms of objective function value, the QA performance was similar to Tabu but less effective than the SA. However, its speed was 3–4 times faster than the other two methods. This initial experiment suggests that QA-based heuristics may offer significant speedup over conventional clinical optimization methods, as quantum annealing hardware scales to larger sizes.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, E; Yuan, F; Templeton, A

Purpose: The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor-control-probability(TCP) with an acceptable normal-tissue-complication probability(NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. We design treatment plans that optimize TCP directly and contrast them with the clinical dose-based plans. PET image is incorporated to evaluate gain in TCP for dose escalation. Methods: We build a nonlinear mixed integer programming optimization model that maximizes TCP directly while satisfying the dose requirements on themore » targeted organ and healthy tissues. The solution strategy first fits the TCP function with a piecewise-linear approximation, then solves the problem that maximizes the piecewise linear approximation of TCP, and finally performs a local neighborhood search to improve the TCP value. To gauge the feasibility, characteristics, and potential benefit of PET-image guided dose escalation, initial validation consists of fifteen cervical cancer HDR patient cases. These patients have all received prior 45Gy of external radiation dose. For both escalated strategies, we consider 35Gy PTV-dose, and two variations (37Gy-boost to BTV vs 40Gy-boost) to PET-image-pockets. Results: TCP for standard clinical plans range from 59.4% - 63.6%. TCP for dose-based PET-guided escalated-dose-plan ranges from 63.8%–98.6% for all patients; whereas TCP-optimized plans achieves over 91% for all patients. There is marginal difference in TCP among those with 37Gy-boosted vs 40Gy-boosted. There is no increase in rectum and bladder dose among all plans. Conclusion: Optimizing TCP directly results in highly conformed treatment plans. The TCP-optimized plan is individualized based on the biological PET-image of the patients. The TCP-optimization framework is generalizable and has been applied successfully to other external-beam delivery modalities. A clinical trial is on-going to gauge the clinical significance. Partially supported by the National Science Foundation.« less

Modeling and investigation of submerged fermentation process to produce extracellular polysaccharide using Lactobacillus confusus.

PubMed

Thirugnanasambandham, K; Sivakumar, V; Prakash Maran, J

2014-12-19

The main objective of the present study is to investigate and optimize the Submerged fermentation (SMF) process parameters such as addition of coconut water, NaCl dose, incubation time and temperature on the production of extracellular polysaccharide (EPS) and biomass production using Lactobacillus confuses. Response surface methodology (RSM) coupled with four factors three level Box-Behnken design (BBD) was employed to model the SMF process. RSM analysis indicated good correspondence between experimental and predicted values. Three dimentional (3D) response surface plots were used to study the interactive effects of process variables on SMF process. The optimum process conditions for the maximum production of EPS and biomass were found to be as follows; addition of coconut water of 40%, NaCl dose of 15%, incubation time of 24h and temperature of 35°C. Under these conditions, 10.57 g/L of EPS and 3.9 g/L of biomass were produced. Copyright © 2014 Elsevier Ltd. All rights reserved.

MO-DE-204-02: Optimization of the Patient CT Dose in Europe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsapaki, V.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Dose optimization of total or partial skin electron irradiation by thermoluminescent dosimetry.

PubMed

Schüttrumpf, Lars; Neumaier, Klement; Maihoefer, Cornelius; Niyazi, Maximilian; Ganswindt, Ute; Li, Minglun; Lang, Peter; Reiner, Michael; Belka, Claus; Corradini, Stefanie

2018-05-01

Due to the complex surface of the human body, total or partial skin irradiation using large electron fields is challenging. The aim of the present study was to quantify the magnitude of dose optimization required after the application of standard fields. Total skin electron irradiation (TSEI) was applied using the Stanford technique with six dual-fields. Patients presenting with localized lesions were treated with partial skin electron irradiation (PSEI) using large electron fields, which were individually adapted. In order to verify and validate the dose distribution, in vivo dosimetry with thermoluminescent dosimeters (TLD) was performed during the first treatment fraction to detect potential dose heterogeneity and to allow for an individual dose optimization with adjustment of the monitor units (MU). Between 1984 and 2017, a total of 58 patients were treated: 31 patients received TSEI using 12 treatment fields, while 27 patients underwent PSEI and were treated with 4-8 treatment fields. After evaluation of the dosimetric results, an individual dose optimization was necessary in 21 patients. Of these, 7 patients received TSEI (7/31). Monitor units (MU) needed to be corrected by a mean value of 117 MU (±105, range 18-290) uniformly for all 12 treatment fields, corresponding to a mean relative change of 12% of the prescribed MU. In comparison, the other 14 patients received PSEI (14/27) and the mean adjustment of monitor units was 282 MU (±144, range 59-500) to single or multiple fields, corresponding to a mean relative change of 22% of the prescribed MU. A second dose optimization to obtain a satisfying dose at the prescription point was need in 5 patients. Thermoluminescent dosimetry allows an individual dose optimization in TSEI and PSEI to enable a reliable adjustment of the MUs to obtain the prescription dose. Especially in PSEI in vivo dosimetry is of fundamental importance.

TU-AB-BRB-01: Coverage Evaluation and Probabilistic Treatment Planning as a Margin Alternative

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siebers, J.

The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To understand robust-planning as a clinical alternative to using margin-based planning. To understand conceptual differences between uncertainty and predictable motion. To understand fundamental limitations of the PTV concept that probabilistic planning can overcome. To understand the major contributing factors to target and normal tissue coverage probability. To understand the similarities and differences of various robust planning techniques To understand the benefits and limitations of robust planning techniques.« less

TU-AB-BRB-03: Coverage-Based Treatment Planning to Accommodate Organ Deformable Motions and Contouring Uncertainties for Prostate Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, H.

The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To understand robust-planning as a clinical alternative to using margin-based planning. To understand conceptual differences between uncertainty and predictable motion. To understand fundamental limitations of the PTV concept that probabilistic planning can overcome. To understand the major contributing factors to target and normal tissue coverage probability. To understand the similarities and differences of various robust planning techniques To understand the benefits and limitations of robust planning techniques.« less

TU-AB-BRB-02: Stochastic Programming Methods for Handling Uncertainty and Motion in IMRT Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, J.

The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To understand robust-planning as a clinical alternative to using margin-based planning. To understand conceptual differences between uncertainty and predictable motion. To understand fundamental limitations of the PTV concept that probabilistic planning can overcome. To understand the major contributing factors to target and normal tissue coverage probability. To understand the similarities and differences of various robust planning techniques To understand the benefits and limitations of robust planning techniques.« less

TU-AB-BRB-00: New Methods to Ensure Target Coverage

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2015-06-15

The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To understand robust-planning as a clinical alternative to using margin-based planning. To understand conceptual differences between uncertainty and predictable motion. To understand fundamental limitations of the PTV concept that probabilistic planning can overcome. To understand the major contributing factors to target and normal tissue coverage probability. To understand the similarities and differences of various robust planning techniques To understand the benefits and limitations of robust planning techniques.« less

Drug interactions: volatile anesthetics and opioids.

PubMed

Glass, P S; Gan, T J; Howell, S; Ginsberg, B

1997-09-01

Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly combined with opioids. Several studies have demonstrated that small doses of opioid (i.e., within the analgesic range) result in a marked reduction in minimum alveolar concentration (MAC) of the volatile anesthetic that will prevent purposeful movement in 50% of patients at skin incision). Further increases in opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect of the opioid is observed at a MAC value of the volatile anesthetic equal to its MAC awake. Recovery from anesthesia when an opioid is combined with a volatile anesthetic is dependent on the rate of decrease of both drugs to their respective concentrations that are associated with adequate spontaneous ventilation and awakening. Through an understanding of the pharmacodynamic interaction of volatile anesthetics with opioids and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can thus be developed. A review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anesthetic is provided.

Falcon: automated optimization method for arbitrary assessment criteria

DOEpatents

Yang, Tser-Yuan; Moses, Edward I.; Hartmann-Siantar, Christine

2001-01-01

FALCON is a method for automatic multivariable optimization for arbitrary assessment criteria that can be applied to numerous fields where outcome simulation is combined with optimization and assessment criteria. A specific implementation of FALCON is for automatic radiation therapy treatment planning. In this application, FALCON implements dose calculations into the planning process and optimizes available beam delivery modifier parameters to determine the treatment plan that best meets clinical decision-making criteria. FALCON is described in the context of the optimization of external-beam radiation therapy and intensity modulated radiation therapy (IMRT), but the concepts could also be applied to internal (brachytherapy) radiotherapy. The radiation beams could consist of photons or any charged or uncharged particles. The concept of optimizing source distributions can be applied to complex radiography (e.g. flash x-ray or proton) to improve the imaging capabilities of facilities proposed for science-based stockpile stewardship.

Concept development of X-ray mass thickness detection for irradiated items upon electron beam irradiation processing

NASA Astrophysics Data System (ADS)

Qin, Huaili; Yang, Guang; Kuang, Shan; Wang, Qiang; Liu, Jingjing; Zhang, Xiaomin; Li, Cancan; Han, Zhiwei; Li, Yuanjing

2018-02-01

The present project will adopt the principle and technology of X-ray imaging to quickly measure the mass thickness (wherein the mass thickness of the item =density of the item × thickness of the item) of the irradiated items and thus to determine whether the packaging size and inside location of the item will meet the requirements for treating thickness upon electron beam irradiation processing. The development of algorithm of X-ray mass thickness detector as well as the prediction of dose distribution have been completed. The development of the algorithm was based on the X-ray attenuation. 4 standard modules, Al sheet, Al ladders, PMMA sheet and PMMA ladders, were selected for the algorithm development. The algorithm was optimized until the error between tested mass thickness and standard mass thickness was less than 5%. Dose distribution of all energy (1-10 MeV) for each mass thickness was obtained using Monte-carlo method and used for the analysis of dose distribution, which provides the information of whether the item will be penetrated or not, as well as the Max. dose, Min. dose and DUR of the whole item.

RENEB intercomparisons applying the conventional Dicentric Chromosome Assay (DCA).

PubMed

Oestreicher, Ursula; Samaga, Daniel; Ainsbury, Elizabeth; Antunes, Ana Catarina; Baeyens, Ans; Barrios, Leonardo; Beinke, Christina; Beukes, Philip; Blakely, William F; Cucu, Alexandra; De Amicis, Andrea; Depuydt, Julie; De Sanctis, Stefania; Di Giorgio, Marina; Dobos, Katalin; Dominguez, Inmaculada; Duy, Pham Ngoc; Espinoza, Marco E; Flegal, Farrah N; Figel, Markus; Garcia, Omar; Monteiro Gil, Octávia; Gregoire, Eric; Guerrero-Carbajal, C; Güçlü, İnci; Hadjidekova, Valeria; Hande, Prakash; Kulka, Ulrike; Lemon, Jennifer; Lindholm, Carita; Lista, Florigio; Lumniczky, Katalin; Martinez-Lopez, Wilner; Maznyk, Nataliya; Meschini, Roberta; M'kacher, Radia; Montoro, Alegria; Moquet, Jayne; Moreno, Mercedes; Noditi, Mihaela; Pajic, Jelena; Radl, Analía; Ricoul, Michelle; Romm, Horst; Roy, Laurence; Sabatier, Laure; Sebastià, Natividad; Slabbert, Jacobus; Sommer, Sylwester; Stuck Oliveira, Monica; Subramanian, Uma; Suto, Yumiko; Que, Tran; Testa, Antonella; Terzoudi, Georgia; Vral, Anne; Wilkins, Ruth; Yanti, LusiYanti; Zafiropoulos, Demetre; Wojcik, Andrzej

2017-01-01

Two quality controlled inter-laboratory exercises were organized within the EU project 'Realizing the European Network of Biodosimetry (RENEB)' to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network. The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants. The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point. In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners.

The Impact of Monte Carlo Dose Calculations on Intensity-Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

Siebers, J. V.; Keall, P. J.; Mohan, R.

The effect of dose calculation accuracy for IMRT was studied by comparing different dose calculation algorithms. A head and neck IMRT plan was optimized using a superposition dose calculation algorithm. Dose was re-computed for the optimized plan using both Monte Carlo and pencil beam dose calculation algorithms to generate patient and phantom dose distributions. Tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) were computed to estimate the plan outcome. For the treatment plan studied, Monte Carlo best reproduces phantom dose measurements, the TCP was slightly lower than the superposition and pencil beam results, and the NTCP values differed little.

Adaptive radiation therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Wen, Ning

ART is a close-loop feedback algorithm which evaluates the organ deformation and motion right before the treatment and takes into account dose delivery variation daily to compensate for the difference between planned and delivered dose. It also has potential to allow further dose escalation and margin reduction to improve the clinical outcome. This retrospective study evaluated ART for prostate cancer treatment and radiobiological consequences. An IRB approved protocol has been used to evaluate actual dose delivery of patients with prostate cancer undergoing treatment with daily CBCT. The dose from CBCT was measured in phantom using TLD and ion chamber techniques in the pelvic scan setting. There were two major findings from the measurements of CBCT dose: (1) the lateral dose distribution was not symmetrical, with Lt Lat being ˜40% higher than Rt Lat and (2) AP skin dose varies with patient size, ranging 3.2--6.1 cGy for patient's AP separation of 20--33 cm (the larger the separation, the less the skin dose) but lateral skin doses depend little on separations. Dose was recalculated on each CBCT set under the same treatment plan. DIR was performed between SIM-CT and evaluated for each CT sets. Dose was reconstructed and accumulated to reflect the actual dose delivered to the patient. Then the adaptive plans were compared to the original plan to evaluate tumor control and normal tissue complication using radiobiological model. Different PTV margins were also studied to access margin reduction techniques. If the actual dose delivered to the PTV deviated significantly from the prescription dose for the given fractions or the OAR received higher dose than expected, the treatment plan would be re-optimized based on the previously delivered dose. The optimal schedule was compared based on the balance of PTV dose coverage and inhomogeneity, OAR dose constraints and labor involved. DIR was validated using fiducial marker position, visual comparison and UE. The mean and standard deviation of markers after rigid registration in L-R direction was 0 and 1 mm. But the mean was 2--4 mm in the A-P and S-I direction and standard deviation was about 2 mm. After DIR, the mean in all three directions became 0 and standard deviation was within sub millimeter. UE images were generated for each CT set and carefully reviewed in the prostate region. DIR provided accurate transformation matrix to be used for dose reconstruction. The delivered dose was evaluated with radiobiological models. TCP for the CTV was calculated to evaluate tumor control in different margin settings. TCP calculated from the reconstructed dose agreed within 5% of the value in the plan for all patients with three different margins. EUD and NTCP were calculated to evaluate reaction of rectum to radiation. Similar biological evaluation was performed for bladder. EUD of actual dose was 3%--9% higher than that of planned dose of patient 1--3, 11%--20% higher of patient 4--5. Smaller margins could not reduce late GU toxicity effectively since bladder complication was directly related to Dmax which was at the same magnitude in the bladder no matter which margin was applied. Re-optimization was performed at the 10th, 20th , 30th, and 40th fraction to evaluate the effectiveness to limit OAR dose while maintaining the target coverage. Reconstructed dose was added to dose from remaining fractions after optimization to show the total dose patient would receive. It showed that if the plan was re-optimized at 10th or 20th fraction, total dose to rectum and bladder were very similar to planned dose with minor deviations. If the plan was re-optimized at the 30th fraction, since there was a large deviation between reconstructed dose and planned dose to OAR, optimization could not limit the OAR dose to the original plan with only 12 fractions left. If the re-optimization was done at the 40th fraction, it was impossible to compensate in the last 2 fractions. Large deviations of total dose to bladder and rectum still existed while dose inhomogeneity to PTV was significantly increased due to hard constraints set in the optimization to reduce OAR dose. In summary, ART did not show improvements in TCP if the patient was setup with CBCT. However, EUD of rectum and bladder was increased significantly due to tissue deformation which varied daily. With the power of ART, margins added to the CTV could be further reduced to preserve critical organs surrounding the target. (Abstract shortened by UMI.)

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin

2015-01-01

Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727

Generation of uniformly distributed dose points for anatomy-based three-dimensional dose optimization methods in brachytherapy.

PubMed

Lahanas, M; Baltas, D; Giannouli, S; Milickovic, N; Zamboglou, N

2000-05-01

We have studied the accuracy of statistical parameters of dose distributions in brachytherapy using actual clinical implants. These include the mean, minimum and maximum dose values and the variance of the dose distribution inside the PTV (planning target volume), and on the surface of the PTV. These properties have been studied as a function of the number of uniformly distributed sampling points. These parameters, or the variants of these parameters, are used directly or indirectly in optimization procedures or for a description of the dose distribution. The accurate determination of these parameters depends on the sampling point distribution from which they have been obtained. Some optimization methods ignore catheters and critical structures surrounded by the PTV or alternatively consider as surface dose points only those on the contour lines of the PTV. D(min) and D(max) are extreme dose values which are either on the PTV surface or within the PTV. They must be avoided for specification and optimization purposes in brachytherapy. Using D(mean) and the variance of D which we have shown to be stable parameters, achieves a more reliable description of the dose distribution on the PTV surface and within the PTV volume than does D(min) and D(max). Generation of dose points on the real surface of the PTV is obligatory and the consideration of catheter volumes results in a realistic description of anatomical dose distributions.

Optimization of the bake-on siliconization of cartridges. Part I: Optimization of the spray-on parameters.

PubMed

Funke, Stefanie; Matilainen, Julia; Nalenz, Heiko; Bechtold-Peters, Karoline; Mahler, Hanns-Christian; Friess, Wolfgang

2016-07-01

Biopharmaceutical products are increasingly commercialized as drug/device combinations to enable self-administration. Siliconization of the inner syringe/cartridge glass barrel for adequate functionality is either performed at the supplier or drug product manufacturing site. Yet, siliconization processes are often insufficiently investigated. In this study, an optimized bake-on siliconization process for cartridges using a pilot-scale siliconization unit was developed. The following process parameters were investigated: spray quantity, nozzle position, spray pressure, time for pump dosing and the silicone emulsion concentration. A spray quantity of 4mg emulsion showed best, immediate atomization into a fine spray. 16 and 29mg of emulsion, hence 4-7-times the spray volume, first generated an emulsion jet before atomization was achieved. Poor atomization of higher quantities correlated with an increased spray loss and inhomogeneous silicone distribution, e.g., due to runlets forming build-ups at the cartridge lower edge and depositing on the star wheel. A prolonged time for pump dosing of 175ms led to a more intensive, long-lasting spray compared to 60ms as anticipated from a higher air-to-liquid ratio. A higher spray pressure of 2.5bar did not improve atomization but led to an increased spray loss. At a 20mm nozzle-to-flange distance the spray cone exactly reached the cartridge flange, which was optimal for thicker silicone layers at the flange to ease piston break-loose. Initially, 10μg silicone was sufficient for adequate extrusion in filled cartridges. However, both maximum break-loose and gliding forces in filled cartridges gradually increased from 5-8N to 21-22N upon 80weeks storage at room temperature. The increase for a 30μg silicone level from 3-6N to 10-12N was moderate. Overall, the study provides a comprehensive insight into critical process parameters during the initial spray-on process and the impact of these parameters on the characteristics of the silicone layer, also in context of long-term product storage. The presented experimental toolbox may be utilized for development or evaluation of siliconization processes. Copyright © 2016 Elsevier B.V. All rights reserved.

Multi-Case Knowledge-Based IMRT Treatment Planning in Head and Neck Cancer

NASA Astrophysics Data System (ADS)

Grzetic, Shelby Mariah

Head and neck cancer (HNC) IMRT treatment planning is a challenging process that relies heavily on the planner's experience. Previously, we used the single, best match from a library of manually planned cases to semi-automatically generate IMRT plans for a new patient. The current multi-case Knowledge Based Radiation Therapy (MC-KBRT) study utilized different matching cases for each of six individual organs-at-risk (OARs), then combined those six cases to create the new treatment plan. From a database of 103 patient plans created by experienced planners, MC-KBRT plans were created for 40 (17 unilateral and 23 bilateral) HNC "query" patients. For each case, 2D beam's-eye-view images were used to find similar geometric "match" patients separately for each of 6 OARs. Dose distributions for each OAR from the 6 matching cases were combined and then warped to suit the query case's geometry. The dose-volume constraints were used to create the new query treatment plan without the need for human decision-making throughout the IMRT optimization. The optimized MC-KBRT plans were compared against the clinically approved plans and Version 1 (previous KBRT using only one matching case with dose warping) using the dose metrics: mean, median, and maximum (brainstem and cord+5mm) doses. Compared to Version 1, MC-KBRT had no significant reduction of the dose to any of the OARs in either unilateral or bilateral cases. Compared to the manually planned unilateral cases, there was significant reduction of the oral cavity mean/median dose (>2Gy) at the expense of the contralateral parotid. Compared to the manually planned bilateral cases, reduction of dose was significant in the ipsilateral parotid, larynx, and oral cavity (>3Gy mean/median) while maintaining PTV coverage. MC-KBRT planning in head and neck cancer generates IMRT plans with better dose sparing than manually created plans. MC-KBRT using multiple case matches does not show significant dose reduction compared to using a single match case with dose warping.

Application of response surface methodology (RSM) for the removal of methylene blue dye from water by nano zero-valent iron (NZVI).

PubMed

Khosravi, Morteza; Arabi, Simin

In this study, iron zero-valent nanoparticles were synthesized, characterized and studied for removal of methylene blue dye in water solution. The reactions were mathematically described as the function of parameters such as nano zero-valent iron (NZVI) dose, pH, contact time and initial dye concentration, and were modeled by the use of response surface methodology. These experiments were carried out as a central composite design consisting of 30 experiments determined by the 2(4) full factorial designs with eight axial points and six center points. The results revealed that the optimal conditions for dye removal were NZVI dose 0.1-0.9 g/L, pH 3-11, contact time 20-100 s, and initial dye concentration 10-50 mg/L, respectively. Under these optimal values of process parameters, the dye removal efficiency of 92.87% was observed, which very close to the experimental value (92.21%) in batch experiment. In the optimization, R(2) and R(2)adj correlation coefficients for the model were evaluated as 0.96 and 0.93, respectively.

Guaranteed epsilon-optimal treatment plans with the minimum number of beams for stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Yarmand, Hamed; Winey, Brian; Craft, David

2013-09-01

Stereotactic body radiation therapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam’s-eye-view) known as ‘apertures’. Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan as the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined maximum deviation from the ideal plan is guaranteed). Since the treatment plan optimization is inherently a multi-criteria-optimization problem, the planner can navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing epsilon-optimality. We use mixed integer programming (MIP) for optimization. To reduce the computation time for the resultant MIP, we use two heuristics: a beam elimination scheme and a family of heuristic cuts, known as ‘neighbor cuts’, based on the concept of ‘adjacent beams’. We show the effectiveness of the proposed technique on two clinical cases, a liver and a lung case. Based on our technique we propose an algorithm for fast generation of epsilon-optimal plans.

Role of the parameters involved in the plan optimization based on the generalized equivalent uniform dose and radiobiological implications

NASA Astrophysics Data System (ADS)

Widesott, L.; Strigari, L.; Pressello, M. C.; Benassi, M.; Landoni, V.

2008-03-01

We investigated the role and the weight of the parameters involved in the intensity modulated radiation therapy (IMRT) optimization based on the generalized equivalent uniform dose (gEUD) method, for prostate and head-and-neck plans. We systematically varied the parameters (gEUDmax and weight) involved in the gEUD-based optimization of rectal wall and parotid glands. We found that the proper value of weight factor, still guaranteeing planning treatment volumes coverage, produced similar organs at risks dose-volume (DV) histograms for different gEUDmax with fixed a = 1. Most of all, we formulated a simple relation that links the reference gEUDmax and the associated weight factor. As secondary objective, we evaluated plans obtained with the gEUD-based optimization and ones based on DV criteria, using the normal tissue complication probability (NTCP) models. gEUD criteria seemed to improve sparing of rectum and parotid glands with respect to DV-based optimization: the mean dose, the V40 and V50 values to the rectal wall were decreased of about 10%, the mean dose to parotids decreased of about 20-30%. But more than the OARs sparing, we underlined the halving of the OARs optimization time with the implementation of the gEUD-based cost function. Using NTCP models we enhanced differences between the two optimization criteria for parotid glands, but no for rectum wall.

An optimized computational method for determining the beta dose distribution using a multiple-element thermoluminescent dosimeter system.

PubMed

Shen, L; Levine, S H; Catchen, G L

1987-07-01

This paper describes an optimization method for determining the beta dose distribution in tissue, and it describes the associated testing and verification. The method uses electron transport theory and optimization techniques to analyze the responses of a three-element thermoluminescent dosimeter (TLD) system. Specifically, the method determines the effective beta energy distribution incident on the dosimeter system, and thus the system performs as a beta spectrometer. Electron transport theory provides the mathematical model for performing the optimization calculation. In this calculation, parameters are determined that produce calculated doses for each of the chip/absorber components in the three-element TLD system. The resulting optimized parameters describe an effective incident beta distribution. This method can be used to determine the beta dose specifically at 7 mg X cm-2 or at any depth of interest. The doses at 7 mg X cm-2 in tissue determined by this method are compared to those experimentally determined using an extrapolation chamber. For a great variety of pure beta sources having different incident beta energy distributions, good agreement is found. The results are also compared to those produced by a commonly used empirical algorithm. Although the optimization method produces somewhat better results, the advantage of the optimization method is that its performance is not sensitive to the specific method of calibration.

[Optimization of the pertussis vaccine production process].

PubMed

Germán Santiago, J; Zamora, N; de la Rosa, E; Alba Carrión, C; Padrón, P; Hernández, M; Betancourt, M; Moretti, N

1995-01-01

The production of Pertussis Vaccine was reevaluated at the Instituto Nacional de Higiene "Rafael Rangel" in order to optimise it in terms of vaccine yield, potency, specific toxicity and efficiency (cost per doses). Four different processes, using two culture media (Cohen-Wheeler and Fermentación Glutamato Prolina-1) and two types of bioreactors (25 L Fermentador Caracas and a 450 L industrial fermentor) were compared. Runs were started from freeze-dried strains (134 or 509) and continued until the obtention of the maximal yield. It was found that the combination Fermentación Glutamato Prolina-1/industrial fermentor, shortened the process to 40 hours while consistently yielding a vaccine of higher potency (7.91 +/- 2.56 IU/human dose) and lower specific toxicity in a mice bioassay. In addition, the physical aspect of the preparation was rather homogeneous and free of dark aggregates. Most importantly, the biomass yield more than doubled those of the Fermentador Caracas using the two different media and that in the industrial fermentor with the Cohen-Wheeler medium. Therefore, the cost per doses was substantially decreased.

Mathematical optimization of high dose-rate brachytherapy—derivation of a linear penalty model from a dose-volume model

NASA Astrophysics Data System (ADS)

Morén, B.; Larsson, T.; Carlsson Tedgren, Å.

2018-03-01

High dose-rate brachytherapy is a method for cancer treatment where the radiation source is placed within the body, inside or close to a tumour. For dose planning, mathematical optimization techniques are being used in practice and the most common approach is to use a linear model which penalizes deviations from specified dose limits for the tumour and for nearby organs. This linear penalty model is easy to solve, but its weakness lies in the poor correlation of its objective value and the dose-volume objectives that are used clinically to evaluate dose distributions. Furthermore, the model contains parameters that have no clear clinical interpretation. Another approach for dose planning is to solve mixed-integer optimization models with explicit dose-volume constraints which include parameters that directly correspond to dose-volume objectives, and which are therefore tangible. The two mentioned models take the overall goals for dose planning into account in fundamentally different ways. We show that there is, however, a mathematical relationship between them by deriving a linear penalty model from a dose-volume model. This relationship has not been established before and improves the understanding of the linear penalty model. In particular, the parameters of the linear penalty model can be interpreted as dual variables in the dose-volume model.

CD uniformity control for thick resist process

NASA Astrophysics Data System (ADS)

Huang, Chi-hao; Liu, Yu-Lin; Wang, Weihung; Yang, Mars; Yang, Elvis; Yang, T. H.; Chen, K. C.

2017-03-01

In order to meet the increasing storage capacity demand and reduce bit cost of NAND flash memories, 3D stacked flash cell array has been proposed. In constructing 3D NAND flash memories, the higher bit number per area is achieved by increasing the number of stacked layers. Thus the so-called "staircase" patterning to form electrical connection between memory cells and word lines has become one of the primarily critical processes in 3D memory manufacture. To provide controllable critical dimension (CD) with good uniformity involving thick photo-resist has also been of particular concern for staircase patterning. The CD uniformity control has been widely investigated with relatively thinner resist associated with resolution limit dimension but thick resist coupling with wider dimension. This study explores CD uniformity control associated with thick photo-resist processing. Several critical parameters including exposure focus, exposure dose, baking condition, pattern size and development recipe, were found to strongly correlate with the thick photo-resist profile accordingly affecting the CD uniformity control. To minimize the within-wafer CD variation, the slightly tapered resist profile is proposed through well tailoring the exposure focus and dose together with optimal development recipe. Great improvements on DCD (ADI CD) and ECD (AEI CD) uniformity as well as line edge roughness were achieved through the optimization of photo resist profile.

The art and science of switching antipsychotic medications, part 2.

PubMed

Weiden, Peter J; Miller, Alexander L; Lambert, Tim J; Buckley, Peter F

2007-01-01

In the presentation "Switching and Metabolic Syndrome," Weiden summarizes reasons to switch antipsychotics, highlighting weight gain and other metabolic adverse events as recent treatment targets. In "Texas Medication Algorithm Project (TMAP)," Miller reviews the TMAP study design, discusses results related to the algorithm versus treatment as usual, and concludes with the implications of the study. Lambert's presentation, "Dosing and Titration Strategies to Optimize Patient Outcome When Switching Antipsychotic Therapy," reviews the decision-making process when switching patients' medication, addresses dosing and titration strategies to effectively transition between medications, and examines other factors to consider when switching pharmacotherapy.

WE-AB-BRA-09: Sensitivity of Plan Re-Optimization to Errors in Deformable Image Registration in Online Adaptive Image-Guided Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClain, B; Olsen, J; Green, O

2015-06-15

Purpose: Online adaptive therapy (ART) relies on auto-contouring using deformable image registration (DIR). DIR’s inherent uncertainties require user intervention and manual edits while the patient is on the table. We investigated the dosimetric impact of DIR errors on the quality of re-optimized plans, and used the findings to establish regions for focusing manual edits to where DIR errors can Result in clinically relevant dose differences. Methods: Our clinical implementation of online adaptive MR-IGRT involves using DIR to transfer contours from CT to daily MR, followed by a physicians’ edits. The plan is then re-optimized to meet the organs at riskmore » (OARs) constraints. Re-optimized abdomen and pelvis plans generated based on physician edited OARs were selected as the baseline for evaluation. Plans were then re-optimized on auto-deformed contours with manual edits limited to pre-defined uniform rings (0 to 5cm) around the PTV. A 0cm ring indicates that the auto-deformed OARs were used without editing. The magnitude of the variations caused by the non-deterministic optimizer was quantified by repeat re-optimizations on the same geometry to determine the mean and standard deviation (STD). For each re-optimized plan, various volumetric parameters for the PTV, the OARs were extracted along with DVH and isodose evaluation. A plan was deemed acceptable if the variation from the baseline plan was within one STD. Results: Initial results show that for abdomen and pancreas cases, a minimum of 5cm margin around the PTV is required for contour corrections, while for pelvic and liver cases a 2–3 cm margin is sufficient. Conclusion: Focusing manual contour edits to regions of dosimetric relevance can reduce contouring time in the online ART process while maintaining a clinically comparable plan. Future work will further refine the contouring region by evaluating the path along the beams, dose gradients near the target and OAR dose metrics.« less

Selective robust optimization: A new intensity-modulated proton therapy optimization strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yupeng; Niemela, Perttu; Siljamaki, Sami

2015-08-15

Purpose: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications. Methods: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy. The lung cancer cases had minimal tumor motion less than 5 mm, and, for the demonstration of the methodology,more » are assumed to be static. Results: Selective robust optimization achieved robust clinical target volume (CTV) coverage and at the same time increased nominal planning target volume coverage to 95.8%, compared to the 84.6% coverage achieved with CTV-based robust optimization in one of the lung cases. In the other lung case, the maximum dose in selective robust optimization was lowered from a dose of 131.3% in the CTV-based robust optimization to 113.6%. Selective robust optimization provided robust CTV coverage in the head and neck case, and at the same time improved controls over isodose distribution so that clinical requirements may be readily met. Conclusions: Selective robust optimization may provide the flexibility and capability necessary for meeting various clinical requirements in addition to achieving the required plan robustness in practical proton treatment planning settings.« less

Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

NASA Astrophysics Data System (ADS)

Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

2017-01-01

We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation.

PubMed

Ramakrishnan, Sridhar; Laxminarayan, Srinivas; Wesensten, Nancy J; Kamimori, Gary H; Balkin, Thomas J; Reifman, Jaques

2014-10-07

Caffeine is the most widely consumed stimulant to counter sleep-loss effects. While the pharmacokinetics of caffeine in the body is well-understood, its alertness-restoring effects are still not well characterized. In fact, mathematical models capable of predicting the effects of varying doses of caffeine on objective measures of vigilance are not available. In this paper, we describe a phenomenological model of the dose-dependent effects of caffeine on psychomotor vigilance task (PVT) performance of sleep-deprived subjects. We used the two-process model of sleep regulation to quantify performance during sleep loss in the absence of caffeine and a dose-dependent multiplier factor derived from the Hill equation to model the effects of single and repeated caffeine doses. We developed and validated the model fits and predictions on PVT lapse (number of reaction times exceeding 500 ms) data from two separate laboratory studies. At the population-average level, the model captured the effects of a range of caffeine doses (50-300 mg), yielding up to a 90% improvement over the two-process model. Individual-specific caffeine models, on average, predicted the effects up to 23% better than population-average caffeine models. The proposed model serves as a useful tool for predicting the dose-dependent effects of caffeine on the PVT performance of sleep-deprived subjects and, therefore, can be used for determining caffeine doses that optimize the timing and duration of peak performance. Published by Elsevier Ltd.

Automatic CT simulation optimization for radiation therapy: A general strategy.

PubMed

Li, Hua; Yu, Lifeng; Anastasio, Mark A; Chen, Hsin-Chen; Tan, Jun; Gay, Hiram; Michalski, Jeff M; Low, Daniel A; Mutic, Sasa

2014-03-01

In radiation therapy, x-ray computed tomography (CT) simulation protocol specifications should be driven by the treatment planning requirements in lieu of duplicating diagnostic CT screening protocols. The purpose of this study was to develop a general strategy that allows for automatically, prospectively, and objectively determining the optimal patient-specific CT simulation protocols based on radiation-therapy goals, namely, maintenance of contouring quality and integrity while minimizing patient CT simulation dose. The authors proposed a general prediction strategy that provides automatic optimal CT simulation protocol selection as a function of patient size and treatment planning task. The optimal protocol is the one that delivers the minimum dose required to provide a CT simulation scan that yields accurate contours. Accurate treatment plans depend on accurate contours in order to conform the dose to actual tumor and normal organ positions. An image quality index, defined to characterize how simulation scan quality affects contour delineation, was developed and used to benchmark the contouring accuracy and treatment plan quality within the predication strategy. A clinical workflow was developed to select the optimal CT simulation protocols incorporating patient size, target delineation, and radiation dose efficiency. An experimental study using an anthropomorphic pelvis phantom with added-bolus layers was used to demonstrate how the proposed prediction strategy could be implemented and how the optimal CT simulation protocols could be selected for prostate cancer patients based on patient size and treatment planning task. Clinical IMRT prostate treatment plans for seven CT scans with varied image quality indices were separately optimized and compared to verify the trace of target and organ dosimetry coverage. Based on the phantom study, the optimal image quality index for accurate manual prostate contouring was 4.4. The optimal tube potentials for patient sizes of 38, 43, 48, 53, and 58 cm were 120, 140, 140, 140, and 140 kVp, respectively, and the corresponding minimum CTDIvol for achieving the optimal image quality index 4.4 were 9.8, 32.2, 100.9, 241.4, and 274.1 mGy, respectively. For patients with lateral sizes of 43-58 cm, 120-kVp scan protocols yielded up to 165% greater radiation dose relative to 140-kVp protocols, and 140-kVp protocols always yielded a greater image quality index compared to the same dose-level 120-kVp protocols. The trace of target and organ dosimetry coverage and the γ passing rates of seven IMRT dose distribution pairs indicated the feasibility of the proposed image quality index for the predication strategy. A general strategy to predict the optimal CT simulation protocols in a flexible and quantitative way was developed that takes into account patient size, treatment planning task, and radiation dose. The experimental study indicated that the optimal CT simulation protocol and the corresponding radiation dose varied significantly for different patient sizes, contouring accuracy, and radiation treatment planning tasks.

TU-C-BRE-11: 3D EPID-Based in Vivo Dosimetry: A Major Step Forward Towards Optimal Quality and Safety in Radiation Oncology Practice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mijnheer, B; Mans, A; Olaciregui-Ruiz, I

Purpose: To develop a 3D in vivo dosimetry method that is able to substitute pre-treatment verification in an efficient way, and to terminate treatment delivery if the online measured 3D dose distribution deviates too much from the predicted dose distribution. Methods: A back-projection algorithm has been further developed and implemented to enable automatic 3D in vivo dose verification of IMRT/VMAT treatments using a-Si EPIDs. New software tools were clinically introduced to allow automated image acquisition, to periodically inspect the record-and-verify database, and to automatically run the EPID dosimetry software. The comparison of the EPID-reconstructed and planned dose distribution is donemore » offline to raise automatically alerts and to schedule actions when deviations are detected. Furthermore, a software package for online dose reconstruction was also developed. The RMS of the difference between the cumulative planned and reconstructed 3D dose distributions was used for triggering a halt of a linac. Results: The implementation of fully automated 3D EPID-based in vivo dosimetry was able to replace pre-treatment verification for more than 90% of the patient treatments. The process has been fully automated and integrated in our clinical workflow where over 3,500 IMRT/VMAT treatments are verified each year. By optimizing the dose reconstruction algorithm and the I/O performance, the delivered 3D dose distribution is verified in less than 200 ms per portal image, which includes the comparison between the reconstructed and planned dose distribution. In this way it was possible to generate a trigger that can stop the irradiation at less than 20 cGy after introducing large delivery errors. Conclusion: The automatic offline solution facilitated the large scale clinical implementation of 3D EPID-based in vivo dose verification of IMRT/VMAT treatments; the online approach has been successfully tested for various severe delivery errors.« less

Patient-specific Monte Carlo-based dose-kernel approach for inverse planning in afterloading brachytherapy.

PubMed

D'Amours, Michel; Pouliot, Jean; Dagnault, Anne; Verhaegen, Frank; Beaulieu, Luc

2011-12-01

Brachytherapy planning software relies on the Task Group report 43 dosimetry formalism. This formalism, based on a water approximation, neglects various heterogeneous materials present during treatment. Various studies have suggested that these heterogeneities should be taken into account to improve the treatment quality. The present study sought to demonstrate the feasibility of incorporating Monte Carlo (MC) dosimetry within an inverse planning algorithm to improve the dose conformity and increase the treatment quality. The method was based on precalculated dose kernels in full patient geometries, representing the dose distribution of a brachytherapy source at a single dwell position using MC simulations and the Geant4 toolkit. These dose kernels are used by the inverse planning by simulated annealing tool to produce a fast MC-based plan. A test was performed for an interstitial brachytherapy breast treatment using two different high-dose-rate brachytherapy sources: the microSelectron iridium-192 source and the electronic brachytherapy source Axxent operating at 50 kVp. A research version of the inverse planning by simulated annealing algorithm was combined with MC to provide a method to fully account for the heterogeneities in dose optimization, using the MC method. The effect of the water approximation was found to depend on photon energy, with greater dose attenuation for the lower energies of the Axxent source compared with iridium-192. For the latter, an underdosage of 5.1% for the dose received by 90% of the clinical target volume was found. A new method to optimize afterloading brachytherapy plans that uses MC dosimetric information was developed. Including computed tomography-based information in MC dosimetry in the inverse planning process was shown to take into account the full range of scatter and heterogeneity conditions. This led to significant dose differences compared with the Task Group report 43 approach for the Axxent source. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of respiratory motion on worst-case scenario optimized intensity modulated proton therapy for lung cancers.

PubMed

Liu, Wei; Liao, Zhongxing; Schild, Steven E; Liu, Zhong; Li, Heng; Li, Yupeng; Park, Peter C; Li, Xiaoqiang; Stoker, Joshua; Shen, Jiajian; Keole, Sameer; Anand, Aman; Fatyga, Mirek; Dong, Lei; Sahoo, Narayan; Vora, Sujay; Wong, William; Zhu, X Ronald; Bues, Martin; Mohan, Radhe

2015-01-01

We compared conventionally optimized intensity modulated proton therapy (IMPT) treatment plans against worst-case scenario optimized treatment plans for lung cancer. The comparison of the 2 IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient setup, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. For each of the 9 lung cancer cases, 2 treatment plans were created that accounted for treatment uncertainties in 2 different ways. The first used the conventional method: delivery of prescribed dose to the planning target volume that is geometrically expanded from the internal target volume (ITV). The second used a worst-case scenario optimization scheme that addressed setup and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of changes in patient anatomy attributable to respiratory motion were investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the 2 groups were compared with 2-sided paired Student t tests. Without respiratory motion considered, we affirmed that worst-case scenario optimization is superior to planning target volume-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, worst-case scenario optimization still achieved more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality (D95% ITV, 96.6% vs 96.1% [P = .26]; D5%- D95% ITV, 10.0% vs 12.3% [P = .082]; D1% spinal cord, 31.8% vs 36.5% [P = .035]). Worst-case scenario optimization led to superior solutions for lung IMPT. Despite the fact that worst-case scenario optimization did not explicitly account for respiratory motion, it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Schild, S; Bues, M

Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from themore » internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly account for respiratory motion it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization.« less

Toxicity assessment of tannery effluent treated by an optimized photo-Fenton process.

PubMed

Borba, Fernando Henrique; Módenes, Aparecido Nivaldo; Espinoza-Quiñones, Fernando Rodolfo; Manenti, Diego Ricieri; Bergamasco, Rosangela; Mora, Nora Diaz

2013-01-01

In this work, an optimized photo-Fenton process was applied to remove pollutants from tannery industrial effluent (TIE) with its final toxicity level being assessed by a lettuce-seed-based bioassay test. A full 33 factorial design was applied for the optimization of long-term photo-Fenton experiments. The oPtimum conditions of the photo-Fenton process were attained at concentration values of 0.3 g Fe(2+) L(-1) and 20 g H2O2 L(-1) and pH3, for 120 min UV irradiation time. Reactor operating parameter (ROP) effects on the removal of chemical oxygen demand, colour, turbidity, total suspended solids and total volatile solids were evaluated, suggesting that a broad range of ROP values are also suitable to give results very near to those of the photo-Fenton experiments under optimal conditions. Based on the low calculated median lethal dose (LD50) values from a lettuce-seed-based bioassay test, we suggest that recalcitrant substances are present in treated TIE samples. A possible cause of the high toxicity level could partly be attributed to the nitrate concentration, which was not completely abated by the photo-Fenton process. Apart from this, the photo-Fenton process can be used as a part of an industrial effluent treatment system in order to abate high organic pollutant loads.

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PubMed

Liu, Chenbin; Schild, Steven E; Chang, Joe Y; Liao, Zhongxing; Korte, Shawn; Shen, Jiajian; Ding, Xiaoning; Hu, Yanle; Kang, Yixiu; Keole, Sameer R; Sio, Terence T; Wong, William W; Sahoo, Narayan; Bues, Martin; Liu, Wei

2018-06-01

To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large-spot machine, which gives the planning system more freedom to compensate for the higher sensitivity to uncertainties and interplay effects for lung cancer treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

"SABER": A new software tool for radiotherapy treatment plan evaluation.

PubMed

Zhao, Bo; Joiner, Michael C; Orton, Colin G; Burmeister, Jay

2010-11-01

Both spatial and biological information are necessary in order to perform true optimization of a treatment plan and for predicting clinical outcome. The goal of this work is to develop an enhanced treatment plan evaluation tool which incorporates biological parameters and retains spatial dose information. A software system is developed which provides biological plan evaluation with a novel combination of features. It incorporates hyper-radiosensitivity using the induced-repair model and applies the new concept of dose convolution filter (DCF) to simulate dose wash-out effects due to cell migration, bystander effect, and/or tissue motion during treatment. Further, the concept of spatial DVH (sDVH) is introduced to evaluate and potentially optimize the spatial dose distribution in the target volume. Finally, generalized equivalent uniform dose is derived from both the physical dose distribution (gEUD) and the distribution of equivalent dose in 2 Gy fractions (gEUD2) and the software provides three separate models for calculation of tumor control probability (TCP), normal tissue complication probability (NTCP), and probability of uncomplicated tumor control (P+). TCP, NTCP, and P+ are provided as a function of prescribed dose and multivariable TCP, NTCP, and P+ plots are provided to illustrate the dependence on individual parameters used to calculate these quantities. Ten plans from two clinical treatment sites are selected to test the three calculation models provided by this software. By retaining both spatial and biological information about the dose distribution, the software is able to distinguish features of radiotherapy treatment plans not discernible using commercial systems. Plans that have similar DVHs may have different spatial and biological characteristics and the application of novel tools such as sDVH and DCF within the software may substantially change the apparent plan quality or predicted plan metrics such as TCP and NTCP. For the cases examined, both the calculation method and the application of DCF can change the ranking order of competing plans. The voxel-by-voxel TCP model makes it feasible to incorporate spatial variations of clonogen densities (n), radiosensitivities (SF2), and fractionation sensitivities (alpha/beta) as those data become available. The new software incorporates both spatial and biological information into the treatment planning process. The application of multiple methods for the incorporation of biological and spatial information has demonstrated that the order of application of biological models can change the order of plan ranking. Thus, the results of plan evaluation and optimization are dependent not only on the models used but also on the order in which they are applied. This software can help the planner choose more biologically optimal treatment plans and potentially predict treatment outcome more accurately.

A feasibility study of dynamic adaptive radiotherapy for nonsmall cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Minsun, E-mail: mk688@uw.edu; Phillips, Mark H.

2016-05-15

Purpose: The final state of the tumor at the end of a radiotherapy course is dependent on the doses given in each fraction during the treatment course. This study investigates the feasibility of using dynamic adaptive radiotherapy (DART) in treating lung cancers assuming CBCT is available to observe midtreatment tumor states. DART adapts treatment plans using a dynamic programming technique to consider the expected changes of the tumor in the optimization process. Methods: DART is constructed using a stochastic control formalism framework. It minimizes the total expected number of tumor cells at the end of a treatment course, which ismore » equivalent to maximizing tumor control probability, subject to the uncertainty inherent in the tumor response. This formulation allows for nonstationary dose distributions as well as nonstationary fractional doses as needed to achieve a series of optimal plans that are conformal to the tumor over time, i.e., spatiotemporally optimal plans. Sixteen phantom cases with various sizes and locations of tumors and organs-at-risk (OAR) were generated using in-house software. Each case was planned with DART and conventional IMRT prescribing 60 Gy in 30 fractions. The observations of the change in the tumor volume over a treatment course were simulated using a two-level cell population model. Monte Carlo simulations of the treatment course for each case were run to account for uncertainty in the tumor response. The same OAR dose constraints were applied for both methods. The frequency of replanning was varied between 1, 2, 5 (weekly), and 29 times (daily). The final average tumor dose and OAR doses have been compared to quantify the potential dosimetric benefits of DART. Results: The average tumor max, min, mean, and D95 doses using DART relative to these using conventional IMRT were 124.0%–125.2%, 102.1%–114.7%, 113.7%–123.4%, and 102.0%–115.9% (range dependent on the frequency of replanning). The average relative maximum doses for the cord and esophagus, mean doses for the heart and lungs, and D05 for the unspecified tissue resulting 84%–102.4%, 99.8%–106.9%, 66.9%–85.6%, 58.2%–78.8%, and 85.2%–94.0%, respectively. Conclusions: It is feasible to apply DART to the treatment of NSCLC using CBCT to observe the midtreatment tumor state. Potential increases in the tumor dose and reductions in the OAR dose, particularly for parallel OARs with mean or dose–volume constraints, could be achieved using DART compared to nonadaptive IMRT.« less

Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barragán, A. M., E-mail: ana.barragan@uclouvain.be; Differding, S.; Lee, J. A.

Purpose: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. Methods: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTV{sub PET}) was calculated from {sup 18}FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number ofmore » fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTV{sub PET} inevitably leads to overdosing, which was compared for both optimization schemes. Results: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTV{sub PET} (worst case) were above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. Conclusions: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.« less

Comparison of different treatment planning optimization methods for vaginal HDR brachytherapy with multichannel applicators: A reduction of the high doses to the vaginal mucosa is possible.

