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Sample records for accurate dose delivery

  1. Production of pure quasi-monochromatic 11C beams for accurate radiation therapy and dose delivery verification

    NASA Astrophysics Data System (ADS)

    Lazzeroni, Marta; Brahme, Anders

    2015-09-01

    In the present study we develop a new technique for the production of clean quasi-monochromatic 11C positron emitter beams for accurate radiation therapy and PET-CT dose delivery imaging and treatment verification. The 11C ion beam is produced by projectile fragmentation using a primary 12C ion beam. The practical elimination of the energy spread of the secondary 11C fragments and other beam contaminating fragments is described. Monte Carlo calculation with the SHIELD-HIT10+ code and analytical methods for the transport of the ions in matter are used in the analysis. Production yields, as well as energy, velocity and magnetic rigidity distributions of the fragments generated in a cylindrical target are scored as a function of the depth within 1 cm thick slices for an optimal target consisting of a fixed 20 cm section of liquid hydrogen followed by a variable thickness section of polyethylene. The wide energy and magnetic rigidity spread of the 11C ion beam can be reduced to values around 1% by using a variable monochromatizing wedge-shaped degrader in the beam line. Finally, magnetic rigidity and particle species selection, as well as discrimination of the particle velocity through a combined Time of Flight and Radio Frequency-driven Velocity filter purify the beam from similar magnetic rigidity contaminating fragments (mainly 7Be and 3He fragments). A beam purity of about 99% is expected by the combined method.

  2. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-04-01

    Particle therapy is a field in remarkable development, with the goal of increasing the number of indications which could benefit from such treatments and the access to the therapy. The therapeutic usage of a particle beam defines the technical requirements of all the elements of the therapy chain: we summarize the main characteristics of accelerators, the beam line, the treatment room, the integrated therapy and imaging systems used in particle therapy. Aiming at a higher flexibility in the choice of treatments, an increasing number of centers around the world have chosen to equip their treatment rooms with gantries, rotating beam line structures that allow a complete flexibility in the choice of the treatment angle. We review the current designs. A particle therapy gantry though is a quite expensive structure, and future development will increasingly consider reducing the cost and the footprint. Increasing the number of indications also means development in the delivery techniques and solving some of the issues which traditionally affected particle therapy, for example the precision of the delivery in presence of motion and the large penumbras for low depths. We show the current strategies in these fields, focusing on pencil beam scanning (PBS), and give some hints about future developments.

  3. A generalized a priori dose uncertainty model of IMRT delivery.

    PubMed

    Jin, Hosang; Palta, Jatinder; Suh, Tae-Suk; Kim, Siyong

    2008-03-01

    Multileaf collimator-based intensity modulated radiation therapy (IMRT) is complex because each intensity modulated field consists of hundreds of subfields, each of which is associated with an intricate interplay of uncertainties. In this study, the authors have revised the previously introduced uncertainty model to provide an a priori accurate prediction of dose uncertainty during treatment planning in IMRT. In the previous model, the dose uncertainties were categorized into space-oriented dose uncertainty (SOU) and nonspace-oriented dose uncertainty (NOU). The revised model further divided the uncertainty sources into planning and delivery. SOU and NOU associated with a planning system were defined as inherent dose uncertainty. A convolution method with seven degrees of freedom was also newly applied to generalize the model for practical clinical cases. The model parameters were quantified through a set of measurements, accumulated routine quality assurance (QA) data, and peer-reviewed publications. The predicted uncertainty maps were compared with dose difference distributions between computations and 108 simple open-field measurements using a two-dimensional diode array detector to verify the validity of the model parameters and robustness of the generalized model. To examine the applicability of the model to overall dose uncertainty prediction in IMRT, a retrospective analysis of QA measurements using the diode array detector for 32 clinical IM fields was also performed. A scatter diagram and a correlation coefficient were employed to investigate a correlation of the predicted dose uncertainty distribution with the dose discrepancy distribution between calculation and delivery. In addition, a gamma test was performed to correlate failed regions in dose verification with the dose uncertainty map. The quantified model parameters well correlated the predicted dose uncertainty with the probable dose difference between calculations and measurements. It was visually

  4. Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery

    PubMed Central

    Engelsman, M.; Lu, H.-M.; Herrup, D.; Bussiere, M.; Kooy, H. M.

    2009-01-01

    Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output. PMID:19610306

  5. How accurately can the peak skin dose in fluoroscopy be determined using indirect dose metrics?

    SciTech Connect

    Jones, A. Kyle; Ensor, Joe E.; Pasciak, Alexander S.

    2014-07-15

    Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that result in skin reactions can be reached during these procedures. There is no consensus as to whether or not indirect skin dosimetry is sufficiently accurate for fluoroscopically-guided interventions. However, measuring PSD with film is difficult and the decision to do so must be madea priori. The purpose of this study was to assess the accuracy of different types of indirect dose estimates and to determine if PSD can be calculated within ±50% using indirect dose metrics for embolization procedures. Methods: PSD were measured directly using radiochromic film for 41 consecutive embolization procedures at two sites. Indirect dose metrics from the procedures were collected, including reference air kerma. Four different estimates of PSD were calculated from the indirect dose metrics and compared along with reference air kerma to the measured PSD for each case. The four indirect estimates included a standard calculation method, the use of detailed information from the radiation dose structured report, and two simplified calculation methods based on the standard method. Indirect dosimetry results were compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the different indirect estimates were examined. Results: When using the standard calculation method, calculated PSD were within ±35% for all 41 procedures studied. Calculated PSD were within ±50% for a simplified method using a single source-to-patient distance for all calculations. Reference air kerma was within ±50% for all but one procedure. Cases for which reference air kerma or calculated PSD exhibited large (±35%) differences from the measured PSD were analyzed, and two main causative factors were identified: unusually small or large source-to-patient distances and large contributions to reference air kerma from cone

  6. Bronchodilator delivery with metered-dose inhaler during mechanical ventilation.

    PubMed

    Georgopoulos, D; Mouloudi, E; Kondili, E; Klimathianaki, M

    2000-01-01

    The delivery of bronchodilators with metered-dose inhaler (MDI) in mechanically ventilated patients has attracted considerable interest in recent years. This is because the use of the MDI has several advantages over the nebulizer, such as reduced cost, ease of administration, less personnel time, reliability of dosing and a lower risk of contamination. A spacer device is fundamental in order to demonstrate the efficacy of the bronchodilatory therapy delivered by MDI. Provided that the technique of administration is appropriate, MDIs are as effective as nebulizers, despite a significantly lower dose of bronchodilator given by the MDI.

  7. Bronchodilator delivery with metered-dose inhaler during mechanical ventilation

    PubMed Central

    Georgopoulos, Dimitris; Mouloudi, Eleni; Kondili, Eumorfia; Klimathianaki, Maria

    2000-01-01

    The delivery of bronchodilators with metered-dose inhaler (MDI) in mechanically ventilated patients has attracted considerable interest in recent years. This is because the use of the MDI has several advantages over the nebulizer, such as reduced cost, ease of administration, less personnel time, reliability of dosing and a lower risk of contamination. A spacer device is fundamental in order to demonstrate the efficacy of the bronchodilatory therapy delivered by MDI. Provided that the technique of administration is appropriate, MDIs are as effective as nebulizers, despite a significantly lower dose of bronchodilator given by the MDI. PMID:11094505

  8. Modulation of photodynamic activity with Photofrin: effect of dose, time interval, fluence, and delivery system

    NASA Astrophysics Data System (ADS)

    Garbo, Greta M.; Ballard, Jonathan R.; Harrison, Linda T.; Kik, Peter K.; Wieman, T. J.; Fingar, Victor H.

    2005-04-01

    A goal of our laboratory is to accurately define the parameters of light dose and drug dose that contribute to tissue destruction after Photodynamic therapy (PDT). Using Photofrin as sensitizer, we examined a range of drug doses, various intervals between injection and light treatment, and various fluence rates. The effect of Photofrin photosensitizer encapsulated in liposomal delivery vehicle was also studied. Three liposome delivery vehicles were chosen to deliver the photosensitizer in vivo: DPPC/cholesterol, DMPC/HPC and stealth liposomes. Tumor response and microvessel behaviour were examined in tumor and surrounding skin in a mouse model. Under these conditions, better selectivity of tissue damage was seen using some of the treatment. These data might be used to design better clinical protocols for patient care. In memory of Dr. Victor Fingar (Supported by R01 CA51771).

  9. DICOM organ dose does not accurately represent calculated dose in mammography

    NASA Astrophysics Data System (ADS)

    Suleiman, Moayyad E.; Brennan, Patrick C.; McEntee, Mark F.

    2016-03-01

    This study aims to analyze the agreement between the mean glandular dose estimated by the mammography unit (organ dose) and mean glandular dose calculated using Dance et al published method (calculated dose). Anonymised digital mammograms from 50 BreastScreen NSW centers were downloaded and exposure information required for the calculation of dose was extracted from the DICOM header along with the organ dose estimated by the system. Data from quality assurance annual tests for the included centers were collected and used to calculate the mean glandular dose for each mammogram. Bland-Altman analysis and a two-tailed paired t-test were used to study the agreement between calculated and organ dose and the significance of any differences. A total of 27,869 dose points from 40 centers were included in the study, mean calculated dose and mean organ dose (+/- standard deviation) were 1.47 (+/-0.66) and 1.38 (+/-0.56) mGy respectively. A statistically significant 0.09 mGy bias (t = 69.25; p<0.0001) with 95% limits of agreement between calculated and organ doses ranging from -0.34 and 0.52 were shown by Bland-Altman analysis, which indicates a small yet highly significant difference between the two means. The use of organ dose for dose audits is done at the risk of over or underestimating the calculated dose, hence, further work is needed to identify the causal agents for differences between organ and calculated doses and to generate a correction factor for organ dose.

  10. Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

    SciTech Connect

    Able, Charles M.; Bright, Megan; Frizzell, Bart

    2013-03-01

    Purpose: Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. Methods and Materials: A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles with 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. Results: There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. Conclusions: SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.

  11. Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?

    SciTech Connect

    Wong, Sharon; Back, Michael; Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun; Lu, Jaide Jay

    2012-07-01

    Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio Registered-Sign treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy.

  12. A real time dose monitoring and dose reconstruction tool for patient specific VMAT QA and delivery

    SciTech Connect

    Tyagi, Neelam; Yang Kai; Gersten, David; Yan Di

    2012-12-15

    Purpose: To develop a real time dose monitoring and dose reconstruction tool to identify and quantify sources of errors during patient specific volumetric modulated arc therapy (VMAT) delivery and quality assurance. Methods: The authors develop a VMAT delivery monitor tool called linac data monitor that connects to the linac in clinical mode and records, displays, and compares real time machine parameters with the planned parameters. A new measure, called integral error, keeps a running total of leaf overshoot and undershoot errors in each leaf pair, multiplied by leaf width, and the amount of time during which the error exists in monitor unit delivery. Another tool reconstructs Pinnacle{sup 3} Trade-Mark-Sign format delivered plan based on the saved machine logfile and recalculates actual delivered dose in patient anatomy. Delivery characteristics of various standard fractionation and stereotactic body radiation therapy (SBRT) VMAT plans delivered on Elekta Axesse and Synergy linacs were quantified. Results: The MLC and gantry errors for all the treatment sites were 0.00 {+-} 0.59 mm and 0.05 {+-} 0.31 Degree-Sign , indicating a good MLC gain calibration. Standard fractionation plans had a larger gantry error than SBRT plans due to frequent dose rate changes. On average, the MLC errors were negligible but larger errors of up to 6 mm and 2.5 Degree-Sign were seen when dose rate varied frequently. Large gantry errors occurred during the acceleration and deceleration process, and correlated well with MLC errors (r= 0.858, p= 0.0004). PTV mean, minimum, and maximum dose discrepancies were 0.87 {+-} 0.21%, 0.99 {+-} 0.59%, and 1.18 {+-} 0.52%, respectively. The organs at risk (OAR) doses were within 2.5%, except some OARs that showed up to 5.6% discrepancy in maximum dose. Real time displayed normalized total positive integral error (normalized to the total monitor units) correlated linearly with MLC (r= 0.9279, p < 0.001) and gantry errors (r= 0.742, p= 0.005). There

  13. Is internal target volume accurate for dose evaluation in lung cancer stereotactic body radiotherapy?

    PubMed Central

    Peng, Jiayuan; Zhang, Zhen; Wang, Jiazhou; Xie, Jiang; Hu, Weigang

    2016-01-01

    Purpose 4DCT delineated internal target volume (ITV) was applied to determine the tumor motion and used as planning target in treatment planning in lung cancer stereotactic body radiotherapy (SBRT). This work is to study the accuracy of using ITV to predict the real target dose in lung cancer SBRT. Materials and methods Both for phantom and patient cases, the ITV and gross tumor volumes (GTVs) were contoured on the maximum intensity projection (MIP) CT and ten CT phases, respectively. A SBRT plan was designed using ITV as the planning target on average projection (AVG) CT. This plan was copied to each CT phase and the dose distribution was recalculated. The GTV_4D dose was acquired through accumulating the GTV doses over all ten phases and regarded as the real target dose. To analyze the ITV dose error, the ITV dose was compared to the real target dose by endpoints of D99, D95, D1 (doses received by the 99%, 95% and 1% of the target volume), and dose coverage endpoint of V100(relative volume receiving at least the prescription dose). Results The phantom study shows that the ITV underestimates the real target dose by 9.47%∼19.8% in D99, 4.43%∼15.99% in D95, and underestimates the dose coverage by 5% in V100. The patient cases show that the ITV underestimates the real target dose and dose coverage by 3.8%∼10.7% in D99, 4.7%∼7.2% in D95, and 3.96%∼6.59% in V100 in motion target cases. Conclusions Cautions should be taken that ITV is not accurate enough to predict the real target dose in lung cancer SBRT with large tumor motions. Restricting the target motion or reducing the target dose heterogeneity could reduce the ITV dose underestimation effect in lung SBRT. PMID:26968812

  14. Radiation dose delivery verification in the treatment of carcinoma-cervix

    SciTech Connect

    Shrotriya, D. Srivastava, R. N. L.; Kumar, S.

    2015-06-24

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  15. Radiation dose delivery verification in the treatment of carcinoma-cervix

    NASA Astrophysics Data System (ADS)

    Shrotriya, D.; Kumar, S.; Srivastava, R. N. L.

    2015-06-01

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  16. Accuracy of one algorithm used to modify a planned DVH with data from actual dose delivery.

    PubMed

    Ma, Tianjun; Podgorsak, Matthew B; Kumaraswamy, Lalith K

    2016-01-01

    Detection and accurate quantification of treatment delivery errors is important in radiation therapy. This study aims to evaluate the accuracy of DVH based QA in quantifying delivery errors. Eighteen previously treated VMAT plans (prostate, H&N, and brain) were randomly chosen for this study. Conventional IMRT delivery QA was done with the ArcCHECK diode detector for error-free plans and plans with the following modifications: 1) induced monitor unit differences up to ± 3.0%, 2) control point deletion (3, 5, and 8 control points were deleted for each arc), and 3) gantry angle shift (2° uniform shift clockwise and counterclockwise). 2D and 3D distance-to-agreement (DTA) analyses were performed for all plans with SNC Patient software and 3DVH software, respectively. Subsequently, accuracy of the reconstructed DVH curves and DVH parameters in 3DVH software were analyzed for all selected cases using the plans in the Eclipse treatment planning system as standard. 3D DTA analysis for error-induced plans generally gave high pass rates, whereas the 2D evaluation seemed to be more sensitive to detecting delivery errors. The average differences for DVH parameters between each pair of Eclipse recalculation and 3DVH prediction were within 2% for all three types of error-induced treatment plans. This illustrates that 3DVH accurately quantifies delivery errors in terms of actual dose delivered to the patients. 2D DTA analysis should be routinely used for clinical evaluation. Any concerns or dose discrepancies should be further analyzed through DVH-based QA for clinically relevant results and confirmation of a conventional passing-rate-based QA. PMID:27685140

  17. More accurate fitting of {sup 125}I and {sup 103}Pd radial dose functions

    SciTech Connect

    Taylor, R. E. P.; Rogers, D. W. O.

    2008-09-15

    In this study an improved functional form for fitting the radial dose functions, g(r), of {sup 125}I and {sup 103}Pd brachytherapy seeds is presented. The new function is capable of accurately fitting radial dose functions over ranges as large as 0.05 cm{<=}r{<=}10 cm for {sup 125}I seeds and 0.10 cm{<=}r{<=}10 cm for {sup 103}Pd seeds. The average discrepancies between fit and calculated data are less than 0.5% over the full range of fit and maximum discrepancies are 2% or less. The fitting function is also capable of accounting for the sharp increase in g(r) (upturn) seen for some sources for r<0.1 cm. This upturn has previously been attributed to the breakdown of the approximation of the sources as a line, however, in this study we demonstrate that another contributing factor is the 4.5 keV characteristic x-rays emitted from the Ti seed casing. Radial dose functions are calculated for 18 {sup 125}I seeds and 9 {sup 103}Pd seeds using the EGSnrc Monte Carlo user-code BrachyDose. Fitting coefficients of the new function are tabulated for all 27 seeds. Extrapolation characteristics of the function are also investigated. The new functional form is an improvement over currently used fitting functions with its main strength being the ability to accurately fit the rapidly varying radial dose function at small distances. The new function is an excellent candidate for fitting the radial dose function of all {sup 103}Pd and {sup 125}I brachytherapy seeds and will increase the accuracy of dose distributions calculated around brachytherapy seeds using the TG-43 protocol over a wider range of data. More accurate values of g(r) for r<0.5 cm may be particularly important in the treatment of ocular melanoma.

  18. Monte Carlo calculation of helical tomotherapy dose delivery

    SciTech Connect

    Zhao Yingli; Mackenzie, M.; Kirkby, C.; Fallone, B. G.

    2008-08-15

    Helical tomotherapy delivers intensity modulated radiation therapy using a binary multileaf collimator (MLC) to modulate a fan beam of radiation. This delivery occurs while the linac gantry and treatment couch are both in constant motion, so the beam describes, from a patient/phantom perspective, a spiral or helix of dose. The planning system models this continuous delivery as a large number (51) of discrete gantry positions per rotation, and given the small jaw/fan width setting typically used (1 or 2.5 cm) and the number of overlapping rotations used to cover the target (pitch often <0.5), the treatment planning system (TPS) potentially employs a very large number of static beam directions and leaf opening configurations to model the modulated fields. All dose calculations performed by the system employ a convolution/superposition model. In this work the authors perform a full Monte Carlo (MC) dose calculation of tomotherapy deliveries to phantom computed tomography (CT) data sets to verify the TPS calculations. All MC calculations are performed with the EGSnrc-based MC simulation codes, BEAMnrc and DOSXYZnrc. Simulations are performed by taking the sinogram (leaf opening versus time) of the treatment plan and decomposing it into 51 different projections per rotation, as does the TPS, each of which is segmented further into multiple MLC opening configurations, each with different weights that correspond to leaf opening times. Then the projection is simulated by the summing of all of the opening configurations, and the overall rotational treatment is simulated by the summing of all of the projection simulations. Commissioning of the source model was verified by comparing measured and simulated values for the percent depth dose and beam profiles shapes for various jaw settings. The accuracy of the MLC leaf width and tongue and groove spacing were verified by comparing measured and simulated values for the MLC leakage and a picket fence pattern. The validated source

  19. The CNAO dose delivery system for modulated scanning ion beam radiotherapy

    SciTech Connect

    Giordanengo, S.; Marchetto, F.; Garella, M. A.; Donetti, M.; Bourhaleb, F.; Monaco, V.; Hosseini, M. A.; Peroni, C.; Sacchi, R.; Cirio, R.; Ciocca, M.; Mirandola, A.

    2015-01-15

    Purpose: This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy. Methods: CNAO Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real-time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent to the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery. Results: The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing

  20. A live weight-heart girth relationship for accurate dosing of east African shorthorn zebu cattle.

    PubMed

    Lesosky, Maia; Dumas, Sarah; Conradie, Ilana; Handel, Ian Graham; Jennings, Amy; Thumbi, Samuel; Toye, Phillip; Bronsvoort, Barend Mark de Clare

    2013-01-01

    The accurate estimation of livestock weights is important for many aspects of livestock management including nutrition, production and appropriate dosing of pharmaceuticals. Subtherapeutic dosing has been shown to accelerate pathogen resistance which can have subsequent widespread impacts. There are a number of published models for the prediction of live weight from morphometric measurements of cattle, but many of these models use measurements difficult to gather and include complicated age, size and gender stratification. In this paper, we use data from the Infectious Diseases of East Africa calf cohort study and additional data collected at local markets in western Kenya to develop a simple model based on heart girth circumference to predict live weight of east African shorthorn zebu (SHZ) cattle. SHZ cattle are widespread throughout eastern and southern Africa and are economically important multipurpose animals. We demonstrate model accuracy by splitting the data into training and validation subsets and comparing fitted and predicted values. The final model is weight(0.262) = 0.95 + 0.022 × girth which has an R (2) value of 0.98 and 95 % prediction intervals that fall within the ± 20 % body weight error band regarded as acceptable when dosing livestock. This model provides a highly reliable and accurate method for predicting weights of SHZ cattle using a single heart girth measurement which can be easily obtained with a tape measure in the field setting. PMID:22923040

  1. Oxymetazoline Metered Dose Spray: Factors Affecting Delivery Volume

    PubMed Central

    Walia, Hina; Rafiq, Mahmood; Grannell, Timothy; Cartabuke, Richard S.; Tobias, Joseph D.

    2016-01-01

    OBJECTIVES: The current study compared the amount of oxymetazoline delivered by various anesthesia providers when holding the bottle in the upright and inverted position. Additionally, the amount delivered from a full bottle and a half-full bottle was also investigated. METHODS: Using an analytical balance that was calibrated to zero, we evaluated the impact the position of the bottle and the volume of oxymetazoline in the bottle had on the amount being delivered by both anesthesia staff and trainees. RESULTS: When using both filled and half-filled bottles, the amount delivered increased significantly when comparing the upright versus inverted position. With a full bottle, the amount delivered when the bottle was inverted increased almost 10-fold from 62 ± 80 to 606 ± 366 μL (p < 0.0001). Similarly, even with a half-filled bottle, the amount delivered increased in the inverted positions from 41 ± 48 to 645 ± 393 μL. Regardless of the scenario, we also noted significant variation from provider to provider. CONCLUSIONS: Our results demonstrate that several factors may affect the amount of oxymetazoline delivered for metered dose bottles. Given the potential for severe end-organ effects with excessive dosage, alternative means of delivery are needed for its perioperative use. PMID:27453703

  2. An in vivo dose verification method for SBRT–VMAT delivery using the EPID

    SciTech Connect

    McCowan, P. M.; Van Uytven, E.; Van Beek, T.; Asuni, G.; McCurdy, B. M. C.

    2015-12-15

    Purpose: Radiation treatments have become increasingly more complex with the development of volumetric modulated arc therapy (VMAT) and the use of stereotactic body radiation therapy (SBRT). SBRT involves the delivery of substantially larger doses over fewer fractions than conventional therapy. SBRT–VMAT treatments will strongly benefit from in vivo patient dose verification, as any errors in delivery can be more detrimental to the radiobiology of the patient as compared to conventional therapy. Electronic portal imaging devices (EPIDs) are available on most commercial linear accelerators (Linacs) and their documented use for dosimetry makes them valuable tools for patient dose verification. In this work, the authors customize and validate a physics-based model which utilizes on-treatment EPID images to reconstruct the 3D dose delivered to the patient during SBRT–VMAT delivery. Methods: The SBRT Linac head, including jaws, multileaf collimators, and flattening filter, were modeled using Monte Carlo methods and verified with measured data. The simulation provides energy spectrum data that are used by their “forward” model to then accurately predict fluence generated by a SBRT beam at a plane above the patient. This fluence is then transported through the patient and then the dose to the phosphor layer in the EPID is calculated. Their “inverse” model back-projects the EPID measured focal fluence to a plane upstream of the patient and recombines it with the extra-focal fluence predicted by the forward model. This estimate of total delivered fluence is then forward projected onto the patient’s density matrix and a collapsed cone convolution algorithm calculates the dose delivered to the patient. The model was tested by reconstructing the dose for two prostate, three lung, and two spine SBRT–VMAT treatment fractions delivered to an anthropomorphic phantom. It was further validated against actual patient data for a lung and spine SBRT–VMAT plan. The

  3. A hybrid approach for rapid, accurate, and direct kilovoltage radiation dose calculations in CT voxel space

    SciTech Connect

    Kouznetsov, Alexei; Tambasco, Mauro

    2011-03-15

    Purpose: To develop and validate a fast and accurate method that uses computed tomography (CT) voxel data to estimate absorbed radiation dose at a point of interest (POI) or series of POIs from a kilovoltage (kV) imaging procedure. Methods: The authors developed an approach that computes absorbed radiation dose at a POI by numerically evaluating the linear Boltzmann transport equation (LBTE) using a combination of deterministic and Monte Carlo (MC) techniques. This hybrid approach accounts for material heterogeneity with a level of accuracy comparable to the general MC algorithms. Also, the dose at a POI is computed within seconds using the Intel Core i7 CPU 920 2.67 GHz quad core architecture, and the calculations are performed using CT voxel data, making it flexible and feasible for clinical applications. To validate the method, the authors constructed and acquired a CT scan of a heterogeneous block phantom consisting of a succession of slab densities: Tissue (1.29 cm), bone (2.42 cm), lung (4.84 cm), bone (1.37 cm), and tissue (4.84 cm). Using the hybrid transport method, the authors computed the absorbed doses at a set of points along the central axis and x direction of the phantom for an isotropic 125 kVp photon spectral point source located along the central axis 92.7 cm above the phantom surface. The accuracy of the results was compared to those computed with MCNP, which was cross-validated with EGSnrc, and served as the benchmark for validation. Results: The error in the depth dose ranged from -1.45% to +1.39% with a mean and standard deviation of -0.12% and 0.66%, respectively. The error in the x profile ranged from -1.3% to +0.9%, with standard deviations of -0.3% and 0.5%, respectively. The number of photons required to achieve these results was 1x10{sup 6}. Conclusions: The voxel-based hybrid method evaluates the LBTE rapidly and accurately to estimate the absorbed x-ray dose at any POI or series of POIs from a kV imaging procedure.

  4. A method for estimation of accuracy of dose delivery with dynamic slit windows in medical linear accelerators.

    PubMed

    Ravichandran, R; Binukumar, J P; Sivakumar, S S; Krishnamurthy, K; Davis, C A

    2008-07-01

    Intensity-modulated radiotherapy (IMRT) clinical dose delivery is based on computer-controlled multileaf movements at different velocities. To test the accuracy of modulation of the beam periodically, quality assurance (QA) methods are necessary. Using a cylindrical phantom, dose delivery was checked at a constant geometry for sweeping fields. Repeated measurements with an in-house designed methodology over a period of 1 year indicate that the method is very sensitive to check the proper functioning of such dose delivery in medical linacs. A cylindrical perspex phantom with facility to accurately position a 0.6-cc (FC 65) ion chamber at constant depth at isocenter, (SA 24 constancy check tool phantom for MU check, Scanditronix Wellhofer) was used. Dosimeter readings were integrated for 4-mm, 10-mm, 20-mm sweeping fields and for 3 angular positions of the gantry periodically. Consistency of standard sweeping field output (10-mm slit width) and the ratios of outputs against other slit widths over a long period were reported. A 10-mm sweeping field output was found reproducible within an accuracy of 0.03% (n = 25) over 1 year. Four-millimeter, 20-mm outputs expressed as ratio with respect to 10-mm sweep output remained within a mean deviation of 0.2% and 0.03% respectively. Outputs at 3 gantry angles remained within 0.5%, showing that the effect of dynamic movements of multileaf collimator (MLC) on the output is minimal for angular positions of gantry. This method of QA is very simple and is recommended in addition to individual patient QA measurements, which reflect the accuracy of dose planning system. In addition to standard output and energy checks of linacs, the above measurements can be complemented so as to check proper functioning of multileaf collimator for dynamic field dose delivery.

  5. 3D Dose reconstruction: Banding artefacts in cine mode EPID images during VMAT delivery

    NASA Astrophysics Data System (ADS)

    Woodruff, H. C.; Greer, P. B.

    2013-06-01

    Cine (continuous) mode images obtained during VMAT delivery are heavily degraded by banding artefacts. We have developed a method to reconstruct the pulse sequence (and hence dose deposited) from open field images. For clinical VMAT fields we have devised a frame averaging strategy that greatly improves image quality and dosimetric information for three-dimensional dose reconstruction.

  6. Deformable Dose Reconstruction to Optimize the Planning and Delivery of Liver Cancer Radiotherapy

    NASA Astrophysics Data System (ADS)

    Velec, Michael

    The precise delivery of radiation to liver cancer patients results in improved control with higher tumor doses and minimized normal tissues doses. A margin of normal tissue around the tumor requires irradiation however to account for treatment delivery uncertainties. Daily image-guidance allows targeting of the liver, a surrogate for the tumor, to reduce geometric errors. However poor direct tumor visualization, anatomical deformation and breathing motion introduce uncertainties between the planned dose, calculated on a single pre-treatment computed tomography image, and the dose that is delivered. A novel deformable image registration algorithm based on tissue biomechanics was applied to previous liver cancer patients to track targets and surrounding organs during radiotherapy. Modeling these daily anatomic variations permitted dose accumulation, thereby improving calculations of the delivered doses. The accuracy of the algorithm to track dose was validated using imaging from a deformable, 3-dimensional dosimeter able to optically track absorbed dose. Reconstructing the delivered dose revealed that 70% of patients had substantial deviations from the initial planned dose. An alternative image-guidance technique using respiratory-correlated imaging was simulated, which reduced both the residual tumor targeting errors and the magnitude of the delivered dose deviations. A planning and delivery strategy for liver radiotherapy was then developed that minimizes the impact of breathing motion, and applied a margin to account for the impact of liver deformation during treatment. This margin is 38% smaller on average than the margin used clinically, and permitted an average dose-escalation to liver tumors of 9% for the same risk of toxicity. Simulating the delivered dose with deformable dose reconstruction demonstrated the plans with smaller margins were robust as 90% of patients' tumors received the intended dose. This strategy can be readily implemented with widely

  7. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    PubMed Central

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A.; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E.

    2014-01-01

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables. PMID:24838219

  8. A comprehensive analysis of the IMRT dose delivery process using statistical process control (SPC)

    SciTech Connect

    Gerard, Karine; Grandhaye, Jean-Pierre; Marchesi, Vincent; Kafrouni, Hanna; Husson, Francois; Aletti, Pierre

    2009-04-15

    The aim of this study is to introduce tools to improve the security of each IMRT patient treatment by determining action levels for the dose delivery process. To achieve this, the patient-specific quality control results performed with an ionization chamber--and which characterize the dose delivery process--have been retrospectively analyzed using a method borrowed from industry: Statistical process control (SPC). The latter consisted in fulfilling four principal well-structured steps. The authors first quantified the short term variability of ionization chamber measurements regarding the clinical tolerances used in the cancer center ({+-}4% of deviation between the calculated and measured doses) by calculating a control process capability (C{sub pc}) index. The C{sub pc} index was found superior to 4, which implies that the observed variability of the dose delivery process is not biased by the short term variability of the measurement. Then, the authors demonstrated using a normality test that the quality control results could be approximated by a normal distribution with two parameters (mean and standard deviation). Finally, the authors used two complementary tools--control charts and performance indices--to thoroughly analyze the IMRT dose delivery process. Control charts aim at monitoring the process over time using statistical control limits to distinguish random (natural) variations from significant changes in the process, whereas performance indices aim at quantifying the ability of the process to produce data that are within the clinical tolerances, at a precise moment. The authors retrospectively showed that the analysis of three selected control charts (individual value, moving-range, and EWMA control charts) allowed efficient drift detection of the dose delivery process for prostate and head-and-neck treatments before the quality controls were outside the clinical tolerances. Therefore, when analyzed in real time, during quality controls, they should

  9. A comprehensive analysis of the IMRT dose delivery process using statistical process control (SPC).

    PubMed

    Gérard, Karine; Grandhaye, Jean-Pierre; Marchesi, Vincent; Kafrouni, Hanna; Husson, François; Aletti, Pierre

    2009-04-01

    The aim of this study is to introduce tools to improve the security of each IMRT patient treatment by determining action levels for the dose delivery process. To achieve this, the patient-specific quality control results performed with an ionization chamber--and which characterize the dose delivery process--have been retrospectively analyzed using a method borrowed from industry: Statistical process control (SPC). The latter consisted in fulfilling four principal well-structured steps. The authors first quantified the short-term variability of ionization chamber measurements regarding the clinical tolerances used in the cancer center (+/- 4% of deviation between the calculated and measured doses) by calculating a control process capability (C(pc)) index. The C(pc) index was found superior to 4, which implies that the observed variability of the dose delivery process is not biased by the short-term variability of the measurement. Then, the authors demonstrated using a normality test that the quality control results could be approximated by a normal distribution with two parameters (mean and standard deviation). Finally, the authors used two complementary tools--control charts and performance indices--to thoroughly analyze the IMRT dose delivery process. Control charts aim at monitoring the process over time using statistical control limits to distinguish random (natural) variations from significant changes in the process, whereas performance indices aim at quantifying the ability of the process to produce data that are within the clinical tolerances, at a precise moment. The authors retrospectively showed that the analysis of three selected control charts (individual value, moving-range, and EWMA control charts) allowed efficient drift detection of the dose delivery process for prostate and head-and-neck treatments before the quality controls were outside the clinical tolerances. Therefore, when analyzed in real time, during quality controls, they should improve the

  10. Can glucose be monitored accurately at the site of subcutaneous insulin delivery?

    PubMed

    Ward, W Kenneth; Castle, Jessica R; Jacobs, Peter G; Cargill, Robert S

    2014-05-01

    Because insulin promotes glucose uptake into adipocytes, it has been assumed that during measurement of glucose at the site of insulin delivery, the local glucose level would be much lower than systemic glucose. However, recent investigations challenge this notion. What explanations could account for a reduced local effect of insulin in the subcutaneous space? One explanation is that, in humans, the effect of insulin on adipocytes appears to be small. Another is that insulin monomers and dimers (from hexamer disassociation) might be absorbed into the circulation before they can increase glucose uptake locally. In addition, negative cooperativity of insulin action (a lower than expected effect of very high insulin concentrations)may play a contributing role. Other factors to be considered include dilution of interstitial fluid by the insulin vehicle and the possibility that some of the local decline in glucose might be due to the systemic effect of insulin. With regard to future research, redundant sensing units might be able to quantify the effects of proximity, leading to a compensatory algorithm. In summary, when measured at the site of insulin delivery, the decline in subcutaneous glucose level appears to be minimal, though the literature base is not large. Findings thus far support (1) the development of integrated devices that monitor glucose and deliver insulin and (2) the use of such devices to investigate the relationship between subcutaneous delivery of insulin and its local effects on glucose. A reduction in the number of percutaneous devices needed to manage diabetes would be welcome. PMID:24876621

  11. The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

    PubMed Central

    Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A.; Sheng, Ke

    2015-01-01

    Purpose: Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. Methods: A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. Results: The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was

  12. The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

    SciTech Connect

    Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A.; Sheng, Ke

    2015-11-15

    Purpose: Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. Methods: A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. Results: The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was

  13. Dose calculation for hypofractionated volumetric-modulated arc therapy: approximating continuous arc delivery and tongue-and-groove modeling*

    PubMed Central

    Yang, Jie; Tang, Grace; Zhang, Pengpeng; Hunt, Margie; Lim, Seng B.; LoSasso, Thomas; Mageras, Gig

    2016-01-01

    Hypofractionated treatments generally increase the complexity of a treatment plan due to the more stringent constraints of normal tissues and target coverage. As a result, treatment plans contain more modulated MLC motions that may require extra efforts for accurate dose calculation. This study explores methods to minimize the differences between in-house dose calculation and actual delivery of hypofractionated volumetric-modulated arc therapy (VMAT), by focusing on arc approximation and tongue-and-groove (TG) modeling. For dose calculation, the continuous delivery arc is typically approximated by a series of static beams with an angular spacing of 2°. This causes significant error when there is large MLC movement from one beam to the next. While increasing the number of beams will minimize the dose error, calculation time will increase significantly. We propose a solution by inserting two additional apertures at each of the beam angle for dose calculation. These additional apertures were interpolated at two-thirds’ degree before and after each beam. Effectively, there were a total of three MLC apertures at each beam angle, and the weighted average fluence from the three apertures was used for calculation. Because the number of beams was kept the same, calculation time was only increased by about 6%–8%. For a lung plan, areas of high local dose differences (> 4%) between film measurement and calculation with one aperture were significantly reduced in calculation with three apertures. Ion chamber measurement also showed similar results, where improvements were seen with calculations using additional apertures. Dose calculation accuracy was further improved for TG modeling by developing a sampling method for beam fluence matrix. Single element point sampling for fluence transmitted through MLC was used for our fluence matrix with 1 mm resolution. For Varian HDMLC, grid alignment can cause fluence sampling error. To correct this, transmission volume averaging was

  14. Reducing Dose Uncertainty for Spot-Scanning Proton Beam Therapy of Moving Tumors by Optimizing the Spot Delivery Sequence

    PubMed Central

    Li, Heng; Zhu, X. Ronald; Zhang, Xiaodong

    2016-01-01

    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, 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. PMID:26460997

  15. Radiochromic film based transit dosimetry for verification of dose delivery with intensity modulated radiotherapy

    SciTech Connect

    Chung, Kwangzoo; Lee, Kiho; Shin, Dongho; Kyung Lim, Young; Byeong Lee, Se; Yoon, Myonggeun; Son, Jaeman; Yong Park, Sung

    2013-02-15

    Purpose: To evaluate the transit dose based patient specific quality assurance (QA) of intensity modulated radiation therapy (IMRT) for verification of the accuracy of dose delivered to the patient. Methods: Five IMRT plans were selected and utilized to irradiate a homogeneous plastic water phantom and an inhomogeneous anthropomorphic phantom. The transit dose distribution was measured with radiochromic film and was compared with the computed dose map on the same plane using a gamma index with a 3% dose and a 3 mm distance-to-dose agreement tolerance limit. Results: While the average gamma index for comparisons of dose distributions was less than one for 98.9% of all pixels from the transit dose with the homogeneous phantom, the passing rate was reduced to 95.0% for the transit dose with the inhomogeneous phantom. Transit doses due to a 5 mm setup error may cause up to a 50% failure rate of the gamma index. Conclusions: Transit dose based IMRT QA may be superior to the traditional QA method since the former can show whether the inhomogeneity correction algorithm from TPS is accurate. In addition, transit dose based IMRT QA can be used to verify the accuracy of the dose delivered to the patient during treatment by revealing significant increases in the failure rate of the gamma index resulting from errors in patient positioning during treatment.

  16. Investigation of pulsed low dose rate radiotherapy using dynamic arc delivery techniques

    NASA Astrophysics Data System (ADS)

    Ma, C.-M.; Lin, M. H.; Dai, X. F.; Koren, Sion; Klayton, T.; Wang, L.; Li, J. S.; Chen, L.; Price, R. A.

    2012-07-01

    There has been no consensus standard of care to treat recurrent cancer patients who have previously been irradiated. Pulsed low dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while still providing significant tumor control for recurrent cancers. This work investigates the dosimetry feasibility of PLDR treatment using dynamic arc delivery techniques. Five treatment sites were investigated in this study including breast, pancreas, prostate, head and neck, and lung. Dynamic arc plans were generated using the Varian Eclipse system and the RapidArc delivery technique with 6 and 10 MV photon beams. Each RapidArc plan consisted of two full arcs and the plan was delivered five times to achieve a daily dose of 200 cGy. The dosimetry requirement was to deliver approximately 20 cGy/arc with a 3 min interval to achieve an effective dose rate of 6.7 cGy min-1. Monte Carlo simulations were performed to calculate the actual dose delivered to the planning target volume (PTV) per arc taking into account beam attenuation/scattering and intensity modulation. The maximum, minimum and mean doses to the PTV were analyzed together with the dose volume histograms and isodose distributions. The dose delivery for the five plans was validated using solid water phantoms inserted with an ionization chamber and film, and a cylindrical detector array. Two intensity-modulated arcs were used to efficiently deliver the PLDR plans that provided conformal dose distributions for treating complex recurrent cancers. For the five treatment sites, the mean PTV dose ranged from 18.9 to 22.6 cGy/arc. For breast, the minimum and maximum PTV dose was 8.3 and 35.2 cGy/arc, respectively. The PTV dose varied between 12.9 and 27.5 cGy/arc for pancreas, 12.6 and 28.3 cGy/arc for prostate, 12.1 and 30.4 cGy/arc for H&N, and 16.2 and 27.6 cGy/arc for lung. Advanced radiation therapy can provide superior target coverage and normal tissue sparing for PLDR

  17. SU-E-T-475: An Accurate Linear Model of Tomotherapy MLC-Detector System for Patient Specific Delivery QA

    SciTech Connect

    Chen, Y; Mo, X; Chen, M; Olivera, G; Parnell, D; Key, S; Lu, W; Reeher, M; Galmarini, D

    2014-06-01

    Purpose: An accurate leaf fluence model can be used in applications such as patient specific delivery QA and in-vivo dosimetry for TomoTherapy systems. It is known that the total fluence is not a linear combination of individual leaf fluence due to leakage-transmission, tongue-and-groove, and source occlusion effect. Here we propose a method to model the nonlinear effects as linear terms thus making the MLC-detector system a linear system. Methods: A leaf pattern basis (LPB) consisting of no-leaf-open, single-leaf-open, double-leaf-open and triple-leaf-open patterns are chosen to represent linear and major nonlinear effects of leaf fluence as a linear system. An arbitrary leaf pattern can be expressed as (or decomposed to) a linear combination of the LPB either pulse by pulse or weighted by dwelling time. The exit detector responses to the LPB are obtained by processing returned detector signals resulting from the predefined leaf patterns for each jaw setting. Through forward transformation, detector signal can be predicted given a delivery plan. An equivalent leaf open time (LOT) sinogram containing output variation information can also be inversely calculated from the measured detector signals. Twelve patient plans were delivered in air. The equivalent LOT sinograms were compared with their planned sinograms. Results: The whole calibration process was done in 20 minutes. For two randomly generated leaf patterns, 98.5% of the active channels showed differences within 0.5% of the local maximum between the predicted and measured signals. Averaged over the twelve plans, 90% of LOT errors were within +/−10 ms. The LOT systematic error increases and shows an oscillating pattern when LOT is shorter than 50 ms. Conclusion: The LPB method models the MLC-detector response accurately, which improves patient specific delivery QA and in-vivo dosimetry for TomoTherapy systems. It is sensitive enough to detect systematic LOT errors as small as 10 ms.

  18. Mathematical model accurately predicts protein release from an affinity-based delivery system.

    PubMed

    Vulic, Katarina; Pakulska, Malgosia M; Sonthalia, Rohit; Ramachandran, Arun; Shoichet, Molly S

    2015-01-10

    Affinity-based controlled release modulates the delivery of protein or small molecule therapeutics through transient dissociation/association. To understand which parameters can be used to tune release, we used a mathematical model based on simple binding kinetics. A comprehensive asymptotic analysis revealed three characteristic regimes for therapeutic release from affinity-based systems. These regimes can be controlled by diffusion or unbinding kinetics, and can exhibit release over either a single stage or two stages. This analysis fundamentally changes the way we think of controlling release from affinity-based systems and thereby explains some of the discrepancies in the literature on which parameters influence affinity-based release. The rate of protein release from affinity-based systems is determined by the balance of diffusion of the therapeutic agent through the hydrogel and the dissociation kinetics of the affinity pair. Equations for tuning protein release rate by altering the strength (KD) of the affinity interaction, the concentration of binding ligand in the system, the rate of dissociation (koff) of the complex, and the hydrogel size and geometry, are provided. We validated our model by collapsing the model simulations and the experimental data from a recently described affinity release system, to a single master curve. Importantly, this mathematical analysis can be applied to any single species affinity-based system to determine the parameters required for a desired release profile. PMID:25449806

  19. The dose delivery effect of the different Beam ON interval in FFF SBRT: TrueBEAM

    NASA Astrophysics Data System (ADS)

    Tawonwong, T.; Suriyapee, S.; Oonsiri, S.; Sanghangthum, T.; Oonsiri, P.

    2016-03-01

    The purpose of this study is to determine the dose delivery effect of the different Beam ON interval in Flattening Filter Free Stereotactic Body Radiation Therapy (FFF-SBRT). The three 10MV-FFF SBRT plans (2 half rotating Rapid Arc, 9 to10 Gray/Fraction) were selected and irradiated in three different intervals (100%, 50% and 25%) using the RPM gating system. The plan verification was performed by the ArcCHECK for gamma analysis and the ionization chamber for point dose measurement. The dose delivery time of each interval were observed. For gamma analysis (2%&2mm criteria), the average percent pass of all plans for 100%, 50% and 25% intervals were 86.1±3.3%, 86.0±3.0% and 86.1±3.3%, respectively. For point dose measurement, the average ratios of each interval to the treatment planning were 1.012±0.015, 1.011±0.014 and 1.011±0.013 for 100%, 50% and 25% interval, respectively. The average dose delivery time was increasing from 74.3±5.0 second for 100% interval to 154.3±12.6 and 347.9±20.3 second for 50% and 25% interval, respectively. The same quality of the dose delivery from different Beam ON intervals in FFF-SBRT by TrueBEAM was illustrated. While the 100% interval represents the breath-hold treatment technique, the differences for the free-breathing using RPM gating system can be treated confidently.

  20. Accurate Accumulation of Dose for Improved Understanding of Radiation Effects in Normal Tissue

    SciTech Connect

    Jaffray, David A.; Lindsay, Patricia E.; Brock, Kristy K.; Deasy, Joseph O.; Tome, W.A.

    2010-03-01

    The actual distribution of radiation dose accumulated in normal tissues over the complete course of radiation therapy is, in general, poorly quantified. Differences in the patient anatomy between planning and treatment can occur gradually (e.g., tumor regression, resolution of edema) or relatively rapidly (e.g., bladder filling, breathing motion) and these undermine the accuracy of the planned dose distribution. Current efforts to maximize the therapeutic ratio require models that relate the true accumulated dose to clinical outcome. The needed accuracy can only be achieved through the development of robust methods that track the accumulation of dose within the various tissues in the body. Specific needs include the development of segmentation methods, tissue-mapping algorithms, uncertainty estimation, optimal schedules for image-based monitoring, and the development of informatics tools to support subsequent analysis. These developments will not only improve radiation outcomes modeling but will address the technical demands of the adaptive radiotherapy paradigm. The next 5 years need to see academia and industry bring these tools into the hands of the clinician and the clinical scientist.

  1. Templated open flocs of anisotropic particles for pulmonary delivery with pressurized metered dose inhalers.

    PubMed

    Tam, Jasmine M; Engstrom, Josh D; Ferrer, Domingo; Williams, Robert O; Johnston, Keith P

    2010-07-01

    The challenges in forming stable drug suspensions in hydrofluoroalkane (HFA) propellants have limited drug dosages and efficiency of drug delivery with pressurized metered dose inhalers (pMDI). Herein, stable suspensions of weakly flocculated particles, in the shape of thin plates or needles, of a poorly water-soluble drug, itraconazole (Itz), are efficiently delivered by pMDI at high doses, up to 2.4 mg/actuation. These anisotropic particles pack inefficiently and form low-density flocs that stack upon each other to prevent settling. In contrast, spherical particles formed dense aggregates that settled within minutes. Upon actuation of the pMDI, atomized propellant droplets shear apart and thus template the highly friable flocs. Evaporation of the HFA compacts the flocs to yield porous particles with optimal aerodynamic properties. High fine particle fractions (49-64%) were achieved with the stable suspensions for drug loadings up to 50 mg/mL. Furthermore, the micron-sized particles, ideal for pulmonary delivery, are composed of nanoparticles that dissociate and facilitate rapid dissolution of poorly water-soluble drugs. Pulmonary delivery of stable suspensions of templated, open flocs is broadly applicable to a range of anisotropic particle morphologies for poorly water-soluble drugs and proteins for efficient delivery of high doses, up to several milligrams, using minimal amounts of excipients. PMID:20187139

  2. Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

    PubMed Central

    Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

    2013-01-01

    Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

  3. In vitro study of cell survival following dynamic MLC intensity-modulated radiation therapy dose delivery

    SciTech Connect

    Moiseenko, Vitali; Duzenli, Cheryl; Durand, Ralph E.

    2007-04-15

    The possibility of reduced cell kill following intensity-modulated radiation therapy (IMRT) compared to conventional radiation therapy has been debated in the literature. This potential reduction in cell kill relates to prolonged treatment times typical of IMRT dose delivery and consequently increased repair of sublethal lesions. While there is some theoretical support to this reduction in cell kill published in the literature, direct experimental evidence specific to IMRT dose delivery patterns is lacking. In this study we present cell survival data for three cell lines: Chinese hamster V79 fibroblasts, human cervical carcinoma, SiHa and colon adenocarcinoma, WiDr. Cell survival was obtained for 2.1 Gy delivered as acute dose with parallel-opposed pair (POP), irradiation time 75 s, which served as a reference; regular seven-field IMRT, irradiation time 5 min; and IMRT with a break for multiple leaf collimator (MLC) re-initialization after three fields were delivered, irradiation time 10 min. An actual seven-field dynamic MLC IMRT plan for a head and neck patient was used. The IMRT plan was generated for a Varian EX or iX linear accelerator with 120 leaf Millenium MLC. Survival data were also collected for doses 1x, 2x, 3x, 4x, and 5x 2.1 Gy to establish parameters of the linear-quadratic equation describing survival following acute dose delivery. Cells were irradiated inside an acrylic cylindrical phantom specifically designed for this study. Doses from both IMRT and POP were validated using ion chamber measurements. A reproducible increase in cell survival was observed following IMRT dose delivery. This increase varied from small for V79, with a surviving fraction of 0.8326 following POP vs 0.8420 following uninterrupted IMRT, to very pronounced for SiHa, with a surviving fraction of 0.3903 following POP vs 0.5330 for uninterrupted IMRT. When compared to IMRT or IMRT with a break for MLC initialization, cell survival following acute dose delivery was

  4. Biologically Based Dose-Response Modeling. What is the potential for accurate description of the biological linkages in the applied dose - tissue dose-health effect continuum?

    EPA Science Inventory

    Given knowledge of exposure, the shape of the dose response curve is the key to predicting health risk, which in turn determines allowable levels of exposure and the associated economic costs of compliance.

  5. Small field dose delivery evaluations using cone beam optical computed tomography-based polymer gel dosimetry

    PubMed Central

    Olding, Timothy; Holmes, Oliver; DeJean, Paul; McAuley, Kim B.; Nkongchu, Ken; Santyr, Giles; Schreiner, L. John

    2011-01-01

    This paper explores the combination of cone beam optical computed tomography with an N-isopropylacrylamide (NIPAM)-based polymer gel dosimeter for three-dimensional dose imaging of small field deliveries. Initial investigations indicate that cone beam optical imaging of polymer gels is complicated by scattered stray light perturbation. This can lead to significant dosimetry failures in comparison to dose readout by magnetic resonance imaging (MRI). For example, only 60% of the voxels from an optical CT dose readout of a 1 l dosimeter passed a two-dimensional Low's gamma test (at a 3%, 3 mm criteria, relative to a treatment plan for a well-characterized pencil beam delivery). When the same dosimeter was probed by MRI, a 93% pass rate was observed. The optical dose measurement was improved after modifications to the dosimeter preparation, matching its performance with the imaging capabilities of the scanner. With the new dosimeter preparation, 99.7% of the optical CT voxels passed a Low's gamma test at the 3%, 3 mm criteria and 92.7% at a 2%, 2 mm criteria. The fitted interjar dose responses of a small sample set of modified dosimeters prepared (a) from the same gel batch and (b) from different gel batches prepared on the same day were found to be in agreement to within 3.6% and 3.8%, respectively, over the full dose range. Without drawing any statistical conclusions, this experiment gives a preliminary indication that intrabatch or interbatch NIPAM dosimeters prepared on the same day should be suitable for dose sensitivity calibration. PMID:21430853

  6. Small field dose delivery evaluations using cone beam optical computed tomography-based polymer gel dosimetry.

    PubMed

    Olding, Timothy; Holmes, Oliver; Dejean, Paul; McAuley, Kim B; Nkongchu, Ken; Santyr, Giles; Schreiner, L John

    2011-01-01

    This paper explores the combination of cone beam optical computed tomography with an N-isopropylacrylamide (NIPAM)-based polymer gel dosimeter for three-dimensional dose imaging of small field deliveries. Initial investigations indicate that cone beam optical imaging of polymer gels is complicated by scattered stray light perturbation. This can lead to significant dosimetry failures in comparison to dose readout by magnetic resonance imaging (MRI). For example, only 60% of the voxels from an optical CT dose readout of a 1 l dosimeter passed a two-dimensional Low's gamma test (at a 3%, 3 mm criteria, relative to a treatment plan for a well-characterized pencil beam delivery). When the same dosimeter was probed by MRI, a 93% pass rate was observed. The optical dose measurement was improved after modifications to the dosimeter preparation, matching its performance with the imaging capabilities of the scanner. With the new dosimeter preparation, 99.7% of the optical CT voxels passed a Low's gamma test at the 3%, 3 mm criteria and 92.7% at a 2%, 2 mm criteria. The fitted interjar dose responses of a small sample set of modified dosimeters prepared (a) from the same gel batch and (b) from different gel batches prepared on the same day were found to be in agreement to within 3.6% and 3.8%, respectively, over the full dose range. Without drawing any statistical conclusions, this experiment gives a preliminary indication that intrabatch or interbatch NIPAM dosimeters prepared on the same day should be suitable for dose sensitivity calibration. PMID:21430853

  7. Optimization of monoclonal antibody delivery via the lymphatics: the dose dependence

    SciTech Connect

    Steller, M.A.; Parker, R.J.; Covell, D.G.; Holton, O.D. 3d.; Keenan, A.M.; Sieber, S.M.; Weinstein, J.N.

    1986-04-01

    After interstitial injection in mice, antibody molecules enter local lymphatic vessels, flow with the lymph to regional lymph nodes, and bind to target antigens there. Compared with i.v. administration, delivery via the lymphatics provides a more efficient means for localizing antibody in lymph nodes. An IgG2a (36-7-5) directed against the murine class I major histocompatibility antigen H-2Kk has proved useful for studying the pharmacology of lymphatic delivery. At very low doses, most of the antibody remains at the injection site in Kk-positive animals. As the dose is progressively increased, most effective labeling occurs first in nodes proximal to the injection site and then in the next group of nodes along the lymphatic chain. At higher doses, antibody overflows the lymphatic system and enters the blood-stream via the thoracic duct and other lymphatic-venous connections. Once in the blood, antibody is rapidly cleared, apparently by binding to Kk-bearing cells. These findings indicate that the single-pass distribution of monoclonal antibodies in the lymphatics can be strongly dose dependent, a principle which may be of clinical significance in the improvement of immunolymphoscintigraphic imaging, especially with antibodies directed against normal and malignant lymphoid cells. Monoclonal antibodies directed against normal cell types in the lymph node may be useful for assessing the integrity of lymphatic chains by immunolymphoscintigraphy or, more speculatively, for altering the status of regional immune function. The results presented here indicate that a low or intermediate antibody dose may optimize the signal:noise ratio for imaging. In Kk-negative animals, the percentage of dose taken up in the major organs was essentially independent of the dose administered; there was no evidence for saturable sites of nonspecific binding.

  8. Cobalt-60 tomotherapy: Clinical treatment planning and phantom dose delivery studies

    SciTech Connect

    Dhanesar, Sandeep; Darko, Johnson; Joshi, Chandra P.; Kerr, Andrew; John Schreiner, L.

    2013-08-15

    Purpose: Investigations have shown that a Cobalt-60 (Co-60) radioactive source has the potential to play a role in intensity modulated radiation therapy (IMRT). In this paper, Co-60 tomotherapy's conformal dose delivery potential is evaluated by delivering conformal dose plans on a cylindrical homogeneous phantom containing clinical structures similar to those found in a typical head and neck (H and N) cancer. Also, the clinical potential of Co-60 tomotherapy is investigated by generating 2D clinical treatment plans for H and N and prostate anatomical regions. These plans are compared with the 6 MV based treatment plans for modalities such as linear accelerator-based tomotherapy and broad beam IMRT, and 15 MV based 3D conformal radiation therapy (3DCRT).Methods: For experimental validation studies, clinical and nonclinical conformal dose patterns were delivered on circular, homogeneous phantoms containing GafChromic film. For clinical planning study, dose calculations were performed with the EGSnrc Monte Carlo program, where a Theratronics 780C Co-60 unit and a 6 MV linear accelerator were modeled with a MIMiC binary multileaf collimator. An inhouse inverse treatment planning system was used to optimize tomotherapy plans using the same optimization parameters for both Co-60 and 6 MV beams. The IMRT and 3DCRT plans for the clinical cases were generated entirely in the Eclipse treatment planning system based on inhouse IMRT and 3DCRT site specific protocols.Results: The doses delivered to the homogeneous phantoms agreed with the calculations, indicating that it is possible to deliver highly conformal doses with the Co-60 unit. The dose distributions for Co-60 tomotherapy clinical plans for both clinical cases were similar to those obtained with 6 MV based tomotherapy and IMRT, and much more conformal compared to 3DCRT plans. The dose area histograms showed that the Co-60 plans achieve the dose objectives for the targets and organs at risk.Conclusions: These results

  9. The role of Cobalt-60 source in Intensity Modulated Radiation Therapy: From modeling finite sources to treatment planning and conformal dose delivery

    NASA Astrophysics Data System (ADS)

    Dhanesar, Sandeep Kaur

    Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen's University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system

  10. Is Heparin Effective for the Controlled Delivery of High-Dose Bone Morphogenetic Protein-2?

    PubMed

    Kim, Ri Youn; Lee, Beomseok; Park, Si-Nae; Ko, Jae-Hyung; Kim, In Sook; Hwang, Soon Jung

    2016-05-01

    Sustained release of bone morphogenetic protein (BMP)-2 by heparin-contained biomaterials is advantageous for bone tissue regeneration using low-dose BMP-2. However, its effect with high-dose BMP-2 is still unclear and should be clarified considering the clinical use of a high dose of BMP-2 in spine and oral surgery. This study aimed to evaluate the efficacy of a heparin-conjugated collagen sponge (HCS) with high-dose BMP-2 delivery by investigating in vivo initial osteogenic regulation and bone healing over 12 weeks in comparison with that of an absorbable collagen sponge (ACS). The in vitro BMP-2 release profile in the HCS exhibited a lower burst followed by a sustained release of BMP-2, whereas that of the ACS showed an initial burst phase only. As a result of a lower burst, the HCS-BMP group showed higher expression of bone-forming/resorbing markers and enhanced activation of osteoclasts than the ACS-BMP group within the scaffold of defect after 7 days, which is presumed to be because of retention of relatively higher amounts of BMP-2. However, the surrounding calvariae were less resorbed in the HCS-BMP group, compared with the aggressive resorptive response in the ACS-BMP group. Microcomputed tomography and histology revealed that HCS-BMP guided more effective bone regeneration of central defect over time inducing minor ossification at the defect exterior, whereas ACS-BMP exhibited excessive ossification at the defect exterior. These results showed that HCS-mediated BMP-2 delivery at a high dose has advantages over ACS, including less early resorption of surrounding bone tissue and higher efficacy in compact bone regeneration over a longer period, highlighting a clinical feasibility of this technology. PMID:27098389

  11. Has the use of computers in radiation therapy improved the accuracy in radiation dose delivery?

    NASA Astrophysics Data System (ADS)

    Van Dyk, J.; Battista, J.

    2014-03-01

    Purpose: It is well recognized that computer technology has had a major impact on the practice of radiation oncology. This paper addresses the question as to how these computer advances have specifically impacted the accuracy of radiation dose delivery to the patient. Methods: A review was undertaken of all the key steps in the radiation treatment process ranging from machine calibration to patient treatment verification and irradiation. Using a semi-quantitative scale, each stage in the process was analysed from the point of view of gains in treatment accuracy. Results: Our critical review indicated that computerization related to digital medical imaging (ranging from target volume localization, to treatment planning, to image-guided treatment) has had the most significant impact on the accuracy of radiation treatment. Conversely, the premature adoption of intensity-modulated radiation therapy has actually degraded the accuracy of dose delivery compared to 3-D conformal radiation therapy. While computational power has improved dose calibration accuracy through Monte Carlo simulations of dosimeter response parameters, the overall impact in terms of percent improvement is relatively small compared to the improvements accrued from 3-D/4-D imaging. Conclusions: As a result of computer applications, we are better able to see and track the internal anatomy of the patient before, during and after treatment. This has yielded the most significant enhancement to the knowledge of "in vivo" dose distributions in the patient. Furthermore, a much richer set of 3-D/4-D co-registered dose-image data is thus becoming available for retrospective analysis of radiobiological and clinical responses.

  12. Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors.

    PubMed

    Sheybani, Roya; Cobo, Angelica; Meng, Ellis

    2015-08-01

    We present a fully integrated implantable electrolysis-based micropump with incorporated EI dosing sensors. Wireless powering and data telemetry (through amplitude and frequency modulation) were utilized to achieve variable flow control and a bi-directional data link with the sensors. Wireless infusion rate control (0.14-1.04 μL/min) and dose sensing (bolus resolution of 0.55-2 μL) were each calibrated separately with the final circuit architecture and then simultaneous wireless flow control and dose sensing were demonstrated. Recombination detection using the dosing system, as well as, effects of coil separation distance and misalignment in wireless power and data transfer were studied. A custom-made normally closed spring-loaded ball check valve was designed and incorporated at the reservoir outlet to prevent backflow of fluids as a result of the reverse pressure gradient caused by recombination of electrolysis gases. Successful delivery, infusion rate control, and dose sensing were achieved in simulated brain tissue. PMID:26149696

  13. Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors.

    PubMed

    Sheybani, Roya; Cobo, Angelica; Meng, Ellis

    2015-08-01

    We present a fully integrated implantable electrolysis-based micropump with incorporated EI dosing sensors. Wireless powering and data telemetry (through amplitude and frequency modulation) were utilized to achieve variable flow control and a bi-directional data link with the sensors. Wireless infusion rate control (0.14-1.04 μL/min) and dose sensing (bolus resolution of 0.55-2 μL) were each calibrated separately with the final circuit architecture and then simultaneous wireless flow control and dose sensing were demonstrated. Recombination detection using the dosing system, as well as, effects of coil separation distance and misalignment in wireless power and data transfer were studied. A custom-made normally closed spring-loaded ball check valve was designed and incorporated at the reservoir outlet to prevent backflow of fluids as a result of the reverse pressure gradient caused by recombination of electrolysis gases. Successful delivery, infusion rate control, and dose sensing were achieved in simulated brain tissue.

  14. Dose and Chemical Modification Considerations for Continuous Cyclic AMP Analog Delivery to the Injured CNS

    PubMed Central

    Fouad, Karim; Ghosh, Mousumi; Vavrek, Romana; Tse, Arthur D.

    2009-01-01

    Abstract In this investigation, two cell-permeable synthetic analogs of cAMP, dibutyryl-cAMP (db-cAMP) and 8-bromo-cAMP, which are widely used to elevate intracellular cAMP levels under experimental conditions, were investigated for their ability to dose-dependently improve histological and functional outcomes following continuous delivery in two models of incomplete spinal cord injury (SCI). The cAMP analogs were delivered via osmotic minipumps at 1–250 mM through an indwelling cortical cannula or by intrathecal infusion for up to 4 weeks after either a T8 unilateral over-hemisection or a C2-3 dorsolateral quadrant lesion, respectively. In both SCI models, continuous db-cAMP delivery was associated with histopathological changes that included sporadic micro-hemorrhage formation and cavitation, enhanced macrophage infiltration and tissue damage at regions beyond the immediate application site; no deleterious or beneficial effect of agent delivery was observed at the spinal injury site. Furthermore, these changes were accompanied by pronounced behavioral deficits that included an absence of progressive locomotor recovery, increased extensor tone, paralysis, and sensory abnormalities. These deleterious effects were not observed in saline-treated animals, in animals in which the db-cAMP dose did not exceed 1 mM, or in those animals that received a high dose (250 mM) of the alternative cAMP analog, 8-bromo-cAMP. These results demonstrate that, for continuous intraparenchymal or intrathecal administration of cAMP analogs for the study of biological or therapeutic effects within the central nervous system (CNS), consideration of the effective concentration applied as well as the potential toxicity of chemical moieties on the parent molecule and/or their activity needs to be taken into account. PMID:19397425

  15. The efficacy and safety of low dose epidural butorphanol on postoperative analgesia following cesarean delivery.

    PubMed

    Pokharel, K; Rahman, T R; Singh, S N; Bhattarai, B; Basnet, N; Khaniya, S

    2008-01-01

    Butorphanol is considered an effective and safe analgesic after cesarean delivery but is associated with profound dose-dependent sedation. Somnolence may cause hindrance in early mother-baby interaction. This study was designed to assess the analgesic efficacy and to monitor side-effects of low doses (0.5 mg and 0.75 mg) of epidural butorphanol with bupivacaine compared to bupivacaine alone in parturients following cesarean delivery. One hundred and twenty parturients (American Society of Anesthesiologists physical status 1 and 2) undergoing cesarean delivery were allocated into three groups: group 1 received epidural 0.125% bupivacaine while group 2 and 3 received an additional 0.5 mg and 0.75 mg butorphanol respectively. A combined spinal, epidural technique was used. Spinal anaesthesia was used for surgery. The epidural route was used for postoperative analgesia with the study drug. Onset, duration and quality of analgesia, lowest visual analogue scales (VAS) score, and side effects were noted. The onset and duration of analgesia in group 2 (4.1+/-2.6 min and 202.4+/-62.8 min) and group 3 (4.0+/-2.5 min and 192.3+/-69.1 min) were significantly different (P<0.01) from group 1 (6.6+/-2.7 min and 145.7+/-89.6 min). The quality of analgesia in terms of time to first independent movement and satisfactory VAS were statistically better (P<0.01) in group 2 (3.9+/-0.3 hour and 8.1+/-0.1 mm) and group 3 (3.8+/-0.4 hour and 8.1+/-0.9 mm) than in group 1 (5.2+/-0.4 hour and 6.3+/-1.3 mm). The incidence of sedation was 5% in all the three groups. A lower dose of epidural butorphanol with bupivacaine produces a significantly earlier onset, longer duration and better quality of analgesia than bupivacaine does. PMID:18709032

  16. A non-rigid point matching method with local topology preservation for accurate bladder dose summation in high dose rate cervical brachytherapy

    NASA Astrophysics Data System (ADS)

    Chen, Haibin; Zhong, Zichun; Liao, Yuliang; Pompoš, Arnold; Hrycushko, Brian; Albuquerque, Kevin; Zhen, Xin; Zhou, Linghong; Gu, Xuejun

    2016-02-01

    GEC-ESTRO guidelines for high dose rate cervical brachytherapy advocate the reporting of the D2cc (the minimum dose received by the maximally exposed 2cc volume) to organs at risk. Due to large interfractional organ motion, reporting of accurate cumulative D2cc over a multifractional course is a non-trivial task requiring deformable image registration and deformable dose summation. To efficiently and accurately describe the point-to-point correspondence of the bladder wall over all treatment fractions while preserving local topologies, we propose a novel graphic processing unit (GPU)-based non-rigid point matching algorithm. This is achieved by introducing local anatomic information into the iterative update of correspondence matrix computation in the ‘thin plate splines-robust point matching’ (TPS-RPM) scheme. The performance of the GPU-based TPS-RPM with local topology preservation algorithm (TPS-RPM-LTP) was evaluated using four numerically simulated synthetic bladders having known deformations, a custom-made porcine bladder phantom embedded with twenty one fiducial markers, and 29 fractional computed tomography (CT) images from seven cervical cancer patients. Results show that TPS-RPM-LTP achieved excellent geometric accuracy with landmark residual distance error (RDE) of 0.7  ±  0.3 mm for the numerical synthetic data with different scales of bladder deformation and structure complexity, and 3.7  ±  1.8 mm and 1.6  ±  0.8 mm for the porcine bladder phantom with large and small deformation, respectively. The RDE accuracy of the urethral orifice landmarks in patient bladders was 3.7  ±  2.1 mm. When compared to the original TPS-RPM, the TPS-RPM-LTP improved landmark matching by reducing landmark RDE by 50  ±  19%, 37  ±  11% and 28  ±  11% for the synthetic, porcine phantom and the patient bladders, respectively. This was achieved with a computational time of less than 15 s in all cases

  17. Poster — Thur Eve — 33: The Influence of a Modeled Treatment Couch on Dose Distributions During IMRT and RapidArc Treatment Delivery

    SciTech Connect

    Aldosary, Ghada; Nobah, Ahmad; Al-Zorkani, Faisal; Moftah, Belal; Devic, Slobodan

    2014-08-15

    Treatment couches have been known to perturb dose delivery in patients. This effect is most pronounced in techniques such as IMRT and RapidArc. Although modern treatment planning systems (TPS) include data for a “default” treatment couch, actual couches are not manufactured identically. Thus, variations in their Hounsfield Unit (HU) values may exist. This study demonstrates a practical and simple method of acquiring reliable HU data for any treatment couch. We also investigate the effects of both the default and modeled treatment couches on absorbed dose. Experimental verifications show that by neglecting to incorporate the treatment couch in the TPS, dose differences of up to 9.5% and 7.3% were present for 4 MV and 10 MV photon beams, respectively. Furthermore, a clinical study based on a cohort of 20 RapidArc and IMRT (brain, pelvis and abdominal) cases is performed. 2D dose distributions show that without the couch in the planning phase, differences ≤ 4.6% and 5.9% for RapidArc and IMRT cases are present for the same cases that the default couch was added to. Additionally, in comparison to the default couch, employing the modeled couch in the calculation process influences dose distributions by ≤ 2.7% and 8% for RapidArc and IMRT cases, respectively. This result was found to be site specific; where an accurate couch proves to be preferable for IMRT brain plans. As such, adding the couch during dose calculation decreases dose calculation errors, and a precisely modeled treatment couch offers higher dose delivery accuracy for brain treatment using IMRT.

  18. Treatment planning and delivery of shell dose distribution for precision irradiation

    NASA Astrophysics Data System (ADS)

    Matinfar, Mohammad; Iyer, Santosh; Ford, Eric; Wong, John; Kazanzides, Peter

    2010-02-01

    The motivation for shell dose irradiation is to deliver a high therapeutic dose to the surrounding supplying blood-vessels of a lesion. Our approach's main utility is in enabling laboratory experiments to test the much disputed hypothesis about tumor vascular damage. That is, at high doses, tumor control is driven by damage to the tumor vascular supply and not the damage to the tumor cells themselves. There is new evidence that bone marrow derived cells can reconstitute tumor blood vessels in mice after irradiation. Shell dosimetry is also of interest to study the effect of radiation on neurogenic stem cells that reside in small niche surface of the mouse ventricles, a generalized form of shell. The type of surface that we are considering as a shell is a sphere which is created by intersection of cylinders. The results are then extended to create the contours of different organ shapes. Specifically, we present a routine to identify the 3-D structure of a mouse brain, project it into 2-D contours and convert the contours into trajectories that can be executed by our platform. We use the Small Animal Radiation Research Platform (SARRP) to demonstrate the dose delivery procedure. The SARRP is a portable system for precision irradiation with beam sizes down to 0.5 mm and optimally planned radiation with on-board cone-beam CT guidance.

  19. Detection of IMRT delivery errors based on a simple constancy check of transit dose by using an EPID

    NASA Astrophysics Data System (ADS)

    Baek, Tae Seong; Chung, Eun Ji; Son, Jaeman; Yoon, Myonggeun

    2015-11-01

    Beam delivery errors during intensity modulated radiotherapy (IMRT) were detected based on a simple constancy check of the transit dose by using an electronic portal imaging device (EPID). Twenty-one IMRT plans were selected from various treatment sites, and the transit doses during treatment were measured by using an EPID. Transit doses were measured 11 times for each course of treatment, and the constancy check was based on gamma index (3%/3 mm) comparisons between a reference dose map (the first measured transit dose) and test dose maps (the following ten measured dose maps). In a simulation using an anthropomorphic phantom, the average passing rate of the tested transit dose was 100% for three representative treatment sites (head & neck, chest, and pelvis), indicating that IMRT was highly constant for normal beam delivery. The average passing rate of the transit dose for 1224 IMRT fields from 21 actual patients was 97.6% ± 2.5%, with the lower rate possibly being due to inaccuracies of patient positioning or anatomic changes. An EPIDbased simple constancy check may provide information about IMRT beam delivery errors during treatment.

  20. Delivery of beclomethasone dipropionate from a spacer device: what dose is available for inhalation?

    PubMed Central

    O'Callaghan, C.; Cant, M.; Robertson, C.

    1994-01-01

    BACKGROUND--It is common for inhaled steroids to be delivered through a large volume spacer device. Comparatively little is known about how this practice affects the dose of drug received by patients compared with drug delivered directly from a metered dose inhaler. METHODS--The amount of beclomethasone dipropionate, contained in particles of various size, available for inhalation from a 750 ml polycarbonate spacer (Volumatic) was determined by impinger measurement and high performance liquid chromatography. Three strengths of metered dose inhalers were studied (50 micrograms, 100 micrograms, and 250 micrograms/actuation). The effect of multiple actuations of beclomethasone dipropionate into a Volumatic spacer, and increasing residence times of drug within the spacer before inhalation, on the amount of drug available to the patient for inhalation was determined. RESULTS--The amount of beclomethasone dipropionate in particles < 5 microns when delivered by a spacer device or directly from a metered dose inhaler was similar. The total amount of beclomethasone dipropionate available for inhalation per actuation decreased by 20 micrograms with the 50 micrograms inhaler, 48 micrograms with the 100 micrograms inhaler, and 161 micrograms with the 250 micrograms inhaler, when given via the spacer compared with delivery directly from a metered dose inhaler. There was a progressive decrease in drug available for inhalation per actuation as the number of actuations into the spacer increased, for all strengths of beclomethasone dipropionate tested. A progressive decrease in drug recovered per actuation was also seen with increasing residence times of drug within the spacer before inhalation. CONCLUSIONS--Use of the spacer device significantly reduced the amount of nonrespirable beclomethasone dipropionate available for inhalation. The amount of beclomethasone dipropionate within respirable particles decreased considerably following multiple actuations into the spacer and with

  1. Exploring trade-offs between VMAT dose quality and delivery efficiency using a network optimization approach

    NASA Astrophysics Data System (ADS)

    Salari, Ehsan; Wala, Jeremiah; Craft, David

    2012-09-01

    To formulate and solve the fluence-map merging procedure of the recently-published VMAT treatment-plan optimization method, called vmerge, as a bi-criteria optimization problem. Using an exact merging method rather than the previously-used heuristic, we are able to better characterize the trade-off between the delivery efficiency and dose quality. vmerge begins with a solution of the fluence-map optimization problem with 180 equi-spaced beams that yields the ‘ideal’ dose distribution. Neighboring fluence maps are then successively merged, meaning that they are added together and delivered as a single map. The merging process improves the delivery efficiency at the expense of deviating from the initial high-quality dose distribution. We replace the original merging heuristic by considering the merging problem as a discrete bi-criteria optimization problem with the objectives of maximizing the treatment efficiency and minimizing the deviation from the ideal dose. We formulate this using a network-flow model that represents the merging problem. Since the problem is discrete and thus non-convex, we employ a customized box algorithm to characterize the Pareto frontier. The Pareto frontier is then used as a benchmark to evaluate the performance of the standard vmerge algorithm as well as two other similar heuristics. We test the exact and heuristic merging approaches on a pancreas and a prostate cancer case. For both cases, the shape of the Pareto frontier suggests that starting from a high-quality plan, we can obtain efficient VMAT plans through merging neighboring fluence maps without substantially deviating from the initial dose distribution. The trade-off curves obtained by the various heuristics are contrasted and shown to all be equally capable of initial plan simplifications, but to deviate in quality for more drastic efficiency improvements. This work presents a network optimization approach to the merging problem. Contrasting the trade-off curves of the

  2. Pulmonary peptide delivery: effect of taste-masking excipients on leuprolide suspension metered-dose inhalers.

    PubMed

    Zheng, J Y; Fulu, M Y; Lee, D Y; Barber, T E; Adjei, A L

    2001-11-01

    The purpose of this study was to evaluate the effect of taste-masking excipients on in vitro and in vivo performance of a leuprolide metered-dose inhaler (MDI) suspension formulation. Taste-masking excipients (aspartame and menthol) were added to a leuprolide suspension MDI formulation. The leuprolide MDI formulation with the taste-masking excipients was characterized in terms of milling time, particle size distribution, dose delivery and uniformity, and drug absorption in dogs. The data were compared with a formula that did not contain taste-masking excipients. It was found that the longer milling time for the leuprolide suspension with the taste-masking excipients was required to obtain a similar particle size distribution compared with the formula without taste-masking excipients using a fluid energy mill. Although measurable differences in mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were not observed between the two formulations, the percent of particles < or = 5 microns and the actuator retention for the formula with the taste-masking excipients were significantly different from the formula without taste-masking excipients using the Marple-Miller cascade impactor. Taste-masking excipients did not show a significant effect on valve delivery and through-can dose uniformity. However, the mean ex-actuator dose was 150.4 mg for the formula with the taste-masking excipients and 162.2 mg for the reference formula, respectively, indicating a significant difference. In tracheostomized dogs, both formulations showed comparable pharmacokinetic parameters including Cmax, Tmax, AUC0-12 and bioavailability (F%), indicating that the taste-masking excipients do not have an effect on lung absorption of leuprolide acetate. Therefore, inclusion of taste-masking excipients in the leuprolide MDI suspension formulation showed a significant impact on drug micronization, exactuator dose, and particle deposition pattern. Mechanistically, the

  3. In-phantom dose verification of prostate IMRT and VMAT deliveries using plastic scintillation detectors.

    PubMed

    Klein, David; Briere, Tina Marie; Kudchadker, Rajat; Archambault, Louis; Beaulieu, Luc; Lee, Andrew; Beddar, Sam

    2012-10-01

    treatment by providing accurate in vivo dose reports during treatment and verify in real-time whether treatments are being delivered according to the prescribed plan.

  4. In-phantom dose verification of prostate IMRT and VMAT deliveries using plastic scintillation detectors

    PubMed Central

    Klein, David; Briere, Tina Marie; Kudchadker, Rajat; Archambault, Louis; Beaulieu, Luc; Lee, Andrew; Beddar, Sam

    2012-01-01

    patient treatment by providing accurate in vivo dose reports during treatment and verify in real-time whether treatments are being delivered according to the prescribed plan. PMID:23180976

  5. SU-E-T-335: Transit Dosimetry for Verification of Dose Delivery Using Electronic Portal Imaging Device (EPID)

    SciTech Connect

    Baek, T; Chung, E; Lee, S; Yoon, M

    2014-06-01

    Purpose: To evaluate the effectiveness of transit dose, measured with an electronic portal imaging device (EPID), in verifying actual dose delivery to patients. Methods: Plans of 5 patients with lung cancer, who received IMRT treatment, were examined using homogeneous solid water phantom and inhomogeneous anthropomorphic phantom. To simulate error in patient positioning, the anthropomorphic phantom was displaced from 5 mm to 10 mm in the inferior to superior (IS), superior to inferior (SI), left to right (LR), and right to left (RL) directions. The transit dose distribution was measured with EPID and was compared to the planed dose using gamma index. Results: Although the average passing rate based on gamma index (GI) with a 3% dose and a 3 mm distance-to-dose agreement tolerance limit was 94.34 % for the transit dose with homogeneous phantom, it was reduced to 84.63 % for the transit dose with inhomogeneous anthropomorphic phantom. The Result also shows that the setup error of 5mm (10mm) in IS, SI, LR and SI direction can Result in the decrease in values of GI passing rates by 1.3% (3.0%), 2.2% (4.3%), 5.9% (10.9%), and 8.9% (16.3%), respectively. Conclusion: Our feasibility study suggests that the transit dose-based quality assurance may provide information regarding accuracy of dose delivery as well as patient positioning.

  6. Investigation of dose homogeneity for loose helical tomotherapy delivery in the context of breath-hold radiation therapy

    NASA Astrophysics Data System (ADS)

    Kim, Bryan; Kron, Tomas; Battista, Jerry; Van Dyk, Jake

    2005-05-01

    Loose helical delivery is a potential solution to account for respiration-driven tumour motion in helical tomotherapy (HT). In this approach, a treatment is divided into a set of interlaced 'loose' helices commencing at different gantry angles. Each loose helix covers the entire target length in one gantry rotation during a single breath-hold. The dosimetric characteristics of loose helical delivery were investigated by delivering a 6 MV photon beam in a HT-like manner. Multiple scenarios of conventional 'tight' HT and loose helical deliveries were modelled in treatment planning software, and carried out experimentally with Kodak EDR2 film. The advantage of loose helical delivery lies in its ability to produce a more homogeneous dose distribution by eliminating the 'thread' effect—an inherent characteristic of HT, which results in dose modulations away from the axis of gantry rotation. However, loose helical delivery was also subjected to undesirable dose modulations in the direction of couch motion (termed 'beating' effect), when the ratio between the number of beam projections per gantry rotation (n) and pitch factor (p) was a non-integer. The magnitude of dose modulations decreased with an increasing n/p ratio. The results suggest that for the current HT unit (n = 51), dose modulations could be kept under 5% by selecting a pitch factor smaller than 7. A pitch factor of this magnitude should be able to treat a target up to 30 cm in length. Loose helical delivery should increase the total session time only by a factor of 2, while the planning time should stay the same since the total number of beam projections remains unchanged. Considering its dosimetric advantage and clinical practicality, loose helical delivery is a promising solution for the future HT treatments of respiration-driven targets.

  7. Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of flow pattern.

    PubMed

    Mouloudi, E; Prinianakis, G; Kondili, E; Georgopoulos, D

    2000-08-01

    In mechanically ventilated patients the flow pattern during bronchodilator delivery by metered-dose inhaler (MDI) could be a factor that might influence the effectiveness of this therapy. In order to test this the effect of two different inspiratory flow patterns on the bronchodilation induced by beta2-agonists administered via MDI and spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) was examined. Eighteen mechanically ventilated patients with COPD, were prospectively randomized to receive two (n=8, protocol A) or six (n=10 protocol B) puffs salbutamol (100 microg x puff(-1)) either under pressure control (decelerating flow pattern) or under volume control (square wave flow pattern). With both modes, tidal volume and inspiratory time were identical. Salbutamol was administered via an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud-enhancer spacer. After a 6-h washout, patients were crossed over to receive the same dose of salbutamol (200 or 600 microg, respectively in protocols A and B) by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rint) and maximum (Rrs) inspiratory resistance and the difference between Rrs and Rint (deltaR) were measured before and at 15, 30 and 60 min after salbutamol. Independent of the dose, salbutamol caused a significant decrease in dynamic and static airway pressures, Rint and Rrs. These changes were not influenced by the inspiratory flow pattern and were evident at 15, 30 and 60 min after salbutamol. It is concluded that salbutamol delivered via metered dose inhaler and spacer device, induces significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease, the magnitude of which is not affected by the inspiratory flow/time profile.