PubMed

Carrara, Mauro; Cusumano, Davide; Giandini, Tommaso; Tenconi, Chiara; Mazzarella, Ester; Grisotto, Simone; Massari, Eleonora; Mazzeo, Davide; Cerrotta, Annamaria; Pappalardi, Brigida; Fallai, Carlo; Pignoli, Emanuele

2017-12-01

A direct planning approach with multi-channel vaginal cylinders (MVCs) used for HDR brachytherapy of vaginal cancers is particularly challenging. Purpose of this study was to compare the dosimetric performances of different forward and inverse methods used for the optimization of MVC-based vaginal treatments for endometrial cancer, with a particular attention to the definition of strategies useful to limit the high doses to the vaginal mucosa. Twelve postoperative vaginal HDR brachytherapy treatments performed with MVCs were considered. Plans were retrospectively optimized with three different methods: Dose Point Optimization followed by Graphical Optimization (DPO + GrO), Inverse Planning Simulated Annealing with two different class solutions as starting conditions (surflPSA and homogIPSA) and Hybrid Inverse Planning Optimization (HIPO). Several dosimetric parameters related to target coverage, hot spot extensions and sparing of organs at risk were analyzed to evaluate the quality of the achieved treatment plans. Dose homogeneity index (DHI), conformal index (COIN) and a further parameter quantifying the proportion of the central catheter loading with respect to the overall loading (i.e., the central catheter loading index: CCLI) were also quantified. The achieved PTV coverage parameters were highly correlated with each other but uncorrelated with the hot spot quantifiers. HomogIPSA and HIPO achieved higher DHIs and CCLIs and lower volumes of high doses than DPO + GrO and surflPSA. Within the investigated optimization methods, HIPO and homoglPSA showed the highest dose homogeneity to the target. In particular, homogIPSA resulted also the most effective in reducing hot spots to the vaginal mucosa. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wei, E-mail: Liu.Wei@mayo.edu; Schild, Steven E.; Chang, Joe Y.

Purpose: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods and Materials: IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered.more » In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. Results: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D{sub 95%} CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D{sub 5%}-D{sub 95%} CTV: 10.3 vs 17.7, resspectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D{sub 95%} CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions: Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions.« less

Development of probabilistic internal dosimetry computer code

NASA Astrophysics Data System (ADS)

Noh, Siwan; Kwon, Tae-Eun; Lee, Jai-Ki

2017-02-01

Internal radiation dose assessment involves biokinetic models, the corresponding parameters, measured data, and many assumptions. Every component considered in the internal dose assessment has its own uncertainty, which is propagated in the intake activity and internal dose estimates. For research or scientific purposes, and for retrospective dose reconstruction for accident scenarios occurring in workplaces having a large quantity of unsealed radionuclides, such as nuclear power plants, nuclear fuel cycle facilities, and facilities in which nuclear medicine is practiced, a quantitative uncertainty assessment of the internal dose is often required. However, no calculation tools or computer codes that incorporate all the relevant processes and their corresponding uncertainties, i.e., from the measured data to the committed dose, are available. Thus, the objective of the present study is to develop an integrated probabilistic internal-dose-assessment computer code. First, the uncertainty components in internal dosimetry are identified, and quantitative uncertainty data are collected. Then, an uncertainty database is established for each component. In order to propagate these uncertainties in an internal dose assessment, a probabilistic internal-dose-assessment system that employs the Bayesian and Monte Carlo methods. Based on the developed system, we developed a probabilistic internal-dose-assessment code by using MATLAB so as to estimate the dose distributions from the measured data with uncertainty. Using the developed code, we calculated the internal dose distribution and statistical values ( e.g. the 2.5th, 5th, median, 95th, and 97.5th percentiles) for three sample scenarios. On the basis of the distributions, we performed a sensitivity analysis to determine the influence of each component on the resulting dose in order to identify the major component of the uncertainty in a bioassay. The results of this study can be applied to various situations. In cases of severe internal exposure, the causation probability of a deterministic health effect can be derived from the dose distribution, and a high statistical value ( e.g., the 95th percentile of the distribution) can be used to determine the appropriate intervention. The distribution-based sensitivity analysis can also be used to quantify the contribution of each factor to the dose uncertainty, which is essential information for reducing and optimizing the uncertainty in the internal dose assessment. Therefore, the present study can contribute to retrospective dose assessment for accidental internal exposure scenarios, as well as to internal dose monitoring optimization and uncertainty reduction.

TH-AB-BRA-02: Automated Triplet Beam Orientation Optimization for MRI-Guided Co-60 Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, D; Thomas, D; Cao, M

2016-06-15

Purpose: MRI guided Co-60 provides daily and intrafractional MRI soft tissue imaging for improved target tracking and adaptive radiotherapy. To remedy the low output limitation, the system uses three Co-60 sources at 120° apart, but using all three sources in planning is considerably unintuitive. We automate the beam orientation optimization using column generation, and then solve a novel fluence map optimization (FMO) problem while regularizing the number of MLC segments. Methods: Three patients—1 prostate (PRT), 1 lung (LNG), and 1 head-and-neck boost plan (H&NBoost)—were evaluated. The beamlet dose for 180 equally spaced coplanar beams under 0.35 T magnetic field wasmore » calculated using Monte Carlo. The 60 triplets were selected utilizing the column generation algorithm. The FMO problem was formulated using an L2-norm minimization with anisotropic total variation (TV) regularization term, which allows for control over the number of MLC segments. Our Fluence Regularized and Optimized Selection of Triplets (FROST) plans were compared against the clinical treatment plans (CLN) produced by an experienced dosimetrist. Results: The mean PTV D95, D98, and D99 differ by −0.02%, +0.12%, and +0.44% of the prescription dose between planning methods, showing same PTV dose coverage. The mean PTV homogeneity (D95/D5) was at 0.9360 (FROST) and 0.9356 (CLN). R50 decreased by 0.07 with FROST. On average, FROST reduced Dmax and Dmean of OARs by 6.56% and 5.86% of the prescription dose. The manual CLN planning required iterative trial and error runs which is very time consuming, while FROST required minimal human intervention. Conclusions: MRI guided Co-60 therapy needs the output of all sources yet suffers from unintuitive and laborious manual beam selection processes. Automated triplet orientation optimization is shown essential to overcome the difficulty and improves the dosimetry. A novel FMO with regularization provides additional controls over the number of MLC segments and treatment time. Varian Medical Systems; NIH grant R01CA188300; NIH grant R43CA183390.« less

An efficient inverse radiotherapy planning method for VMAT using quadratic programming optimization.

PubMed

Hoegele, W; Loeschel, R; Merkle, N; Zygmanski, P

2012-01-01

The purpose of this study is to investigate the feasibility of an inverse planning optimization approach for the Volumetric Modulated Arc Therapy (VMAT) based on quadratic programming and the projection method. The performance of this method is evaluated against a reference commercial planning system (eclipse(TM) for rapidarc(TM)) for clinically relevant cases. The inverse problem is posed in terms of a linear combination of basis functions representing arclet dose contributions and their respective linear coefficients as degrees of freedom. MLC motion is decomposed into basic motion patterns in an intuitive manner leading to a system of equations with a relatively small number of equations and unknowns. These equations are solved using quadratic programming under certain limiting physical conditions for the solution, such as the avoidance of negative dose during optimization and Monitor Unit reduction. The modeling by the projection method assures a unique treatment plan with beneficial properties, such as the explicit relation between organ weightings and the final dose distribution. Clinical cases studied include prostate and spine treatments. The optimized plans are evaluated by comparing isodose lines, DVH profiles for target and normal organs, and Monitor Units to those obtained by the clinical treatment planning system eclipse(TM). The resulting dose distributions for a prostate (with rectum and bladder as organs at risk), and for a spine case (with kidneys, liver, lung and heart as organs at risk) are presented. Overall, the results indicate that similar plan qualities for quadratic programming (QP) and rapidarc(TM) could be achieved at significantly more efficient computational and planning effort using QP. Additionally, results for the quasimodo phantom [Bohsung et al., "IMRT treatment planning: A comparative inter-system and inter-centre planning exercise of the estro quasimodo group," Radiother. Oncol. 76(3), 354-361 (2005)] are presented as an example for an extreme concave case. Quadratic programming is an alternative approach for inverse planning which generates clinically satisfying plans in comparison to the clinical system and constitutes an efficient optimization process characterized by uniqueness and reproducibility of the solution.

Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

NASA Astrophysics Data System (ADS)

Gaddy, Melissa R.; Yıldız, Sercan; Unkelbach, Jan; Papp, Dávid

2018-01-01

Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, can potentially lower treatment side effects without compromising tumor control. This can be achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the surrounding tissue. Plan optimization for such treatments is based on biologically effective dose (BED); however, this leads to computationally challenging nonconvex optimization problems. Optimization methods that are in current use yield only locally optimal solutions, and it has hitherto been unclear whether these plans are close to the global optimum. We present an optimization framework to compute rigorous bounds on the maximum achievable normal tissue BED reduction for spatiotemporal plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising any other treatment objective. The BED-based treatment plan optimization problems are formulated as quadratically constrained quadratic programming (QCQP) problems. First, a conventional, uniformly fractionated reference plan is computed using convex optimization. Then, a second, nonconvex, QCQP model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED, subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a rigorous lower bound on the lowest achievable mean liver BED. The method is presented on five cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the optimal uniformly fractionated plans. This reduction corresponds to 79-97% of the gap between the mean liver BED of the uniform reference plans and our lower bounds on the lowest achievable mean liver BED. The results indicate that spatiotemporal treatments can achieve substantial reductions in normal tissue dose and BED, and that local optimization techniques provide high-quality plans that are close to realizing the maximum potential normal tissue dose reduction.

SU-E-T-295: Simultaneous Beam Sampling and Aperture Shape Optimization for Station Parameter Optimized Radiation Therapy (SPORT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zarepisheh, M; Li, R; Xing, L

Purpose: Station Parameter Optimized Radiation Therapy (SPORT) was recently proposed to fully utilize the technical capability of emerging digital LINACs, in which the station parameters of a delivery system, (such as aperture shape and weight, couch position/angle, gantry/collimator angle) are optimized altogether. SPORT promises to deliver unprecedented radiation dose distributions efficiently, yet there does not exist any optimization algorithm to implement it. The purpose of this work is to propose an optimization algorithm to simultaneously optimize the beam sampling and aperture shapes. Methods: We build a mathematical model whose variables are beam angles (including non-coplanar and/or even nonisocentric beams) andmore » aperture shapes. To solve the resulting large scale optimization problem, we devise an exact, convergent and fast optimization algorithm by integrating three advanced optimization techniques named column generation, gradient method, and pattern search. Column generation is used to find a good set of aperture shapes as an initial solution by adding apertures sequentially. Then we apply the gradient method to iteratively improve the current solution by reshaping the aperture shapes and updating the beam angles toward the gradient. Algorithm continues by pattern search method to explore the part of the search space that cannot be reached by the gradient method. Results: The proposed technique is applied to a series of patient cases and significantly improves the plan quality. In a head-and-neck case, for example, the left parotid gland mean-dose, brainstem max-dose, spinal cord max-dose, and mandible mean-dose are reduced by 10%, 7%, 24% and 12% respectively, compared to the conventional VMAT plan while maintaining the same PTV coverage. Conclusion: Combined use of column generation, gradient search and pattern search algorithms provide an effective way to optimize simultaneously the large collection of station parameters and significantly improves quality of resultant treatment plans as compared with conventional VMAT or IMRT treatments.« less

Feasibility study of using statistical process control to customized quality assurance in proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rah, Jeong-Eun; Oh, Do Hoon; Shin, Dongho

Purpose: To evaluate and improve the reliability of proton quality assurance (QA) processes and, to provide an optimal customized tolerance level using the statistical process control (SPC) methodology. Methods: The authors investigated the consistency check of dose per monitor unit (D/MU) and range in proton beams to see whether it was within the tolerance level of the daily QA process. This study analyzed the difference between the measured and calculated ranges along the central axis to improve the patient-specific QA process in proton beams by using process capability indices. Results: The authors established a customized tolerance level of ±2% formore » D/MU and ±0.5 mm for beam range in the daily proton QA process. In the authors’ analysis of the process capability indices, the patient-specific range measurements were capable of a specification limit of ±2% in clinical plans. Conclusions: SPC methodology is a useful tool for customizing the optimal QA tolerance levels and improving the quality of proton machine maintenance, treatment delivery, and ultimately patient safety.« less

Optimization of oncological {sup 18}F-FDG PET/CT imaging based on a multiparameter analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menezes, Vinicius O., E-mail: vinicius@radtec.com.br; Machado, Marcos A. D.; Queiroz, Cleiton C.

2016-02-15

Purpose: This paper describes a method to achieve consistent clinical image quality in {sup 18}F-FDG scans accounting for patient habitus, dose regimen, image acquisition, and processing techniques. Methods: Oncological PET/CT scan data for 58 subjects were evaluated retrospectively to derive analytical curves that predict image quality. Patient noise equivalent count rate and coefficient of variation (CV) were used as metrics in their analysis. Optimized acquisition protocols were identified and prospectively applied to 179 subjects. Results: The adoption of different schemes for three body mass ranges (<60 kg, 60–90 kg, >90 kg) allows improved image quality with both point spread functionmore » and ordered-subsets expectation maximization-3D reconstruction methods. The application of this methodology showed that CV improved significantly (p < 0.0001) in clinical practice. Conclusions: Consistent oncological PET/CT image quality on a high-performance scanner was achieved from an analysis of the relations existing between dose regimen, patient habitus, acquisition, and processing techniques. The proposed methodology may be used by PET/CT centers to develop protocols to standardize PET/CT imaging procedures and achieve better patient management and cost-effective operations.« less

Optimizing phytoremediation of heavy metal-contaminated soil by exploiting plants' stress adaptation.

PubMed

Barocsi, Attila; Csintalan, Zsolt; Kocsanyi, Laszlo; Dushenkov, Slavik; Kuperberg, J Michael; Kucharski, Rafal; Richter, Peter I

2003-01-01

Soil phytoextraction is based on the ability of plants to extract contaminants from the soil. For less bioavailable metals, such as Pb, a chelator is added to the soil to mobilize the metal. The effect can be significant and in certain species, heavy metal accumulation can rapidly increase 10-fold. Accumulation of high levels of toxic metals may result in irreversible damage to the plant. Monitoring and controlling the phytotoxicity caused by EDTA-induced metal accumulation is crucial to optimize the remedial process, i.e. to achieve maximum uptake. We describe an EDTA-application procedure that minimizes phytotoxicity by increasing plant tolerance and allows phytoextraction of elevated levels of Pb and Cd. Brassica juncea is tested in soil with typical Pb and Cd concentrations of 500 mg kg-1 and 15 mg kg-1, respectively. Instead of a single dose treatment, the chelator is applied in multiple doses, that is, in several small increments, thus providing time for plants to initiate their adaptation mechanisms and raise their damage threshold. In situ monitoring of plant stress conditions by chlorophyll fluorescence recording allows for the identification of the saturating heavy metal accumulation process and of simultaneous plant deterioration.

MO-DE-204-01: Radiation Doses in Over 50 Developing Countries of Asia, Africa, Eastern European and Latin America

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rehani, M.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

MO-DE-204-00: International Symposium: Patient Dose Reduction in Diagnostic Radiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

MO-DE-204-03: Radiology Dose Optimisation - An Australian Perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schick, D.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

SU-D-12A-06: A Comprehensive Parameter Analysis for Low Dose Cone-Beam CT Reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, W; Southern Medical University, Guangzhou; Yan, H

Purpose: There is always a parameter in compressive sensing based iterative reconstruction (IR) methods low dose cone-beam CT (CBCT), which controls the weight of regularization relative to data fidelity. A clear understanding of the relationship between image quality and parameter values is important. The purpose of this study is to investigate this subject based on experimental data and a representative advanced IR algorithm using Tight-frame (TF) regularization. Methods: Three data sets of a Catphan phantom acquired at low, regular and high dose levels are used. For each tests, 90 projections covering a 200-degree scan range are used for reconstruction. Threemore » different regions-of-interest (ROIs) of different contrasts are used to calculate contrast-to-noise ratios (CNR) for contrast evaluation. A single point structure is used to measure modulation transfer function (MTF) for spatial-resolution evaluation. Finally, we analyze CNRs and MTFs to study the relationship between image quality and parameter selections. Results: It was found that: 1) there is no universal optimal parameter. The optimal parameter value depends on specific task and dose level. 2) There is a clear trade-off between CNR and resolution. The parameter for the best CNR is always smaller than that for the best resolution. 3) Optimal parameters are also dose-specific. Data acquired under a high dose protocol require less regularization, yielding smaller optimal parameter values. 4) Comparing with conventional FDK images, TF-based CBCT images are better under a certain optimally selected parameters. The advantages are more obvious for low dose data. Conclusion: We have investigated the relationship between image quality and parameter values in the TF-based IR algorithm. Preliminary results indicate optimal parameters are specific to both the task types and dose levels, providing guidance for selecting parameters in advanced IR algorithms. This work is supported in part by NIH (1R01CA154747-01)« less

[Adequate anti-infective treatment : Importance of individual dosing and application].

PubMed

Brinkmann, A; Röhr, A C; Köberer, A; Fuchs, T; Krüger, W A; König, C; Richter, D; Weigand, M A; Frey, O R

2018-05-15

Sepsis-induced changes in pharmacokinetic parameters are a well-known problem in intensive care medicine. Dosing of antibiotics in this setting is therefore challenging. Alterations to the substance-specific kinetics of anti-infective substances have an effect on the distribution and excretion processes in the body. Increased clearance and an increased distribution volume (V d ) and particularly compromized organ function with reduced antibiotic elimination are often encountered in patients with sepsis. Renal replacement treatment, which is frequently used in intensive care medicine, represents a substantial intervention in this system. Current international guidelines recommend individualized dosing strategies and adaptation of doses according to measured serum levels and pharmacokinetic/pharmacodynamic (PK/PD) parameters as concepts to optimize anti-infective therapy in the critically ill. Likewise, the recommendation to adjust the administration form of beat-lactam antibiotics to prolonged or continuous infusion can be found increasingly more often in the literature. This article reviews the background of the individual dosing in intensive care patients and their applicability to the clinical routine.

Dose in x-ray computed tomography

NASA Astrophysics Data System (ADS)

Kalender, Willi A.

2014-02-01

Radiation dose in x-ray computed tomography (CT) has become a topic of high interest due to the increasing numbers of CT examinations performed worldwide. This review aims to present an overview of current concepts for both scanner output metrics and for patient dosimetry and will comment on their strengths and weaknesses. Controversial issues such as the appropriateness of the CT dose index (CTDI) are discussed in detail. A review of approaches to patient dose assessment presently in practice, of the dose levels encountered and options for further dose optimization are also given and discussed. Patient dose assessment remains a topic for further improvement and for international consensus. All approaches presently in use are based on Monte Carlo (MC) simulations. Estimates for effective dose are established, but they are crude and not patient-specific; organ dose estimates are rarely available. Patient- and organ-specific dose estimates can be provided with adequate accuracy and independent of CTDI phantom measurements by fast MC simulations. Such information, in particular on 3D dose distributions, is important and helpful in optimization efforts. Dose optimization has been performed very successfully in recent years and even resulted in applications with effective dose values of below 1 mSv. In general, a trend towards lower dose values based on technical innovations has to be acknowledged. Effective dose values are down to clearly below 10 mSv on average, and there are a number of applications such as cardiac and pediatric CT which are performed routinely below 1 mSv on modern equipment.

Performance Evaluation of a Dedicated Preclinical PET/CT System for the Assessment of Mineralization Process in a Mouse Model of Atherosclerosis.

PubMed

Rucher, Guillaume; Cameliere, Lucie; Fendri, Jihene; Abbas, Ahmed; Dupont, Kevin; Kamel, Said; Delcroix, Nicolas; Dupont, Axel; Berger, Ludovic; Manrique, Alain

2018-04-30

The purpose of this study was to assess the impact of positron emission tomography/X-ray computed tomography (PET/CT) acquisition and reconstruction parameters on the assessment of mineralization process in a mouse model of atherosclerosis. All experiments were performed on a dedicated preclinical PET/CT system. CT was evaluated using five acquisition configurations using both a tungsten wire phantom for in-plane resolution assessment and a bar pattern phantom for cross-plane resolution. Furthermore, the radiation dose of these acquisition configurations was calculated. The PET system was assessed using longitudinal line sources to determine the optimal reconstruction parameters by measuring central resolution and its coefficient of variation. An in vivo PET study was performed using uremic ApoE -/- , non-uremic ApoE -/- , and control mice to evaluate optimal PET reconstruction parameters for the detection of sodium [ 18 F]fluoride (Na[ 18 F]F) aortic uptake and for quantitative measurement of Na[ 18 F]F bone influx (Ki) with a Patlak analysis. For CT, the use of 1 × 1 and 2 × 2 binning detector mode increased both in-plane and cross-plane resolution. However, resolution improvement (163 to 62 μm for in-plane resolution) was associated with an important radiation dose increase (1.67 to 32.78 Gy). With PET, 3D-ordered subset expectation maximization (3D-OSEM) algorithm increased the central resolution compared to filtered back projection (1.42 ± 0.35 mm vs. 1.91 ± 0.08, p < 0.001). The use of 3D-OSEM with eight iterations and a zoom factor 2 yielded optimal PET resolution for preclinical study (FWHM = 0.98 mm). These PET reconstruction parameters allowed the detection of Na[ 18 F]F aortic uptake in 3/14 ApoE -/- mice and demonstrated a decreased Ki in uremic ApoE -/- compared to non-uremic ApoE -/- and control mice (p < 0.006). Optimizing reconstruction parameters significantly impacted on the assessment of mineralization process in a preclinical model of accelerated atherosclerosis using Na[ 18 F]F PET. In addition, improving the CT resolution was associated with a dramatic radiation dose increase.

Minimizing human error in radiopharmaceutical preparation and administration via a bar code-enhanced nuclear pharmacy management system.

PubMed

Hakala, John L; Hung, Joseph C; Mosman, Elton A

2012-09-01

The objective of this project was to ensure correct radiopharmaceutical administration through the use of a bar code system that links patient and drug profiles with on-site information management systems. This new combined system would minimize the amount of manual human manipulation, which has proven to be a primary source of error. The most common reason for dosing errors is improper patient identification when a dose is obtained from the nuclear pharmacy or when a dose is administered. A standardized electronic transfer of information from radiopharmaceutical preparation to injection will further reduce the risk of misadministration. Value stream maps showing the flow of the patient dose information, as well as potential points of human error, were developed. Next, a future-state map was created that included proposed corrections for the most common critical sites of error. Transitioning the current process to the future state will require solutions that address these sites. To optimize the future-state process, a bar code system that links the on-site radiology management system with the nuclear pharmacy management system was proposed. A bar-coded wristband connects the patient directly to the electronic information systems. The bar code-enhanced process linking the patient dose with the electronic information reduces the number of crucial points for human error and provides a framework to ensure that the prepared dose reaches the correct patient. Although the proposed flowchart is designed for a site with an in-house central nuclear pharmacy, much of the framework could be applied by nuclear medicine facilities using unit doses. An electronic connection between information management systems to allow the tracking of a radiopharmaceutical from preparation to administration can be a useful tool in preventing the mistakes that are an unfortunate reality for any facility.

SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, V; Nguyen, D; Pajonk, F

Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to exploremore » the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work is supported by the NSF Graduate Research Fellowship (DGE-1144087)« less

Bayesian dose selection design for a binary outcome using restricted response adaptive randomization.

PubMed

Meinzer, Caitlyn; Martin, Renee; Suarez, Jose I

2017-09-08

In phase II trials, the most efficacious dose is usually not known. Moreover, given limited resources, it is difficult to robustly identify a dose while also testing for a signal of efficacy that would support a phase III trial. Recent designs have sought to be more efficient by exploring multiple doses through the use of adaptive strategies. However, the added flexibility may potentially increase the risk of making incorrect assumptions and reduce the total amount of information available across the dose range as a function of imbalanced sample size. To balance these challenges, a novel placebo-controlled design is presented in which a restricted Bayesian response adaptive randomization (RAR) is used to allocate a majority of subjects to the optimal dose of active drug, defined as the dose with the lowest probability of poor outcome. However, the allocation between subjects who receive active drug or placebo is held constant to retain the maximum possible power for a hypothesis test of overall efficacy comparing the optimal dose to placebo. The design properties and optimization of the design are presented in the context of a phase II trial for subarachnoid hemorrhage. For a fixed total sample size, a trade-off exists between the ability to select the optimal dose and the probability of rejecting the null hypothesis. This relationship is modified by the allocation ratio between active and control subjects, the choice of RAR algorithm, and the number of subjects allocated to an initial fixed allocation period. While a responsive RAR algorithm improves the ability to select the correct dose, there is an increased risk of assigning more subjects to a worse arm as a function of ephemeral trends in the data. A subarachnoid treatment trial is used to illustrate how this design can be customized for specific objectives and available data. Bayesian adaptive designs are a flexible approach to addressing multiple questions surrounding the optimal dose for treatment efficacy within the context of limited resources. While the design is general enough to apply to many situations, future work is needed to address interim analyses and the incorporation of models for dose response.

Inverse Planning Approach for 3-D MRI-Based Pulse-Dose Rate Intracavitary Brachytherapy in Cervix Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chajon, Enrique; Dumas, Isabelle; Touleimat, Mahmoud B.Sc.

2007-11-01

Purpose: The purpose of this study was to evaluate the inverse planning simulated annealing (IPSA) software for the optimization of dose distribution in patients with cervix carcinoma treated with MRI-based pulsed-dose rate intracavitary brachytherapy. Methods and Materials: Thirty patients treated with a technique using a customized vaginal mold were selected. Dose-volume parameters obtained using the IPSA method were compared with the classic manual optimization method (MOM). Target volumes and organs at risk were delineated according to the Gynecological Brachytherapy Group/European Society for Therapeutic Radiology and Oncology recommendations. Because the pulsed dose rate program was based on clinical experience with lowmore » dose rate, dwell time values were required to be as homogeneous as possible. To achieve this goal, different modifications of the IPSA program were applied. Results: The first dose distribution calculated by the IPSA algorithm proposed a heterogeneous distribution of dwell time positions. The mean D90, D100, and V100 calculated with both methods did not differ significantly when the constraints were applied. For the bladder, doses calculated at the ICRU reference point derived from the MOM differed significantly from the doses calculated by the IPSA method (mean, 58.4 vs. 55 Gy respectively; p = 0.0001). For the rectum, the doses calculated at the ICRU reference point were also significantly lower with the IPSA method. Conclusions: The inverse planning method provided fast and automatic solutions for the optimization of dose distribution. However, the straightforward use of IPSA generated significant heterogeneity in dwell time values. Caution is therefore recommended in the use of inverse optimization tools with clinical relevance study of new dosimetric rules.« less

Low-dose CT in clinical diagnostics.

PubMed

Fuentes-Orrego, Jorge M; Sahani, Dushyant V

2013-09-01

Computed tomography (CT) has become key for patient management due to its outstanding capabilities for detecting disease processes and assessing treatment response, which has led to expansion in CT imaging for diagnostic and image-guided therapeutic interventions. Despite these benefits, the growing use of CT has raised concerns as radiation risks associated with radiation exposure. The purpose of this article is to familiarize the reader with fundamental concepts of dose metrics for assessing radiation exposure and weighting radiation-associated risks. The article also discusses general approaches for reducing radiation dose while preserving diagnostic quality. The authors provide additional insight for undertaking protocol optimization, customizing scanning techniques based on the patients' clinical scenario and demographics. Supplemental strategies are postulated using more advanced post-processing techniques for achieving further dose improvements. The technologic offerings of CT are integral to modern medicine and its role will continue to evolve. Although, the estimated risks from low levels of radiation of a single CT exam are uncertain, it is prudent to minimize the dose from CT by applying common sense solutions and using other simple strategies as well as exploiting technologic innovations. These efforts will enable us to take advantage of all the clinical benefits of CT while minimizing the likelihood of harm to patients.

MO-AB-BRA-01: A Global Level Set Based Formulation for Volumetric Modulated Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, D; Lyu, Q; Ruan, D

2016-06-15

Purpose: The current clinical Volumetric Modulated Arc Therapy (VMAT) optimization is formulated as a non-convex problem and various greedy heuristics have been employed for an empirical solution, jeopardizing plan consistency and quality. We introduce a novel global direct aperture optimization method for VMAT to overcome these limitations. Methods: The global VMAT (gVMAT) planning was formulated as an optimization problem with an L2-norm fidelity term and an anisotropic total variation term. A level set function was used to describe the aperture shapes and adjacent aperture shapes were penalized to control MLC motion range. An alternating optimization strategy was implemented to solvemore » the fluence intensity and aperture shapes simultaneously. Single arc gVMAT plans, utilizing 180 beams with 2° angular resolution, were generated for a glioblastoma multiforme (GBM), lung (LNG), and 2 head and neck cases—one with 3 PTVs (H&N3PTV) and one with 4 PTVs (H&N4PTV). The plans were compared against the clinical VMAT (cVMAT) plans utilizing two overlapping coplanar arcs. Results: The optimization of the gVMAT plans had converged within 600 iterations. gVMAT reduced the average max and mean OAR dose by 6.59% and 7.45% of the prescription dose. Reductions in max dose and mean dose were as high as 14.5 Gy in the LNG case and 15.3 Gy in the H&N3PTV case. PTV coverages (D95, D98, D99) were within 0.25% of the prescription dose. By globally considering all beams, the gVMAT optimizer allowed some beams to deliver higher intensities, yielding a dose distribution that resembles a static beam IMRT plan with beam orientation optimization. Conclusions: The novel VMAT approach allows for the search of an optimal plan in the global solution space and generates deliverable apertures directly. The single arc VMAT approach fully utilizes the digital linacs’ capability in dose rate and gantry rotation speed modulation. Varian Medical Systems, NIH grant R01CA188300, NIH grant R43CA183390.« less

A two‐point scheme for optimal breast IMRT treatment planning

PubMed Central

2013-01-01

We propose an approach to determining optimal beam weights in breast/chest wall IMRT treatment plans. The goal is to decrease breathing effect and to maximize skin dose if the skin is included in the target or, otherwise, to minimize the skin dose. Two points in the target are utilized to calculate the optimal weights. The optimal plan (i.e., the plan with optimal beam weights) consists of high energy unblocked beams, low energy unblocked beams, and IMRT beams. Six breast and five chest wall cases were retrospectively planned with this scheme in Eclipse, including one breast case where CTV was contoured by the physician. Compared with 3D CRT plans composed of unblocked and field‐in‐field beams, the optimal plans demonstrated comparable or better dose uniformity, homogeneity, and conformity to the target, especially at beam junction when supraclavicular nodes are involved. Compared with nonoptimal plans (i.e., plans with nonoptimized weights), the optimal plans had better dose distributions at shallow depths close to the skin, especially in cases where breathing effect was taken into account. This was verified with experiments using a MapCHECK device attached to a motion simulation table (to mimic motion caused by breathing). PACS number: 87.55 de PMID:24257291

Multiparameter optimization of mammography: an update

NASA Astrophysics Data System (ADS)

Jafroudi, Hamid; Muntz, E. P.; Jennings, Robert J.

1994-05-01

Previously in this forum we have reported the application of multiparameter optimization techniques to the design of a minimum dose mammography system. The approach used a reference system to define the physical imaging performance required and the dose to which the dose for the optimized system should be compared. During the course of implementing the resulting design in hardware suitable for laboratory testing, the state of the art in mammographic imaging changed, so that the original reference system, which did not have a grid, was no longer appropriate. A reference system with a grid was selected in response to this change, and at the same time the optimization procedure was modified, to make it more general and to facilitate study of the optimized design under a variety of conditions. We report the changes in the procedure, and the results obtained using the revised procedure and the up- to-date reference system. Our results, which are supported by laboratory measurements, indicate that the optimized design can image small objects as well as the reference system using only about 30% of the dose required by the reference system. Hardware meeting the specification produced by the optimization procedure and suitable for clinical use is currently under evaluation in the Diagnostic Radiology Department at the Clinical Center, NH.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of thismore » novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for small–tumor target patients. This optimizer will be used in an upcoming feasibility trial on LET{sub d} painting for radioresistant tumors.« less

Optimizing dosing of oncology drugs.

PubMed

Minasian, L; Rosen, O; Auclair, D; Rahman, A; Pazdur, R; Schilsky, R L

2014-11-01

The purpose of this article is to acknowledge the challenges in optimizing the dosing of oncology drugs and to propose potential approaches to address these challenges in order to optimize effectiveness, minimize toxicity, and promote adherence in patients. These approaches could provide better opportunities to understand the sources of variability in drug exposure and clinical outcomes during the development and premarketing evaluation of investigational new drugs.

Inclusion of a variable RBE into proton and photon plan comparison for various fractionation schedules in prostate radiation therapy.

PubMed

Ödén, Jakob; Eriksson, Kjell; Toma-Dasu, Iuliana

2017-03-01

A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction, and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions. Photon and proton dose plans were created for three generic prostate cancer cases. Three BED 3Gy equivalent schedules were studied, 78, 57.2, and 42.8 Gy in 39, 15, and 7 fractions, respectively. The proton plans were optimized assuming a constant RBE of 1.1. By using the Monte Carlo calculated dose-averaged LET (LET d ) distribution and assuming α/β values on voxel level, three variable RBE models were applied to the proton dose plans. The impact of the variable RBE was studied in the plan comparison, which was based on the dose distribution, DVHs, and normal tissue complication probabilities (NTCP) for the rectum. Subsequently, the physical proton dose was reoptimized for each proton plan based on the LET d distribution, to achieve a homogeneous RBE-weighted target dose when applying a specific RBE model and still fulfill the clinical goals for the rectum and bladder. All the photon and proton plans assuming RBE = 1.1 met the clinical goals with similar target coverage. The proton plans fulfilled the robustness criteria in terms of range and setup uncertainty. Applying the variable RBE models generally resulted in higher target doses and rectum NTCP compared to the photon plans. The increase was most pronounced for the fractionation dose of 2 Gy(RBE), whereas it was of less magnitude and more dependent on model and α/β assumption for the hypofractionated schedules. The reoptimized proton plans proved to be robust and showed similar target coverage and doses to the organs at risk as the proton plans optimized with a constant RBE. Model predicted RBE values may differ substantially from 1.1. This is most pronounced for fractionation doses of around 2 Gy(RBE) with higher doses to the target and the OARs, whereas the effect seems to be of less importance for the hypofractionated schedules. This could result in misleading conclusions when comparing proton plans to photon plans. By accounting for a variable RBE in the optimization process, robust and clinically acceptable dose plans, with the potential of lowering rectal NTCP, may be generated by reoptimizing the physical dose. However, the direction and magnitude of the changes in the physical proton dose to the prostate are dependent on RBE model and α/β assumptions and should therefore be used conservatively. © 2017 American Association of Physicists in Medicine.

Process change evaluation framework for allogeneic cell therapies: impact on drug development and commercialization.

PubMed

Hassan, Sally; Huang, Hsini; Warren, Kim; Mahdavi, Behzad; Smith, David; Jong, Simcha; Farid, Suzanne S

2016-04-01

Some allogeneic cell therapies requiring a high dose of cells for large indication groups demand a change in cell expansion technology, from planar units to microcarriers in single-use bioreactors for the market phase. The aim was to model the optimal timing for making this change. A development lifecycle cash flow framework was created to examine the implications of process changes to microcarrier cultures at different stages of a cell therapy's lifecycle. The analysis performed under assumptions used in the framework predicted that making this switch earlier in development is optimal from a total expected out-of-pocket cost perspective. From a risk-adjusted net present value view, switching at Phase I is economically competitive but a post-approval switch can offer the highest risk-adjusted net present value as the cost of switching is offset by initial market penetration with planar technologies. The framework can facilitate early decision-making during process development.

Commissioning of a 3D image‐based treatment planning system for high‐dose‐rate brachytherapy of cervical cancer

PubMed Central

Kim, Yongbok; Modrick, Joseph M.; Pennington, Edward C.

2016-01-01

The objective of this work is to present commissioning procedures to clinically implement a three‐dimensional (3D), image‐based, treatment‐planning system (TPS) for high‐dose‐rate (HDR) brachytherapy (BT) for gynecological (GYN) cancer. The physical dimensions of the GYN applicators and their values in the virtual applicator library were varied by 0.4 mm of their nominal values. Reconstruction uncertainties of the titanium tandem and ovoids (T&O) were less than 0.4 mm on CT phantom studies and on average between 0.8‐1.0 mm on MRI when compared with X‐rays. In‐house software, HDRCalculator, was developed to check HDR plan parameters such as independently verifying active tandem or cylinder probe length and ovoid or cylinder size, source calibration and treatment date, and differences between average Point A dose and prescription dose. Dose‐volume histograms were validated using another independent TPS. Comprehensive procedures to commission volume optimization algorithms and process in 3D image‐based planning were presented. For the difference between line and volume optimizations, the average absolute differences as a percentage were 1.4% for total reference air KERMA (TRAK) and 1.1% for Point A dose. Volume optimization consistency tests between versions resulted in average absolute differences in 0.2% for TRAK and 0.9 s (0.2%) for total treatment time. The data revealed that the optimizer should run for at least 1 min in order to avoid more than 0.6% dwell time changes. For clinical GYN T&O cases, three different volume optimization techniques (graphical optimization, pure inverse planning, and hybrid inverse optimization) were investigated by comparing them against a conventional Point A technique. End‐to‐end testing was performed using a T&O phantom to ensure no errors or inconsistencies occurred from imaging through to planning and delivery. The proposed commissioning procedures provide a clinically safe implementation technique for 3D image‐based TPS for HDR BT for GYN cancer. PACS number(s): 87.55.D‐ PMID:27074463

Study of a chemically amplified resist for X-ray lithography by Fourier transform infrared spectroscopy.

PubMed

Tan, T L; Wong, D; Lee, P; Rawat, R S; Patran, A

2004-11-01

Future applications of microelectromechanical systems (MEMS) require lithographic performance of very high aspect ratio. Chemically amplified resists (CARs) such as the negative tone commercial SU-8 provide critical advantages in sensitivity, resolution, and process efficiency in deep ultraviolet, electron-beam, and X-ray lithographies (XRLs), which result in a very high aspect ratio. In this investigation, an SU-8 resist was characterized and optimized for X-ray lithographic applications by studying the cross-linking process of the resist under different conditions of resist thickness and X-ray exposure dose. The exposure dose of soft X-ray (SXR) irradiation at the average weighted wavelength of 1.20 nm from a plasma focus device ranges from 100 to 1600 mJ/cm(2) on the resist surface. Resist thickness varies from 3.5 to 15 mum. The cross-linking process of the resist during post-exposure bake (PEB) was accurately monitored using Fourier transform infrared (FT-IR) spectroscopy. The infrared absorption peaks at 862, 914, 972, and 1128 cm(-1) in the spectrum of the SU-8 resist were found to be useful indicators for the completion of cross-linking in the resist. Results of the experiments showed that the cross-linking of SU-8 was optimized at the exposure dose of 800 mJ/cm(2) for resist thicknesses of 3.5, 9.5, and 15 microm. PEB temperature was set at 95 degrees C and time at 3 min. The resist thickness was measured using interference patterns in the FT-IR spectra of the resist. Test structures with an aspect ratio 3:1 on 10 microm thick SU-8 resist film were obtained using scanning electron microscopy (SEM).

Development, validation, and implementation of a patient-specific Monte Carlo 3D internal dosimetry platform

NASA Astrophysics Data System (ADS)

Besemer, Abigail E.

Targeted radionuclide therapy is emerging as an attractive treatment option for a broad spectrum of tumor types because it has the potential to simultaneously eradicate both the primary tumor site as well as the metastatic disease throughout the body. Patient-specific absorbed dose calculations for radionuclide therapies are important for reducing the risk of normal tissue complications and optimizing tumor response. However, the only FDA approved software for internal dosimetry calculates doses based on the MIRD methodology which estimates mean organ doses using activity-to-dose scaling factors tabulated from standard phantom geometries. Despite the improved dosimetric accuracy afforded by direct Monte Carlo dosimetry methods these methods are not widely used in routine clinical practice because of the complexity of implementation, lack of relevant standard protocols, and longer dose calculation times. The main goal of this work was to develop a Monte Carlo internal dosimetry platform in order to (1) calculate patient-specific voxelized dose distributions in a clinically feasible time frame, (2) examine and quantify the dosimetric impact of various parameters and methodologies used in 3D internal dosimetry methods, and (3) develop a multi-criteria treatment planning optimization framework for multi-radiopharmaceutical combination therapies. This platform utilizes serial PET/CT or SPECT/CT images to calculate voxelized 3D internal dose distributions with the Monte Carlo code Geant4. Dosimetry can be computed for any diagnostic or therapeutic radiopharmaceutical and for both pre-clinical and clinical applications. In this work, the platform's dosimetry calculations were successfully validated against previously published reference doses values calculated in standard phantoms for a variety of radionuclides, over a wide range of photon and electron energies, and for many different organs and tumor sizes. Retrospective dosimetry was also calculated for various pre-clinical and clinical patients and large dosimetric differences resulted when using conventional organ-level methods and the patient-specific voxelized methods described in this work. The dosimetric impact of various steps in the 3D voxelized dosimetry process were evaluated including quantitative imaging acquisition, image coregistration, voxel resampling, ROI contouring, CT-based material segmentation, and pharmacokinetic fitting. Finally, a multi-objective treatment planning optimization framework was developed for multi-radiopharmaceutical combination therapies.

Treatment regimens of classical and newer taxanes.

PubMed

Joerger, Markus

2016-02-01

The classical taxanes (paclitaxel, docetaxel), the newer taxane cabazitaxel and the nanoparticle-bound nab-paclitaxel are among the most widely used anticancer drugs. The taxanes share the characteristics of extensive hepatic metabolism and biliary excretion, the need for dose adaptation in patients with liver dysfunction, and a substantial pharmacokinetic variability even after taking into account known covariates. Data from clinical studies suggest that optimal scheduling of the taxanes is dependent not only on the specific taxane compound, but also on the tumor type and line of treatment. Still, the optimal dosing regimen (weekly vs 3 weekly) and optimal dose of the taxanes are controversial, as is the value of pharmacological personalization of taxane dosing. In this article, an overview is given on the pharmacological properties of the taxanes, including metabolism, pharmacokinetics-pharmacodynamics and aspects in the clinical use of taxanes. The latter includes the ongoing debate on the most active and safe regimen, the recommended initial dose and the issue of therapeutic drug dosing.

Pediatric stroke and transcranial direct current stimulation: methods for rational individualized dose optimization

PubMed Central

Gillick, Bernadette T.; Kirton, Adam; Carmel, Jason B.; Minhas, Preet; Bikson, Marom

2014-01-01

Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior ad hoc adult montages vs. de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process. Results: Brain electric fields modeled and compared to values previously predicted models (Datta et al., 2011; Minhas et al., 2012). Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 min with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5 × 7 cm2 with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events. Conclusion: Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials. PMID:25285077

SU-F-J-178: A Computer Simulation Model Observer for Task-Based Image Quality Assessment in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dolly, S; Mutic, S; Anastasio, M

Purpose: Traditionally, image quality in radiation therapy is assessed subjectively or by utilizing physically-based metrics. Some model observers exist for task-based medical image quality assessment, but almost exclusively for diagnostic imaging tasks. As opposed to disease diagnosis, the task for image observers in radiation therapy is to utilize the available images to design and deliver a radiation dose which maximizes patient disease control while minimizing normal tissue damage. The purpose of this study was to design and implement a new computer simulation model observer to enable task-based image quality assessment in radiation therapy. Methods: A modular computer simulation framework wasmore » developed to resemble the radiotherapy observer by simulating an end-to-end radiation therapy treatment. Given images and the ground-truth organ boundaries from a numerical phantom as inputs, the framework simulates an external beam radiation therapy treatment and quantifies patient treatment outcomes using the previously defined therapeutic operating characteristic (TOC) curve. As a preliminary demonstration, TOC curves were calculated for various CT acquisition and reconstruction parameters, with the goal of assessing and optimizing simulation CT image quality for radiation therapy. Sources of randomness and bias within the system were analyzed. Results: The relationship between CT imaging dose and patient treatment outcome was objectively quantified in terms of a singular value, the area under the TOC (AUTOC) curve. The AUTOC decreases more rapidly for low-dose imaging protocols. AUTOC variation introduced by the dose optimization algorithm was approximately 0.02%, at the 95% confidence interval. Conclusion: A model observer has been developed and implemented to assess image quality based on radiation therapy treatment efficacy. It enables objective determination of appropriate imaging parameter values (e.g. imaging dose). Framework flexibility allows for incorporation of additional modules to include any aspect of the treatment process, and therefore has great potential for both assessment and optimization within radiation therapy.« less

An imaging informatics-based ePR (electronic patient record) system for providing decision support in evaluating dose optimization in stroke rehabilitation

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Winstein, Carolee; Wang, Ximing; Konersman, Matt; Martinez, Clarisa; Schweighofer, Nicolas

2012-02-01

Stroke is one of the major causes of death and disability in America. After stroke, about 65% of survivors still suffer from severe paresis, while rehabilitation treatment strategy after stroke plays an essential role in recovery. Currently, there is a clinical trial (NIH award #HD065438) to determine the optimal dose of rehabilitation for persistent recovery of arm and hand paresis. For DOSE (Dose Optimization Stroke Evaluation), laboratory-based measurements, such as the Wolf Motor Function test, behavioral questionnaires (e.g. Motor Activity Log-MAL), and MR, DTI, and Transcranial Magnetic Stimulation (TMS) imaging studies are planned. Current data collection processes are tedious and reside in various standalone systems including hardcopy forms. In order to improve the efficiency of this clinical trial and facilitate decision support, a web-based imaging informatics system has been implemented together with utilizing mobile devices (eg, iPAD, tablet PC's, laptops) for collecting input data and integrating all multi-media data into a single system. The system aims to provide clinical imaging informatics management and a platform to develop tools to predict the treatment effect based on the imaging studies and the treatment dosage with mathematical models. Since there is a large amount of information to be recorded within the DOSE project, the system provides clinical data entry through mobile device applications thus allowing users to collect data at the point of patient interaction without typing into a desktop computer, which is inconvenient. Imaging analysis tools will also be developed for structural MRI, DTI, and TMS imaging studies that will be integrated within the system and correlated with the clinical and behavioral data. This system provides a research platform for future development of mathematical models to evaluate the differences between prediction and reality and thus improve and refine the models rapidly and efficiently.

Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures.

PubMed

Guiu-Souto, Jacobo; Sánchez-García, Manuel; Vázquez-Vázquez, Rubén; Otero, Carlos; Luna, Victor; Mosquera, Javier; Busto, Ramón Lobato; Aguiar, Pablo; Ruibal, Álvaro; Pardo-Montero, Juan; Pombar-Cameán, Miguel

2016-06-01

The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.

Optimal iodine-131 dose for eliminating hyperthyroidism in Graves' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nordyke, R.A.; Gilbert, F.I. Jr.

1991-03-01

Since hypothyroidism is commonplace after treatment of Graves' disease with radioiodine, the goal should be cure of hyperthyroidism rather than avoidance of hypothyroidism. To find the optimal dose to accomplish cure, we treated 605 patients with stepwise increasing doses of 3, 4, 5, 6, 8, and 10 mCi, analyzing the relationship of dose, age, sex, gland weight, and thyroidal uptake to cure. Estimates of cure at doses above 10 mCi were made from the literature. Cure was directly related to dose between 5 and 10 mCi. There was no significant relationship between cure and age (chi-square, p = 0.74), sexmore » (chi-square, p = 0.12), and 24-hr uptake if over 30% (chi-square for slope, p greater than 0.10). Cure and gland weight had an inverse relationship (chi-square for slope, 0.01 less than p less than 0.02). We concluded that the optimal 131I dose for curing hyperthyroidism is approximated by starting with 10 mCi and increasing it for unusually large glands or for special patient circumstances.« less

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

PubMed

Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Wen, Ning

2016-09-30

Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.

SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taleei, R; Qin, N; Jiang, S

2016-06-15

Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relativemore » Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.« less

Role of step size and max dwell time in anatomy based inverse optimization for prostate implants

PubMed Central

Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R.; Sresty, N.V. Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha

2013-01-01

In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants. PMID:24049323

Radiation-hardened backside-illuminated 512 x 512 charge-coupled device

NASA Astrophysics Data System (ADS)

Bates, Philip A.; Levine, Peter A.; Sauer, Donald J.; Hsueh, Fu-Lung; Shallcross, Frank V.; Smeltzer, Ronald K.; Meray, Grazyna M.; Taylor, Gordon C.; Tower, John R.