  8. Avoiding cytotoxicity of transposases by dose-controlled mRNA delivery

    PubMed Central

    Galla, Melanie; Schambach, Axel; Falk, Christine S.; Maetzig, Tobias; Kuehle, Johannes; Lange, Kathrin; Zychlinski, Daniela; Heinz, Niels; Brugman, Martijn H.; Göhring, Gudrun; Izsvák, Zsuzsanna; Ivics, Zoltán; Baum, Christopher

    2011-01-01

    The Sleeping Beauty (SB) transposase and its newly developed hyperactive variant, SB100X, are of increasing interest for genome modification in experimental models and gene therapy. The potential cytotoxicity of transposases requires careful assessment, considering that residual integration events of transposase expression vectors delivered by physicochemical transfection or episomal retroviral vectors may lead to permanent transposase expression and resulting uncontrollable transposition. Comparing retrovirus-based approaches for delivery of mRNA, episomal DNA or integrating DNA, we found that conventional SB transposase, SB100X and a newly developed codon-optimized SB100Xo may trigger premitotic arrest and apoptosis. Cell stress induced by continued SB overexpression was self-limiting due to the induction of cell death, which occurred even in the absence of a co-transfected transposable element. The cytotoxic effects of SB transposase were strictly dose dependent and heralded by induction of p53 and c-Jun. Inactivating mutations in SB’s catalytic domain could not abrogate cytotoxicity, suggesting a mechanism independent of DNA cleavage activity. An improved approach of retrovirus particle-mediated mRNA transfer allowed transient and dose-controlled expression of SB100X, supported efficient transposition and prevented cytotoxicity. Transposase-mediated gene transfer can thus be tuned to maintain high efficiency in the absence of overt cell damage. PMID:21609958

  9. Use of dose-dependent absorption into target tissues to more accurately predict cancer risk at low oral doses of hexavalent chromium.

    PubMed

    Haney, J

    2015-02-01

    The mouse dose at the lowest water concentration used in the National Toxicology Program hexavalent chromium (CrVI) drinking water study (NTP, 2008) is about 74,500 times higher than the approximate human dose corresponding to the 35-city geometric mean reported in EWG (2010) and over 1000 times higher than that based on the highest reported tap water concentration. With experimental and environmental doses differing greatly, it is a regulatory challenge to extrapolate high-dose results to environmental doses orders of magnitude lower in a meaningful and toxicologically predictive manner. This seems particularly true for the low-dose extrapolation of results for oral CrVI-induced carcinogenesis since dose-dependent differences in the dose fraction absorbed by mouse target tissues are apparent (Kirman et al., 2012). These data can be used for a straightforward adjustment of the USEPA (2010) draft oral slope factor (SFo) to be more predictive of risk at environmentally-relevant doses. More specifically, the evaluation of observed and modeled differences in the fraction of dose absorbed by target tissues at the point-of-departure for the draft SFo calculation versus lower doses suggests that the draft SFo be divided by a dose-specific adjustment factor of at least an order of magnitude to be less over-predictive of risk at more environmentally-relevant doses.

  10. Development of dose delivery verification by PET imaging of photonuclear reactions following high energy photon therapy

    NASA Astrophysics Data System (ADS)

    Janek, S.; Svensson, R.; Jonsson, C.; Brahme, A.

    2006-11-01

    A method for dose delivery monitoring after high energy photon therapy has been investigated based on positron emission tomography (PET). The technique is based on the activation of body tissues by high energy bremsstrahlung beams, preferably with energies well above 20 MeV, resulting primarily in 11C and 15O but also 13N, all positron-emitting radionuclides produced by photoneutron reactions in the nuclei of 12C, 16O and 14N. A PMMA phantom and animal tissue, a frozen hind leg of a pig, were irradiated to 10 Gy and the induced positron activity distributions were measured off-line in a PET camera a couple of minutes after irradiation. The accelerator used was a Racetrack Microtron at the Karolinska University Hospital using 50 MV scanned photon beams. From photonuclear cross-section data integrated over the 50 MV photon fluence spectrum the predicted PET signal was calculated and compared with experimental measurements. Since measured PET images change with time post irradiation, as a result of the different decay times of the radionuclides, the signals from activated 12C, 16O and 14N within the irradiated volume could be separated from each other. Most information is obtained from the carbon and oxygen radionuclides which are the most abundant elements in soft tissue. The predicted and measured overall positron activities are almost equal (-3%) while the predicted activity originating from nitrogen is overestimated by almost a factor of two, possibly due to experimental noise. Based on the results obtained in this first feasibility study the great value of a combined radiotherapy-PET-CT unit is indicated in order to fully exploit the high activity signal from oxygen immediately after treatment and to avoid patient repositioning. With an RT-PET-CT unit a high signal could be collected even at a dose level of 2 Gy and the acquisition time for the PET could be reduced considerably. Real patient dose delivery verification by means of PET imaging seems to be

  11. Impact of small MU/segment and dose rate on delivery accuracy of volumetric-modulated arc therapy (VMAT).

    PubMed

    Huang, Long; Zhuang, Tingliang; Mastroianni, Anthony; Djemil, Toufik; Cui, Taoran; Xia, Ping

    2016-05-08

    Volumetric-modulated arc therapy (VMAT) plans may require more control points (or segments) than some of fixed-beam IMRT plans that are created with a limited number of segments. Increasing number of control points in a VMAT plan for a given prescription dose could create a large portion of the total number of segments with small number monitor units (MUs) per segment. The purpose of this study is to investigate the impact of the small number MU/segment on the delivery accuracy of VMAT delivered with various dose rates. Ten patient datasets were planned for hippocampus sparing for whole brain irradiation. For each dataset, two VMAT plans were created with maximum dose rates of 600 MU/min (the maximum field size of 21 × 40 cm2) and 1000 MU/min (the maximum field size of 15 × 15 cm2) for a daily dose of 3 Gy. Without reoptimization, the daily dose of these plans was purposely reduced to 1.5 Gy and 1.0 Gy while keeping the same total dose. Using the two dose rates and three different daily doses, six VMAT plans for each dataset were delivered to a physical phantom to investigate how the changes of dose rate and daily doses impact on delivery accuracy. Using the gamma index, we directly compared the delivered planar dose profiles with the reduced daily doses (1.5 Gy and 1.0 Gy) to the delivered planar dose at 3 Gy daily dose, delivered at dose rate of 600 MU/min and 1000 MU/min, respectively. The average numbers of segments with MU/segment ≤ 1 were 35 ± 8, 87 ± 6 for VMAT-600 1.5 Gy, VMAT-600 1 Gy plans, and 30 ± 7 and 42 ± 6 for VMAT-1000 1.5 Gy and VMAT-1000 1 Gy plans, respectively. When delivered at 600 MU/min dose rate, the average gamma index passing rates (1%/1 mm criteria) of comparing delivered 1.5 Gy VMAT planar dose profiles to 3.0 Gy VMAT delivered planar dose profiles was 98.28% ± 1.66%, and the average gamma index passing rate of comparing delivered 1.0 Gy VMAT planar dose to 3.0 Gy VMAT delivered planar dose was 83.75% ± 4.86%. If using 2%/2mm

  12. An accurate derivation of the air dose-rate and the deposition concentration distribution by aerial monitoring in a low level contaminated area

    NASA Astrophysics Data System (ADS)

    Nishizawa, Yukiyasu; Sugita, Takeshi; Sanada, Yukihisa; Torii, Tatsuo

    2015-04-01

    Since 2011, MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan) have been conducting aerial monitoring to investigate the distribution of radioactive cesium dispersed into the atmosphere after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), Tokyo Electric Power Company. Distribution maps of the air dose-rate at 1 m above the ground and the radioactive cesium deposition concentration on the ground are prepared using spectrum obtained by aerial monitoring. The radioactive cesium deposition is derived from its dose rate, which is calculated by excluding the dose rate of the background radiation due to natural radionuclides from the air dose-rate at 1 m above the ground. The first step of the current method of calculating the dose rate due to natural radionuclides is calculate the ratio of the total count rate of areas where no radioactive cesium is detected and the count rate of regions with energy levels of 1,400 keV or higher (BG-Index). Next, calculate the air dose rate of radioactive cesium by multiplying the BG-Index and the integrated count rate of 1,400 keV or higher for the area where the radioactive cesium is distributed. In high dose-rate areas, however, the count rate of the 1,365-keV peak of Cs-134, though small, is included in the integrated count rate of 1,400 keV or higher, which could cause an overestimation of the air dose rate of natural radionuclides. We developed a method for accurately evaluating the distribution maps of natural air dose-rate by excluding the effect of radioactive cesium, even in contaminated areas, and obtained the accurate air dose-rate map attributed the radioactive cesium deposition on the ground. Furthermore, the natural dose-rate distribution throughout Japan has been obtained by this method.

  13. SU-E-T-107: Development of a GPU-Based Dose Delivery System for Adaptive Pencil Beam Scanning

    SciTech Connect

    Giordanengo, S; Russo, G; Marchetto, F; Attili, A; Monaco, V; Varasteh, M; Pella, A

    2014-06-01

    Purpose: A description of a GPU-based dose delivery system (G-DDS) to integrate a fast forward planning implementing in real-time the prescribed sequence of pencil beams. The system, which is under development, is designed to evaluate the dose distribution deviations due to range variations and interplay effects affecting mobile tumors treatments. Methods: The Dose Delivery System (DDS) in use at the Italian Centro Nazionale di Adroterapia Oncologica (CNAO), is the starting point for the presented system. A fast and partial forward planning (FP) tool has been developed to evaluate in few seconds the delivered dose distributions using the DDS data (on-line measurements of spot properties, i.e. number of particles and positions). The computation is performed during the intervals between synchrotron spills and, made available at the end of each spill. In the interval between two spills, the G-DDS will evaluate the delivered dose distributions taking into account the real-time target positions measured by a tracking system. The sequence of prescribed pencil beams for the following spill will be adapted taking into account the variations with respect to the original plan due to the target motion. In order to speed up the computation required to modify pencil beams distribution (up to 400 times has been reached), the Graphics Processing Units (GPUs) and advanced Field Programmable Gate Arrays (FPGAs) are used. Results: An existing offline forward planning is going to be optimized for the CUDA architecture: the gain in time will be presented. The preliminary performances of the developed GPU-based FP algorithms will be shown. Conclusion: A prototype of a GPU-based dose delivery system is under development and will be presented. The system workflow will be illustrated together with the approach adopted to integrate the three main systems, i.e. CNAO dose delivery system, fast forward planning, and tumor tracking system.

  14. Influence of robust optimization in intensity-modulated proton therapy with different dose delivery techniques

    SciTech Connect

    Liu Wei; Li Yupeng; Li Xiaoqiang; Cao Wenhua; Zhang Xiaodong

    2012-06-15

    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

  15. Towards the development of lipid multilayer microarrays for dose dependent in vitro delivery and screening

    NASA Astrophysics Data System (ADS)

    Kusi-Appiah, Aubrey Emmanuel

    Screening for effects of small molecules on cells grown in culture is a well-established method for drug discovery and testing, and faster throughput at lower cost is needed especially for lipophilic materials. Small-molecule arrays present a promising approach. However, it has been a challenge to use them to obtain quantitative surface based dose-response curves in vitro, especially for lipophilic compounds. This thesis first introduces a simple novel method of surface-mediated delivery of drugs to cells from a microarray of phospholipid multilayers (layers thicker than a bilayer) encapsulating small molecules. The capability of controlling the dosage of the lipophilic molecules delivered to cells using the lipid multilayer microarray assay is further demonstrated using the nanointaglio printing method. This control enabled the variation of the volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. The surface supported lipid volume information was used to obtain EC-50 values for the response of HeLa cells to treatment with three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. Features with sub-cellular lateral dimensions were found to be necessary to obtain normal cell adhesion with HeLa cells. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which may be explained in terms of cell-adhesion playing a more important role in the surface-based assay. Finally, solution encapsulation was done for a library of hydrophilic silicon nanocrystals in order to set a solution standard for comparison with future surface supported delivery of the library. The

  16. Optimizing human in vivo dosing and delivery of β-alanine supplements for muscle carnosine synthesis.

    PubMed

    Stellingwerff, Trent; Decombaz, Jacques; Harris, Roger C; Boesch, Chris

    2012-07-01

    Interest into the effects of carnosine on cellular metabolism is rapidly expanding. The first study to demonstrate in humans that chronic β-alanine (BA) supplementation (~3-6 g BA/day for ~4 weeks) can result in significantly augmented muscle carnosine concentrations (>50%) was only recently published. BA supplementation is potentially poised for application beyond the niche exercise and performance-enhancement field and into other more clinical populations. When examining all BA supplementation studies that directly measure muscle carnosine (n=8), there is a significant linear correlation between total grams of BA consumed (of daily intake ranges of 1.6-6.4 g BA/day) versus both the relative and absolute increases in muscle carnosine. Supporting this, a recent dose-response study demonstrated a large linear dependency (R2=0.921) based on the total grams of BA consumed over 8 weeks. The pre-supplementation baseline carnosine or individual subjects' body weight (from 65 to 90 kg) does not appear to impact on subsequent carnosine synthesis from BA consumption. Once muscle carnosine is augmented, the washout is very slow (~2%/week). Recently, a slow-release BA tablet supplement has been developed showing a smaller peak plasma BA concentration and delayed time to peak, with no difference in the area under the curve compared to pure BA in solution. Further, this slow-release profile resulted in a reduced urinary BA loss and improved retention, while at the same time, eliciting minimal paraesthesia symptoms. However, our complete understanding of optimizing in vivo delivery and dosing of BA is still in its infancy. Thus, this review will clarify our current knowledge of BA supplementation to augment muscle carnosine as well as highlight future research questions on the regulatory points of control for muscle carnosine synthesis.

  17. Propellant-driven metered-dose inhalers for pulmonary drug delivery.

    PubMed

    Smyth, Hugh D C

    2005-01-01

    The current market for pulmonary drug delivery is at a bottleneck. The therapeutic advantages of inhalation aerosols, and the potential for the lungs as a route for systemically acting drugs, vaccines and gene therapeutic agents, have resulted in a rapid growth of the industry. Alongside this, the environment of inhaler design and formulation has changed markedly in recent years. Environmental concerns over propellants, the commercial success of dry powder inhalers, and the apparent lack of advancement of propellant-driven metered-dose inhalers (pMDIs) has led to a less clear future for these devices. This review critically assesses these pressures and also potential opportunities for the pMDI. It is proposed that the future role of pMDIs will be determined by several important forces that can be classified under 'technology development' or 'market climate' categories. Technology development forces will be strengthened by the ability of the industry to have a systematic understanding of mechanisms of spray formation, perform subsequent and continued device and formulation advances, and a focus on all patient groups: particularly paediatric and geriatric populations. The ability to succeed in these areas will be largely determined by the willingness to invest in fundamental research of pMDI technologies.

  18. TH-C-BRD-07: Minimizing Dose Uncertainty for Spot Scanning Beam Proton Therapy of Moving Tumor with Optimization of Delivery Sequence

    SciTech Connect

    Li, H; Zhang, X; Zhu, X; Li, Y

    2014-06-15

    Purpose: Intensity modulated proton therapy (IMPT) has been shown to be able to reduce dose to normal tissue compared to intensity modulated photon radio-therapy (IMRT), and has been implemented for selected lung cancer patients. However, respiratory motion-induced dose uncertainty remain one of the major concerns for the radiotherapy of lung cancer, and the utility of IMPT for lung patients was limited because of the proton dose uncertainty induced by motion. Strategies such as repainting and tumor tracking have been proposed and studied but repainting could result in unacceptable long delivery time and tracking is not yet clinically available. We propose a novel delivery strategy for spot scanning proton beam therapy. Method: The effective number of delivery (END) for each spot position in a treatment plan was calculated based on the parameters of the delivery system, including time required for each spot, spot size and energy. The dose uncertainty was then calculated with an analytical formula. The spot delivery sequence was optimized to maximize END and minimize the dose uncertainty. 2D Measurements with a detector array on a 1D moving platform were performed to validate the calculated results. Results: 143 2D measurements on a moving platform were performed for different delivery sequences of a single layer uniform pattern. The measured dose uncertainty is a strong function of the delivery sequence, the worst delivery sequence results in dose error up to 70% while the optimized delivery sequence results in dose error of <5%. END vs. measured dose uncertainty follows the analytical formula. Conclusion: With optimized delivery sequence, it is feasible to minimize the dose uncertainty due to motion in spot scanning proton therapy.

  19. Spatial variation of dosimetric leaf gap and its impact on dose delivery

    SciTech Connect

    Kumaraswamy, Lalith K.; Schmitt, Jonathan D.; Bailey, Daniel W.; Xu, Zheng Zheng; Podgorsak, Matthew B.

    2014-11-01

    Purpose: During dose calculation, the Eclipse treatment planning system (TPS) retracts the multileaf collimator (MLC) leaf positions by half of the dosimetric leaf gap (DLG) value (measured at central axis) for all leaf positions in a dynamic MLC plan to accurately model the rounded leaf ends. The aim of this study is to map the variation of DLG along the travel path of each MLC leaf pair and quantify how this variation impacts delivered dose. Methods: 6 MV DLG values were measured for all MLC leaf pairs in increments of 1.0 cm (from the line intersecting the CAX and perpendicular to MLC motion) to 13.0 cm off axis distance at dmax. The measurements were performed on two Varian linear accelerators, both employing the Millennium 120-leaf MLCs. The measurements were performed at several locations in the beam with both a Sun Nuclear MapCHECK device and a PTW pinpoint ion chamber. Results: The measured DLGs for the middle 40 MLC leaf pairs (each 0.5 cm width) at positions along a line through the CAX and perpendicular to MLC leaf travel direction were very similar, varying maximally by only 0.2 mm. The outer 20 MLC leaf pairs (each 1.0 cm width) have much lower DLG values, about 0.3–0.5 mm lower than the central MLC leaf pair, at their respective central line position. Overall, the mean and the maximum variation between the 0.5 cm width leaves and the 1.0 cm width leaf pairs are 0.32 and 0.65 mm, respectively. Conclusions: The spatial variation in DLG is caused by the variation of intraleaf transmission through MLC leaves. Fluences centered on the CAX would not be affected since DLG does not vary; but any fluences residing significantly off axis with narrow sweeping leaves may exhibit significant dose differences. This is due to the fact that there are differences in DLG between the true DLG exhibited by the 1.0 cm width outer leaves and the constant DLG value utilized by the TPS for dose calculation. Since there are large differences in DLG between the 0.5 cm width

  20. Albuterol delivery in a neonatal ventilated lung model: Nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers.

    PubMed

    Lugo, R A; Kenney, J K; Keenan, J; Salyer, J W; Ballard, J; Ward, R M

    2001-03-01

    The aim of this study was to compare albuterol delivery in a neonatal ventilated lung model, using three delivery methods: 1) jet nebulizer; 2) chlorofluorocarbon-pressurized metered dose inhaler (CFC-MDI) actuated into an ACE(R) spacer; and 3) hydrofluoroalkane-pressurized MDI (HFA-MDI) actuated into an ACE(R) spacer. The bench model consisted of a mechanically ventilated infant test lung with ventilator settings to simulate a very low birth weight neonate with moderate lung disease. Albuterol solution (0.5%) was nebulized at the humidifier and temperature port, 125 cm and 30 cm from the Y-piece, respectively. Albuterol metered dose inhalers (MDIs) were actuated into an ACE(R) spacer that was tested in two positions: 1) inline between the endotracheal (ET) tube and the Y-piece; and 2) attached to the ET tube and administered by manual ventilation. Albuterol was collected on a filter at the distal end of the ET tube and was quantitatively analyzed by high performance liquid chromatography. Albuterol delivery by CFC-MDI (position 1, 4.8 +/- 1.0%, vs. position 2, 3.8 +/- 1.6%, P > 0.05) and HFA-MDI (position 1, 5.7 +/- 1.6%, vs. position 2, 5.5 +/- 2.4%, P > 0.05) were significantly greater than delivery by nebulization at 30 cm (0.16 +/- 0.07%) and 125 cm (0.15 +/- 0.03%) from the Y-piece (P < 0.001). A single actuation of albuterol MDI delivered the equivalent of nebulizing 2.5-3.7 mg of albuterol solution. We conclude that albuterol administered by MDI and ACE(R) spacer resulted in more efficient delivery than by nebulization in this mechanically ventilated neonatal lung model. There was no significant difference in drug delivery between CFC-MDI and HFA-MDI; nor did the placement of the spacer significantly affect drug delivery.

  1. Establishment of an x-ray standard calibration curve by conventional dicentric analysis as prerequisite for accurate radiation dose assessment.

    PubMed

    Beinke, Christina; Braselmann, Herbert; Meineke, Viktor

    2010-02-01

    The dicentric assay was established to carry out cytogenetic biodosimetry after suspected radiation overexposure, including a comprehensive documentation system to record the processing of the specimen, all data, results, and stored information. As an essential prerequisite for retrospective radiation dose assessment, a dose-response curve for dicentric induction by in vitro x-ray irradiation of peripheral blood samples was produced. The accelerating potential was 240 kV (maximum photon energy: 240 keV). A total of 8,377 first-division metaphases of four healthy volunteers were analyzed after exposure to doses ranging from 0.2 to 4.0 Gy at a dose rate of 1.0 Gy min. The background level of aberrations at 0-dose was determined by the analysis of 14,522 first-division metaphases obtained from unirradiated blood samples of 10 healthy volunteers. The dose-response relationship follows a linear-quadratic equation, Y = c + alphaD + betaD, with the coefficients c = 0.0005 +/- 0.0002, alpha = 0.043 +/- 0.006, and beta = 0.063 +/- 0.004. The technical competence and the quality of the calibration curve were assessed by determination of the dose prediction accuracy in an in vitro experiment simulating whole-body exposures within a range of 0.2 to 2.0 Gy. Dose estimations were derived by scoring up to 500-1,000 metaphase spreads or more (full estimation mode) and by evaluating only 50 metaphase spreads (triage mode) per subject. The triage mode was applied by performing manifold evaluations of the full estimation data in order to test the robustness of the curve for triage purposes and to assess possible variations among the estimated doses referring to a single exposure and preparation.

  2. Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

    PubMed Central

    McCrudden, Maelíosa T.C.; Alkilani, Ahlam Zaid; McCrudden, Cian M.; McAlister, Emma; McCarthy, Helen O.; Woolfson, A. David; Donnelly, Ryan F.

    2014-01-01

    We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5 mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33 mg (90%) of the drug initially loaded into the arrays was delivered over 24 h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263 μg ml− 1 at the 24 h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10 cm2 could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs. PMID:24556420

  3. Adaptive Liver Stereotactic Body Radiation Therapy: Automated Daily Plan Reoptimization Prevents Dose Delivery Degradation Caused by Anatomy Deformations

    SciTech Connect

    Leinders, Suzanne M.; Breedveld, Sebastiaan; Méndez Romero, Alejandra; Schaart, Dennis; Seppenwoolde, Yvette; Heijmen, Ben J.M.

    2013-12-01

    Purpose: To investigate how dose distributions for liver stereotactic body radiation therapy (SBRT) can be improved by using automated, daily plan reoptimization to account for anatomy deformations, compared with setup corrections only. Methods and Materials: For 12 tumors, 3 strategies for dose delivery were simulated. In the first strategy, computed tomography scans made before each treatment fraction were used only for patient repositioning before dose delivery for correction of detected tumor setup errors. In adaptive second and third strategies, in addition to the isocenter shift, intensity modulated radiation therapy beam profiles were reoptimized or both intensity profiles and beam orientations were reoptimized, respectively. All optimizations were performed with a recently published algorithm for automated, multicriteria optimization of both beam profiles and beam angles. Results: In 6 of 12 cases, violations of organs at risk (ie, heart, stomach, kidney) constraints of 1 to 6 Gy in single fractions occurred in cases of tumor repositioning only. By using the adaptive strategies, these could be avoided (<1 Gy). For 1 case, this needed adaptation by slightly underdosing the planning target volume. For 2 cases with restricted tumor dose in the planning phase to avoid organ-at-risk constraint violations, fraction doses could be increased by 1 and 2 Gy because of more favorable anatomy. Daily reoptimization of both beam profiles and beam angles (third strategy) performed slightly better than reoptimization of profiles only, but the latter required only a few minutes of computation time, whereas full reoptimization took several hours. Conclusions: This simulation study demonstrated that replanning based on daily acquired computed tomography scans can improve liver stereotactic body radiation therapy dose delivery.

  4. Topical corticosteroid delivery into human skin using hydrofluoroalkane metered dose aerosol sprays.

    PubMed

    Reid, Monica L; Benaouda, Faiza; Khengar, Rajeshree; Jones, Stuart A; Brown, Marc B

    2013-08-16

    Drug loaded hydrofluoroalkane (HFA) sprays can generate effective pharmaceutical formulations, but a deeper understanding of the manner in which these dynamic systems drive the process of in situ semi-solid dosage form assembly is required. The aim of this study was to investigate the effect of the matrix assembly and composition on drug localisation in human skin. Comparing the characteristics of sprays constituting HFA 134a, ethanol (EtOH), poly(vinyl pyrrolidone) K90, isopropyl myristate (IPM), and poly(ethylene glycol) (PEG) demonstrated that the addition of non-volatile solvents acted to delay EtOH evaporation, control the degree of drug saturation (DS) and enhance the corticosteroid delivery from HFA spray formulations. In a dose matched skin penetration study the HFA sprays containing only EtOH as a co-solvent delivered 2.1 μg BMV (DS 13.5) into the tissue, adding IPM to the EtOH HFA delivered 4.03 μg BMV (DS 11.2), whist adding PEG to the EtOH HFA delivered 6.1 μg BMV (DS 0.3). Compared to commercial cream (delivering 0.91 μg BMV) the EtOH/PEG HFA spray deposited over 6 times (p<0.05) more drug into the skin. Post spray deposition characterisation of the semi-solid suggested that the superior performance of the EtOH/PEG HFA spray was a consequence of retarding EtOH evaporation and presenting the drug in an EtOH rich PEG residual phase, which promoted BMV passage through the SC and into epidermis.

  5. WE-E-18A-03: How Accurately Can the Peak Skin Dose in Fluoroscopy Be Determined Using Indirect Dose Metrics?

    SciTech Connect

    Jones, A; Pasciak, A

    2014-06-15

    Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that Result in skin reactions can be reached during these procedures. The purpose of this study was to assess the accuracy of different indirect dose estimates and to determine if PSD can be calculated within ±50% for embolization procedures. Methods: PSD were measured directly using radiochromic film for 41 consecutive embolization procedures. Indirect dose metrics from procedures were collected, including reference air kerma (RAK). Four different estimates of PSD were calculated and compared along with RAK to the measured PSD. The indirect estimates included a standard method, use of detailed information from the RDSR, and two simplified calculation methods. Indirect dosimetry was compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the indirect estimates were examined. Results: PSD calculated with the standard calculation method were within ±50% for all 41 procedures. This was also true for a simplified method using a single source-to-patient distance (SPD) for all calculations. RAK was within ±50% for all but one procedure. Cases for which RAK or calculated PSD exhibited large differences from the measured PSD were analyzed, and two causative factors were identified: ‘extreme’ SPD and large contributions to RAK from rotational angiography or runs acquired at large gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD. Conclusions: Using indirect dose metrics, PSD can be determined within ±50% for embolization procedures, and usually to within ±35%. RAK can be used without modification to set notification limits and substantial radiation dose levels. These results can be extended to similar procedures, including vascular and interventional oncology

  6. Calibrating the High Density Magnetic Port within Tissue Expanders to Achieve more Accurate Dose Calculations for Postmastectomy Patients with Immediate Breast Reconstruction

    NASA Astrophysics Data System (ADS)

    Jones, Jasmine; Zhang, Rui; Heins, David; Castle, Katherine

    In postmastectomy radiotherapy, an increasing number of patients have tissue expanders inserted subpectorally when receiving immediate breast reconstruction. These tissue expanders are composed of silicone and are inflated with saline through an internal metallic port; this serves the purpose of stretching the muscle and skin tissue over time, in order to house a permanent implant. The issue with administering radiation therapy in the presence of a tissue expander is that the port's magnetic core can potentially perturb the dose delivered to the Planning Target Volume, causing significant artifacts in CT images. Several studies have explored this problem, and suggest that density corrections must be accounted for in treatment planning. However, very few studies accurately calibrated commercial TP systems for the high density material used in the port, and no studies employed fusion imaging to yield a more accurate contour of the port in treatment planning. We compared depth dose values in the water phantom between measurement and TPS calculations, and we were able to overcome some of the inhomogeneities presented by the image artifact by fusing the KVCT and MVCT images of the tissue expander together, resulting in a more precise comparison of dose calculations at discrete locations. We expect this method to be pivotal in the quantification of dose distribution in the PTV. Research funded by the LS-AMP Award.

  7. Novel lung IMRT planning algorithms with nonuniform dose delivery strategy to account for respiratory motion.

    PubMed

    Li, Xiang; Zhang, Pengpeng; Mah, Dennis; Gewanter, Richard; Kutcher, Gerald

    2006-09-01

    To effectively deliver radiation dose to lung tumors, respiratory motion has to be considered in treatment planning. In this paper we first present a new lung IMRT planning algorithm, referred as the dose shaping (DS) method, that shapes the dose distribution according to the probability distribution of the tumor over the breathing cycle to account for respiratory motion. In IMRT planning a dose-based convolution method was generally adopted to compensate for random organ motion by performing 4-D dose calculations using a tumor motion probability density function. We modified the CON-DOSE method to a dose volume histogram based convolution method (CON-DVH) that allows nonuniform dose distribution to account for respiratory motion. We implemented the two new planning algorithms on an in-house IMRT planning system that uses the Eclipse (Varian, Palo Alto, CA) planning workstation as the dose calculation engine. The new algorithms were compared with (1) the conventional margin extension approach in which margin is generated based on the extreme positions of the tumor, (2) the dose-based convolution method, and (3) gating with 3 mm residual motion. Dose volume histogram, tumor control probability, normal tissue complication probability, and mean lung dose were calculated and used to evaluate the relative performance of these approaches at the end-exhale phase of the respiratory cycle. We recruited six patients in our treatment planning study. The study demonstrated that the two new methods could significantly reduce the ipsilateral normal lung dose and outperformed the margin extension method and the dose-based convolution method. Compared with the gated approach that has the best performance in the low dose region, the two methods we proposed have similar potential to escalate tumor dose, but could be more efficient because dose is delivered continuously. PMID:17022235

  8. A multi-head intradermal electroporation device allows for tailored and increased dose DNA vaccine delivery to the skin

    PubMed Central

    McCoy, Jay R; Mendoza, Janess M; Spik, Kristin W; Badger, Catherine; Gomez, Alan F; Schmaljohn, Connie S; Sardesai, Niranjan Y; Broderick, Kate E

    2015-01-01

    The identification of an effective and tolerable delivery method is a necessity for the success of DNA vaccines in the clinic. This article describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple DNA vaccine plasmids simultaneously but spatially separated. Reporter gene plasmids expressing green and red fluorescent proteins were used to demonstrate the impact of spatial separation on DNA delivery to increase the number of transfected cells and avoid interference through visible expression patterns. To investigate the impact of plasmid interference on immunogenicity, a disease target was investigated where issues with multi-valent vaccines had been previously described. DNA-based Hantaan and Puumala virus vaccines were delivered separately or as a combination and the effect of multi-valence was determined by appropriate assays. While a negative impact was observed for both antigenic vaccines when delivered together, these effects were mitigated when the vaccine was delivered using the multi-head device. We also demonstrate how the multi-head device facilitates higher dose delivery to the skin resulting in improved immune responses. This new multi-head platform device is an efficient, tolerable and non-invasive method to deliver multiple plasmid DNA constructs simultaneously allowing the tailoring of delivery sites for combination vaccines. Additionally, this device would allow the delivery of multi-plasmid vaccine formulations without risk of impacted immune responses through interference. Such a low-cost, easy to use device platform for the delivery of multi-agent DNA vaccines would have direct applications by the military and healthcare sectors for mass vaccination purposes. PMID:25839221

  9. The impacts of dental filling materials on RapidArc treatment planning and dose delivery: Challenges and solution

    SciTech Connect

    Mail, Noor; Al-Ghamdi, S.; Saoudi, A.; Albarakati, Y.; Ahmad Khan, M.; Saeedi, F.; Safadi, N.

    2013-08-15

    Purpose: The presence of high-density material in the oral cavity creates dose perturbation in both downstream and upstream directions at the surfaces of dental filling materials (DFM). In this study, the authors have investigated the effect of DFM on head and neck RapidArc treatment plans and delivery. Solutions are proposed to address (1) the issue of downstream dose perturbation, which might cause target under dosage, and (2) to reduce the upstream dose from DFM which may be the primary source of mucositis. In addition, an investigation of the clinical role of a custom-made plastic dental mold/gutter (PDM) in sparing the oral mucosa and tongue reaction is outlined.Methods: The influence of the dental filling artifacts on dose distribution was investigated using a geometrically well-defined head and neck intensity modulated radiation therapy (IMRT) verification phantom (PTW, Freiberg, Germany) with DFM inserts called amalgam, which contained 50% mercury, 25% silver, 14% tin, 8% copper, and 3% other trace metals. Three RapidArc plans were generated in the Varian Eclipse System to treat the oral cavity using the same computer tomography (CT) dataset, including (1) a raw CT image, (2) a streaking artifacts region, which was replaced with a mask of 10 HU, and (3) a 2 cm-thick 6000 HU virtual filter [a volume created in treatment planning system to compensate for beam attenuation, where the thickness of this virtual filter is based on the measured percent depth dose (PDD) data and Eclipse calculation]. The dose delivery for the three plans was verified using Gafchromic-EBT2 film measurements. The custom-made PDM technique to reduce backscatter dose was clinically tested on four head and neck cancer patients (T3, N1, M0) with DFM, two patients with PDM and the other two patients without PDM. The thickness calculation of the PDM toward the mucosa and tongue was purely based on the measured upstream dose. Patients’ with oral mucosal reaction was clinically examined

  10. Effects of ramp-up of inspired airflow on in vitro aerosol dose delivery performance for certain dry powder inhalers.

    PubMed

    Ung, Keith T; Chan, Hak-Kim

    2016-03-10

    This study investigated the effect of airflow ramp-up on the dose delivery performance of seven dry powder inhalers, covering a broad range of powder formulations and powder dispersion mechanisms. In vitro performance tests were performed at a target pressure drop of 4kPa, using two inspiratory flow ramp-up conditions, representing slow and fast ramp-up of airflow, respectively. The fluidization of bulk powder and aerosol clearance from the inhaler was assessed by laser photometer evaluation of aerosol emission kinetics and measurement of the delivered dose (DD). The quality of aerosol dispersion (i.e. de-agglomeration) and associated lung targeting performance was assessed by measuring the total lung dose (TLD) using the Alberta idealized mouth-throat model. The ratio of DD and TLD under slow/fast ramp conditions was used as a metric to rank-order flow ramp effects. Test results show that the delivered dose is relatively unaffected by flow ramp (DD ratio ~1 for all dry powder inhalers). In contrast, the total lung dose showed significantly more variation as a function of flow ramp and inhaler type. Engineered (spray dried) powder formulations were associated with relatively high TLD (>50% of nominal dose) compared to lactose blend and agglomerate based formulations, which had a lower TLD (7-40% of nominal dose), indicative of less efficient targeting of the lung. The TLD for the Tobi Podhaler was the least influenced by flow ramp (TLD ratio ~1), while the TLD for the Asmanex Twisthaler was the most sensitive to flow ramp (TLD ratio ≪1). The relatively high sensitivity of the Asmanex Twisthaler to flow ramp is attributed to rapid aerosol clearance (from the inhaler) combined with a strong effect of flow-rate on particle de-agglomeration and resulting size distribution.

  11. Motion as a perturbation: Measurement-guided dose estimates to moving patient voxels during modulated arc deliveries

    SciTech Connect

    Feygelman, Vladimir; Zhang, Geoffrey; Hunt, Dylan; Opp, Daniel; Stambaugh, Cassandra; Wolf, Theresa K.; Nelms, Benjamin E.

    2013-02-15

    MLC sequences. For all phantoms and plans, time-resolved (10 Hz) ion chamber dose was collected. In addition, coronal (XY) films were exposed in the cube phantom to a VMAT beam with two different starting phases, and compared to the reconstructed motion-perturbed dose planes. Results: For the X or Y motions with the moving strip and geometrical phantoms, the maximum difference between perturbation-reconstructed and ion chamber doses did not exceed 1.9%, and the average for any motion pattern/starting phase did not exceed 1.3%. For the VMAT plans on the cubic and thoracic phantoms, one point exhibited a 3.5% error, while the remaining five were all within 1.1%. Across all the measurements (N = 22), the average disagreement was 0.5 {+-} 1.3% (1 SD). The films exhibited {gamma}(3%/3 mm) passing rates {>=}90%. Conclusions: The dose to an arbitrary moving voxel in a patient can be estimated with acceptable accuracy for a VMAT delivery, by performing a single QA measurement with a cylindrical phantom and applying two consecutive perturbations to the TPS-calculated patient dose. The first one accounts for the differences between the planned and delivered static doses, while the second one corrects for the motion.

  12. SU-D-16A-02: A Novel Methodology for Accurate, Semi-Automated Delineation of Oral Mucosa for Radiation Therapy Dose-Response Studies

    SciTech Connect

    Dean, J; Welsh, L; Gulliford, S; Harrington, K; Nutting, C

    2014-06-01

    Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in

  13. Direct absorbed dose to water determination based on water calorimetry in scanning proton beam delivery

    SciTech Connect

    Sarfehnia, A.; Clasie, B.; Chung, E.; Lu, H. M.; Flanz, J.; Cascio, E.; Engelsman, M.; Paganetti, H.; Seuntjens, J.

    2010-07-15

    Purpose: The aim of this manuscript is to describe the direct measurement of absolute absorbed dose to water in a scanned proton radiotherapy beam using a water calorimeter primary standard. Methods: The McGill water calorimeter, which has been validated in photon and electron beams as well as in HDR {sup 192}Ir brachytherapy, was used to measure the absorbed dose to water in double scattering and scanning proton irradiations. The measurements were made at the Massachusetts General Hospital proton radiotherapy facility. The correction factors in water calorimetry were numerically calculated and various parameters affecting their magnitude and uncertainty were studied. The absorbed dose to water was compared to that obtained using an Exradin T1 Chamber based on the IAEA TRS-398 protocol. Results: The overall 1-sigma uncertainty on absorbed dose to water amounts to 0.4% and 0.6% in scattered and scanned proton water calorimetry, respectively. This compares to an overall uncertainty of 1.9% for currently accepted IAEA TRS-398 reference absorbed dose measurement protocol. The absorbed dose from water calorimetry agrees with the results from TRS-398 well to within 1-sigma uncertainty. Conclusions: This work demonstrates that a primary absorbed dose standard based on water calorimetry is feasible in scattered and scanned proton beams.

  14. Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.

    PubMed

    Goldberg, J; Freund, E; Beckers, B; Hinzmann, R

    2001-02-01

    Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler. PMID:11334124

  15. Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats.

    PubMed

    Howdeshell, Kembra L; Rider, Cynthia V; Wilson, Vickie S; Furr, Johnathan R; Lambright, Christy R; Gray, L Earl

    2015-12-01

    Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the current study were 2-fold: (1) to test whether a mixture model of dose addition based on the fetal T production data of individual phthalates would predict the effects of a 5 phthalate mixture on androgen-sensitive postnatal male reproductive tract development, and (2) to determine the biological relevance of the reductions in fetal T to induce abnormal postnatal reproductive tract development using data from the mixture study. We administered a dose range of the mixture (60, 40, 20, 10, and 5% of the top dose used in the previous fetal T production study consisting of 300 mg/kg per chemical of benzyl butyl (BBP), di(n)butyl (DBP), diethyl hexyl phthalate (DEHP), di-isobutyl phthalate (DiBP), and 100 mg dipentyl (DPP) phthalate/kg; the individual phthalates were present in equipotent doses based on their ability to reduce fetal T production) via gavage to Sprague Dawley rat dams on GD8-postnatal day 3. We compared observed mixture responses to predictions of dose addition based on the previously published potencies of the individual phthalates to reduce fetal T production relative to a reference chemical and published postnatal data for the reference chemical (called DAref). In addition, we predicted DA (called DAall) and response addition (RA) based on logistic regression analysis of all 5 individual phthalates when complete data were available. DA ref and DA all accurately predicted the observed mixture effect for 11 of 14 endpoints. Furthermore, reproductive tract malformations were seen in 17-100% of F1 males when fetal T production was reduced by about 25-72%, respectively. PMID:26350170

  16. Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low-dose rate delivery techniques.

    PubMed

    Li, Jie; Lang, Jinyi; Wang, Pei; Kang, Shengwei; Lin, Mu-Han; Chen, Xiaoming; Chen, Fu; Guo, Ming; Chen, Lili; Ma, Chang-Ming Charlie

    2014-01-01

    Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low-dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatment planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4cGy. The maximum doses ranged between 22.9 and 34.8cGy. The minimum doses ranged from 8.2 to 17.5cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6cGy. The maximum doses per gantry angle were between 24.0 and 34.7cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. The

  17. Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low–dose rate delivery techniques

    SciTech Connect

    Li, Jie; Lang, Jinyi; Wang, Pei; Kang, Shengwei; Lin, Mu-han; Chen, Xiaoming; Chen, Fu; Guo, Ming; Chen, Lili; Ma, Chang-Ming Charlie

    2014-01-01

    Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low–dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatment planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7 cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4 cGy. The maximum doses ranged between 22.9 and 34.8 cGy. The minimum doses ranged from 8.2 to 17.5 cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6 cGy. The maximum doses per gantry angle were between 24.0 and 34.7 cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4 cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT

  18. Leakage-Penumbra effect in intensity modulated radiation therapy step-and-shoot dose delivery

    PubMed Central

    Grigorov, Grigor N; Chow, James CL

    2016-01-01

    AIM: To study the leakage-penumbra (LP) effect with a proposed correction method for the step-and-shoot intensity modulated radiation therapy (IMRT). METHODS: Leakage-penumbra dose profiles from 10 randomly selected prostate IMRT plans were studied. The IMRT plans were delivered by a Varian 21 EX linear accelerator equipped with a 120-leaf multileaf collimator (MLC). For each treatment plan created by the Pinnacle3 treatment planning system, a 3-dimensional LP dose distribution generated by 5 coplanar photon beams, starting from 0o with equal separation of 72o, was investigated. For each photon beam used in the step-and-shoot IMRT plans, the first beam segment was set to have the largest area in the MLC leaf-sequencing, and was equal to the planning target volume (PTV). The overshoot effect (OSE) and the segment positional errors were measured using a solid water phantom with Kodak (TL and X-OMAT V) radiographic films. Film dosimetric analysis and calibration were carried out using a film scanner (Vidar VXR-16). The LP dose profiles were determined by eliminating the OSE and segment positional errors with specific individual irradiations. RESULTS: A non-uniformly distributed leaf LP dose ranging from 3% to 5% of the beam dose was measured in clinical IMRT beams. An overdose at the gap between neighboring segments, represented as dose peaks of up to 10% of the total BP, was measured. The LP effect increased the dose to the PTV and surrounding critical tissues. In addition, the effect depends on the number of beams and segments for each beam. Segment positional error was less than the maximum tolerance of 1 mm under a dose rate of 600 monitor units per minute in the treatment plans. The OSE varying with the dose rate was observed in all photon beams, and the effect increased from 1 to 1.3 Gy per treatment of the rectal intersection. As the dosimetric impacts from the LP effect and OSE may increase the rectal post-radiation effects, a correction of LP was proposed and

  19. Experimental study on the application of a compressed-sensing (CS) algorithm to dental cone-beam CT (CBCT) for accurate, low-dose image reconstruction

    NASA Astrophysics Data System (ADS)

    Oh, Jieun; Cho, Hyosung; Je, Uikyu; Lee, Minsik; Kim, Hyojeong; Hong, Daeki; Park, Yeonok; Lee, Seonhwa; Cho, Heemoon; Choi, Sungil; Koo, Yangseo

    2013-03-01

    In practical applications of three-dimensional (3D) tomographic imaging, there are often challenges for image reconstruction from insufficient data. In computed tomography (CT); for example, image reconstruction from few views would enable fast scanning with reduced doses to the patient. In this study, we investigated and implemented an efficient reconstruction method based on a compressed-sensing (CS) algorithm, which exploits the sparseness of the gradient image with substantially high accuracy, for accurate, low-dose dental cone-beam CT (CBCT) reconstruction. We applied the algorithm to a commercially-available dental CBCT system (Expert7™, Vatech Co., Korea) and performed experimental works to demonstrate the algorithm for image reconstruction in insufficient sampling problems. We successfully reconstructed CBCT images from several undersampled data and evaluated the reconstruction quality in terms of the universal-quality index (UQI). Experimental demonstrations of the CS-based reconstruction algorithm appear to show that it can be applied to current dental CBCT systems for reducing imaging doses and improving the image quality.

  20. The effect of flattening filter free delivery on endothelial dose enhancement with gold nanoparticles

    SciTech Connect

    Detappe, Alexandre; Tsiamas, Panagiotis; Ngwa, Wilfred; Zygmanski, Piotr; Makrigiorgos, Mike; Berbeco, Ross

    2013-03-15

    Purpose: The aim of this study is to quantify and to compare the dose enhancement factor from gold nanoparticles (AuNP) to tumor endothelial cells for different concentrations of AuNP, and clinical MV beam configurations. Methods: Tumor endothelial cells are modeled as slabs measuring 10 Multiplication-Sign 10 Multiplication-Sign 2 {mu}m. A spherical AuNP is simulated on the surface of the endothelial cell, within the blood vessel. 6 MV photon beams with and without the flattening filter are investigated for different field sizes, depths in material and beam modulation. The incident photon energy spectra for each configuration is generated using EGSnrc. The dose enhancement in the tumor endothelial cell is found using an analytical calculation. The endothelial dose enhancement factor is defined to be the ratio of the dose deposited with and without AuNPs. Results: It is found that clinical beam parameters may be chosen to maximize the effect of gold nanoparticles during radiotherapy. This effect is further amplified {approx}20% by the removal of the flattening filter. Modulation of the clinical beam with the multileaf collimator tends to decrease the proportion of low energy photons, therefore providing less enhancement than the corresponding open field. Conclusions: The results of this work predict a dose enhancement to tumor blood vessel endothelial cells using conventional therapeutic (MV) x-rays and quantify the relative change in enhancement with treatment depth and field size.

  1. Delivery.

    PubMed

    Miller, Thomas A

    2013-11-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms.

  2. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry PMID:23852646

  3. Delivery characteristics and patients' handling of two single-dose dry-powder inhalers used in COPD.

    PubMed

    Chapman, Kenneth R; Fogarty, Charles M; Peckitt, Clare; Lassen, Cheryl; Jadayel, Dalal; Dederichs, Juergen; Dalvi, Mukul; Kramer, Benjamin

    2011-01-01

    For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction. The delivery characteristics, patients' correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies. The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD. Patients' correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use. Patients' preference was assessed after completion of both study periods. Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler. For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively. In the second study, correct use of Breezhaler and HandiHaler was achieved by > 77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities. Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler. These are important factors for optimum dose delivery and successful COPD management.

  4. Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

    NASA Astrophysics Data System (ADS)

    Asimakopoulou, Akrivi; Daskalos, Emmanouil; Lewinski, Nastassja; Riediker, Michael; Papaioannou, Eleni; Konstandopoulos, Athanasios G.

    2013-04-01

    In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

  5. Cumulative dose on fractional delivery of tomotherapy to periodically moving organ: A phantom QA suggestion

    SciTech Connect

    Shin, Eunhyuk; Han, Youngyih; Park, Hee-Chul; Sung Kim, Jin; Hwan Ahn, Sung; Suk Shin, Jung; Gyu Ju, Sang; Ho Choi, Doo; Lee, Jaiki

    2013-01-01

    This study was conducted to evaluate the cumulative dosimetric error that occurs in both target and surrounding normal tissues when treating a moving target in multifractional treatment with tomotherapy. An experiment was devised to measure cumulative error in multifractional treatments delivered to a horseshoe-shaped clinical target volume (CTV) surrounding a cylinder shape of organ at risk (OAR). Treatments differed in jaw size (1.05 vs 2.5 cm), pitch (0.287 vs 0.660), and modulation factor (1.5 vs 2.5), and tumor motion characteristics differing in amplitude (1 to 3 cm), period (3 to 5 second), and regularity (sinusoidal vs irregular) were tested. Treatment plans were delivered to a moving phantom up to 5-times exposure. Dose distribution on central coronal plane from 1 to 5 times exposure was measured with GAFCHROMIC EBT film. Dose differences occurring across 1 to 5 times exposure of treatment and between treatment plans were evaluated by analyzing measurements of gamma index, gamma index histogram, histogram changes, and dose at the center of the OAR. The experiment showed dose distortion due to organ motion increased between multiexposure 1 to 3 times but plateaued and remained constant after 3-times exposure. In addition, although larger motion amplitude and a longer period of motion both increased dosimetric error, the dose at the OAR was more significantly affected by motion amplitude rather than motion period. Irregularity of motion did not contribute significantly to dosimetric error when compared with other motion parameters. Restriction of organ motion to have small amplitude and short motion period together with larger jaw size and small modulation factor (with small pitch) is effective in reducing dosimetric error. Pretreatment measurements for 3-times exposure of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution.

  6. Boron self-shielding effects on dose delivery of neutron capture therapy using epithermal beam and boronophenylalanine.

    PubMed

    Ye, S J

    1999-11-01

    Previous dosimetry studies for boron neutron capture therapy have often neglected the thermal neutron self-shielding effects caused by the 10B accumulation in the brain and the tumor. The neglect of thermal neutron flux depression, therefore, results in an overestimation of the actual dose delivery. The relevant errors are expected to be more pronounced when boronophenylalanine is used in conjunction with an epithermal neutron beam. In this paper, the boron self-shielding effects are calculated in terms of the thermal neutron flux depression across the brain and the dose delivered to the tumors. The degree of boron self-shielding is indicated by the difference between the thermal neutron fluxes calculated with and without considering a 10B concentration as part of the head phantom composition. The boron self-shielding effect is found to increase with increasing 10B concentrations and penetration depths from the skin. The calculated differences for 10B concentrations of 7.5-30 ppm are 2.3%-8.3% at 2.3 cm depth (depth of the maximum brain dose) and 4.6%-17% at 7.3 cm depth (the center of the brain). The additional self-shielding effects by the 10B concentration in a bulky tumor are investigated for a 3-cm-diam spherical tumor located either near the surface (3.3 cm depth) or at the center of the brain (7.3 cm depth) along the beam centerline. For 45 ppm of 10B in the tumor and 15 ppm of 10B in the brain, the dose delivered to the tumors is approximately 10% lower at 3.3 cm depth and 20% lower at the center of the brain, compared to the dose neglecting the boron self-shielding in transport calculations.

  7. SU-F-BRF-09: A Non-Rigid Point Matching Method for Accurate Bladder Dose Summation in Cervical Cancer HDR Brachytherapy

    SciTech Connect

    Chen, H; Zhen, X; Zhou, L; Zhong, Z; Pompos, A; Yan, H; Jiang, S; Gu, X

    2014-06-15

    Purpose: To propose and validate a deformable point matching scheme for surface deformation to facilitate accurate bladder dose summation for fractionated HDR cervical cancer treatment. Method: A deformable point matching scheme based on the thin plate spline robust point matching (TPSRPM) algorithm is proposed for bladder surface registration. The surface of bladders segmented from fractional CT images is extracted and discretized with triangular surface mesh. Deformation between the two bladder surfaces are obtained by matching the two meshes' vertices via the TPS-RPM algorithm, and the deformation vector fields (DVFs) characteristic of this deformation is estimated by B-spline approximation. Numerically, the algorithm is quantitatively compared with the Demons algorithm using five clinical cervical cancer cases by several metrics: vertex-to-vertex distance (VVD), Hausdorff distance (HD), percent error (PE), and conformity index (CI). Experimentally, the algorithm is validated on a balloon phantom with 12 surface fiducial markers. The balloon is inflated with different amount of water, and the displacement of fiducial markers is benchmarked as ground truth to study TPS-RPM calculated DVFs' accuracy. Results: In numerical evaluation, the mean VVD is 3.7(±2.0) mm after Demons, and 1.3(±0.9) mm after TPS-RPM. The mean HD is 14.4 mm after Demons, and 5.3mm after TPS-RPM. The mean PE is 101.7% after Demons and decreases to 18.7% after TPS-RPM. The mean CI is 0.63 after Demons, and increases to 0.90 after TPS-RPM. In the phantom study, the mean Euclidean distance of the fiducials is 7.4±3.0mm and 4.2±1.8mm after Demons and TPS-RPM, respectively. Conclusions: The bladder wall deformation is more accurate using the feature-based TPS-RPM algorithm than the intensity-based Demons algorithm, indicating that TPS-RPM has the potential for accurate bladder dose deformation and dose summation for multi-fractional cervical HDR brachytherapy. This work is supported in part by

  8. Efficient, Long-term Hepatic Gene Transfer Using Clinically Relevant HDAd Doses by Balloon Occlusion Catheter Delivery in Nonhuman Primates

    PubMed Central

    Brunetti-Pierri, Nicola; Stapleton, Gary E; Law, Mark; Breinholt, John; Palmer, Donna J; Zuo, Yu; Grove, Nathan C; Finegold, Milton J; Rice, Karen; Beaudet, Arthur L; Mullins, Charles E; Ng, Philip

    2008-01-01

    Helper-dependent adenoviral vectors (HDAd) are devoid of all viral coding sequences and are thus an improvement over early generation Ad because they can provide long-term transgene expression in vivo without chronic toxicity. However, high vector doses are required to achieve efficient hepatic transduction by systemic intravenous injection, and this unfortunately results in dose-dependent acute toxicity. To overcome this important obstacle, we have developed a minimally invasive method to preferentially deliver HDAd into the liver of nonhuman primates. Briefly, a balloon occlusion catheter was percutaneously positioned in the inferior vena cava to occlude hepatic venous outflow. HDAd was injected directly into the occluded liver via a percutaneously placed hepatic artery catheter. Compared to systemic vector injection, this approach resulted in substantially higher hepatic transduction efficiency using clinically relevant low vector doses and was accompanied by mild-to-moderate acute but transient toxicities. Transgene expression was sustained for up to 964 days. These results suggest that our minimally invasive method of delivery can significantly improve the vector's therapeutic index and may be a first step toward clinical application of HDAd for liver-directed gene therapy. PMID:19050700

  9. Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system.

    PubMed

    Ross, D L; Gabrio, B J

    1999-01-01

    The impending phaseout of chlorofluorocarbon (CFC)-containing metered dose inhalers (MDIs) has challenged the pharmaceutical industry to rethink and redesign many components of the technology involved in delivering asthma medication to the lungs. Along with the emergence of the first formulation using the nonozone-depleting propellant, hydrofluoroalkane (HFA) 134a to replace CFC propellants, advances in drug delivery technology have improved the performance characteristics of the MDI itself. Although MDIs have remained the mainstay of asthma therapy for 40 years, MDI technology still presents challenges. Some of the shortcomings of existing CFC MDIs affect the reliability of dosing. These challenges have been addressed in the development of the first CFC-free beta-agonist for the treatment of asthma. Airomir CFC-free (salbutamol sulfate; 3M Pharmaceuticals, St. Paul, MN), which is currently available in over 30 countries and was recently approved in the United States (Proventil HFA; Schering-Plough, Madison, NJ), incorporates numerous design and technological improvements which together with the introduction of CFC-free propellants mark the beginning of the next generation of asthma therapy. Although the new generation of CFC-free MDIs incorporates several improvements in dose reproducibility, these changes should be virtually transparent to the patient switching from a CFC MDI to a CFC-free MDI. What may be noticeable is a "softer puff," which is the result of valve and actuator redesign. The taste of the new CFC-free product may also be a little different yet totally acceptable to users.

  10. SU-E-T-303: Spot Scanning Dose Delivery with Rapid Cycling Proton Beams From RCMS

    SciTech Connect

    Cheng, C; Liu, H; Lee, S

    2014-06-01

    Purpose: A rapid cycling proton beam has several distinct characteristics superior to a slow extraction synchrotron: The beam energy and energy spread, beam intensity and spot size can be varied spot by spot. The feasibility of using a spot scanning beam from a rapidc-ycling-medical-synchrotron (RCMS) at 10 Hz repetition frequency is investigated in this study for its application in proton therapy. Methods: The versatility of the beam is illustrated by two examples in water phantoms: (1) a cylindrical PTV irradiated by a single field and (2) a spherical PTV irradiated by two parallel opposed fields. A uniform dose distribution is to be delivered to the volumes. Geant4 Monte Carlo code is used to validate the dose distributions in each example. Results: Transverse algorithms are developed to produce uniform distributions in each transverseplane in the two examples with a cylindrical and a spherical PTV respectively. Longitudinally, different proton energies are used in successive transverse planes toproduce the SOBP required to cover the PTVs. In general, uniformity of dosedistribution within 3% is obtained for the cylinder and 3.5% for the sphere. The transversealgorithms requires only few hundred beam spots for each plane The algorithms may beapplied to larger volumes by increasing the intensity spot by spot for the same deliverytime of the same dose. The treatment time can be shorter than 1 minute for any fieldconfiguration and tumor shape. Conclusion: The unique beam characteristics of a spot scanning beam from a RCMS at 10 Hz repetitionfrequency are used to design transverse and longitudinal algorithms to produce uniformdistribution for any arbitrary shape and size of targets. The proposed spot scanning beam ismore versatile than existing spot scanning beams in proton therapy with better beamcontrol and lower neutron dose. This work is supported in part by grants from the US Department of Energy under contract; DE-FG02-12ER41800 and the National Science

  11. Feasibility study for application of the compressed-sensing framework to interior computed tomography (ICT) for low-dose, high-accurate dental x-ray imaging

    NASA Astrophysics Data System (ADS)

    Je, U. K.; Cho, H. M.; Cho, H. S.; Park, Y. O.; Park, C. K.; Lim, H. W.; Kim, K. S.; Kim, G. A.; Park, S. Y.; Woo, T. H.; Choi, S. I.

    2016-02-01

    In this paper, we propose a new/next-generation type of CT examinations, the so-called Interior Computed Tomography (ICT), which may presumably lead to dose reduction to the patient outside the target region-of-interest (ROI), in dental x-ray imaging. Here an x-ray beam from each projection position covers only a relatively small ROI containing a target of diagnosis from the examined structure, leading to imaging benefits such as decreasing scatters and system cost as well as reducing imaging dose. We considered the compressed-sensing (CS) framework, rather than common filtered-backprojection (FBP)-based algorithms, for more accurate ICT reconstruction. We implemented a CS-based ICT algorithm and performed a systematic simulation to investigate the imaging characteristics. Simulation conditions of two ROI ratios of 0.28 and 0.14 between the target and the whole phantom sizes and four projection numbers of 360, 180, 90, and 45 were tested. We successfully reconstructed ICT images of substantially high image quality by using the CS framework even with few-view projection data, still preserving sharp edges in the images.

  12. Clinical utility of transdermal delivery of oxybutynin gel via a metered-dose pump in the management of overactive bladder

    PubMed Central

    Wagg, Adrian

    2012-01-01

    Oxybutynin is an efficacious treatment for overactive bladder, but its clinical utility is hampered by relative intolerability due to its side effect profile. Over the last few years, various attempts to enhance the tolerability of oxybutynin by varying the drug delivery mechanism have been introduced and have included extended release, rectal suppository, transdermal patch, and gel formulations. The recent introduction of a transdermal oxybutynin gel in a sachet form has been complemented by the administration of gel in a metered dose pump. This paper reviews the available evidence for transdermal oxybutynin gel and, where it exists, for the pump-based gel. The clinical utility of the pump-based gel is discussed. PMID:24199182

  13. IMRT planning and delivery incorporating daily dose from mega-voltage cone-beam computed tomography imaging.

    PubMed

    Miften, Moyed; Gayou, Olivier; Reitz, Bodo; Fuhrer, Russell; Leicher, Brian; Parda, David S

    2007-10-01

    The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200 degrees gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6 +/- 1.0 Gy for the bladder and comparable for the rectum (-0.3 +/- 1.4 Gy). In addition, an average mean dose increase of 1.9 +/- 0.8 Gy in the femoral heads and 1.7 +/- 0.6 Gy in irradiated tissue was observed. However, the V65 and V70 values for bladder and rectum were lower by 2.3 +/- 1.5% and 2.4 +/- 2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It allows

  14. IMRT planning and delivery incorporating daily dose from mega-voltage cone-beam computed tomography imaging

    SciTech Connect

    Miften, Moyed; Gayou, Olivier; Reitz, Bodo; Fuhrer, Russell; Leicher, Brian; Parda, David S.

    2007-10-15

    The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200 deg. gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6{+-}1.0 Gy for the bladder and comparable for the rectum (-0.3{+-}1.4 Gy). In addition, an average mean dose increase of 1.9{+-}0.8 Gy in the femoral heads and 1.7{+-}0.6 Gy in irradiated tissue was observed. However, the V{sub 65} and V{sub 70} values for bladder and rectum were lower by 2.3{+-}1.5% and 2.4{+-}2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It

  15. Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of end-inspiratory pause.

    PubMed

    Mouloudi, E; Katsanoulas, K; Anastasaki, M; Askitopoulou, E; Georgopoulos, D

    1998-07-01

    The delivery of bronchodilators with a metered-dose inhaler (MDI) and a spacer in mechanically ventilated patients has become widespread practice. However, the various ventilator settings that influence the efficacy of MDI are not well established. Application of an end-inspiratory pause (EIP) during drug delivery has been suggested as one of the factors that might increase the effectiveness of this therapy. To test this, the effect of EIP on the bronchodilation induced by beta2-agonists administered with MDI and a spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) was examined. Twelve patients with COPD, mechanically ventilated on volume-controlled mode, were prospectively randomized to receive six puffs of salbutamol (100 microg x puff(-1)) either with or without EIP of 5 s duration. Salbutamol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud-enhancer spacer. After a 6 h wash-out, patients were crossed over to receive salbutamol by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rmin) and maximum (Rmax) airflow resistance, the difference between Rmax and Rmin (deltaR), static end-inspiratory respiratory system compliance (Cst,rs) and cardiac frequency (fc) were measured before and at 15, 30 and 60 min after salbutamol administration. Salbutamol caused a significant decrease in dynamic and static airway pressures, Rmin and Rmax. These changes were not influenced by application of EIP and were evident at 15, 30 and 60 min after salbutamol. With and without EIP, Cst,rs,deltaR and fc did not change after salbutamol. In conclusion, salbutamol delivered with a metered-dose inhaler and a spacer device induced significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease, the magnitude of which was not affected by an end-expiratory pause of 5 s. These results do not support the

  16. A Phase I Trial of Preoperative Partial Breast Radiotherapy: Patient Selection, Target Delineation, and Dose Delivery

    PubMed Central

    Blitzblau, Rachel C.; Arya, Ritu; Yoo, Sua; Baker, Jay A.; Chang, Zheng; Palta, Manisha; Duffy, Eileen; Horton, Janet K.

    2015-01-01

    Purpose Diffusion of accelerated partial breast irradiation (APBI) into clinical practice is limited by the need for specialized equipment and training. The accessible external beam technique yields unacceptable complication rates, likely due to large post-operative target volumes. We designed a phase I trial evaluating preoperative radiotherapy to the intact tumor utilizing widely available technology. Methods Patients received 15, 18, or 21Gy in a single fraction to the breast tumor plus margin. Magnetic resonance imaging (MRI) was used in conjunction with standard computed tomography (CT)-based planning to identify contrast enhancing tumor. Skin markers and an intra-tumor biopsy marker were utilized for verification during treatment. Results MRI imaging was critical for target delineation as not all breast tumors were reliably identified on CT scan. Breast shape differences were consistently seen between CT and MRI but did not impede image registration or tumor identification. Target volumes were markedly smaller than historical post-operative volumes and normal tissue constraints were easily met. A biopsy marker within the breast proved sufficient for set up localization. Conclusions This single fraction linear-accelerator based ABPI approach can be easily incorporated at most treatment centers. In vivo targeting may improve accuracy and can reduce the dose to normal tissues. PMID:25834942

  17. A Broad Range of Dose Optima Achieve High-level, Long-term Gene Expression After Hydrodynamic Delivery of Sleeping Beauty Transposons Using Hyperactive SB100x Transposase

    PubMed Central

    Podetz-Pedersen, Kelly M; Olson, Erik R; Somia, Nikunj V; Russell, Stephen J; McIvor, R Scott

    2016-01-01

    The Sleeping Beauty (SB) transposon system has been shown to enable long-term gene expression by integrating new sequences into host cell chromosomes. We found that the recently reported SB100x hyperactive transposase conferred a surprisingly high level of long-term expression after hydrodynamic delivery of luciferase-encoding reporter transposons in the mouse. We conducted dose-ranging studies to determine the effect of varying the amount of SB100x transposase-encoding plasmid (pCMV-SB100x) at a set dose of luciferase transposon and of varying the amount of transposon-encoding DNA at a set dose of pCMV-SB100x in hydrodynamically injected mice. Animals were immunosuppressed using cyclophosphamide in order to prevent an antiluciferase immune response. At a set dose of transposon DNA (25 µg), we observed a broad range of pCMV-SB100x doses (0.1–2.5 µg) conferring optimal levels of long-term expression (>1011 photons/second/cm2). At a fixed dose of 0.5 μg of pCMV-SB100x, maximal long-term luciferase expression (>1010 photons/second/cm2) was achieved at a transposon dose of 5–125 μg. We also found that in the linear range of transposon doses (100 ng), co-delivering the CMV-SB100x sequence on the same plasmid was less effective in achieving long-term expression than delivery on separate plasmids. These results show marked flexibility in the doses of SB transposon plus pCMV-SB100x that achieve maximal SB-mediated gene transfer efficiency and long-term gene expression after hydrodynamic DNA delivery to mouse liver. PMID:26784638

  18. A Broad Range of Dose Optima Achieve High-level, Long-term Gene Expression After Hydrodynamic Delivery of Sleeping Beauty Transposons Using Hyperactive SB100x Transposase.

    PubMed

    Podetz-Pedersen, Kelly M; Olson, Erik R; Somia, Nikunj V; Russell, Stephen J; McIvor, R Scott

    2016-01-19

    The Sleeping Beauty (SB) transposon system has been shown to enable long-term gene expression by integrating new sequences into host cell chromosomes. We found that the recently reported SB100x hyperactive transposase conferred a surprisingly high level of long-term expression after hydrodynamic delivery of luciferase-encoding reporter transposons in the mouse. We conducted dose-ranging studies to determine the effect of varying the amount of SB100x transposase-encoding plasmid (pCMV-SB100x) at a set dose of luciferase transposon and of varying the amount of transposon-encoding DNA at a set dose of pCMV-SB100x in hydrodynamically injected mice. Animals were immunosuppressed using cyclophosphamide in order to prevent an antiluciferase immune response. At a set dose of transposon DNA (25 µg), we observed a broad range of pCMV-SB100x doses (0.1-2.5 µg) conferring optimal levels of long-term expression (>10(11) photons/second/cm(2)). At a fixed dose of 0.5 μg of pCMV-SB100x, maximal long-term luciferase expression (>10(10) photons/second/cm(2)) was achieved at a transposon dose of 5-125 μg. We also found that in the linear range of transposon doses (100 ng), co-delivering the CMV-SB100x sequence on the same plasmid was less effective in achieving long-term expression than delivery on separate plasmids. These results show marked flexibility in the doses of SB transposon plus pCMV-SB100x that achieve maximal SB-mediated gene transfer efficiency and long-term gene expression after hydrodynamic DNA delivery to mouse liver.

  19. A Broad Range of Dose Optima Achieve High-level, Long-term Gene Expression After Hydrodynamic Delivery of Sleeping Beauty Transposons Using Hyperactive SB100x Transposase.

    PubMed

    Podetz-Pedersen, Kelly M; Olson, Erik R; Somia, Nikunj V; Russell, Stephen J; McIvor, R Scott

    2016-01-01

    The Sleeping Beauty (SB) transposon system has been shown to enable long-term gene expression by integrating new sequences into host cell chromosomes. We found that the recently reported SB100x hyperactive transposase conferred a surprisingly high level of long-term expression after hydrodynamic delivery of luciferase-encoding reporter transposons in the mouse. We conducted dose-ranging studies to determine the effect of varying the amount of SB100x transposase-encoding plasmid (pCMV-SB100x) at a set dose of luciferase transposon and of varying the amount of transposon-encoding DNA at a set dose of pCMV-SB100x in hydrodynamically injected mice. Animals were immunosuppressed using cyclophosphamide in order to prevent an antiluciferase immune response. At a set dose of transposon DNA (25 µg), we observed a broad range of pCMV-SB100x doses (0.1-2.5 µg) conferring optimal levels of long-term expression (>10(11) photons/second/cm(2)). At a fixed dose of 0.5 μg of pCMV-SB100x, maximal long-term luciferase expression (>10(10) photons/second/cm(2)) was achieved at a transposon dose of 5-125 μg. We also found that in the linear range of transposon doses (100 ng), co-delivering the CMV-SB100x sequence on the same plasmid was less effective in achieving long-term expression than delivery on separate plasmids. These results show marked flexibility in the doses of SB transposon plus pCMV-SB100x that achieve maximal SB-mediated gene transfer efficiency and long-term gene expression after hydrodynamic DNA delivery to mouse liver. PMID:26784638

  20. Development of an algorithm to improve the accuracy of dose delivery in Gamma Knife radiosurgery

    NASA Astrophysics Data System (ADS)

    Cernica, George Dumitru

    2007-12-01

    Gamma Knife stereotactic radiosurgery has demonstrated decades of successful treatments. Despite its high spatial accuracy, the Gamma Knife's planning software, GammaPlan, uses a simple exponential as the TPR curve for all four collimator sizes, and a skull scaling device to acquire ruler measurements to interpolate a threedimensional spline to model the patient's skull. The consequences of these approximations have not been previously investigated. The true TPR curves of the four collimators were measured by blocking 200 of the 201 sources with steel plugs. Additional attenuation was provided through the use of a 16 cm tungsten sphere, designed to enable beamlet measurements along one axis. TPR, PDD, and beamlet profiles were obtained using both an ion chamber and GafChromic EBT film for all collimators. Additionally, an in-house planning algorithm able to calculate the contour of the skull directly from an image set and implement the measured beamlet data in shot time calculations was developed. Clinical and theoretical Gamma Knife cases were imported into our algorithm. The TPR curves showed small deviations from a simple exponential curve, with average discrepancies under 1%, but with a maximum discrepancy of 2% found for the 18 mm collimator beamlet at shallow depths. The consequences on the PDD of the of the beamlets were slight, with a maximum of 1.6% found with the 18 mm collimator beamlet. Beamlet profiles of the 4 mm, 8 mm, and 14 mm showed some underestimates of the off-axis ratio near the shoulders (up to 10%). The toes of the profiles were underestimated for all collimators, with differences up to 7%. Shot times were affected by up to 1.6% due to TPR differences, but clinical cases showed deviations by no more than 0.5%. The beamlet profiles affected the dose calculations more significantly, with shot time calculations differing by as much as 0.8%. The skull scaling affected the shot time calculations the most significantly, with differences of up to 5

  1. Sci—Thur AM: YIS - 06: An EPID-based 3D patient dose verification method for SBRT-VMAT delivery

    SciTech Connect

    McCowan, P.; Uytven, E van; Beek, T van; McCurdy, B

    2014-08-15

    Purpose: Stereotactic body radiation therapy (SBRT) delivered via volumetric modulated arc therapy (VMAT) can strongly benefit from an in vivo patient dose verification due to the large doses per fraction. Electronic portal imaging devices (EPIDs) can be utilized as a patient dose dosimeter. In this work we present a physics-based model which utilizes on-treatment EPID images to reconstruct the dose delivered to an anthropomorphic phantom during SBRT-VMAT delivery. Methods: An SBRT linac beam was modeled using Monte Carlo methods and verified with measured data. Our dose reconstruction model back-projects EPID measured focal fluence upstream of the patient and adds a predicted extra-focal fluence component. This fluence is forward projected onto the patient's density matrix and convolved with dose kernels to calculate dose. The model was validated for two prostate, three lung, and two spine SBRT-VMAT treatments. Results were compared to the treatment planning system's calculation. Results: 2%/2 mm chi comparison calculations gave pass rates for the whole volume, infield, and high dose region respectively, and no lower than: 98%, 95%, 99% for the prostate plans, 99%, 92%, 85% for the lung plans, and 91%, 85%, 81% for the spine plans. A 3%/3mm calculation gave pass rates no lower than 99%, 94%, and 90% for all dose regions for the prostate, lung, and spine respectively. Conclusions: We have developed a physics-based model which calculates delivered dose to phantom (or patient) for SBRT-VMAT delivery using on treatment EPID images. The accuracy of the results has allowed us to test this model clinically.

  2. SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

    SciTech Connect

    Chen, Y; Souri, S; Gill, G; Rea, A; Kuruvilla, A; Riegel, A; Cao, Y; Jamshidi, A

    2015-06-15

    Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose to its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.

  3. Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial☆, ☆

    PubMed Central

    Stevens, Allen D.; Hernandez, Caleb; Jones, Seth; Moreira, Maria E.; Blumen, Jason R.; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S.

    2016-01-01

    Background Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. Methods We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded-syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Results Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28–39) seconds and 42 (95% CI: 36–51) seconds, respectively (difference = 9 [95% CI: 4–14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference = 39%, 95% CI: 13–61%). Conclusions A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. PMID:26247145

  4. Compensating for the impact of non-stationary spherical air cavities on IMRT dose delivery in transverse magnetic fields.

    PubMed

    Bol, G H; Lagendijk, J J W; Raaymakers, B W

    2015-01-21

    With the development of the 1.5 T MRI linear accelerator and the clinical introduction of the 0.35 T ViewRay™ system, delivering intensity-modulated radiotherapy (IMRT) in a transverse magnetic field becomes increasingly important. When delivering dose in the presence of a transverse magnetic field, one of the most prominent phenomena occurs around air cavities: the electron return effect (ERE). For stationary, spherical air cavities which are centrally located in the phantom, the ERE can be compensated by using opposing beams configurations in combination with IMRT. In this paper we investigate the effects of non-stationary spherical air cavities, centrally located within the target in a phantom containing no organs at risk, on IMRT dose delivery in 0.35 T and 1.5 T transverse magnetic fields by using Monte Carlo simulations. We show that IMRT can be used for compensating ERE around those air cavities, except for intrafraction appearing or disappearing air cavities. For these cases, gating or plan re-optimization should be used. We also analyzed the option of using IMRT plans optimized at 0 T to be delivered in the presence of 0.35 T and 1.5 T magnetic field. When delivering dose at 0.35 T, IMRT plans optimized at 0 T and 0.35 T perform equally well regarding ERE compensation. Within a 1.5 T environment, the 1.5 T optimized plans perform slightly better for the static and random intra- and interfraction air cavity movement cases than the 0 T optimized plans. For non-stationary spherical air cavities with a baseline shift (intra- and interfraction) the 0 T optimized plans perform better. These observations show the intrinsic ERE compensation by equidistant and opposing beam configurations for spherical air cavities within the target area. IMRT gives some additional compensation, but only in case of correct positioning of the air cavity according to the IMRT compensation. For intrafraction appearing or disappearing air cavities this correct positioning is absent

  5. Compensating for the impact of non-stationary spherical air cavities on IMRT dose delivery in transverse magnetic fields.

    PubMed

    Bol, G H; Lagendijk, J J W; Raaymakers, B W

    2015-01-21

    With the development of the 1.5 T MRI linear accelerator and the clinical introduction of the 0.35 T ViewRay™ system, delivering intensity-modulated radiotherapy (IMRT) in a transverse magnetic field becomes increasingly important. When delivering dose in the presence of a transverse magnetic field, one of the most prominent phenomena occurs around air cavities: the electron return effect (ERE). For stationary, spherical air cavities which are centrally located in the phantom, the ERE can be compensated by using opposing beams configurations in combination with IMRT. In this paper we investigate the effects of non-stationary spherical air cavities, centrally located within the target in a phantom containing no organs at risk, on IMRT dose delivery in 0.35 T and 1.5 T transverse magnetic fields by using Monte Carlo simulations. We show that IMRT can be used for compensating ERE around those air cavities, except for intrafraction appearing or disappearing air cavities. For these cases, gating or plan re-optimization should be used. We also analyzed the option of using IMRT plans optimized at 0 T to be delivered in the presence of 0.35 T and 1.5 T magnetic field. When delivering dose at 0.35 T, IMRT plans optimized at 0 T and 0.35 T perform equally well regarding ERE compensation. Within a 1.5 T environment, the 1.5 T optimized plans perform slightly better for the static and random intra- and interfraction air cavity movement cases than the 0 T optimized plans. For non-stationary spherical air cavities with a baseline shift (intra- and interfraction) the 0 T optimized plans perform better. These observations show the intrinsic ERE compensation by equidistant and opposing beam configurations for spherical air cavities within the target area. IMRT gives some additional compensation, but only in case of correct positioning of the air cavity according to the IMRT compensation. For intrafraction appearing or disappearing air cavities this correct positioning is absent

  6. Compensating for the impact of non-stationary spherical air cavities on IMRT dose delivery in transverse magnetic fields

    NASA Astrophysics Data System (ADS)

    Bol, G. H.; Lagendijk, J. J. W.; Raaymakers, B. W.

    2015-01-01

    With the development of the 1.5 T MRI linear accelerator and the clinical introduction of the 0.35 T ViewRay™ system, delivering intensity-modulated radiotherapy (IMRT) in a transverse magnetic field becomes increasingly important. When delivering dose in the presence of a transverse magnetic field, one of the most prominent phenomena occurs around air cavities: the electron return effect (ERE). For stationary, spherical air cavities which are centrally located in the phantom, the ERE can be compensated by using opposing beams configurations in combination with IMRT. In this paper we investigate the effects of non-stationary spherical air cavities, centrally located within the target in a phantom containing no organs at risk, on IMRT dose delivery in 0.35 T and 1.5 T transverse magnetic fields by using Monte Carlo simulations. We show that IMRT can be used for compensating ERE around those air cavities, except for intrafraction appearing or disappearing air cavities. For these cases, gating or plan re-optimization should be used. We also analyzed the option of using IMRT plans optimized at 0 T to be delivered in the presence of 0.35 T and 1.5 T magnetic field. When delivering dose at 0.35 T, IMRT plans optimized at 0 T and 0.35 T perform equally well regarding ERE compensation. Within a 1.5 T environment, the 1.5 T optimized plans perform slightly better for the static and random intra- and interfraction air cavity movement cases than the 0 T optimized plans. For non-stationary spherical air cavities with a baseline shift (intra- and interfraction) the 0 T optimized plans perform better. These observations show the intrinsic ERE compensation by equidistant and opposing beam configurations for spherical air cavities within the target area. IMRT gives some additional compensation, but only in case of correct positioning of the air cavity according to the IMRT compensation. For intrafraction appearing or disappearing air cavities this correct positioning is absent

  7. Performance evaluation of an improved optical computed tomography polymer gel dosimeter system for 3D dose verification of static and dynamic phantom deliveries

    SciTech Connect

    Lopatiuk-Tirpak, O.; Langen, K. M.; Meeks, S. L.; Kupelian, P. A.; Zeidan, O. A.; Maryanski, M. J.

    2008-09-15

    The performance of a next-generation optical computed tomography scanner (OCTOPUS-5X) is characterized in the context of three-dimensional gel dosimetry. Large-volume (2.2 L), muscle-equivalent, radiation-sensitive polymer gel dosimeters (BANG-3) were used. Improvements in scanner design leading to shorter acquisition times are discussed. The spatial resolution, detectable absorbance range, and reproducibility are assessed. An efficient method for calibrating gel dosimeters using the depth-dose relationship is applied, with photon- and electron-based deliveries yielding equivalent results. A procedure involving a preirradiation scan was used to reduce the edge artifacts in reconstructed images, thereby increasing the useful cross-sectional area of the dosimeter by nearly a factor of 2. Dose distributions derived from optical density measurements using the calibration coefficient show good agreement with the treatment planning system simulations and radiographic film measurements. The feasibility of use for motion (four-dimensional) dosimetry is demonstrated on an example comparing dose distributions from static and dynamic delivery of a single-field photon plan. The capability to visualize three-dimensional dose distributions is also illustrated.

  8. TH-C-12A-07: Implementation of a Pulsed Low Dose Date Radiotherapy (PLRT) Protocol for Recurrent Cancers Using Advanced Beam Delivery

    SciTech Connect

    Ma, C; Lin, M; Chen, L; Price, R; Li, J; Kang, S; Wang, P; Lang, J

    2014-06-15

    Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategies were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.

  9. SU-E-J-100: The Combination of Deformable Image Registration and Regions-Of-Interest Mapping Technique to Accomplish Accurate Dose Calculation On Cone Beam Computed Tomography for Esophageal Cancer

    SciTech Connect

    Huang, B-T; Lu, J-Y

    2015-06-15

    Purpose: We introduce a new method combined with the deformable image registration (DIR) and regions-of-interest mapping (ROIM) technique to accurately calculate dose on daily CBCT for esophageal cancer. Methods: Patients suffered from esophageal cancer were enrolled in the study. Prescription was set to 66 Gy/30 F and 54 Gy/30 F to the primary tumor (PTV66) and subclinical disease (PTV54) . Planning CT (pCT) were segmented into 8 substructures in terms of their differences in physical density, such as gross target volume (GTV), venae cava superior (SVC), aorta, heart, spinal cord, lung, muscle and bones. The pCT and its substructures were transferred to the MIM software to readout their mean HU values. Afterwards, a deformable planning CT to daily KV-CBCT image registration method was then utilized to acquire a new structure set on CBCT. The newly generated structures on CBCT were then transferred back to the treatment planning system (TPS) and its HU information were overridden manually with mean HU values obtained from pCT. Finally, the treatment plan was projected onto the CBCT images with the same beam arrangements and monitor units (MUs) to accomplish dose calculation. Planning target volume (PTV) and organs at risk (OARs) from both of the pCT and CBCT were compared to evaluate the dose calculation accuracy. Results: It was found that the dose distribution in the CBCT showed little differences compared to the pCT, regardless of whether PTV or OARs were concerned. Specifically, dose variation in GTV, PTV54, PTV66, SVC, lung and heart were within 0.1%. The maximum dose variation was presented in the spinal cord, which was up to 2.7% dose difference. Conclusion: The proposed method combined with DIR and ROIM technique to accurately calculate dose distribution on CBCT for esophageal cancer is feasible.

  10. Accurate dosimetry in scanning transmission X-ray microscopes via the cross-linking threshold dose of poly(methyl methacrylate).

    PubMed

    Leontowich, Adam F G; Hitchcock, Adam P; Tyliszczak, Tolek; Weigand, Markus; Wang, Jian; Karunakaran, Chithra

    2012-11-01

    The sensitivity of various polymers to radiation damage by soft X-rays has been measured previously with scanning transmission X-ray microscopes. However, the critical dose values reported by different groups for the same material differ by more than 100%. Possible sources of this variability are investigated here for poly(methyl methacrylate) (PMMA) using controlled exposure to monochromatic soft X-rays at 300 eV. Radiation sensitivity, judged by several different criteria, was evaluated as a function of dose rate, pre-exposure thermal treatments and X-ray polarization. Both the measured critical dose and the dose required to initiate negative mode (cross-linking) were observed to depend only on dose, not the other factors explored. A method of determining detector efficiency from the dose required to initiate negative mode in PMMA is outlined. This method was applied to many of the soft X-ray STXMs presently operating to derive the efficiencies of their transmitted X-ray detectors in the C 1s absorption-edge region.

  11. Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy

    NASA Astrophysics Data System (ADS)

    Hälg, R. A.; Besserer, J.; Boschung, M.; Mayer, S.; Lomax, A. J.; Schneider, U.