1995-04-01

A four-port 512 X 512 charge coupled device (CCD) imager hardened against proton displacement damage and total dose degradation has been fabricated and tested. The device is based upon an established thinned, backside illuminated, triple polysilicon, buried channel CCD process technology. The technology includes buried blooming drains. A three step approach has been taken to hardening the device. The first phase addressed hardening against proton displacement damage. The second phase addressed hardening against both proton displacement damage and total dose degradation. The third phase addresses final optimization of the design. Test results from the first and second phase efforts are presented. Plans for the third phase are discussed.

Design of a modulated orthovoltage stereotactic radiosurgery system.

PubMed

Fagerstrom, Jessica M; Bender, Edward T; Lawless, Michael J; Culberson, Wesley S

2017-07-01

To achieve stereotactic radiosurgery (SRS) dose distributions with sharp gradients using orthovoltage energy fluence modulation with inverse planning optimization techniques. A pencil beam model was used to calculate dose distributions from an orthovoltage unit at 250 kVp. Kernels for the model were derived using Monte Carlo methods. A Genetic Algorithm search heuristic was used to optimize the spatial distribution of added tungsten filtration to achieve dose distributions with sharp dose gradients. Optimizations were performed for depths of 2.5, 5.0, and 7.5 cm, with cone sizes of 5, 6, 8, and 10 mm. In addition to the beam profiles, 4π isocentric irradiation geometries were modeled to examine dose at 0.07 mm depth, a representative skin depth, for the low energy beams. Profiles from 4π irradiations of a constant target volume, assuming maximally conformal coverage, were compared. Finally, dose deposition in bone compared to tissue in this energy range was examined. Based on the results of the optimization, circularly symmetric tungsten filters were designed to modulate the orthovoltage beam across the apertures of SRS cone collimators. For each depth and cone size combination examined, the beam flatness and 80-20% and 90-10% penumbrae were calculated for both standard, open cone-collimated beams as well as for optimized, filtered beams. For all configurations tested, the modulated beam profiles had decreased penumbra widths and flatness statistics at depth. Profiles for the optimized, filtered orthovoltage beams also offered decreases in these metrics compared to measured linear accelerator cone-based SRS profiles. The dose at 0.07 mm depth in the 4π isocentric irradiation geometries was higher for the modulated beams compared to unmodulated beams; however, the modulated dose at 0.07 mm depth remained <0.025% of the central, maximum dose. The 4π profiles irradiating a constant target volume showed improved statistics for the modulated, filtered distribution compared to the standard, open cone-collimated distribution. Simulations of tissue and bone confirmed previously published results that a higher energy beam (≥ 200 keV) would be preferable, but the 250 kVp beam was chosen for this work because it is available for future measurements. A methodology has been described that may be used to optimize the spatial distribution of added filtration material in an orthovoltage SRS beam to result in dose distributions with decreased flatness and penumbra statistics compared to standard open cones. This work provides the mathematical foundation for a novel, orthovoltage energy fluence-modulated SRS system. © 2017 American Association of Physicists in Medicine.

Patient Dose Management: Focus on Practical Actions

PubMed Central

2016-01-01

Medical radiation is a very important part of modern medicine, and should be only used when needed and optimized. Justification and optimization of radiation examinations must be performed. The first step of reduction of medical exposure is to know the radiation dose in currently performed examinations. This review covers radiation units, how various imaging modalities report dose, and the current status of radiation dose reports and legislation. Also, practical tips that can be applied to clinical practice are introduced. Afterwards, the importance of radiology exposure related education is emphasized and the current status of education for medical personal and the public is explained, and appropriate education strategies are suggested. Commonly asked radiation dose related example questions and answers are provided in detail to allow medical personnel to answer patients. Lastly, we talk about computerized programs that can be used in medical facilities for managing patient dose. While patient dose monitoring and management should be used to decrease and optimize overall radiation dose, it should not be used to assess individual cancer risk. One must always remember that medically justified examinations should always be performed, and unneeded examinations should be avoided in the first place. PMID:26908988

Optimization of photocatalytic degradation of methyl blue using silver ion doped titanium dioxide by combination of experimental design and response surface approach.

PubMed

Sahoo, C; Gupta, A K

2012-05-15

Photocatalytic degradation of methyl blue (MYB) was studied using Ag(+) doped TiO(2) under UV irradiation in a batch reactor. Catalytic dose, initial concentration of dye and pH of the reaction mixture were found to influence the degradation process most. The degradation was found to be effective in the range catalytic dose (0.5-1.5g/L), initial dye concentration (25-100ppm) and pH of reaction mixture (5-9). Using the three factors three levels Box-Behnken design of experiment technique 15 sets of experiments were designed considering the effective ranges of the influential parameters. The results of the experiments were fitted to two quadratic polynomial models developed using response surface methodology (RSM), representing functional relationship between the decolorization and mineralization of MYB and the experimental parameters. Design Expert software version 8.0.6.1 was used to optimize the effects of the experimental parameters on the responses. The optimum values of the parameters were dose of Ag(+) doped TiO(2) 0.99g/L, initial concentration of MYB 57.68ppm and pH of reaction mixture 7.76. Under the optimal condition the predicted decolorization and mineralization rate of MYB were 95.97% and 80.33%, respectively. Regression analysis with R(2) values >0.99 showed goodness of fit of the experimental results with predicted values. Copyright © 2012 Elsevier B.V. All rights reserved.

Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides.

PubMed

Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

2005-07-01

We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (microg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r=0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA.

SU-F-BRD-08: Guaranteed Epsilon-Optimal Treatment Plans with Minimum Number of Beams for SBRT Using RayStation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yarmand, H; Winey, B; Craft, D

2014-06-15

Purpose: To efficiently find quality-guaranteed treatment plans with the minimum number of beams for stereotactic body radiation therapy using RayStation. Methods: For a pre-specified pool of candidate beams we use RayStation (a treatment planning software for clinical use) to identify the deliverable plan which uses all the beams with the minimum dose to organs at risk (OARs) and dose to the tumor and other structures in specified ranges. Then use the dose matrix information for the generated apertures from RayStation to solve a linear program to find the ideal plan with the same objective and constraints allowing use of allmore » beams. Finally we solve a mixed integer programming formulation of the beam angle optimization problem (BAO) with the objective of minimizing the number of beams while remaining in a predetermined epsilon-optimality of the ideal plan with respect to the dose to OARs. Since the treatment plan optimization is a multicriteria optimization problem, the planner can exploit the multicriteria optimization capability of RayStation to navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing quality. For the numerical experiments two liver cases and one lung case with 33 non-coplanar beams are considered. Results: The ideal plan uses an impractically large number of beams. The proposed technique reduces the number of beams to the range of practical application (5 to 9 beams) while remaining in the epsilon-optimal range of 1% to 5% optimality gap. Conclusion: The proposed method can be integrated into a general algorithm for fast navigation of the ideal dose distribution Pareto surface and finding the treatment plan with the minimum number of beams, which corresponds to the delivery time, in epsilon-optimality range of the desired ideal plan. The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center and partially by RaySearch Laboratories.« less

Optimization of cDNA microarrays procedures using criteria that do not rely on external standards.

PubMed

Bruland, Torunn; Anderssen, Endre; Doseth, Berit; Bergum, Hallgeir; Beisvag, Vidar; Laegreid, Astrid

2007-10-18

The measurement of gene expression using microarray technology is a complicated process in which a large number of factors can be varied. Due to the lack of standard calibration samples such as are used in traditional chemical analysis it may be a problem to evaluate whether changes done to the microarray procedure actually improve the identification of truly differentially expressed genes. The purpose of the present work is to report the optimization of several steps in the microarray process both in laboratory practices and in data processing using criteria that do not rely on external standards. We performed a cDNA microarry experiment including RNA from samples with high expected differential gene expression termed "high contrasts" (rat cell lines AR42J and NRK52E) compared to self-self hybridization, and optimized a pipeline to maximize the number of genes found to be differentially expressed in the "high contrasts" RNA samples by estimating the false discovery rate (FDR) using a null distribution obtained from the self-self experiment. The proposed high-contrast versus self-self method (HCSSM) requires only four microarrays per evaluation. The effects of blocking reagent dose, filtering, and background corrections methodologies were investigated. In our experiments a dose of 250 ng LNA (locked nucleic acid) dT blocker, no background correction and weight based filtering gave the largest number of differentially expressed genes. The choice of background correction method had a stronger impact on the estimated number of differentially expressed genes than the choice of filtering method. Cross platform microarray (Illumina) analysis was used to validate that the increase in the number of differentially expressed genes found by HCSSM was real. The results show that HCSSM can be a useful and simple approach to optimize microarray procedures without including external standards. Our optimizing method is highly applicable to both long oligo-probe microarrays which have become commonly used for well characterized organisms such as man, mouse and rat, as well as to cDNA microarrays which are still of importance for organisms with incomplete genome sequence information such as many bacteria, plants and fish.

Optimization of cDNA microarrays procedures using criteria that do not rely on external standards

PubMed Central

Bruland, Torunn; Anderssen, Endre; Doseth, Berit; Bergum, Hallgeir; Beisvag, Vidar; Lægreid, Astrid

2007-01-01

Background The measurement of gene expression using microarray technology is a complicated process in which a large number of factors can be varied. Due to the lack of standard calibration samples such as are used in traditional chemical analysis it may be a problem to evaluate whether changes done to the microarray procedure actually improve the identification of truly differentially expressed genes. The purpose of the present work is to report the optimization of several steps in the microarray process both in laboratory practices and in data processing using criteria that do not rely on external standards. Results We performed a cDNA microarry experiment including RNA from samples with high expected differential gene expression termed "high contrasts" (rat cell lines AR42J and NRK52E) compared to self-self hybridization, and optimized a pipeline to maximize the number of genes found to be differentially expressed in the "high contrasts" RNA samples by estimating the false discovery rate (FDR) using a null distribution obtained from the self-self experiment. The proposed high-contrast versus self-self method (HCSSM) requires only four microarrays per evaluation. The effects of blocking reagent dose, filtering, and background corrections methodologies were investigated. In our experiments a dose of 250 ng LNA (locked nucleic acid) dT blocker, no background correction and weight based filtering gave the largest number of differentially expressed genes. The choice of background correction method had a stronger impact on the estimated number of differentially expressed genes than the choice of filtering method. Cross platform microarray (Illumina) analysis was used to validate that the increase in the number of differentially expressed genes found by HCSSM was real. Conclusion The results show that HCSSM can be a useful and simple approach to optimize microarray procedures without including external standards. Our optimizing method is highly applicable to both long oligo-probe microarrays which have become commonly used for well characterized organisms such as man, mouse and rat, as well as to cDNA microarrays which are still of importance for organisms with incomplete genome sequence information such as many bacteria, plants and fish. PMID:17949480

A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

NASA Astrophysics Data System (ADS)

Borot de Battisti, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; Maenhout, M.; Moerland, M. A.

2017-05-01

MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kofler, J.

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

TH-E-BRF-01: Exploiting Tumor Shrinkage in Split-Course Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, J; Craft, D; Hong, T

2014-06-15

Purpose: In split-course radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated by radiobiological considerations. However, using modern image-guidance, it also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. In this work, we consider the optimal design of split-course treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. Methods: We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cellmore » repopulation. The design of splitcourse radiotherapy is formulated as a mathematical optimization problem in which the total dose to the liver is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. Results: We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one third of the dose should be delivered in the first stage. The projected benefit of split-course treatments in terms of liver sparing depends on model assumptions. However, the model predicts large liver dose reductions by more than a factor of two for plausible model parameters. Conclusion: The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at split-course radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes.« less

Novel Approaches for Visualizing and Analyzing Dose-Timing Data from Electronic Drug Monitors, or "How the 'Broken Window' Theory Pertains to ART Adherence".

PubMed

Gill, Christopher J; DeSilva, Mary Bachman; Hamer, Davidson H; Keyi, Xu; Wilson, Ira B; Sabin, Lora

2015-11-01

Adherence to antiretroviral medications is usually expressed in terms of the proportion of doses taken. However, the timing of doses taken may also be an important dimension to overall adherence. Little is known about whether patients who mistime doses are also more likely to skip doses. Using data from the completed Adherence for Life randomized controlled trial, we created visual and statistical models to capture and analyze dose timing data collected longitudinally with electronic drug monitors (EDM). From scatter plots depicting dose time versus calendar date, we identified dominant patterns of dose taking and calculated key features [slope of line over calendar date; residual mean standard error (RMSE)]. Each was assessed for its ability to categorize subjects with 'sub-optimal' (<95 % of doses taken) using area under the receiver operating characteristic (AROC) curve analysis. Sixty eight subjects contributed EDM data, with ~300 to 400 observations/subject. While regression line slopes did not predict 'sub-optimal' adherence (AROC 0.51, 95 % CI 0.26-0.75), the variability in dose timing (RMSE) was strongly predictive (AROC 0.79, 95 % CI 0.62-0.97). Compared with the lowest quartile of RMSE (minimal dose time variability), each successive quartile roughly doubled the odds of 'sub-optimal' adherence (OR 2.1, 95 % CI 1.3-3.4). Patterns of dose timing and mistiming are strongly related to overall adherence behavior. Notably, individuals who skip doses are more likely to mistime doses, with the degree of risk positively correlated with the extent of dose timing variability.

A systematic study on photocatalysis of antipyrine: Catalyst characterization, parameter optimization, reaction mechanism a toxicity evolution to plankton.

PubMed

Gong, Han; Chu, Wei; Chen, Meijuan; Wang, Qinxing

2017-04-01

The toxicity of antipyrine (AP) in the photodegradation using UV/CoFe 2 O 4 /TiO 2 was investigated by analyzing the characteristic of the catalyst, the effect of parameters (light source wavelength, catalyst dose, pH and initial AP concentration), the reaction mechanism (the organic intermediates, TOC reduction and inorganic ions release) and the newly proposed low-dosage-high-effective radical reaction approach. The catalyst shows the optimal removal efficiency under the conditions of wavelength at 350 nm, the catalyst dose at 0.5 g/L, and pH value at 5.5. Ten organic intermediates were identified, and five of them were newly reported in AP treatment process. Hydroxylation, demethylation and the cleavage of the pentacyclic ring were included in the decomposition pathways. The ring opening was certified by the 45% TOC reduction and 60% ammonia release during the process. The parent compound AP and its degradation products show positive effects on the growth of the algae. However, acute toxicity of AP was detected on brine shrimps Artemia salina. The toxicity was eliminated gradually with the decomposition of AP and the generation of the byproducts. The results indicate that the photocatalysis process is effective in AP removal, TOC reduction and toxicity elimination. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-E-T-270: Optimized Shielding Calculations for Medical Linear Accelerators (LINACs).

PubMed

Muhammad, W; Lee, S; Hussain, A

2012-06-01

The purpose of radiation shielding is to reduce the effective equivalent dose from a medical linear accelerator (LINAC) to a point outside the room to a level determined by individual state/international regulations. The study was performed to design LINAC's room for newly planned radiotherapy centers. Optimized shielding calculations were performed for LINACs having maximum photon energy of 20 MV based on NCRP 151. The maximum permissible dose limits were kept 0.04 mSv/week and 0.002 mSv/week for controlled and uncontrolled areas respectively by following ALARA principle. The planned LINAC's room was compared to the already constructed (non-optimized) LINAC's room to evaluate the shielding costs and the other facilities those are directly related to the room design. In the evaluation process it was noted that the non-optimized room size (i.e., 610 × 610 cm 2 or 20 feet × 20 feet) is not suitable for total body irradiation (TBI) although the machine installed inside was having not only the facility of TBI but the license was acquired. By keeping this point in view, the optimized INAC's room size was kept 762 × 762 cm 2. Although, the area of the optimized rooms was greater than the non-planned room (i.e., 762 × 762 cm 2 instead of 610 × 610 cm 2), the shielding cost for the optimized LINAC's rooms was reduced by 15%. When optimized shielding calculations were re-performed for non-optimized shielding room (i.e., keeping room size, occupancy factors, workload etc. same), it was found that the shielding cost may be lower to 41 %. In conclusion, non- optimized LINAC's room can not only put extra financial burden on the hospital but also can cause of some serious issues related to providing health care facilities for patients. © 2012 American Association of Physicists in Medicine.

New PSM optimized for stable resolution of fine holes in FPD

NASA Astrophysics Data System (ADS)

Imashiki, Nobuhisa; Yoshikawa, Yutaka; Hayase, Michihiko

2017-07-01

Recently, due to increases in the definition of high function panels for mobile devices such as smartphones and tablets, LCD panel TFT and OLED (organic electro luminescence display) circuits are becoming increasingly denser and more miniaturized by the year. TFT and OLED circuits are composed of several layers, such as gate, semiconductor and contact hole (C / H). It is particularly difficult to obtain a stable resolution for C/H due to the decrease in the C/H process margin (EL, DOF, MEEF) as a result of increases in the density of the circuit. Moreover, C/H productivity has also markedly decreased due to an increase in the exposure dose. In response to this, attenuated phase shift mask (Att. PSM) for large size photomasks have been proposed as a means to improve the process margin in FPD. We have developed new PSM that can further improve the process margin and the productivity of C/H via the effective positioning of a high transmittance phase shift film. Using a 1.5um sized hole as the target, we confirmed the improvement effect of the optimized PSM via a software simulation and an exposure test. Hereafter it is necessary for us to optimize the new PSM for each panel process so as to allow us to use this mask in actual processes.

TH-CD-202-08: Feasibility Study of Planning Phase Optimization Using Patient Geometry-Driven Information for Better Dose Sparing of Organ at Risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, S; Kim, D; Kim, T

2016-06-15

Purpose: To propose a simple and effective cost value function to search optimal planning phase (gating window) and demonstrated its feasibility for respiratory correlated radiation therapy. Methods: We acquired 4DCT of 10 phases for 10 lung patients who have tumor located near OARs such as esophagus, heart, and spinal cord (i.e., central lung cancer patients). A simplified mathematical optimization function was established by using overlap volume histogram (OVH) between the target and organ at risk (OAR) at each phase and the tolerance dose of selected OARs to achieve surrounding OARs dose-sparing. For all patients and all phases, delineation of themore » target volume and selected OARs (esophagus, heart, and spinal cord) was performed (by one observer to avoid inter-observer variation), then cost values were calculated for all phases. After the breathing phases were ranked according to cost value function, the relationship between score and dose distribution at highest and lowest cost value phases were evaluated by comparing the mean/max dose. Results: A simplified mathematical cost value function showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. The lowest cost value which may result in lower mean/max dose to OARs was distributed at various phases for all patients. The mean doses of the OARs significantly decreased about 10% with statistical significance for all 3 OARs at the phase with the lowest cost value. Also, the max doses of the OARs were decreased about 2∼5% at the phase with the lowest cost value compared to the phase with the highest cost value. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist differently through each patient and the proposed cost value function can be a useful tool for determining such phases without performing dose optimization calculations. This research was supported by the Mid-career Researcher Program through NRF funded by the Ministry of Science, ICT & Future Planning of Korea (NRF-2014R1A2A1A10050270) and by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)« less

The impact of different dose response parameters on biologically optimized IMRT in breast cancer

NASA Astrophysics Data System (ADS)

Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.

2008-05-01

The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.

Spatiotemporal radiotherapy planning using a global optimization approach

NASA Astrophysics Data System (ADS)

Adibi, Ali; Salari, Ehsan

2018-02-01

This paper aims at quantifying the extent of potential therapeutic gain, measured using biologically effective dose (BED), that can be achieved by altering the radiation dose distribution over treatment sessions in fractionated radiotherapy. To that end, a spatiotemporally integrated planning approach is developed, where the spatial and temporal dose modulations are optimized simultaneously. The concept of equivalent uniform BED (EUBED) is used to quantify and compare the clinical quality of spatiotemporally heterogeneous dose distributions in target and critical structures. This gives rise to a large-scale non-convex treatment-plan optimization problem, which is solved using global optimization techniques. The proposed spatiotemporal planning approach is tested on two stylized cancer cases resembling two different tumor sites and sensitivity analysis is performed for radio-biological and EUBED parameters. Numerical results validate that spatiotemporal plans are capable of delivering a larger BED to the target volume without increasing the BED in critical structures compared to conventional time-invariant plans. In particular, this additional gain is attributed to the irradiation of different regions of the target volume at different treatment sessions. Additionally, the trade-off between the potential therapeutic gain and the number of distinct dose distributions is quantified, which suggests a diminishing marginal gain as the number of dose distributions increases.

A detailed dosimetric comparison between manual and inverse plans in HDR intracavitary/interstitial cervical cancer brachytherapy.

PubMed

Trnková, Petra; Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian

2010-12-01

The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning.

A detailed dosimetric comparison between manual and inverse plans in HDR intracavitary/interstitial cervical cancer brachytherapy

PubMed Central

Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian

2011-01-01

Purpose The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. Material and methods For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. Results HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. Conclusions HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning. PMID:27853479

Optimization of dose and image quality in adult and pediatric computed tomography scans

NASA Astrophysics Data System (ADS)

Chang, Kwo-Ping; Hsu, Tzu-Kun; Lin, Wei-Ting; Hsu, Wen-Lin

2017-11-01

Exploration to maximize CT image and reduce radiation dose was conducted while controlling for multiple factors. The kVp, mAs, and iteration reconstruction (IR), affect the CT image quality and radiation dose absorbed. The optimal protocols (kVp, mAs, IR) are derived by figure of merit (FOM) based on CT image quality (CNR) and CT dose index (CTDIvol). CT image quality metrics such as CT number accuracy, SNR, low contrast materials' CNR and line pair resolution were also analyzed as auxiliary assessments. CT protocols were carried out with an ACR accreditation phantom and a five-year-old pediatric head phantom. The threshold values of the adult CT scan parameters, 100 kVp and 150 mAs, were determined from the CT number test and line pairs in ACR phantom module 1and module 4 respectively. The findings of this study suggest that the optimal scanning parameters for adults be set at 100 kVp and 150-250 mAs. However, for improved low- contrast resolution, 120 kVp and 150-250 mAs are optimal. Optimal settings for pediatric head CT scan were 80 kVp/50 mAs, for maxillary sinus and brain stem, while 80 kVp /300 mAs for temporal bone. SNR is not reliable as the independent image parameter nor the metric for determining optimal CT scan parameters. The iteration reconstruction (IR) approach is strongly recommended for both adult and pediatric CT scanning as it markedly improves image quality without affecting radiation dose.

Impact of imaging approach on radiation dose and associated cancer risk in children undergoing cardiac catheterization

PubMed Central

Einstein, Andrew J.; Januzis, Natalie; Nguyen, Giao; Li, Jennifer S.; Fleming, Gregory A.; Yoshizumi, Terry K.

2016-01-01

Objectives To quantify the impact of image optimization on absorbed radiation dose and associated risk in children undergoing cardiac catheterization. Background Various imaging and fluoroscopy system technical parameters including camera magnification, source-to-image distance, collimation, anti-scatter grids, beam quality, and pulse rates, all affect radiation dose but have not been well studied in younger children. Methods We used anthropomorphic phantoms (ages: newborn and 5-years-old) to measure surface radiation exposure from various imaging approaches and estimated absorbed organ doses and effective doses (ED) using Monte Carlo simulations. Models developed in the National Academies’ Biological Effects of Ionizing Radiation VII report were used to compare an imaging protocol optimized for dose reduction versus suboptimal imaging (+20cm source-to-image-distance, +1 magnification setting, no collimation) on lifetime attributable risk (LAR) of cancer. Results For the newborn and 5-year-old phantoms respectively ED changes were as follows: +157% and +232% for an increase from 6-inch to 10-inch camera magnification; +61% and +59% for a 20cm increase in source-to-image-distance; −42% and −48% with addition of 1-inch periphery collimation; −31% and −46% with removal of the anti-scatter grid. Compared to an optimized protocol, suboptimal imaging increased ED by 2.75-fold (newborn) and 4-fold (5-year-old). Estimated cancer LAR from 30-minutes of postero-anterior fluoroscopy using optimized versus sub-optimal imaging respectively was: 0.42% versus 1.23% (newborn female), 0.20% vs 0.53% (newborn male), 0.47% versus 1.70% (5-year-old female) and 0.16% vs 0.69% (5-year-old male). Conclusions Radiation-related risks to children undergoing cardiac catheterization can be substantial but are markedly reduced with an optimized imaging approach. PMID:27315598

SU-F-T-306: Validation of Mobius 3D and FX for Elekta Linear Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, C; Garcia, M; Calderon, E

2016-06-15

Purpose: Log file based IMRT and VMAT QA is a system that analyzes treatment log files and uses delivery parameters to compute the dose to the patient/phantom. This system was previously commissioned for Varian machines, the purpose of this work is to describe the process for commissioning Mobius for use with Elekta machines. Methods: Twelve IMRT and VMAT plans (6×) were planned and delivered and dose was measured using MapCheck, the results were compared to that computed by Mobius. For 10x and 18x, plans were generated, copied to a phantom and delivered, the dose was measured using a single ionmore » chamber. The difference in measured dose to computed dose (Mobius) was used to adjust the dynamic leaf gap (DLG) in Mobius to achieve optimal agreement between measurements, Mobius and treatment plans. Results: For the measured dose comparison, the average 3%/3mm gamma 97.1% of pixels passed criteria using MapCheck where Mobius computed 96.9% of voxels passing. For 10×, a DLG of −5.5 was determined to achieve optimal results for TPS and measured ion chamber data with an average 0.1% difference and −1.7% respectively. For 18×, a DLG of −3 was determined to achieve optimal results from the TPS and measured data with an average of −0.7% and −1.4% difference on average from a set of IMRT and VMAT plans. The 6x data needed no DLG correction to arrive at agreement with the TPS and the MapCheck measured data. Conclusion: We have validated with measurements for IMRT and VMAT cases the use of Mobius FX with Elekta treatment machines for IMRT and VMAT QA. For 6×, no adjustments to the DLG were required to obtain good results utilizing Mobius whereas for 10× and 18×, the DLG had to be adjusted to obtain optimum agreement with measured data and our TPS.« less

SU-E-T-278: Realization of Dose Verification Tool for IMRT Plan Based On DPM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Jinfeng; Cao, Ruifen; Dai, Yumei

Purpose: To build a Monte Carlo dose verification tool for IMRT Plan by implementing a irradiation source model into DPM code. Extend the ability of DPM to calculate any incident angles and irregular-inhomogeneous fields. Methods: With the virtual source and the energy spectrum which unfolded from the accelerator measurement data,combined with optimized intensity maps to calculate the dose distribution of the irradiation irregular-inhomogeneous field. The irradiation source model of accelerator was substituted by a grid-based surface source. The contour and the intensity distribution of the surface source were optimized by ARTS (Accurate/Advanced Radiotherapy System) optimization module based on the tumormore » configuration. The weight of the emitter was decided by the grid intensity. The direction of the emitter was decided by the combination of the virtual source and the emitter emitting position. The photon energy spectrum unfolded from the accelerator measurement data was adjusted by compensating the contaminated electron source. For verification, measured data and realistic clinical IMRT plan were compared with DPM dose calculation. Results: The regular field was verified by comparing with the measured data. It was illustrated that the differences were acceptable (<2% inside the field, 2–3mm in the penumbra). The dose calculation of irregular field by DPM simulation was also compared with that of FSPB (Finite Size Pencil Beam) and the passing rate of gamma analysis was 95.1% for peripheral lung cancer. The regular field and the irregular rotational field were all within the range of permitting error. The computing time of regular fields were less than 2h, and the test of peripheral lung cancer was 160min. Through parallel processing, the adapted DPM could complete the calculation of IMRT plan within half an hour. Conclusion: The adapted parallelized DPM code with irradiation source model is faster than classic Monte Carlo codes. Its computational accuracy and speed satisfy the clinical requirement, and it is expectable to be a Monte Carlo dose verification tool for IMRT Plan. Strategic Priority Research Program of the China Academy of Science(XDA03040000); National Natural Science Foundation of China (81101132)« less

Concurrent Monte Carlo transport and fluence optimization with fluence adjusting scalable transport Monte Carlo

PubMed Central

Svatos, M.; Zankowski, C.; Bednarz, B.

2016-01-01

Purpose: The future of radiation therapy will require advanced inverse planning solutions to support single-arc, multiple-arc, and “4π” delivery modes, which present unique challenges in finding an optimal treatment plan over a vast search space, while still preserving dosimetric accuracy. The successful clinical implementation of such methods would benefit from Monte Carlo (MC) based dose calculation methods, which can offer improvements in dosimetric accuracy when compared to deterministic methods. The standard method for MC based treatment planning optimization leverages the accuracy of the MC dose calculation and efficiency of well-developed optimization methods, by precalculating the fluence to dose relationship within a patient with MC methods and subsequently optimizing the fluence weights. However, the sequential nature of this implementation is computationally time consuming and memory intensive. Methods to reduce the overhead of the MC precalculation have been explored in the past, demonstrating promising reductions of computational time overhead, but with limited impact on the memory overhead due to the sequential nature of the dose calculation and fluence optimization. The authors propose an entirely new form of “concurrent” Monte Carlo treat plan optimization: a platform which optimizes the fluence during the dose calculation, reduces wasted computation time being spent on beamlets that weakly contribute to the final dose distribution, and requires only a low memory footprint to function. In this initial investigation, the authors explore the key theoretical and practical considerations of optimizing fluence in such a manner. Methods: The authors present a novel derivation and implementation of a gradient descent algorithm that allows for optimization during MC particle transport, based on highly stochastic information generated through particle transport of very few histories. A gradient rescaling and renormalization algorithm, and the concept of momentum from stochastic gradient descent were used to address obstacles unique to performing gradient descent fluence optimization during MC particle transport. The authors have applied their method to two simple geometrical phantoms, and one clinical patient geometry to examine the capability of this platform to generate conformal plans as well as assess its computational scaling and efficiency, respectively. Results: The authors obtain a reduction of at least 50% in total histories transported in their investigation compared to a theoretical unweighted beamlet calculation and subsequent fluence optimization method, and observe a roughly fixed optimization time overhead consisting of ∼10% of the total computation time in all cases. Finally, the authors demonstrate a negligible increase in memory overhead of ∼7–8 MB to allow for optimization of a clinical patient geometry surrounded by 36 beams using their platform. Conclusions: This study demonstrates a fluence optimization approach, which could significantly improve the development of next generation radiation therapy solutions while incurring minimal additional computational overhead. PMID:27277051

SU-G-BRC-16: Theory and Clinical Implications of the Constant Dosimetric Leaf Gap (DLG) Approximation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumaraswamy, L; Xu, Z; Podgorsak, M

Purpose: Commercial dose calculation algorithms incorporate a single DLG value for a given beam energy that is applied across an entire treatment field. However, the physical processes associated with beam generation and dose delivery suggest that the DLG is not constant. The aim of this study is to evaluate the variation of DLG among all leaf pairs, to quantify how this variation impacts delivered dose, and to establish a novel method to correct dose distributions calculated using the approximation of constant DLG. Methods: A 2D diode array was used to measure the DLG for all 60 leaf pairs at severalmore » points along each leaf pair travel direction. This approach was validated by comparison to DLG values measured at select points using a 0.6 cc ion chamber with the standard formalism. In-house software was developed to enable incorporation of position dependent DLG values into dose distribution optimization and calculation. The accuracy of beam delivery of both the corrected and uncorrected treatment plans was studied through gamma pass rate evaluation. A comparison of DVH statistics in corrected and uncorrected treatment plans was made. Results: The outer 20 MLC leaf pairs (1.0 cm width) have DLG values that are 0.32 mm (mean) to 0.65 mm (maximum) lower than the central leaf-pair. VMAT plans using a large number of 1 cm wide leaves were more accurately delivered (gamma pass rate increased by 5%) and dose coverage was higher (D100 increased by 3%) when the 2D DLG was modeled. Conclusion: Using a constant DLG value for a given beam energy will result in dose optimization, dose calculation and treatment delivery inaccuracies that become significant for treatment plans with high modulation complexity scores delivered with 1 cm wide leaves.« less

SU-F-T-35: Optimization of Bladder and Rectal Doses Using a Multi-Lumen Intracavitary Applicator for Gynecological Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laoui, S; Dietrich, S; Sehgal, V

2016-06-15

Purpose: Radiation dose delivery for endometrial cancer using HDR techniques is limited by dose to bladder and rectum. A dosimetric study was performed using Varian Capri vaginal brachytherapy applicator to determine the optimal channel configuration which minimizes dose to bladder and rectum, while providing good target coverage. Methods: A total of 17 patients, 63 plans clinically delivered, and 252 simulated plans using Varian BrachyVision planning system were generated to investigate optimal channel configuration which results in minimum dose to bladder and rectum while providing adequate target coverage. The Capri applicator consists of 13 lumens arranged in two concentric rings, onemore » central lumen and six lumens per ring. Manual dose shaping is invariably required to lower the dose to critical organs. Three-dimensional plans were simulated for 4 channel arrangements, all 13 channels, channel 12 o’clock (close to bladder) and 6 o’clock (close to rectum) deactivated, central channel deactivated, and central channel in addition to 12 o’clock and 6 o’clock deactivated. A relationship between V100, the volume that receives the prescribed dose, and the amount of curie-seconds required to deliver it, was established. Results: Using all 13 channels results in maximum dose to bladder and rectum. Deactivating central channel in addition to 12 o’clock and 6 o’clock resulted in minimizing bladder and rectum doses but compromised target coverage. The relationship between V100, the volume that receives the prescribed dose, and the curie seconds was found to be linear. Conclusion: Deactivating channels 12 o’clock and 6 o’clock was shown to be the optimal configuration leading to minimum dose to bladder and rectum without compromising target coverage. The linear relationship between V100 and the curie- seconds can be used as a verification parameter.« less

Explicit optimization of plan quality measures in intensity-modulated radiation therapy treatment planning.

PubMed

Engberg, Lovisa; Forsgren, Anders; Eriksson, Kjell; Hårdemark, Björn

2017-06-01

To formulate convex planning objectives of treatment plan multicriteria optimization with explicit relationships to the dose-volume histogram (DVH) statistics used in plan quality evaluation. Conventional planning objectives are designed to minimize the violation of DVH statistics thresholds using penalty functions. Although successful in guiding the DVH curve towards these thresholds, conventional planning objectives offer limited control of the individual points on the DVH curve (doses-at-volume) used to evaluate plan quality. In this study, we abandon the usual penalty-function framework and propose planning objectives that more closely relate to DVH statistics. The proposed planning objectives are based on mean-tail-dose, resulting in convex optimization. We also demonstrate how to adapt a standard optimization method to the proposed formulation in order to obtain a substantial reduction in computational cost. We investigated the potential of the proposed planning objectives as tools for optimizing DVH statistics through juxtaposition with the conventional planning objectives on two patient cases. Sets of treatment plans with differently balanced planning objectives were generated using either the proposed or the conventional approach. Dominance in the sense of better distributed doses-at-volume was observed in plans optimized within the proposed framework. The initial computational study indicates that the DVH statistics are better optimized and more efficiently balanced using the proposed planning objectives than using the conventional approach. © 2017 American Association of Physicists in Medicine.

Investigation of effective decision criteria for multiobjective optimization in IMRT.

PubMed

Holdsworth, Clay; Stewart, Robert D; Kim, Minsun; Liao, Jay; Phillips, Mark H

2011-06-01

To investigate how using different sets of decision criteria impacts the quality of intensity modulated radiation therapy (IMRT) plans obtained by multiobjective optimization. A multiobjective optimization evolutionary algorithm (MOEA) was used to produce sets of IMRT plans. The MOEA consisted of two interacting algorithms: (i) a deterministic inverse planning optimization of beamlet intensities that minimizes a weighted sum of quadratic penalty objectives to generate IMRT plans and (ii) an evolutionary algorithm that selects the superior IMRT plans using decision criteria and uses those plans to determine the new weights and penalty objectives of each new plan. Plans resulting from the deterministic algorithm were evaluated by the evolutionary algorithm using a set of decision criteria for both targets and organs at risk (OARs). Decision criteria used included variation in the target dose distribution, mean dose, maximum dose, generalized equivalent uniform dose (gEUD), an equivalent uniform dose (EUD(alpha,beta) formula derived from the linear-quadratic survival model, and points on dose volume histograms (DVHs). In order to quantatively compare results from trials using different decision criteria, a neutral set of comparison metrics was used. For each set of decision criteria investigated, IMRT plans were calculated for four different cases: two simple prostate cases, one complex prostate Case, and one complex head and neck Case. When smaller numbers of decision criteria, more descriptive decision criteria, or less anti-correlated decision criteria were used to characterize plan quality during multiobjective optimization, dose to OARs and target dose variation were reduced in the final population of plans. Mean OAR dose and gEUD (a = 4) decision criteria were comparable. Using maximum dose decision criteria for OARs near targets resulted in inferior populations that focused solely on low target variance at the expense of high OAR dose. Target dose range, (D(max) - D(min)), decision criteria were found to be most effective for keeping targets uniform. Using target gEUD decision criteria resulted in much lower OAR doses but much higher target dose variation. EUD(alpha,beta) based decision criteria focused on a region of plan space that was a compromise between target and OAR objectives. None of these target decision criteria dominated plans using other criteria, but only focused on approaching a different area of the Pareto front. The choice of decision criteria implemented in the MOEA had a significant impact on the region explored and the rate of convergence toward the Pareto front. When more decision criteria, anticorrelated decision criteria, or decision criteria with insufficient information were implemented, inferior populations are resulted. When more informative decision criteria were used, such as gEUD, EUD(alpha,beta), target dose range, and mean dose, MOEA optimizations focused on approaching different regions of the Pareto front, but did not dominate each other. Using simple OAR decision criteria and target EUD(alpha,beta) decision criteria demonstrated the potential to generate IMRT plans that significantly reduce dose to OARs while achieving the same or better tumor control when clinical requirements on target dose variance can be met or relaxed.

Poster — Thur Eve — 35: The impact of intensity- and energy-modulated photon radiotherapy (XMRT) optimization on a variety of organ geometries

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGeachy, P.; Villarreal-Barajas, J. E.; Khan, R.

2014-08-15

We previously reported on a novel, modulated in both energy and intensity; photon radiotherapy (XMRT) optimization technique. The purpose of this investigation was to test this XMRT optimization against conventional intensity modulated radiotherapy (IMRT) optimization on four different organ test geometries. All geometries mimicked clinically relevant scenarios. Both IMRT and XMRT were based on a linear programming approach where the objective function was the mean dose to healthy organs and organ-specific linear dose-point constraints were used. For IMRT, the beam energy was fixed to 6 MV while XMRT optimized in terms of both 6 and 18 MV beams. All plansmore » consisted of a seven beam coplanar arrangement. All organ geometries were contoured on a 25cm diameter cylindrical water phantom in open source radiotherapy research software known as CERR. Solutions for both IMRT and XMRT were obtained for each geometry using a numerical solver Gurobi. Analyzing the quality of the solutions was done by comparing dose distributions and dose volume histograms calculated using CERR. For all four geometries, IMRT and XMRT solutions were comparable in terms of target coverage. For two of the geometries, IMRT provided an advantage in terms of reduced dose to the healthy structures. XMRT showed improved dose reduction to healthy organs for one geometry and a comparable dose distribution to IMRT for the remaining geometry. The inability to exploit the benefits of using multiple energies may be attributed to limited water phantom diameter and having the majority of the organs in close proximity to the transverse axis.« less

Optimized Orthovoltage Stereotactic Radiosurgery

NASA Astrophysics Data System (ADS)

Fagerstrom, Jessica M.

Because of its ability to treat intracranial targets effectively and noninvasively, stereotactic radiosurgery (SRS) is a prevalent treatment modality in modern radiation therapy. This work focused on SRS delivering rectangular function dose distributions, which are desirable for some targets such as those with functional tissue included within the target volume. In order to achieve such distributions, this work used fluence modulation and energies lower than those utilized in conventional SRS. In this work, the relationship between prescription isodose and dose gradients was examined for standard, unmodulated orthovoltage SRS dose distributions. Monte Carlo-generated energy deposition kernels were used to calculate 4pi, isocentric dose distributions for a polyenergetic orthovoltage spectrum, as well as monoenergetic orthovoltage beams. The relationship between dose gradients and prescription isodose was found to be field size and energy dependent, and values were found for prescription isodose that optimize dose gradients. Next, a pencil-beam model was used with a Genetic Algorithm search heuristic to optimize the spatial distribution of added tungsten filtration within apertures of cone collimators in a moderately filtered 250 kVp beam. Four cone sizes at three depths were examined with a Monte Carlo model to determine the effects of the optimized modulation compared to open cones, and the simulations found that the optimized cones were able to achieve both improved penumbra and flatness statistics at depth compared to the open cones. Prototypes of the filter designs calculated using mathematical optimization techniques and Monte Carlo simulations were then manufactured and inserted into custom built orthovoltage SRS cone collimators. A positioning system built in-house was used to place the collimator and filter assemblies temporarily in the 250 kVp beam line. Measurements were performed in water using radiochromic film scanned with both a standard white light flatbed scanner as well as a prototype laser densitometry system. Measured beam profiles showed that the modulated beams could more closely approach rectangular function dose profiles compared to the open cones. A methodology has been described and implemented to achieve optimized SRS delivery, including the development of working prototypes. Future work may include the construction of a full treatment platform.

WE-EF-BRA-07: High Performance Preclinical Irradiation Through Optimized Dual Focal Spot Dose Painting and Online Virtual Isocenter Radiation Field Targeting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, J; Princess Margaret Cancer Centre, University Health Network, Toronto, CA; Lindsay, P

Purpose: Advances in radiotherapy practice facilitated by collimation systems to shape radiation fields and image guidance to target these conformal beams have motivated proposals for more complex dose patterns to improve the therapeutic ratio. Recent progress in small animal radiotherapy platforms has provided the foundation to validate the efficacy of such interventions, but robustly delivering heterogeneous dose distributions at the scale and accuracy demanded by preclinical studies remains challenging. This work proposes a dual focal spot optimization method to paint spatially heterogeneous dose regions and an online virtual isocenter targeting method to accurately target the dose distributions. Methods: Two-dimensional dosemore » kernels were empirically measured for the 1 mm diameter circular collimator with radiochromic film in a solid water phantom for the small and large x-ray focal spots on the X-RAD 225Cx microirradiator. These kernels were used in an optimization framework which determined a set of animal stage positions, beam-on times, and focal spot settings to optimally deliver a given desired dose distribution. An online method was developed which defined a virtual treatment isocenter based on a single image projection of the collimated radiation field. The method was demonstrated by optimization of a 6 mm circular 2 Gy target adjoining a 4 mm semicircular avoidance region. Results: The dual focal spot technique improved the optimized dose distribution with the proportion of avoidance region receiving more than 0.5 Gy reduced by 40% compared to the large focal spot technique. Targeting tests performed by irradiating ball bearing targets on radiochromic film pieced revealed the online targeting method improved the three-dimensional accuracy from 0.48 mm to 0.15 mm. Conclusion: The dual focal spot optimization and online virtual isocenter targeting framework is a robust option for delivering dose at the preclinical level and provides a new experimental option for unique radiobiological investigations This work is supported, in part, by the Natural Sciences and Engineering Research Council of Canada and a Mitacs-Accelerate fellowship. P.E. Lindsay, and D.A. Jaffray are listed as inventors of the system described herein. This system has been licensed to Precision X-Ray Inc. for commercial development.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Espinoza, I; Peschke, P; Karger, C

Purpose: In radiotherapy, it is important to predict the response of tumour to irradiation prior to the treatment. Mathematical modelling of tumour control probability (TCP) based on the dose distribution, medical imaging and other biological information may help to improve this prediction and to optimize the treatment plan. The aim of this work is to develop an image based 3D multiscale radiobiological model, which describes the growth and the response to radiotherapy of hypoxic tumors. Methods: The computer model is based on voxels, containing tumour, normal (including capillary) and dead cells. Killing of tumour cells due to irradiation is calculatedmore » by the Linear Quadratic Model (extended for hypoxia), and the proliferation and resorption of cells are modelled by exponential laws. The initial shape of the tumours is taken from CT images and the initial vascular and cell density information from PET and/or MR images. Including the fractionation regime and the physical dose distribution of the radiation treatment, the model simulates the spatial-temporal evolution of the tumor. Additionally, the dose distribution may be biologically optimized. Results: The model describes the appearance of hypoxia during tumour growth and the reoxygenation processes during radiotherapy. Among other parameters, the TCP is calculated for different dose distributions. The results are in accordance with published results. Conclusion: The simulation model may contribute to the understanding of the influence of biological parameters on tumor response during treatment, and specifically on TCP. It may be used to implement dose-painting approaches. Experimental and clinical validation is needed. This study is supported by a grant from the Ministry of Education of Chile, Programa Mece Educacion Superior (2)« less

A comprehensive study on the relationship between the image quality and imaging dose in low-dose cone beam CT

NASA Astrophysics Data System (ADS)

Yan, Hao; Cervino, Laura; Jia, Xun; Jiang, Steve B.

2012-04-01

While compressed sensing (CS)-based algorithms have been developed for the low-dose cone beam CT (CBCT) reconstruction, a clear understanding of the relationship between the image quality and imaging dose at low-dose levels is needed. In this paper, we qualitatively investigate this subject in a comprehensive manner with extensive experimental and simulation studies. The basic idea is to plot both the image quality and imaging dose together as functions of the number of projections and mAs per projection over the whole clinically relevant range. On this basis, a clear understanding of the tradeoff between the image quality and imaging dose can be achieved and optimal low-dose CBCT scan protocols can be developed to maximize the dose reduction while minimizing the image quality loss for various imaging tasks in image-guided radiation therapy (IGRT). Main findings of this work include (1) under the CS-based reconstruction framework, image quality has little degradation over a large range of dose variation. Image quality degradation becomes evident when the imaging dose (approximated with the x-ray tube load) is decreased below 100 total mAs. An imaging dose lower than 40 total mAs leads to a dramatic image degradation, and thus should be used cautiously. Optimal low-dose CBCT scan protocols likely fall in the dose range of 40-100 total mAs, depending on the specific IGRT applications. (2) Among different scan protocols at a constant low-dose level, the super sparse-view reconstruction with the projection number less than 50 is the most challenging case, even with strong regularization. Better image quality can be acquired with low mAs protocols. (3) The optimal scan protocol is the combination of a medium number of projections and a medium level of mAs/view. This is more evident when the dose is around 72.8 total mAs or below and when the ROI is a low-contrast or high-resolution object. Based on our results, the optimal number of projections is around 90 to 120. (4) The clinically acceptable lowest imaging dose level is task dependent. In our study, 72.8 mAs is a safe dose level for visualizing low-contrast objects, while 12.2 total mAs is sufficient for detecting high-contrast objects of diameter greater than 3 mm.

SU-E-T-562: Motion Tracking Optimization for Conformal Arc Radiotherapy Plans: A QUASAR Phantom Based Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Z; Wang, I; Yao, R

Purpose: This study is to use plan parameters optimization (Dose rate, collimator angle, couch angle, initial starting phase) to improve the performance of conformal arc radiotherapy plans with motion tracking by increasing the plan performance score (PPS). Methods: Two types of 3D conformal arc plans were created based on QUASAR respiratory motion phantom with spherical and cylindrical targets. Sinusoidal model was applied to the MLC leaves to generate motion tracking plans. A MATLAB program was developed to calculate PPS of each plan (ranges from 0–1) and optimize plan parameters. We first selected the dose rate for motion tracking plans andmore » then used simulated annealing algorithm to search for the combination of the other parameters that resulted in the plan of the maximal PPS. The optimized motion tracking plan was delivered by Varian Truebeam Linac. In-room cameras and stopwatch were used for starting phase selection and synchronization between phantom motion and plan delivery. Gaf-EBT2 dosimetry films were used to measure the dose delivered to the target in QUASAR phantom. Dose profiles and Truebeam trajectory log files were used for plan delivery performance evaluation. Results: For spherical target, the maximal PPS (PPSsph) of the optimized plan was 0.79: (Dose rate: 500MU/min, Collimator: 90°, Couch: +10°, starting phase: 0.83π). For cylindrical target, the maximal PPScyl was 0.75 (Dose rate: 300MU/min, Collimator: 87°, starting phase: 0.97π) with couch at 0°. Differences of dose profiles between motion tracking plans (with the maximal and the minimal PPS) and 3D conformal plans were as follows: PPSsph=0.79: %ΔFWHM: 8.9%, %Dmax: 3.1%; PPSsph=0.52: %ΔFWHM: 10.4%, %Dmax: 6.1%. PPScyl=0.75: %ΔFWHM: 4.7%, %Dmax: 3.6%; PPScyl=0.42: %ΔFWHM: 12.5%, %Dmax: 9.6%. Conclusion: By achieving high plan performance score through parameters optimization, we can improve target dose conformity of motion tracking plan by decreasing total MLC leaf travel distance and leaf speed.« less

Optimizing global liver function in radiation therapy treatment planning

NASA Astrophysics Data System (ADS)

Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

2016-09-01

Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than \\ell \\text{EUD} model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Y. M., E-mail: ymingy@gmail.com; Bednarz, B.; Svatos, M.