    2014-05-01

    In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

  12. NOTE: How accurate is a CT-based dose calculation on a pencil beam TPS for a patient with a metallic prosthesis?

    NASA Astrophysics Data System (ADS)

    Roberts, Ralph

    2001-09-01

    The accuracy of a CT-based dose calculation on a treatment planning system (TPS) for a radiotherapy patient with a metallic prosthesis has not previously been reported. In this study, the accuracy of the CT-based inhomogeneity correction on a pencil beam TPS (Helax TMS) was determined in a phantom containing a metallic prosthesis. A steel prosthesis phantom and a titanium prosthesis phantom were investigated. The phantoms were CT-scanned and dose plans produced on the TPS, using the CT images to provide density information for the inhomogeneity corrections. Verification measurements were performed on a linear accelerator for 6 and 15 MV x-rays. Measured dose profiles at three different depths were compared to the calculations of the TPS. For the titanium prosthesis and for 6 MV x-rays, the TPS overestimated the beam attenuation by approximately 20% at 15 and 20 cm depths in the phantom. This is due to a limitation in the density allocation of this TPS: any Hounsfield number (HN) above a certain threshold is allocated the density of steel. For the steel prosthesis, the TPS performed the correct mapping of HN to mass density. The dose calculation was within 6% for 6 MV x-rays at 15 and 20 cm depths. However, the accuracy of dose calculation varied with beam energy and depth, with large errors in the region close to the prosthesis. The TPS overestimated the dose by 11% for 6 MV and 15% for 15 MV x-rays at 11 cm depth, 2.5 cm beyond the steel prosthesis. These results highlight the limitations in the density allocation of this TPS and demonstrate shortcomings in the pencil beam dose calculation.

  13. Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection

    PubMed Central

    Cheng, Chu-Hsun; Lin, Chi-Te; Lee, Meng-Jen; Tsai, May-Jywan; Huang, Wen-Hung; Huang, Ming-Chao; Lin, Yi-Lo; Chen, Ching-Jung

    2015-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are glial scar-associated molecules considered axonal regeneration inhibitors and can be digested by chondroitinase ABC (ChABC) to promote axonal regeneration after spinal cord injury (SCI). We previously demonstrated that intrathecal delivery of low-dose ChABC (1 U) in the acute stage of SCI promoted axonal regrowth and functional recovery. In this study, high-dose ChABC (50 U) introduced via intrathecal delivery induced subarachnoid hemorrhage and death within 48 h. However, most SCI patients are treated in the sub-acute or chronic stages, when the dense glial scar has formed and is minimally digested by intrathecal delivery of ChABC at the injury site. The present study investigated whether intraparenchymal delivery of ChABC in the sub-acute stage of complete spinal cord transection would promote axonal outgrowth and improve functional recovery. We observed no functional recovery following the low-dose ChABC (1 U or 5 U) treatments. Furthermore, animals treated with high-dose ChABC (50 U or 100 U) showed decreased CSPGs levels. The extent and area of the lesion were also dramatically decreased after ChABC treatment. The outgrowth of the regenerating axons was significantly increased, and some partially crossed the lesion site in the ChABC-treated groups. In addition, retrograde Fluoro-Gold (FG) labeling showed that the outgrowing axons could cross the lesion site and reach several brain stem nuclei involved in sensory and motor functions. The Basso, Beattie and Bresnahan (BBB) open field locomotor scores revealed that the ChABC treatment significantly improved functional recovery compared to the control group at eight weeks after treatment. Our study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. Thus, our results will aid in

  14. Multileaf Collimator Tracking Improves Dose Delivery for Prostate Cancer Radiation Therapy: Results of the First Clinical Trial

    SciTech Connect

    Colvill, Emma; Booth, Jeremy T.; O'Brien, Ricky T.; Eade, Thomas N.; Kneebone, Andrew B.; Poulsen, Per R.; Keall, Paul J.

    2015-08-01

    Purpose: To test the hypothesis that multileaf collimator (MLC) tracking improves the consistency between the planned and delivered dose compared with the dose without MLC tracking, in the setting of a prostate cancer volumetric modulated arc therapy trial. Methods and Materials: Multileaf collimator tracking was implemented for 15 patients in a prostate cancer radiation therapy trial; in total, 513 treatment fractions were delivered. During each treatment fraction, the prostate trajectory and treatment MLC positions were collected. These data were used as input for dose reconstruction (multiple isocenter shift method) to calculate the treated dose (with MLC tracking) and the dose that would have been delivered had MLC tracking not been applied (without MLC tracking). The percentage difference from planned for target and normal tissue dose-volume points were calculated. The hypothesis was tested for each dose-volume value via analysis of variance using the F test. Results: Of the 513 fractions delivered, 475 (93%) were suitable for analysis. The mean difference and standard deviation between the planned and treated MLC tracking doses and the planned and without-MLC tracking doses for all 475 fractions were, respectively, PTV D{sub 99%} −0.8% ± 1.1% versus −2.1% ± 2.7%; CTV D{sub 99%} −0.6% ± 0.8% versus −0.6% ± 1.1%; rectum V{sub 65%} 1.6% ± 7.9% versus −1.2% ± 18%; and bladder V{sub 65%} 0.5% ± 4.4% versus −0.0% ± 9.2% (P<.001 for all dose-volume results). Conclusion: This study shows that MLC tracking improves the consistency between the planned and delivered doses compared with the modeled doses without MLC tracking. The implications of this finding are potentially improved patient outcomes, as well as more reliable dose-volume data for radiobiological parameter determination.

  15. The development of new devices for accurate radiation dose measurement: A guarded liquid ionization chamber and an electron sealed water calorimeter

    NASA Astrophysics Data System (ADS)

    Stewart, Kristin J.

    In this work we developed two new devices that aim to improve the accuracy of relative and reference dosimetry for radiation therapy: a guarded liquid ionization chamber (GLIC) and an electron sealed water (ESW) calorimeter. With the GLIC we aimed to develop a perturbation-free energy-independent detector with high spatial resolution for relative dosimetry. We achieved sufficient stability for short-term measurements using the GLIC-03, which has a sensitive volume of approximately 2 mm3. We evaluated ion recombination in pulsed photon beams using a theoretical model and also determined a new empirical method to correct for relative differences in general recombination which could be used in cases where the theoretical model was not applicable. The energy dependence of the GLIC-03 was 1.1% between 6 and 18 MV photon beams. Measurements in the build-up region of an 18 MV beam indicated that this detector produces minimal perturbation to the radiation field and confirmed the validity of the empirical recombination correction. The ESW calorimeter was designed to directly measure absorbed dose to water in clinical electron beams. We obtained reproducible measurements for 6 to 20 MeV beams. We determined corrections for perturbations to the radiation field caused by the glass calorimeter vessel and for conductive heat transfer due to the dose gradient and non-water materials. The overall uncertainty on the ESW calorimeter dose was 0.5% for the 9 to 20 MeV beams and 1.0% for 6 MeV, showing for the first time that the development of a water-calorimeter-based standard for electron beams over a wide range of energies is feasible. Comparison between measurements with the ESW calorimeter and the NRC photon beam standard calorimeter in a 6 MeV beam revealed a discrepancy of 0.7+/-0.2% which is still under investigation. Absorbed-dose beam quality conversion factors in electron beams were measured using the ESW calorimeter for the Exradin A12 and PTW Roos ionization chambers

  16. Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic-Cationic Drugs to the Brain.

    PubMed

    Kitamura, Atsushi; Okura, Takashi; Higuchi, Kei; Deguchi, Yoshiharu

    2016-02-01

    Brain microdialysis is a powerful tool to estimate brain-to-plasma unbound concentration ratio at the steady state (Kp,uu) of compounds by direct measurement of the unbound concentration in brain interstitial fluid. Here, we evaluated a method to estimate Kp,uu values of multiple organic-cationic drugs simultaneously, by means of brain microdialysis combined with cocktail dosing. Five cationic drugs (diphenhydramine, memantine, oxycodone, pyrilamine, and tramadol), substrates of the proton-coupled organic cation antiport system, were selected as model drugs, and compared under single-dosing and cocktail-dosing conditions. We selected doses of the drugs at which no significant drug-drug interaction occurs at the proton-coupled organic cation antiport system in the blood-brain barrier (BBB). This was confirmed by uptake studies in hCMEC/D3 cells, an in vitro BBB model. The Kp,uu values after cocktail administration were in the range of 1.8-5.2, and were in good agreement with those after single administration. These results suggest that the microdialysis method with cocktail dosing is suitable to estimate Kp,uu values of several cationic drugs simultaneously, if there is no drug-drug interaction during BBB transport. The method could be useful for evaluating drug candidates with high Kp,uu values at an early stage in the development of central nervous system-acting drugs.

  17. Radiobiological evaluation of breast cancer radiotherapy accounting for the effects of patient positioning and breathing in dose delivery. A meta analysis.

    PubMed

    Tzikas, A; Komisopoulos, G; Ferreira, B C; Hyodynmaa, S; Axelsson, S; Papanikolaou, N; Lavdas, E; Lind, B K; Mavroidis, P

    2013-02-01

    In breast cancer radiotherapy, significant discrepancies in dose delivery can contribute to underdosage of the tumor or overdosage of normal tissue, which is potentially related to a reduction of local tumor control and an increase of side effects. To study the impact of these factors in breast cancer radiotherapy, a meta analysis of the clinical data reported by Mavroidis et al. (2002) in Acta Oncol (41:471-85), showing the patient setup and breathing uncertainties characterizing three different irradiation techniques, were employed. The uncertainties in dose delivery are simulated based on fifteen breast cancer patients (5 mastectomized, 5 resected with negative node involvement (R-) and 5 resected with positive node involvement (R1)), who were treated by three different irradiation techniques, respectively. The positioning and breathing effects were taken into consideration in the determination of the real dose distributions delivered to the CTV and lung in each patient. The combined frequency distributions of the positioning and breathing distributions were obtained by convolution. For each patient the effectiveness of the dose distribution applied is calculated by the Poisson and relative seriality models and a set of parameters that describe the dose-response relations of the target and lung. The three representative radiation techniques are compared based on radiobiological measures by using the complication-free tumor control probability, P(+) and the biologically effective uniform dose, (BEUD)concepts. For the Mastectomy case, the average P(+) values of the planned and delivered dose distributions are 93.8% for a (BEUD)(CTV) of 51.8 Gy and 85.0% for a (BEUD)(CTV) of 50.3 Gy, respectively. The respective total control probabilities, P(B) values are 94.8% and 92.5%, whereas the corresponding total complication probabilities, P(1) values are 0.9% and 7.4%. For the R- case, the average P(+) values are 89.4% for a (BEUD)(CTV) of 48.9 Gy and 88.6% for a

  18. Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria

    PubMed Central

    2013-01-01

    Background Human cerebral malaria (HCM) is a life-threatening complication caused by Plasmodium falciparum infection that continues to be a major global health problem despite optimal anti-malarial treatment. In the experimental model of cerebral malaria (ECM) by Plasmodium berghei ANKA, bolus administration of nimodipine at high doses together with artemether, increases survival of mice with ECM. However, the dose and administration route used is associated with cardiovascular side effects such as hypotension and bradycardia in humans and mice, which could preclude its potential use as adjunctive treatment in HCM. Methods In the present study, alternative delivery systems for nimodipine during late-stage ECM in association with artesunate were searched to define optimal protocols to achieve maximum efficacy in increasing survival in rescue therapy while causing the least cardiac side effects. The baseline electrocardiogram (ECG) and arterial pressure characteristics of uninfected control animals and of mice with ECM and its response upon rescue treatment with artesunate associated or not with nimodipine is also analysed. Results Nimodipine, given at 0.5 mg/kg/day via a slow and continuous delivery system by osmotic pumps, increases survival of mice with ECM when used as adjunctive treatment to artesunate. Mice with ECM showed hypotension and ECG changes, including bradycardia and increases in PR, QRS, QTc and ST interval duration. ECM mice also show increased QTc dispersion, heart rate variability (HRV), RMSSD, low frequency (LF) and high frequency (HF) bands of the power spectrum. Both sympathetic and parasympathetic inputs to the heart were increased, but there was a predominance of sympathetic tone as demonstrated by an increased LF/HF ratio. Nimodipine potentiated bradycardia when given by bolus injection, but not when via osmotic pumps. In addition, nimodipine shortened PR duration and improved HRV, RMSSD, LF and HF powers in mice with ECM. In addition

  19. Local delivery of antitumor necrosis factor-α through conjugation to hyaluronic acid: dosing strategies and early healing effects in a rat burn model.

    PubMed

    Friedrich, Emily E; Azofiefa, Andrea; Fisch, Evan; Washburn, Newell R

    2015-01-01

    The objective of this study was to measure dose-response effects of topical delivery of inhibitors of tumor necrosis factor-α (TNF-α) through conjugation to hyaluronic acid in a rat burn model to determine effects on inflammatory responses, burn progression, and early stages of healing. Monoclonal antibodies against TNF-α were conjugated to hyaluronic acid and applied topically in a rat partial-thickness burn model. Metrics of inflammatory responses and tissue necrosis were measured as well as the quantitative analysis of collagen composition and organization. The minimum effective conjugated antibody dose was found to be 100 μg with three applications 48 hours apart. Nonviable tissue thicknesses decreased with increasing dose and dose frequency. Free antibody retarded macrophage infiltration in the periphery but not at the surface, while the conjugated antibody was able to hinder macrophage infiltration at both the periphery and the surface. Quantification of collagen I and III staining ratios at days 4, 7, and 14 and quantitative image analysis of collagen organization at day 14 demonstrated differences between saline and conjugate treatment. This correlated with increases in re-epithelialization observed in conjugate-treated sites. Reductions in inflammatory markers and secondary tissue necrosis under treatment with the conjugates were understood in terms of differences in antibody transport compared to nonconjugated antibody. Differences in collagen composition and organization at Day 14 suggested that the reductions in inflammatory responses altered early healing responses. These results indicate anti-TNF-α conjugated to hyaluronic acid can be an effective treatment for reducing secondary necrosis and improving healing outcomes in burns.

  20. Development of a novel ArcCHECK{sup Trade-Mark-Sign} insert for routine quality assurance of VMAT delivery including dose calculation with inhomogeneities

    SciTech Connect

    Fakir, H.; Gaede, S.; Mulligan, M.; Chen, J. Z.

    2012-07-15

    Purpose: To design a versatile, nonhomogeneous insert for the dose verification phantom ArcCHECK{sup Trade-Mark-Sign} (Sun Nuclear Corp., FL) and to demonstrate its usefulness for the verification of dose distributions in inhomogeneous media. As an example, we demonstrate it can be used clinically for routine quality assurance of two volumetric modulated arc therapy (VMAT) systems for lung stereotactic body radiation therapy (SBRT): SmartArc{sup Registered-Sign} (Pinnacle{sup 3}, Philips Radiation Oncology Systems, Fitchburg, WI) and RapidArc{sup Registered-Sign} (Eclipse{sup Trade-Mark-Sign }, Varian Medical Systems, Palo Alto, CA). Methods: The cylindrical detector array ArcCHECK{sup Trade-Mark-Sign} has a retractable homogeneous acrylic insert. In this work, we designed and manufactured a customized heterogeneous insert with densities that simulate soft tissue, lung, bone, and air. The insert offers several possible heterogeneity configurations and multiple locations for point dose measurements. SmartArc{sup Registered-Sign} and RapidArc{sup Registered-Sign} plans for lung SBRT were generated and copied to ArcCHECK{sup Trade-Mark-Sign} for each inhomogeneity configuration. Dose delivery was done on a Varian 2100 ix linac. The evaluation of dose distributions was based on gamma analysis of the diode measurements and point doses measurements at different positions near the inhomogeneities. Results: The insert was successfully manufactured and tested with different measurements of VMAT plans. Dose distributions measured with the homogeneous insert showed gamma passing rates similar to our clinical results ({approx}99%) for both treatment-planning systems. Using nonhomogeneous inserts decreased the passing rates by up to 3.6% in the examples studied. Overall, SmartArc{sup Registered-Sign} plans showed better gamma passing rates for nonhomogeneous measurements. The discrepancy between calculated and measured point doses was increased up to 6.5% for the nonhomogeneous

  1. An injectable elastin-based gene delivery platform for dose-dependent modulation of angiogenesis and inflammation for critical limb ischemia.

    PubMed

    Dash, Biraja C; Thomas, Dilip; Monaghan, Michael; Carroll, Oliver; Chen, Xizhe; Woodhouse, Kimberly; O'Brien, Timothy; Pandit, Abhay

    2015-10-01

    Critical limb ischemia is a major clinical problem. Despite rigorous treatment regimes, there has been only modest success in reducing the rate of amputations in affected patients. Reduced level of blood flow and enhanced inflammation are the two major pathophysiological changes that occur in the ischemic tissue. The objective of this study was to develop a controlled dual gene delivery system capable of delivering therapeutic plasmid eNOS and IL-10 in a temporal manner. In order to deliver multiple therapeutic genes, an elastin-like polypeptide (ELP) based injectable system was designed. The injectable system was comprised of hollow spheres and an in situ-forming gel scaffold of elastin-like polypeptide capable of carrying gene complexes, with an extended manner release profile. In addition, the ELP based injectable system was used to deliver human eNOS and IL-10 therapeutic genes in vivo. A subcutaneous dose response study showed enhanced blood vessel density in the treatment groups of eNOS (20 μg) and IL-10 (10 μg)/eNOS (20 μg) and reduced inflammation with IL-10 (10 μg) alone. Next, we carried out a hind-limb ischemia model comparing the efficacy of the following interventions; Saline; IL-10, eNOS and IL-10/eNOS. The selected dose of eNOS, exhibited enhanced angiogenesis. IL-10 treatment groups showed reduction in the level of inflammatory cells. Furthermore, we demonstrated that eNOS up-regulated major proangiogenic growth factors such as vascular endothelial growth factors, platelet derived growth factor B, and fibroblast growth factor 1, which may explain the mechanism of this approach. These factors help in formation of a stable vascular network. Thus, ELP injectable system mediating non-viral delivery of human IL10-eNOS is a promising therapy towards treating limb ischemia.

  2. Considerations in insulin delivery device selection.

    PubMed

    Valentine, Virginia; Kruger, Davida F

    2010-06-01

    Recent guidelines from the American Diabetes Association and the European Association for the Study of Diabetes promote the use of insulin sooner rather than later in patients with type 2 diabetes to achieve goal range glucose control (< 7%) but remain silent on a recommendation for delivery system. Even though there is widespread consensus among experts and payers that people with type 2 diabetes should use insulin earlier to achieve tight control, it still remains an elusive goal. Benefits of pen-type delivery devices include accurate dosing, faster and easier setting of dose and injection times, and increased patient acceptance and adherence. Before healthcare professionals can recommend a delivery device, it is critical they understand not only the medication in the device but also the various features and benefits to the different devices available and how those impact the patient. We will present considerations to assist in making appropriate device selection, to optimize patient success. PMID:20515315

  3. SU-E-T-426: Dose Delivery Accuracy in Breast Field Junction for Free Breath and Deep Inspiration Breath Hold Techniques

    SciTech Connect

    Epstein, D; Shekel, E; Levin, D

    2014-06-01

    Purpose: The purpose of this work was to verify the accuracy of the dose distribution along the field junction in a half beam irradiation technique for breast cancer patients receiving radiation to the breast or chest wall (CW) and the supraclavicular LN region for both free breathing and deep inspiration breath hold (DIBH) technique. Methods: We performed in vivo measurements for nine breast cancer patients receiving radiation to the breast/CW and to the supraclavicular LN region. Six patients were treated to the left breast/CW using DIBH technique and three patients were treated to the right breast/CW in free breath. We used five microMOSFET dosimeters: three located along the field junction, one located 1 cm above the junction and the fifth microMOSFET located 1 cm below the junction. We performed consecutive measurements over several days for each patient and compared the measurements to the TPS calculation (Eclipse, Varian™). Results: The calculated and measured doses along the junction were 0.97±0.08 Gy and 1.02±0.14 Gy, respectively. Above the junction calculated and measured doses were 0.91±0.08 Gy and 0.98±0.09 Gy respectively, and below the junction calculated and measured doses were 1.70±0.15 Gy and 1.61±0.09 Gy, respectively. All differences were not statistically significant. When comparing calculated and measured doses for DIBH patients only, there was still no statistically significant difference between values for all dosimeter locations. Analysis was done using the Mann-Whitney Rank-Sum Test. Conclusion: We found excellent correlation between calculated doses from the TPS and measured skin doses at the junction of several half beam fields. Even for the DIBH technique, where there is more potential for variance due to depth of breath, there is no over or underdose along the field junction. This correlation validates the TPS, as well an accurate, reproducible patient setup.

  4. In Vitro Determination of Respimat® Dose Delivery in Children: An Evaluation Based on Inhalation Flow Profiles and Mouth–Throat Models

    PubMed Central

    Bickmann, Deborah; Kamin, Wolfgang; Sharma, Ashish; Moroni-Zentgraf, Petra; Zielen, Stefan

    2016-01-01

    Abstract Background: Aerosol therapy in young children can be difficult. A realistic model based on handling studies and in vitro investigations can complement clinical deposition studies and be used to enable dose-to-the-lung (DTL) predictions. Methods: Predictions on dose delivery to the lung were based on (1) representative inhalation flow profiles from children enrolled in a Respimat® handling study, (2) in vitro measurement of the fine-particle DTL using mouth–throat models derived from nuclear magnetic resonance/computed tomography (NMR/CT) scans of children, and (3) a mathematical model to predict the tiotropium DTL. Accuracy of the prediction was confirmed using pharmacokinetic (PK) data from children with cystic fibrosis enrolled in a phase 3 clinical trial of tiotropium Respimat with valved holding chamber (VHC). Results: Representative inhalation flow profiles for each age group were obtained from 56 children who successfully inhaled a volume >0.15 L from the Respimat with VHC. Average dimensions of the mouth–throat region for 38 children aged 1–<2 years, 2–<3 years, 3–<4 years, and 4–<5 years were determined from NMR/CT scans. The DTL from the Respimat plus VHC were determined by in vitro measurement and were 5.1±1.1%, 15.6%±1.4%, 17.9%±1.5%, and 37.1%±1.8% of the delivered dose for child models 0–<2 years, 2–<3 years, 3–<4 years, and 4–<5 years, respectively. This provides a possible explanation for the age dependence of clinical PK data obtained from the phase 3 tiotropium trial. Calculated in vitro DTL per body mass (μg/kg [±SD]) were 0.031±0.014, 0.066±0.031, 0.058±0.024, and 0.059±0.029, respectively, compared to 0.046 in adults. Therefore, efficacy of the treatment was not negatively impacted in spite of the seemingly low percentages of the DTL. Conclusions: We conclude that the combination of real-life inhalation profiles with respective mouth–throat models and in vitro determination of delivered DTL is a good

  5. Articulating feedstock delivery device

    DOEpatents

    Jordan, Kevin

    2013-11-05

    A fully articulable feedstock delivery device that is designed to operate at pressure and temperature extremes. The device incorporates an articulating ball assembly which allows for more accurate delivery of the feedstock to a target location. The device is suitable for a variety of applications including, but not limited to, delivery of feedstock to a high-pressure reaction chamber or process zone.

  6. SU-E-J-269: Assessing the Precision of Dose Delivery in CBCT-Guided Stereotactic Body Radiation Therapy for Lung and Soft Tissue Metastatic Lesions

    SciTech Connect

    Parsai, S; Dalhart, A; Chen, C; Parsai, E; Pearson, D; Sperling, N; Reddy, K

    2014-06-01

    Purpose: Ensuring reproducibility of target localization is critical to accurate stereotactic body radiation treatment (SBRT) for lung and soft tissue metastatic lesions. To characterize interfraction variability in set-up and evaluate PTV margins utilized for SBRT, daily CBCTs were used to calculate delivered target and OAR doses compared to those expected from planning. Methods: CBCT images obtained prior to each fraction of SBRT for a lung and thyroid metastatic lesion were evaluated. The target CTV/ITV and OARs on each of 8 CBCT data sets were contoured. Using MIM fusion software and Pinnacle{sup 3} RTP system, delivered dose distribution was reconstructed on each CBCT, utilizing translational shifts performed prior to treatment. Actual delivered vs. expected doses received by target CTV/ITV and adjacent critical structures were compared to characterize accuracy of pre-treatment translational shifts and PTV margins. Results: The planned CTV/ITV D95% and V100% were 4595cGy and 91.47% for the lung lesion, and 3010cGy and 96.34% for the thyroid lesion. Based on CBCT analysis, actual mean D95% and V100% for lung ITV were 4542±344.4cGy and 91.54±3.45%; actual mean D95% and V100% for thyroid metastasis CTV were 3005±25.98cGy and 95.20±2.522%. For the lung lesion, ipsilateral lung V20, heart V32 (cc) and spinal cord (.03 cc) max were 110.15cc, 3.33cc, and 1680cGy vs. 110.27±14.79cc, 6.74±3.76cc, and 1711±46.56cGy for planned vs. delivered doses, respectively. For the thyroid metastatic lesion, esophagus V18, trachea (.03 cc) max, and spinal cord (.03 cc) max were 0.35cc, 2555cGy, and 850cGy vs. 0.16±0.13cc, 2147±367cGy, and 838±45cGy for planned vs. delivered treatments, respectively. Conclusion: Minimal variability in SBRT target lesion dose delivered based on pre-treatment CBCT-based translational shifts suggests tighter PTV margins may be considered to further decrease dose to surrounding critical structures. Guidelines for optimal target alignment during

  7. Ocular delivery of macromolecules

    PubMed Central

    Kim, Yoo-Chun; Chiang, Bryce; Wu, Xianggen; Prausnitz, Mark R.

    2014-01-01

    Biopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non--invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects. This review discusses the barriers to drug delivery via various ophthalmic routes of administration in the context of macromolecule delivery and discusses efforts to develop controlled-release systems for delivery of biopharmaceuticals to the eye. The growing number of macromolecular therapies in the eye needs improved drug delivery methods that increase drug efficacy, safety and patient compliance. PMID:24998941

  8. Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration.

    PubMed

    Bouyer, Michael; Guillot, Raphael; Lavaud, Jonathan; Plettinx, Cedric; Olivier, Cécile; Curry, Véronique; Boutonnat, Jean; Coll, Jean-Luc; Peyrin, Françoise; Josserand, Véronique; Bettega, Georges; Picart, Catherine

    2016-10-01

    The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine. PMID:27454063

  9. Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration.

    PubMed

    Bouyer, Michael; Guillot, Raphael; Lavaud, Jonathan; Plettinx, Cedric; Olivier, Cécile; Curry, Véronique; Boutonnat, Jean; Coll, Jean-Luc; Peyrin, Françoise; Josserand, Véronique; Bettega, Georges; Picart, Catherine

    2016-10-01

    The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine.

  10. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    PubMed

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-01

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs.

  11. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    PubMed

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-01

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs. PMID:26756920

  12. Independent dose calculations for commissioning, quality assurance and dose reconstruction of PBS proton therapy

    NASA Astrophysics Data System (ADS)

    Meier, G.; Besson, R.; Nanz, A.; Safai, S.; Lomax, A. J.

    2015-04-01

    Pencil beam scanning proton therapy allows the delivery of highly conformal dose distributions by delivering several thousand pencil beams. These beams have to be individually optimised and accurately delivered requiring a significant quality assurance workload. In this work we describe a toolkit for independent dose calculations developed at Paul Scherrer Institut which allows for dose reconstructions at several points in the treatment workflow. Quality assurance based on reconstructed dose distributions was shown to be favourable to pencil beam by pencil beam comparisons for the detection of delivery uncertainties and estimation of their effects. Furthermore the dose reconstructions were shown to have a sensitivity of the order of or higher than the measurements currently employed in the clinical verification procedures. The design of the independent dose calculation tool allows for a high modifiability of the dose calculation parameters (e.g. depth dose profiles, angular spatial distributions) allowing for a safe environment outside of the clinical treatment planning system for investigating the effect of such parameters on the resulting dose distributions and thus distinguishing between different contributions to measured dose deviations. The presented system could potentially reduce the amount of patient-specific quality assurance measurements which currently constitute a bottleneck in the clinical workflow.

  13. Independent dose calculations for commissioning, quality assurance and dose reconstruction of PBS proton therapy.

    PubMed

    Meier, G; Besson, R; Nanz, A; Safai, S; Lomax, A J

    2015-04-01

    Pencil beam scanning proton therapy allows the delivery of highly conformal dose distributions by delivering several thousand pencil beams. These beams have to be individually optimised and accurately delivered requiring a significant quality assurance workload. In this work we describe a toolkit for independent dose calculations developed at Paul Scherrer Institut which allows for dose reconstructions at several points in the treatment workflow. Quality assurance based on reconstructed dose distributions was shown to be favourable to pencil beam by pencil beam comparisons for the detection of delivery uncertainties and estimation of their effects. Furthermore the dose reconstructions were shown to have a sensitivity of the order of or higher than the measurements currently employed in the clinical verification procedures. The design of the independent dose calculation tool allows for a high modifiability of the dose calculation parameters (e.g. depth dose profiles, angular spatial distributions) allowing for a safe environment outside of the clinical treatment planning system for investigating the effect of such parameters on the resulting dose distributions and thus distinguishing between different contributions to measured dose deviations. The presented system could potentially reduce the amount of patient-specific quality assurance measurements which currently constitute a bottleneck in the clinical workflow. PMID:25779992

  14. Formulation and in Vitro Evaluation of Self-microemulsifying Drug Delivery System Containing Fixed-Dose Combination of Atorvastatin and Ezetimibe.

    PubMed

    Hwang, Kyu-Mok; Park, Shin-Ae; Kim, Ju-Young; Park, Chun-Woong; Rhee, Yun-Seok; Park, Eun-Seok

    2015-01-01

    This paper focuses on the development and physicochemical characterization of a self-microemulsifying drug delivery system (SMEDDS) containing a fixed-dose combination of atorvastatin (ATR) and ezetimibe (EZT). The solubility of both drugs was determined in excipient screening studies. Ternary-phase diagrams were drawn for 27 systems composed of different surfactants, cosurfactants, and oils at different surfactant-to-cosurfactant (S/CoS) ratios, and the system exhibiting the largest percentage area of the self-microemulsifying region was selected. The optimum oil ratio in the SMEDDS was selected by evaluating the mean droplet size of the resultant microemulsions. The underlying mechanism of the lower ATR loading capacity compared with EZT was elucidated by measurement of the zeta potential and UV absorption analysis. The results implied that ATR was located exclusively in the surfactant-cosurfactant layer, whereas EZT was located both in the microemulsion core and the surfactant-cosurfactant layer. In vitro dissolution studies showed that the SMEDDS had higher initial dissolution rates for both drugs when compared with marketed products. More importantly, EZT had a significantly increased dissolution profile in distilled water and pH 4.0 acetate buffer, implying enhanced bioavailability.

  15. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  16. Safety and Efficacy of High Dose AAV9 Encoding SERCA2a Delivered by Molecular Cardiac Surgery with Recirculating Delivery (MCARD) in Ovine Ischemic Cardiomyopathy

    PubMed Central

    Katz, Michael G.; Fargnoli, Anthony S.; Williams, Richard D.; Steuerwald, Nury M.; Isidro, Alice; Ivanina, Anna V.; Sokolova, Inna M.; Bridges, Charles R.

    2014-01-01

    Objective Therapeutic safety and efficacy are the basic prerequisites for clinical gene therapy. Herein we investigate the effect of high dose MCARD-mediated AAV9/SERCA2a gene delivery on clinical parameters, oxidative stress, humoral and cellular immune response, and cardiac remodeling. Methods Ischemic cardiomyopathy was generated in a sheep model. Then animals were assigned to one of two groups: control (n=10), and study (MCARD, n=6). The control had no intervention while the study group received 1014 gc of AAV9.SERCA2a 4 weeks post-infarction. Results Our ischemic model produced reliable infarcts leading to heart failure. The baseline ejection fraction (EF) in the MCARD group was 57.6±1.6 vs. 61.2±1.9 in the control group, (p>0.05). Twelve weeks post-infarction, the MCARD group had superior LV function compared to control: stroke volume index (46.6±1.8 vs. 35.8±2.5 mL/m2, p<0.05), EF (46.2±1.9 vs. 38.7±2.5%, p<0.05); and LV end systolic and end diastolic dimensions [41.3±1.7 vs. 48.2±1.4 mm; 51.2±1.5 vs. 57.6±1.7 mm], p<0.05. Markers of oxidative stress were significantly reduced in the infarct zone in the MCARD group. There was no positive T cell mediated immune response in the MCARD group at any time point. Myocyte hypertrophy was also significantly attenuated in the MCARD group compared to control. Conclusions Cardiac overexpression of the SERCA2a gene via MCARD is a safe therapeutic intervention. It significantly improves LV function, decreases markers of oxidative stress, abrogates myocyte hypertrophy, arrests remodeling and does not induce a T cell mediated immune response. PMID:25037619

  17. Benchmark Dose Modeling

    EPA Science Inventory

    Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...

  18. Delivery validation of an automated modulated electron radiotherapy plan

    SciTech Connect

    Connell, T. Papaconstadopoulos, P.; Alexander, A.; Serban, M.; Devic, S.; Seuntjens, J.

    2014-06-15

    Purpose: Modulated electron radiation therapy (MERT) represents an active area of interest that offers the potential to improve healthy tissue sparing in treatment of certain cancer cases. Challenges remain however in accurate beamlet dose calculation, plan optimization, collimation method, and delivery accuracy. In this work, the authors investigate the accuracy and efficiency of an end-to-end MERT plan and automated delivery method. Methods: Treatment planning was initiated on a previously treated whole breast irradiation case including an electron boost. All dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. Results: The automated delivery, which covered four electron energies, 196 subfields, and 6183 total MU was completed in 25.8 min, including 6.2 min of beam-on time. The remainder of the delivery time was spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. Comparison of the planned and delivered film dose gave 3%/3mm gamma pass rates of 62.1%, 99.8%, 97.8%, 98.3%, and 98.7% for the 9, 12, 16, and 20 MeV, and combined energy deliveries, respectively. Delivery was also performed with a MapCHECK device and resulted in 3%/3  mm gamma pass rates of 88.8%, 86.1%, 89.4%, and 94.8% for the 9, 12, 16, and 20 MeV energies, respectively. Conclusions: Results of the authors’ study showed that an accurate delivery utilizing an add-on tertiary electron collimator is possible using Monte Carlo calculated plans and inverse optimization, which brings MERT closer to becoming a viable option for physicians in treating superficial malignancies.

  19. Experimental evaluation of actual delivered dose using mega-voltage cone-beam CT and direct point dose measurement

    SciTech Connect

    Matsubara, Kana; Kohno, Ryosuke; Nishioka, Shie; Shibuya, Toshiyuki; Ariji, Takaki; Akimoto, Tetsuo; Saitoh, Hidetoshi

    2013-07-01

    Radiation therapy in patients is planned by using computed tomography (CT) images acquired before start of the treatment course. Here, tumor shrinkage or weight loss or both, which are common during the treatment course for patients with head-and-neck (H and N) cancer, causes unexpected differences from the plan, as well as dose uncertainty with the daily positional error of patients. For accurate clinical evaluation, it is essential to identify these anatomical changes and daily positional errors, as well as consequent dosimetric changes. To evaluate the actual delivered dose, the authors proposed direct dose measurement and dose calculation with mega-voltage cone-beam CT (MVCBCT). The purpose of the present study was to experimentally evaluate dose calculation by MVCBCT. Furthermore, actual delivered dose was evaluated directly with accurate phantom setup. Because MVCBCT has CT-number variation, even when the analyzed object has a uniform density, a specific and simple CT-number correction method was developed and applied for the H and N site of a RANDO phantom. Dose distributions were calculated with the corrected MVCBCT images of a cylindrical polymethyl methacrylate phantom. Treatment processes from planning to beam delivery were performed for the H and N site of the RANDO phantom. The image-guided radiation therapy procedure was utilized for the phantom setup to improve measurement reliability. The calculated dose in the RANDO phantom was compared to the measured dose obtained by metal-oxide-semiconductor field-effect transistor detectors. In the polymethyl methacrylate phantom, the calculated and measured doses agreed within about +3%. In the RANDO phantom, the dose difference was less than +5%. The calculated dose based on simulation-CT agreed with the measured dose within±3%, even in the region with a high dose gradient. The actual delivered dose was successfully determined by dose calculation with MVCBCT, and the point dose measurement with the image

  20. Total Body Irradiation, Toward Optimal Individual Delivery: Dose Evaluation With Metal Oxide Field Effect Transistors, Thermoluminescence Detectors, and a Treatment Planning System

    SciTech Connect

    Bloemen-van Gurp, Esther J. Mijnheer, Ben J.; Verschueren, Tom A.M.; Lambin, Philippe

    2007-11-15

    Purpose: To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. Methods and Materials: A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. Results: The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. Conclusions: The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

  1. Sci—Thur PM: Planning and Delivery — 03: Automated delivery and quality assurance of a modulated electron radiation therapy plan

    SciTech Connect

    Connell, T; Papaconstadopoulos, P; Alexander, A; Serban, M; Devic, S; Seuntjens, J

    2014-08-15

    Modulated electron radiation therapy (MERT) offers the potential to improve healthy tissue sparing through increased dose conformity. Challenges remain, however, in accurate beamlet dose calculation, plan optimization, collimation method and delivery accuracy. In this work, we investigate the accuracy and efficiency of an end-to-end MERT plan and automated-delivery workflow for the electron boost portion of a previously treated whole breast irradiation case. Dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. The automated delivery, which covered 4 electron energies, 196 subfields and 6183 total MU was completed in 25.8 minutes, including 6.2 minutes of beam-on time with the remainder of the delivery time spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. The delivery time could be reduced by 5.3 minutes with minor electron collimator modifications and the beam-on time could be reduced by and estimated factor of 2–3 through redesign of the scattering foils. Comparison of the planned and delivered film dose gave 3%/3 mm gamma pass rates of 62.1, 99.8, 97.8, 98.3, and 98.7 percent for the 9, 12, 16, 20 MeV, and combined energy deliveries respectively. Good results were also seen in the delivery verification performed with a MapCHECK 2 device. The results showed that accurate and efficient MERT delivery is possible with current technologies.

  2. Dose reconstruction for intensity-modulated radiation therapy using a non-iterative method and portal dose image

    NASA Astrophysics Data System (ADS)

    Yeo, Inhwan Jason; Jung, Jae Won; Chew, Meng; Kim, Jong Oh; Wang, Brian; Di Biase, Steven; Zhu, Yunping; Lee, Dohyung

    2009-09-01

    A straightforward and accurate method was developed to verify the delivery of intensity-modulated radiation therapy (IMRT) and to reconstruct the dose in a patient. The method is based on a computational algorithm that linearly describes the physical relationship between beamlets and dose-scoring voxels in a patient and the dose image from an electronic portal imaging device (EPID). The relationship is expressed in the form of dose response functions (responses) that are quantified using Monte Carlo (MC) particle transport techniques. From the dose information measured by the EPID the received patient dose is reconstructed by inversely solving the algorithm. The unique and novel non-iterative feature of this algorithm sets it apart from many existing dose reconstruction methods in the literature. This study presents the algorithm in detail and validates it experimentally for open and IMRT fields. Responses were first calculated for each beamlet of the selected fields by MC simulation. In-phantom and exit film dosimetry were performed on a flat phantom. Using the calculated responses and the algorithm, the exit film dose was used to inversely reconstruct the in-phantom dose, which was then compared with the measured in-phantom dose. The dose comparison in the phantom for all irradiated fields showed a pass rate of higher than 90% dose points given the criteria of dose difference of 3% and distance to agreement of 3 mm.

  3. Profitable capitation requires accurate costing.

    PubMed

    West, D A; Hicks, L L; Balas, E A; West, T D

    1996-01-01

    In the name of costing accuracy, nurses are asked to track inventory use on per treatment basis when more significant costs, such as general overhead and nursing salaries, are usually allocated to patients or treatments on an average cost basis. Accurate treatment costing and financial viability require analysis of all resources actually consumed in treatment delivery, including nursing services and inventory. More precise costing information enables more profitable decisions as is demonstrated by comparing the ratio-of-cost-to-treatment method (aggregate costing) with alternative activity-based costing methods (ABC). Nurses must participate in this costing process to assure that capitation bids are based upon accurate costs rather than simple averages. PMID:8788799

  4. Relationship of glucose values to sliding scale insulin (correctional insulin) dose delivery and meal time in acute care patients with diabetes mellitus.

    PubMed

    Trotter, Barbara; Conaway, Mark R; Burns, Suzanne M

    2013-01-01

    Findings of this study suggest the traditional sliding scale insulin (SSI) method does not improve target glucose values among adult medical inpatients. Timing of blood glucose (BC) measurement does affect the required SSI dose. BC measurement and insulin dose administration should be accomplished immediately prior to mealtime. PMID:23802496

  5. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed.

  6. Impact of conventional fractionated RT to pelvic lymph nodes and dose-escalated hypofractionated RT to prostate gland using IMRT treatment delivery in high-risk prostate cancer

    NASA Astrophysics Data System (ADS)

    Pervez, Nadeem

    Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

  7. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate

    PubMed Central

    Costa-Nunes, João P.; Cline, Brandon H.; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W. M.

    2015-01-01

    Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies. PMID:26064929

  8. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate.

    PubMed

    Costa-Nunes, João P; Cline, Brandon H; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W M; Strekalova, Tatyana

    2015-01-01

    Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies. PMID:26064929

  9. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate.

    PubMed

    Costa-Nunes, João P; Cline, Brandon H; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W M; Strekalova, Tatyana

    2015-01-01

    Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies.

  10. In vitro biotransformation rates in fish liver S9: effect of dosing techniques.

    PubMed

    Lee, Yung-Shan; Lee, Danny H Y; Delafoulhouze, Maximilien; Otton, S Victoria; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

    2014-08-01

    In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [KOW ] =10(5.60) ) and benzo[a]pyrene (KOW  =10(6.04) ), whereas there were no statistical differences in pyrene (KOW  =10(5.18) ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals.

  11. SU-C-BRB-06: Utilizing 3D Scanner and Printer for Dummy Eye-Shield: Artifact-Free CT Images of Tungsten Eye-Shield for Accurate Dose Calculation

    SciTech Connect

    Park, J; Lee, J; Kim, H; Kim, I; Ye, S

    2015-06-15

    Purpose: To evaluate the effect of a tungsten eye-shield on the dose distribution of a patient. Methods: A 3D scanner was used to extract the dimension and shape of a tungsten eye-shield in the STL format. Scanned data was transferred into a 3D printer. A dummy eye shield was then produced using bio-resin (3D systems, VisiJet M3 Proplast). For a patient with mucinous carcinoma, the planning CT was obtained with the dummy eye-shield placed on the patient’s right eye. Field shaping of 6 MeV was performed using a patient-specific cerrobend block on the 15 x 15 cm{sup 2} applicator. The gantry angle was 330° to cover the planning target volume near by the lens. EGS4/BEAMnrc was commissioned from our measurement data from a Varian 21EX. For the CT-based dose calculation using EGS4/DOSXYZnrc, the CT images were converted to a phantom file through the ctcreate program. The phantom file had the same resolution as the planning CT images. By assigning the CT numbers of the dummy eye-shield region to 17000, the real dose distributions below the tungsten eye-shield were calculated in EGS4/DOSXYZnrc. In the TPS, the CT number of the dummy eye-shield region was assigned to the maximum allowable CT number (3000). Results: As compared to the maximum dose, the MC dose on the right lens or below the eye shield area was less than 2%, while the corresponding RTP calculated dose was an unrealistic value of approximately 50%. Conclusion: Utilizing a 3D scanner and a 3D printer, a dummy eye-shield for electron treatment can be easily produced. The artifact-free CT images were successfully incorporated into the CT-based Monte Carlo simulations. The developed method was useful in predicting the realistic dose distributions around the lens blocked with the tungsten shield.

  12. Low-dose RUTF protocol and improved service delivery lead to good programme outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar.

    PubMed

    James, Philip T; Van den Briel, Natalie; Rozet, Aurélie; Israël, Anne-Dominique; Fenn, Bridget; Navarro-Colorado, Carlos

    2015-10-01

    The treatment of uncomplicated severe acute malnutrition (SAM) requires substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was adopted. In this protocol, RUTF was dosed according to beneficiary's body weight, until the child reached a Weight-for-Height z-score of ≥-3 and mid-upper arm circumference ≥110 mm. From this point, the child received a fixed quantity of RUTF per day, independent of body weight until discharge. Specific measures were implemented as part of this low-dose RUTF protocol in order to improve service quality and beneficiary support. We analysed individual records of 3083 children treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0% defaulted and 0.9% were classified as non-responders. No deaths were recorded. Among children who recovered, median [IQR] length of stay and weight gain were 42 days [28; 56] and 4.0 g kg(-1) day(-1) [3.0; 5.7], respectively. Multivariable logistic regression showed that children older than 48 months had higher odds of non-response to treatment than younger children (adjusted odds ratio: 3.51, 95% CI: 1.67-7.42). Our results indicate that a low-dose RUTF protocol, combined with specific measures to ensure good service quality and beneficiary support, was successful in treating uncomplicated SAM in this setting. This programmatic experience should be validated by randomised studies aiming to test, quantify and attribute the effect of the protocol adaptation and programme improvements presented here.

  13. Low–dose RUTF protocol and improved service delivery lead to good programme outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar

    PubMed Central

    James, Philip T; Van den Briel, Natalie; Rozet, Aurélie; Israël, Anne-Dominique; Fenn, Bridget; Navarro-Colorado, Carlos

    2015-01-01

    The treatment of uncomplicated severe acute malnutrition (SAM) requires substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was adopted. In this protocol, RUTF was dosed according to beneficiary's body weight, until the child reached a Weight-for-Height z-score of ≥−3 and mid-upper arm circumference ≥110 mm. From this point, the child received a fixed quantity of RUTF per day, independent of body weight until discharge. Specific measures were implemented as part of this low-dose RUTF protocol in order to improve service quality and beneficiary support. We analysed individual records of 3083 children treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0% defaulted and 0.9% were classified as non-responders. No deaths were recorded. Among children who recovered, median [IQR] length of stay and weight gain were 42 days [28; 56] and 4.0 g kg–1 day–1 [3.0; 5.7], respectively. Multivariable logistic regression showed that children older than 48 months had higher odds of non-response to treatment than younger children (adjusted odds ratio: 3.51, 95% CI: 1.67–7.42). Our results indicate that a low-dose RUTF protocol, combined with specific measures to ensure good service quality and beneficiary support, was successful in treating uncomplicated SAM in this setting. This programmatic experience should be validated by randomised studies aiming to test, quantify and attribute the effect of the protocol adaptation and programme improvements presented here. PMID:25850698

  14. Low-dose RUTF protocol and improved service delivery lead to good programme outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar.

    PubMed

    James, Philip T; Van den Briel, Natalie; Rozet, Aurélie; Israël, Anne-Dominique; Fenn, Bridget; Navarro-Colorado, Carlos

    2015-10-01

    The treatment of uncomplicated severe acute malnutrition (SAM) requires substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was adopted. In this protocol, RUTF was dosed according to beneficiary's body weight, until the child reached a Weight-for-Height z-score of ≥-3 and mid-upper arm circumference ≥110 mm. From this point, the child received a fixed quantity of RUTF per day, independent of body weight until discharge. Specific measures were implemented as part of this low-dose RUTF protocol in order to improve service quality and beneficiary support. We analysed individual records of 3083 children treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0% defaulted and 0.9% were classified as non-responders. No deaths were recorded. Among children who recovered, median [IQR] length of stay and weight gain were 42 days [28; 56] and 4.0 g kg(-1) day(-1) [3.0; 5.7], respectively. Multivariable logistic regression showed that children older than 48 months had higher odds of non-response to treatment than younger children (adjusted odds ratio: 3.51, 95% CI: 1.67-7.42). Our results indicate that a low-dose RUTF protocol, combined with specific measures to ensure good service quality and beneficiary support, was successful in treating uncomplicated SAM in this setting. This programmatic experience should be validated by randomised studies aiming to test, quantify and attribute the effect of the protocol adaptation and programme improvements presented here. PMID:25850698

  15. Novel in vivo imaging analysis of an inner ear drug delivery system: Drug availability in inner ear following different dose of systemic drug injections.

    PubMed

    Kanzaki, Sho; Watanabe, Kotaro; Fujioka, Masato; Shibata, Shinsuke; Nakamura, Masaya; Okano, Hirotaka James; Okano, Hideyuki; Ogawa, Kaoru

    2015-12-01

    Systemic application of drugs is commonly used in clinical situations. Some of these drugs are ototoxic. Since there are few studies on in vivo monitoring of drug delivery dynamics, the time course or bioavailability of drugs in the inner ear of live animals following systemic drug application remains unknown. For instance, it is unknown whether the volume of a drug delivered systemically correlates with its inner ear pharmacokinetics. We previously established a new in vivo imaging system to monitor drug delivery in live mice. In the present study, we used this system to compare drug concentration in the inner ear over time after systemic drug injections. We used transgenic GFAP-Luc mice that harbor a firefly luciferase gene expression cassette regulated by 12 kb of murine GFAP promoter and human beta-globin intron 2. Luciferin delivered into the inner ear of these mice reacts with luciferase, and the resulting signals are detected in GFAP-expressing cells in the cochlear nerve. Thus, we assessed in the inner ear the intensity and duration of luciferin/luciferase signals after systemic injections of different volumes of luciferin. An IVIS(®) imaging system was used to observe signals, and these signals were compared to the drug dynamics of luciferin delivered through subcutaneous (sc) injections. The volume of sc-injected drug correlated significantly with photon counts measured in the inner ear. Photons were detected almost immediately after injection, peaking 20 min after injection. Drug concentration did not affect inner ear signals. Luciferin injected systemically appeared in the inner ear between highest and lowest concentration. Drug volume is an important parameter to know if the inner ear requires a higher level of the drug. We observed that it is the volume of a drug-not its concentration-that is the important factor. Indeed, the more volume of a drug injected systemically increased the concentration of that drug in the inner ear. This study provides a

  16. Curtailing patient-specific IMRT QA procedures from 2D dose error distribution

    PubMed Central

    Kurosu, Keita; Sumida, Iori; Mizuno, Hirokazu; Otani, Yuki; Oda, Michio; Isohashi, Fumiaki; Seo, Yuji; Suzuki, Osamu; Ogawa, Kazuhiko

    2016-01-01

    A patient-specific quality assurance (QA) test is conducted to verify the accuracy of dose delivery. It generally consists of three verification processes: the absolute point dose difference, the planar dose differences at each gantry angle, and the planar dose differences by 3D composite irradiation. However, this imposes a substantial workload on medical physicists. The objective of this study was to determine whether our novel method that predicts the 3D delivered dose allows certain patient-specific IMRT QAs to be curtailed. The object was IMRT QA for the pelvic region with regard to point dose and composite planar dose differences. We compared measured doses, doses calculated in the treatment planning system, and doses predicted by in-house software. The 3D predicted dose was reconstructed from the per-field measurement by incorporating the relative dose error distribution into the original dose grid of each beam. All point dose differences between the measured and the calculated dose were within ±3%, whereas 93.3% of them between the predicted and the calculated dose were within ±3%. As for planar dose differences, the gamma passing rates between the calculated and the predicted dose were higher than those between the calculated and the measured dose. Comparison and statistical analysis revealed a correlation between the predicted and the measured dose with regard to both point dose and planar dose differences. We concluded that the prediction-based approach is an accurate substitute for the conventional measurement-based approach in IMRT QA for the pelvic region. Our novel approach will help medical physicists save time on IMRT QA. PMID:26661854

  17. Dose profile measurements during respiratory-gated lung stereotactic radiotherapy: A phantom study

    NASA Astrophysics Data System (ADS)

    Jong, W. L.; Wong, J. H. D.; Ng, K. H.; Ung, N. M.

    2016-03-01

    During stereotactic body radiotherapy, high radiation dose (∼60 Gy) is delivered to the tumour in small fractionation regime. In this study, the dosimetric characteristics were studied using radiochromic film during respiratory-gated and non-gated lung stereotactic body radiotherapy (SBRT). Specifically, the effect of respiratory cycle and amplitude, as well as gating window on the dosimetry were studied. In this study, the dose profiles along the irradiated area were measured. The dose profiles for respiratory-gated radiation delivery with different respiratory or tumour motion amplitudes, gating windows and respiratory time per cycle were in agreement with static radiation delivery. The respiratory gating system was able to deliver the radiation dose accurately (±1.05 mm) in the longitudinal direction. Although the treatment time for respiratory-gated SBRT was prolonged, this approach can potentially reduce the margin for internal tumour volume without compromising the tumour coverage. In addition, the normal tissue sparing effect can be improved.

  18. How much does it cost to get a dose of vaccine to the service delivery location? Empirical evidence from Vietnam's Expanded Program on Immunization.

    PubMed

    Mvundura, Mercy; Kien, Vu Duy; Nga, Nguyen Tuyet; Robertson, Joanie; Cuong, Nguyen Van; Tung, Ho Thanh; Hong, Duong Thi; Levin, Carol

    2014-02-01

    Few studies document the costs of operating vaccine supply chains, but decision-makers need this information to inform cost projections for investments to accommodate new vaccine introduction. This paper presents empirical estimates of vaccine supply chain costs for Vietnam's Expanded Program on Immunization (EPI) for routine vaccines at each level of the supply chain, before and after the introduction of the pentavalent vaccine. We used micro-costing methods to collect resource-use data associated with storage and transportation of vaccines and immunization supplies at the national store, the four regional stores, and a sample of provinces, districts, and commune health centers. We collected stock ledger data on the total number of doses of vaccines handled by each facility during the assessment year. Total supply chain costs were estimated at approximately US$65,000 at the national store and an average of US$39,000 per region, US$5800 per province, US$2200 per district, and US$300 per commune health center. Across all levels, cold chain equipment capital costs and labor were the largest drivers of costs. The cost per dose delivered was estimated at US$0.19 before the introduction of pentavalent and US$0.24 cents after introduction. At commune health centers, supply chain costs were 104% of the value of vaccines before introduction of pentavalent vaccine and 24% after introduction, mainly due to the higher price per dose of the pentavalent vaccine. The aggregated costs at the last tier of the health system can be substantial because of the large number of facilities. Even in countries with high-functioning systems, empirical evidence on current costs from all levels of the system can help estimate resource requirements for expanding and strengthening resources to meet future immunization program needs. Other low- and middle-income countries can benefit from similar studies, in view of new vaccine introductions that will put strains on existing systems. PMID

  19. Dynamically accumulated dose and 4D accumulated dose for moving tumors

    SciTech Connect

    Li Heng; Li Yupeng; Zhang Xiaodong; Li Xiaoqiang; Liu Wei; Gillin, Michael T.; Zhu, X. Ronald

    2012-12-15

    Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove the principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference

  20. Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement.

    PubMed

    Crawford, Keith W; Ripin, David H Brown; Levin, Andrew D; Campbell, Jennifer R; Flexner, Charles

    2012-07-01

    It is expected that funding limitations for worldwide HIV treatment and prevention in resource-limited settings will continue, and, because the need for treatment scale-up is urgent, the emphasis on value for money has become an increasing priority. The Conference on Antiretroviral Drug Optimization--a collaborative project between the Clinton Health Access Initiative, the Johns Hopkins University School of Medicine, and the Bill & Melinda Gates Foundation--brought together process chemists, clinical pharmacologists, pharmaceutical scientists, physicians, pharmacists, and regulatory specialists to explore strategies for the reduction of antiretroviral drug costs. The antiretroviral drugs discussed were prioritised for consideration on the basis of their market impact, and the objectives of the conference were framed as discussion questions generated to guide scientific assessment of potential strategies. These strategies included modifications to the synthesis of the active pharmaceutical ingredient (API) and use of cheaper sources of raw materials in synthesis of these ingredients. Innovations in product formulation could improve bioavailability thus needing less API. For several antiretroviral drugs, studies show efficacy is maintained at doses below the approved dose (eg, efavirenz, lopinavir plus ritonavir, atazanavir, and darunavir). Optimising pharmacoenhancement and extending shelf life are additional strategies. The conference highlighted a range of interventions; optimum cost savings could be achieved through combining approaches. PMID:22742638

  1. Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement.

    PubMed

    Crawford, Keith W; Ripin, David H Brown; Levin, Andrew D; Campbell, Jennifer R; Flexner, Charles

    2012-07-01

    It is expected that funding limitations for worldwide HIV treatment and prevention in resource-limited settings will continue, and, because the need for treatment scale-up is urgent, the emphasis on value for money has become an increasing priority. The Conference on Antiretroviral Drug Optimization--a collaborative project between the Clinton Health Access Initiative, the Johns Hopkins University School of Medicine, and the Bill & Melinda Gates Foundation--brought together process chemists, clinical pharmacologists, pharmaceutical scientists, physicians, pharmacists, and regulatory specialists to explore strategies for the reduction of antiretroviral drug costs. The antiretroviral drugs discussed were prioritised for consideration on the basis of their market impact, and the objectives of the conference were framed as discussion questions generated to guide scientific assessment of potential strategies. These strategies included modifications to the synthesis of the active pharmaceutical ingredient (API) and use of cheaper sources of raw materials in synthesis of these ingredients. Innovations in product formulation could improve bioavailability thus needing less API. For several antiretroviral drugs, studies show efficacy is maintained at doses below the approved dose (eg, efavirenz, lopinavir plus ritonavir, atazanavir, and darunavir). Optimising pharmacoenhancement and extending shelf life are additional strategies. The conference highlighted a range of interventions; optimum cost savings could be achieved through combining approaches.

  2. Direct dose mapping versus energy/mass transfer mapping for 4D dose accumulation: fundamental differences and dosimetric consequences

    NASA Astrophysics Data System (ADS)

    Li, Haisen S.; Zhong, Hualiang; Kim, Jinkoo; Glide-Hurst, Carri; Gulam, Misbah; Nurushev, Teamour S.; Chetty, Indrin J.

    2014-01-01

    The direct dose mapping (DDM) and energy/mass transfer (EMT) mapping are two essential algorithms for accumulating the dose from different anatomic phases to the reference phase when there is organ motion or tumor/tissue deformation during the delivery of radiation therapy. DDM is based on interpolation of the dose values from one dose grid to another and thus lacks rigor in defining the dose when there are multiple dose values mapped to one dose voxel in the reference phase due to tissue/tumor deformation. On the other hand, EMT counts the total energy and mass transferred to each voxel in the reference phase and calculates the dose by dividing the energy by mass. Therefore it is based on fundamentally sound physics principles. In this study, we implemented the two algorithms and integrated them within the Eclipse treatment planning system. We then compared the clinical dosimetric difference between the two algorithms for ten lung cancer patients receiving stereotactic radiosurgery treatment, by accumulating the delivered dose to the end-of-exhale (EE) phase. Specifically, the respiratory period was divided into ten phases and the dose to each phase was calculated and mapped to the EE phase and then accumulated. The displacement vector field generated by Demons-based registration of the source and reference images was used to transfer the dose and energy. The DDM and EMT algorithms produced noticeably different cumulative dose in the regions with sharp mass density variations and/or high dose gradients. For the planning target volume (PTV) and internal target volume (ITV) minimum dose, the difference was up to 11% and 4% respectively. This suggests that DDM might not be adequate for obtaining an accurate dose distribution of the cumulative plan, instead, EMT should be considered.

  3. Convection-enhanced delivery of Ls-TPT enables an effective, continuous, low-dose chemotherapy against malignant glioma xenograft model.

    PubMed

    Saito, Ryuta; Krauze, Michal T; Noble, Charles O; Drummond, Daryl C; Kirpotin, Dmitri B; Berger, Mitchel S; Park, John W; Bankiewicz, Krystof S

    2006-07-01

    Treatment of malignant gliomas represents one of the most formidable challenges in oncology. The combination of surgery, radiation, and chemotherapy yields median survivals of less than one year. Here we demonstrate the use of a minimally invasive surgical technique, convection-enhanced delivery (CED), for local administration of a novel nanoparticle liposome containing topotecan. CED of this liposomal topotecan (Ls-TPT) resulted in extended brain tissue retention (t1/2 = 1.5 days), whereas free topotecan was rapidly cleared (t1/2 = 0.1 days) after CED. The favorable pharmacokinetic profile of extended topotecan release for about seven days, along with biodistribution featuring perivascular accumulation of the nanoparticles, provided, in addition to the known topoisomerase I inhibition, an effective antiangiogenic therapy. In the rat intracranial U87MG tumor model, vascular targeting of Ls-TPT with CED was associated with reductions in laminin expression and vascular density compared to free topotecan or control treatments. A single CED treatment on day 7 showed that free topotecan conferred no survival benefit versus control. However, Ls-TPT produced a significant (P = 0.0002) survival benefit, with six of seven complete cures. Larger U87MG tumors, where CED of Ls-TPT on day 12 resulted in one of six cures, indicated the necessity to cover the entire tumor with the infused therapeutic agent. CED of Ls-TPT was also efficacious in the intracranial U251MG tumor model (P = 0.0005 versus control). We conclude that the combination of a novel nanoparticle Ls-TPT and CED administration was very effective in treating experimental brain tumors.

  4. Delivery Systems.

    ERIC Educational Resources Information Center

    Hutchison, Betty

    This paper on delivery systems for preparing and training early childhood educators focuses on three main topics: (1) adequacy of delivery systems and access; (2) market influences on delivery systems; and (3) linking preparation and professional development components. Questions addressed include the following: Would the current preparation and…

  5. Feasibility study of volumetric modulated arc therapy with constant dose rate for endometrial cancer

    SciTech Connect

    Yang, Ruijie; Wang, Junjie; Xu, Feng; Li, Hua; Zhang, Xile

    2013-10-01

    To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. The nine-field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V{sub 20} of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability.

  6. Nanomedicine in pulmonary delivery

    PubMed Central

    Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

    2009-01-01

    The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

  7. Accurate monotone cubic interpolation

    NASA Technical Reports Server (NTRS)

    Huynh, Hung T.

    1991-01-01

    Monotone piecewise cubic interpolants are simple and effective. They are generally third-order accurate, except near strict local extrema where accuracy degenerates to second-order due to the monotonicity constraint. Algorithms for piecewise cubic interpolants, which preserve monotonicity as well as uniform third and fourth-order accuracy are presented. The gain of accuracy is obtained by relaxing the monotonicity constraint in a geometric framework in which the median function plays a crucial role.

  8. Accurate Finite Difference Algorithms

    NASA Technical Reports Server (NTRS)

    Goodrich, John W.

    1996-01-01

    Two families of finite difference algorithms for computational aeroacoustics are presented and compared. All of the algorithms are single step explicit methods, they have the same order of accuracy in both space and time, with examples up to eleventh order, and they have multidimensional extensions. One of the algorithm families has spectral like high resolution. Propagation with high order and high resolution algorithms can produce accurate results after O(10(exp 6)) periods of propagation with eight grid points per wavelength.

  9. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  10. Fast convolution-superposition dose calculation on graphics hardware.

    PubMed

    Hissoiny, Sami; Ozell, Benoît; Després, Philippe

    2009-06-01

    The numerical calculation of dose is central to treatment planning in radiation therapy and is at the core of optimization strategies for modern delivery techniques. In a clinical environment, dose calculation algorithms are required to be accurate and fast. The accuracy is typically achieved through the integration of patient-specific data and extensive beam modeling, which generally results in slower algorithms. In order to alleviate execution speed problems, the authors have implemented a modern dose calculation algorithm on a massively parallel hardware architecture. More specifically, they have implemented a convolution-superposition photon beam dose calculation algorithm on a commodity graphics processing unit (GPU). They have investigated a simple porting scenario as well as slightly more complex GPU optimization strategies. They have achieved speed improvement factors ranging from 10 to 20 times with GPU implementations compared to central processing unit (CPU) implementations, with higher values corresponding to larger kernel and calculation grid sizes. In all cases, they preserved the numerical accuracy of the GPU calculations with respect to the CPU calculations. These results show that streaming architectures such as GPUs can significantly accelerate dose calculation algorithms and let envision benefits for numerically intensive processes such as optimizing strategies, in particular, for complex delivery techniques such as IMRT and are therapy.

  11. Fast motion-including dose error reconstruction for VMAT with and without MLC tracking.

    PubMed

    Ravkilde, Thomas; Keall, Paul J; Grau, Cai; Høyer, Morten; Poulsen, Per R

    2014-12-01

    Multileaf collimator (MLC) tracking is a promising and clinically emerging treatment modality for radiotherapy of mobile tumours. Still, new quality assurance (QA) methods are warranted to safely introduce MLC tracking in the clinic. The purpose of this study was to create and experimentally validate a simple model for fast motion-including dose error reconstruction applicable to intrafractional QA of MLC tracking treatments of moving targets.MLC tracking experiments were performed on a standard linear accelerator with prototype MLC tracking software guided by an electromagnetic transponder system. A three-axis motion stage reproduced eight representative tumour trajectories; four lung and four prostate. Low and high modulation 6 MV single-arc volumetric modulated arc therapy treatment plans were delivered for each trajectory with and without MLC tracking, as well as without motion for reference. Temporally resolved doses were measured during all treatments using a biplanar dosimeter. Offline, the dose delivered to each of 1069 diodes in the dosimeter was reconstructed with 500 ms temporal resolution by a motion-including pencil beam convolution algorithm developed in-house. The accuracy of the algorithm for reconstruction of dose and motion-induced dose errors throughout the tracking and non-tracking beam deliveries was quantified. Doses were reconstructed with a mean dose difference relative to the measurements of-0.5% (5.5% standard deviation) for cumulative dose. More importantly, the root-mean-square deviation between reconstructed and measured motion-induced 3%/3 mm γ failure rates (dose error) was 2.6%. The mean computation time for each calculation of dose and dose error was 295 ms. The motion-including dose reconstruction allows accurate temporal and spatial pinpointing of errors in absorbed dose and is adequately fast to be feasible for online use. An online implementation could allow treatment intervention in case of erroneous dose delivery in both

  12. Computing proton dose to irregularly moving targets

    NASA Astrophysics Data System (ADS)

    Phillips, Justin; Gueorguiev, Gueorgui; Shackleford, James A.; Grassberger, Clemens; Dowdell, Stephen; Paganetti, Harald; Sharp, Gregory C.

    2014-08-01

    Purpose: While four-dimensional computed tomography (4DCT) and deformable registration can be used to assess the dose delivered to regularly moving targets, there are few methods available for irregularly moving targets. 4DCT captures an idealized waveform, but human respiration during treatment is characterized by gradual baseline shifts and other deviations from a periodic signal. This paper describes a method for computing the dose delivered to irregularly moving targets based on 1D or 3D waveforms captured at the time of delivery. Methods: The procedure uses CT or 4DCT images for dose calculation, and 1D or 3D respiratory waveforms of the target position at time of delivery. Dose volumes are converted from their Cartesian geometry into a beam-specific radiological depth space, parameterized in 2D by the beam aperture, and longitudinally by the radiological depth. In this new frame of reference, the proton doses are translated according to the motion found in the 1D or 3D trajectory. These translated dose volumes are weighted and summed, then transformed back into Cartesian space, yielding an estimate of the dose that includes the effect of the measured breathing motion. The method was validated using a synthetic lung phantom and a single representative patient CT. Simulated 4DCT was generated for the phantom with 2 cm peak-to-peak motion. Results: A passively-scattered proton treatment plan was generated using 6 mm and 5 mm smearing for the phantom and patient plans, respectively. The method was tested without motion, and with two simulated breathing signals: a 2 cm amplitude sinusoid, and a 2 cm amplitude sinusoid with 3 cm linear drift in the phantom. The tumor positions were equally weighted for the patient calculation. Motion-corrected dose was computed based on the mid-ventilation CT image in the phantom and the peak exhale position in the patient. Gamma evaluation was 97.8% without motion, 95.7% for 2 cm sinusoidal motion, 95.7% with 3 cm drift in the

  13. Computing Proton Dose to Irregularly Moving Targets

    PubMed Central

    Phillips, Justin; Gueorguiev, Gueorgui; Shackleford, James A.; Grassberger, Clemens; Dowdell, Stephen; Paganetti, Harald; Sharp, Gregory C.

    2014-01-01

    Purpose While four-dimensional computed tomography (4DCT) and deformable registration can be used to assess the dose delivered to regularly moving targets, there are few methods available for irregularly moving targets. 4DCT captures an idealized waveform, but human respiration during treatment is characterized by gradual baseline shifts and other deviations from a periodic signal. This paper describes a method for computing the dose delivered to irregularly moving targets based on 1D or 3D waveforms captured at the time of delivery. Methods The procedure uses CT or 4DCT images for dose calculation, and 1D or 3D respiratory waveforms of the target position at time of delivery. Dose volumes are converted from their Cartesian geometry into a beam-specific radiological depth space, parameterized in 2D by the beam aperture, and longitudinally by the radiological depth. In this new frame of reference, the proton doses are translated according to the motion found in the 1D or 3D trajectory. These translated dose volumes are weighted and summed, then transformed back into Cartesian space, yielding an estimate of the dose that includes the effect of the measured breathing motion. The method was validated using a synthetic lung phantom and a single representative patient CT. Simulated 4DCT was generated for the phantom with 2 cm peak-to-peak motion. Results A passively-scattered proton treatment plan was generated using 6 mm and 5 mm smearing for the phantom and patient plans, respectively. The method was tested without motion, and with two simulated breathing signals: a 2 cm amplitude sinusoid, and a 2 cm amplitude sinusoid with 3 cm linear drift in the phantom. The tumor positions were equally weighted for the patient calculation. Motion-corrected dose was computed based on the mid-ventilation CT image in the phantom and the peak exhale position in the patient. Gamma evaluation was 97.8% without motion, 95.7% for 2 cm sinusoidal motion, and 95.7% with 3 cm drift in the

  14. Synchronized dynamic dose reconstruction

    SciTech Connect

    Litzenberg, Dale W.; Hadley, Scott W.; Tyagi, Neelam; Balter, James M.; Ten Haken, Randall K.; Chetty, Indrin J.

    2007-01-15

    Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined.

  15. An algorithm to calculate a collapsed arc dose matrix in volumetric modulated arc therapy

    SciTech Connect

    Arumugam, Sankar; Xing Aitang; Jameson, Michael; Holloway, Lois

    2013-07-15

    Purpose: The delivery of volumetric modulated arc therapy (VMAT) is more complex than other conformal radiotherapy techniques. In this work, the authors present the feasibility of performing routine verification of VMAT delivery using a dose matrix measured by a gantry mounted 2D ion chamber array and corresponding dose matrix calculated by an inhouse developed algorithm.Methods: Pinnacle, v9.0, treatment planning system (TPS) was used in this study to generate VMAT plans for a 6 MV photon beam from an Elekta-Synergy linear accelerator. An algorithm was developed and implemented with inhouse computer code to calculate the dose matrix resulting from a VMAT arc in a plane perpendicular to the beam at isocenter. The algorithm was validated using measurement of standard patterns and clinical VMAT plans with a 2D ion chamber array. The clinical VMAT plans were also validated using ArcCHECK measurements. The measured and calculated dose matrices were compared using gamma ({gamma}) analysis with 3%/3 mm criteria and {gamma} tolerance of 1.Results: The dose matrix comparison of standard patterns has shown excellent agreement with the mean {gamma} pass rate 97.7 ({sigma}= 0.4)%. The validation of clinical VMAT plans using the dose matrix predicted by the algorithm and the corresponding measured dose matrices also showed good agreement with the mean {gamma} pass rate of 97.6 ({sigma}= 1.6)%. The validation of clinical VMAT plans using ArcCHECK measurements showed a mean pass rate of 95.6 ({sigma}= 1.8)%.Conclusions: The developed algorithm was shown to accurately predict the dose matrix, in a plane perpendicular to the beam, by considering all possible leaf trajectories in a VMAT delivery. This enables the verification of VMAT delivery using a 2D array detector mounted on a treatment head.

  16. VMAT linear accelerator commissioning and quality assurance: dose control and gantry speed tests.

    PubMed

    Barnes, Michael P; Rowshanfarzad, Pejman; Greer, Peter B

    2016-01-01

    In VMAT treatment delivery the ability of the linear accelerator (linac) to accurately control dose versus gantry angle is critical to delivering the plan correctly. A new VMAT test delivery was developed to specifically test the dose versus gantry angle with the full range of allowed gantry speeds and dose rates. The gantry-mounted IBA MatriXX with attached inclinometer was used in movie mode to measure the instantaneous relative dose versus gantry angle during the plan every 0.54 s. The results were compared to the expected relative dose at each gantry angle calculated from the plan. The same dataset was also used to compare the instantaneous gan-try speeds throughout the delivery compared to the expected gantry speeds from the plan. Measurements performed across four linacs generally show agreement between measurement and plan to within 1.5% in the constant dose rate regions and dose rate modulation within 0.1 s of the plan. Instantaneous gantry speed was measured to be within 0.11°/s of the plan (1 SD). An error in one linac was detected in that the nominal gantry speed was incorrectly calibrated. This test provides a practical method to quality-assure critical aspects of VMAT delivery including dose versus gantry angle and gantry speed control. The method can be performed with any detector that can acquire time-resolved dosimetric information that can be synchronized with a measurement of gantry angle. The test fulfils several of the aims of the recent Netherlands Commission on Radiation Dosimetry (NCS) Report 24, which provides recommendations for comprehensive VMAT quality assurance. PMID:27167282

  17. Accurate quantum chemical calculations

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

    1989-01-01

    An important goal of quantum chemical calculations is to provide an understanding of chemical bonding and molecular electronic structure. A second goal, the prediction of energy differences to chemical accuracy, has been much harder to attain. First, the computational resources required to achieve such accuracy are very large, and second, it is not straightforward to demonstrate that an apparently accurate result, in terms of agreement with experiment, does not result from a cancellation of errors. Recent advances in electronic structure methodology, coupled with the power of vector supercomputers, have made it possible to solve a number of electronic structure problems exactly using the full configuration interaction (FCI) method within a subspace of the complete Hilbert space. These exact results can be used to benchmark approximate techniques that are applicable to a wider range of chemical and physical problems. The methodology of many-electron quantum chemistry is reviewed. Methods are considered in detail for performing FCI calculations. The application of FCI methods to several three-electron problems in molecular physics are discussed. A number of benchmark applications of FCI wave functions are described. Atomic basis sets and the development of improved methods for handling very large basis sets are discussed: these are then applied to a number of chemical and spectroscopic problems; to transition metals; and to problems involving potential energy surfaces. Although the experiences described give considerable grounds for optimism about the general ability to perform accurate calculations, there are several problems that have proved less tractable, at least with current computer resources, and these and possible solutions are discussed.

  18. Radiation delivery system and method

    DOEpatents

    Sorensen, Scott A.; Robison, Thomas W.; Taylor, Craig M. V.

    2002-01-01

    A radiation delivery system and method are described. The system includes a treatment configuration such as a stent, balloon catheter, wire, ribbon, or the like, a portion of which is covered with a gold layer. Chemisorbed to the gold layer is a radiation-emitting self-assembled monolayer or a radiation-emitting polymer. The radiation delivery system is compatible with medical catheter-based technologies to provide a therapeutic dose of radiation to a lesion following an angioplasty procedure.

  19. Image-guided radiation therapy for treatment delivery and verification

    NASA Astrophysics Data System (ADS)

    Schubert, Leah Kayomi

    Target conformity and normal tissue sparing provided by modern radiation therapy techniques often result in steep dose gradients, which increase the need for more accurate patient setup and treatment delivery. Image guidance is starting to play a major role in determining the accuracy of treatment setup. A typical objective of image-guided radiation therapy (IGRT) is to minimize differences between planned and delivered treatment by imaging the patient prior to delivery. This step verifies and corrects for patient setup and is referred to as setup verification. This dissertation evaluates the efficacy of daily imaging for setup verification and investigates new uses of IGRT for potential improvements in treatment delivery. The necessity of daily imaging can first be determined by assessing differences in setup corrections between patient groups. Therefore, the first objective of this investigation was to evaluate the application of IGRT for setup verification by quantifying differences in patient positioning for several anatomical disease sites. Detailed analysis of setup corrections for brain, head and neck, lung, and prostate treatments is presented. In this analysis, large setup errors were observed for prostate treatments. Further assessment of prostate treatments was performed, and patient-specific causes of setup errors investigated. Setup corrections are applied via rigid shifts or rotations of the patient or machine, but anatomical deformations occur for which rigid shifts cannot correct. Fortunately, IGRT provides images on which anatomical changes occurring throughout the course of treatment can be detected. From those images, the efficacy of IGRT in ensuring accurate treatment delivery can be evaluated and improved by determining delivered doses and adapting the plan during treatment. The second objective of this dissertation was to explore new applications of IGRT to further improve treatment. By utilizing daily IGRT images, a retrospective analysis of

  20. Neutron dose equivalent meter

    DOEpatents

    Olsher, Richard H.; Hsu, Hsiao-Hua; Casson, William H.; Vasilik, Dennis G.; Kleck, Jeffrey H.; Beverding, Anthony

    1996-01-01

    A neutron dose equivalent detector for measuring neutron dose capable of accurately responding to neutron energies according to published fluence to dose curves. The neutron dose equivalent meter has an inner sphere of polyethylene, with a middle shell overlying the inner sphere, the middle shell comprising RTV.RTM. silicone (organosiloxane) loaded with boron. An outer shell overlies the middle shell and comprises polyethylene loaded with tungsten. The neutron dose equivalent meter defines a channel through the outer shell, the middle shell, and the inner sphere for accepting a neutron counter tube. The outer shell is loaded with tungsten to provide neutron generation, increasing the neutron dose equivalent meter's response sensitivity above 8 MeV.

  1. Electronic compensation technique to deliver a total body dose

    NASA Astrophysics Data System (ADS)

    Lakeman, Tara E.

    Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been conventionally used to compensate for the varying thickness throughout the body in large-field TBI. The goal of this study is to pursue utilizing the modern electronic compensation technique to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the electronic compensation to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Each treatment plan includes two pair of parallel opposed fields. One pair of large fields is used to encompass the majority of the patient's anatomy. The other pair are very small open fields focused only on the thin bottom portion of the patient's anatomy, which requires much less radiation than the rest of the body to reach 100% of the prescribed dose. A desirable fluence pattern was manually painted within each of the larger fields for each patient to provide a more uniform distribution. Results: Dose-volume histograms (DVH) were calculated for evaluating the electronic compensation technique. In the electronically compensated plans, the maximum body doses calculated from the DVH were reduced from the conventionally-compensated plans by an average of 15%, indicating a more uniform dose. The mean body doses calculated from the electronically compensated DVH remained comparable to that of the conventionally-compensated plans, indicating an accurate delivery of the prescription dose using electronic compensation. All calculated monitor units were within clinically acceptable limits. Conclusion: Electronic compensation technique for TBI will not increase the beam on time beyond clinically acceptable limits while it can substantially reduce the compensator setup

  2. Accurate Optical Reference Catalogs

    NASA Astrophysics Data System (ADS)

    Zacharias, N.

    2006-08-01

    Current and near future all-sky astrometric catalogs on the ICRF are reviewed with the emphasis on reference star data at optical wavelengths for user applications. The standard error of a Hipparcos Catalogue star position is now about 15 mas per coordinate. For the Tycho-2 data it is typically 20 to 100 mas, depending on magnitude. The USNO CCD Astrograph Catalog (UCAC) observing program was completed in 2004 and reductions toward the final UCAC3 release are in progress. This all-sky reference catalogue will have positional errors of 15 to 70 mas for stars in the 10 to 16 mag range, with a high degree of completeness. Proper motions for the about 60 million UCAC stars will be derived by combining UCAC astrometry with available early epoch data, including yet unpublished scans of the complete set of AGK2, Hamburg Zone astrograph and USNO Black Birch programs. Accurate positional and proper motion data are combined in the Naval Observatory Merged Astrometric Dataset (NOMAD) which includes Hipparcos, Tycho-2, UCAC2, USNO-B1, NPM+SPM plate scan data for astrometry, and is supplemented by multi-band optical photometry as well as 2MASS near infrared photometry. The Milli-Arcsecond Pathfinder Survey (MAPS) mission is currently being planned at USNO. This is a micro-satellite to obtain 1 mas positions, parallaxes, and 1 mas/yr proper motions for all bright stars down to about 15th magnitude. This program will be supplemented by a ground-based program to reach 18th magnitude on the 5 mas level.

  3. Dose-calculation algorithms in the context of inhomogeneity corrections for high energy photon beams

    SciTech Connect

    Papanikolaou, Niko; Stathakis, Sotirios

    2009-10-15

    Radiation therapy has witnessed a plethora of innovations and developments in the past 15 years. Since the introduction of computed tomography for treatment planning there has been a steady introduction of new methods to refine treatment delivery. Imaging continues to be an integral part of the planning, but also the delivery, of modern radiotherapy. However, all the efforts of image guided radiotherapy, intensity-modulated planning and delivery, adaptive radiotherapy, and everything else that we pride ourselves in having in the armamentarium can fall short, unless there is an accurate dose-calculation algorithm. The agreement between the calculated and delivered doses is of great significance in radiation therapy since the accuracy of the absorbed dose as prescribed determines the clinical outcome. Dose-calculation algorithms have evolved greatly over the years in an effort to be more inclusive of the effects that govern the true radiation transport through the human body. In this Vision 20/20 paper, we look back to see how it all started and where things are now in terms of dose algorithms for photon beams and the inclusion of tissue heterogeneities. Convolution-superposition algorithms have dominated the treatment planning industry for the past few years. Monte Carlo techniques have an inherent accuracy that is superior to any other algorithm and as such will continue to be the gold standard, along with measurements, and maybe one day will be the algorithm of choice for all particle treatment planning in radiation therapy.

  4. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    SciTech Connect

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory; Chu, Connel; Carver, Robert A.

    2013-02-15

    .62%, respectively, for the bolus ECT plans and 89.2% and 95.1%, respectively, for the mixed beam plans. For all regions, pass rates for the parotid and CW plans were 98.8% and 97.3%, respectively, for the bolus ECT plans and 97.5% and 95.9%, respectively, for the mixed beam plans. For the IMXT component of the mixed beam plans, pass rates for the parotid and CW plans were 93.7% and 95.8%. Conclusions: Bolus ECT and mixed beam therapy dose delivery to the phantom were more accurate than IMXT delivery, adding confidence to the use of planning, fabrication, and delivery for bolus ECT tools either alone or as part of mixed beam therapy. The methodology reported in this work could serve as a basis for future standardization of the commissioning of bolus ECT or mixed beam therapy. When applying this technology to patients, it is recommended that an electron dose algorithm more accurate than the pencil beam algorithm, e.g., a Monte Carlo algorithm or analytical transport such as the pencil beam redefinition algorithm, be used for planning to ensure the desired accuracy.

  5. A Monte Carlo tool for evaluating VMAT and DIMRT treatment deliveries including planar detectors.

    PubMed

    Asuni, G; van Beek, T A; Venkataraman, S; Popescu, I A; McCurdy, B M C

    2013-06-01

    , we defined an acceptable pass rate of >90% of percentage pixels with γ <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system.

  6. A Monte Carlo tool for evaluating VMAT and DIMRT treatment deliveries including planar detectors

    NASA Astrophysics Data System (ADS)

    Asuni, G.; van Beek, T. A.; Venkataraman, S.; Popescu, I. A.; McCurdy, B. M. C.

    2013-06-01

    , we defined an acceptable pass rate of >90% of percentage pixels with γ <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system.