Purpose: The future of radiation therapy will require advanced inverse planning solutions to support single-arc, multiple-arc, and “4π” delivery modes, which present unique challenges in finding an optimal treatment plan over a vast search space, while still preserving dosimetric accuracy. The successful clinical implementation of such methods would benefit from Monte Carlo (MC) based dose calculation methods, which can offer improvements in dosimetric accuracy when compared to deterministic methods. The standard method for MC based treatment planning optimization leverages the accuracy of the MC dose calculation and efficiency of well-developed optimization methods, by precalculating the fluence to dose relationship withinmore » a patient with MC methods and subsequently optimizing the fluence weights. However, the sequential nature of this implementation is computationally time consuming and memory intensive. Methods to reduce the overhead of the MC precalculation have been explored in the past, demonstrating promising reductions of computational time overhead, but with limited impact on the memory overhead due to the sequential nature of the dose calculation and fluence optimization. The authors propose an entirely new form of “concurrent” Monte Carlo treat plan optimization: a platform which optimizes the fluence during the dose calculation, reduces wasted computation time being spent on beamlets that weakly contribute to the final dose distribution, and requires only a low memory footprint to function. In this initial investigation, the authors explore the key theoretical and practical considerations of optimizing fluence in such a manner. Methods: The authors present a novel derivation and implementation of a gradient descent algorithm that allows for optimization during MC particle transport, based on highly stochastic information generated through particle transport of very few histories. A gradient rescaling and renormalization algorithm, and the concept of momentum from stochastic gradient descent were used to address obstacles unique to performing gradient descent fluence optimization during MC particle transport. The authors have applied their method to two simple geometrical phantoms, and one clinical patient geometry to examine the capability of this platform to generate conformal plans as well as assess its computational scaling and efficiency, respectively. Results: The authors obtain a reduction of at least 50% in total histories transported in their investigation compared to a theoretical unweighted beamlet calculation and subsequent fluence optimization method, and observe a roughly fixed optimization time overhead consisting of ∼10% of the total computation time in all cases. Finally, the authors demonstrate a negligible increase in memory overhead of ∼7–8 MB to allow for optimization of a clinical patient geometry surrounded by 36 beams using their platform. Conclusions: This study demonstrates a fluence optimization approach, which could significantly improve the development of next generation radiation therapy solutions while incurring minimal additional computational overhead.« less

Simultaneously optimizing dose and schedule of a new cytotoxic agent.

PubMed

Braun, Thomas M; Thall, Peter F; Nguyen, Hoang; de Lima, Marcos

2007-01-01

Traditionally, phase I clinical trial designs are based upon one predefined course of treatment while varying among patients the dose given at each administration. In actual medical practice, patients receive a schedule comprised of several courses of treatment, and some patients may receive one or more dose reductions or delays during treatment. Consequently, the overall risk of toxicity for each patient is a function of both actual schedule of treatment and the differing doses used at each adminstration. Our goal is to provide a practical phase I clinical trial design that more accurately reflects actual medical practice by accounting for both dose per administration and schedule. We propose an outcome-adaptive Bayesian design that simultaneously optimizes both dose and schedule in terms of the overall risk of toxicity, based on time-to-toxicity outcomes. We use computer simulation as a tool to calibrate design parameters. We describe a phase I trial in allogeneic bone marrow transplantation that was designed and is currently being conducted using our new method. Our computer simulations demonstrate that our method outperforms any method that searches for an optimal dose but does not allow schedule to vary, both in terms of the probability of identifying optimal (dose, schedule) combinations, and the numbers of patients assigned to those combinations in the trial. Our design requires greater sample sizes than those seen in traditional phase I studies due to the larger number of treatment combinations examined. Our design also assumes that the effects of multiple administrations are independent of each other and that the hazard of toxicity is the same for all administrations. Our design is the first for phase I clinical trials that is sufficiently flexible and practical to truly reflect clinical practice by varying both dose and the timing and number of administrations given to each patient.

Toward reliable and repeatable automated STEM-EDS metrology with high throughput

NASA Astrophysics Data System (ADS)

Zhong, Zhenxin; Donald, Jason; Dutrow, Gavin; Roller, Justin; Ugurlu, Ozan; Verheijen, Martin; Bidiuk, Oleksii

2018-03-01

New materials and designs in complex 3D architectures in logic and memory devices have raised complexity in S/TEM metrology. In this paper, we report about a newly developed, automated, scanning transmission electron microscopy (STEM) based, energy dispersive X-ray spectroscopy (STEM-EDS) metrology method that addresses these challenges. Different methodologies toward repeatable and efficient, automated STEM-EDS metrology with high throughput are presented: we introduce the best known auto-EDS acquisition and quantification methods for robust and reliable metrology and present how electron exposure dose impacts the EDS metrology reproducibility, either due to poor signalto-noise ratio (SNR) at low dose or due to sample modifications at high dose conditions. Finally, we discuss the limitations of the STEM-EDS metrology technique and propose strategies to optimize the process both in terms of throughput and metrology reliability.

A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

PubMed

Zang, Yong; Lee, J Jack

2017-01-15

We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Single line source with and without vaginal loading and the impact on target coverage and organ at risk doses for cervix cancer Stages IB, II, and IIIB: treatment planning simulation in patients treated with MRI-guided adaptive brachytherapy in a multicentre study (EMBRACE).

PubMed

Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian

2013-01-01

Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Optimizing treatment of hypothyroidism.

PubMed

Clarke, Nick; Kabadi, Udaya M

2004-01-01

Several thyroid hormone preparations are currently available, including levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid extract, as well as a combination of levothyroxine sodium and liothyronine. Levothyroxine sodium monotherapy at an appropriate daily dose provides uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation. Therefore, it is the preparation of choice in most patients with hypothyroidism of both the primary and central types. A normal thyrotropin (TSH) level of 1-2 mU/L is considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism, whereas normal thyroxine and triiodothyronine levels in the mid or upper normal range may denote optimal replacement in patients with central hypothyroidism. Optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism. Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, reducing the need for follow-up visits and repeated laboratory testing for dose titration. In the elderly and in patients with a history of coronary artery disease (CAD), the well established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option. Levothyroxine sodium can and should be continued in patients receiving treatment for CAD. Even minor over-replacement during initial titration of levothyroxine sodium should be avoided, because of the risk of cardiac events. Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided.

CT dose minimization using personalized protocol optimization and aggressive bowtie

NASA Astrophysics Data System (ADS)

Wang, Hui; Yin, Zhye; Jin, Yannan; Wu, Mingye; Yao, Yangyang; Tao, Kun; Kalra, Mannudeep K.; De Man, Bruno

2016-03-01

In this study, we propose to use patient-specific x-ray fluence control to reduce the radiation dose to sensitive organs while still achieving the desired image quality (IQ) in the region of interest (ROI). The mA modulation profile is optimized view by view, based on the sensitive organs and the ROI, which are obtained from an ultra-low-dose volumetric CT scout scan [1]. We use a clinical chest CT scan to demonstrate the feasibility of the proposed concept: the breast region is selected as the sensitive organ region while the cardiac region is selected as IQ ROI. Two groups of simulations are performed based on the clinical CT dataset: (1) a constant mA scan adjusted based on the patient attenuation (120 kVp, 300 mA), which serves as baseline; (2) an optimized scan with aggressive bowtie and ROI centering combined with patient-specific mA modulation. The results shows that the combination of the aggressive bowtie and the optimized mA modulation can result in 40% dose reduction in the breast region, while the IQ in the cardiac region is maintained. More generally, this paper demonstrates the general concept of using a 3D scout scan for optimal scan planning.

A pragmatic approach to determine the optimal kVp in cone beam CT: balancing contrast-to-noise ratio and radiation dose

PubMed Central

Silkosessak, O; Jacobs, R; Bogaerts, R; Bosmans, H; Panmekiate, S

2014-01-01

Objectives: To determine the optimal kVp setting for a particular cone beam CT (CBCT) device by maximizing technical image quality at a fixed radiation dose. Methods: The 3D Accuitomo 170 (J. Morita Mfg. Corp., Kyoto, Japan) CBCT was used. The radiation dose as a function of kVp was measured in a cylindrical polymethyl methacrylate (PMMA) phantom using a small-volume ion chamber. Contrast-to-noise ratio (CNR) was measured using a PMMA phantom containing four materials (air, aluminium, polytetrafluoroethylene and low-density polyethylene), which was scanned using 180 combinations of kVp/mA, ranging from 60/1 to 90/8. The CNR was measured for each material using PMMA as background material. The pure effect of kVp and mAs on the CNR values was analysed. Using a polynomial fit for CNR as a function of mA for each kVp value, the optimal kVp was determined at five dose levels. Results: Absorbed doses ranged between 0.034 mGy mAs−1 (14 × 10 cm, 60 kVp) and 0.108 mGy mAs−1 (14 × 10 cm, 90 kVp). The relation between kVp and dose was quasilinear (R2 > 0.99). The effect of mA and kVp on CNR could be modelled using a second-degree polynomial. At a fixed dose, there was a tendency for higher CNR values at increasing kVp values, especially at low dose levels. A dose reduction through mA was more efficient than an equivalent reduction through kVp in terms of image quality deterioration. Conclusions: For the investigated CBCT model, the most optimal contrast at a fixed dose was found at the highest available kVp setting. There is great potential for dose reduction through mA with a minimal loss in image quality. PMID:24708447

SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, K; Aldoohan, S; Collier, J

Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measuremore » CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.« less

Effects of Pharmacokinetic Processes and Varied Dosing Schedules on the Dynamics of Acquired Resistance to Erlotinib in EGFR-Mutant Lung Cancer

PubMed Central

Foo, Jasmine; Chmielecki, Juliann; Pao, William; Michor, Franziska

2013-01-01

Introduction Erlotinib (Tarceva) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which effectively targets EGFR-mutant driven non–small-cell lung cancer. However, the evolution of acquired resistance because of a second-site mutation (T790M) within EGFR remains an obstacle to successful treatment. Methods We used mathematical modeling and available clinical trial data to predict how different pharmacokinetic parameters (fast versus slow metabolism) and dosing schedules (low dose versus high dose; missed doses with and without make-up doses) might affect the evolution of T790M-mediated resistance in mixed populations of tumor cells. Results We found that high-dose pulses with low-dose continuous therapy impede the development of resistance to the maximum extent, both pre- and post-emergence of resistance. The probability of resistance is greater in fast versus slow drug metabolizers, suggesting a potential mechanism, unappreciated to date, influencing acquired resistance in patients. In case of required dose modifications because of toxicity, little difference is observed in terms of efficacy and resistance dynamics between the standard daily dose (150 mg/d) and 150 mg/d alternating with 100 mg/d. Missed doses are expected to lead to resistance faster, even if make-up doses are attempted. Conclusions For existing and new kinase inhibitors, this novel framework can be used to rationally and rapidly design optimal dosing strategies to minimize the development of acquired resistance. PMID:22982659

Optimal Clinical Doses of Faropenem, Linezolid, and Moxifloxacin in Children With Disseminated Tuberculosis: Goldilocks

PubMed Central

Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

2016-01-01

Background. When treated with the same antibiotic dose, children achieve different 0- to 24-hour area under the concentration-time curves (AUC0–24) because of maturation and between-child physiological variability on drug clearance. Children are also infected by Mycobacterium tuberculosis isolates with different antibiotic minimum inhibitory concentrations (MICs). Thus, each child will achieve different AUC0–24/MIC ratios when treated with the same dose. Methods. We used 10 000-subject Monte Carlo experiments to identify the oral doses of linezolid, moxifloxacin, and faropenem that would achieve optimal target exposures associated with optimal efficacy in children with disseminated tuberculosis. The linezolid and moxifloxacin exposure targets were AUC0–24/MIC ratios of 62 and 122, and a faropenem percentage of time above MIC >60%, in combination therapy. A linezolid AUC0–24 of 93.4 mg × hour/L was target for toxicity. Population pharmacokinetic parameters of each drug and between-child variability, as well as MIC distribution, were used, and the cumulative fraction of response (CFR) was calculated. We also considered drug penetration indices into meninges, bone, and peritoneum. Results. The linezolid dose of 15 mg/kg in full-term neonates and infants aged up to 3 months and 10 mg/kg in toddlers, administered once daily, achieved CFR ≥ 90%, with <10% achieving linezolid AUC0–24 associated with toxicity. The moxifloxacin dose of 25 mg/kg/day achieved a CFR > 90% in infants, but the optimal dose was 20 mg/kg/day in older children. The faropenem medoxomil optimal dosage was 30 mg/kg 3–4 times daily. Conclusions. The regimen and doses of linezolid, moxifloxacin, and faropenem identified are proposed to be adequate for all disseminated tuberculosis syndromes, whether drug-resistant or -susceptible. PMID:27742641

Low-dose computed tomography scans with automatic exposure control for patients of different ages undergoing cardiac PET/CT and SPECT/CT.

PubMed

Yang, Ching-Ching; Yang, Bang-Hung; Tu, Chun-Yuan; Wu, Tung-Hsin; Liu, Shu-Hsin

2017-06-01

This study aimed to evaluate the efficacy of automatic exposure control (AEC) in order to optimize low-dose computed tomography (CT) protocols for patients of different ages undergoing cardiac PET/CT and single-photon emission computed tomography/computed tomography (SPECT/CT). One PET/CT and one SPECT/CT were used to acquire CT images for four anthropomorphic phantoms representative of 1-year-old, 5-year-old and 10-year-old children and an adult. For the hybrid systems investigated in this study, the radiation dose and image quality of cardiac CT scans performed with AEC activated depend mainly on the selection of a predefined image quality index. Multiple linear regression methods were used to analyse image data from anthropomorphic phantom studies to investigate the effects of body size and predefined image quality index on CT radiation dose in cardiac PET/CT and SPECT/CT scans. The regression relationships have a coefficient of determination larger than 0.9, indicating a good fit to the data. According to the regression models, low-dose protocols using the AEC technique were optimized for patients of different ages. In comparison with the standard protocol with AEC activated for adult cardiac examinations used in our clinical routine practice, the optimized paediatric protocols in PET/CT allow 32.2, 63.7 and 79.2% CT dose reductions for anthropomorphic phantoms simulating 10-year-old, 5-year-old and 1-year-old children, respectively. The corresponding results for cardiac SPECT/CT are 8.4, 51.5 and 72.7%. AEC is a practical way to reduce CT radiation dose in cardiac PET/CT and SPECT/CT, but the AEC settings should be determined properly for optimal effect. Our results show that AEC does not eliminate the need for paediatric protocols and CT examinations using the AEC technique should be optimized for paediatric patients to reduce the radiation dose as low as reasonably achievable.

SU-E-I-43: Pediatric CT Dose and Image Quality Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, G; Singh, R

2014-06-01

Purpose: To design an approach to optimize radiation dose and image quality for pediatric CT imaging, and to evaluate expected performance. Methods: A methodology was designed to quantify relative image quality as a function of CT image acquisition parameters. Image contrast and image noise were used to indicate expected conspicuity of objects, and a wide-cone system was used to minimize scan time for motion avoidance. A decision framework was designed to select acquisition parameters as a weighted combination of image quality and dose. Phantom tests were used to acquire images at multiple techniques to demonstrate expected contrast, noise and dose.more » Anthropomorphic phantoms with contrast inserts were imaged on a 160mm CT system with tube voltage capabilities as low as 70kVp. Previously acquired clinical images were used in conjunction with simulation tools to emulate images at different tube voltages and currents to assess human observer preferences. Results: Examination of image contrast, noise, dose and tube/generator capabilities indicates a clinical task and object-size dependent optimization. Phantom experiments confirm that system modeling can be used to achieve the desired image quality and noise performance. Observer studies indicate that clinical utilization of this optimization requires a modified approach to achieve the desired performance. Conclusion: This work indicates the potential to optimize radiation dose and image quality for pediatric CT imaging. In addition, the methodology can be used in an automated parameter selection feature that can suggest techniques given a limited number of user inputs. G Stevens and R Singh are employees of GE Healthcare.« less

Integrated beam orientation and scanning-spot optimization in intensity-modulated proton therapy for brain and unilateral head and neck tumors.

PubMed

Gu, Wenbo; O'Connor, Daniel; Nguyen, Dan; Yu, Victoria Y; Ruan, Dan; Dong, Lei; Sheng, Ke

2018-04-01

Intensity-Modulated Proton Therapy (IMPT) is the state-of-the-art method of delivering proton radiotherapy. Previous research has been mainly focused on optimization of scanning spots with manually selected beam angles. Due to the computational complexity, the potential benefit of simultaneously optimizing beam orientations and spot pattern could not be realized. In this study, we developed a novel integrated beam orientation optimization (BOO) and scanning-spot optimization algorithm for intensity-modulated proton therapy (IMPT). A brain chordoma and three unilateral head-and-neck patients with a maximal target size of 112.49 cm 3 were included in this study. A total number of 1162 noncoplanar candidate beams evenly distributed across 4π steradians were included in the optimization. For each candidate beam, the pencil-beam doses of all scanning spots covering the PTV and a margin were calculated. The beam angle selection and spot intensity optimization problem was formulated to include three terms: a dose fidelity term to penalize the deviation of PTV and OAR doses from ideal dose distribution; an L1-norm sparsity term to reduce the number of active spots and improve delivery efficiency; a group sparsity term to control the number of active beams between 2 and 4. For the group sparsity term, convex L2,1-norm and nonconvex L2,1/2-norm were tested. For the dose fidelity term, both quadratic function and linearized equivalent uniform dose (LEUD) cost function were implemented. The optimization problem was solved using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA). The IMPT BOO method was tested on three head-and-neck patients and one skull base chordoma patient. The results were compared with IMPT plans created using column generation selected beams or manually selected beams. The L2,1-norm plan selected spatially aggregated beams, indicating potential degeneracy using this norm. L2,1/2-norm was able to select spatially separated beams and achieve smaller deviation from the ideal dose. In the L2,1/2-norm plans, the [mean dose, maximum dose] of OAR were reduced by an average of [2.38%, 4.24%] and[2.32%, 3.76%] of the prescription dose for the quadratic and LEUD cost function, respectively, compared with the IMPT plan using manual beam selection while maintaining the same PTV coverage. The L2,1/2 group sparsity plans were dosimetrically superior to the column generation plans as well. Besides beam orientation selection, spot sparsification was observed. Generally, with the quadratic cost function, 30%~60% spots in the selected beams remained active. With the LEUD cost function, the percentages of active spots were in the range of 35%~85%.The BOO-IMPT run time was approximately 20 min. This work shows the first IMPT approach integrating noncoplanar BOO and scanning-spot optimization in a single mathematical framework. This method is computationally efficient, dosimetrically superior and produces delivery-friendly IMPT plans. © 2018 American Association of Physicists in Medicine.

Is patient size important in dose determination and optimization in cardiology?

NASA Astrophysics Data System (ADS)

Reay, J.; Chapple, C. L.; Kotre, C. J.

2003-12-01

Patient dose determination and optimization have become more topical in recent years with the implementation of the Medical Exposures Directive into national legislation, the Ionising Radiation (Medical Exposure) Regulations. This legislation incorporates a requirement for new equipment to provide a means of displaying a measure of patient exposure and introduces the concept of diagnostic reference levels. It is normally assumed that patient dose is governed largely by patient size; however, in cardiology, where procedures are often very complex, the significance of patient size is less well understood. This study considers over 9000 cardiology procedures, undertaken throughout the north of England, and investigates the relationship between patient size and dose. It uses simple linear regression to calculate both correlation coefficients and significance levels for data sorted by both room and individual clinician for the four most common examinations, left ventrical and/or coronary angiography, single vessel stent insertion and single vessel angioplasty. This paper concludes that the correlation between patient size and dose is weak for the procedures considered. It also illustrates the use of an existing method for removing the effect of patient size from dose survey data. This allows typical doses and, therefore, reference levels to be defined for the purposes of dose optimization.

SU-F-BRD-01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity-Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Shen, J; Stoker, J

2015-06-15

Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses tomore » achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest compared to TV. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research; Mayo ASU Seed Grant; The Kemper Marley Foundation.« less

WE-G-16A-01: Evolution of Radiation Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothenberg, L; Mohan, R; Van Dyk, J

Welcome and Introduction - Lawrence N. Rothenberg This symposium is one a continuing series of presentations at AAPM Annual Meetings on the historical aspects of medical physics, radiology, and radiation oncology that have been organized by the AAPM History Committee. Information on previous presentations including “Early Developments in Teletherapy” (Indianapolis 2013), “Historical Aspects of Cross-Sectional Imaging” (Charlotte 2012), “Historical Aspects of Brachytherapy” (Vancouver 2011), “50 Years of Women in Medical Physics” (Houston 2008), and “Roentgen's Early Investigations” (Minneapolis 2007) can be found in the Education Section of the AAPM Website. The Austin 2014 History Symposium will be on “Evolution ofmore » Radiation Treatment Planning.” Overview - Radhe Mohan Treatment planning is one of the most critical components in the chain of radiation therapy of cancers. Treatment plans of today contain a wide variety of sophisticated information conveying the potential clinical effectiveness of the designed treatment to practitioners. Examples of such information include dose distributions superimposed on three- or even four-dimensional anatomic images; dose volume histograms, dose, dose-volume and dose-response indices for anatomic structures of interest; etc. These data are used for evaluating treatment plans and for making treatment decisions. The current state-of-the-art has evolved from the 1940s era when the dose to the tumor and normal tissues was estimated approximately by manual means. However, the symposium will cover the history of the field from the late-1950's, when computers were first introduced for treatment planning, to the present state involving the use of high performance computing and advanced multi-dimensional anatomic, functional and biological imaging, focusing only on external beam treatment planning. The symposium will start with a general overview of the treatment planning process including imaging, structure delineation, assignment of dose requirements, consideration of uncertainties, selection of beam configurations and shaping of beams, and calculations, optimization and evaluation of dose distributions. This will be followed by three presentations covering the evolution of treatment planning, which parallels the evolution of computers, availability of advanced volumetric imaging and the development of novel technologies such as dynamic multi-leaf collimators and online image guidance. This evolution will be divided over three distinct periods - prior to 1970's, the 2D era; from 1980 to the mid-1990's, the 3D era; and from the mid 1990's to today, the IMRT era. When the World was Flat: The Two-Dimensional Radiation Therapy Era” - Jacob Van Dyk In the 2D era, anatomy was defined with the aid of solder wires, special contouring devices and projection x-rays. Dose distributions were calculated manually from single field, flat surface isodoses on transparencies. Precalculated atlases of generic dose distributions were produced by the International Atomic Energy Agency. Massive time-shared main frames and mini-computers were used to compute doses at individual points or dose distributions in a single plane. Beam shapes were generally rectangular, with wedges, missing tissue compensators and occasional blocks to shield critical structures. Dose calculations were measurement-based or they used primary and scatter calculations based on scatter-air ratio methodologies. Dose distributions were displayed on line printers as alpha-numeric character maps or isodose patterns made with pen plotters. More than Pretty Pictures: 3D Treatment Planning and Conformal Therapy - Benedick A. Fraass The introduction of computed tomography allowed the delineation of anatomy three-dimensionally and, supported partly by contracts from the National Cancer Institute, made possible the introduction and clinical use of 3D treatment planning, leading to development and use of 3D conformal therapy in the 1980's. 3D computer graphics and 3D anatomical structure definitions made possible Beam's Eye View (BEV) displays, making conformal beam shaping and much more sophisticated beam arrangements possible. These conformal plans significantly improved target dose coverage as well as normal tissue sparing. The use of dose volume histograms, gross/clinical/planning target volumes, MRI and PET imaging, multileaf collimators, and computer-controlled treatment delivery made sophisticated planning approaches practical. The significant improvements in dose distributions and analysis achievable with 3D conformal therapy made possible formal dose escalation and normal tissue tolerance clinical studies that set new and improved expectations for improved local control and decreasing complications in many clinical sites. From the Art to the State of the Art: Inverse Planning and IMRT - Thomas R. Bortfeld While the potential of intensity modulation was recognized in the mid- 1980's, intensity-modulated radiotherapy (IMRT) did not become a reality until the mid-1990's. Broad beams of photons could be sub-divided into narrow beamlets whose intensities could be determined using sophisticated optimization algorithms to appropriately balance tumor dose with normal tissue sparing. The development of dynamic multi-leaf collimators (on conventional linear accelerators as well as in helical delivery devices) enabled the efficient delivery of IMRT. The evolution of IMRT planning is continuing in the form of Volumetric Modulated Arc Therapy (VMAT) and through advanced optimization tools, such as multi-criteria optimization, automated IMRT planning, and robust optimization to protect dose distributions against uncertainties. IMRT also facilitates “dose painting” in which different sub-volumes of the target are prescribed different doses. Clearly, these advancements are being made possible by the increasing power and lower cost of computers and developments in other fields such as imaging and operations research. Summary - Radhe Mohan The history does not end here. The advancement of treatment planning is expected to continue, leading to further automation and improvements in conformality and robustness of dose distributions, particularly in the area of particle therapy. Radiobiological modeling will gain emphasis as part of the planning process. Learning Objectives: The scope of changes in technology and the capabilities of radiation treatment planning The impact of these changes in the quality of treatment plans and optimality of dose distributions The impact of development in other fields (imaging, computers, operations research, etc.) on the evolution of radiation treatment planning.« less

Frame average optimization of cine-mode EPID images used for routine clinical in vivo patient dose verification of VMAT deliveries

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCowan, P. M., E-mail: pmccowan@cancercare.mb.ca; McCurdy, B. M. C.; Medical Physics Department, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9

Purpose: The in vivo 3D dose delivered to a patient during volumetric modulated arc therapy (VMAT) delivery can be calculated using electronic portal imaging device (EPID) images. These images must be acquired in cine-mode (i.e., “movie” mode) in order to capture the time-dependent delivery information. The angle subtended by each cine-mode EPID image during an arc can be changed via the frame averaging number selected within the image acquisition software. A large frame average number will decrease the EPID’s angular resolution and will result in a decrease in the accuracy of the dose information contained within each image. Alternatively, lessmore » EPID images acquired per delivery will decrease the overall 3D patient dose calculation time, which is appealing for large-scale clinical implementation. Therefore, the purpose of this study was to determine the optimal frame average value per EPID image, defined as the highest frame averaging that can be used without an appreciable loss in 3D dose reconstruction accuracy for VMAT treatments. Methods: Six different VMAT plans and six different SBRT-VMAT plans were delivered to an anthropomorphic phantom. Delivery was carried out on a Varian 2300ix model linear accelerator (Linac) equipped with an aS1000 EPID running at a frame acquisition rate of 7.5 Hz. An additional PC was set up at the Linac console area, equipped with specialized frame-grabber hardware and software packages allowing continuous acquisition of all EPID frames during delivery. Frames were averaged into “frame-averaged” EPID images using MATLAB. Each frame-averaged data set was used to calculate the in vivo dose to the patient and then compared to the single EPID frame in vivo dose calculation (the single frame calculation represents the highest possible angular resolution per EPID image). A mean percentage dose difference of low dose (<20% prescription dose) and high dose regions (>80% prescription dose) was calculated for each frame averaged scenario for each plan. The authors defined their unacceptable loss of accuracy as no more than a ±1% mean dose difference in the high dose region. Optimal frame average numbers were then determined as a function of the Linac’s average gantry speed and the dose per fraction. Results: The authors found that 9 and 11 frame averages were suitable for all VMAT and SBRT-VMAT treatments, respectively. This resulted in no more than a 1% loss to any of the dose region’s mean percentage difference when compared to the single frame reconstruction. The optimized number was dependent on the treatment’s dose per fraction and was determined to be as high as 14 for 12 Gy/fraction (fx), 15 for 8 Gy/fx, 11 for 6 Gy/fx, and 9 for 2 Gy/fx. Conclusions: The authors have determined an optimal EPID frame averaging number for multiple VMAT-type treatments. These are given as a function of the dose per fraction and average gantry speed. These optimized values are now used in the authors’ clinical, 3D, in vivo patient dosimetry program. This provides a reduction in calculation time while maintaining the authors’ required level of accuracy in the dose reconstruction.« less

Impact of organic polyelectrolytes on coagulation of source-separated black water.

PubMed

Kozminykh, Pavlo; Heistad, Arve; Ratnaweera, Harsha C; Todt, Daniel

2016-01-01

Household wastewater is originated from common people's activities and has a potential harmful impact on the environment if discharged directly without proper treatment. Toilet wastewater or black water (BW) contains urine, faeces, toilet paper and flushing water and it contains the majority of pollutants obtained from a single household. In this study, the focus was on BW treatment using chemical methods. The main goal of current research was to define the possibility and applicability of conventional coagulants and flocculants in direct chemical treatment of vacuum-collected BW to remove particles, organic matter and phosphorous. After the definition of dosing ranges, based on the equivalent doses in conventional municipal and industrial wastewater treatment data, aluminium and iron coagulants, organic polyelectrolytes (polymers with anionic, neutral and cationic charge with different molecular weights) and their various combinations were tested using the well-known jar-test laboratory method to study aggregation and solid-liquid separation processes in raw BW. The most important process parameter during the coagulation was pH level, dependent on the type and doses of metal salts. Some side processes were found to occur while using iron-based coagulants. Dosing of either single coagulants or single polymers did not give satisfactory results, while a combination of aluminium salts and cationic polymers showed high removal rates in total suspended solids, total chemical oxygen demand and ortho-phosphates, reaching 97.8%, 92% and 98.6%, respectively, with the optimal doses of chemicals. Cationic polymers with the lowest molecular weight and highest charge density were the most efficient in combination with aluminium coagulants.

Inverse planning in the age of digital LINACs: station parameter optimized radiation therapy (SPORT)

NASA Astrophysics Data System (ADS)

Xing, Lei; Li, Ruijiang

2014-03-01

The last few years have seen a number of technical and clinical advances which give rise to a need for innovations in dose optimization and delivery strategies. Technically, a new generation of digital linac has become available which offers features such as programmable motion between station parameters and high dose-rate Flattening Filter Free (FFF) beams. Current inverse planning methods are designed for traditional machines and cannot accommodate these features of new generation linacs without compromising either dose conformality and/or delivery efficiency. Furthermore, SBRT is becoming increasingly important, which elevates the need for more efficient delivery, improved dose distribution. Here we will give an overview of our recent work in SPORT designed to harness the digital linacs and highlight the essential components of SPORT. We will summarize the pros and cons of traditional beamlet-based optimization (BBO) and direct aperture optimization (DAO) and introduce a new type of algorithm, compressed sensing (CS)-based inverse planning, that is capable of automatically removing the redundant segments during optimization and providing a plan with high deliverability in the presence of a large number of station control points (potentially non-coplanar, non-isocentric, and even multi-isocenters). We show that CS-approach takes the interplay between planning and delivery into account and allows us to balance the dose optimality and delivery efficiency in a controlled way and, providing a viable framework to address various unmet demands of the new generation linacs. A few specific implementation strategies of SPORT in the forms of fixed-gantry and rotational arc delivery are also presented.

Research on Ratio of Dosage of Drugs in Traditional Chinese Prescriptions by Data Mining.

PubMed

Yu, Xing-Wen; Gong, Qing-Yue; Hu, Kong-Fa; Mao, Wen-Jing; Zhang, Wei-Ming

2017-01-01

Maximizing the effectiveness of prescriptions and minimizing adverse effects of drugs is a key component of the health care of patients. In the practice of traditional Chinese medicine (TCM), it is important to provide clinicians a reference for dosing of prescribed drugs. The traditional Cheng-Church biclustering algorithm (CC) is optimized and the data of TCM prescription dose is analyzed by using the optimization algorithm. Based on an analysis of 212 prescriptions related to TCM treatment of kidney diseases, the study generated 87 prescription dose quantum matrices and each sub-matrix represents the referential value of the doses of drugs in different recipes. The optimized CC algorithm can effectively eliminate the interference of zero in the original dose matrix of TCM prescriptions and avoid zero appearing in output sub-matrix. This results in the ability to effectively analyze the reference value of drugs in different prescriptions related to kidney diseases, so as to provide valuable reference for clinicians to use drugs rationally.

Dosimetric comparison between VMAT and RC3D techniques: case of prostate treatment

NASA Astrophysics Data System (ADS)

Chemingui, Fatima Zohra; Benrachi, Fatima; Bali, Mohamed Saleh; Ladjal, Hamid

2017-09-01

Considered as the second men cancer in Algeria, prostate cancer is treated in 70% by radiation. That's why radiation therapy is therapeutic weapon for prostate cancer. Conformational Radiotherapy in 3D is the most common technique [1-5]. The use of conventionally optimized treatment plans was compared at case scenario of optimized treatment plans VMAT for prostate cancer. The evaluation of the two optimizations strategies focused on the resulting plans ability to retain dose objectives under the influence of patient set up. Dose Volume Histogram in the Planning Target Volume and dose in the Organs At Risks were used to calculate the conformity index, and evaluation ratio of irradiated volume which represent the main tool of comparison [6,7]. The situation was analysed systematically. The 14% dose increase in the target leads to a decrease in the dose in adjacent organs with 39% in the bladder. Therefore, the criterion for better efficacy and less toxicity reveal that VMAT is the best choice.

Overview of CMOS process and design options for image sensor dedicated to space applications

NASA Astrophysics Data System (ADS)

Martin-Gonthier, P.; Magnan, P.; Corbiere, F.

2005-10-01

With the growth of huge volume markets (mobile phones, digital cameras...) CMOS technologies for image sensor improve significantly. New process flows appear in order to optimize some parameters such as quantum efficiency, dark current, and conversion gain. Space applications can of course benefit from these improvements. To illustrate this evolution, this paper reports results from three technologies that have been evaluated with test vehicles composed of several sub arrays designed with some space applications as target. These three technologies are CMOS standard, improved and sensor optimized process in 0.35μm generation. Measurements are focussed on quantum efficiency, dark current, conversion gain and noise. Other measurements such as Modulation Transfer Function (MTF) and crosstalk are depicted in [1]. A comparison between results has been done and three categories of CMOS process for image sensors have been listed. Radiation tolerance has been also studied for the CMOS improved process in the way of hardening the imager by design. Results at 4, 15, 25 and 50 krad prove a good ionizing dose radiation tolerance applying specific techniques.

Early experiences of planning stereotactic radiosurgery using 3D printed models of eyes with uveal melanomas

PubMed Central

Furdová, Alena; Sramka, Miron; Thurzo, Andrej; Furdová, Adriana

2017-01-01

Objective The objective of this study was to determine the use of 3D printed model of an eye with intraocular tumor for linear accelerator-based stereotactic radiosurgery. Methods The software for segmentation (3D Slicer) created virtual 3D model of eye globe with tumorous mass based on tissue density from computed tomography and magnetic resonance imaging data. A virtual model was then processed in the slicing software (Simplify3D®) and printed on 3D printer using fused deposition modeling technology. The material that was used for printing was polylactic acid. Results In 2015, stereotactic planning scheme was optimized with the help of 3D printed model of the patient’s eye with intraocular tumor. In the period 2001–2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma and 11 ciliary body melanoma) were treated. The median tumor volume was 0.5 cm3 (0.2–1.6 cm3). The radiation dose was 35.0 Gy by 99% of dose volume histogram. Conclusion The 3D printed model of eye with tumor was helpful in planning the process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures. PMID:28203052

Dosimetric benefit of adaptive re-planning in pancreatic cancer stereotactic body radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yongbao; Center for Advanced Radiotherapy Technologies University of California San Diego, La Jolla, CA; Department of Radiation Oncology, University of California San Diego, La Jolla, CA

Stereotactic body radiotherapy (SBRT) shows promise in unresectable pancreatic cancer, though this treatment modality has high rates of normal tissue toxicity. This study explores the dosimetric utility of daily adaptive re-planning with pancreas SBRT. We used a previously developed supercomputing online re-planning environment (SCORE) to re-plan 10 patients with pancreas SBRT. Tumor and normal tissue contours were deformed from treatment planning computed tomographies (CTs) and transferred to daily cone-beam CT (CBCT) scans before re-optimizing each daily treatment plan. We compared the intended radiation dose, the actual radiation dose, and the optimized radiation dose for the pancreas tumor planning target volumemore » (PTV) and the duodenum. Treatment re-optimization improved coverage of the PTV and reduced dose to the duodenum. Within the PTV, the actual hot spot (volume receiving 110% of the prescription dose) decreased from 4.5% to 0.5% after daily adaptive re-planning. Within the duodenum, the volume receiving the prescription dose decreased from 0.9% to 0.3% after re-planning. It is noteworthy that variation in the amount of air within a patient's stomach substantially changed dose to the PTV. Adaptive re-planning with pancreas SBRT has the ability to improve dose to the tumor and decrease dose to the nearby duodenum, thereby reducing the risk of toxicity.« less

MO-FG-CAMPUS-TeP3-04: Deliverable Robust Optimization in IMPT Using Quadratic Objective Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shan, J; Liu, W; Bues, M

Purpose: To find and evaluate the way of applying deliverable MU constraints into robust spot intensity optimization in Intensity-Modulated- Proton-Therapy (IMPT) to prevent plan quality and robustness from degrading due to machine deliverable MU-constraints. Methods: Currently, the influence of the deliverable MU-constraints is retrospectively evaluated by post-processing immediately following optimization. In this study, we propose a new method based on the quasi-Newton-like L-BFGS-B algorithm with which we turn deliverable MU-constraints on and off alternatively during optimization. Seven patients with two different machine settings (small and large spot size) were planned with both conventional and new methods. For each patient, threemore » kinds of plans were generated — conventional non-deliverable plan (plan A), conventional deliverable plan with post-processing (plan B), and new deliverable plan (plan C). We performed this study with both realistic (small) and artificial (large) deliverable MU-constraints. Results: With small minimum MU-constraints considered, new method achieved a slightly better plan quality than conventional method (D95% CTV normalized to the prescription dose: 0.994[0.992∼0.996] (Plan C) vs 0.992[0.986∼0.996] (Plan B)). With large minimum MU constraints considered, results show that the new method maintains plan quality while plan quality from the conventional method is degraded greatly (D95% CTV normalized to the prescription dose: 0.987[0.978∼0.994] (Plan C) vs 0.797[0.641∼1.000] (Plan B)). Meanwhile, plan robustness of these two method’s results is comparable. (For all 7 patients, CTV DVH band gap at D95% normalized to the prescription dose: 0.015[0.005∼0.043] (Plan C) vs 0.012[0.006∼0.038] (Plan B) with small MU-constraints and 0.019[0.009∼0.039] (Plan C) vs 0.030[0.015∼0.041] (Plan B) with large MU-constraints) Conclusion: Positive correlation has been found between plan quality degeneration and magnitude of deliverable minimal MU. Compared to conventional post-processing method, our new method of incorporating deliverable minimal MU-constraints directly into plan optimization, can produce machine-deliverable plans with better plan qualities and non-compromised plan robustness. This research was supported by the National Cancer Institute Career Developmental Award K25CA168984, by the Fraternal Order of Eagles Cancer Research Fund Career Development Award, by The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, by Mayo Arizona State University Seed Grant and by The Kemper Marley Foundation.« less

Exploration of optimal dosing regimens of haloperidol, a D2 Antagonist, via modeling and simulation analysis in a D2 receptor occupancy study.

PubMed

Lim, Hyeong-Seok; Kim, Su Jin; Noh, Yook-Hwan; Lee, Byung Chul; Jin, Seok-Joon; Park, Hyun Soo; Kim, Soohyeon; Jang, In-Jin; Kim, Sang Eun

2013-03-01

To evaluate the potential usage of D(2) receptor occupancy (D2RO) measured by positron emission tomography (PET) in antipsychotic development. In this randomized, parallel group study, eight healthy male volunteers received oral doses of 0.5 (n = 3), 1 (n = 2), or 3 mg (n = 3) of haloperidol once daily for 7 days. PET's were scanned before haloperidol, and on days 8, 12, with serial pharmacokinetic sampling on day 7. Pharmacokinetics and binding potential to D(2) receptor in putamen and caudate nucleus over time were analyzed using NONMEM, and simulations for the profiles of D2RO over time on various regimens of haloperidol were conducted to find the optimal dosing regimens. One compartment model with a saturable binding compartment, and inhibitory E(max) model in the effect compartment best described the data. Plasma haloperidol concentrations at half-maximal inhibition were 0.791 and 0.650 ng/ml, in putamen and caudate nucleus. Simulation suggested haloperidol 2 mg every 12 h is near the optimal dose. This study showed that sparse D2RO measurements in steady state pharmacodynamic design after multiple dosing could reveal the possibility of treatment effect of D(2) antagonist, and could identify the potential optimal doses for later clinical studies by modeling and simulation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, J; Perko, Z; Wolfgang, J

Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulativemore » BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less

SU-E-CAMPUS-T-04: Statistical Process Control for Patient-Specific QA in Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

LAH, J; SHIN, D; Kim, G

Purpose: To evaluate and improve the reliability of proton QA process, to provide an optimal customized level using the statistical process control (SPC) methodology. The aim is then to suggest the suitable guidelines for patient-specific QA process. Methods: We investigated the constancy of the dose output and range to see whether it was within the tolerance level of daily QA process. This study analyzed the difference between the measured and calculated ranges along the central axis to suggest the suitable guidelines for patient-specific QA in proton beam by using process capability indices. In this study, patient QA plans were classifiedmore » into 6 treatment sites: head and neck (41 cases), spinal cord (29 cases), lung (28 cases), liver (30 cases), pancreas (26 cases), and prostate (24 cases). Results: The deviations for the dose output and range of daily QA process were ±0.84% and ±019%, respectively. Our results show that the patient-specific range measurements are capable at a specification limit of ±2% in all treatment sites except spinal cord cases. In spinal cord cases, comparison of process capability indices (Cp, Cpm, Cpk ≥1, but Cpmk ≤1) indicated that the process is capable, but not centered, the process mean deviates from its target value. The UCL (upper control limit), CL (center line) and LCL (lower control limit) for spinal cord cases were 1.37%, −0.27% and −1.89%, respectively. On the other hands, the range differences in prostate cases were good agreement between calculated and measured values. The UCL, CL and LCL for prostate cases were 0.57%, −0.11% and −0.78%, respectively. Conclusion: SPC methodology has potential as a useful tool to customize an optimal tolerance levels and to suggest the suitable guidelines for patient-specific QA in clinical proton beam.« less

SU-F-T-377: Monte Carlo Re-Evaluation of Volumetric-Modulated Arc Plans of Advanced Stage Nasopharygeal Cancers Optimized with Convolution-Superposition Algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, K; Leung, R; Law, G

Background: Commercial treatment planning system Pinnacle3 (Philips, Fitchburg, WI, USA) employs a convolution-superposition algorithm for volumetric-modulated arc radiotherapy (VMAT) optimization and dose calculation. Study of Monte Carlo (MC) dose recalculation of VMAT plans for advanced-stage nasopharyngeal cancers (NPC) is currently limited. Methods: Twenty-nine VMAT prescribed 70Gy, 60Gy, and 54Gy to the planning target volumes (PTVs) were included. These clinical plans achieved with a CS dose engine on Pinnacle3 v9.0 were recalculated by the Monaco TPS v5.0 (Elekta, Maryland Heights, MO, USA) with a XVMC-based MC dose engine. The MC virtual source model was built using the same measurement beam datasetmore » as for the Pinnacle beam model. All MC recalculation were based on absorbed dose to medium in medium (Dm,m). Differences in dose constraint parameters per our institution protocol (Supplementary Table 1) were analyzed. Results: Only differences in maximum dose to left brachial plexus, left temporal lobe and PTV54Gy were found to be statistically insignificant (p> 0.05). Dosimetric differences of other tumor targets and normal organs are found in supplementary Table 1. Generally, doses outside the PTV in the normal organs are lower with MC than with CS. This is also true in the PTV54-70Gy doses but higher dose in the nasal cavity near the bone interfaces is consistently predicted by MC, possibly due to the increased backscattering of short-range scattered photons and the secondary electrons that is not properly modeled by the CS. The straight shoulders of the PTV dose volume histograms (DVH) initially resulted from the CS optimization are merely preserved after MC recalculation. Conclusion: Significant dosimetric differences in VMAT NPC plans were observed between CS and MC calculations. Adjustments of the planning dose constraints to incorporate the physics differences from conventional CS algorithm should be made when VMAT optimization is carried out directly with MC dose engine.« less

Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

PubMed

Sargento, Luis; Simões, Andre Vicente; Longo, Susana; Lousada, Nuno; Reis, Roberto Palma Dos

2017-05-01

Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

NASA Astrophysics Data System (ADS)

Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

2015-10-01

Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Q; Snyder, K; Liu, C

Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas weremore » the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.« less

Multivariable normal tissue complication probability model-based treatment plan optimization for grade 2-4 dysphagia and tube feeding dependence in head and neck radiotherapy.

PubMed

Kierkels, Roel G J; Wopken, Kim; Visser, Ruurd; Korevaar, Erik W; van der Schaaf, Arjen; Bijl, Hendrik P; Langendijk, Johannes A

2016-12-01

Radiotherapy of the head and neck is challenged by the relatively large number of organs-at-risk close to the tumor. Biologically-oriented objective functions (OF) could optimally distribute the dose among the organs-at-risk. We aimed to explore OFs based on multivariable normal tissue complication probability (NTCP) models for grade 2-4 dysphagia (DYS) and tube feeding dependence (TFD). One hundred head and neck cancer patients were studied. Additional to the clinical plan, two more plans (an OF DYS and OF TFD -plan) were optimized per patient. The NTCP models included up to four dose-volume parameters and other non-dosimetric factors. A fully automatic plan optimization framework was used to optimize the OF NTCP -based plans. All OF NTCP -based plans were reviewed and classified as clinically acceptable. On average, the Δdose and ΔNTCP were small comparing the OF DYS -plan, OF TFD -plan, and clinical plan. For 5% of patients NTCP TFD reduced >5% using OF TFD -based planning compared to the OF DYS -plans. Plan optimization using NTCP DYS - and NTCP TFD -based objective functions resulted in clinically acceptable plans. For patients with considerable risk factors of TFD, the OF TFD steered the optimizer to dose distributions which directly led to slightly lower predicted NTCP TFD values as compared to the other studied plans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

D-optimal experimental designs to test for departure from additivity in a fixed-ratio mixture ray.

PubMed

Coffey, Todd; Gennings, Chris; Simmons, Jane Ellen; Herr, David W

2005-12-01

Traditional factorial designs for evaluating interactions among chemicals in a mixture may be prohibitive when the number of chemicals is large. Using a mixture of chemicals with a fixed ratio (mixture ray) results in an economical design that allows estimation of additivity or nonadditive interaction for a mixture of interest. This methodology is extended easily to a mixture with a large number of chemicals. Optimal experimental conditions can be chosen that result in increased power to detect departures from additivity. Although these designs are used widely for linear models, optimal designs for nonlinear threshold models are less well known. In the present work, the use of D-optimal designs is demonstrated for nonlinear threshold models applied to a fixed-ratio mixture ray. For a fixed sample size, this design criterion selects the experimental doses and number of subjects per dose level that result in minimum variance of the model parameters and thus increased power to detect departures from additivity. An optimal design is illustrated for a 2:1 ratio (chlorpyrifos:carbaryl) mixture experiment. For this example, and in general, the optimal designs for the nonlinear threshold model depend on prior specification of the slope and dose threshold parameters. Use of a D-optimal criterion produces experimental designs with increased power, whereas standard nonoptimal designs with equally spaced dose groups may result in low power if the active range or threshold is missed.

SU-E-T-07: 4DCT Robust Optimization for Esophageal Cancer Using Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, L; Department of Industrial Engineering, University of Houston, Houston, TX; Yu, J

2015-06-15

Purpose: To develop a 4DCT robust optimization method to reduce the dosimetric impact from respiratory motion in intensity modulated proton therapy (IMPT) for esophageal cancer. Methods: Four esophageal cancer patients were selected for this study. The different phases of CT from a set of 4DCT were incorporated into the worst-case dose distribution robust optimization algorithm. 4DCT robust treatment plans were designed and compared with the conventional non-robust plans. Result doses were calculated on the average and maximum inhale/exhale phases of 4DCT. Dose volume histogram (DVH) band graphic and ΔD95%, ΔD98%, ΔD5%, ΔD2% of CTV between different phases were used tomore » evaluate the robustness of the plans. Results: Compare to the IMPT plans optimized using conventional methods, the 4DCT robust IMPT plans can achieve the same quality in nominal cases, while yield a better robustness to breathing motion. The mean ΔD95%, ΔD98%, ΔD5% and ΔD2% of CTV are 6%, 3.2%, 0.9% and 1% for the robustly optimized plans vs. 16.2%, 11.8%, 1.6% and 3.3% from the conventional non-robust plans. Conclusion: A 4DCT robust optimization method was proposed for esophageal cancer using IMPT. We demonstrate that the 4DCT robust optimization can mitigate the dose deviation caused by the diaphragm motion.« less

Rational Selection and Use of Antimicrobials in Patients with Burn Injuries.