  7. Improving Delivery Accuracy of Stereotactic Body Radiotherapy to a Moving Tumor Using Simplified Volumetric Modulated Arc Therapy

    PubMed Central

    Ko, Young Eun; Cho, Byungchul; Kim, Su Ssan; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Yi, Byongyong

    2016-01-01

    Purpose To develop a simplified volumetric modulated arc therapy (VMAT) technique for more accurate dose delivery in thoracic stereotactic body radiation therapy (SBRT). Methods and Materials For each of the 22 lung SBRT cases treated with respiratory-gated VMAT, a dose rate modulated arc therapy (DrMAT) plan was retrospectively generated. A dynamic conformal arc therapy plan with 33 adjoining coplanar arcs was designed and their beam weights were optimized by an inverse planning process. All sub-arc beams were converted into a series of control points with varying MLC segment and dose rates and merged into an arc beam for a DrMAT plan. The plan quality of original VMAT and DrMAT was compared in terms of target coverage, compactness of dose distribution, and dose sparing of organs at risk. To assess the delivery accuracy, the VMAT and DrMAT plans were delivered to a motion phantom programmed with the corresponding patients’ respiratory signal; results were compared using film dosimetry with gamma analysis. Results The plan quality of DrMAT was equivalent to that of VMAT in terms of target coverage, dose compactness, and dose sparing for the normal lung. In dose sparing for other critical organs, DrMAT was less effective than VMAT for the spinal cord, heart, and esophagus while being well within the limits specified by the Radiation Therapy Oncology Group. Delivery accuracy of DrMAT to a moving target was similar to that of VMAT using a gamma criterion of 2%/2mm but was significantly better using a 2%/1mm criterion, implying the superiority of DrMAT over VMAT in SBRT for thoracic/abdominal tumors with respiratory movement. Conclusion We developed a DrMAT technique for SBRT that produces plans of a quality similar to that achieved with VMAT but with better delivery accuracy. This technique is well-suited for small tumors with motion uncertainty. PMID:27333199

  8. [Definition of accurate planning target volume margins for esophageal cancer radiotherapy].

    PubMed

    Lesueur, P; Servagi-Vernat, S

    2016-10-01

    More than 4000 cases of esophagus neoplasms are diagnosed every year in France. Radiotherapy, which can be delivered in preoperative or exclusive with a concomitant chemotherapy, plays a central role in treatment of esophagus cancer. Even if efficacy of radiotherapy no longer has to be proved, the prognosis of esophagus cancer remains unfortunately poor with a high recurrence rate. Toxicity of esophageal radiotherapy is correlated with the irradiation volume, and limits dose escalation and local control. Esophagus is a deep thoracic organ, which undergoes cardiac and respiratory motion, making the radiotherapy delivery more difficult and increasing the planning target volume margins. Definition of accurate planning target volume margins, taking into account the esophagus' intrafraction motion and set up margins is very important to be sure to cover the clinical target volume and restrains acute and late radiotoxicity. In this article, based on a review of the literature, we propose planning target volume margins adapted to esophageal radiotherapy.

  9. Monte Carlo dose calculation in dental amalgam phantom.

    PubMed

    Aziz, Mohd Zahri Abdul; Yusoff, A L; Osman, N D; Abdullah, R; Rabaie, N A; Salikin, M S

    2015-01-01

    It has become a great challenge in the modern radiation treatment to ensure the accuracy of treatment delivery in electron beam therapy. Tissue inhomogeneity has become one of the factors for accurate dose calculation, and this requires complex algorithm calculation like Monte Carlo (MC). On the other hand, computed tomography (CT) images used in treatment planning system need to be trustful as they are the input in radiotherapy treatment. However, with the presence of metal amalgam in treatment volume, the CT images input showed prominent streak artefact, thus, contributed sources of error. Hence, metal amalgam phantom often creates streak artifacts, which cause an error in the dose calculation. Thus, a streak artifact reduction technique was applied to correct the images, and as a result, better images were observed in terms of structure delineation and density assigning. Furthermore, the amalgam density data were corrected to provide amalgam voxel with accurate density value. As for the errors of dose uncertainties due to metal amalgam, they were reduced from 46% to as low as 2% at d80 (depth of the 80% dose beyond Zmax) using the presented strategies. Considering the number of vital and radiosensitive organs in the head and the neck regions, this correction strategy is suggested in reducing calculation uncertainties through MC calculation.

  10. Patient dose and image quality from mega-voltage cone beam computed tomography imaging.

    PubMed

    Gayou, Olivier; Parda, David S; Johnson, Mark; Miften, Moyed

    2007-02-01

    The evolution of ever more conformal radiation delivery techniques makes the subject of accurate localization of increasing importance in radiotherapy. Several systems can be utilized including kilo-voltage and mega-voltage cone-beam computed tomography (MV-CBCT), CT on rail or helical tomography. One of the attractive aspects of mega-voltage cone-beam CT is that it uses the therapy beam along with an electronic portal imaging device to image the patient prior to the delivery of treatment. However, the use of a photon beam energy in the mega-voltage range for volumetric imaging degrades the image quality and increases the patient radiation dose. To optimize image quality and patient dose in MV-CBCT imaging procedures, a series of dose measurements in cylindrical and anthropomorphic phantoms using an ionization chamber, radiographic films, and thermoluminescent dosimeters was performed. Furthermore, the dependence of the contrast to noise ratio and spatial resolution of the image upon the dose delivered for a 20-cm-diam cylindrical phantom was evaluated. Depending on the anatomical site and patient thickness, we found that the minimum dose deposited in the irradiated volume was 5-9 cGy and the maximum dose was between 9 and 17 cGy for our clinical MV-CBCT imaging protocols. Results also demonstrated that for high contrast areas such as bony anatomy, low doses are sufficient for image registration and visualization of the three-dimensional boundaries between soft tissue and bony structures. However, as the difference in tissue density decreased, the dose required to identify soft tissue boundaries increased. Finally, the dose delivered by MV-CBCT was simulated using a treatment planning system (TPS), thereby allowing the incorporation of MV-CBCT dose in the treatment planning process. The TPS-calculated doses agreed well with measurements for a wide range of imaging protocols.

  11. Investigation of Advanced Dose Verification Techniques for External Beam Radiation Treatment

    NASA Astrophysics Data System (ADS)

    Asuni, Ganiyu Adeniyi

    Intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) have been introduced in radiation therapy to achieve highly conformal dose distributions around the tumour while minimizing dose to surrounding normal tissues. These techniques have increased the need for comprehensive quality assurance tests, to verify that customized patient treatment plans are accurately delivered during treatment. in vivo dose verification, performed during treatment delivery, confirms that the actual dose delivered is the same as the prescribed dose, helping to reduce treatment delivery errors. in vivo measurements may be accomplished using entrance or exit detectors. The objective of this project is to investigate a novel entrance detector designed for in vivo dose verification. This thesis is separated into three main investigations, focusing on a prototype entrance transmission detector (TRD) developed by IBA Dosimetry, Germany. First contaminant electrons generated by the TRD in a 6 MV photon beam were investigated using Monte Carlo (MC) simulation. This study demonstrates that modification of the contaminant electron model in the treatment planning system is required for accurate patient dose calculation in buildup regions when using the device. Second, the ability of the TRD to accurately measure dose from IMRT and VMAT was investigated by characterising the spatial resolution of the device. This was accomplished by measuring the point spread function with further validation provided by MC simulation. Comparisons of measured and calculated doses show that the spatial resolution of the TRD allows for measurement of clinical IMRT fields within acceptable tolerance. Finally, a new general research tool was developed to perform MC simulations for VMAT and IMRT treatments, simultaneously tracking dose deposition in both the patient CT geometry and an arbitrary planar detector system, generalized to handle either entrance or exit orientations. It was

  12. Two-dimensional inverse planning and delivery with a preclinical image guided microirradiator

    SciTech Connect

    Stewart, James M. P.; Lindsay, Patricia E.; Jaffray, David A.

    2013-10-15

    Purpose: Recent advances in preclinical radiotherapy systems have provided the foundation for scaling many of the elements of clinical radiation therapy practice to the dimensions and energy demanded in small animal studies. Such systems support the technical capabilities to accurately deliver highly complex dose distributions, but methods to optimize and deliver such distributions remain in their infancy. This study developed an optimization method based on empirically measured two-dimensional dose kernel measurements to deliver arbitrary planar dose distributions on a recently developed small animal radiotherapy platform.Methods: A two-dimensional dose kernel was measured with repeated radiochromic film measurements for the circular 1 mm diameter fixed collimator of the small animal radiotherapy system at 1 cm depth in a solid water phantom. This kernel was utilized in a sequential quadratic programming optimization framework to determine optimal beam positions and weights to deliver an arbitrary desired dose distribution. The positions and weights were then translated to a set of stage motions to automatically deliver the optimized dose distribution. End-to-end efficacy of the framework was quantified through five repeated deliveries of two dosimetric challenges: (1) a 5 mm radius bullseye distribution, and (2) a “sock” distribution contained within a 9 × 13 mm bounding box incorporating rectangular, semicircular, and exponentially decaying geometric constructs and a rectangular linear dose gradient region. These two challenges were designed to gauge targeting, geometric, and dosimetric fidelity.Results: Optimization of the bullseye and sock distributions required 2.1 and 5.9 min and utilized 50 and 77 individual beams for delivery, respectively. Automated delivery of the resulting optimized distributions, validated using radiochromic film measurements, revealed an average targeting accuracy of 0.32 mm, and a dosimetric delivery error along four line

  13. Temporal characterization and in vitro comparison of cell survival following the delivery of 3D-conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)

    NASA Astrophysics Data System (ADS)

    McGarry, Conor K.; Butterworth, Karl T.; Trainor, Colman; O'Sullivan, Joe M.; Prise, Kevin M.; Hounsell, Alan R.

    2011-04-01

    A phantom was designed and implemented for the delivery of treatment plans to cells in vitro. Single beam, 3D-conformal radiotherapy (3D-CRT) plans, inverse planned five-field intensity-modulated radiation therapy (IMRT), nine-field IMRT, single-arc volumetric modulated arc therapy (VMAT) and dual-arc VMAT plans were created on a CT scan of the phantom to deliver 3 Gy to the cell layer and verified using a Farmer chamber, 2D ionization chamber array and gafchromic film. Each plan was delivered to a 2D ionization chamber array to assess the temporal characteristics of the plan including delivery time and 'cell's eye view' for the central ionization chamber. The effective fraction time, defined as the percentage of the fraction time where any dose is delivered to each point examined, was also assessed across 120 ionization chambers. Each plan was delivered to human prostate cancer DU-145 cells and normal primary AGO-1522b fibroblast cells. Uniform beams were delivered to each cell line with the delivery time varying from 0.5 to 20.54 min. Effective fraction time was found to increase with a decreasing number of beams or arcs. For a uniform beam delivery, AGO-1552b cells exhibited a statistically significant trend towards increased survival with increased delivery time. This trend was not repeated when the different modulated clinical delivery methods were used. Less sensitive DU-145 cells did not exhibit a significant trend towards increased survival with increased delivery time for either the uniform or clinical deliveries. These results confirm that dose rate effects are most prevalent in more radiosensitive cells. Cell survival data generated from uniform beam deliveries over a range of dose rates and delivery times may not always be accurate in predicting response to more complex delivery techniques, such as IMRT and VMAT.

  14. Nanoparticle-based cancer treatment: can delivered dose and biological dose be reliably modeled and quantified?

    NASA Astrophysics Data System (ADS)

    Hoopes, P. Jack; Petryk, Alicia A.; Giustini, Andrew J.; Stigliano, Robert V.; D'Angelo, Robert N.; Tate, Jennifer A.; Cassim, Shiraz M.; Foreman, Allan; Bischof, John C.; Pearce, John A.; Ryan, Thomas

    2011-03-01

    the target cells/tissue, and an effective and matching alternating magnetic field (AMF) for optimal and safe excitation of the nanoparticles. Our initial studies have shown that appropriately delivered and targeted nanoparticles are capable of achieving effective tumor cytotoxicity at measured thermal doses significantly less than the understood thermal dose values necessary to achieve equivalent treatment effects using conventional heat delivery techniques. Therefore conventional CEM based thermal dose - tissues effect relationships will not hold for mNPH. The goal of this effort is to provide a platform for determining the biological and physical parameters that will be necessary for accurately planning and performing safe and effective mNPH, creating a new, viable primary or adjuvant cancer therapy.

  15. SU-E-J-89: Motion Effects On Organ Dose in Respiratory Gated Stereotactic Body Radiation Therapy

    SciTech Connect

    Wang, T; Zhu, L; Khan, M; Landry, J; Rajpara, R; Hawk, N

    2014-06-01

    Purpose: Existing reports on gated radiation therapy focus mainly on optimizing dose delivery to the target structure. This work investigates the motion effects on radiation dose delivered to organs at risk (OAR) in respiratory gated stereotactic body radiation therapy (SBRT). A new algorithmic tool of dose analysis is developed to evaluate the optimality of gating phase for dose sparing on OARs while ensuring adequate target coverage. Methods: Eight patients with pancreatic cancer were treated on a phase I prospective study employing 4DCT-based SBRT. For each patient, 4DCT scans are acquired and sorted into 10 respiratory phases (inhale-exhale- inhale). Treatment planning is performed on the average CT image. The average CT is spatially registered to other phases. The resultant displacement field is then applied on the plan dose map to estimate the actual dose map for each phase. Dose values of each voxel are fitted to a sinusoidal function. Fitting parameters of dose variation, mean delivered dose and optimal gating phase for each voxel over respiration cycle are mapped on the dose volume. Results: The sinusoidal function accurately models the dose change during respiratory motion (mean fitting error 4.6%). In the eight patients, mean dose variation is 3.3 Gy on OARs with maximum of 13.7 Gy. Two patients have about 100cm{sup 3} volumes covered by more than 5 Gy deviation. The mean delivered dose maps are similar to plan dose with slight deformation. The optimal gating phase highly varies across the patient, with phase 5 or 6 on about 60% of the volume, and phase 0 on most of the rest. Conclusion: A new algorithmic tool is developed to conveniently quantify dose deviation on OARs from plan dose during the respiratory cycle. The proposed software facilitates the treatment planning process by providing the optimal respiratory gating phase for dose sparing on each OAR.

  16. Bioresponsive matrices in drug delivery

    PubMed Central

    2010-01-01

    For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli. PMID:21114841

  17. Drug delivery to the ear.

    PubMed

    Hoskison, E; Daniel, M; Al-Zahid, S; Shakesheff, K M; Bayston, R; Birchall, J P

    2013-01-01

    Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drug delivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions.

  18. Establishment and validation of a method for multi-dose irradiation of cells in 96-well microplates

    SciTech Connect

    Abatzoglou, Ioannis; Zois, Christos E.; Pouliliou, Stamatia

    2013-02-15

    Highlights: ► We established a method for multi-dose irradiation of cell cultures within a 96-well plate. ► Equations to adjust to preferable dose levels are produced and provided. ► Up to eight different dose levels can be tested in one microplate. ► This method results in fast and reliable estimation of radiation dose–response curves. -- Abstract: Microplates are useful tools in chemistry, biotechnology and molecular biology. In radiobiology research, these can be also applied to assess the effect of a certain radiation dose delivered to the whole microplate, to test radio-sensitivity, radio-sensitization or radio-protection. Whether different radiation doses can be accurately applied to a single 96-well plate to further facilitate and accelerated research by one hand and spare funds on the other, is a question dealt in the current paper. Following repeated ion-chamber, TLD and radiotherapy planning dosimetry we established a method for multi-dose irradiation of cell cultures within a 96-well plate, which allows an accurate delivery of desired doses in sequential columns of the microplate. Up to eight different dose levels can be tested in one microplate. This method results in fast and reliable estimation of radiation dose–response curves.

  19. Persistent Expression of FLAG-tagged Micro dystrophin in Nonhuman Primates Following Intramuscular and Vascular Delivery

    PubMed Central

    Rodino-Klapac, Louise R; Montgomery, Chrystal L; Bremer, William G; Shontz, Kimberly M; Malik, Vinod; Davis, Nancy; Sprinkle, Spencer; Campbell, Katherine J; Sahenk, Zarife; Clark, K Reed; Walker, Christopher M; Mendell, Jerry R; Chicoine, Louis G

    2009-01-01

    Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct that encodes an eight amino-acid FLAG epitope at the C-terminus of micro-dystrophin to facilitate translational studies targeting DMD. Intramuscular (IM) injection of AAV8.MCK.micro-dys.FLAG in the tibialis anterior (TA) of macaques demonstrated robust gene expression, with muscle transduction (50–79%) persisting for up to 5 months. Success by IM injection was followed by targeted vascular delivery studies using a fluoroscopy-guided catheter threaded through the femoral artery. Three months after gene transfer, >80% of muscle fibers showed gene expression in the targeted muscle. No cellular immune response to AAV8 capsid, micro-dystrophin, or the FLAG tag was detected by interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) at any time point with either route. In summary, an epitope-tagged micro-dystrophin cassette enhances the ability to evaluate site-specific localization and distribution of gene expression in the NHP in preparation for vascular delivery clinical trials. PMID:19904237

  20. MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

    SciTech Connect

    Yang, D; Li, X; Li, H; Wooten, H; Green, O; Rodriguez, V; Mutic, S

    2014-06-15

    Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beam segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly chart

  1. Controlled delivery of antibodies from injectable hydrogels.

    PubMed

    Fletcher, Nathan A; Babcock, Lyndsey R; Murray, Ellen A; Krebs, Melissa D

    2016-02-01

    Therapeutic antibodies are currently used for the treatment of various diseases, but large doses delivered systemically are typically required. Localized controlled delivery techniques would afford major benefits such as decreasing side effects and required doses. Injectable biopolymer systems are an attractive solution due to their minimally invasive potential for controlled release in a localized area. Here, alginate-chitosan hydrogels are demonstrated to provide controlled delivery of IgG model antibodies and also of Fab antibody fragments. Also, an alternate delivery system comprised of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with antibodies and encapsulated in alginate was shown to successfully provide another level of control over release. These biopolymer systems that offer controlled delivery for antibodies and antibody fragments will be promising for many applications in drug delivery and regenerative medicine.

  2. Temporal compartmental dosing effects for robotic prostate stereotactic body radiotherapy

    NASA Astrophysics Data System (ADS)

    Shiao, Stephen L.; Sahgal, Arjun; Hu, Weigang; Jabbari, Siavash; Chuang, Cynthia; Descovich, Martina; Hsu, I.-Chow; Gottschalk, Alexander R.; Roach, Mack, III; Ma, Lijun

    2011-12-01

    The rate of dose accumulation within a given area of a target volume tends to vary significantly for non-isocentric delivery systems such as Cyberknife stereotactic body radiotherapy. In this study, we investigated whether intra-target temporal dose distributions produce significant variations in the biological equivalent dose. For the study, time courses of ten patients were reconstructed and calculation of a biologically equivalent uniform dose (EUD) was performed using a formula derived from the linear quadratic model (α/β = 3 for prostate cancer cells). The calculated EUD values obtained for the actual patient treatments were then compared with theoretical EUD values for delivering the same physical dose distribution except that the whole target being irradiated continuously (e.g. large-field ‘dose-bathing’ type of delivery). For all the case, the EUDs for the actual treatment delivery were found to correlate strongly with the EUDs for the large-field delivery: a linear correlation coefficient of R2 = 0.98 was obtained and the average EUD for the actual Cyberknife delivery was somewhat higher (5.0 ± 4.7%) than that for the large-field delivery. However, no statistical significance was detected between the two types of delivery (p = 0.21). We concluded that non-isocentric small-field Cyberknife delivery produced consistent biological dosing that tracked well with the constant-dose-rate, large-field-type delivery for prostate stereotactic body radiotherapy.

  3. When microchip implants do more than drug delivery: blending, blurring, and bundling of protected health information and patient monitoring.

    PubMed

    Bramstedt, Katrina A

    2005-01-01

    Although currently in the research stage, scientists argue that drug-releasing microchip implants are on the horizon for future patients. This paper presents ethical reflection on these implants and identifies specific areas of concern; namely, patient monitoring and tracking, and patient privacy and confidentiality. It is foreseeable that drug delivery chips could be multifunctional with the overt or covert addition of sensors that monitor more than just the bloodstream concentrations of prescribed drugs (e.g., cotinine and alcohol in non-compliant patients, patient location via radio frequency or global positioning satellite). Similarly, it is foreseeable that these chips could be embedded with a patient's protected health information that could potentially be accessed and used by unauthorized persons. While drug delivery microchips are theoretically convenient and accurate for dosing, and might offer faster drug delivery with fewer side effects, ethical issues loom and should be contemplated now, while the technology is still under development.

  4. Intrathecal Drug Delivery (ITDD) systems for cancer pain

    PubMed Central

    Bhatia, Gaurav; Lau, Mary E; Koury, Katharine M; Gulur, Padma

    2014-01-01

    Intrathecal drug delivery is an effective pain management option for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics to minimize side effects while significantly improving quality of life. This article aims to provide a general overview of the use of intrathecal drug delivery to manage pain, dosing recommendations, potential risks and complications, and growing trends in the field. PMID:24555051

  5. Delivery devices for the administration of paediatric formulations: overview of current practice, challenges and recent developments.

    PubMed

    Walsh, Jennifer; Bickmann, Deborah; Breitkreutz, Joerg; Chariot-Goulet, Maryvonne

    2011-08-30

    The European Paediatric Formulation Initiative (EuPFI), a group consisting of paediatric formulation experts from industry, academia and clinical pharmacy was founded with the aim of raising awareness of paediatric formulation issues. It is imperative that paediatric medicines can be administered accurately to ensure the correct dose is provided and that the administration device is easy to use and acceptable from the patient's and carer's perspectives. This reflection paper provides an overview of currently available paediatric administration devices and highlights some of the challenges associated with, recommendations and recent developments in delivery devices for the oral, inhaled, parenteral, nasal and ocular administration of paediatric formulations, on behalf of the EuPFI.

  6. NNLOPS accurate associated HW production

    NASA Astrophysics Data System (ADS)

    Astill, William; Bizon, Wojciech; Re, Emanuele; Zanderighi, Giulia

    2016-06-01

    We present a next-to-next-to-leading order accurate description of associated HW production consistently matched to a parton shower. The method is based on reweighting events obtained with the HW plus one jet NLO accurate calculation implemented in POWHEG, extended with the MiNLO procedure, to reproduce NNLO accurate Born distributions. Since the Born kinematics is more complex than the cases treated before, we use a parametrization of the Collins-Soper angles to reduce the number of variables required for the reweighting. We present phenomenological results at 13 TeV, with cuts suggested by the Higgs Cross section Working Group.

  7. Imaging dose in breast radiotherapy: does breast size affect the dose to the organs at risk and the risk of secondary cancer to the contralateral breast?

    SciTech Connect

    Batumalai, Vikneswary; Quinn, Alexandra; Jameson, Michael; Delaney, Geoff; Holloway, Lois

    2015-03-15

    Correct target positioning is crucial for accurate dose delivery in breast radiotherapy resulting in utilisation of daily imaging. However, the radiation dose from daily imaging is associated with increased probability of secondary induced cancer. The aim of this study was to quantify doses associated with three imaging modalities and investigate the correlation of dose and varying breast size in breast radiotherapy. Planning computed tomography (CT) data sets of 30 breast cancer patients were utilised to simulate the dose received by various organs from a megavoltage computed tomography (MV-CT), megavoltage electronic portal image (MV-EPI) and megavoltage cone-beam computed tomography (MV-CBCT). The mean dose to organs adjacent to the target volume (contralateral breast, lungs, spinal cord and heart) were analysed. Pearson correlation analysis was performed to determine the relationship between imaging dose and primary breast volume and the lifetime attributable risk (LAR) of induced secondary cancer was calculated for the contralateral breast. The highest contralateral breast mean dose was from the MV-CBCT (1.79 Gy), followed by MV-EPI (0.22 Gy) and MV-CT (0.11 Gy). A similar trend was found for all organs at risk (OAR) analysed. The primary breast volume inversely correlated with the contralateral breast dose for all three imaging modalities. As the primary breast volume increases, the likelihood of a patient developing a radiation-induced secondary cancer to the contralateral breast decreases. MV-CBCT showed a stronger relationship between breast size and LAR of developing a radiation-induced contralateral breast cancer in comparison with the MV-CT and MV-EPI. For breast patients, imaging dose to OAR depends on imaging modality and treated breast size. When considering the use of imaging during breast radiotherapy, the patient's breast size and contralateral breast dose should be taken into account.

  8. Helical tomotherapy superficial dose measurements

    SciTech Connect

    Ramsey, Chester R.; Seibert, Rebecca M.; Robison, Benjamin; Mitchell, Martha

    2007-08-15

    Helical tomotherapy is a treatment technique that is delivered from a 6 MV fan beam that traces a helical path while the couch moves linearly into the bore. In order to increase the treatment delivery dose rate, helical tomotherapy systems do not have a flattening filter. As such, the dose distributions near the surface of the patient may be considerably different from other forms of intensity-modulated delivery. The purpose of this study was to measure the dose distributions near the surface for helical tomotherapy plans with a varying separation between the target volume and the surface of an anthropomorphic phantom. A hypothetical planning target volume (PTV) was defined on an anthropomorphic head phantom to simulate a 2.0 Gy per fraction IMRT parotid-sparing head and neck treatment of the upper neck nodes. A total of six target volumes were created with 0, 1, 2, 3, 4, and 5 mm of separation between the surface of the phantom and the outer edge of the PTV. Superficial doses were measured for each of the treatment deliveries using film placed in the head phantom and thermoluminescent dosimeters (TLDs) placed on the phantom's surface underneath an immobilization mask. In the 0 mm test case where the PTV extends to the phantom surface, the mean TLD dose was 1.73{+-}0.10 Gy (or 86.6{+-}5.1% of the prescribed dose). The measured superficial dose decreases to 1.23{+-}0.10 Gy (61.5{+-}5.1% of the prescribed dose) for a PTV-surface separation of 5 mm. The doses measured by the TLDs indicated that the tomotherapy treatment planning system overestimates superficial doses by 8.9{+-}3.2%. The radiographic film dose for the 0 mm test case was 1.73{+-}0.07 Gy, as compared to the calculated dose of 1.78{+-}0.05 Gy. Given the results of the TLD and film measurements, the superficial calculated doses are overestimated between 3% and 13%. Without the use of bolus, tumor volumes that extend to the surface may be underdosed. As such, it is recommended that bolus be added for these

  9. Physically facilitating drug-delivery systems

    PubMed Central

    Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

    2012-01-01

    Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

  10. [Dialysis dose quantification in critically ill patients].

    PubMed

    Casino, Francesco Gaetano

    2010-01-01

    Acute kidney injury affects about 35% of intensive care unit patients. Renal replacement therapy is required in about 5% of such patients and is associated with a mortality rate as high as 50% to 80%. The latter is likely more related to the failure of extrarenal organs than to an insufficient dialysis dose. This could explain, at least in part, the findings of 2 recent trials (VA/ NIH and RENAL) where the expected dose-outcome relationship was not confirmed. These results cannot be taken to infer that assessing the dialysis dose is no longer required. The contrary is true, in that the common finding of large differences between prescribed and delivered doses calls for accurate dose assessment, at least to avoid underdialysis. The minimum adequate levels are now a Kt/V urea of 1.2 to 1.4 three times a week (3x/wk) on intermittent hemodialysis (IHD), and an effluent of 20 mL/kg/h for 85% of the time on continuous renal replacement therapy (CRTT). Both these parameters can be easily measured but are far from ideal indices because they account neither for residual renal function nor for irregular dose delivery. The equivalent renal urea clearance (EKRjc), by expressing the averaged renal+dialytic urea clearance over the whole treatment period, is able to account for the above factors. Although assessing EKRjc is quite complex, for regular 3x/wk IHD one could use the formula EKRjc=10 Kt/V+1 to compute that a Kt/V of 1.2 and 1.4 corresponds to an EKRjc of 13 and 15 mL/min, respectively. On the other hand, the hourly effluent per kg is numerically similar to EKRjc. On this basis it can be calculated that in non-prediluted really continuous treatment, the recommended CRRT dose (EKRjc=20 mL/min) is 33% higher than the EKRjc of 15 mL/min, corresponding to the recommended Kt/V of 1.4 on 3x/wk IHD.

  11. TH-A-9A-10: Prostate SBRT Delivery with Flattening-Filter-Free Mode: Benefit and Accuracy

    SciTech Connect

    Li, T; Yuan, L; Sheng, Y; Wu, Q

    2014-06-15

    Purpose: Flattening-filter-free (FFF) beam mode offered on TrueBeam™ linac enables delivering IMRT at 2400 MU/min dose rate. This study investigates the benefit and delivery accuracy of using high dose rate in the context of prostate SBRT. Methods: 8 prostate SBRT patients were retrospectively studied. In 5 cases treated with 600-MU/min dose rate, continuous prostate motion data acquired during radiation-beam-on was used to analyze motion range. In addition, the initial 1/3 of prostate motion trajectories during each radiation-beam-on was separated to simulate motion range if 2400-MU/min were used. To analyze delivery accuracy in FFF mode, MLC trajectory log files from an additional 3 cases treated at 2400-MU/min were acquired. These log files record MLC expected and actual positions every 20ms, and therefore can be used to reveal delivery accuracy. Results: (1) Benefit. On average treatment at 600-MU/min takes 30s per beam; whereas 2400-MU/min requires only 11s. When shortening delivery time to ~1/3, the prostate motion range was significantly smaller (p<0.001). Largest motion reduction occurred in Sup-Inf direction, from [−3.3mm, 2.1mm] to [−1.7mm, 1.7mm], followed by reduction from [−2.1mm, 2.4mm] to [−1.0mm, 2.4mm] in Ant-Pos direction. No change observed in LR direction [−0.8mm, 0.6mm]. The combined motion amplitude (vector norm) confirms that average motion and ranges are significantly smaller when beam-on was limited to the 1st 1/3 of actual delivery time. (2) Accuracy. Trajectory log file analysis showed excellent delivery accuracy with at 2400 MU/min. Most leaf deviations during beam-on were within 0.07mm (99-percentile). Maximum leaf-opening deviations during each beam-on were all under 0.1mm for all leaves. Dose-rate was maintained at 2400-MU/min during beam-on without dipping. Conclusion: Delivery prostate SBRT with 2400 MU/min is both beneficial and accurate. High dose rates significantly reduced both treatment time and intra-beam prostate

  12. How flatbed scanners upset accurate film dosimetry

    NASA Astrophysics Data System (ADS)

    van Battum, L. J.; Huizenga, H.; Verdaasdonk, R. M.; Heukelom, S.

    2016-01-01

    Film is an excellent dosimeter for verification of dose distributions due to its high spatial resolution. Irradiated film can be digitized with low-cost, transmission, flatbed scanners. However, a disadvantage is their lateral scan effect (LSE): a scanner readout change over its lateral scan axis. Although anisotropic light scattering was presented as the origin of the LSE, this paper presents an alternative cause. Hereto, LSE for two flatbed scanners (Epson 1680 Expression Pro and Epson 10000XL), and Gafchromic film (EBT, EBT2, EBT3) was investigated, focused on three effects: cross talk, optical path length and polarization. Cross talk was examined using triangular sheets of various optical densities. The optical path length effect was studied using absorptive and reflective neutral density filters with well-defined optical characteristics (OD range 0.2-2.0). Linear polarizer sheets were used to investigate light polarization on the CCD signal in absence and presence of (un)irradiated Gafchromic film. Film dose values ranged between 0.2 to 9 Gy, i.e. an optical density range between 0.25 to 1.1. Measurements were performed in the scanner’s transmission mode, with red-green-blue channels. LSE was found to depend on scanner construction and film type. Its magnitude depends on dose: for 9 Gy increasing up to 14% at maximum lateral position. Cross talk was only significant in high contrast regions, up to 2% for very small fields. The optical path length effect introduced by film on the scanner causes 3% for pixels in the extreme lateral position. Light polarization due to film and the scanner’s optical mirror system is the main contributor, different in magnitude for the red, green and blue channel. We concluded that any Gafchromic EBT type film scanned with a flatbed scanner will face these optical effects. Accurate dosimetry requires correction of LSE, therefore, determination of the LSE per color channel and dose delivered to the film.

  13. How flatbed scanners upset accurate film dosimetry.

    PubMed

    van Battum, L J; Huizenga, H; Verdaasdonk, R M; Heukelom, S

    2016-01-21

    Film is an excellent dosimeter for verification of dose distributions due to its high spatial resolution. Irradiated film can be digitized with low-cost, transmission, flatbed scanners. However, a disadvantage is their lateral scan effect (LSE): a scanner readout change over its lateral scan axis. Although anisotropic light scattering was presented as the origin of the LSE, this paper presents an alternative cause. Hereto, LSE for two flatbed scanners (Epson 1680 Expression Pro and Epson 10000XL), and Gafchromic film (EBT, EBT2, EBT3) was investigated, focused on three effects: cross talk, optical path length and polarization. Cross talk was examined using triangular sheets of various optical densities. The optical path length effect was studied using absorptive and reflective neutral density filters with well-defined optical characteristics (OD range 0.2-2.0). Linear polarizer sheets were used to investigate light polarization on the CCD signal in absence and presence of (un)irradiated Gafchromic film. Film dose values ranged between 0.2 to 9 Gy, i.e. an optical density range between 0.25 to 1.1. Measurements were performed in the scanner's transmission mode, with red-green-blue channels. LSE was found to depend on scanner construction and film type. Its magnitude depends on dose: for 9 Gy increasing up to 14% at maximum lateral position. Cross talk was only significant in high contrast regions, up to 2% for very small fields. The optical path length effect introduced by film on the scanner causes 3% for pixels in the extreme lateral position. Light polarization due to film and the scanner's optical mirror system is the main contributor, different in magnitude for the red, green and blue channel. We concluded that any Gafchromic EBT type film scanned with a flatbed scanner will face these optical effects. Accurate dosimetry requires correction of LSE, therefore, determination of the LSE per color channel and dose delivered to the film.

  14. Multiple anatomy optimization of accumulated dose

    SciTech Connect

    Watkins, W. Tyler Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.

    2014-11-01

    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 dose 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.

  15. Multiple anatomy optimization of accumulated dose

    PubMed Central

    Watkins, W. Tyler; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.; Siebers, Jeffrey V.

    2014-01-01

    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 dose 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. PMID:25370619

  16. Actual Dose Variation of Parotid Glands and Spinal Cord for Nasopharyngeal Cancer Patients During Radiotherapy

    SciTech Connect

    Han Chunhui Chen Yijen; Liu An; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

    2008-03-15

    Purpose: For intensity-modulated radiotherapy of nasopharyngeal cancer, accurate dose delivery is crucial to the success of treatment. This study aimed to evaluate the significance of daily image-guided patient setup corrections and to quantify the parotid gland volume and dose variations for nasopharyngeal cancer patients using helical tomotherapy megavoltage computed tomography (CT). Methods and Materials: Five nasopharyngeal cancer patients who underwent helical tomotherapy were selected retrospectively. Each patient had received 70 Gy in 35 fractions. Daily megavoltage CT scans were registered with the planning CT images to correct the patient setup errors. Contours of the spinal cord and parotid glands were drawn on the megavoltage CT images at fixed treatment intervals. The actual doses delivered to the critical structures were calculated using the helical tomotherapy Planned Adaptive application. Results: The maximal dose to the spinal cord showed a significant increase and greater variation without daily setup corrections. The significant decrease in the parotid gland volume led to a greater median dose in the later phase of treatment. The average parotid gland volume had decreased from 20.5 to 13.2 cm{sup 3} by the end of treatment. On average, the median dose to the parotid glands was 83 cGy and 145 cGy for the first and the last treatment fractions, respectively. Conclusions: Daily image-guided setup corrections can eliminate significant dose variations to critical structures. Constant monitoring of patient anatomic changes and selective replanning should be used during radiotherapy to avoid critical structure complications.

  17. Positron Emission Tomography Image-Guided Drug Delivery: Current Status and Future Perspectives

    PubMed Central

    2015-01-01

    Positron emission tomography (PET) is an important modality in the field of molecular imaging, which is gradually impacting patient care by providing safe, fast, and reliable techniques that help to alter the course of patient care by revealing invasive, de facto procedures to be unnecessary or rendering them obsolete. Also, PET provides a key connection between the molecular mechanisms involved in the pathophysiology of disease and the according targeted therapies. Recently, PET imaging is also gaining ground in the field of drug delivery. Current drug delivery research is focused on developing novel drug delivery systems with emphasis on precise targeting, accurate dose delivery, and minimal toxicity in order to achieve maximum therapeutic efficacy. At the intersection between PET imaging and controlled drug delivery, interest has grown in combining both these paradigms into clinically effective formulations. PET image-guided drug delivery has great potential to revolutionize patient care by in vivo assessment of drug biodistribution and accumulation at the target site and real-time monitoring of the therapeutic outcome. The expected end point of this approach is to provide fundamental support for the optimization of innovative diagnostic and therapeutic strategies that could contribute to emerging concepts in the field of “personalized medicine”. This review focuses on the recent developments in PET image-guided drug delivery and discusses intriguing opportunities for future development. The preclinical data reported to date are quite promising, and it is evident that such strategies in cancer management hold promise for clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in enhanced quality of life for cancer patients. PMID:24865108

  18. Using In-Service and Coaching to Increase Teachers' Accurate Use of Research-Based Strategies

    ERIC Educational Resources Information Center

    Kretlow, Allison G.; Cooke, Nancy L.; Wood, Charles L.

    2012-01-01

    Increasing the accurate use of research-based practices in classrooms is a critical issue. Professional development is one of the most practical ways to provide practicing teachers with training related to research-based practices. This study examined the effects of in-service plus follow-up coaching on first grade teachers' accurate delivery of…

  19. Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters

    SciTech Connect

    Bache, Steven T.; Juang, Titania; Belley, Matthew D.; Koontz, Bridget F.; Yoshizumi, Terry T.; Kirsch, David G.; Oldham, Mark; Adamovics, John

    2015-02-15

    Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1–15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm{sup 3}) optical computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180

  20. Using corrected Cone-Beam CT image for accelerated partial breast irradiation treatment dose verification: the preliminary experience

    PubMed Central

    2013-01-01

    Background Accurate target localization is mandatory in the accelerated partial breast irradiation (APBI) delivery. Dosimetric verification for positional error will further guarantee the accuracy of treatment delivery. The purpose of this study is to evaluate the clinical feasibility of a cone beam computer tomographic (CBCT) image correction method in APBI. Methods A CBCT image correction method was developed. First, rigid image registration was proceeded for CTs and CBCTs; second, these images were separated into four parts; then, ratio images for each of the four parts of planning CTs/CBCTs were calculated and filtered to reduce the high spatial frequency; finally, the enhanced CBCT images were generated combing the four parts. An anthropomorphic thorax rando phantom was used to evaluate the feasibility and accuracy of the CBCT correction method. The CBCT images of consecutive 10 patients receiving APBI were corrected using the above method and dosimetric variations were evaluated. Each set of CBCT is composed of three images: one acquired after skin-marker setup, one after online setup correction and one after treatment delivery. Results The phantom study showed the improved accuracy of dose calculation with corrected CBCT. The Dose Volume Histogram (DVH) difference between the planning CT and corrected CBCT is less than the difference between the planning CT and original CBCT. The maximum dose difference between the corrected CBCT and planning CT is 0.8% in PTV_EVAL V100, which is 3.8% between original CBCT and planning. In the patient study, 67.4% of fractions benefit from CBCT setup corrections in PTV_EVAL D95, while in 47.4% of the fractions, reduced dose coverage was found on the post-treatment CBCT. Overall, the CBCT based initial setup correction guaranteed target dose coverage in 9 patients. Conclusions A generic CBCT image correction algorithm was created and proved to be easily implemented in clinic. Compared to the original CBCT, the corrected CBCT

  1. Adaptations and innovations in drug delivery.

    PubMed

    Cavalla, D

    2001-10-01

    The most recent meeting organized by the Society for Medicines Research, entitled Improving Medicines Through Drug Delivery, was held at the National Heart and Lung Institute in London on July 5, 2001. Drug delivery is increasingly becoming a central technology in the research and development of better medicines. This is so for at least three reasons. First, new drugs are being derived from complex biological molecules that are not readily amenable to oral delivery. Second, improved medicine is recognized as requiring better dosing regimens for the patient. Both compliance and preference are improved by reduced dosing frequency, and it is rare for new products to require three-times-daily administration. Lastly, drug delivery technology has come a long way in the past 20 years, beyond controlled-release pharmaceuticals to polymer conjugates and dry powder-inhaled proteins. PMID:12806435

  2. The effect of low dose fentanyl as a premedication before induction of general anesthesia on the neonatal apgar score in cesarean section delivery: randomized, double-blind controlled trial

    PubMed Central

    Karbasy, Seyyed Hasan; Derakhshan, Pooya

    2016-01-01

    Background: The administration of opioids before induction of general anesthesia can be considered as a problem in cesarean section. The aim of this study was to compare the effects of intravenous Fentanyl as a premedication before induction of general anesthesia versus placebo on maternal hemodynamic parameters and on the first and fifth minutes Apgar score in the neonates in elective cesarean delivery. Methods: This double- blinded, randomized, clinical trial study was conducted in 2014-2015 at Vali-e-Asr hospital, Birjand, Iran. Ninety full term pregnant women undergoing elective cesarean section delivery under general anesthesia were selected. The participants were randomly classified into two groups: The Fentanyl group and the placebo. Iintravenous Fentanyl 1μg/kg was administrated three minutes before anesthesia induction for the Fentanyl group, and 2 milliliter normal saline was administered for the placebo group. Maternal mean arterial pressure, heart rate before the start of anesthesia induction and thirty seconds after intubation were measured. Also, the first and fifth minutes Apgar scores of the neonates were evaluated and recorded by a blinded anesthesiologist. The clinical trial registration number was IRCT2015010320112N3. Results: Maternal mean arterial pressure was significantly lower in the Fentanyl group than the placebo group after intubation. Heart rate was significantly higher in the placebo group before the start of anesthesia induction and after intubation compared to the Fentanyl group. The first and fifth minutes’ Apgar scores of the neonates were not statistically different between the two groups. Conclusion: Administration of 1μg/Kg intravenous Fentanyl before the induction of anesthesia for cesarean section delivery decreases maternal hemodynamic changes after intubation. In addition, it does not have any effect on Apgar scores of the neonate in the 1st and 5th minutes after birth. PMID:27493905

  3. Real time sensor for therapeutic radiation delivery

    DOEpatents

    Bliss, Mary; Craig, Richard A.; Reeder, Paul L.