PubMed

Hill, David M; Sinclair, Scott E; Hickerson, William L

2017-07-01

Caring for patients with burn injuries is challenging secondary to the acute disease process, chronic comorbidities, and underrepresentation in evidence-based literature. Much current practice relies on extrapolation of guidance from different patient populations and wide variations in universal practices. Identifying infections or sepsis in this hypermetabolic population is imperfect and often leads to overprescribing of antimicrobials, suboptimal dosing, and multidrug resistance. An understanding of pharmacokinetics and pharmacodynamics may aid optimization of dosing regimens to better attain treatment targets. This article provides an overview of the current status of burn infection and attempts recommendations for consideration to improve universally accepted care. Copyright © 2017 Elsevier Inc. All rights reserved.

A study of optimization techniques in HDR brachytherapy for the prostate

NASA Astrophysics Data System (ADS)

Pokharel, Ghana Shyam

Several studies carried out thus far are in favor of dose escalation to the prostate gland to have better local control of the disease. But optimal way of delivery of higher doses of radiation therapy to the prostate without hurting neighboring critical structures is still debatable. In this study, we proposed that real time high dose rate (HDR) brachytherapy with highly efficient and effective optimization could be an alternative means of precise delivery of such higher doses. This approach of delivery eliminates the critical issues such as treatment setup uncertainties and target localization as in external beam radiation therapy. Likewise, dosimetry in HDR brachytherapy is not influenced by organ edema and potential source migration as in permanent interstitial implants. Moreover, the recent report of radiobiological parameters further strengthen the argument of using hypofractionated HDR brachytherapy for the management of prostate cancer. Firstly, we studied the essential features and requirements of real time HDR brachytherapy treatment planning system. Automating catheter reconstruction with fast editing tools, fast yet accurate dose engine, robust and fast optimization and evaluation engine are some of the essential requirements for such procedures. Moreover, in most of the cases we performed, treatment plan optimization took significant amount of time of overall procedure. So, making treatment plan optimization automatic or semi-automatic with sufficient speed and accuracy was the goal of the remaining part of the project. Secondly, we studied the role of optimization function and constraints in overall quality of optimized plan. We have studied the gradient based deterministic algorithm with dose volume histogram (DVH) and more conventional variance based objective functions for optimization. In this optimization strategy, the relative weight of particular objective in aggregate objective function signifies its importance with respect to other objectives. Based on our study, DVH based objective function performed better than traditional variance based objective function in creating a clinically acceptable plan when executed under identical conditions. Thirdly, we studied the multiobjective optimization strategy using both DVH and variance based objective functions. The optimization strategy was to create several Pareto optimal solutions by scanning the clinically relevant part of the Pareto front. This strategy was adopted to decouple optimization from decision such that user could select final solution from the pool of alternative solutions based on his/her clinical goals. The overall quality of treatment plan improved using this approach compared to traditional class solution approach. In fact, the final optimized plan selected using decision engine with DVH based objective was comparable to typical clinical plan created by an experienced physicist. Next, we studied the hybrid technique comprising both stochastic and deterministic algorithm to optimize both dwell positions and dwell times. The simulated annealing algorithm was used to find optimal catheter distribution and the DVH based algorithm was used to optimize 3D dose distribution for given catheter distribution. This unique treatment planning and optimization tool was capable of producing clinically acceptable highly reproducible treatment plans in clinically reasonable time. As this algorithm was able to create clinically acceptable plans within clinically reasonable time automatically, it is really appealing for real time procedures. Next, we studied the feasibility of multiobjective optimization using evolutionary algorithm for real time HDR brachytherapy for the prostate. The algorithm with properly tuned algorithm specific parameters was able to create clinically acceptable plans within clinically reasonable time. However, the algorithm was let to run just for limited number of generations not considered optimal, in general, for such algorithms. This was done to keep time window desirable for real time procedures. Therefore, it requires further study with improved conditions to realize the full potential of the algorithm.

Nonlinear system identification for prostate cancer and optimality of intermittent androgen suppression therapy.

PubMed

Suzuki, Taiji; Aihara, Kazuyuki

2013-09-01

These days prostate cancer is one of the most common types of malignant neoplasm in men. Androgen ablation therapy (hormone therapy) has been shown to be effective for advanced prostate cancer. However, continuous hormone therapy often causes recurrence. This results from the progression of androgen-dependent cancer cells to androgen-independent cancer cells during the continuous hormone therapy. One possible method to prevent the progression to the androgen-independent state is intermittent androgen suppression (IAS) therapy, which ceases dosing intermittently. In this paper, we propose two methods to estimate the dynamics of prostate cancer, and investigate the IAS therapy from the viewpoint of optimality. The two methods that we propose for dynamics estimation are a variational Bayesian method for a piecewise affine (PWA) system and a Gaussian process regression method. We apply the proposed methods to real clinical data and compare their predictive performances. Then, using the estimated dynamics of prostate cancer, we observe how prostate cancer behaves for various dosing schedules. It can be seen that the conventional IAS therapy is a way of imposing high cost for dosing while keeping the prostate cancer in a safe state. We would like to dedicate this paper to the memory of Professor Luigi M. Ricciardi. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

MO-PIS-Exhibit Hall-01: Imaging: CT Dose Optimization Technologies I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denison, K; Smith, S

Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The imaging topic this year is CT scanner dose optimization capabilities. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Dose Optimization Capabilities of GE Computed Tomography Scanners Presentation Time: 11:15 – 11:45 AM GE Healthcare is dedicated to the delivery of high quality clinical images through the development of technologies, whichmore » optimize the application of ionizing radiation. In computed tomography, dose management solutions fall into four categories: employs projection data and statistical modeling to decrease noise in the reconstructed image - creating an opportunity for mA reduction in the acquisition of diagnostic images. Veo represents true Model Based Iterative Reconstruction (MBiR). Using high-level algorithms in tandem with advanced computing power, Veo enables lower pixel noise standard deviation and improved spatial resolution within a single image. Advanced Adaptive Image Filters allow for maintenance of spatial resolution while reducing image noise. Examples of adaptive image space filters include Neuro 3-D filters and Cardiac Noise Reduction Filters. AutomA adjusts mA along the z-axis and is the CT equivalent of auto exposure control in conventional x-ray systems. Dynamic Z-axis Tracking offers an additional opportunity for dose reduction in helical acquisitions while SmartTrack Z-axis Tracking serves to ensure beam, collimator and detector alignment during tube rotation. SmartmA provides angular mA modulation. ECG Helical Modulation reduces mA during the systolic phase of the heart cycle. SmartBeam optimization uses bowtie beam-shaping hardware and software to filter off-axis x-rays - minimizing dose and reducing x-ray scatter. The DICOM Radiation Dose Structured Report (RDSR) generates a dose report at the conclusion of every examination. Dose Check preemptively notifies CT operators when scan parameters exceed user-defined dose thresholds. DoseWatch is an information technology application providing vendor-agnostic dose tracking and analysis for CT (and all other diagnostic x-ray modalities) SnapShot Pulse improves coronary CTA dose management. VolumeShuttle uses two acquisitions to increase coverage, decrease dose, and conserve on contrast administration. Color-Coding for Kids applies the Broselow-Luten Pediatric System to facilitate pediatric emergency care and reduce medical errors. FeatherLight achieves dose optimization through pediatric procedure-based protocols. Adventure Series scanners provide a child-friendly imaging environment promoting patient cooperation with resultant reduction in retakes and patient motion. Philips CT Dose Optimization Tools and Advanced Reconstruction Presentation Time: 11:45 ‘ 12:15 PM The first part of the talk will cover “Dose Reduction and Dose Optimization Technologies” present in Philips CT Scanners. The main Technologies to be presented include: DoseRight and tube current modulation (DoseRight, Z-DOM, 3D-DOM, DoseRight Cardiac) Special acquisition modes Beam filtration and beam shapers Eclipse collimator and ClearRay collimator NanoPanel detector DoseRight will cover automatic tube current selection that automatically adjusts the dose for the individual patient. The presentation will explore the modulation techniques currently employed in Philips CT scanners and will include the algorithmic concepts as well as illustrative examples. Modulation and current selection technologies to be covered include the Automatic Current Selection component of DoseRight, ZDOM longitudinal dose modulation, 3D-DOM (combination of longitudinal and rotational dose modulation), Cardiac Dose right (an ECG based dose modulation scheme), and the DoseRight Index (DRI) IQ index. The special acquisition modes covers acquisition techniques such as prospective gating that is designed to reduce exposure to the patient through the Cardiac Step and Shoot scan mode. This mode can substitute the much higher dose retrospective scan modes for certain types of cardiac imaging. The beam filtration and beam shaper portion will discuss the variety of filtration and beam shaping configurations available on Philips scanners. This topic includes the x-ray beam characteristics, tube filtration as well as dose compensator characteristics. The Eclipse collimator, ClearRay collimator and the NanoPanel detector portion will discuss additional technologies specific to wide coverage CT that address some of the unique challenges encountered and techniques employed to optimize image quality and optimize dose utilization. The Eclipse collimator reduces extraneous exposure by actively blocking the radiation tails at either end of helical scans that do not contribute to the image generation. The ClearRay collimator and the NanoPanel detector optimize the quality of the signal that reaches the detectors by addressing the increased scattered radiation present in wide coverage and the NanoPanel detector adds superior electronic noise characteristics valuable when imaging at a low dose level. The second part of the talk will present “Advanced Reconstruction Technologies” currently available on Philips CT Scanners. The talk will cover filtered back projection (FBP), iDose4 and Iterative Model Reconstruction (IMR). Each reconstruction method will include a discussion of the algorithm as well as similarities and differences between the algorithms. Examples illustrating the merits of each algorithm will be presented, and techniques and metrics to characterize the performance of each type of algorithm will be presented. The Filtered Back projection portion will discuss and provide a brief summary of relevant standard image reconstruction techniques in common use, and discuss the common tradeoffs when using the FBP algorithm. The iDose4 portion will present the algorithms used for iDose4 as well the different levels. The meaning of different levels of iDose4 available will be presented and quantified. Guidelines for selection iDose4 parameters based on the imaging need will be explained. The different image quality goals available with iDose4 and specifically how iDose4 enables noise reduction, spatial resolution improvement or both will be explained. The approaches to leveraging the benefits of iDose4 such as improved spatial resolution, decreased noise, and artifact prevention will be described and quantified; and measurements and metrics behind the improvements will be presented. The image quality benefits in specific imaging situations as well as how to best combine the technology with other dose reduction strategies to ensure the best image quality at a given dose level will be presented. Insight into the IMR algorithm as well as contrast to the iDose4 techniques and performance characteristics will be discussed. Metrics and techniques for characterizing this class of algorithm and IQ performance will be presented. The image quality benefits and the dose reduction capabilities of IMR will be explored. Illustrative examples of the noise reduction, spatial resolution improvement, and low contrast detectability improvements of the reconstruction method will be presented: clinical cases and phantom measurements demonstrating the benefits of IMR in the areas of low dose imaging, spatial resolution and low contrast resolution are discussed and the technical details behind the measurements will be presented compared to both iDose4 and traditional filtered back projection (FBP)« less

Optimal radiotherapy dose schedules under parametric uncertainty

NASA Astrophysics Data System (ADS)

Badri, Hamidreza; Watanabe, Yoichi; Leder, Kevin

2016-01-01

We consider the effects of parameter uncertainty on the optimal radiation schedule in the context of the linear-quadratic model. Our interest arises from the observation that if inter-patient variability in normal and tumor tissue radiosensitivity or sparing factor of the organs-at-risk (OAR) are not accounted for during radiation scheduling, the performance of the therapy may be strongly degraded or the OAR may receive a substantially larger dose than the allowable threshold. This paper proposes a stochastic radiation scheduling concept to incorporate inter-patient variability into the scheduling optimization problem. Our method is based on a probabilistic approach, where the model parameters are given by a set of random variables. Our probabilistic formulation ensures that our constraints are satisfied with a given probability, and that our objective function achieves a desired level with a stated probability. We used a variable transformation to reduce the resulting optimization problem to two dimensions. We showed that the optimal solution lies on the boundary of the feasible region and we implemented a branch and bound algorithm to find the global optimal solution. We demonstrated how the configuration of optimal schedules in the presence of uncertainty compares to optimal schedules in the absence of uncertainty (conventional schedule). We observed that in order to protect against the possibility of the model parameters falling into a region where the conventional schedule is no longer feasible, it is required to avoid extremal solutions, i.e. a single large dose or very large total dose delivered over a long period. Finally, we performed numerical experiments in the setting of head and neck tumors including several normal tissues to reveal the effect of parameter uncertainty on optimal schedules and to evaluate the sensitivity of the solutions to the choice of key model parameters.

SU-F-T-497: Spatiotemporally Optimal, Personalized Prescription Scheme for Glioblastoma Patients Using the Proliferation and Invasion Glioma Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M; Rockhill, J; Phillips, M

Purpose: To investigate a spatiotemporally optimal radiotherapy prescription scheme and its potential benefit for glioblastoma (GBM) patients using the proliferation and invasion (PI) glioma model. Methods: Standard prescription for GBM was assumed to deliver 46Gy in 23 fractions to GTV1+2cm margin and additional 14Gy in 7 fractions to GTV2+2cm margin. We simulated the tumor proliferation and invasion in 2D according to the PI glioma model with a moving velocity of 0.029(slow-move), 0.079(average-move), and 0.13(fast-move) mm/day for GTV2 with a radius of 1 and 2cm. For each tumor, the margin around GTV1 and GTV2 was varied to 0–6 cm and 1–3more » cm respectively. Total dose to GTV1 was constrained such that the equivalent uniform dose (EUD) to normal brain equals EUD with the standard prescription. A non-stationary dose policy, where the fractional dose varies, was investigated to estimate the temporal effect of the radiation dose. The efficacy of an optimal prescription scheme was evaluated by tumor cell-surviving fraction (SF), EUD, and the expected survival time. Results: Optimal prescription for the slow-move tumors was to use 3.0(small)-3.5(large) cm margins to GTV1, and 1.5cm margin to GTV2. For the average- and fast-move tumors, it was optimal to use 6.0cm margin for GTV1 suggesting that whole brain therapy is optimal, and then 1.5cm (average-move) and 1.5–3.0cm (fast-move, small-large) margins for GTV2. It was optimal to deliver the boost sequentially using a linearly decreasing fractional dose for all tumors. Optimal prescription led to 0.001–0.465% of the tumor SF resulted from using the standard prescription, and increased tumor EUD by 25.3–49.3% and the estimated survival time by 7.6–22.2 months. Conclusion: It is feasible to optimize a prescription scheme depending on the individual tumor characteristics. A personalized prescription scheme could potentially increase tumor EUD and the expected survival time significantly without increasing EUD to normal brain.« less

Measurements on a full-field digital mammography system with a photon counting crystalline silicon detector

NASA Astrophysics Data System (ADS)

Lundqvist, Mats; Danielsson, Mats; Cederstroem, Bjoern; Chmill, Valery; Chuntonov, Alexander; Aslund, Magnus

2003-06-01

Sectra Microdose is the first single photon counting mammography detector. An edge-on crystalline silicon detector is connected to application specific integrated circuits that individually process each photon. The detector is scanned across the breast and the rejection of scattered radiation exceeds 97% without the use of a Bucky. Processing of each x-rays individually enables an optimization of the information transfer from the x-rays to the image in a way previously not possible. Combined with an almost absence of noise from scattered radiation and from electronics we foresee a possibility to reduce the radiation dose and/or increase the image quality. We will discuss fundamental features of the new direct photon counting technique in terms of dose efficiency and present preliminary measurements for a prototype on physical parameters such as Noise Power Spectra (NPS), MTF and DQE.

A technique for multi-dimensional optimization of radiation dose, contrast dose, and image quality in CT imaging

NASA Astrophysics Data System (ADS)

Sahbaee, Pooyan; Abadi, Ehsan; Sanders, Jeremiah; Becchetti, Marc; Zhang, Yakun; Agasthya, Greeshma; Segars, Paul; Samei, Ehsan

2016-03-01

The purpose of this study was to substantiate the interdependency of image quality, radiation dose, and contrast material dose in CT towards the patient-specific optimization of the imaging protocols. The study deployed two phantom platforms. First, a variable sized phantom containing an iodinated insert was imaged on a representative CT scanner at multiple CTDI values. The contrast and noise were measured from the reconstructed images for each phantom diameter. Linearly related to iodine-concentration, contrast to noise ratio (CNR), was calculated for different iodine-concentration levels. Second, the analysis was extended to a recently developed suit of 58 virtual human models (5D-XCAT) with added contrast dynamics. Emulating a contrast-enhanced abdominal image procedure and targeting a peak-enhancement in aorta, each XCAT phantom was "imaged" using a CT simulation platform. 3D surfaces for each patient/size established the relationship between iodine-concentration, dose, and CNR. The Sensitivity of Ratio (SR), defined as ratio of change in iodine-concentration versus dose to yield a constant change in CNR was calculated and compared at high and low radiation dose for both phantom platforms. The results show that sensitivity of CNR to iodine concentration is larger at high radiation dose (up to 73%). The SR results were highly affected by radiation dose metric; CTDI or organ dose. Furthermore, results showed that the presence of contrast material could have a profound impact on optimization results (up to 45%).

Dose Monitoring in Radiology Departments: Status Quo and Future Perspectives.

PubMed

Boos, J; Meineke, A; Bethge, O T; Antoch, G; Kröpil, P

2016-05-01

The number of computed tomography examinations has continuously increased over the last decades and accounts for a major part of the collective radiation dose from medical investigations. For purposes of quality assurance in modern radiology a systematic monitoring and analysis of dose related data from radiological examinations is mandatory. Various ways of collecting dose data are available today, for example the Digital Imaging and Communication in Medicine - Structured Report (DICOM-SR), optical character recognition and DICOM-modality performed procedure steps (MPPS). The DICOM-SR is part of the DICOM-standard and provides the DICOM-Radiation Dose Structured Report, which is an easily applicable and comprehensive solution to collect radiation dose parameters. This standard simplifies the process of data collection and enables comprehensive dose monitoring. Various commercial dose monitoring software devices with varying characteristics are available today. In this article, we discuss legal obligations, various ways to monitor dose data, current dose monitoring software solutions and future perspectives in regard to the EU Council Directive 2013/59/EURATOM. • Automated, systematic dose monitoring is an important element in quality assurance of radiology departments. • DICOM-RDSR-capable CT scanners facilitate the monitoring of dose data. • A variety of commercial and non-commercial dose monitoring software tools are available today. • Successful dose monitoring requires comprehensive infrastructure for monitoring, analysing and optimizing radiation exposure. Citation Format: • Boos J, Meineke A, Bethge OT et al. Dose Monitoring in Radiology Departments: Status Quo and Future Perspectives. Fortschr Röntgenstr 2016; 188: 443 - 450. © Georg Thieme Verlag KG Stuttgart · New York.

Accounting for range uncertainties in the optimization of intensity modulated proton therapy.

PubMed

Unkelbach, Jan; Chan, Timothy C Y; Bortfeld, Thomas

2007-05-21

Treatment plans optimized for intensity modulated proton therapy (IMPT) may be sensitive to range variations. The dose distribution may deteriorate substantially when the actual range of a pencil beam does not match the assumed range. We present two treatment planning concepts for IMPT which incorporate range uncertainties into the optimization. The first method is a probabilistic approach. The range of a pencil beam is assumed to be a random variable, which makes the delivered dose and the value of the objective function a random variable too. We then propose to optimize the expectation value of the objective function. The second approach is a robust formulation that applies methods developed in the field of robust linear programming. This approach optimizes the worst case dose distribution that may occur, assuming that the ranges of the pencil beams may vary within some interval. Both methods yield treatment plans that are considerably less sensitive to range variations compared to conventional treatment plans optimized without accounting for range uncertainties. In addition, both approaches--although conceptually different--yield very similar results on a qualitative level.

A rivastigmine patch for the treatment of Alzheimer's disease and Parkinson's disease dementia.

PubMed

Cummings, Jeffrey; Winblad, Bengt

2007-11-01

Rivastigmine patch is the first transdermal treatment to be approved for Alzheimer's disease (AD) and Parkinson's disease dementia in the USA and for AD in Europe. It provides smooth, continuous drug delivery, and has the potential to maintain rivastigmine concentrations within an optimal therapeutic window while avoiding the peaks and troughs associated with oral drug delivery. The target dose, rivastigmine 9.5 mg/24 h patch (a 10 cm(2) patch), is given once daily and requires a simple one-step dose titration to the therapeutic dose. In a 24-week study in 1195 AD patients, the rivastigmine 9.5 mg/24 h patch provided similar efficacy to the highest dose range of capsules, with approximately three-times fewer reports of nausea and vomiting. Patients in the 9.5 mg/24 h patch and 12 mg/day capsule groups evidenced significant improvements versus placebo on both primary outcome measures: the Alzheimer's Disease Assessment Scale-Cognitive subscale; and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change; in addition to the following secondary outcome measures: Alzheimer's Disease Cooperative Study-Activities of Daily Living scale; Mini-Mental State Examination; and Trail Making Test Part A for assessment of attention, visual tracking and motor processing speed. Treatment differences on the Neuropsychiatric Inventory and Ten Point Clock-drawing Test did not reach statistical significance in this study. The patch may be the optimal way to treat dementia patients with rivastigmine.

SU-E-T-424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eldib, A; Al-Azhar University Cairo; Jin, L

2014-06-01

Purpose: Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC). Methods: We have used the MCBEAM code for treatment head simulation and formore » generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in-house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations. Results: The eMLC allows effective treatment of scalps with multi-lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup. Conclusion: MERT can improve treatment plan quality for patients with scalp cancers. Our in-house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.« less

SU-C-17A-07: The Development of An MR Accelerator-Enabled Planning-To-Delivery Technique for Stereotactic Palliative Radiotherapy Treatment of Spinal Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoogcarspel, S J; Kontaxis, C; Velden, J M van der

2014-06-01

Purpose: To develop an MR accelerator-enabled online planning-todelivery technique for stereotactic palliative radiotherapy treatment of spinal metastases. The technical challenges include; automated stereotactic treatment planning, online MR-based dose calculation and MR guidance during treatment. Methods: Using the CT data of 20 patients previously treated at our institution, a class solution for automated treatment planning for spinal bone metastases was created. For accurate dose simulation right before treatment, we fused geometrically correct online MR data with pretreatment CT data of the target volume (TV). For target tracking during treatment, a dynamic T2-weighted TSE MR sequence was developed. An in house developedmore » GPU based IMRT optimization and dose calculation algorithm was used for fast treatment planning and simulation. An automatically generated treatment plan developed with this treatment planning system was irradiated on a clinical 6 MV linear accelerator and evaluated using a Delta4 dosimeter. Results: The automated treatment planning method yielded clinically viable plans for all patients. The MR-CT fusion based dose calculation accuracy was within 2% as compared to calculations performed with original CT data. The dynamic T2-weighted TSE MR Sequence was able to provide an update of the anatomical location of the TV every 10 seconds. Dose calculation and optimization of the automatically generated treatment plans using only one GPU took on average 8 minutes. The Delta4 measurement of the irradiated plan agreed with the dose calculation with a 3%/3mm gamma pass rate of 86.4%. Conclusions: The development of an MR accelerator-enabled planning-todelivery technique for stereotactic palliative radiotherapy treatment of spinal metastases was presented. Future work will involve developing an intrafraction motion adaptation strategy, MR-only dose calculation, radiotherapy quality-assurance in a magnetic field, and streamlining the entire treatment process on an MR accelerator.« less

SU-F-J-57: Effectiveness of Daily CT-Based Three-Dimensional Image Guided and Adaptive Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moriya, S; National Cancer Center, Kashiwa, Chiba; Tachibana, H

Purpose: Daily CT-based three-dimensional image-guided and adaptive (CTIGRT-ART) proton therapy system was designed and developed. We also evaluated the effectiveness of the CTIGRT-ART. Methods: Retrospective analysis was performed in three lung cancer patients: Proton treatment planning was performed using CT image datasets acquired by Toshiba Aquilion ONE. Planning target volume and surrounding organs were contoured by a well-trained radiation oncologist. Dose distribution was optimized using 180-deg. and 270-deg. two fields in passive scattering proton therapy. Well commissioned Simplified Monte Carlo algorithm was used as dose calculation engine. Daily consecutive CT image datasets was acquired by an in-room CT (Toshiba Aquilionmore » LB). In our in-house program, two image registrations for bone and tumor were performed to shift the isocenter using treatment CT image dataset. Subsequently, dose recalculation was performed after the shift of the isocenter. When the dose distribution after the tumor registration exhibits change of dosimetric parameter of CTV D90% compared to the initial plan, an additional process of was performed that the range shifter thickness was optimized. Dose distribution with CTV D90% for the bone registration, the tumor registration only and adaptive plan with the tumor registration was compared to the initial plan. Results: In the bone registration, tumor dose coverage was decreased by 16% on average (Maximum: 56%). The tumor registration shows better coverage than the bone registration, however the coverage was also decreased by 9% (Maximum: 22%) The adaptive plan shows similar dose coverage of the tumor (Average: 2%, Maximum: 7%). Conclusion: There is a high possibility that only image registration for bone and tumor may reduce tumor coverage. Thus, our proposed methodology of image guidance and adaptive planning using the range adaptation after tumor registration would be effective for proton therapy. This research is partially supported by Japan Agency for Medical Research and Development (AMED).« less

Fast online Monte Carlo-based IMRT planning for the MRI linear accelerator

NASA Astrophysics Data System (ADS)

Bol, G. H.; Hissoiny, S.; Lagendijk, J. J. W.; Raaymakers, B. W.

2012-03-01

The MRI accelerator, a combination of a 6 MV linear accelerator with a 1.5 T MRI, facilitates continuous patient anatomy updates regarding translations, rotations and deformations of targets and organs at risk. Accounting for these demands high speed, online intensity-modulated radiotherapy (IMRT) re-optimization. In this paper, a fast IMRT optimization system is described which combines a GPU-based Monte Carlo dose calculation engine for online beamlet generation and a fast inverse dose optimization algorithm. Tightly conformal IMRT plans are generated for four phantom cases and two clinical cases (cervix and kidney) in the presence of the magnetic fields of 0 and 1.5 T. We show that for the presented cases the beamlet generation and optimization routines are fast enough for online IMRT planning. Furthermore, there is no influence of the magnetic field on plan quality and complexity, and equal optimization constraints at 0 and 1.5 T lead to almost identical dose distributions.

Automatic treatment planning facilitates fast generation of high-quality treatment plans for esophageal cancer.

PubMed

Hansen, Christian Rønn; Nielsen, Morten; Bertelsen, Anders Smedegaard; Hazell, Irene; Holtved, Eva; Zukauskaite, Ruta; Bjerregaard, Jon Kroll; Brink, Carsten; Bernchou, Uffe

2017-11-01

The quality of radiotherapy planning has improved substantially in the last decade with the introduction of intensity modulated radiotherapy. The purpose of this study was to analyze the plan quality and efficacy of automatically (AU) generated VMAT plans for inoperable esophageal cancer patients. Thirty-two consecutive inoperable patients with esophageal cancer originally treated with manually (MA) generated volumetric modulated arc therapy (VMAT) plans were retrospectively replanned using an auto-planning engine. All plans were optimized with one full 6MV VMAT arc giving 60 Gy to the primary target and 50 Gy to the elective target. The planning techniques were blinded before clinical evaluation by three specialized oncologists. To supplement the clinical evaluation, the optimization time for the AU plan was recorded along with DVH parameters for all plans. Upon clinical evaluation, the AU plan was preferred for 31/32 patients, and for one patient, there was no difference in the plans. In terms of DVH parameters, similar target coverage was obtained between the two planning methods. The mean dose for the spinal cord increased by 1.8 Gy using AU (p = .002), whereas the mean lung dose decreased by 1.9 Gy (p < .001). The AU plans were more modulated as seen by the increase of 12% in mean MUs (p = .001). The median optimization time for AU plans was 117 min. The AU plans were in general preferred and showed a lower mean dose to the lungs. The automation of the planning process generated esophageal cancer treatment plans quickly and with high quality.

American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy.

PubMed

Hepel, Jaroslaw T; Arthur, Douglas; Shaitelman, Simona; Polgár, Csaba; Todor, Dorin; Zoberi, Imran; Kamrava, Mitchell; Major, Tibor; Yashar, Catheryn; Wazer, David E

To develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB). The American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel. Randomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6-0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to <60%, skin dose to ≤100% of prescription dose (≤60-70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to >0.75 (>0.85 preferred), V 150  < 45 cc, and V 200  < 14 cc. Using an optimal implant technique coupled with optimal planning and appropriate dose constraints, a low rate of toxicity and a good-to-excellent cosmetic outcome of ≥90% is expected. IMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB

PubMed Central

Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne

2017-01-01

Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended. PMID:28644875

Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

PubMed

Taylor, Olivia; Van Laeken, Nick; Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne

2017-01-01

Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

ON THE PROBLEM OF THE OPTIMAL DOSE IN THE RADIOTHERAPY OF NONMALIGNANT DISEASES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pape, R.

1961-01-01

Dosage for the treatment of benign conditions is considered from the viewpoint of 15 yr experience with 2514 patients. It was judged that doses of 1 to 20 r are optimal for treatment of inflammatory and degenerative joint diseases, although many authors call for 30- to 50-r single doses for these conditions. Equally good subjective results were obtained in arthritis and spondylitis cases with the lower doses, but suggestion plays a large role in improvement following radiotherapy. For juvenile mastitis, surface doses of 10 to 12 r, giving depth doses of approximates 1 r at 5 cm, are recommended. Somemore » estimates were made of gonadal doses encountered in various types of nonabdominal radiotherapy. For example, 10-r doses of 90-kv x rays given in the axillary region result in ovarian doses of 0.2 mr. The effect of radiation on the brain and other neural structures is discussed. (H.H.D.)« less

A fast - Monte Carlo toolkit on GPU for treatment plan dose recalculation in proton therapy

NASA Astrophysics Data System (ADS)

Senzacqua, M.; Schiavi, A.; Patera, V.; Pioli, S.; Battistoni, G.; Ciocca, M.; Mairani, A.; Magro, G.; Molinelli, S.

2017-10-01

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement.

A systematic study of posterior cervical lymph node irradiation with electrons: Conventional versus customized planning.

PubMed

Jankowska, Petra J; Kong, Christine; Burke, Kevin; Harrington, Kevin J; Nutting, Christopher

2007-10-01

High dose irradiation of the posterior cervical lymph nodes usually employs applied electron fields to treat the target volume and maintain the spinal cord dose within tolerance. In the light of recent advances in elective lymph node localisation we investigated optimization of field shape and electron energy to treat this target volume. In this study, three sequential hypotheses were tested. Firstly, that customization of the electron fields based on the nodal PTV outlined gives better PTV coverage than conventional field delineation. Using the consensus guidelines, customization of the electron field shape was compared to conventional fields based on bony landmarks. Secondly, that selection of electron energy using DVHs for spinal cord and PTV improves the minimum dose to PTV. Electron dose-volume histograms (DVHs) for the PTV, spinal cord and para-vertebral muscles, were generated using the Monte Carlo electron algorithm. These DVHs were used to compare standard vs optimized electron energy calculations. Finally, that combination of field customization and electron energy optimization improves both the minimum and mean doses to PTV compared with current standard practice. Customized electron beam shaping based on the consensus guidelines led to fewer geographical misses than standard field shaping. Customized electron energy calculation led to higher minimum doses to the PTV. Overall, the customization of field shape and energy resulted in an improved mean dose to the PTV (92% vs 83% p=0.02) and a 27% improvement in the minimum dose delivered to the PTV (45% vs 18% p=0.0009). Optimization of electron field shape and beam energy based on current consensus guidelines led to significant improvement in PTV coverage and may reduce recurrence rates.

SU-E-T-531: Performance Evaluation of Multithreaded Geant4 for Proton Therapy Dose Calculations in a High Performance Computing Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, J; Coss, D; McMurry, J

Purpose: To evaluate the efficiency of multithreaded Geant4 (Geant4-MT, version 10.0) for proton Monte Carlo dose calculations using a high performance computing facility. Methods: Geant4-MT was used to calculate 3D dose distributions in 1×1×1 mm3 voxels in a water phantom and patient's head with a 150 MeV proton beam covering approximately 5×5 cm2 in the water phantom. Three timestamps were measured on the fly to separately analyze the required time for initialization (which cannot be parallelized), processing time of individual threads, and completion time. Scalability of averaged processing time per thread was calculated as a function of thread number (1,more » 100, 150, and 200) for both 1M and 50 M histories. The total memory usage was recorded. Results: Simulations with 50 M histories were fastest with 100 threads, taking approximately 1.3 hours and 6 hours for the water phantom and the CT data, respectively with better than 1.0 % statistical uncertainty. The calculations show 1/N scalability in the event loops for both cases. The gains from parallel calculations started to decrease with 150 threads. The memory usage increases linearly with number of threads. No critical failures were observed during the simulations. Conclusion: Multithreading in Geant4-MT decreased simulation time in proton dose distribution calculations by a factor of 64 and 54 at a near optimal 100 threads for water phantom and patient's data respectively. Further simulations will be done to determine the efficiency at the optimal thread number. Considering the trend of computer architecture development, utilizing Geant4-MT for radiotherapy simulations is an excellent cost-effective alternative for a distributed batch queuing system. However, because the scalability depends highly on simulation details, i.e., the ratio of the processing time of one event versus waiting time to access for the shared event queue, a performance evaluation as described is recommended.« less

TH-A-19A-04: Latent Uncertainties and Performance of a GPU-Implemented Pre-Calculated Track Monte Carlo Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renaud, M; Seuntjens, J; Roberge, D

Purpose: Assessing the performance and uncertainty of a pre-calculated Monte Carlo (PMC) algorithm for proton and electron transport running on graphics processing units (GPU). While PMC methods have been described in the past, an explicit quantification of the latent uncertainty arising from recycling a limited number of tracks in the pre-generated track bank is missing from the literature. With a proper uncertainty analysis, an optimal pre-generated track bank size can be selected for a desired dose calculation uncertainty. Methods: Particle tracks were pre-generated for electrons and protons using EGSnrc and GEANT4, respectively. The PMC algorithm for track transport was implementedmore » on the CUDA programming framework. GPU-PMC dose distributions were compared to benchmark dose distributions simulated using general-purpose MC codes in the same conditions. A latent uncertainty analysis was performed by comparing GPUPMC dose values to a “ground truth” benchmark while varying the track bank size and primary particle histories. Results: GPU-PMC dose distributions and benchmark doses were within 1% of each other in voxels with dose greater than 50% of Dmax. In proton calculations, a submillimeter distance-to-agreement error was observed at the Bragg Peak. Latent uncertainty followed a Poisson distribution with the number of tracks per energy (TPE) and a track bank of 20,000 TPE produced a latent uncertainty of approximately 1%. Efficiency analysis showed a 937× and 508× gain over a single processor core running DOSXYZnrc for 16 MeV electrons in water and bone, respectively. Conclusion: The GPU-PMC method can calculate dose distributions for electrons and protons to a statistical uncertainty below 1%. The track bank size necessary to achieve an optimal efficiency can be tuned based on the desired uncertainty. Coupled with a model to calculate dose contributions from uncharged particles, GPU-PMC is a candidate for inverse planning of modulated electron radiotherapy and scanned proton beams. This work was supported in part by FRSQ-MSSS (Grant No. 22090), NSERC RG (Grant No. 432290) and CIHR MOP (Grant No. MOP-211360)« less

Minimum number of spermatozoa per dose in Mediterranean Italian buffalo (Bubalus bubalis) using sexed frozen semen and conventional artificial insemination.

PubMed

Gaviraghi, A; Puglisi, R; Balduzzi, D; Severgnini, A; Bornaghi, V; Bongioni, G; Frana, A; Gandini, L M; Lukaj, A; Bonacina, C; Galli, A

2013-05-01

In buffaloes, AI with sexed semen is not fully optimized, and the procedure has only been performed using the approach currently in use for cattle. The objective of the present work was to compare the pregnancy rates in Mediterranean Italian buffalo cows inseminated with sexed frozen-thawed semen at 2, 4, 6, and 8 million sperm per dose, using the Ovsynch protocol and conventional AI at a fixed time. Fresh ejaculates from three buffalo bulls were processed according to Beltsville sperm sorting technology, and packaged in 0.25-mL straws with two total concentrations of 2 and 4 million live sorted sperm per straw. After thawing, semen was evaluated for total motility, forward motility, average path velocity, membrane and DNA integrity, and membrane fluidity. Sorting efficiency was estimated using a real time polymerase chain reaction method developed and validated in our laboratory. The artificial inseminations were conducted during the breeding season on 849 Italian Mediterranean buffalo heifers and cows distributed in 13 farms in northern and central Italy. No significant difference in quality parameters was reported between nonsexed and sexed straws produced with 2 and 4 million sperm. Lower pregnancy rate (P < 0.001) was reported when inseminating doses of sexed semen at 2 million were used (53/170; 31.2%), with respect to conventional nonsexed (78/142; 54.9%), and sexed doses at 4, 6, and 8 million spermatozoa (102/205, 49.8%; 84/175, 48.0%; and 74/157, 47.1%, respectively). No differences were evident using conventional doses and sexed semen with sperm numbers equal or higher than 4 million per dose. Pregnancies were not affected by the sire; 39/82 (47.6%), 120/270 (44.4%), and 151/355 (42.5%), respectively, for the three bulls. Variability in pregnancy rates observed in different herds was not significant. Furthermore, no significant difference was reported between pregnancies obtained with sexed semen in heifers and multiparous, respectively, 179/407 (44.0%) and 131/300 (43.7%). The results of the present work indicate that in Mediterranean Italian buffalo the dose of 4 million represents an optimal compromise when using sexed semen with conventional technologies of insemination, together with estrus synchronization, and the minimum number of spermatozoa per dose. In addition, the real time polymerase chain reaction method was optimized and is now available for estimating sorting efficiency in buffalo. Copyright © 2013 Elsevier Inc. All rights reserved.

Initial results of the use of prescription order change forms to achieve dose form optimization (consolidation and tablet splitting) of SSRI antidepressants in a state Medicaid program.

PubMed

Hamer, Ann M; Hartung, Daniel M; Haxby, Dean G; Ketchum, Kathy L; Pollack, David A

2006-01-01

One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule. To determine if voluntary prescription change forms for antidepressant drugs could induce dosing changes and reduce the cost of antidepressant therapy in a Medicaid population. Specific regimens of 4 selective serotonin reuptake inhibitors (SSRIs)- citalopram, escitalopram, paroxetine, and sertraline- were identified for conversion to half tablets or dose optimization. Change forms, which served as valid prescriptions, were faxed to Oregon prescribers in October 2004. The results from both the returned forms and subsequent drug claims data were evaluated using a segmented linear regression. Citalopram claims were excluded from the cost analysis because the drug became available in generic form in October 2004. A total of 1,582 change forms were sent to 556 unique prescribers; 9.2% of the change forms were for dose consolidation and 90.8% were for tablet splitting. Of the 1,118 change forms (70.7%) that were returned, 956 (60.4% of those sent and 85.5% of those returned) authorized a prescription change to a lower-cost dose regimen. The average drug cost per day declined by 14.2%, from Dollars 2.26 to Dollars 1.94 in the intervention group, versus a 1.6% increase, from Dollars 2.52 to Dollars 2.56, in the group without dose consolidation or tablet splitting of the 3 SSRIs (sertraline, escitalopram, and immediate-release paroxetine). Total drug cost for the 3 SSRIs declined by 35.6%, from Dollars 333,567 to Dollars 214,794, as a result of a 24.8% decline in the total days of SSRI drug therapy and the 14.2% decline in average SSRI drug cost per day. The estimated monthly cost avoidance from this intervention, based on pharmacy claims data, was approximately Dollars 35,285, about 2% of the entire spending on SSRI drugs each month, or about Dollars 0.09 per member per month. Program administration costs, excluding costs incurred by prescribers and pharmacy providers, were about 2% of SSRI drug cost savings. Voluntary prescription change forms appear to be an effective and well-accepted tool for obtaining dose form optimization through dose form consolidation and tablet splitting, resulting in reduction in the direct costs of SSRI antidepressant drug therapy with minimal additional program administration costs.

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dogan, N; Padgett, K; Evans, J

Purpose: Adaptive Radiotherapy (ART) with frequent CT imaging has been used to improve dosimetric accuracy by accounting for anatomical variations, such as primary tumor shrinkage and/or body weight loss, in Head and Neck (H&N) patients. In most ART strategies, the difference between the planned and the delivered dose is estimated by generating new plans on repeated CT scans using dose-volume constraints used with the initial planning CT without considering already delivered dose. The aim of this study was to assess the dosimetric gains achieved by re-planning based on prior dose by comparing them to re-planning not based-on prior dose formore » H&N patients. Methods: Ten locally-advanced H&N cancer patients were selected for this study. For each patient, six weekly CT imaging were acquired during the course of radiotherapy. PTVs, parotids, cord, brainstem, and esophagus were contoured on both planning and six weekly CT images. ART with weekly re-plans were done by two strategies: 1) Generating a new optimized IMRT plan without including prior dose from previous fractions (NoPriorDose) and 2) Generating a new optimized IMRT plan based on the prior dose given from previous fractions (PriorDose). Deformable image registration was used to accumulate the dose distributions between planning and six weekly CT scans. The differences in accumulated doses for both strategies were evaluated using the DVH constraints for all structures. Results: On average, the differences in accumulated doses for PTV1, PTV2 and PTV3 for NoPriorDose and PriorDose strategies were <2%. The differences in Dmean to the cord and brainstem were within 3%. The esophagus Dmean was reduced by 2% using PriorDose. PriorDose strategy, however, reduced the left parotid D50 and Dmean by 15% and 14% respectively. Conclusion: This study demonstrated significant parotid sparing, potentially reducing xerostomia, by using ART with IMRT optimization based on prior dose for weekly re-planning of H&N cancer patients.« less

Dose-response relationship in the treatment of gastrointestinal disorders.

PubMed

Weihrauch, T R; Demol, P

1989-08-01

Numerous clinical studies have been performed to establish efficacy and safety of drugs in gastroenterological disorders. Only in a few if any of these studies, however, the rationale for the optimal dose and the dose regimens, respectively, have been addressed. Adequate and well-controlled dose finding studies play a key role in the clinical assessment of new drugs and in the evaluation of new indications. Hereby the range from the minimal effective dose to the maximal effective and well tolerated dose can be assessed and thus the optimal dose-range and dosage regimen be determined. Meaningful pharmacodynamic studies can be performed in the gastrointestinal tract also in healthy volunteers provided that a method with a high predictability for the desired therapeutic effect is available such as measurement of gastric acid secretion and its inhibition by a drug. Dose finding studies in gastroenterology can be carried out under two main aspects: First, to assess the pharmacodynamic and therapeutic effect of a compound on the gastrointestinal tract (e.g. anti-ulcer drug). Second, to evaluate the side effects of a drug on the gastrointestinal tract (e.g. gastric mucosal damage by non-steroidal anti-inflammatory drugs). For the evaluation of new drugs in gastrointestinal therapy a number of methods are available which yield accurate and reproducible data. While careful clinical-pharmacological dose-response studies using these methods have been carried out already more than a decade ago, it is surprising that therapeutic dose finding studies have become available only during the past few years. For scientific as well as for ethical reasons more trials which determine the optimal therapeutic dose are warranted.

The Optimal Dose of Nicardipine for Enhancement of Indirect Portography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Yutaka; Nakamura, Hironobu; Akaji, Hideyo

1998-01-15

Purpose: To determine the optimal dose of nicardipine (NCR) for enhancement of indirect portography. Methods: Forty-eight patients underwent conventional film indirect portography via the superior mesenteric artery (SMA) first without and then with preinjection of 1/64-2 mg of NCR into the SMA. Results: NCR (1/8-2 mg) shortened the arterial phase to 50% and the portal appearance time to 60% of control without reflux of contrast medium into the aorta. Portal enhancement was excellent at doses of 1/32 mg or more. Blood pressures and pulse rate showed no significant change at 1/4 mg or less. Conclusion: NCR (1/8-1/4 mg) into themore » SMA is the optimal dose for achieving sufficient contrast enhancement on indirect portography while reducing the transit time of contrast medium and minimizing effects on the systemic circulation.« less

Application of the method of steepest descent to laminated shield weight optimization with several constraints: Theory

NASA Technical Reports Server (NTRS)

Lahti, G. P.

1971-01-01

The method of steepest descent used in optimizing one-dimensional layered radiation shields is extended to multidimensional, multiconstraint situations. The multidimensional optimization algorithm and equations are developed for the case of a dose constraint in any one direction being dependent only on the shield thicknesses in that direction and independent of shield thicknesses in other directions. Expressions are derived for one-, two-, and three-dimensional cases (one, two, and three constraints). The precedure is applicable to the optimization of shields where there are different dose constraints and layering arrangements in the principal directions.

Switching from oral extended-release methylphenidate to the methylphenidate transdermal system: continued ADHD symptom control and tolerability after abrupt conversion

PubMed Central

Arnold, L. E.; Hodgkins, P.; McKay, M.; Beckett-Thurman, L.; Greenbaum, M.; Bukstein, O.; Patel, A.; Bozzolo, D. R.

2013-01-01

Objective To evaluate symptom control and tolerability after abrupt conversion from oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD). Methods In a 4-week, prospective, multisite, open-label study, 171 children (164 intent-to-treat) with diagnosed ADHD aged 6–12 years abruptly switched from a stable dose of oral ER-MPH to MTS in nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. After the first week on the scheduled dose, the dose was titrated to optimal effect. The primary effectiveness outcome was the change from baseline (while taking ER-MPH) to week 4 in ADHD-Rating Scale-IV (ADHD-RS-IV) total scores. Adverse events (AEs) were assessed throughout the study. Results Most subjects (58%) remained on the initial MTS dose defined by the dose-transition schedule; 38% increased and 4% decreased their MTS dose for optimization. MTS dose optimization resulted in significantly better ADHD-RS-IV total (mean ± SD) scores at week 4 than at baseline (9.9±7.47 vs 14.1±7.48; p<0.0001). The most commonly reported AEs included headache, decreased appetite, insomnia, and upper abdominal pain. Four subjects (2.3%) discontinued because of application site reactions and 3 discontinued because of other AEs. Conclusions Abrupt conversion from a stable dose of oral ER-MPH to MTS was accomplished using a predefined dose-transition schedule without loss of symptom control; however, careful titration to optimal dose is recommended. Most AEs were mild to moderate and, with the exception of application site reactions, were similar to AEs typically observed with oral MPH. Limitations of this study included its open-label sequential design without placebo, which could result in spurious attribution of improvement to the study treatment and precluded superiority determinations of MTS over baseline ER-MPH treatment. The apparent superiority of MTS was likely due to more careful titration and clinical monitoring rather than the product itself. NCT NCT00151983 PMID:19916704

Impact of electronic health record-based, pharmacist-driven valganciclovir dose optimization in solid organ transplant recipients.

PubMed

Hensler, David; Richardson, Chad L; Brown, Joslyn; Tseng, Christine; DeCamp, Phyllis J; Yang, Amy; Pawlowski, Anna; Ho, Bing; Ison, Michael G

2018-04-01

Prophylaxis with valganciclovir reduces the incidence of cytomegalovirus (CMV) infection following solid organ transplant (SOT). Under-dosing of valganciclovir is associated with an increased risk of CMV infection and development of ganciclovir-resistant CMV. An automated electronic health record (EHR)-based, pharmacist-driven program was developed to optimize dosing of valganciclovir in solid organ transplant recipients at a large transplant center. Two cohorts of kidney, pancreas-kidney, and liver transplant recipients from our center pre-implementation (April 2011-March 2012, n = 303) and post-implementation of the optimization program (September 2012-August 2013, n=263) had demographic and key outcomes data collected for 1 year post-transplant. The 1-year incidence of CMV infection dropped from 56 (18.5%) to 32 (12.2%, P = .05) and the incidence of breakthrough infections on prophylaxis was cut in half (61% vs 34%, P = .03) after implementation of the dose optimization program. The hazard ratio of developing CMV was 1.64 (95% CI 1.06-2.60, P = .027) for the pre-implementation group after adjusting for potential confounders. The program also resulted in a numerical reduction in the number of ganciclovir-resistant CMV cases (2 [0.7%] pre-implementation vs 0 post-implementation). An EHR-based, pharmacist-driven valganciclovir dose optimization program was associated with reduction in CMV infections. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Optimization of Catheter Based rtPA Thrombolysis in a Novel In Vitro Clot Model for Intracerebral Hemorrhage

PubMed Central

Masomi-Bornwasser, Julia; Müller-Werkmeister, Hendrik; Kantelhardt, Sven Rainer; König, Jochem; Kempski, Oliver; Giese, Alf

2017-01-01

Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH). Optimal dose and schedule are still unclear. The aim of this study was to create a reliable in vitro blood clot model for investigation of optimal drug dose and timing. An in vitro clot model was established, using 25 mL and 50 mL of human blood. Catheters were placed into the clots and three groups, using intraclot application of rtPA, placebo, and catheter alone, were analyzed. Dose-response relationship, repetition, and duration of rtPA treatment and its effectiveness in aged clots were investigated. A significant relative end weight difference was found in rtPA treated clots compared to catheter alone (p = 0.002) and placebo treated clots (p < 0.001). Dose-response analysis revealed 95% effective dose around 1 mg rtPA in 25 and 50 mL clots. Approximately 80% of relative clot lysis could be achieved after 15 min incubation. Lysis of aged clots was less effective. A new clot model for in vitro investigation was established. Our data suggest that current protocols for rtPA based ICH therapy may be optimized by using less rtPA at shorter incubation times. PMID:28459065

Optimization of Catheter Based rtPA Thrombolysis in a Novel In Vitro Clot Model for Intracerebral Hemorrhage.

PubMed

Keric, Naureen; Masomi-Bornwasser, Julia; Müller-Werkmeister, Hendrik; Kantelhardt, Sven Rainer; König, Jochem; Kempski, Oliver; Giese, Alf

2017-01-01

Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH). Optimal dose and schedule are still unclear. The aim of this study was to create a reliable in vitro blood clot model for investigation of optimal drug dose and timing. An in vitro clot model was established, using 25 mL and 50 mL of human blood. Catheters were placed into the clots and three groups, using intraclot application of rtPA, placebo, and catheter alone, were analyzed. Dose-response relationship, repetition, and duration of rtPA treatment and its effectiveness in aged clots were investigated. A significant relative end weight difference was found in rtPA treated clots compared to catheter alone ( p = 0.002) and placebo treated clots ( p < 0.001). Dose-response analysis revealed 95% effective dose around 1 mg rtPA in 25 and 50 mL clots. Approximately 80% of relative clot lysis could be achieved after 15 min incubation. Lysis of aged clots was less effective. A new clot model for in vitro investigation was established. Our data suggest that current protocols for rtPA based ICH therapy may be optimized by using less rtPA at shorter incubation times.

A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning.

PubMed

Zhang, H H; Gao, S; Chen, W; Shi, L; D'Souza, W D; Meyer, R R

2013-03-21

An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equallyspaced beams (eplans), we have developed a global search metaheuristic process based on the nested partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are of superior quality.

A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning

PubMed Central

Zhang, H H; Gao, S; Chen, W; Shi, L; D’Souza, W D; Meyer, R R

2013-01-01

An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equally-spaced beams (eplans), we have developed a global search metaheuristic process based on the Nested Partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are superior quality. PMID:23459411

Minimizing metastatic risk in radiotherapy fractionation schedules

NASA Astrophysics Data System (ADS)

Badri, Hamidreza; Ramakrishnan, Jagdish; Leder, Kevin

2015-11-01

Metastasis is the process by which cells from a primary tumor disperse and form new tumors at distant anatomical locations. The treatment and prevention of metastatic cancer remains an extremely challenging problem. This work introduces a novel biologically motivated objective function to the radiation optimization community that takes into account metastatic risk instead of the status of the primary tumor. In this work, we consider the problem of developing fractionated irradiation schedules that minimize production of metastatic cancer cells while keeping normal tissue damage below an acceptable level. A dynamic programming framework is utilized to determine the optimal fractionation scheme. We evaluated our approach on a breast cancer case using the heart and the lung as organs-at-risk (OAR). For small tumor α /β values, hypo-fractionated schedules were optimal, which is consistent with standard models. However, for relatively larger α /β values, we found the type of schedule depended on various parameters such as the time when metastatic risk was evaluated, the α /β values of the OARs, and the normal tissue sparing factors. Interestingly, in contrast to standard models, hypo-fractionated and semi-hypo-fractionated schedules (large initial doses with doses tapering off with time) were suggested even with large tumor α/β values. Numerical results indicate the potential for significant reduction in metastatic risk.

Uncertainty reduction in intensity modulated proton therapy by inverse Monte Carlo treatment planning

NASA Astrophysics Data System (ADS)

Morávek, Zdenek; Rickhey, Mark; Hartmann, Matthias; Bogner, Ludwig

2009-08-01

Treatment plans for intensity-modulated proton therapy may be sensitive to some sources of uncertainty. One source is correlated with approximations of the algorithms applied in the treatment planning system and another one depends on how robust the optimization is with regard to intra-fractional tissue movements. The irradiated dose distribution may substantially deteriorate from the planning when systematic errors occur in the dose algorithm. This can influence proton ranges and lead to improper modeling of the Braggpeak degradation in heterogeneous structures or particle scatter or the nuclear interaction part. Additionally, systematic errors influence the optimization process, which leads to the convergence error. Uncertainties with regard to organ movements are related to the robustness of a chosen beam setup to tissue movements on irradiation. We present the inverse Monte Carlo treatment planning system IKO for protons (IKO-P), which tries to minimize the errors described above to a large extent. Additionally, robust planning is introduced by beam angle optimization according to an objective function penalizing paths representing strongly longitudinal and transversal tissue heterogeneities. The same score function is applied to optimize spot planning by the selection of a robust choice of spots. As spots can be positioned on different energy grids or on geometric grids with different space filling factors, a variety of grids were used to investigate the influence on the spot-weight distribution as a result of optimization. A tighter distribution of spot weights was assumed to result in a more robust plan with respect to movements. IKO-P is described in detail and demonstrated on a test case and a lung cancer case as well. Different options of spot planning and grid types are evaluated, yielding a superior plan quality with dose delivery to the spots from all beam directions over optimized beam directions. This option shows a tighter spot-weight distribution and should therefore be less sensitive to movements compared to optimized directions. But accepting a slight loss in plan quality, the latter choice could potentially improve robustness even further by accepting only spots from the most proper direction. The choice of a geometric grid instead of an energy grid for spot positioning has only a minor influence on the plan quality, at least for the investigated lung case.

Transferring Patients From Methadone to Buprenorphine: The Feasibility and Evaluation of Practice Guidelines.

PubMed

Lintzeris, Nicholas; Monds, Lauren A; Rivas, Consuelo; Leung, Stefanie; Dunlop, Adrian; Newcombe, David; Walters, Carina; Galea, Susanna; White, Nancy; Montebello, Mark; Demirkol, Apo; Swanson, Nicola; Ali, Robert

Transfer from methadone to buprenorphine is problematic for many opioid-dependent patients, with limited documented evidence or practical clinical guidance, particularly for the range of methadone doses routinely prescribed for most patients (>50 mg). This study aimed to implement and evaluate recent national Australian guidelines for transferring patients from methadone to buprenorphine. A multisite prospective cohort study. Participants were patients who transferred from methadone to buprenorphine-naloxone at 1 of 4 specialist addiction centers in Australia and New Zealand. Clinicians were trained in the guidelines, and medical records were reviewed to examine process (eg, transfer setting, doses, and guideline adherence) and safety (precipitated withdrawal) measures. Participants completed research interviews before and after transfer-assessing changes in substance use, health outcomes, and side effects. In all, 33 participants underwent transfer, 9 from low methadone doses (<30 mg), 9 from medium doses (30-50 mg), and 15 from high doses (>50 mg). The majority of high-dose transfers occurred in inpatient settings. There was reasonable guideline adherence, and no complications identified in the low and medium-dose transfers. Three high-dose transfers (20%) experienced precipitated withdrawal, and 7/33 participants (21%) returned to methadone within 1 week of attempted transfer. Transfer is feasible in outpatient settings for those transferring from methadone doses below 50 mg; however, inpatient settings and specialist supervision is recommended for higher-dose transfers. The Australian clinical guidelines appear safe and feasible, although further research is required to optimize high-dose transfer procedures.

SU-E-J-193: Feasibility of MRI-Only Based IMRT Planning for Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prior, P; Botros, M; Chen, X

2014-06-01

Purpose: With the increasing use of MRI simulation and the advent of MRI-guided delivery, it is desirable to use MRI only for treatment planning. In this study, we assess the dosimetric difference between MRI- and CTbased IMRT planning for pancreatic cancer. Methods: Planning CTs and MRIs acquired for a representative pancreatic cancer patient were used. MRI-based planning utilized forced relative electron density (rED) assignment of organ specific values from IRCU report 46, where rED = 1.029 for PTV and a rED = 1.036 for non-specified tissue (NST). Six IMRT plans were generated with clinical dose-volume (DV) constraints using a researchmore » Monaco planning system employing Monte Carlo dose calculation with optional perpendicular magnetic field (MF) of 1.5T. The following five plans were generated and compared with the planning CT: 1.) CT plan with MF and dose recalculation without optimization; 2.) MRI (T2) plan with target and OARs redrawn based on MRI, forced rED, no MF, and recalculation without optimization; 3.) Similar as in 2 but with MF; 4.) MRI plan with MF but without optimization; and 5.) Similar as in 4 but with optimization. Results: Generally, noticeable differences in PTV point doses and DV parameters (DVPs) between the CT-and MRI-based plans with and without the MF were observed. These differences between the optimized plans were generally small, mostly within 2%. Larger differences were observed in point doses and mean doses for certain OARs between the CT and MRI plan, mostly due to differences between image acquisition times. Conclusion: MRI only based IMRT planning for pancreatic cancer is feasible. The differences observed between the optimized CT and MRI plans with or without the MF were practically negligible if excluding the differences between MRI and CT defined structures.« less

Population Pharmacokinetics and Optimal Sampling Strategy for Model-Based Precision Dosing of Melphalan in Patients Undergoing Hematopoietic Stem Cell Transplantation.

PubMed

Mizuno, Kana; Dong, Min; Fukuda, Tsuyoshi; Chandra, Sharat; Mehta, Parinda A; McConnell, Scott; Anaissie, Elias J; Vinks, Alexander A

2018-05-01

High-dose melphalan is an important component of conditioning regimens for patients undergoing hematopoietic stem cell transplantation. The current dosing strategy based on body surface area results in a high incidence of oral mucositis and gastrointestinal and liver toxicity. Pharmacokinetically guided dosing will individualize exposure and help minimize overexposure-related toxicity. The purpose of this study was to develop a population pharmacokinetic model and optimal sampling strategy. A population pharmacokinetic model was developed with NONMEM using 98 observations collected from 15 adult patients given the standard dose of 140 or 200 mg/m 2 by intravenous infusion. The determinant-optimal sampling strategy was explored with PopED software. Individual area under the curve estimates were generated by Bayesian estimation using full and the proposed sparse sampling data. The predictive performance of the optimal sampling strategy was evaluated based on bias and precision estimates. The feasibility of the optimal sampling strategy was tested using pharmacokinetic data from five pediatric patients. A two-compartment model best described the data. The final model included body weight and creatinine clearance as predictors of clearance. The determinant-optimal sampling strategies (and windows) were identified at 0.08 (0.08-0.19), 0.61 (0.33-0.90), 2.0 (1.3-2.7), and 4.0 (3.6-4.0) h post-infusion. An excellent correlation was observed between area under the curve estimates obtained with the full and the proposed four-sample strategy (R 2  = 0.98; p < 0.01) with a mean bias of -2.2% and precision of 9.4%. A similar relationship was observed in children (R 2  = 0.99; p < 0.01). The developed pharmacokinetic model-based sparse sampling strategy promises to achieve the target area under the curve as part of precision dosing.

A novel applicator design for intracavitary brachytherapy of the nasopharynx: Simulated reconstruction, image-guided adaptive brachytherapy planning, and dosimetry.

PubMed

Bacorro, Warren R; Agas, Ryan Anthony F; Cabrera, Stellar Marie R; Bojador, Maureen R; Sogono, Paolo G; Mejia, Michael Benedict A; Sy Ortin, Teresa T

2018-05-11

In nasopharyngeal cancer, brachytherapy is given as boost in primary treatment or as salvage for recurrent or persistent disease. The Rotterdam nasopharyngeal applicator (RNA) allows for suboptimal reduction of soft palate radiation dose, based on image-guided brachytherapy plans. Building on the RNA, we propose a novel design, the Benavides nasopharyngeal applicator (BNA). The virtual BNA was reconstructed on two cases (one T1, one T2) previously treated with intracavitary brachytherapy using the RNA. Dose was prescribed to the high-risk clinical target volumes (CTVs) and optimization was such that high-risk CTV D90 ≥ 100% of prescribed dose (PD), intermediate-risk-CTV D90 ≥ 75% PD, and soft palate D2cc ≤ 120% PD. The optimized RNA and BNA image-guided brachytherapy plans were compared in terms of CTV coverage and organs-at-risk sparing. Optimization objectives were more easily met with the BNA. For the T1 case, all three planning objectives were easily achieved in both the RNA and BNA, but with 18-19% lower soft palate doses with the BNA. For the T2 case, the CTV planning objectives were achieved in both the RNA and BNA, but the soft palate constraint was only achieved with the BNA, with 38-41% lower soft palate doses. Compared to the RNA, the BNA permits easier optimization and improves therapeutic ratio by a significant reduction of soft palate doses, based on simulation using a proposed system for CTV/organs-at-risk delineation, prescription, and optimization for image-guided adaptive brachytherapy. Clinical piloting using a prototype is necessary to evaluate its feasibility and utility. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Impact of imaging approach on radiation dose and associated cancer risk in children undergoing cardiac catheterization.

PubMed

Hill, Kevin D; Wang, Chu; Einstein, Andrew J; Januzis, Natalie; Nguyen, Giao; Li, Jennifer S; Fleming, Gregory A; Yoshizumi, Terry K

2017-04-01

To quantify the impact of image optimization on absorbed radiation dose and associated risk in children undergoing cardiac catheterization. Various imaging and fluoroscopy system technical parameters including camera magnification, source-to-image distance, collimation, antiscatter grids, beam quality, and pulse rates, all affect radiation dose but have not been well studied in younger children. We used anthropomorphic phantoms (ages: newborn and 5 years old) to measure surface radiation exposure from various imaging approaches and estimated absorbed organ doses and effective doses (ED) using Monte Carlo simulations. Models developed in the National Academies' Biological Effects of Ionizing Radiation VII report were used to compare an imaging protocol optimized for dose reduction versus suboptimal imaging (+20 cm source-to-image-distance, +1 magnification setting, no collimation) on lifetime attributable risk (LAR) of cancer. For the newborn and 5-year-old phantoms, respectively ED changes were as follows: +157% and +232% for an increase from 6-inch to 10-inch camera magnification; +61% and +59% for a 20 cm increase in source-to-image-distance; -42% and -48% with addition of 1-inch periphery collimation; -31% and -46% with removal of the antiscatter grid. Compared with an optimized protocol, suboptimal imaging increased ED by 2.75-fold (newborn) and fourfold (5 years old). Estimated cancer LAR from 30-min of posteroanterior fluoroscopy using optimized versus suboptimal imaging, respectively was 0.42% versus 1.23% (newborn female), 0.20% versus 0.53% (newborn male), 0.47% versus 1.70% (5-year-old female) and 0.16% versus 0.69% (5-year-old male). Radiation-related risks to children undergoing cardiac catheterization can be substantial but are markedly reduced with an optimized imaging approach. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Childress, Ann C; Wigal, Sharon B; Brams, Matthew N; Turnbow, John M; Pincus, Yulia; Belden, Heidi W; Berry, Sally A

2018-06-01

To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study. Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10-20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs. The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache. AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

Medical image enhancement using resolution synthesis

NASA Astrophysics Data System (ADS)

Wong, Tak-Shing; Bouman, Charles A.; Thibault, Jean-Baptiste; Sauer, Ken D.

2011-03-01

We introduce a post-processing approach to improve the quality of CT reconstructed images. The scheme is adapted from the resolution-synthesis (RS)1 interpolation algorithm. In this approach, we consider the input image, scanned at a particular dose level, as a degraded version of a high quality image scanned at a high dose level. Image enhancement is achieved by predicting the high quality image by classification based linear regression. To improve the robustness of our scheme, we also apply the minimum description length principle to determine the optimal number of predictors to use in the scheme, and the ridge regression to regularize the design of the predictors. Experimental results show that our scheme is effective in reducing the noise in images reconstructed from filtered back projection without significant loss of image details. Alternatively, our scheme can also be applied to reduce dose while maintaining image quality at an acceptable level.

Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

PubMed

Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

2016-01-01

We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

Treatment planning systems for external whole brain radiation therapy: With and without MLC (multi leaf collimator) optimization

NASA Astrophysics Data System (ADS)

Budiyono, T.; Budi, W. S.; Hidayanto, E.

2016-03-01

Radiation therapy for brain malignancy is done by giving a dose of radiation to a whole volume of the brain (WBRT) followed by a booster at the primary tumor with more advanced techniques. Two external radiation fields given from the right and left side. Because the shape of the head, there will be an unavoidable hotspot radiation dose of greater than 107%. This study aims to optimize planning of radiation therapy using field in field multi-leaf collimator technique. A study of 15 WBRT samples with CT slices is done by adding some segments of radiation in each field of radiation and delivering appropriate dose weighting using a TPS precise plan Elekta R 2.15. Results showed that this optimization a more homogeneous radiation on CTV target volume, lower dose in healthy tissue, and reduced hotspots in CTV target volume. Comparison results of field in field multi segmented MLC technique with standard conventional technique for WBRT are: higher average minimum dose (77.25% ± 0:47%) vs (60% ± 3:35%); lower average maximum dose (110.27% ± 0.26%) vs (114.53% ± 1.56%); lower hotspot volume (5.71% vs 27.43%); and lower dose on eye lenses (right eye: 9.52% vs 18.20%); (left eye: 8.60% vs 16.53%).

Quantitative Analysis of the Effect of Iterative Reconstruction Using a Phantom: Determining the Appropriate Blending Percentage

PubMed Central

Kim, Hyun Gi; Lee, Young Han; Choi, Jin-Young; Park, Mi-Suk; Kim, Myeong-Jin; Kim, Ki Whang

2015-01-01

Purpose To investigate the optimal blending percentage of adaptive statistical iterative reconstruction (ASIR) in a reduced radiation dose while preserving a degree of image quality and texture that is similar to that of standard-dose computed tomography (CT). Materials and Methods The CT performance phantom was scanned with standard and dose reduction protocols including reduced mAs or kVp. Image quality parameters including noise, spatial, and low-contrast resolution, as well as image texture, were quantitatively evaluated after applying various blending percentages of ASIR. The optimal blending percentage of ASIR that preserved image quality and texture compared to standard dose CT was investigated in each radiation dose reduction protocol. Results As the percentage of ASIR increased, noise and spatial-resolution decreased, whereas low-contrast resolution increased. In the texture analysis, an increasing percentage of ASIR resulted in an increase of angular second moment, inverse difference moment, and correlation and in a decrease of contrast and entropy. The 20% and 40% dose reduction protocols with 20% and 40% ASIR blending, respectively, resulted in an optimal quality of images with preservation of the image texture. Conclusion Blending the 40% ASIR to the 40% reduced tube-current product can maximize radiation dose reduction and preserve adequate image quality and texture. PMID:25510772

Derivative-free generation and interpolation of convex Pareto optimal IMRT plans

NASA Astrophysics Data System (ADS)

Hoffmann, Aswin L.; Siem, Alex Y. D.; den Hertog, Dick; Kaanders, Johannes H. A. M.; Huizenga, Henk

2006-12-01

In inverse treatment planning for intensity-modulated radiation therapy (IMRT), beamlet intensity levels in fluence maps of high-energy photon beams are optimized. Treatment plan evaluation criteria are used as objective functions to steer the optimization process. Fluence map optimization can be considered a multi-objective optimization problem, for which a set of Pareto optimal solutions exists: the Pareto efficient frontier (PEF). In this paper, a constrained optimization method is pursued to iteratively estimate the PEF up to some predefined error. We use the property that the PEF is convex for a convex optimization problem to construct piecewise-linear upper and lower bounds to approximate the PEF from a small initial set of Pareto optimal plans. A derivative-free Sandwich algorithm is presented in which these bounds are used with three strategies to determine the location of the next Pareto optimal solution such that the uncertainty in the estimated PEF is maximally reduced. We show that an intelligent initial solution for a new Pareto optimal plan can be obtained by interpolation of fluence maps from neighbouring Pareto optimal plans. The method has been applied to a simplified clinical test case using two convex objective functions to map the trade-off between tumour dose heterogeneity and critical organ sparing. All three strategies produce representative estimates of the PEF. The new algorithm is particularly suitable for dynamic generation of Pareto optimal plans in interactive treatment planning.

Impact of database quality in knowledge-based treatment planning for prostate cancer.

PubMed

Wall, Phillip D H; Carver, Robert L; Fontenot, Jonas D

2018-03-13

This article investigates dose-volume prediction improvements in a common knowledge-based planning (KBP) method using a Pareto plan database compared with using a conventional, clinical plan database. Two plan databases were created using retrospective, anonymized data of 124 volumetric modulated arc therapy (VMAT) prostate cancer patients. The clinical plan database (CPD) contained planning data from each patient's clinically treated VMAT plan, which were manually optimized by various planners. The multicriteria optimization database (MCOD) contained Pareto-optimal plan data from VMAT plans created using a standardized multicriteria optimization protocol. Overlap volume histograms, incorporating fractional organ at risk volumes only within the treatment fields, were computed for each patient and used to match new patient anatomy to similar database patients. For each database patient, CPD and MCOD KBP predictions were generated for D 10 , D 30 , D 50 , D 65 , and D 80 of the bladder and rectum in a leave-one-out manner. Prediction achievability was evaluated through a replanning study on a subset of 31 randomly selected database patients using the best KBP predictions, regardless of plan database origin, as planning goals. MCOD predictions were significantly lower than CPD predictions for all 5 bladder dose-volumes and rectum D 50 (P = .004) and D 65 (P < .001), whereas CPD predictions for rectum D 10 (P = .005) and D 30 (P < .001) were significantly less than MCOD predictions. KBP predictions were statistically achievable in the replans for all predicted dose-volumes, excluding D 10 of bladder (P = .03) and rectum (P = .04). Compared with clinical plans, replans showed significant average reductions in D mean for bladder (7.8 Gy; P < .001) and rectum (9.4 Gy; P < .001), while maintaining statistically similar planning target volume, femoral head, and penile bulb dose. KBP dose-volume predictions derived from Pareto plans were more optimal overall than those resulting from manually optimized clinical plans, which significantly improved KBP-assisted plan quality. This work investigates how the plan quality of knowledge databases affects the performance and achievability of dose-volume predictions from a common knowledge-based planning approach for prostate cancer. Bladder and rectum dose-volume predictions derived from a database of standardized Pareto-optimal plans were compared with those derived from clinical plans manually designed by various planners. Dose-volume predictions from the Pareto plan database were significantly lower overall than those from the clinical plan database, without compromising achievability. Copyright © 2018 Elsevier Inc. All rights reserved.

Magnetization transfer proportion: a simplified measure of dose response for polymer gel dosimetry.

PubMed

Whitney, Heather M; Gochberg, Daniel F; Gore, John C

2008-12-21

The response to radiation of polymer gel dosimeters has most often been described by measuring the nuclear magnetic resonance transverse relaxation rate as a function of dose. This approach is highly dependent upon the choice of experimental parameters, such as the echo spacing time for Carr-Purcell-Meiboom-Gill-type pulse sequences, and is difficult to optimize in imaging applications where a range of doses are applied to a single gel, as is typical for practical uses of polymer gel dosimetry. Moreover, errors in computing dose can arise when there are substantial variations in the radiofrequency (B1) field or resonant frequency, as may occur for large samples. Here we consider the advantages of using magnetization transfer imaging as an alternative approach and propose the use of a simplified quantity, the magnetization transfer proportion (MTP), to assess doses. This measure can be estimated through two simple acquisitions and is more robust in the presence of some sources of system imperfections. It also has a dependence upon experimental parameters that is independent of dose, allowing simultaneous optimization at all dose levels. The MTP is shown to be less susceptible to B1 errors than are CPMG measurements of R2. The dose response can be optimized through appropriate choices of the power and offset frequency of the pulses used in magnetization transfer imaging.

SU-G-TeP3-01: A New Approach for Calculating Variable Relative Biological Effectiveness in IMPT Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, W; Randeniya, K; Grosshans, D

2016-06-15

Purpose: To investigate the impact of a new approach for calculating relative biological effectiveness (RBE) in intensity-modulated proton therapy (IMPT) optimization on RBE-weighted dose distributions. This approach includes the nonlinear RBE for the high linear energy transfer (LET) region, which was revealed by recent experiments at our institution. In addition, this approach utilizes RBE data as a function of LET without using dose-averaged LET in calculating RBE values. Methods: We used a two-piece function for calculating RBE from LET. Within the Bragg peak, RBE is linearly correlated to LET. Beyond the Bragg peak, we use a nonlinear (quadratic) RBE functionmore » of LET based on our experimental. The IMPT optimization was devised to incorporate variable RBE by maximizing biological effect (based on the Linear Quadratic model) in tumor and minimizing biological effect in normal tissues. Three glioblastoma patients were retrospectively selected from our institution in this study. For each patient, three optimized IMPT plans were created based on three RBE resolutions, i.e., fixed RBE of 1.1 (RBE-1.1), variable RBE based on linear RBE and LET relationship (RBE-L), and variable RBE based on linear and quadratic relationship (RBE-LQ). The RBE weighted dose distributions of each optimized plan were evaluated in terms of different RBE values, i.e., RBE-1.1, RBE-L and RBE-LQ. Results: The RBE weighted doses recalculated from RBE-1.1 based optimized plans demonstrated an increasing pattern from using RBE-1.1, RBE-L to RBE-LQ consistently for all three patients. The variable RBE (RBE-L and RBE-LQ) weighted dose distributions recalculated from RBE-L and RBE-LQ based optimization were more homogenous within the targets and better spared in the critical structures than the ones recalculated from RBE-1.1 based optimization. Conclusion: We implemented a new approach for RBE calculation and optimization and demonstrated potential benefits of improving tumor coverage and normal sparing in IMPT planning.« less

Iterative Reconstruction Techniques in Abdominopelvic CT: Technical Concepts and Clinical Implementation.

PubMed

Patino, Manuel; Fuentes, Jorge M; Singh, Sarabjeet; Hahn, Peter F; Sahani, Dushyant V

2015-07-01

This article discusses the clinical challenge of low-radiation-dose examinations, the commonly used approaches for dose optimization, and their effect on image quality. We emphasize practical aspects of the different iterative reconstruction techniques, along with their benefits, pitfalls, and clinical implementation. The widespread use of CT has raised concerns about potential radiation risks, motivating diverse strategies to reduce the radiation dose associated with CT. CT manufacturers have developed alternative reconstruction algorithms intended to improve image quality on dose-optimized CT studies, mainly through noise and artifact reduction. Iterative reconstruction techniques take unique approaches to noise reduction and provide distinct strength levels or settings.

Advantages and limitations of navigation-based multicriteria optimization (MCO) for localized prostate cancer IMRT planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGarry, Conor K., E-mail: conor.mcgarry@belfasttrust.hscni.net; Bokrantz, Rasmus; RaySearch Laboratories, Stockholm

2014-10-01

Efficacy of inverse planning is becoming increasingly important for advanced radiotherapy techniques. This study’s aims were to validate multicriteria optimization (MCO) in RayStation (v2.4, RaySearch Laboratories, Sweden) against standard intensity-modulated radiation therapy (IMRT) optimization in Oncentra (v4.1, Nucletron BV, the Netherlands) and characterize dose differences due to conversion of navigated MCO plans into deliverable multileaf collimator apertures. Step-and-shoot IMRT plans were created for 10 patients with localized prostate cancer using both standard optimization and MCO. Acceptable standard IMRT plans with minimal average rectal dose were chosen for comparison with deliverable MCO plans. The trade-off was, for the MCO plans, managedmore » through a user interface that permits continuous navigation between fluence-based plans. Navigated MCO plans were made deliverable at incremental steps along a trajectory between maximal target homogeneity and maximal rectal sparing. Dosimetric differences between navigated and deliverable MCO plans were also quantified. MCO plans, chosen as acceptable under navigated and deliverable conditions resulted in similar rectal sparing compared with standard optimization (33.7 ± 1.8 Gy vs 35.5 ± 4.2 Gy, p = 0.117). The dose differences between navigated and deliverable MCO plans increased as higher priority was placed on rectal avoidance. If the best possible deliverable MCO was chosen, a significant reduction in rectal dose was observed in comparison with standard optimization (30.6 ± 1.4 Gy vs 35.5 ± 4.2 Gy, p = 0.047). Improvements were, however, to some extent, at the expense of less conformal dose distributions, which resulted in significantly higher doses to the bladder for 2 of the 3 tolerance levels. In conclusion, similar IMRT plans can be created for patients with prostate cancer using MCO compared with standard optimization. Limitations exist within MCO regarding conversion of navigated plans to deliverable apertures, particularly for plans that emphasize avoidance of critical structures. Minimizing these differences would result in better quality treatments for patients with prostate cancer who were treated with radiotherapy using MCO plans.« less

SU-F-T-347: An Absolute Dose-Volume Constraint Based Deterministic Optimization Framework for Multi-Co60 Source Focused Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, B; Liu, B; Li, Y

2016-06-15

Purpose: Treatment plan optimization in multi-Co60 source focused radiotherapy with multiple isocenters is challenging, because dose distribution is normalized to maximum dose during optimization and evaluation. The objective functions are traditionally defined based on relative dosimetric distribution. This study presents an alternative absolute dose-volume constraint (ADC) based deterministic optimization framework (ADC-DOF). Methods: The initial isocenters are placed on the eroded target surface. Collimator size is chosen based on the area of 2D contour on corresponding axial slice. The isocenter spacing is determined by adjacent collimator sizes. The weights are optimized by minimizing the deviation from ADCs using the steepest descentmore » technique. An iterative procedure is developed to reduce the number of isocenters, where the isocenter with lowest weight is removed without affecting plan quality. The ADC-DOF is compared with the genetic algorithm (GA) using the same arbitrary shaped target (254cc), with a 15mm margin ring structure representing normal tissues. Results: For ADC-DOF, the ADCs imposed on target and ring are (D100>10Gy, D50,10, 0<12Gy, 15Gy and 20Gy) and (D40<10Gy). The resulting D100, 50, 10, 0 and D40 are (9.9Gy, 12.0Gy, 14.1Gy and 16.2Gy) and (10.2Gy). The objectives of GA are to maximize 50% isodose target coverage (TC) while minimize the dose delivered to the ring structure, which results in 97% TC and 47.2% average dose in ring structure. For ADC-DOF (GA) techniques, 20 out of 38 (10 out of 12) initial isocenters are used in the final plan, and the computation time is 8.7s (412.2s) on an i5 computer. Conclusion: We have developed a new optimization technique using ADC and deterministic optimization. Compared with GA, ADC-DOF uses more isocenters but is faster and more robust, and achieves a better conformity. For future work, we will focus on developing a more effective mechanism for initial isocenter determination.« less

Technical Note: Dose effects of 1.5 T transverse magnetic field on tissue interfaces in MRI-guided radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Xinfeng; Prior, Phil; Chen, Guang-Pei

Purpose: The integration of MRI with a linear accelerator (MR-linac) offers great potential for high-precision delivery of radiation therapy (RT). However, the electron deflection resulting from the presence of a transverse magnetic field (TMF) can affect the dose distribution, particularly the electron return effect (ERE) at tissue interfaces. The purpose of the study is to investigate the dose effects of ERE at air-tissue and lung-tissue interfaces during intensity-modulated radiation therapy (IMRT) planning. Methods: IMRT and volumetric modulated arc therapy (VMAT) plans for representative pancreas, lung, breast, and head and neck (HN) cases were generated following commonly used clinical dose volumemore » (DV) criteria. In each case, three types of plans were generated: (1) the original plan generated without a TMF; (2) the reconstructed plan generated by recalculating the original plan with the presence of a TMF of 1.5 T (no optimization); and (3) the optimized plan generated by a full optimization with TMF = 1.5 T. These plans were compared using a variety of DV parameters, including V{sub 100%}, D{sub 95%}, DHI [dose heterogeneity index: (D{sub 20%}–D{sub 80%})/D{sub prescription}], D{sub max}, and D{sub 1cc} in OARs (organs at risk) and tissue interface. All the optimizations and calculations in this work were performed on static data. Results: The dose recalculation under TMF showed the presence of the 1.5 T TMF can slightly reduce V{sub 100%} and D{sub 95%} for PTV, with the differences being less than 4% for all but one lung case studied. The TMF results in considerable increases in D{sub max} and D{sub 1cc} on the skin in all cases, mostly between 10% and 35%. The changes in D{sub max} and D{sub 1cc} on air cavity walls are dependent upon site, geometry, and size, with changes ranging up to 15%. The VMAT plans lead to much smaller dose effects from ERE compared to fixed-beam IMRT in pancreas case. When the TMF is considered in the plan optimization, the dose effects of the TMF at tissue interfaces (e.g., air-cavity wall, lung-tissue interfaces, skin) are significantly reduced in most cases. Conclusions: The doses on tissue interfaces can be significantly changed by the presence of a TMF during MR-guided RT when the magnetic field is not included in plan optimization. These changes can be substantially reduced or even eliminated during VMAT/IMRT optimization that specifically considers the TMF, without deteriorating overall plan quality.« less

Poster - Thur Eve - 57: Craniospinal irradiation with jagged-junction IMRT approach without beam edge matching for field junctions.

PubMed

Cao, F; Ramaseshan, R; Corns, R; Harrop, S; Nuraney, N; Steiner, P; Aldridge, S; Liu, M; Carolan, H; Agranovich, A; Karva, A

2012-07-01

Craniospinal irradiation were traditionally treated the central nervous system using two or three adjacent field sets. A intensity-modulated radiotherapy (IMRT) plan (Jagged-Junction IMRT) which overcomes problems associated with field junctions and beam edge matching, improves planning and treatment setup efficiencies with homogenous target dose distribution was developed. Jagged-Junction IMRT was retrospectively planned on three patients with prescription of 36 Gy in 20 fractions and compared to conventional treatment plans. Planning target volume (PTV) included the whole brain and spinal canal to the S3 vertebral level. The plan employed three field sets, each with a unique isocentre. One field set with seven fields treated the cranium. Two field sets treated the spine, each set using three fields. Fields from adjacent sets were overlapped and the optimization process smoothly integrated the dose inside the overlapped junction. For the Jagged-Junction IMRT plans vs conventional technique, average homogeneity index equaled 0.08±0.01 vs 0.12±0.02, and conformity number equaled 0.79±0.01 vs 0.47±0.12. The 95% isodose surface covered (99.5±0.3)% of the PTV vs (98.1±2.0)%. Both Jagged-Junction IMRT plans and the conventional plans had good sparing of the organs at risk. Jagged-Junction IMRT planning provided good dose homogeneity and conformity to the target while maintaining a low dose to the organs at risk. Jagged-Junction IMRT optimization smoothly distributed dose in the junction between field sets. Since there was no beam matching, this treatment technique is less likely to produce hot or cold spots at the junction in contrast to conventional techniques. © 2012 American Association of Physicists in Medicine.

SU-E-T-229: Craniospinal Radiotherapy Planning with VMAT, Two First Years Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lliso, F; Carmona, V; Gimeno, J

2015-06-15

Purpose: To describe how we moved to VMAT in the craniospinal radiotherapy planning process, the actual procedure details, and the results for the patients treated. Methods: Twelve patients underwent craniospinal irradiation with the new procedure, based on the paper by Lee et al. (IJROBP 82, 2012), with some additional modifications. Patients were treated in supine position in Varian Clinac iX linacs with 6 MV RapidArc; prescription doses ranged from 23.4 to 40 Gy (13 to 20 fractions); depending on the PTV length, 2 or 3 isocenters were used, all coordinates being equal except the longitudinal one, setting a few centimeter-longmore » overlapping region; 2 arcs (RA) sharing isocentre for the cranial region, RA1 encompassing cranium and superior spinal region, and RA2 intended to improve conformity, only for cranium; for spine, 1 or 2 isocenters were employed; optimization was performed with Eclipse (V 13.0) using AAA algorithm, establishing sets of optimization parameters to give high conformity while sparing OAR. In pediatric patients, homogeneous irradiation of the vertebrae was also required.Conformity (CI) and heterogeneity (HI) indices (same as Lee et al.), and mean and maximum doses for OAR were calculated. Several pre-treatment verification methods were used: Octavius4D (PTW) for each isocentre, point dose at the junction region, Portal Dosimetry (when possible), and independent MU verification software (Diamond, PTW). Results: CI median value was 1.02 (0.99–1.07) and HI, 1.07 (1.06–1.09); a great reduction was observed for CI and OAR mean doses with respect to Lee et al. data; median maximum eye lens dose was 7.3 Gy (4.0–12.0); mean LungV20Gy was 1.9%; in children, vertebrae were homogeneously irradiated (D95%=20.8 Gy, Dmean= 23.2 Gy).All pre-treatment verifications were found within our action levels except for Portal Dosimetry. Conclusion: A RapidArc planning process for craniospinal axis irradiation has been implemented with significant advantages on conformity, homogeneity, feasibility and efficiency. and increase brain tissue sparing. Variations in volume decrease may be related to shape or location of the tumor.« less

A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE®

PubMed Central

von Krempelhuber, Alfred; Vollmar, Jens; Pokorny, Rolf; Rapp, Petra; Wulff, Niels; Petzold, Barbara; Handley, Amanda; Mateo, Lyn; Siersbol, Henriette; Kollaritsch, Herwig; Chaplin, Paul

2009-01-01

IMVAMUNE® is a Modified Vaccinia Ankara-based virus that is being developed as a safer 3rd generation smallpox vaccine. In order to determine the optimal dose for further development, a double-blind, randomized Phase II trial was performed testing three different doses of IMVAMUNE® in 164 healthy volunteers. All three IMVAMUNE® doses displayed a favourable safety profile, with local reactions as the most frequent observation. The 1×108 TCID50 IMVAMUNE® dose induced a total antibody response in 94% of the subjects following the first vaccination and the highest peak seroconversion rates by ELISA (100%) and PRNT (71%). This IMVAMUNE® dose was considered to be optimal for the further clinical development of this highly attenuated poxvirus as a safer smallpox vaccine. PMID:19944151

Optimization of combined electron and photon beams for breast cancer

NASA Astrophysics Data System (ADS)

Xiong, W.; Li, J.; Chen, L.; Price, R. A.; Freedman, G.; Ding, M.; Qin, L.; Yang, J.; Ma, C.-M.

2004-05-01

Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.

Optimization of the temporal pattern of applied dose for a single fraction of radiation: Implications for radiation therapy

NASA Astrophysics Data System (ADS)

Altman, Michael B.

The increasing prevalence of intensity modulated radiation therapy (IMRT) as a treatment modality has led to a renewed interest in the potential for interaction between prolonged treatment time, as frequently associated with IMRT, and the underlying radiobiology of the irradiated tissue. A particularly relevant aspect of radiobiology is cell repair capacity, which influences cell survival, and thus directly relates to the ability to control tumors and spare normal tissues. For a single fraction of radiation, the linear quadratic (LQ) model is commonly used to relate the radiation dose to the fraction of cells surviving. The LQ model implies a dependence on two time-related factors which correlate to radiobiological effects: the duration of radiation application, and the functional form of how the dose is applied over that time (the "temporal pattern of applied dose"). Although the former has been well studied, the latter has not. Thus, the goal of this research is to investigate the impact of the temporal pattern of applied dose on the survival of human cells and to explore how the manipulation of this temporal dose pattern may be incorporated into an IMRT-based radiation therapy treatment planning scheme. The hypothesis is that the temporal pattern of applied dose in a single fraction of radiation can be optimized to maximize or minimize cell kill. Furthermore, techniques which utilize this effect could have clinical ramifications. In situations where increased cell kill is desirable, such as tumor control, or limiting the degree of cell kill is important, such as the sparing of normal tissue, temporal sequences of dose which maximize or minimize cell kill (temporally "optimized" sequences) may provide greater benefit than current clinically used radiation patterns. In the first part of this work, an LQ-based modeling analysis of effects of the temporal pattern of dose on cell kill is performed. Through this, patterns are identified for maximizing cell kill for a given radiation pattern by concentrating the highest doses in the middle of a fraction (a "Triangle" pattern), or minimizing cell kill by placing the highest doses near the beginning and end (a "V-shaped" pattern). The conditions under which temporal optimization effects are most acute are also identified: irradiation of low alpha/beta tissues, long fraction durations, and high doses/fx. An in vitro study is then performed which verifies that the temporal effects and trends predicted by the modeling study are clearly manifested in human cells. Following this a phantom which could allow similar in vitro radiobiological experiments in a 3-dimensional clinically-based environment is designed, created, and dosimetrically assessed using TLDs, film, and biological assay-based techniques. The phantom is found to be a useful and versatile tool for such experiments. A scheme for utilizing the phantom in a clinical treatment environment is then developed. This includes a demonstration of prototype methods for optimizing the temporal pattern of applied dose in clinical IMRT plans to manipulate tissue-dependent effects. Looking toward future experimental validation of such plans using the phantom, an analysis of the suitability of biological assays for use in phantom-based in vitro experiments is performed. Finally, a discussion is provided about the steps necessary to integrate temporal optimization into in vivo experiments and ultimately into a clinical radiation therapy environment. If temporal optimization is ultimately shown to have impact in vivo, the successful implementation of the methods developed in this study could enhance the efficacy and care of thousands of patients receiving radiotherapy.

Bridging the gap: a review of dose investigations in paediatric investigation plans

PubMed Central

Hampson, Lisa V; Herold, Ralf; Posch, Martin; Saperia, Julia; Whitehead, Anne

2014-01-01

Aims In the EU, development of new medicines for children should follow a prospectively agreed paediatric investigation plan (PIP). Finding the right dose for children is crucial but challenging due to the variability of pharmacokinetics across age groups and the limited sample sizes available. We examined strategies adopted in PIPs to support paediatric dosing recommendations to identify common assumptions underlying dose investigations and the attempts planned to verify them in children. Methods We extracted data from 73 PIP opinions recently adopted by the Paediatric Committee of the European Medicines Agency. These opinions represented 79 medicinal development programmes and comprised a total of 97 dose investigation studies. We identified the design of these dose investigation studies, recorded the analyses planned and determined the criteria used to define target doses. Results Most dose investigation studies are clinical trials (83 of 97) that evaluate a single dosing rule. Sample sizes used to investigate dose are highly variable across programmes, with smaller numbers used in younger children (< 2 years). Many studies (40 of 97) do not pre-specify a target dose criterion. Of those that do, most (33 of 57 studies) guide decisions using pharmacokinetic data alone. Conclusions Common assumptions underlying dose investigation strategies include dose proportionality and similar exposure−response relationships in adults and children. Few development programmes pre-specify steps to verify assumptions in children. There is scope for the use of Bayesian methods as a framework for synthesizing existing information to quantify prior uncertainty about assumptions. This process can inform the design of optimal drug development strategies. PMID:24720849

Autologous islet transplantation: challenges and lessons.

PubMed

Dunn, Ty B; Wilhelm, Joshua J; Bellin, Melena D; Pruett, Timothy L

2017-08-01

Human islet isolation and autotransplantation [autologous islet transplant (AUTX)] is performed to prevent or ameliorate brittle diabetes after total pancreatectomy performed for benign disease. The success or failure of the transplant can be associated with a profound impact on the individual's quality of life and even survival. AUTX offers unique insights into the effects of pancreas quality, islet number, isolation technique and alternate site engraftment on transplant efficacy. Herein, we review islet isolation with a focus on potential pathways to further optimize the endocrine outcome of AUTX, and compare and contrast differences in islet processing for AUTX and allotransplantation (allogeneic islet transplant). New knowledge of human islet biology and issues surrounding the engraftment process offer opportunities for innovative approaches toward optimizing islet cell transplantation. Improving the rate and durability of insulin independence in the often-times marginal dose model of AUTX may provide new insight toward improving the efficiency and durability of single donor islet (allogeneic islet transplant).

Enzymatic catalysis treatment method of meat industry wastewater using lacasse.

PubMed

Thirugnanasambandham, K; Sivakumar, V

2015-01-01

The process of meat industry produces in a large amount of wastewater that contains high levels of colour and chemical oxygen demand (COD). So they must be pretreated before their discharge into the ecological system. In this paper, enzymatic catalysis (EC) was adopted to treat the meat wastewater. Box-Behnken design (BBD), an experimental design for response surface methodology (RSM), was used to create a set of 29 experimental runs needed for optimizing of the operating conditions. Quadratic regression models with estimated coefficients were developed to describe the colour and COD removals. The experimental results show that EC could effectively reduce colour (95 %) and COD (86 %) at the optimum conditions of enzyme dose of 110 U/L, incubation time of 100 min, pH of 7 and temperature of 40 °C. RSM could be effectively adopted to optimize the operating multifactors in complex EC process.

The DOPEX code: An application of the method of steepest descent to laminated-shield-weight optimization with several constraints

NASA Technical Reports Server (NTRS)

Lahti, G. P.

1972-01-01

A two- or three-constraint, two-dimensional radiation shield weight optimization procedure and a computer program, DOPEX, is described. The DOPEX code uses the steepest descent method to alter a set of initial (input) thicknesses for a shield configuration to achieve a minimum weight while simultaneously satisfying dose constaints. The code assumes an exponential dose-shield thickness relation with parameters specified by the user. The code also assumes that dose rates in each principal direction are dependent only on thicknesses in that direction. Code input instructions, FORTRAN 4 listing, and a sample problem are given. Typical computer time required to optimize a seven-layer shield is about 0.1 minute on an IBM 7094-2.

A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Dan; Ruan, Dan; O’Connor, Daniel

Purpose: To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. Methods: A total of seven patients—two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung—were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-basedmore » IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle–Pock algorithm, a first-order primal–dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. Results: Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and mean critical organ doses were reduced by 1.94% and 1.44% of the prescription dose. The average number of delivery segments was 12.68 segments per beam for both the RAO and DMS plans. The N = 2 and N = 4 SOC designs were, on average, 1.56 and 1.80 times more efficient than the N = 1 SOC design to deliver. The mean aperture size produced by the RAO plans was 3.9 times larger than that of the DMS plans. Conclusions: The DAO and dose domain optimization approach enabled high quality IMRT plans using a low-complexity collimator setup. The dosimetric quality is comparable or slightly superior to conventional MLC-based IMRT plans using the same number of delivery segments. The SOC IMRT delivery efficiency can be significantly improved by increasing the leaf numbers, but the number is still significantly lower than the number of leaves in a typical MLC.« less

A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy.

PubMed

Nguyen, Dan; Ruan, Dan; O'Connor, Daniel; Woods, Kaley; Low, Daniel A; Boucher, Salime; Sheng, Ke

2016-02-01

To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. A total of seven patients-two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung-were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-based IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle-Pock algorithm, a first-order primal-dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and mean critical organ doses were reduced by 1.94% and 1.44% of the prescription dose. The average number of delivery segments was 12.68 segments per beam for both the RAO and DMS plans. The N = 2 and N = 4 SOC designs were, on average, 1.56 and 1.80 times more efficient than the N = 1 SOC design to deliver. The mean aperture size produced by the RAO plans was 3.9 times larger than that of the DMS plans. The DAO and dose domain optimization approach enabled high quality IMRT plans using a low-complexity collimator setup. The dosimetric quality is comparable or slightly superior to conventional MLC-based IMRT plans using the same number of delivery segments. The SOC IMRT delivery efficiency can be significantly improved by increasing the leaf numbers, but the number is still significantly lower than the number of leaves in a typical MLC.

SU-E-T-436: Fluence-Based Trajectory Optimization for Non-Coplanar VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smyth, G; Bamber, JC; Bedford, JL

2015-06-15

Purpose: To investigate a fluence-based trajectory optimization technique for non-coplanar VMAT for brain cancer. Methods: Single-arc non-coplanar VMAT trajectories were determined using a heuristic technique for five patients. Organ at risk (OAR) volume intersected during raytracing was minimized for two cases: absolute volume and the sum of relative volumes weighted by OAR importance. These trajectories and coplanar VMAT formed starting points for the fluence-based optimization method. Iterative least squares optimization was performed on control points 24° apart in gantry rotation. Optimization minimized the root-mean-square (RMS) deviation of PTV dose from the prescription (relative importance 100), maximum dose to the brainstemmore » (10), optic chiasm (5), globes (5) and optic nerves (5), plus mean dose to the lenses (5), hippocampi (3), temporal lobes (2), cochleae (1) and brain excluding other regions of interest (1). Control point couch rotations were varied in steps of up to 10° and accepted if the cost function improved. Final treatment plans were optimized with the same objectives in an in-house planning system and evaluated using a composite metric - the sum of optimization metrics weighted by importance. Results: The composite metric decreased with fluence-based optimization in 14 of the 15 plans. In the remaining case its overall value, and the PTV and OAR components, were unchanged but the balance of OAR sparing differed. PTV RMS deviation was improved in 13 cases and unchanged in two. The OAR component was reduced in 13 plans. In one case the OAR component increased but the composite metric decreased - a 4 Gy increase in OAR metrics was balanced by a reduction in PTV RMS deviation from 2.8% to 2.6%. Conclusion: Fluence-based trajectory optimization improved plan quality as defined by the composite metric. While dose differences were case specific, fluence-based optimization improved both PTV and OAR dosimetry in 80% of cases.« less

Inverse optimization of objective function weights for treatment planning using clinical dose-volume histograms

NASA Astrophysics Data System (ADS)

Babier, Aaron; Boutilier, Justin J.; Sharpe, Michael B.; McNiven, Andrea L.; Chan, Timothy C. Y.

2018-05-01

We developed and evaluated a novel inverse optimization (IO) model to estimate objective function weights from clinical dose-volume histograms (DVHs). These weights were used to solve a treatment planning problem to generate ‘inverse plans’ that had similar DVHs to the original clinical DVHs. Our methodology was applied to 217 clinical head and neck cancer treatment plans that were previously delivered at Princess Margaret Cancer Centre in Canada. Inverse plan DVHs were compared to the clinical DVHs using objective function values, dose-volume differences, and frequency of clinical planning criteria satisfaction. Median differences between the clinical and inverse DVHs were within 1.1 Gy. For most structures, the difference in clinical planning criteria satisfaction between the clinical and inverse plans was at most 1.4%. For structures where the two plans differed by more than 1.4% in planning criteria satisfaction, the difference in average criterion violation was less than 0.5 Gy. Overall, the inverse plans were very similar to the clinical plans. Compared with a previous inverse optimization method from the literature, our new inverse plans typically satisfied the same or more clinical criteria, and had consistently lower fluence heterogeneity. Overall, this paper demonstrates that DVHs, which are essentially summary statistics, provide sufficient information to estimate objective function weights that result in high quality treatment plans. However, as with any summary statistic that compresses three-dimensional dose information, care must be taken to avoid generating plans with undesirable features such as hotspots; our computational results suggest that such undesirable spatial features were uncommon. Our IO-based approach can be integrated into the current clinical planning paradigm to better initialize the planning process and improve planning efficiency. It could also be embedded in a knowledge-based planning or adaptive radiation therapy framework to automatically generate a new plan given a predicted or updated target DVH, respectively.

Composite Resin Dosimeters: A New Concept and Design for a Fibrous Color Dosimeter.

PubMed

Kinashi, Kenji; Iwata, Takato; Tsuchida, Hayato; Sakai, Wataru; Tsutsumi, Naoto

2018-04-11

Polystyrene (PS)-based composite microfibers combined with a photochromic spiropyran dye, 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran (6-nitro BIPS), and a photostimulable phosphor, europium-doped barium fluorochloride (BaFCl:Eu 2+ ), were developed for the detection of X-ray exposure doses on the order of approximately 1 Gy. To produce the PS-based composite microfibers, we employed a forcespinning method that embeds a high concentration of phosphor in PS in a safe, inexpensive, and simple procedure. On the basis of the optimization of the forcespinning process, fibrous color dosimeters with a high radiation dose sensitivity of 1.2-4.4 Gy were fabricated. The color of the dosimeters was found to transition from white to blue in response to X-ray exposure. The optimized fibrous color dosimeter, made from a solution having a PS/6-nitro BIPS/BaFCl:Eu 2+ /C 2 Cl 4 ratio of 7.0/0.21/28.0/28.0 (wt %) and produced with a 290 mm distance between the needle and collectors, a 0.34 mm 23 G needle nozzle, and a spinneret rotational rate of 3000 rpm, exhibited sensitivity to a dose as low as 1.2 Gy. To realize practical applications, we manufactured the optimized fibrous color dosimeter into a clothlike color dosimeter. The clothlike color dosimeter was mounted on a stuffed bear, and its coloring behavior was demonstrated upon X-ray exposure. After exposure with X-ray, a blue colored and shaped in the form of the letter "[Formula: see text]" clearly appeared on the surface of the clothlike color dosimeter. The proposed fibrous color dosimeters having excellent workability will be an unprecedented dosimetry and contributed to all industries utilizing radiation dosimeters. This new fibrous "composite resin dosimeter" should be able to replace traditional, wearable, and individual radiation dose monitoring devices, such as film badges.

Inverse optimization of objective function weights for treatment planning using clinical dose-volume histograms.

PubMed

Babier, Aaron; Boutilier, Justin J; Sharpe, Michael B; McNiven, Andrea L; Chan, Timothy C Y

2018-05-10

We developed and evaluated a novel inverse optimization (IO) model to estimate objective function weights from clinical dose-volume histograms (DVHs). These weights were used to solve a treatment planning problem to generate 'inverse plans' that had similar DVHs to the original clinical DVHs. Our methodology was applied to 217 clinical head and neck cancer treatment plans that were previously delivered at Princess Margaret Cancer Centre in Canada. Inverse plan DVHs were compared to the clinical DVHs using objective function values, dose-volume differences, and frequency of clinical planning criteria satisfaction. Median differences between the clinical and inverse DVHs were within 1.1 Gy. For most structures, the difference in clinical planning criteria satisfaction between the clinical and inverse plans was at most 1.4%. For structures where the two plans differed by more than 1.4% in planning criteria satisfaction, the difference in average criterion violation was less than 0.5 Gy. Overall, the inverse plans were very similar to the clinical plans. Compared with a previous inverse optimization method from the literature, our new inverse plans typically satisfied the same or more clinical criteria, and had consistently lower fluence heterogeneity. Overall, this paper demonstrates that DVHs, which are essentially summary statistics, provide sufficient information to estimate objective function weights that result in high quality treatment plans. However, as with any summary statistic that compresses three-dimensional dose information, care must be taken to avoid generating plans with undesirable features such as hotspots; our computational results suggest that such undesirable spatial features were uncommon. Our IO-based approach can be integrated into the current clinical planning paradigm to better initialize the planning process and improve planning efficiency. It could also be embedded in a knowledge-based planning or adaptive radiation therapy framework to automatically generate a new plan given a predicted or updated target DVH, respectively.

The first clinical implementation of electromagnetic transponder-guided MLC tracking.

PubMed

Keall, Paul J; Colvill, Emma; O'Brien, Ricky; Ng, Jin Aun; Poulsen, Per Rugaard; Eade, Thomas; Kneebone, Andrew; Booth, Jeremy T

2014-02-01

We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy.

The first clinical implementation of electromagnetic transponder-guided MLC tracking

PubMed Central

Keall, Paul J.; Colvill, Emma; O’Brien, Ricky; Ng, Jin Aun; Poulsen, Per Rugaard; Eade, Thomas; Kneebone, Andrew; Booth, Jeremy T.

2014-01-01

Purpose: We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. Methods: An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. Results: The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. Conclusions: The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy. PMID:24506591

Individualized Selection of Beam Angles and Treatment Isocenter in Tangential Breast Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penninkhof, Joan, E-mail: j.penninkhof@erasmusmc.nl; Spadola, Sara; Department of Physics and Astronomy, Alma Mater Studiorum, University of Bologna, Bologna

Purpose and Objective: Propose a novel method for individualized selection of beam angles and treatment isocenter in tangential breast intensity modulated radiation therapy (IMRT). Methods and Materials: For each patient, beam and isocenter selection starts with the fully automatic generation of a large database of IMRT plans (up to 847 in this study); each of these plans belongs to a unique combination of isocenter position, lateral beam angle, and medial beam angle. The imposed hard planning constraint on patient maximum dose may result in plans with unacceptable target dose delivery. Such plans are excluded from further analyses. Owing to differencesmore » in beam setup, database plans differ in mean doses to organs at risk (OARs). These mean doses are used to construct 2-dimensional graphs, showing relationships between: (1) contralateral breast dose and ipsilateral lung dose; and (2) contralateral breast dose and heart dose (analyzed only for left-sided). The graphs can be used for selection of the isocenter and beam angles with the optimal, patient-specific tradeoffs between the mean OAR doses. For 30 previously treated patients (15 left-sided and 15 right-sided tumors), graphs were generated considering only the clinically applied isocenter with 121 tangential beam angle pairs. For 20 of the 30 patients, 6 alternative isocenters were also investigated. Results: Computation time for automatic generation of 121 IMRT plans took on average 30 minutes. The generated graphs demonstrated large variations in tradeoffs between conflicting OAR objectives, depending on beam angles and patient anatomy. For patients with isocenter optimization, 847 IMRT plans were considered. Adding isocenter position optimization next to beam angle optimization had a small impact on the final plan quality. Conclusion: A method is proposed for individualized selection of beam angles in tangential breast IMRT. This may be especially important for patients with cardiac risk factors or an enhanced risk for the development of contralateral breast cancer.« less

SU-E-T-294: Dosimetric Analysis of Planning Phase Using Overlap Volume Histogram for Respiratory Gated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, S; Kim, D; Kim, T

2015-06-15

Purpose: End-of-exhale (EOE) phase is generally preferred for gating window because tumor position is more reproducible. However, other gating windows might be more appropriate for dose distribution perspective. In this pilot study, we proposed to utilize overlap volume histogram (OVH) to search optimized gating window and demonstrated its feasibility. Methods: We acquired 4DCT of 10 phases for 3 lung patients (2 with a target at right middle lobe and 1 at right upper lobe). After structures were defined in every phase, the OVH of each OAR was generated to quantify the three dimensional spatial relationship between the PTV and OARsmore » (bronchus, esophagus, heart and cord etc.) at each phase. OVH tells the overlap volume of an OAR according to outward distance from the PTV. Relative overlap volume at 20 mm outward distance from the PTV (ROV-20) was also defined as a metric for measuring overlap volume and obtained. For dose calculation, 3D CRT plans were made for all phases under the same beam angles and objectives (e.g., 95% of the PTV coverage with at least 100% of the prescription dose of 50 Gy). The gating window phase was ranked according to ROV-20, and the relationship between the OVH and dose distribution at each phase was evaluated by comparing the maximum dose, mean dose, and equivalent uniform dose of OAR. Results: OVHs showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. For 2 out of 3 patients (both with a target at RML), maximum dose, mean dose, and EUD increased as ROV-20 increased. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist and OVH can be a useful tool for determining such phases without performing dose optimization calculations in all phases. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2012-007883) through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea.« less

Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

PubMed

Elhennawy, Mai Gamal; Lin, Hai-Shu

2018-06-15

Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

Incorporating uncertainty and motion in Intensity Modulated Radiation Therapy treatment planning

NASA Astrophysics Data System (ADS)

Martin, Benjamin Charles

In radiation therapy, one seeks to destroy a tumor while minimizing the damage to surrounding healthy tissue. Intensity Modulated Radiation Therapy (IMRT) uses overlapping beams of x-rays that add up to a high dose within the target and a lower dose in the surrounding healthy tissue. IMRT relies on optimization techniques to create high quality treatments. Unfortunately, the possible conformality is limited by the need to ensure coverage even if there is organ movement or deformation. Currently, margins are added around the tumor to ensure coverage based on an assumed motion range. This approach does not ensure high quality treatments. In the standard IMRT optimization problem, an objective function measures the deviation of the dose from the clinical goals. The optimization then finds the beamlet intensities that minimize the objective function. When modeling uncertainty, the dose delivered from a given set of beamlet intensities is a random variable. Thus the objective function is also a random variable. In our stochastic formulation we minimize the expected value of this objective function. We developed a problem formulation that is both flexible and fast enough for use on real clinical cases. While working on accelerating the stochastic optimization, we developed a technique of voxel sampling. Voxel sampling is a randomized algorithms approach to a steepest descent problem based on estimating the gradient by only calculating the dose to a fraction of the voxels within the patient. When combined with an automatic sampling rate adaptation technique, voxel sampling produced an order of magnitude speed up in IMRT optimization. We also develop extensions of our results to Intensity Modulated Proton Therapy (IMPT). Due to the physics of proton beams the stochastic formulation yields visibly different and better plans than normal optimization. The results of our research have been incorporated into a software package OPT4D, which is an IMRT and IMPT optimization tool that we developed.

Optimal clinical trial design based on a dichotomous Markov-chain mixed-effect sleep model.

PubMed

Steven Ernest, C; Nyberg, Joakim; Karlsson, Mats O; Hooker, Andrew C

2014-12-01

D-optimal designs for discrete-type responses have been derived using generalized linear mixed models, simulation based methods and analytical approximations for computing the fisher information matrix (FIM) of non-linear mixed effect models with homogeneous probabilities over time. In this work, D-optimal designs using an analytical approximation of the FIM for a dichotomous, non-homogeneous, Markov-chain phase advanced sleep non-linear mixed effect model was investigated. The non-linear mixed effect model consisted of transition probabilities of dichotomous sleep data estimated as logistic functions using piecewise linear functions. Theoretical linear and nonlinear dose effects were added to the transition probabilities to modify the probability of being in either sleep stage. D-optimal designs were computed by determining an analytical approximation the FIM for each Markov component (one where the previous state was awake and another where the previous state was asleep). Each Markov component FIM was weighted either equally or by the average probability of response being awake or asleep over the night and summed to derive the total FIM (FIM(total)). The reference designs were placebo, 0.1, 1-, 6-, 10- and 20-mg dosing for a 2- to 6-way crossover study in six dosing groups. Optimized design variables were dose and number of subjects in each dose group. The designs were validated using stochastic simulation/re-estimation (SSE). Contrary to expectations, the predicted parameter uncertainty obtained via FIM(total) was larger than the uncertainty in parameter estimates computed by SSE. Nevertheless, the D-optimal designs decreased the uncertainty of parameter estimates relative to the reference designs. Additionally, the improvement for the D-optimal designs were more pronounced using SSE than predicted via FIM(total). Through the use of an approximate analytic solution and weighting schemes, the FIM(total) for a non-homogeneous, dichotomous Markov-chain phase advanced sleep model was computed and provided more efficient trial designs and increased nonlinear mixed-effects modeling parameter precision.

[Simplicity or complexity of the radiopharmaceutical production process in the light of optimization of radiation protection of staff - 99mTc vs. 18F].

PubMed

Wrzesień, Małgorzata

2018-05-22

A radiopharmaceutical is a combination of a non-radioactive compound with a radioactive isotope. Two isotopes: technetium-99m (99mTc) and fluorine-18 (18F) are worth mentioning on the rich list of isotopes which have found numerous medical applications. Their similarity is limited only to the diagnostic area of applicability. The type and the energy of emitted radiation, the half-life and, in particular, the production method demonstrate their diversity. The 99mTc isotope is produced by a short-lived nuclide generator - molybdenum-99 (99Mo)/99mTc, while 18F is resulting from nuclear reaction occurring in a cyclotron. A relatively simple and easy handling of the 99Mo/99mTc generator, compared to the necessary use a cyclotron, seems to favor the principle of optimizing the radiological protection of personnel. The thesis on the effect of automation of both the 18F isotope production and the deoxyglucose labelling process on the optimization of radiological protection of workers compared to manual procedures during handling of radiopharmaceuticals labelled with 99Tc need to be verified. Measurements of personal dose equivalent Hp(0.07) were made in 5 nuclear medicine departments and 2 radiopharmaceuticals production centers. High-sensitivity thermoluminescent detectors (LiF: Mg, Cu, P - MCP-N) were used to determine the doses. Among the activities performed by employees of both 18F-fluorodeoxyglucose (18F-FDG) production centers and nuclear medicine departments, the manual quality control procedures and labelling of radiopharmaceuticals with 99mTc isotope manifest the greatest contribution to the recorded Hp(0.07). The simplicity of obtaining the 99mTc isotope as well as the complex, but fully automated production process of the 18F-FDG radiopharmaceutical optimize the radiation protection of workers, excluding manual procedures labelling with 99mTc or quality control of 18F-FDG. Med Pr 2018;69(3):317–327. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Layout optimization of DRAM cells using rigorous simulation model for NTD

NASA Astrophysics Data System (ADS)

Jeon, Jinhyuck; Kim, Shinyoung; Park, Chanha; Yang, Hyunjo; Yim, Donggyu; Kuechler, Bernd; Zimmermann, Rainer; Muelders, Thomas; Klostermann, Ulrich; Schmoeller, Thomas; Do, Mun-hoe; Choi, Jung-Hoe

2014-03-01

DRAM chip space is mainly determined by the size of the memory cell array patterns which consist of periodic memory cell features and edges of the periodic array. Resolution Enhancement Techniques (RET) are used to optimize the periodic pattern process performance. Computational Lithography such as source mask optimization (SMO) to find the optimal off axis illumination and optical proximity correction (OPC) combined with model based SRAF placement are applied to print patterns on target. For 20nm Memory Cell optimization we see challenges that demand additional tool competence for layout optimization. The first challenge is a memory core pattern of brick-wall type with a k1 of 0.28, so it allows only two spectral beams to interfere. We will show how to analytically derive the only valid geometrically limited source. Another consequence of two-beam interference limitation is a "super stable" core pattern, with the advantage of high depth of focus (DoF) but also low sensitivity to proximity corrections or changes of contact aspect ratio. This makes an array edge correction very difficult. The edge can be the most critical pattern since it forms the transition from the very stable regime of periodic patterns to non-periodic periphery, so it combines the most critical pitch and highest susceptibility to defocus. Above challenge makes the layout correction to a complex optimization task demanding a layout optimization that finds a solution with optimal process stability taking into account DoF, exposure dose latitude (EL), mask error enhancement factor (MEEF) and mask manufacturability constraints. This can only be achieved by simultaneously considering all criteria while placing and sizing SRAFs and main mask features. The second challenge is the use of a negative tone development (NTD) type resist, which has a strong resist effect and is difficult to characterize experimentally due to negative resist profile taper angles that perturb CD at bottom characterization by scanning electron microscope (SEM) measurements. High resist impact and difficult model data acquisition demand for a simulation model that hat is capable of extrapolating reliably beyond its calibration dataset. We use rigorous simulation models to provide that predictive performance. We have discussed the need of a rigorous mask optimization process for DRAM contact cell layout yielding mask layouts that are optimal in process performance, mask manufacturability and accuracy. In this paper, we have shown the step by step process from analytical illumination source derivation, a NTD and application tailored model calibration to layout optimization such as OPC and SRAF placement. Finally the work has been verified with simulation and experimental results on wafer.

SU-G-JeP2-05: Dose Effects of a 1.5T Magnetic Field On Air-Tissue and Lung-Tissue Interfaces in MRI-Guided Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Xinfeng; Prior, Phillip; Chen, Guangpei

Purpose: The purpose of the study is to investigate the dose effects of electron-return-effect (ERE) at air-tissue and lung-tissue interfaces under a 1.5T transverse-magnetic-field (TMF). Methods: IMRT and VMAT plans for representative pancreas, lung, breast and head & neck (H&N) cases were generated following clinical dose volume (DV) criteria. The air-cavity walls, as well as the lung wall, were delineated to examine the ERE. In each case, the original plan generated without TMF is compared with the reconstructed plan (generated by recalculating the original plan with the presence of TMF) and the optimized plan (generated by a full optimization withmore » TMF), using a variety of DV parameters, including V100%, D95% and dose heterogeneity index for PTV, Dmax, and D1cc for OARs (organs at risk) and tissue interface. Results: The dose recalculation under TMF showed the presence of the 1.5 T TMF can slightly reduce V100% and D95% for PTV, with the differences being less than 4% for all but lung case studied. The TMF results in considerable increases in Dmax and D1cc on the skin in all cases, mostly between 10-35%. The changes in Dmax and D1cc on air cavity walls are dependent upon site, geometry, and size, with changes ranging up to 15%. In general, the VMAT plans lead to much smaller dose effects from ERE compared to fixed-beam IMRT. When the TMF is considered in the plan optimization, the dose effects of the TMF at tissue interfaces are significantly reduced in most cases. Conclusion: The doses on tissue interfaces can be significantly changed by the presence of a 1.5T TMF during MR-guided RT when the TMF is not included in plan optimization. These changes can be substantially reduced or even removed during VMAT/IMRT optimization that specifically considers the TMF, without deteriorating overall plan quality.« less

A geometrically based method for automated radiosurgery planning.

PubMed

Wagner, T H; Yi, T; Meeks, S L; Bova, F J; Brechner, B L; Chen, Y; Buatti, J M; Friedman, W A; Foote, K D; Bouchet, L G

2000-12-01

A geometrically based method of multiple isocenter linear accelerator radiosurgery treatment planning optimization was developed, based on a target's solid shape. Our method uses an edge detection process to determine the optimal sphere packing arrangement with which to cover the planning target. The sphere packing arrangement is converted into a radiosurgery treatment plan by substituting the isocenter locations and collimator sizes for the spheres. This method is demonstrated on a set of 5 irregularly shaped phantom targets, as well as a set of 10 clinical example cases ranging from simple to very complex in planning difficulty. Using a prototype implementation of the method and standard dosimetric radiosurgery treatment planning tools, feasible treatment plans were developed for each target. The treatment plans generated for the phantom targets showed excellent dose conformity and acceptable dose homogeneity within the target volume. The algorithm was able to generate a radiosurgery plan conforming to the Radiation Therapy Oncology Group (RTOG) guidelines on radiosurgery for every clinical and phantom target examined. This automated planning method can serve as a valuable tool to assist treatment planners in rapidly and consistently designing conformal multiple isocenter radiosurgery treatment plans.

A fast method to emulate an iterative POCS image reconstruction algorithm.

PubMed

Zeng, Gengsheng L

2017-10-01

Iterative image reconstruction algorithms are commonly used to optimize an objective function, especially when the objective function is nonquadratic. Generally speaking, the iterative algorithms are computationally inefficient. This paper presents a fast algorithm that has one backprojection and no forward projection. This paper derives a new method to solve an optimization problem. The nonquadratic constraint, for example, an edge-preserving denoising constraint is implemented as a nonlinear filter. The algorithm is derived based on the POCS (projections onto projections onto convex sets) approach. A windowed FBP (filtered backprojection) algorithm enforces the data fidelity. An iterative procedure, divided into segments, enforces edge-enhancement denoising. Each segment performs nonlinear filtering. The derived iterative algorithm is computationally efficient. It contains only one backprojection and no forward projection. Low-dose CT data are used for algorithm feasibility studies. The nonlinearity is implemented as an edge-enhancing noise-smoothing filter. The patient studies results demonstrate its effectiveness in processing low-dose x ray CT data. This fast algorithm can be used to replace many iterative algorithms. © 2017 American Association of Physicists in Medicine.

Optimum coagulant forecasting by modeling jar test experiments using ANNs

NASA Astrophysics Data System (ADS)

Haghiri, Sadaf; Daghighi, Amin; Moharramzadeh, Sina

2018-01-01

Currently, the proper utilization of water treatment plants and optimizing their use is of particular importance. Coagulation and flocculation in water treatment are the common ways through which the use of coagulants leads to instability of particles and the formation of larger and heavier particles, resulting in improvement of sedimentation and filtration processes. Determination of the optimum dose of such a coagulant is of particular significance. A high dose, in addition to adding costs, can cause the sediment to remain in the filtrate, a dangerous condition according to the standards, while a sub-adequate dose of coagulants can result in the reducing the required quality and acceptable performance of the coagulation process. Although jar tests are used for testing coagulants, such experiments face many constraints with respect to evaluating the results produced by sudden changes in input water because of their significant costs, long time requirements, and complex relationships among the many factors (turbidity, temperature, pH, alkalinity, etc.) that can influence the efficiency of coagulant and test results. Modeling can be used to overcome these limitations; in this research study, an artificial neural network (ANN) multi-layer perceptron (MLP) with one hidden layer has been used for modeling the jar test to determine the dosage level of used coagulant in water treatment processes. The data contained in this research have been obtained from the drinking water treatment plant located in Ardabil province in Iran. To evaluate the performance of the model, the mean squared error (MSE) and correlation coefficient (R2) parameters have been used. The obtained values are within an acceptable range that demonstrates the high accuracy of the models with respect to the estimation of water-quality characteristics and the optimal dosages of coagulants; so using these models will allow operators to not only reduce costs and time taken to perform experimental jar tests but also to predict a proper dosage for coagulant amounts and to project the quality of the output water under real conditions.

A fast optimization approach for treatment planning of volumetric modulated arc therapy.

PubMed

Yan, Hui; Dai, Jian-Rong; Li, Ye-Xiong

2018-05-30

Volumetric modulated arc therapy (VMAT) is widely used in clinical practice. It not only significantly reduces treatment time, but also produces high-quality treatment plans. Current optimization approaches heavily rely on stochastic algorithms which are time-consuming and less repeatable. In this study, a novel approach is proposed to provide a high-efficient optimization algorithm for VMAT treatment planning. A progressive sampling strategy is employed for beam arrangement of VMAT planning. The initial beams with equal-space are added to the plan in a coarse sampling resolution. Fluence-map optimization and leaf-sequencing are performed for these beams. Then, the coefficients of fluence-maps optimization algorithm are adjusted according to the known fluence maps of these beams. In the next round the sampling resolution is doubled and more beams are added. This process continues until the total number of beams arrived. The performance of VMAT optimization algorithm was evaluated using three clinical cases and compared to those of a commercial planning system. The dosimetric quality of VMAT plans is equal to or better than the corresponding IMRT plans for three clinical cases. The maximum dose to critical organs is reduced considerably for VMAT plans comparing to those of IMRT plans, especially in the head and neck case. The total number of segments and monitor units are reduced for VMAT plans. For three clinical cases, VMAT optimization takes < 5 min accomplished using proposed approach and is 3-4 times less than that of the commercial system. The proposed VMAT optimization algorithm is able to produce high-quality VMAT plans efficiently and consistently. It presents a new way to accelerate current optimization process of VMAT planning.

Influence of robust optimization in intensity-modulated proton therapy with different dose delivery techniques

PubMed Central

Liu, Wei; Li, Yupeng; Li, Xiaoqiang; Cao, Wenhua; Zhang, Xiaodong

2012-01-01

Purpose: The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique’s sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved. Methods: They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans’ sensitivity to uncertainties. Results: With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies. Conclusions: IMPT’s sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the optimization algorithm attempts to produce a single-field uniform dose distribution while minimizing the patching field as much as possible; and (2) perturbed dose distribution, which follows the change in anatomical geometry. Multiple-instance optimization has more knowledge of the influence matrices; this greater knowledge improves IMPT plans’ ability to retain robustness despite the presence of uncertainties. PMID:22755694

Optimization of Ammonium Sulfate Concentration for Purification of Colorectal Cancer Vaccine Candidate Recombinant Protein GA733-FcK Isolated from Plants.

PubMed

Park, Se-Ra; Lim, Chae-Yeon; Kim, Deuk-Su; Ko, Kisung

2015-01-01

A protein purification procedure is required to obtain high-value recombinant injectable vaccine proteins produced in plants as a bioreactor. However, existing purification procedures for plant-derived recombinant proteins are often not optimized and are inefficient, with low recovery rates. In our previous study, we used 25-30% ammonium sulfate to precipitate total soluble proteins (TSPs) in purification process for recombinant proteins from plant leaf biomass which has not been optimized. Thus, the objective in this study is to optimize the conditions for plant-derived protein purification procedures. Various ammonium sulfate concentrations (15-80%) were compared to determine their effects on TSPs yield. With 50% ammonium sulfate, the yield of precipitated TSP was the highest, and that of the plant-derived colorectal cancer-specific surface glycoprotein GA733 fused to the Fc fragment of human IgG tagged with endoplasmic reticulum retention signal KDEL (GA733(P)-FcK) protein significantly increased 1.8-fold. SDS-PAGE analysis showed that the purity of GA733(P)-FcK protein band appeared to be similar to that of an equal dose of mammalian-derived GA733-Fc (GA733(M)-Fc). The binding activity of purified GA733(P)-FcK to anti-GA733 mAb was as efficient as the native GA733(M)-Fc. Thus, the purification process was effectively optimized for obtaining a high yield of plant-derived antigenic protein with good quality. In conclusion, the purification recovery rate of large quantities of recombinant protein from plant expression systems can be enhanced via optimization of ammonium sulfate concentration during downstream processes, thereby offering a promising solution for production of recombinant GA733-Fc protein in plants.

Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity.

PubMed

Yasasvini, S; Anusa, R S; VedhaHari, B N; Prabhu, P C; RamyaDevi, D

2017-03-01

A prolonged release drug delivery system was developed by loading Simvastatin-chitosan microparticles into poly vinyl alcohol (PVA) hydrogels for enhanced wound healing efficiency. The microparticles prepared by ionic gelation method with varying composition of chitosan and surfactants (Tween 80/Pluronic F-127) were optimized for entrapment efficiency, morphology and drug-polymer interactions. Microparticles prepared with 0.3% between 80 and 0.5:5 chitosan: drug ratio showed maximum entrapment efficiency of 82% with spherical morphology and mild interaction between drug and chitosan. 5% PVA solutions loaded with pure drug and drug loaded microparticles at three different doses (2.5mg, 5mg and 10mg equivalent of drug) were chemically cross linked using gluteraldehyde and HCl. The formulated hydrogels were optimized for swelling, in vitro release behavior and in vivo wound healing effect. Hydrogels containing 2.5mg equivalent dose of Simvastatin microparticles exhibited maximum cumulative percentage drug release of 92% (n=3) at the end of 7days. The in vitro drug release data was supported by the higher swelling index of the low dose hydrogels. The in vivo wound healing study was performed using Wistar rats (n=30, 5 groups with 6 animals in each group) for the formulated hydrogels (at 3 doses) and compared with the untreated animals and the positive control group treated with conventional topical Simvastatin ointment (1%). The wound healing effect was comparable to the in vitro results, wherein the animals treated with low dose hydrogels (replaced every 7days) exhibited considerable reduction in the wound area compared to medium and high dose hydrogels. Statistically significant difference (P<0.05) was observed in the wound area of the animals treated with low dose hydrogels compared to 1% ointment and untreated animals, as estimated by two-way ANOVA. The histopathology images of the different groups of animals also displayed the comparative changes in the wound healing process. Hence, the incorporation of Simvastatin-chitosan microparticles in PVA hydrogels has demonstrated significant wound healing efficiency at optimum dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Discovery and Optimization of 4-(8-(3-Fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic Acid, an Improved PDE4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Press, Neil J; Taylor, Roger J; Fullerton, Joseph D; Tranter, Pamela; McCarthy, Clive; Keller, Thomas H; Arnold, Nicola; Beer, David; Brown, Lyndon; Cheung, Robert; Christie, Julie; Denholm, Alastair; Haberthuer, Sandra; Hatto, Julia D I; Keenan, Mark; Mercer, Mark K; Oakman, Helen; Sahri, Helene; Tuffnell, Andrew R; Tweed, Morris; Trifilieff, Alexandre

2015-09-10

Herein we describe the optimization of a series of PDE4 inhibitors, with special focus on solubility and pharamcokinetics, to clinical compound 2, 4-(8-(3-fluorophenyl)-1,7-naphthyridin-6-yl)transcyclohexanecarboxylic acid. Although compound 2 produces emesis in humans when given as a single dose, its exemplary pharmacokinetic properties enabled a novel dosing regime comprising multiple escalating doses and the resultant achievement of high plasma drug levels without associated nausea or emesis.

Defining robustness protocols: a method to include and evaluate robustness in clinical plans

NASA Astrophysics Data System (ADS)

McGowan, S. E.; Albertini, F.; Thomas, S. J.; Lomax, A. J.

2015-04-01

We aim to define a site-specific robustness protocol to be used during the clinical plan evaluation process. Plan robustness of 16 skull base IMPT plans to systematic range and random set-up errors have been retrospectively and systematically analysed. This was determined by calculating the error-bar dose distribution (ebDD) for all the plans and by defining some metrics used to define protocols aiding the plan assessment. Additionally, an example of how to clinically use the defined robustness database is given whereby a plan with sub-optimal brainstem robustness was identified. The advantage of using different beam arrangements to improve the plan robustness was analysed. Using the ebDD it was found range errors had a smaller effect on dose distribution than the corresponding set-up error in a single fraction, and that organs at risk were most robust to the range errors, whereas the target was more robust to set-up errors. A database was created to aid planners in terms of plan robustness aims in these volumes. This resulted in the definition of site-specific robustness protocols. The use of robustness constraints allowed for the identification of a specific patient that may have benefited from a treatment of greater individuality. A new beam arrangement showed to be preferential when balancing conformality and robustness for this case. The ebDD and error-bar volume histogram proved effective in analysing plan robustness. The process of retrospective analysis could be used to establish site-specific robustness planning protocols in proton therapy. These protocols allow the planner to determine plans that, although delivering a dosimetrically adequate dose distribution, have resulted in sub-optimal robustness to these uncertainties. For these cases the use of different beam start conditions may improve the plan robustness to set-up and range uncertainties.

Kinetic modeling and energy efficiency of UV/H₂O₂ treatment of iodinated trihalomethanes.

PubMed

Xiao, Yongjun; Zhang, Lifeng; Yue, Junqi; Webster, Richard D; Lim, Teik-Thye

2015-05-15

Photodegradation of I-THMs including CHCl2I and CHI3 by the UV/H2O2 system was investigated in this study. CHCl2I and CHI3 react rapidly with hydroxyl radical (OH) produced by the UV/H2O2 system, with second-order rate constants of 8.0 × 10(9) and 8.9 × 10(9) M(-1) s(-1), respectively. A fraction of CHCl2I could be completely mineralized within 15 min and the remaining fraction was mainly converted to formic acid (HCO2H). Cl(-) and I(-) were identified as the predominant end-products. No ClO3(-) was observed during the photodegradation process, while IO3(-) was detected but at less than 2% of the total liberated iodine species at the end of the reaction. The effects of pH, H2O2 dose, and matrix species such as humic acid (HA), HCO3(-), SO4(2-), Cl(-), NO3(-) on the photodegradation kinetics were evaluated. The steady-state kinetic model has been proven to successfully predict the destruction of CHCl2I and CHI3 by UV/H2O2 in different water matrices. On this basis, the kinetic model combined with electrical energy per order (EE/O) concept was applied to evaluate the efficiency of the photodegradation process and to optimize the H2O2 dose for different scenarios. The optimal H2O2 doses in deionized (DI) water, model natural water, and surface water are estimated at 5, 12, and 16 mg L(-1), respectively, which correspond to the lowest total energy consumption (EE/Ototal) of 0.2, 0.31, and 0.45 kWhm(-3)order(-1). Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanoscale Fe/Ag particles activated persulfate: optimization using response surface methodology.

PubMed

Silveira, Jefferson E; Barreto-Rodrigues, Marcio; Cardoso, Tais O; Pliego, Gema; Munoz, Macarena; Zazo, Juan A; Casas, José A

2017-05-01

This work studied the bimetallic nanoparticles Fe-Ag (nZVI-Ag) activated persulfate (PS) in aqueous solution using response surface methodology. The Box-Behnken design (BBD) was employed to optimize three parameters (nZVI-Ag dose, reaction temperature, and PS concentration) using 4-chlorophenol (4-CP) as the target pollutant. The synthesis of nZVI-Ag particles was carried out through a reduction of FeCl 2 with NaBH 4 followed by reductive deposition of Ag. The catalyst was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Brunauer-Emmett-Teller (BET) surface area. The BBD was considered a satisfactory model to optimize the process. Confirmatory tests were carried out using predicted and experimental values under the optimal conditions (50 mg L -1 nZVI-Ag, 21 mM PS at 57 °C) and the complete removal of 4-CP achieved experimentally was successfully predicted by the model, whereas the mineralization degree predicted (90%) was slightly overestimated against the measured data (83%).

Feasibility of TCP-based dose painting by numbers applied to a prostate case with (18)F-choline PET imaging.

PubMed

Dirscherl, Thomas; Rickhey, Mark; Bogner, Ludwig

2012-02-01

A biologically adaptive radiation treatment method to maximize the TCP is shown. Functional imaging is used to acquire a heterogeneous dose prescription in terms of Dose Painting by Numbers and to create a patient-specific IMRT plan. Adapted from a method for selective dose escalation under the guidance of spatial biology distribution, a model, which translates heterogeneously distributed radiobiological parameters into voxelwise dose prescriptions, was developed. At the example of a prostate case with (18)F-choline PET imaging, different sets of reported values for the parameters were examined concerning their resulting range of dose values. Furthermore, the influence of each parameter of the linear-quadratic model was investigated. A correlation between PET signal and proliferation as well as cell density was assumed. Using our in-house treatment planning software Direct Monte Carlo Optimization (DMCO), a treatment plan based on the obtained dose prescription was generated. Gafchromic EBT films were irradiated for evaluation. When a TCP of 95% was aimed at, the maximal dose in a voxel of the prescription exceeded 100Gy for most considered parameter sets. One of the parameter sets resulted in a dose range of 87.1Gy to 99.3Gy, yielding a TCP of 94.7%, and was investigated more closely. The TCP of the plan decreased to 73.5% after optimization based on that prescription. The dose difference histogram of optimized and prescribed dose revealed a mean of -1.64Gy and a standard deviation of 4.02Gy. Film verification showed a reasonable agreement of planned and delivered dose. If the distribution of radiobiological parameters within a tumor is known, this model can be used to create a dose-painting by numbers plan which maximizes the TCP. It could be shown, that such a heterogeneous dose distribution is technically feasible. Copyright © 2012. Published by Elsevier GmbH.

Multicriteria plan optimization in the hands of physicians: a pilot study in prostate cancer and brain tumors.

PubMed

Müller, Birgit S; Shih, Helen A; Efstathiou, Jason A; Bortfeld, Thomas; Craft, David

2017-11-06

The purpose of this study was to demonstrate the feasibility of physician driven planning in intensity modulated radiotherapy (IMRT) with a multicriteria optimization (MCO) treatment planning system and template based plan optimization. Exploiting the full planning potential of MCO navigation, this alternative planning approach intends to improve planning efficiency and individual plan quality. Planning was retrospectively performed on 12 brain tumor and 10 post-prostatectomy prostate patients previously treated with MCO-IMRT. For each patient, physicians were provided with a template-based generated Pareto surface of optimal plans to navigate, using the beam angles from the original clinical plans. We compared physician generated plans to clinically delivered plans (created by dosimetrists) in terms of dosimetric differences, physician preferences and planning times. Plan qualities were similar, however physician generated and clinical plans differed in the prioritization of clinical goals. Physician derived prostate plans showed significantly better sparing of the high dose rectum and bladder regions (p(D1) < 0.05; D1: dose received by 1% of the corresponding structure). Physicians' brain tumor plans indicated higher doses for targets and brainstem (p(D1) < 0.05). Within blinded plan comparisons physicians preferred the clinical plans more often (brain: 6:3 out of 12, prostate: 2:6 out of 10) (not statistically significant). While times of physician involvement were comparable for prostate planning, the new workflow reduced the average involved time for brain cases by 30%. Planner times were reduced for all cases. Subjective benefits, such as a better understanding of planning situations, were observed by clinicians through the insight into plan optimization and experiencing dosimetric trade-offs. We introduce physician driven planning with MCO for brain and prostate tumors as a feasible planning workflow. The proposed approach standardizes the planning process by utilizing site specific templates and integrates physicians more tightly into treatment planning. Physicians' navigated plan qualities were comparable to the clinical plans. Given the reduction of planning time of the planner and the equal or lower planning time of physicians, this approach has the potential to improve departmental efficiencies.

Optimal medication dosing from suboptimal clinical examples: a deep reinforcement learning approach.

PubMed

Nemati, Shamim; Ghassemi, Mohammad M; Clifford, Gari D

2016-08-01

Misdosing medications with sensitive therapeutic windows, such as heparin, can place patients at unnecessary risk, increase length of hospital stay, and lead to wasted hospital resources. In this work, we present a clinician-in-the-loop sequential decision making framework, which provides an individualized dosing policy adapted to each patient's evolving clinical phenotype. We employed retrospective data from the publicly available MIMIC II intensive care unit database, and developed a deep reinforcement learning algorithm that learns an optimal heparin dosing policy from sample dosing trails and their associated outcomes in large electronic medical records. Using separate training and testing datasets, our model was observed to be effective in proposing heparin doses that resulted in better expected outcomes than the clinical guidelines. Our results demonstrate that a sequential modeling approach, learned from retrospective data, could potentially be used at the bedside to derive individualized patient dosing policies.

Randomized Controlled Double-Blind Trial of Optimal Dose Methylphenidate in Children and Adolescents with Severe Attention Deficit Hyperactivity Disorder and Intellectual Disability

ERIC Educational Resources Information Center

Simonoff, Emily; Taylor, Eric; Baird, Gillian; Bernard, Sarah; Chadwick, Oliver; Liang, Holan; Whitwell, Susannah; Riemer, Kirsten; Sharma, Kishan; Sharma, Santvana Pandey; Wood, Nicky; Kelly, Joanna; Golaszewski, Ania; Kennedy, Juliet; Rodney, Lydia; West, Nicole; Walwyn, Rebecca; Jichi, Fatima

2013-01-01

Background: Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks. Method: One hundred and…

A Randomized, Double-Blind, Placebo-Controlled, Laboratory Classroom Assessment of Methylphenidate Transdermal System in Children with ADHD

ERIC Educational Resources Information Center

McGough, James J.; Wigal, Sharon B.; Abikoff, Howard; Turnbow, John M.; Posner, Kelly; Moon, Eliot

2006-01-01

Objective: This study evaluates the efficacy, duration of action, and tolerability of methylphenidate transdermal system (MTS) in children with ADHD. Method: Participants were dose optimized over 5 weeks utilizing patch doses of 10, 16, 20, and 27 mg applied in the morning and worn for 9 hours. Following optimization, 80 participants were…

Comparison of optimization algorithms in intensity-modulated radiation therapy planning

NASA Astrophysics Data System (ADS)

Kendrick, Rachel

Intensity-modulated radiation therapy is used to better conform the radiation dose to the target, which includes avoiding healthy tissue. Planning programs employ optimization methods to search for the best fluence of each photon beam, and therefore to create the best treatment plan. The Computational Environment for Radiotherapy Research (CERR), a program written in MATLAB, was used to examine some commonly-used algorithms for one 5-beam plan. Algorithms include the genetic algorithm, quadratic programming, pattern search, constrained nonlinear optimization, simulated annealing, the optimization method used in Varian EclipseTM, and some hybrids of these. Quadratic programing, simulated annealing, and a quadratic/simulated annealing hybrid were also separately compared using different prescription doses. The results of each dose-volume histogram as well as the visual dose color wash were used to compare the plans. CERR's built-in quadratic programming provided the best overall plan, but avoidance of the organ-at-risk was rivaled by other programs. Hybrids of quadratic programming with some of these algorithms seems to suggest the possibility of better planning programs, as shown by the improved quadratic/simulated annealing plan when compared to the simulated annealing algorithm alone. Further experimentation will be done to improve cost functions and computational time.

Application of low-mixing energy input for the coagulation process.

PubMed

Vadasarukkai, Yamuna S; Gagnon, Graham A

2015-11-01

Rapid-mixing tanks with mechanical mixers are a common design used in treatment plants. Yet, the role of such rapid-mixing systems on the effectiveness of the coagulation performance is unclear. This study looked at optimizing the direct energy used in the coagulation process for removal of natural dissolved organic matter (DOM). The role of coagulation mixing intensity (G-value) on total organic carbon (TOC) and turbidity removal was examined for the water types with high organic content, with a specific ultraviolet absorbance (SUVA) of at least 2-2.5 units of m(-1) of absorbance per mg/L. A standard jar test using ferric sulfate coagulant was performed to optimize the chemical condition in coagulation for removal of dissolved organics as well as particles. The jar test analysis at an acidic pH (4.5 ± 0.3) required an iron dose <0.3 mM to arrive at an optimal coagulant concentration and resulted in above 75% of TOC removal. The influence of coagulation mixing on TOC and turbidity removal was evaluated at G varying from 0 to 1500 s(-1) at the optimized coagulant dose and pH conditions for enhanced coagulation. In this study, a combined effective removal of TOC and turbidity was achieved at a low-mixing intensity range of 110 s(-1) < G < 450 s(-1). Coagulation operated at G greater than 450 s(-1) showed negligible improvement in TOC removal. Minimizing energy consumption in enhanced coagulation is feasible at the proposed mixing intensity range (i.e., 110 s(-1) < G < 450 s(-1)), without sacrificing the effectiveness of DOM removal by coagulation. These findings represent an opportunity for energy savings for the water industry without sacrificing quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prediction of an Optimal Dose of Aripiprazole in the Treatment of Schizophrenia From Plasma Concentrations of Aripiprazole Plus Its Active Metabolite Dehydroaripiprazole at Week 1.

PubMed

Nagai, Goyo; Mihara, Kazuo; Nakamura, Akifumi; Nemoto, Kenji; Kagawa, Shoko; Suzuki, Takeshi; Kondo, Tsuyoshi

2017-02-01

It has been suggested that a plasma trough concentration of aripiprazole plus its active metabolite, dehydroaripiprazole of 225 ng/mL is a threshold for a good therapeutic response in the treatment of acutely exacerbated patients with schizophrenia. The present study investigated whether or not an optimal dose of aripiprazole could be predicted from these concentrations at week 1. The subjects were 26 inpatients with schizophrenia, who received aripiprazole once a day for 3 weeks. The daily doses were 12 mg for the first week and 24 mg for the next 2 weeks. No other drugs except biperiden and flunitrazepam were coadministered. Blood samples were taken at weeks 1 and 3 after the treatment. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass-spectrometric detection. There was a significant linear relationship between the plasma concentrations of aripiprazole plus dehydroaripiprazole at weeks 1 (x) and 3 (y) (P < 0.001). Regression equation was y = 2.580x + 34.86 (R = 0.698). Based on the equation, a nomogram to estimate an optimal dose of aripiprazole could be constructed. The present study suggests that an optimal dose of aripiprazole for the treatment of patients with schizophrenia can be predicted from the plasma concentrations of the sum of the 2 compounds at week 1.

Design of gefitinib-loaded poly (l-lactic acid) microspheres via a supercritical anti-solvent process for dry powder inhalation.

PubMed

Lin, Qing; Liu, Guijin; Zhao, Ziyi; Wei, Dongwei; Pang, Jiafeng; Jiang, Yanbin

2017-10-30

To develop a safer, more stable and potent formulation of gefitinib (GFB), micro-spheres of GFB encapsulated into poly (l-lactic acid) (PLLA) have been prepared by supercritical anti-solvent (SAS) technology in this study. Operating factors were optimized using a selected OA 16 (4 5 ) orthogonal array design, and the properties of the raw material and SAS processed samples were characterized by different methods The results show that the GFB-loaded PLLA particles prepared were spherical, having a smaller and narrower particle size compared with raw GFB. The optimal GFB-loaded PLLA sample was prepared with less aggregation, highest GFB loading (15.82%) and smaller size (D 50 =2.48μm, which meets the size of dry powder inhalers). The results of XRD and DSC indicate that GFB is encapsulated into PLLA matrix in a polymorphic form different from raw GFB. FT-IR results show that the chemical structure of GFB does not change after the SAS process. The results of in vitro release show that the optimal sample release was slower compared with raw GFB particles. Moreover, the results of in vitro anti-cancer trials show that the optimal sample had a higher cytotoxicity than raw GFB. After blending with sieved lactose, the flowability and aerosolization performance of the optimal sample for DPI were improved, with angle of repose, emitted dose and fine particles fractions from 38.4° to 23°, 63.21% to >90%, 23.37% to >30%, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of DVH parameters and loading patterns of standard loading, manual and inverse optimization for intracavitary brachytherapy on a subset of tandem/ovoid cases.

PubMed

Jamema, Swamidas V; Kirisits, Christian; Mahantshetty, Umesh; Trnkova, Petra; Deshpande, Deepak D; Shrivastava, Shyam K; Pötter, Richard

2010-12-01

Comparison of inverse planning with the standard clinical plan and with the manually optimized plan based on dose-volume parameters and loading patterns. Twenty-eight patients who underwent MRI based HDR brachytherapy for cervix cancer were selected for this study. Three plans were calculated for each patient: (1) standard loading, (2) manual optimized, and (3) inverse optimized. Dosimetric outcomes from these plans were compared based on dose-volume parameters. The ratio of Total Reference Air Kerma of ovoid to tandem (TRAK(O/T)) was used to compare the loading patterns. The volume of HR CTV ranged from 9-68 cc with a mean of 41(±16.2) cc. Mean V100 for standard, manual optimized and inverse plans was found to be not significant (p=0.35, 0.38, 0.4). Dose to bladder (7.8±1.6 Gy) and sigmoid (5.6±1.4 Gy) was high for standard plans; Manual optimization reduced the dose to bladder (7.1±1.7 Gy p=0.006) and sigmoid (4.5±1.0 Gy p=0.005) without compromising the HR CTV coverage. The inverse plan resulted in a significant reduction to bladder dose (6.5±1.4 Gy, p=0.002). TRAK was found to be 0.49(±0.02), 0.44(±0.04) and 0.40(±0.04) cGy m(-2) for the standard loading, manual optimized and inverse plans, respectively. It was observed that TRAK(O/T) was 0.82(±0.05), 1.7(±1.04) and 1.41(±0.93) for standard loading, manual optimized and inverse plans, respectively, while this ratio was 1 for the traditional loading pattern. Inverse planning offers good sparing of critical structures without compromising the target coverage. The average loading pattern of the whole patient cohort deviates from the standard Fletcher loading pattern. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Incorporating geometric ray tracing to generate initial conditions for intensity modulated arc therapy optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oliver, Mike; Gladwish, Adam; Craig, Jeff

2008-07-15

Purpose and background: Intensity modulated arc therapy (IMAT) is a rotational variant of Intensity modulated radiation therapy (IMRT) that is achieved by allowing the multileaf collimator (MLC) positions to vary as the gantry rotates around the patient. This work describes a method to generate an IMAT plan through the use of a fast ray tracing technique based on dosimetric and geometric information for setting initial MLC leaf positions prior to final IMAT optimization. Methods and materials: Three steps were used to generate an IMAT plan. The first step was to generate arcs based on anatomical contours. The second step wasmore » to generate ray importance factor (RIF) maps by ray tracing the dose distribution inside the planning target volume (PTV) to modify the MLC leaf positions of the anatomical arcs to reduce the maximum dose inside the PTV. The RIF maps were also segmented to create a new set of arcs to improve the dose to low dose voxels within the PTV. In the third step, the MLC leaf positions from all arcs were put through a leaf position optimization (LPO) algorithm and brought into a fast Monte Carlo dose calculation engine for a final dose calculation. The method was applied to two phantom cases, a clinical prostate case and the Radiological Physics Center (RPC)'s head and neck phantom. The authors assessed the plan improvements achieved by each step and compared plans with and without using RIF. They also compared the IMAT plan with an IMRT plan for the RPC phantom. Results: All plans that incorporated RIF and LPO had lower objective function values than those that incorporated LPO only. The objective function value was reduced by about 15% after the generation of RIF arcs and 52% after generation of RIF arcs and leaf position optimization. The IMAT plan for the RPC phantom had similar dose coverage for PTV1 and PTV2 (the same dose volume histogram curves), however, slightly lower dose to the normal tissues compared to a six-field IMRT plan. Conclusion: The use of a ray importance factor can generate initial IMAT arcs efficiently for further MLC leaf position optimization to obtain more favorable IMAT plan.« less

Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.

PubMed

Kim, Kyu Nam; Kim, Kyo Sang; Choi, Hoon Il; Jeong, Ji Seon; Lee, Hee-Jong

2014-06-01

Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Precurarization with 0.04 mg/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.

An FDA oncology analysis of immune activating products and first-in-human dose selection.

PubMed

Saber, Haleh; Gudi, Ramadevi; Manning, Michael; Wearne, Emily; Leighton, John K

2016-11-01

As sub-therapeutic doses are not medically justifiable in patients with cancer, we retrospectively analyzed data on immune activating products, to assess approaches used in first-in-human (FIH) dose selection, the utility of animal toxicology studies in dose selection, and the length of time to complete FIH trials. The information collected included pharmacology and toxicology data, FIH dose and rationale, and dose-finding trial design. We used the principles of the Hill equation to estimate the FIH doses for antibodies and compared them to the doses administered to patients with acceptable toxicities. For approximately half the antibodies (44%) examined, the FIH doses were at least a hundred-fold lower than the doses safely administered to patients, indicating optimization of FIH dose selection and/or optimization of dose-finding trial design is needed to minimize patient exposure to sub-therapeutic doses. However, selection of the FIH dose for antibodies based on animal toxicology studies using 1/6th the HNSTD or 1/10th the NOAEL resulted in human doses that were unsafe for several antibodies examined. We also concluded that antibodies with Fc-modifications for increased effector function may be less tolerated, resulting in toxicities at lower doses than those without such modifications. There was insufficient information to evaluate CD3 bispecific products. Published by Elsevier Inc.

Clinical applications of advanced rotational radiation therapy

NASA Astrophysics Data System (ADS)

Nalichowski, Adrian

Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates. Methods and Materials: An anthropomorphic phantom was used to create TMI plans using the new GPU based treatment planning system and the existing CPU cluster based system. Optimization parameters were selected based on clinically used values for field width, modulation factor and pitch. Treatment plans were also created on Eclipse treatment planning system (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) for dose delivery on IX treatment unit. A retrospective review was performed of 42 publications that reported IP rates along with lung dose, fractionation regimen, dose rate and chemotherapy. The analysis consisted of nearly thirty two hundred patients and 34 unique radiation regimens. Multivariate logistic regression was performed to determine parameters associated with IP and establish does response function. Results: The results showed very good dosimetric agreement between the GPU and CPU calculated plans. The results from SBRT study show that GPU planning system can maintain 90% target coverage while meeting all the constraints of RTOG 0631 protocol. Beam on time for Tomotherapy and flattening filter free RapidArc was much faster than for Vero or Cyberknife. Retrospective data analysis showed that lung dose and Cyclophosphomide (Cy) are both predictors of IP in TBI/TMI treatments. The dose rate was not found to be an independent risk factor for IP. The model failed to establish accurate dose response function, but the discrete data indicated a radiation dose threshold of 7.6Gy (EQD2_repair) and 120 mg/kg of Cy below which no IP cases were reported. Conclusion: The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation. The new system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing when compared to Eclipse treatment planning system for VMAT delivery. The machine optimization parameters tested for TMI cases provide a comprehensive overview of the capabilities of the treatment planning station and associated helical delivery system. The new system also proved to be dosimetrically compatible with other leading modalities for treatments of small and complicated target volumes and was even superior when treatment delivery times were compared. These finding demonstrate that the advanced treatment planning and delivery system from TomoTherapy is well suitable for treatments of complicated cases such as TMI and SRS and it's often dosimetrically and/or logistically superior to other modalities. The new planning system can easily meet the constraint of threshold lung dose established in this study. The results presented here on the capabilities of Tomotherapy and on the identified lung dose threshold provide an opportunity to explore alternative fractionation schemes without sacrificing target coverage or lung toxicity. (Abstract shortened by ProQuest.).

Evaluation of automatic exposure control system chamber for the dose optimization when examining pelvic in digital radiography.

PubMed

Kim, Sung-Chul; Lee, Hae-Kag; Lee, Yang-Sub; Cho, Jae-Hwan

2015-01-01

We found a way to optimize the image quality and reduce the exposure dose of patients through the proper activity combination of the automatic exposure control system chamber for the dose optimization when examining the pelvic anteroposterior side using the phantom of the human body standard model. We set 7 combinations of the chamber of automatic exposure control system. The effective dose was yielded by measuring five times for each according to the activity combination of the chamber for the dose measurement. Five radiologists with more than five years of experience evaluated the image through picture archiving and communication system using double blind test while classifying the 6 anatomical sites into 3-point level (improper, proper, perfect). When only one central chamber was activated, the effective dose was found to be the highest level, 0.287 mSv; and lowest when only the top left chamber was used, 0.165 mSv. After the subjective evaluation by five panel members on the pelvic image was completed, there was no statistically meaningful difference between the 7 chamber combinations, and all had good image quality. When testing the pelvic anteroposterior side with digital radiography, we were able to reduce the exposure dose of patients using the combination of the top right side of or the top two of the chamber.

Dose responses in a normoxic polymethacrylic acid gel dosimeter using optimal CT scanning parameters

NASA Astrophysics Data System (ADS)

Cho, K. H.; Cho, S. J.; Lee, S.; Lee, S. H.; Min, C. K.; Kim, Y. H.; Moon, S. K.; Kim, E. S.; Chang, A. R.; Kwon, S. I.

2012-05-01

The dosimetric characteristics of normoxic polymethacrylic acid gels are investigated using optimal CT scanning parameters and the possibility of their clinical application is also considered. The effects of CT scanning parameters (tube voltage, tube current, scan time, slick thickness, field of view, and reconstruction algorithm) are experimentally investigated to determine the optimal parameters for minimizing the amount of noise in images obtained using normoxic polymethacrylic acid gel. In addition, the dose sensitivity, dose response, accuracy, and reproducibility of the normoxic polymethacrylic acid gel are evaluated. CT images are obtained using a head phantom that is fabricated for clinical applications. In addition, IMRT treatment planning is performed using a Tomotherapy radiation treatment planning system. A program for analyzing the results is produced using Visual C. A comparison between the treatment planning and the CT images of irradiated gels is performed. The dose sensitivity is found to be 2.41±0.04 HGy-1. The accuracies of dose evaluation at doses of 2 Gy and 4 Gy are 3.0% and 2.6%, respectively, and their reproducibilities are 2.0% and 2.1%, respectively. In the comparison of gel and Tomotherpay planning, the pass rate of the γ-index, based on the reference values of a dose error of 3% and a DTA of 3 mm, is 93.7%.

Development of a Chlorine Dosing Strategy for Fresh Produce Washing Process to Maintain Microbial Food Safety and Minimize Residual Chlorine.

PubMed

Chen, Xi; Hung, Yen-Con

2018-06-01

The residual free chlorine level in fresh produce wash solution is closely correlated to the chemical and microbial safety of produce. Excess amount of free chlorine can quickly react with organic matters to form hazardous disinfection by-products (DBPs) above EPA-permitted levels, whereas deficiency of residual chlorine in produce wash solution may result in incompletely removing pathogens on produce. The purpose of this study was to develop a chlorine dosing strategy to optimize the chlorine dosage during produce washing process without impacting the microbial safety of fresh produce. Prediction equations were developed to estimate free chlorine needed to reach targeted residual chlorine at various sanitizer pH and organic loads, and then validated using fresh-cut iceberg lettuce and whole strawberries in an automated produce washer. Validation results showed that equations successfully predicted the initial chlorine concentration needed to achieve residual chlorine at 10, 30, 60, and 90 mg/L for both lettuce and strawberry washing processes, with the root mean squared error at 4.45 mg/L. The Escherichia coli O157:H7 reductions only slightly increased on iceberg lettuce and strawberries with residual chlorine increasing from 10 to 90 mg/L, indicating that lowering residual chlorine to 10 mg/L would not compromise the antimicrobial efficacy of chlorine-based sanitizer. Based on the prediction equations and E. coli O157:H7 reduction results, a chlorine dosing strategy was developed to help the produce industry to maintain microbial inactivation efficacy without adding excess amount of free chlorine. The chlorine dosing strategy can be used for fresh produce washing process to enhance the microbial food safety and minimize the DBPs formation potential. © 2018 Institute of Food Technologists®.

Multi-Constraint Multi-Variable Optimization of Source-Driven Nuclear Systems

NASA Astrophysics Data System (ADS)

Watkins, Edward Francis

1995-01-01

A novel approach to the search for optimal designs of source-driven nuclear systems is investigated. Such systems include radiation shields, fusion reactor blankets and various neutron spectrum-shaping assemblies. The novel approach involves the replacement of the steepest-descents optimization algorithm incorporated in the code SWAN by a significantly more general and efficient sequential quadratic programming optimization algorithm provided by the code NPSOL. The resulting SWAN/NPSOL code system can be applied to more general, multi-variable, multi-constraint shield optimization problems. The constraints it accounts for may include simple bounds on variables, linear constraints, and smooth nonlinear constraints. It may also be applied to unconstrained, bound-constrained and linearly constrained optimization. The shield optimization capabilities of the SWAN/NPSOL code system is tested and verified in a variety of optimization problems: dose minimization at constant cost, cost minimization at constant dose, and multiple-nonlinear constraint optimization. The replacement of the optimization part of SWAN with NPSOL is found feasible and leads to a very substantial improvement in the complexity of optimization problems which can be efficiently handled.

Lens dose in routine head CT: comparison of different optimization methods with anthropomorphic phantoms.

PubMed

Nikupaavo, Ulla; Kaasalainen, Touko; Reijonen, Vappu; Ahonen, Sanna-Mari; Kortesniemi, Mika

2015-01-01

The purpose of this study was to study different optimization methods for reducing eye lens dose in head CT. Two anthropomorphic phantoms were scanned with a routine head CT protocol for evaluation of the brain that included bismuth shielding, gantry tilting, organ-based tube current modulation, or combinations of these techniques. Highsensitivity metal oxide semiconductor field effect transistor dosimeters were used to measure local equivalent doses in the head region. The relative changes in image noise and contrast were determined by ROI analysis. The mean absorbed lens doses varied from 4.9 to 19.7 mGy and from 10.8 to 16.9 mGy in the two phantoms. The most efficient method for reducing lens dose was gantry tilting, which left the lenses outside the primary radiation beam, resulting in an approximately 75% decrease in lens dose. Image noise decreased, especially in the anterior part of the brain. The use of organ-based tube current modulation resulted in an approximately 30% decrease in lens dose. However, image noise increased as much as 30% in the posterior and central parts of the brain. With bismuth shields, it was possible to reduce lens dose as much as 25%. Our results indicate that gantry tilt, when possible, is an effective method for reducing exposure of the eye lenses in CT of the brain without compromising image quality. Measurements in two different phantoms showed how patient geometry affects the optimization. When lenses can only partially be cropped outside the primary beam, organ-based tube current modulation or bismuth shields can be useful in lens dose reduction.

Pharmacological management of anticholinergic delirium - theory, evidence and practice.

PubMed

Dawson, Andrew H; Buckley, Nicholas A

2016-03-01

The spectrum of anticholinergic delirium is a common complication following drug overdose. Patients with severe toxicity can have significant distress and behavioural problems that often require pharmacological management. Cholinesterase inhibitors, such as physostigmine, are effective but widespread use has been limited by concerns about safety, optimal dosing and variable supply. Case series support efficacy in reversal of anticholinergic delirium. However doses vary widely and higher doses commonly lead to cholinergic toxicity. Seizures are reported in up to 2.5% of patients and occasional cardiotoxic effects are also recorded. This article reviews the serendipitous path whereby physostigmine evolved into the preferred anticholinesterase antidote largely without any research to indicate the optimal dosing strategy. Adverse events observed in case series should be considered in the context of pharmacokinetic/pharmacodynamic studies of physostigmine which suggest a much longer latency before the maximal increase in brain acetylcholine than had been previously assumed. This would favour protocols that use lower doses and longer re-dosing intervals. We propose based on the evidence reviewed that the use of cholinesterase inhibitors should be considered in anticholinergic delirium that has not responded to non-pharmacological delirium management. The optimal risk/benefit would be with a titrated dose of 0.5 to 1 mg physostigmine (0.01-0.02 mg kg(-1) in children) with a minimum delay of 10-15 min before re-dosing. Slower onset and longer acting agents such as rivastigmine would also be logical but more research is needed to guide the appropriate dose in this setting. © 2015 The British Pharmacological Society.

Finding optimal vaccination strategies for pandemic influenza using genetic algorithms.

PubMed

Patel, Rajan; Longini, Ira M; Halloran, M Elizabeth

2005-05-21

In the event of pandemic influenza, only limited supplies of vaccine may be available. We use stochastic epidemic simulations, genetic algorithms (GA), and random mutation hill climbing (RMHC) to find optimal vaccine distributions to minimize the number of illnesses or deaths in the population, given limited quantities of vaccine. Due to the non-linearity, complexity and stochasticity of the epidemic process, it is not possible to solve for optimal vaccine distributions mathematically. However, we use GA and RMHC to find near optimal vaccine distributions. We model an influenza pandemic that has age-specific illness attack rates similar to the Asian pandemic in 1957-1958 caused by influenza A(H2N2), as well as a distribution similar to the Hong Kong pandemic in 1968-1969 caused by influenza A(H3N2). We find the optimal vaccine distributions given that the number of doses is limited over the range of 10-90% of the population. While GA and RMHC work well in finding optimal vaccine distributions, GA is significantly more efficient than RMHC. We show that the optimal vaccine distribution found by GA and RMHC is up to 84% more effective than random mass vaccination in the mid range of vaccine availability. GA is generalizable to the optimization of stochastic model parameters for other infectious diseases and population structures.

Design of experiments in medical physics: Application to the AAA beam model validation.

PubMed

Dufreneix, S; Legrand, C; Di Bartolo, C; Bremaud, M; Mesgouez, J; Tiplica, T; Autret, D

2017-09-01

The purpose of this study is to evaluate the usefulness of the design of experiments in the analysis of multiparametric problems related to the quality assurance in radiotherapy. The main motivation is to use this statistical method to optimize the quality assurance processes in the validation of beam models. Considering the Varian Eclipse system, eight parameters with several levels were selected: energy, MLC, depth, X, Y 1 and Y 2 jaw dimensions, wedge and wedge jaw. A Taguchi table was used to define 72 validation tests. Measurements were conducted in water using a CC04 on a TrueBeam STx, a TrueBeam Tx, a Trilogy and a 2300IX accelerator matched by the vendor. Dose was computed using the AAA algorithm. The same raw data was used for all accelerators during the beam modelling. The mean difference between computed and measured doses was 0.1±0.5% for all beams and all accelerators with a maximum difference of 2.4% (under the 3% tolerance level). For all beams, the measured doses were within 0.6% for all accelerators. The energy was found to be an influencing parameter but the deviations observed were smaller than 1% and not considered clinically significant. Designs of experiment can help define the optimal measurement set to validate a beam model. The proposed method can be used to identify the prognostic factors of dose accuracy. The beam models were validated for the 4 accelerators which were found dosimetrically equivalent even though the accelerator characteristics differ. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-E-J-52: Dosimetric Benefit of Adaptive Re-Planning in Lung Cancer Stereotactic Body Radiotherapy (SBRT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jia, J; Tian, Z; Gu, X

Purpose: To investigate the dosimetric benefit of adaptive re-planning for lung stereotactic body radiotherapy(SBRT). Methods: Five lung cancer patients with SBRT treatment were retrospectively investigated. Our in-house supercomputing online re-planning environment (SCORE) was used to realize the re-planning process. First a deformable image registration was carried out to transfer contours from treatment planning CT to each treatment CBCT. Then an automatic re-planning using original plan DVH guided fluence-map optimization is performed to get a new plan for the up-to-date patient geometry. We compared the re-optimized plan to the original plan projected on the up-to-date patient geometry in critical dosimetric parameters,more » such as PTV coverage, spinal cord maximum and volumetric constraint dose, esophagus maximum and volumetric constraint dose. Results: The average volume of PTV covered by prescription dose for all patients was improved by 7.56% after the adaptive re-planning. The volume of the spinal cord receiving 14.5Gy and 23Gy (V14.5, V23) decreased by 1.48% and 0.68%, respectively. For the esophagus, the volume receiving 19.5Gy (V19.5) reduced by 1.37%. Meanwhile, the maximum dose dropped off by 2.87% for spinal cord and 4.80% for esophagus. Conclusion: Our experimental results demonstrate that adaptive re-planning for lung SBRT has the potential to minimize the dosimetric effect of inter-fraction deformation and thus improve target coverage while reducing the risk of toxicity to nearby normal tissues.« less

SU-D-BRB-02: Combining a Commercial Autoplanning Engine with Database Dose Predictions to Further Improve Plan Quality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, SP; Moore, JA; Hui, X

Purpose: Database dose predictions and a commercial autoplanning engine both improve treatment plan quality in different but complimentary ways. The combination of these planning techniques is hypothesized to further improve plan quality. Methods: Four treatment plans were generated for each of 10 head and neck (HN) and 10 prostate cancer patients, including Plan-A: traditional IMRT optimization using clinically relevant default objectives; Plan-B: traditional IMRT optimization using database dose predictions; Plan-C: autoplanning using default objectives; and Plan-D: autoplanning using database dose predictions. One optimization was used for each planning method. Dose distributions were normalized to 95% of the planning target volumemore » (prostate: 8000 cGy; HN: 7000 cGy). Objectives used in plan optimization and analysis were the larynx (25%, 50%, 90%), left and right parotid glands (50%, 85%), spinal cord (0%, 50%), rectum and bladder (0%, 20%, 50%, 80%), and left and right femoral heads (0%, 70%). Results: All objectives except larynx 25% and 50% resulted in statistically significant differences between plans (Friedman’s χ{sup 2} ≥ 11.2; p ≤ 0.011). Maximum dose to the rectum (Plans A-D: 8328, 8395, 8489, 8537 cGy) and bladder (Plans A-D: 8403, 8448, 8527, 8569 cGy) were significantly increased. All other significant differences reflected a decrease in dose. Plans B-D were significantly different from Plan-A for 3, 17, and 19 objectives, respectively. Plans C-D were also significantly different from Plan-B for 8 and 13 objectives, respectively. In one case (cord 50%), Plan-D provided significantly lower dose than plan C (p = 0.003). Conclusion: Combining database dose predictions with a commercial autoplanning engine resulted in significant plan quality differences for the greatest number of objectives. This translated to plan quality improvements in most cases, although special care may be needed for maximum dose constraints. Further evaluation is warranted in a larger cohort across HN, prostate, and other treatment sites. This work is supported by Philips Radiation Oncology Systems.« less

Optimal and safe standard doses of midazolam and propofol to achieve patient and doctor satisfaction with dental treatment: A prospective cohort study

PubMed Central

Nonaka, Mutsumi; Nishimura, Akiko; Gotoh, Kinuko; Oka, Shuichirou; Iijima, Takehiko

2017-01-01

Background The incidences of morbidity and mortality caused by pharmacosedation for dental treatment have not yet reached zero. Adverse events are related to inappropriate respiratory management, mostly originating from an overdose of sedatives. Since sedation is utilized for the satisfaction of both the dentist and the patient, the optimal dose should be minimized to prevent adverse events. We attempted to define the optimal doses of midazolam and propofol required to achieve high levels of patient and dentist satisfaction. Methods One thousand dental patients, including those undergoing third molar extractions, were enrolled in this study. A dose of 1 mg of midazolam was administered at 1-minute intervals until adequate sedation was achieved. Propofol was then infused continuously to maintain the sedation level. Both the patients and the dentists were subsequently interviewed and asked to complete a questionnaire. A multivariate logistic regression analysis was used to examine the factors that contributed to patient and dentist satisfaction. Results The peak midazolam dose resulting in the highest percentage of patient satisfaction was 3 mg. Both a lower dose and a higher dose reduced patient satisfaction. Patient satisfaction increased with an increasing dosage of propofol up until 4 mg/kg/hr, reaching a peak of 78.6%. The peak midazolam dose resulting in the highest percentage of dentist satisfaction (78.8%) was 2 mg. Incremental propofol doses reduced dentist satisfaction, in contrast to their effect on patient satisfaction. The strongest independent predictors of patient satisfaction and dentist satisfaction were no intraoperative memory (OR, 5.073; 95% CI, 3.532–7.287; P<0.001) and unintentional movements by the patient (OR, 0.035; 95% CI, 0.012–0.104; P<0.001), respectively. No serious adverse events were reported. Conclusion We found that 3 mg of midazolam and 3 mg/kg/hr of propofol may be the optimal doses for maximizing both patient and dentist satisfaction. Although this level of sedation is relatively light, memory loss and an absence of unintentional patient movements can be expected without adverse events. PMID:28182732

[Statistical process control applied to intensity modulated radiotherapy pretreatment controls with portal dosimetry].

PubMed

Villani, N; Gérard, K; Marchesi, V; Huger, S; François, P; Noël, A

2010-06-01

The first purpose of this study was to illustrate the contribution of statistical process control for a better security in intensity modulated radiotherapy (IMRT) treatments. This improvement is possible by controlling the dose delivery process, characterized by pretreatment quality control results. So, it is necessary to put under control portal dosimetry measurements (currently, the ionisation chamber measurements were already monitored by statistical process control thanks to statistical process control tools). The second objective was to state whether it is possible to substitute ionisation chamber with portal dosimetry in order to optimize time devoted to pretreatment quality control. At Alexis-Vautrin center, pretreatment quality controls in IMRT for prostate and head and neck treatments were performed for each beam of each patient. These controls were made with an ionisation chamber, which is the reference detector for the absolute dose measurement, and with portal dosimetry for the verification of dose distribution. Statistical process control is a statistical analysis method, coming from industry, used to control and improve the studied process quality. It uses graphic tools as control maps to follow-up process, warning the operator in case of failure, and quantitative tools to evaluate the process toward its ability to respect guidelines: this is the capability study. The study was performed on 450 head and neck beams and on 100 prostate beams. Control charts, showing drifts, both slow and weak, and also both strong and fast, of mean and standard deviation have been established and have shown special cause introduced (manual shift of the leaf gap of the multileaf collimator). Correlation between dose measured at one point, given with the EPID and the ionisation chamber has been evaluated at more than 97% and disagreement cases between the two measurements were identified. The study allowed to demonstrate the feasibility to reduce the time devoted to pretreatment controls, by substituting the ionisation chamber's measurements with those performed with EPID, and also that a statistical process control monitoring of data brought security guarantee. 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Moving Beyond Maximum Tolerated Dose for Targeted Oncology Drugs: Use of Clinical Utility Index to Optimize Venetoclax Dosage in Multiple Myeloma Patients.

PubMed

Freise, K J; Jones, A K; Verdugo, M E; Menon, R M; Maciag, P C; Salem, A H

2017-12-01

Exposure-response analyses of venetoclax in combination with bortezomib and dexamethasone in previously treated patients with multiple myeloma (MM) were performed on a phase Ib venetoclax dose-ranging study. Logistic regression models were utilized to determine relationships, identify subpopulations with different responses, and optimize the venetoclax dosage that balanced both efficacy and safety. Bortezomib refractory status and number of prior treatments were identified to impact the efficacy response to venetoclax treatment. Higher venetoclax exposures were estimated to increase the probability of achieving a very good partial response (VGPR) or better through venetoclax doses of 1,200 mg. However, the probability of neutropenia (grade ≥3) was estimated to increase at doses >800 mg. Using a clinical utility index, a venetoclax dosage of 800 mg daily was selected to optimally balance the VGPR or better rates and neutropenia rates in MM patients administered 1-3 prior lines of therapy and nonrefractory to bortezomib. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer.

PubMed

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony; Bowen, Stephen R

2018-04-01

Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung V RX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. In this ten-patient sample, CTV V95 decreased significantly from 99-100% for PBopt to 77-94% for MCrecalc and recovered to 99-100% for MCopt (P<10 -5 ). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10 -3 ). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =-1%) compared to MCrecalc (ΔD95 =-6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., V RX ). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10 -3 ). MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer

PubMed Central

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony

2018-01-01

Background Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. Methods With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung VRX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. Results In this ten-patient sample, CTV V95 decreased significantly from 99–100% for PBopt to 77–94% for MCrecalc and recovered to 99–100% for MCopt (P<10−5). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10−3). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =−1%) compared to MCrecalc (ΔD95 =−6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., VRX). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10−3). Conclusions MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy. PMID:29876310

Food groups and risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies.

PubMed

Schwingshackl, Lukas; Hoffmann, Georg; Lampousi, Anna-Maria; Knüppel, Sven; Iqbal, Khalid; Schwedhelm, Carolina; Bechthold, Angela; Schlesinger, Sabrina; Boeing, Heiner

2017-05-01

The aim of this systematic review and meta-analysis was to synthesize the knowledge about the relation between intake of 12 major food groups and risk of type 2 diabetes (T2D). We conducted a systematic search in PubMed, Embase, Medline (Ovid), Cochrane Central, and Google Scholar for prospective studies investigating the association between whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages (SSB) on risk of T2D. Summary relative risks were estimated using a random effects model by contrasting categories, and for linear and non-linear dose-response relationships. Six out of the 12 food-groups showed a significant relation with risk of T2D, three of them a decrease of risk with increasing consumption (whole grains, fruits, and dairy), and three an increase of risk with increasing consumption (red meat, processed meat, and SSB) in the linear dose-response meta-analysis. There was evidence of a non-linear relationship between fruits, vegetables, processed meat, whole grains, and SSB and T2D risk. Optimal consumption of risk-decreasing foods resulted in a 42% reduction, and consumption of risk-increasing foods was associated with a threefold T2D risk, compared to non-consumption. The meta-evidence was graded "low" for legumes and nuts; "moderate" for refined grains, vegetables, fruit, eggs, dairy, and fish; and "high" for processed meat, red meat, whole grains, and SSB. Among the investigated food groups, selecting specific optimal intakes can lead to a considerable change in risk of T2D.

Statistical optimization and artificial neural network modeling for acridine orange dye degradation using in-situ synthesized polymer capped ZnO nanoparticles.

PubMed

Dhiman, Nitesh; Markandeya; Singh, Amrita; Verma, Neeraj K; Ajaria, Nidhi; Patnaik, Satyakam

2017-05-01

ZnO NPs were synthesized by a prudent green chemistry approach in presence of polyacrylamide grafted guar gum polymer (pAAm-g-GG) to ensure uniform morphology, and functionality and appraised for their ability to degrade photocatalytically Acridine Orange (AO) dye. These ZnO@pAAm-g-GG NPs were thoroughly characterized by various spectroscopic, XRD and electron microscopic techniques. The relative quantity of ZnO NPs in polymeric matrix has been estimated by spectro-analytical procedure; AAS and TGA analysis. The impact of process parameters viz. NP's dose, contact time and AO dye concentration on percentage photocatalytic degradation of AO dyes were evaluated using multivariate optimizing tools, Response Surface Methodology (RSM) involving Box-Behnken Design (BBD) and Artificial Neural Network (ANN). Congruity of the BBD statistical model was implied by R 2 value 0.9786 and F-value 35.48. At RSM predicted optimal condition viz. ZnO@pAAm-g-GG NP's dose of 0.2g/L, contact time of 210min and AO dye concentration 10mg/L, a maximum of 98% dye degradation was obtained. ANOVA indicated appropriateness of the model for dye degradation owing to "Prob.>F" less than 0.05 for variable parameters. We further, employed three layers feed forward ANN model for validating the BBD process parameters and suitability of our chosen model. The evaluation of Levenberg-Marquardt algorithm (ANN1) and Gradient Descent with adaptive learning rate (ANN2) model employed to scrutinize the best method and found experimental values of AO dye degradation were in close to those with predicated value of ANN 2 modeling with minimum error. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Low (5 mg) vs. High (20-40 mg) Rosuvastatin Dose on 24h Arterial Stiffness, Central Haemodynamics, and Non-Alcoholic Fatty Liver Disease in Patients with Optimally Controlled Arterial Hypertension.

PubMed

Mitsiou, Eudoxia; Boutari, Chrysoula; Kotsis, Vasilios; Georgianou, Eleni; Doumas, Michael; Karagiannis, Asterios; Athyros, Vasilios G

2018-01-01

Arterial Stiffness (AS) and Non-Alcoholic Fatty Liver Diseases (NAFLD) are 2 related, prevalent, risk predictors of Cardiovascular Disease (CVD). We assessed the effect of low dose (5 mg/day) vs. high dose (20-40 mg/day) rosuvastatin on aortic elasticity and central haemodynamics as well as on NAFLD in patients with Arterial Hypertension (AH). Forty patients with optimally controlled AH were randomised to 2 rosuvastatin doses and followed for 6 months. 24h AS was assessed by Mobil-O-Graph, which calculates (adjusted for age and gender) Pulse Wave Velocity (PWV), adjusted for Heart Rate (HR) augmentation index (AIx75%) and central haemodynamics. The diagnosis of NAFLD was based on >5% liver steatosis on ultrasound and moderately elevated serum levels of liver enzymes. Both doses of rosuvastatin reduced Central Pulse Pressure (cPP), PWV and AIx75% (adjusted for HR) to normal values (p = NS adjusted for age, gender and HR). Liver enzymes were reduced in those with NAFLD to normal, but steatosis was reduced more by the 20-40 mg/day rosuvastatin dose (p=0.01) compared with the 5 mg/day dose. Both doses of rosuvastatin had a beneficial effect on AS; the high dose was more efficient in reducing PWVs and central haemodynamics, and also the high dose was more effective in ameliorating NAFLD. Given that AH control was optimal and lipid values attained targets, 4 other CVD predictors were also addressed. Larger and longer term studies are needed to demonstrate the clinical benefit of such treatment preference. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparative evaluation of two dose optimization methods for image-guided, highly-conformal, tandem and ovoids cervix brachytherapy planning

NASA Astrophysics Data System (ADS)

Ren, Jiyun; Menon, Geetha; Sloboda, Ron

2013-04-01

Although the Manchester system is still extensively used to prescribe dose in brachytherapy (BT) for locally advanced cervix cancer, many radiation oncology centers are transitioning to 3D image-guided BT, owing to the excellent anatomy definition offered by modern imaging modalities. As automatic dose optimization is highly desirable for 3D image-based BT, this study comparatively evaluates the performance of two optimization methods used in BT treatment planning—Nelder-Mead simplex (NMS) and simulated annealing (SA)—for a cervix BT computer simulation model incorporating a Manchester-style applicator. Eight model cases were constructed based on anatomical structure data (for high risk-clinical target volume (HR-CTV), bladder, rectum and sigmoid) obtained from measurements on fused MR-CT images for BT patients. D90 and V100 for HR-CTV, D2cc for organs at risk (OARs), dose to point A, conformation index and the sum of dwell times within the tandem and ovoids were calculated for optimized treatment plans designed to treat the HR-CTV in a highly conformal manner. Compared to the NMS algorithm, SA was found to be superior as it could perform optimization starting from a range of initial dwell times, while the performance of NMS was strongly dependent on their initial choice. SA-optimized plans also exhibited lower D2cc to OARs, especially the bladder and sigmoid, and reduced tandem dwell times. For cases with smaller HR-CTV having good separation from adjoining OARs, multiple SA-optimized solutions were found which differed markedly from each other and were associated with different choices for initial dwell times. Finally and importantly, the SA method yielded plans with lower dwell time variability compared with the NMS method.

TU-H-BRC-05: Stereotactic Radiosurgery Optimized with Orthovoltage Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fagerstrom, J; Culberson, W; Bender, E

2016-06-15

Purpose: To achieve improved stereotactic radiosurgery (SRS) dose distributions using orthovoltage energy fluence modulation with inverse planning optimization techniques. Methods: A pencil beam model was used to calculate dose distributions from the institution’s orthovoltage unit at 250 kVp. Kernels for the model were derived using Monte Carlo methods as well as measurements with radiochromic film. The orthovoltage photon spectra, modulated by varying thicknesses of attenuating material, were approximated using open-source software. A genetic algorithm search heuristic routine was used to optimize added tungsten filtration thicknesses to approach rectangular function dose distributions at depth. Optimizations were performed for depths of 2.5,more » 5.0, and 7.5 cm, with cone sizes of 8, 10, and 12 mm. Results: Circularly-symmetric tungsten filters were designed based on the results of the optimization, to modulate the orthovoltage beam across the aperture of an SRS cone collimator. For each depth and cone size combination examined, the beam flatness and 80–20% and 90–10% penumbrae were calculated for both standard, open cone-collimated beams as well as for the optimized, filtered beams. For all configurations tested, the modulated beams were able to achieve improved penumbra widths and flatness statistics at depth, with flatness improving between 33 and 52%, and penumbrae improving between 18 and 25% for the modulated beams compared to the unmodulated beams. Conclusion: A methodology has been described that may be used to optimize the spatial distribution of added filtration material in an orthovoltage SRS beam to result in dose distributions at depth with improved flatness and penumbrae compared to standard open cones. This work provides the mathematical foundation for a novel, orthovoltage energy fluence-modulated SRS system.« less

Comparison of DNQ/novolac resists for e-beam exposure

NASA Astrophysics Data System (ADS)

Fedynyshyn, Theodore H.; Doran, Scott P.; Lind, Michele L.; Lyszczarz, Theodore M.; DiNatale, William F.; Lennon, Donna; Sauer, Charles A.; Meute, Jeff

1999-12-01

We have surveyed the commercial resist market with the dual purpose of identifying diazoquinone/novolac based resists that have potential for use as e-beam mask making resists and baselining these resists for comparison against future mask making resist candidates. For completeness, this survey would require that each resist be compared with an optimized developer and development process. To accomplish this task in an acceptable time period, e-beam lithography modeling was employed to quickly identify the resist and developer combinations that lead to superior resist performance. We describe the verification of a method to quickly screen commercial i-line resists with different developers, by determining modeling parameters for i-line resists from e-beam exposures, modeling the resist performance, and comparing predicted performance versus actual performance. We determined the lithographic performance of several DNQ/novolac resists whose modeled performance suggests that sensitivities of less than 40 (mu) C/cm2 coupled with less than 10-nm CD change per percent change in dose are possible for target 600-nm features. This was accomplished by performing a series of statistically designed experiments on the leading resists candidates to optimize processing variables, followed by comparing experimentally determined resist sensitivities, latitudes, and profiles of the DNQ/novolac resists a their optimized process.

Comparative dosimetric characterization for different types of detectors in high-energy electron beams

NASA Astrophysics Data System (ADS)

Lee, Chang Yeol; Kim, Woo Chul; Kim, Hun Jeong; Huh, Hyun Do; Park, Seungwoo; Choi, Sang Hyoun; Kim, Kum Bae; Min, Chul Kee; Kim, Seong Hoon; Shin, Dong Oh

2017-02-01

The purpose of this study is to perform a comparison and on analysis of measured dose factor values by using various commercially available high-energy electron beam detectors to measure dose profiles and energy property data. By analyzing the high-energy electron beam data from each detector, we determined the optimal detector for measuring electron beams in clinical applications. The dose linearity, dose-rate dependence, percentage depth dose, and dose profile of each detector were measured to evaluate the dosimetry characteristics of high-energy electron beams. The dose profile and the energy characteristics of high-energy electron beams were found to be different when measured by different detectors. Through comparison with other detectors based on the analyzed data, the microdiamond detector was found to have outstanding dose linearity, a low dose-rate dependency, and a small effective volume. Thus, this detector has outstanding spatial resolution and is the optimal detector for measuring electron beams. Radiation therapy results can be improved and related medical accidents can be prevented by using the procedure developed in this research in clinical practice for all beam detectors when measuring the electron beam dose.

A feasibility study: Selection of a personalized radiotherapy fractionation schedule using spatiotemporal optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Minsun, E-mail: mk688@uw.edu; Stewart, Robert D.; Phillips, Mark H.

2015-11-15

Purpose: To investigate the impact of using spatiotemporal optimization, i.e., intensity-modulated spatial optimization followed by fractionation schedule optimization, to select the patient-specific fractionation schedule that maximizes the tumor biologically equivalent dose (BED) under dose constraints for multiple organs-at-risk (OARs). Methods: Spatiotemporal optimization was applied to a variety of lung tumors in a phantom geometry using a range of tumor sizes and locations. The optimal fractionation schedule for a patient using the linear-quadratic cell survival model depends on the tumor and OAR sensitivity to fraction size (α/β), the effective tumor doubling time (T{sub d}), and the size and location of tumormore » target relative to one or more OARs (dose distribution). The authors used a spatiotemporal optimization method to identify the optimal number of fractions N that maximizes the 3D tumor BED distribution for 16 lung phantom cases. The selection of the optimal fractionation schedule used equivalent (30-fraction) OAR constraints for the heart (D{sub mean} ≤ 45 Gy), lungs (D{sub mean} ≤ 20 Gy), cord (D{sub max} ≤ 45 Gy), esophagus (D{sub max} ≤ 63 Gy), and unspecified tissues (D{sub 05} ≤ 60 Gy). To assess plan quality, the authors compared the minimum, mean, maximum, and D{sub 95} of tumor BED, as well as the equivalent uniform dose (EUD) for optimized plans to conventional intensity-modulated radiation therapy plans prescribing 60 Gy in 30 fractions. A sensitivity analysis was performed to assess the effects of T{sub d} (3–100 days), tumor lag-time (T{sub k} = 0–10 days), and the size of tumors on optimal fractionation schedule. Results: Using an α/β ratio of 10 Gy, the average values of tumor max, min, mean BED, and D{sub 95} were up to 19%, 21%, 20%, and 19% larger than those from conventional prescription, depending on T{sub d} and T{sub k} used. Tumor EUD was up to 17% larger than the conventional prescription. For fast proliferating tumors with T{sub d} less than 10 days, there was no significant increase in tumor BED but the treatment course could be shortened without a loss in tumor BED. The improvement in the tumor mean BED was more pronounced with smaller tumors (p-value = 0.08). Conclusions: Spatiotemporal optimization of patient plans has the potential to significantly improve local tumor control (larger BED/EUD) of patients with a favorable geometry, such as smaller tumors with larger distances between the tumor target and nearby OAR. In patients with a less favorable geometry and for fast growing tumors, plans optimized using spatiotemporal optimization and conventional (spatial-only) optimization are equivalent (negligible differences in tumor BED/EUD). However, spatiotemporal optimization yields shorter treatment courses than conventional spatial-only optimization. Personalized, spatiotemporal optimization of treatment schedules can increase patient convenience and help with the efficient allocation of clinical resources. Spatiotemporal optimization can also help identify a subset of patients that might benefit from nonconventional (large dose per fraction) treatments that are ineligible for the current practice of stereotactic body radiation therapy.« less

SU-E-T-09: A Clinical Implementation and Optimized Dosimetry Study of Freiberg Flap Skin Surface Treatment in High Dose Rate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syh, J; Syh, J; Patel, B

Purpose: This case study was designated to confirm the optimized plan was used to treat skin surface of left leg in three stages. 1. To evaluate dose distribution and plan quality by alternating of the source loading catheters pattern in flexible Freiberg Flap skin surface (FFSS) applicator. 2. To investigate any impact on Dose Volume Histogram (DVH) of large superficial surface target volume coverage. 3. To compare the dose distribution if it was treated with electron beam. Methods: The Freiburg Flap is a flexible mesh style surface mold for skin radiation or intraoperative surface treatments. The Freiburg Flap consists ofmore » multiple spheres that are attached to each other, holding and guiding up to 18 treatment catheters. The Freiburg Flap also ensures a constant distance of 5mm from the treatment catheter to the surface. Three treatment trials with individual planning optimization were employed: 18 channels, 9 channels of FF and 6 MeV electron beam. The comparisons were highlighted in target coverage, dose conformity and dose sparing of surrounding tissues. Results: The first 18 channels brachytherapy plan was generated with 18 catheters inside the skin-wrapped up flap (Figure 1A). A second 9 catheters plan was generated associated with the same calculation points which were assigned to match prescription for target coverage as 18 catheters plan (Figure 1B). The optimized inverse plan was employed to reduce the dose to adjacent structures such as tibia or fibula. The comparison of DVH’s was depicted on Figure 2. External beam of electron RT plan was depicted in Figure 3. Overcall comparisons among these three were illustrated in Conclusion: The 9-channel Freiburg flap flexible skin applicator offers a reasonably acceptable plan without compromising the coverage. Electron beam was discouraged to use to treat curved skin surface because of low target coverage and high dose in adjacent tissues.« less

Bridging the gap: a review of dose investigations in paediatric investigation plans.

PubMed

Hampson, Lisa V; Herold, Ralf; Posch, Martin; Saperia, Julia; Whitehead, Anne

2014-10-01

In the EU, development of new medicines for children should follow a prospectively agreed paediatric investigation plan (PIP). Finding the right dose for children is crucial but challenging due to the variability of pharmacokinetics across age groups and the limited sample sizes available. We examined strategies adopted in PIPs to support paediatric dosing recommendations to identify common assumptions underlying dose investigations and the attempts planned to verify them in children. We extracted data from 73 PIP opinions recently adopted by the Paediatric Committee of the European Medicines Agency. These opinions represented 79 medicinal development programmes and comprised a total of 97 dose investigation studies. We identified the design of these dose investigation studies, recorded the analyses planned and determined the criteria used to define target doses. Most dose investigation studies are clinical trials (83 of 97) that evaluate a single dosing rule. Sample sizes used to investigate dose are highly variable across programmes, with smaller numbers used in younger children (< 2 years). Many studies (40 of 97) do not pre-specify a target dose criterion. Of those that do, most (33 of 57 studies) guide decisions using pharmacokinetic data alone. Common assumptions underlying dose investigation strategies include dose proportionality and similar exposure-response relationships in adults and children. Few development programmes pre-specify steps to verify assumptions in children. There is scope for the use of Bayesian methods as a framework for synthesizing existing information to quantify prior uncertainty about assumptions. This process can inform the design of optimal drug development strategies. © 2014 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

YouTube Video Educational Package Increased Acceptance of Antibiotic Clinical Decision Support System Recommendations

PubMed Central

Heng, Shi Thong; Tan, Michelle; Young, Barnaby; Lye, David; Ng, Tat Ming

2017-01-01

Abstract Background Antibiotic clinical decision support systems (CDSS) were implemented to provide stewardship at the point of ordering of broad-spectrum antibiotics (piperacillin-tazobactam and carbapenems). We postulated that a YouTube based educational video package (EP) with quizzes can help to improve CDSS acceptance. Methods A before-after study was conducted in general wards at Tan Tock Seng Hospital from April 2016 to March 2017. Baseline data were collected for 6 months before EP was implemented and during the next 6 months with EP dissemination to all doctors. Acceptance of CDSS recommendations between both phases were compared. Independent factors associated with acceptance of specific CDSS recommendations were identified by logistic regression. Results Patients recruited before and after EP was 1642 and 1313 respectively. Overall CDSS acceptance rate was similar before and after EP. There was improved acceptance for recommendations for dose optimizaton, antibiotic optimization and set duration (Figures 1 and 2). Independent factors of CDSS acceptance for dose optimizaton, antibiotic optimization and set duration are shown in Table 1. EP implementation was independently associated with acceptance of recommendations to set duration and optimize antibiotics. Conclusion EP was independently associated with increased CDSS acceptance on antibiotic duration and antibiotic optimization. Although acceptance of dose optimization was improved, EP was not associated independently with acceptance of the recommendations. Figure 2 Acceptance of CDSS recommendations by classifications of recommendations Table 1 3 multivariate models of acceptance of CDSS recommendations on antibiotic optimization, dose optimization and duration setting Set duration Antibiotic optimization Dose optimization Factor Odds ratio [95% CI] Lung infection 2.71[2.13–3.45] 2.08[1.71–2.52] 2.79[2.19-3.55] Unknown sepsis source 1.73[1.27–2.35] – 1.44[1.05-1.96] Piperacillin-tazobactam use 3.02[2.17–4.19] – – Temperature during initiation of antibiotics 0.86[0.79–0.94] – – The presence of oxygen supplementation during initiation of antibiotics – 0.76[0.64–0.91] 0.76[0.64–0.91] EP implementation 1.38[1.18–1.62] 1.21[1.02–1.43] - Disclosures All authors: No reported disclosures.

SU-F-T-451: Doses to Organs-At-Risk in the Presence and Absence of a 1.5 T Magnetic Field for NSCLC Patients Undergoing SABR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Ward, S; Kim, A; McCann, C

2016-06-15

Purpose: To determine whether the electron return effect (ERE) has deleterious effects on lung SABR plans optimized in the presence of an orthogonal 1.5 T magnetic field. Methods: Data from five NSCLC-SABR patients were used. The Dose was modeled with a 2.5 mm dose grid in the presence and absence of a magnetic field using the Monaco (Elekta) TPS with the Monte Carlo GPUMCD (v5.1) algorithm. For each patient, two plans were generated, one using our conventional Elekta Agility linac beam model and another using the Elekta MRI Linac (MRL) model. Both plans were generated on the average CT usingmore » similar dose constraints and a 5 mm PTV. The optimization was performed using our clinic’s planning criteria, with normalization of the targets such that their V99% was equal to 99%. The OAR DVHs were compared for each patient. Results: The DVH plots revealed that there were limited differences when optimizing plans in the presence or absence of the magnetic field. The mean of the absolute differences, between the two planning types, in the equivalent uniform doses (EUDs) for the OARs were: 0.3 Gy (range of 0.0 - 1.0 Gy) for the esophagus, 0.6 Gy (range of 0.1 – 1.9 Gy) for the heart, 0.5 Gy (range of 0.2 – 0.8 Gy) for the lungs, and 0.6 Gy (range of 0.2 – 1.5 Gy) for the spinal canal. Regarding the maximum doses to the serial organs, the mean of the differences were 3.0 Gy (esophagus) and 0.9 Gy (spinal canal). No trends in the differences were observed. Conclusion: This study has demonstrated that there were no major differences between plans optimized using a conventional linac and those optimized using an MRI linac with an orthogonal 1.5 T magnetic field. This is attributed to the consideration of the ERE in the optimization. This project was made possible with the financial support of Elekta.« less