    1998-01-01

    The invention is a real time sensor for therapeutic radiation. A probe is placed in or near the patient that senses in real time the dose at the location of the probe. The strength of the dose is determined by either an insertion or an exit probe. The location is determined by a series of vertical and horizontal sensing elements that gives the operator a real time read out dose location relative to placement of the patient. The increased accuracy prevents serious tissue damage to the patient by preventing overdose or delivery of a dose to a wrong location within the body.

  4. Real time sensor for therapeutic radiation delivery

    DOEpatents

    Bliss, M.; Craig, R.A.; Reeder, P.L.

    1998-01-06

    The invention is a real time sensor for therapeutic radiation. A probe is placed in or near the patient that senses in real time the dose at the location of the probe. The strength of the dose is determined by either an insertion or an exit probe. The location is determined by a series of vertical and horizontal sensing elements that gives the operator a real time read out dose location relative to placement of the patient. The increased accuracy prevents serious tissue damage to the patient by preventing overdose or delivery of a dose to a wrong location within the body. 14 figs.

  5. The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit

    NASA Astrophysics Data System (ADS)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

    2008-11-01

    Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D50) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D50 value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the

  6. Imaging doses in radiation therapy from kilovoltage cone-beam computed tomography

    NASA Astrophysics Data System (ADS)

    Hyer, Daniel Ellis

    Advances in radiation treatment delivery, such as intensity modulated radiation therapy (IMRT), have made it possible to deliver large doses of radiation with a high degree of conformity. While highly conformal treatments offers the advantage of sparing surrounding normal tissue, this benefit can only be realized if the patient is accurately positioned during each treatment fraction. The need to accurately position the patient has led to the development and use of gantry mounted kilovoltage cone-beam computed tomography (kV-CBCT) systems. These systems are used to acquire high resolution volumetric images of the patient which are then digitally registered with the planning CT dataset to confirm alignment of the patient on the treatment table. While kV-CBCT is a very useful tool for aligning the patient prior to treatment, daily use in a high fraction therapy regimen results in a substantial radiation dose. In order to quantify the radiation dose associated with CBCT imaging, an anthropomorphic phantom representing a 50th percentile adult male and a fiber-optic coupled (FOC) dosimetry system were both constructed as part of this dissertation. These tools were then used to directly measure organ doses incurred during clinical protocols for the head, chest, and pelvis. For completeness, the dose delivered from both the X-ray Volumetric Imager (XVI, Elekta Oncology Systems, Crawley, UK) and the On-Board Imager (OBI, Varian Medical Systems, Palo Alto, CA) were investigated. While this study provided a direct measure of organ doses for estimating risk to the patient, a practical method for estimating organ doses that could be performed with phantoms and dosimeters currently available at most clinics was also desired. To accomplish this goal, a 100 mm pencil ion chamber was used to measure the "cone beam dose index" (CBDI) inside standard CT dose index (CTDI) acrylic phantoms. A weighted CBDI (CBDIw), similar to the weighted CT dose index (CTDIw), was then calculated to

  7. Recent Patents in Pulmonary Delivery of Macromolecules.

    PubMed

    Ray, Animikh; Mandal, Abhirup; Mitra, Ashim K

    2015-01-01

    Pulmonary delivery is a non-invasive form of delivery that holds tremendous therapeutic promise for topical and systemic administration of several macromolecules. Oral administration of macromolecules has several limitations such as low bioavailability, degradation of drug before reaching circulation and insufficient absorption across intestinal membrane. Administration of macromolecules such as proteins, peptides and nucleic acids via inhalation offers great potential due to the avoidance of first pass metabolism, higher surface area and rapid clinical response. However, delivery of reproducible, uniform and safe doses of inhaled particles remains a major challenge for clinical translation. Recent advances in the fields of biotechnology and particle engineering led to progress in novel pulmonary drug delivery systems. Moreover, significant developments in carriers and delivery devices prevent denaturation of macromolecules and control their release within the lungs. This article reviews the advances in pulmonary drug delivery systems by focusing on the recent patents in delivery of macromolecules. Furthermore, recent patents in gene delivery to the lungs have also been discussed. List of patents included in this review is comprehensive in terms of pulmonary delivery of therapeutics. It includes inventions related to proteins and peptides, DNA therapeutics, siRNA and other genetic materials with therapeutic applications. The diseases targeted by these therapeutic molecules are varied including but not limited to different forms of cancer, respiratory diseases etc.

  8. Optical-CT imaging of complex 3D dose distributions

    NASA Astrophysics Data System (ADS)

    Oldham, Mark; Kim, Leonard; Hugo, Geoffrey

    2005-04-01

    The limitations of conventional dosimeters restrict the comprehensiveness of verification that can be performed for advanced radiation treatments presenting an immediate and substantial problem for clinics attempting to implement these techniques. In essence, the rapid advances in the technology of radiation delivery have not been paralleled by corresponding advances in the ability to verify these treatments. Optical-CT gel-dosimetry is a relatively new technique with potential to address this imbalance by providing high resolution 3D dose maps in polymer and radiochromic gel dosimeters. We have constructed a 1st generation optical-CT scanner capable of high resolution 3D dosimetry and applied it to a number of simple and increasingly complex dose distributions including intensity-modulated-radiation-therapy (IMRT). Prior to application to IMRT, the robustness of optical-CT gel dosimetry was investigated on geometry and variable attenuation phantoms. Physical techniques and image processing methods were developed to minimize deleterious effects of refraction, reflection, and scattered laser light. Here we present results of investigations into achieving accurate high-resolution 3D dosimetry with optical-CT, and show clinical examples of 3D IMRT dosimetry verification. In conclusion, optical-CT gel dosimetry can provide high resolution 3D dose maps that greatly facilitate comprehensive verification of complex 3D radiation treatments. Good agreement was observed at high dose levels (>50%) between planned and measured dose distributions. Some systematic discrepancies were observed however (rms discrepancy 3% at high dose levels) indicating further work is required to eliminate confounding factors presently compromising the accuracy of optical-CT 3D gel-dosimetry.

  9. Evaluation of relative transmitted dose for a step and shoot head and neck intensity modulated radiation therapy using a scanning liquid ionization chamber electronic portal imaging device

    PubMed Central

    Mohammadi, Mohammad; Bezak, Eva

    2012-01-01

    The dose delivery verification for a head and neck static intensity modulated radiation therapy (IMRT) case using a scanning liquid ionization chamber electronic portal imaging device (SLIC-EPID) was investigated. Acquired electronic portal images were firstly converted into transmitted dose maps using an in-house developed method. The dose distributions were then compared with those calculated in a virtual EPID using the Pinnacle3 treatment planning system (TPS). Using gamma evaluation with the ΔDmax and DTA criteria of 3%/2.54 mm, an excellent agreement was observed between transmitted dose measured using SLIC-EPID and that calculated by TPS (gamma score approximately 95%) for large MLC fields. In contrast, for several small subfields, due to SLIC-EPID image blurring, significant disagreement was found in the gamma results. Differences between EPID and TPS dose maps were also observed for several parts of the radiation subfields, when the radiation beam passed through air on the outside of tissue. The transmitted dose distributions measured using portal imagers such as SLIC-EPID can be used to verify the dose delivery to a patient. However, several aspects such as accurate calibration procedure and imager response under different conditions should be taken into the consideration. In addition, SLIC-EPID image blurring is another important issue, which should be considered if the SLIC-EPID is used for clinical dosimetry verification. PMID:22363108

  10. Evaluation of relative transmitted dose for a step and shoot head and neck intensity modulated radiation therapy using a scanning liquid ionization chamber electronic portal imaging device.

    PubMed

    Mohammadi, Mohammad; Bezak, Eva

    2012-01-01

    The dose delivery verification for a head and neck static intensity modulated radiation therapy (IMRT) case using a scanning liquid ionization chamber electronic portal imaging device (SLIC-EPID) was investigated. Acquired electronic portal images were firstly converted into transmitted dose maps using an in-house developed method. The dose distributions were then compared with those calculated in a virtual EPID using the Pinnacle(3) treatment planning system (TPS). Using gamma evaluation with the ΔD(max) and DTA criteria of 3%/2.54 mm, an excellent agreement was observed between transmitted dose measured using SLIC-EPID and that calculated by TPS (gamma score approximately 95%) for large MLC fields. In contrast, for several small subfields, due to SLIC-EPID image blurring, significant disagreement was found in the gamma results. Differences between EPID and TPS dose maps were also observed for several parts of the radiation subfields, when the radiation beam passed through air on the outside of tissue. The transmitted dose distributions measured using portal imagers such as SLIC-EPID can be used to verify the dose delivery to a patient. However, several aspects such as accurate calibration procedure and imager response under different conditions should be taken into the consideration. In addition, SLIC-EPID image blurring is another important issue, which should be considered if the SLIC-EPID is used for clinical dosimetry verification.

  11. A novel time dependent gamma evaluation function for dynamic 2D and 3D dose distributions

    NASA Astrophysics Data System (ADS)

    Podesta, Mark; CGG Persoon, Lucas; Verhaegen, Frank

    2014-10-01

    Modern external beam radiotherapy requires detailed verification and quality assurance so that confidence can be placed on both the delivery of a single treatment fraction and on the consistency of delivery throughout the treatment course. To verify dose distributions, a comparison between prediction and measurement must be made. Comparisons between two dose distributions are commonly performed using a Gamma evaluation which is a calculation of two quantities on a pixel by pixel basis; the dose difference, and the distance to agreement. By providing acceptance criteria (e.g. 3%, 3 mm), the function will find the most appropriate match within its two degrees of freedom. For complex dynamic treatments such as IMRT or VMAT it is important to verify the dose delivery in a time dependent manner and so a gamma evaluation that includes a degree of freedom in the time domain via a third parameter, time to agreement, is presented here. A C++ (mex) based gamma function was created that could be run on either CPU and GPU computing platforms that would allow a degree of freedom in the time domain. Simple test cases were created in both 2D and 3D comprising of simple geometrical shapes with well-defined boundaries varying over time. Changes of varying magnitude in either space or time were introduced and repeated gamma analyses were performed varying the criteria. A clinical VMAT case was also included, artificial air bubbles of varying size were introduced to a patient geometry, along with shifts of varying magnitude in treatment time. For all test cases where errors in distance, dose or time were introduced, the time dependent gamma evaluation could accurately highlight the errors. The time dependent gamma function presented here allows time to be included as a degree of freedom in gamma evaluations. The function allows for 2D and 3D data sets which are varying over time to be compared using appropriate criteria without penalising minor offsets of subsequent radiation

  12. A novel time dependent gamma evaluation function for dynamic 2D and 3D dose distributions.

    PubMed

    Podesta, Mark; Persoon, Lucas C G G; Verhaegen, Frank

    2014-10-21

    Modern external beam radiotherapy requires detailed verification and quality assurance so that confidence can be placed on both the delivery of a single treatment fraction and on the consistency of delivery throughout the treatment course. To verify dose distributions, a comparison between prediction and measurement must be made. Comparisons between two dose distributions are commonly performed using a Gamma evaluation which is a calculation of two quantities on a pixel by pixel basis; the dose difference, and the distance to agreement. By providing acceptance criteria (e.g. 3%, 3 mm), the function will find the most appropriate match within its two degrees of freedom. For complex dynamic treatments such as IMRT or VMAT it is important to verify the dose delivery in a time dependent manner and so a gamma evaluation that includes a degree of freedom in the time domain via a third parameter, time to agreement, is presented here. A C++ (mex) based gamma function was created that could be run on either CPU and GPU computing platforms that would allow a degree of freedom in the time domain. Simple test cases were created in both 2D and 3D comprising of simple geometrical shapes with well-defined boundaries varying over time. Changes of varying magnitude in either space or time were introduced and repeated gamma analyses were performed varying the criteria. A clinical VMAT case was also included, artificial air bubbles of varying size were introduced to a patient geometry, along with shifts of varying magnitude in treatment time. For all test cases where errors in distance, dose or time were introduced, the time dependent gamma evaluation could accurately highlight the errors.The time dependent gamma function presented here allows time to be included as a degree of freedom in gamma evaluations. The function allows for 2D and 3D data sets which are varying over time to be compared using appropriate criteria without penalising minor offsets of subsequent radiation fields

  13. Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies.

    PubMed

    Glide-Hurst, Carri K; Chetty, Indrin J

    2014-04-01

    In the United States, more than half of all new invasive cancers diagnosed are non-small cell lung cancer, with a significant number of these cases presenting at locally advanced stages, resulting in about one-third of all cancer deaths. While the advent of stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiotherapy, or SBRT) for early-staged patients has improved local tumor control to >90%, survival results for locally advanced stage lung cancer remain grim. Significant challenges exist in lung cancer radiation therapy including tumor motion, accurate dose calculation in low density media, limiting dose to nearby organs at risk, and changing anatomy over the treatment course. However, many recent technological advancements have been introduced that can meet these challenges, including four-dimensional computed tomography (4DCT) and volumetric cone-beam computed tomography (CBCT) to enable more accurate target definition and precise tumor localization during radiation, respectively. In addition, advances in dose calculation algorithms have allowed for more accurate dosimetry in heterogeneous media, and intensity modulated and arc delivery techniques can help spare organs at risk. New delivery approaches, such as tumor tracking and gating, offer additional potential for further reducing target margins. Image-guided adaptive radiation therapy (IGART) introduces the potential for individualized plan adaptation based on imaging feedback, including bulky residual disease, tumor progression, and physiological changes that occur during the treatment course. This review provides an overview of the current state of the art technology for lung cancer volume definition, treatment planning, localization, and treatment plan adaptation.

  14. Accurate Monte Carlo simulations for nozzle design, commissioning and quality assurance for a proton radiation therapy facility.

    PubMed

    Paganetti, H; Jiang, H; Lee, S Y; Kooy, H M

    2004-07-01

    Monte Carlo dosimetry calculations are essential methods in radiation therapy. To take full advantage of this tool, the beam delivery system has to be simulated in detail and the initial beam parameters have to be known accurately. The modeling of the beam delivery system itself opens various areas where Monte Carlo calculations prove extremely helpful, such as for design and commissioning of a therapy facility as well as for quality assurance verification. The gantry treatment nozzles at the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital (MGH) were modeled in detail using the GEANT4.5.2 Monte Carlo code. For this purpose, various novel solutions for simulating irregular shaped objects in the beam path, like contoured scatterers, patient apertures or patient compensators, were found. The four-dimensional, in time and space, simulation of moving parts, such as the modulator wheel, was implemented. Further, the appropriate physics models and cross sections for proton therapy applications were defined. We present comparisons between measured data and simulations. These show that by modeling the treatment nozzle with millimeter accuracy, it is possible to reproduce measured dose distributions with an accuracy in range and modulation width, in the case of a spread-out Bragg peak (SOBP), of better than 1 mm. The excellent agreement demonstrates that the simulations can even be used to generate beam data for commissioning treatment planning systems. The Monte Carlo nozzle model was used to study mechanical optimization in terms of scattered radiation and secondary radiation in the design of the nozzles. We present simulations on the neutron background. Further, the Monte Carlo calculations supported commissioning efforts in understanding the sensitivity of beam characteristics and how these influence the dose delivered. We present the sensitivity of dose distributions in water with respect to various beam parameters and geometrical misalignments

  15. SU-E-T-421: Feasibility Study of Volumetric Modulated Arc Therapy with Constant Dose Rate for Endometrial Cancer

    SciTech Connect

    Yang, R; Wang, J

    2014-06-01

    Purpose: To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. Methods: The nine-Field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry Run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs Decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. Conclusion: VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability. This work is supported by the grant project, National Natural; Science Foundation of China (No. 81071237)

  16. Accurate documentation and wound measurement.

    PubMed

    Hampton, Sylvie

    This article, part 4 in a series on wound management, addresses the sometimes routine yet crucial task of documentation. Clear and accurate records of a wound enable its progress to be determined so the appropriate treatment can be applied. Thorough records mean any practitioner picking up a patient's notes will know when the wound was last checked, how it looked and what dressing and/or treatment was applied, ensuring continuity of care. Documenting every assessment also has legal implications, demonstrating due consideration and care of the patient and the rationale for any treatment carried out. Part 5 in the series discusses wound dressing characteristics and selection.

  17. Characterization of dose in stereotactic body radiation therapy of lung lesions via Monte Carlo calculation

    NASA Astrophysics Data System (ADS)

    Rassiah, Premavathy

    Stereotactic Body Radiation Therapy is a new form of treatment where hypofractionated (i.e., large dose fractions), conformal doses are delivered to small extracranial target volumes. This technique has proven to be especially effective for treating lung lesions. The inability of most commercially available algorithms/treatment planning systems to accurately account for electron transport in regions of heterogeneous electron density and tissue interfaces make prediction of accurate doses especially challenging for such regions. Monte Carlo which a model based calculation algorithm has proven to be extremely accurate for dose calculation in both homogeneous and inhomogeneous environment. This study attempts to accurately characterize the doses received by static targets located in the lung, as well as critical structures (contra and ipsi -lateral lung, major airways, esophagus and spinal cord) for the serial tomotherapeutic intensity-modulated delivery method used for stereotactic body radiation therapy at the Cancer Therapy and Research Center. PEREGRINERTM (v 1.6. NOMOS) Monte Carlo, doses were compared to the Finite Sized Pencil Beam/Effective Path Length predicted values from the CORVUS 5.0 planning system. The Monte Carlo based treatment planning system was first validated in both homogenous and inhomogeneous environments. 77 stereotactic body radiation therapy lung patients previously treated with doses calculated using the Finite Sized Pencil Beam/Effective Path Length, algorithm were then retrieved and recalculated with Monte Carlo. All 77 patients plans were also recalculated without inhomogeneity correction in an attempt to counteract the known overestimation of dose at the periphery of the target by EPL with increased attenuation. The critical structures were delineated in order to standardize the contouring. Both the ipsi-lateral and contra-lateral lungs were contoured. The major airways were contoured from the apex of the lungs (trachea) to 4 cm below

  18. SPLASH: Accurate OH maser positions

    NASA Astrophysics Data System (ADS)

    Walsh, Andrew; Gomez, Jose F.; Jones, Paul; Cunningham, Maria; Green, James; Dawson, Joanne; Ellingsen, Simon; Breen, Shari; Imai, Hiroshi; Lowe, Vicki; Jones, Courtney

    2013-10-01

    The hydroxyl (OH) 18 cm lines are powerful and versatile probes of diffuse molecular gas, that may trace a largely unstudied component of the Galactic ISM. SPLASH (the Southern Parkes Large Area Survey in Hydroxyl) is a large, unbiased and fully-sampled survey of OH emission, absorption and masers in the Galactic Plane that will achieve sensitivities an order of magnitude better than previous work. In this proposal, we request ATCA time to follow up OH maser candidates. This will give us accurate (~10") positions of the masers, which can be compared to other maser positions from HOPS, MMB and MALT-45 and will provide full polarisation measurements towards a sample of OH masers that have not been observed in MAGMO.

  19. Accurate thickness measurement of graphene

    NASA Astrophysics Data System (ADS)

    Shearer, Cameron J.; Slattery, Ashley D.; Stapleton, Andrew J.; Shapter, Joseph G.; Gibson, Christopher T.

    2016-03-01

    Graphene has emerged as a material with a vast variety of applications. The electronic, optical and mechanical properties of graphene are strongly influenced by the number of layers present in a sample. As a result, the dimensional characterization of graphene films is crucial, especially with the continued development of new synthesis methods and applications. A number of techniques exist to determine the thickness of graphene films including optical contrast, Raman scattering and scanning probe microscopy techniques. Atomic force microscopy (AFM), in particular, is used extensively since it provides three-dimensional images that enable the measurement of the lateral dimensions of graphene films as well as the thickness, and by extension the number of layers present. However, in the literature AFM has proven to be inaccurate with a wide range of measured values for single layer graphene thickness reported (between 0.4 and 1.7 nm). This discrepancy has been attributed to tip-surface interactions, image feedback settings and surface chemistry. In this work, we use standard and carbon nanotube modified AFM probes and a relatively new AFM imaging mode known as PeakForce tapping mode to establish a protocol that will allow users to accurately determine the thickness of graphene films. In particular, the error in measuring the first layer is reduced from 0.1-1.3 nm to 0.1-0.3 nm. Furthermore, in the process we establish that the graphene-substrate adsorbate layer and imaging force, in particular the pressure the tip exerts on the surface, are crucial components in the accurate measurement of graphene using AFM. These findings can be applied to other 2D materials.

  20. Accurate thickness measurement of graphene.

    PubMed

    Shearer, Cameron J; Slattery, Ashley D; Stapleton, Andrew J; Shapter, Joseph G; Gibson, Christopher T

    2016-03-29

    Graphene has emerged as a material with a vast variety of applications. The electronic, optical and mechanical properties of graphene are strongly influenced by the number of layers present in a sample. As a result, the dimensional characterization of graphene films is crucial, especially with the continued development of new synthesis methods and applications. A number of techniques exist to determine the thickness of graphene films including optical contrast, Raman scattering and scanning probe microscopy techniques. Atomic force microscopy (AFM), in particular, is used extensively since it provides three-dimensional images that enable the measurement of the lateral dimensions of graphene films as well as the thickness, and by extension the number of layers present. However, in the literature AFM has proven to be inaccurate with a wide range of measured values for single layer graphene thickness reported (between 0.4 and 1.7 nm). This discrepancy has been attributed to tip-surface interactions, image feedback settings and surface chemistry. In this work, we use standard and carbon nanotube modified AFM probes and a relatively new AFM imaging mode known as PeakForce tapping mode to establish a protocol that will allow users to accurately determine the thickness of graphene films. In particular, the error in measuring the first layer is reduced from 0.1-1.3 nm to 0.1-0.3 nm. Furthermore, in the process we establish that the graphene-substrate adsorbate layer and imaging force, in particular the pressure the tip exerts on the surface, are crucial components in the accurate measurement of graphene using AFM. These findings can be applied to other 2D materials.

  1. A convolution-superposition dose calculation engine for GPUs

    SciTech Connect

    Hissoiny, Sami; Ozell, Benoit; Despres, Philippe

    2010-03-15

    Purpose: Graphic processing units (GPUs) are increasingly used for scientific applications, where their parallel architecture and unprecedented computing power density can be exploited to accelerate calculations. In this paper, a new GPU implementation of a convolution/superposition (CS) algorithm is presented. Methods: This new GPU implementation has been designed from the ground-up to use the graphics card's strengths and to avoid its weaknesses. The CS GPU algorithm takes into account beam hardening, off-axis softening, kernel tilting, and relies heavily on raytracing through patient imaging data. Implementation details are reported as well as a multi-GPU solution. Results: An overall single-GPU acceleration factor of 908x was achieved when compared to a nonoptimized version of the CS algorithm implemented in PlanUNC in single threaded central processing unit (CPU) mode, resulting in approximatively 2.8 s per beam for a 3D dose computation on a 0.4 cm grid. A comparison to an established commercial system leads to an acceleration factor of approximately 29x or 0.58 versus 16.6 s per beam in single threaded mode. An acceleration factor of 46x has been obtained for the total energy released per mass (TERMA) calculation and a 943x acceleration factor for the CS calculation compared to PlanUNC. Dose distributions also have been obtained for a simple water-lung phantom to verify that the implementation gives accurate results. Conclusions: These results suggest that GPUs are an attractive solution for radiation therapy applications and that careful design, taking the GPU architecture into account, is critical in obtaining significant acceleration factors. These results potentially can have a significant impact on complex dose delivery techniques requiring intensive dose calculations such as intensity-modulated radiation therapy (IMRT) and arc therapy. They also are relevant for adaptive radiation therapy where dose results must be obtained rapidly.

  2. Chronic, programmed polypeptide delivery from an implanted, multireservoir microchip device.

    PubMed

    Prescott, James H; Lipka, Sara; Baldwin, Samuel; Sheppard, Norman F; Maloney, John M; Coppeta, Jonathan; Yomtov, Barry; Staples, Mark A; Santini, John T

    2006-04-01

    Implanted drug delivery systems are being increasingly used to realize the therapeutic potential of peptides and proteins. Here we describe the controlled pulsatile release of the polypeptide leuprolide from microchip implants over 6 months in dogs. Each microchip contains an array of discrete reservoirs from which dose delivery can be controlled by telemetry.

  3. Assessing dose rate distributions in VMAT plans.

    PubMed

    Mackeprang, P-H; Volken, W; Terribilini, D; Frauchiger, D; Zaugg, K; Aebersold, D M; Fix, M K; Manser, P

    2016-04-21

    Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within ±0.4 s and doses ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min(-1) for conventional fractionation

  4. VMAT QA: Measurement-guided 4D dose reconstruction on a patient

    SciTech Connect

    Nelms, Benjamin E.; Opp, Daniel; Robinson, Joshua; Wolf, Theresa K.; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2012-07-15

    global fluence change. Results: Across four TG-119 plans, the average PTV point dose difference in the cube between 3DVH and ion chamber is 0.1 {+-} 1.0%. Average film vs TPS {gamma}-analysis passing rates are 83.0%, 91.1%, and 98.4% for 1%/2 mm, 2%/2 mm, and 3%/3 mm threshold combinations, respectively, while average film vs 3DVH {gamma}-analysis passing rates are 88.6%, 96.1%, and 99.5% for the same respective criteria. 4D MGDR was also sufficiently accurate. First, for 99.5% voxels in each case, the doses from 3D and 4D MGDR at the end of delivery agree within 0.5%local dose-error/1 mm distance. Moreover, all failing voxels are confined to the edge of the cylindrical reconstruction volume. Second, dose vs time curves track between the ion chamber and 4D MGDR within 1%. Finally, 4D MGDR dose changes linearly with the accelerator output: the difference between cumulative ion chamber and MGDR dose changed by no more than 1% (randomly) with the output variation range of 10%. Conclusions: Even for a well-commissioned TPS, comparison metrics show better agreement on average to MGDR than to TPS on the arbitrary-shaped measurable 'patient.' The method requires no more accelerator time than standard QA, while producing more clinically relevant information. Validation in a heterogeneous thoracic phantom is under way, as is the ultimate application of 4D MGDR to virtual motion studies.

  5. Helical tomotherapy with dynamic running-start-stop delivery compared to conventional tomotherapy delivery

    SciTech Connect

    Rong, Yi; Chen, Yu; Lu, Weiguo; Shang, Lu; Zuo, Li; Chen, Quan

    2014-05-15

    Purpose: Despite superior target dose uniformity, helical tomotherapy{sup ®} (HT) may involve a trade-off between longitudinal dose conformity and beam-on time (BOT), due to the limitation of only three available jaw sizes with the conventional HT (1.0, 2.5, and 5.0 cm). The recently introduced dynamic running-start-stop (RSS) delivery allows smaller jaw opening at the superior and inferior ends of the target when a sharp penumbra is needed. This study compared the dosimetric performance of RSS delivery with the fixed jaw HT delivery. Methods: Twenty patient cases were selected and deidentified prior to treatment planning, including 16 common clinical cases (brain, head and neck (HN), lung, and prostate) and four special cases of whole brain with hippocampus avoidance (WBHA) that require a high degree of dose modulation. HT plans were generated for common clinical cases using the fixed 2.5 cm jaw width (HT2.5) and WBHA cases using 1.0 cm (HT1.0). The jaw widths for RSS were preset with a larger size (RSS5.0 vs HT2.5 and RSS2.5 vs HT1.0). Both delivery techniques were planned based on identical contours, prescriptions, and planning objectives. Dose indices for targets and critical organs were compared using dose-volume histograms, BOT, and monitor units. Results: The average BOT was reduced from 4.8 min with HT2.5 to 2.5 min with RSS5.0. Target dose homogeneity with RSS5.0 was shown comparable to HT2.5 for common clinical sites. Superior normal tissue sparing was observed in RSS5.0 for optic nerves and optic chiasm in brain and HN cases. RSS5.0 demonstrated improved dose sparing for cord and esophagus in lung cases, as well as penile bulb in prostate cases. The mean body dose was comparable for both techniques. For the WBHA cases, the target homogeneity was significantly degraded in RSS2.5 without distinct dose sparing for hippocampus, compared to HT1.0. Conclusions: Compared to the fixed jaw HT delivery, RSS combined with a larger jaw width provides faster

  6. Assessing dose rate distributions in VMAT plans

    NASA Astrophysics Data System (ADS)

    Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.

    2016-04-01

    Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within  ±0.4 s and doses  ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional

  7. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  8. Radiobiological advantages of an immediate interstitial boost dose in conservative treatment of breast cancer

    SciTech Connect

    Krishnan, E.C.; Krishnan, L.; Cytaki, E.P.; Woolf, C.D.; Henry, M.M.; Lin, F.; Jewell, W.R. )

    1990-02-01

    Minimum surgery with irradiation is emerging as one of the main modalities of therapy for operable early breast cancer. Between June 1982 and June 1986, 110 breasts with Tis, T1 to T3 lesions have been treated at our institution with lumpectomy and interstitial irradiation to the tumor bed with Iridium-192 perioperatively followed by external beam irradiation. There have been two local recurrences at or near the vicinity of the primary, at a median follow-up of 60 months. To analyze the parameters that might have contributed to the local control, we have examined the treatment volumes, prescribed dose to the tumor bed, dose at the core of the tumor bed, and dose to the surrounding normal tissue. Immediate interstitial implant has the radiobiological advantage of delivering continuous low dose irradiation, immediately upon removal of gross tumor to residual foci. Implantation of the afterloading catheters intraoperatively facilitates accurate dose delivery and avoidance of geographical misses. By precise treatment of any residual foci, immediately upon removal of the gross mass, perioperative interstitial irradiation improves local control and by facilitating less radical surgical excision, leads to better cosmetic results.

  9. SU-E-T-373: A Motorized Stage for Fast and Accurate QA of Machine Isocenter

    SciTech Connect

    Moore, J; Velarde, E; Wong, J

    2014-06-01

    Purpose: Precision delivery of radiation dose relies on accurate knowledge of the machine isocenter under a variety of machine motions. This is typically determined by performing a Winston-Lutz test consisting of imaging a known object at multiple gantry/collimator/table angles and ensuring that the maximum offset is within specified tolerance. The first step in the Winston-Lutz test is careful placement of a ball bearing at the machine isocenter as determined by repeated imaging and shifting until accurate placement has been determined. Conventionally this is performed by adjusting a stage manually using vernier scales which carry the limitation that each adjustment must be done inside the treatment room with the risks of inaccurate adjustment of the scale and physical bumping of the table. It is proposed to use a motorized system controlled outside of the room to improve the required time and accuracy of these tests. Methods: The three dimensional vernier scales are replaced by three motors with accuracy of 1 micron and a range of 25.4mm connected via USB to a computer in the control room. Software is designed which automatically detects the motors and assigns them to proper axes and allows for small shifts to be entered and performed. Input values match calculated offsets in magnitude and sign to reduce conversion errors. Speed of setup, number of iterations to setup, and accuracy of final placement are assessed. Results: Automatic BB placement required 2.25 iterations and 13 minutes on average while manual placement required 3.76 iterations and 37.5 minutes. The average final XYZ offsets is 0.02cm, 0.01cm, 0.04cm for automatic setup and 0.04cm, 0.02cm, 0.04cm for manual setup. Conclusion: Automatic placement decreased time and repeat iterations for setup while improving placement accuracy. Automatic placement greatly reduces the time required to perform QA.

  10. Magnetizable implants for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Forbes, Zachary Graham

    The capability to deliver high effective dosages to specific sites in the human body has become the holy grail of drug delivery research. Drugs with proven effectiveness under in vitro investigation often reach a major roadblock under in vivo testing due to a lack of an effective delivery strategy. In addition, many clinical scenarios require delivery of agents that are therapeutic at the desired delivery point, but otherwise systemically toxic. This project proposes a method for targeted drug delivery by applying high magnetic field gradients within the body to an injected superparamagnetic colloidal fluid carrying a drug, with the aid of modest uniform magnetic field. The design involves patterning of endovascular implants, such as coronary stents, with soft magnetic coatings capable of applying high local magnetic field gradients within the body. Examination of the feasibility of the design has been focused around the treatment of coronary restenosis following angioplasty. Drug-eluting stents, which have debuted in hospitals over the past two years, have thus far reduced restenosis rates to below 10%. Our local drug delivery system is a viable alternative or enhancement to drug-eluting stents, offering increased clinician control of dose size, the ability to treat a site repeatedly, and a wide array of applications for treatment of other pathologies. The theoretical models, parallel plate and pipe flow analysis, and cell culture models presented give insight into the use of micron and sub-micron scale magnetic particles for site-specific delivery of pharmaceuticals and magnetically labeled cells.

  11. Dose homogeneity specification for reference dosimetry of nonstandard fields

    SciTech Connect

    Chung, Eunah; Soisson, Emilie; Seuntjens, Jan

    2012-01-15

    Purpose: To investigate the sensitivity of the plan-class specific correction factor to dose distributions in composite nonstandard field dosimetry. Methods: A cylindrical water-filled PMMA phantom was constructed at the center of which reference absorbed dose could be measured. Ten different TomoTherapy-based IMRT fields were created on the CT images of the phantom. The dose distribution for each IMRT field was estimated at the position of a radiation detector or ionization chamber. The dose in each IMRT field normalized to that in a reference 10 x 10 cm{sup 2} field was measured using a PTW micro liquid ion chamber. Based on the new dosimetry formalism, a plan-class specific correction factor k{sub Q{sub p{sub c{sub s{sub r,Q}{sup f{sub p}{sub c}{sub s}{sub r},f{sub r}{sub e}{sub f}}}}}} for each field was measured for two Farmer-type chambers, Exradin A12 and NE2571, as well as for a smaller Exradin A1SL chamber. The dependence of the measured correction factor on parameters characterizing dose distribution was analyzed. Results: Uncertainty on the plan-class specific correction factor measurement was in the range of 0.3%-0.5% and 0.3%-0.8% for the Farmer-type chambers and the Exradin A1SL, respectively. When the heterogeneity of the central region of the target volume was less than 5%, the correction factor did not differ from unity by more than 0.7% for the three air-filled ionization chambers. For more heterogeneous dose deliveries, the correction factor differed from unity by up to 2.4% for the Farmer-type chambers. For the Exradin A1SL, the correction factor was closer to unity due to the reduced effect of dose gradients, while it was highly variable in different IMRT fields because of a more significant impact of positioning uncertainties on the response of this chamber. Conclusions: The authors have shown that a plan-class specific correction factor can be specified as a function of plan evaluation parameters especially for Farmer-type chambers. This work

  12. Accurate respiration measurement using DC-coupled continuous-wave radar sensor for motion-adaptive cancer radiotherapy.

    PubMed

    Gu, Changzhan; Li, Ruijiang; Zhang, Hualiang; Fung, Albert Y C; Torres, Carlos; Jiang, Steve B; Li, Changzhi

    2012-11-01

    Accurate respiration measurement is crucial in motion-adaptive cancer radiotherapy. Conventional methods for respiration measurement are undesirable because they are either invasive to the patient or do not have sufficient accuracy. In addition, measurement of external respiration signal based on conventional approaches requires close patient contact to the physical device which often causes patient discomfort and undesirable motion during radiation dose delivery. In this paper, a dc-coupled continuous-wave radar sensor was presented to provide a noncontact and noninvasive approach for respiration measurement. The radar sensor was designed with dc-coupled adaptive tuning architectures that include RF coarse-tuning and baseband fine-tuning, which allows the radar sensor to precisely measure movement with stationary moment and always work with the maximum dynamic range. The accuracy of respiration measurement with the proposed radar sensor was experimentally evaluated using a physical phantom, human subject, and moving plate in a radiotherapy environment. It was shown that respiration measurement with radar sensor while the radiation beam is on is feasible and the measurement has a submillimeter accuracy when compared with a commercial respiration monitoring system which requires patient contact. The proposed radar sensor provides accurate, noninvasive, and noncontact respiration measurement and therefore has a great potential in motion-adaptive radiotherapy.

  13. Ultraviolet radiation cataract: dose dependence

    NASA Astrophysics Data System (ADS)

    Soderberg, Per G.; Loefgren, Stefan

    1994-07-01

    Current safety limits for cataract development after acute exposure to ultraviolet radiation (UVR) are based on experiments analyzing experimental data with a quantal, effect-no effect, dose-response model. The present study showed that intensity of forward light scattering is better described with a continuous dose-response model. It was found that 3, 30 and 300 kJ/m2UVR300nm induces increased light scattering within 6 h. For all three doses the intensity of forward light scattering was constant after 6 h. The intensity of forward light scattering was proportional to the log dose of UVR300nm. There was a slight increase of the intensity of forward light scattering on the contralateral side in animals that received 300 kJ/m2. Altogether 72 Sprague-Dawley male rats were included. Half of the rats were exposed in vivo on one side to UVR300nm. The other half was kept as a control group, receiving the same treatment as exposed rats but without delivery of UVR300nm to the eye. Subgroups of the rats received either of the three doses. Rats were sacrificed at varying intervals after the exposure. The lenses were extracted and the forward light scattering was estimated. It is concluded that intensity of forward light scattering in the lens after exposure to UVR300nm should be described with a continuous dose-reponse model.

  14. Current therapies and technological advances in aqueous aerosol drug delivery.

    PubMed

    Watts, Alan B; McConville, Jason T; Williams, Robert O

    2008-09-01

    Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods.

  15. Tuberculosis chemotherapy: current drug delivery approaches

    PubMed Central

    du Toit, Lisa Claire; Pillay, Viness; Danckwerts, Michael Paul

    2006-01-01

    Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance. PMID:16984627

  16. Multimodality image guided total marrow irradiation and verification of the dose delivered to the lung, PTV, and thoracic bone in a patient: a case study.

    PubMed

    Hui, Susanta K; Verneris, M R; Froelich, Jerry; Dusenbery, K; Welsh, James S

    2009-02-01

    This work reports our initial experience using multimodality image guidance to improve total marrow irradiation (TMI) using helical tomotherapy. We also monitored the details of the treatment delivery to glean information necessary for the implementation of future adaptive processes. A patient with metastatic Ewing's sarcoma underwent MRI, and bone scan imaging prior to TMI. A whole body kilovoltage CT (kVCT) scan was obtained for intensity modulated TMI treatment planning, including a boost treatment to areas of bony involvement. The delivered dose was estimated by using MVCT images from the helical tomotherapy treatment unit, compared to the expected dose distributions mapped onto the kVCT images. Clinical concerns regarding patient treatment and dosimetric uncertainties were also evaluated. A small fraction of thoracic bone volume received lower radiation dose than the prescribed dose. Reconstructed planned treatment volume (PTV) and the dose delivered to the lung were identical to planned dose. Bone scan imaging had a higher sensitivity for detecting skeletal metastasis compared to MR imaging. However the bone scan lacked sufficient specificity in three dimensions to be useful for planning conformal radiation boost treatments. Inclusion of appropriate imaging modalities improves detection of metastases, which allows the possibility of a radiation dose boost to metastases during TMI. Conformal intensity modulated radiation therapy via helical tomotherapy permitted radiation delivery to metastases in the skull with reduced dose to brain in conjunction with TMI. While TMI reduces irradiation to the lungs, onboard megavoltage computed tomography (MVCT) to verify accurate volumetric dose coverage to marrow-containing thoracic bones may be essential for successful conformal TMI treatment.

  17. Monte Carlo calculations and measurements of absorbed dose per monitor unit for the treatment of uveal melanoma with proton therapy

    PubMed Central

    Koch, Nicholas; Newhauser, Wayne D; Titt, Uwe; Gombos, Dan; Coombes, Kevin; Starkschall, George

    2014-01-01

    The treatment of uveal melanoma with proton radiotherapy has provided excellent clinical outcomes. However, contemporary treatment planning systems use simplistic dose algorithms that limit the accuracy of relative dose distributions. Further, absolute predictions of absorbed dose per monitor unit are not yet available in these systems. The purpose of this study was to determine if Monte Carlo methods could predict dose per monitor unit (D/MU) value at the center of a proton spread-out Bragg peak (SOBP) to within 1% on measured values for a variety of treatment fields relevant to ocular proton therapy. The MCNPX Monte Carlo transport code, in combination with realistic models for the ocular beam delivery apparatus and a water phantom, was used to calculate dose distributions and D/MU values, which were verified by the measurements. Measured proton beam data included central-axis depth dose profiles, relative cross-field profiles and absolute D/MU measurements under several combinations of beam penetration ranges and range-modulation widths. The Monte Carlo method predicted D/MU values that agreed with measurement to within 1% and dose profiles that agreed with measurement to within 3% of peak dose or within 0.5 mm distance-to-agreement. Lastly, a demonstration of the clinical utility of this technique included calculations of dose distributions and D/MU values in a realistic model of the human eye. It is possible to predict D/MU values accurately for clinical relevant range-modulated proton beams for ocular therapy using the Monte Carlo method. It is thus feasible to use the Monte Carlo method as a routine absolute dose algorithm for ocular proton therapy. PMID:18367789

  18. The FLUKA Code: An Accurate Simulation Tool for Particle Therapy

    PubMed Central

    Battistoni, Giuseppe; Bauer, Julia; Boehlen, Till T.; Cerutti, Francesco; Chin, Mary P. W.; Dos Santos Augusto, Ricardo; Ferrari, Alfredo; Ortega, Pablo G.; Kozłowska, Wioletta; Magro, Giuseppe; Mairani, Andrea; Parodi, Katia; Sala, Paola R.; Schoofs, Philippe; Tessonnier, Thomas; Vlachoudis, Vasilis

    2016-01-01

    Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved. In addition, accurate prediction of emerging secondary radiation is of utmost importance in innovative areas of research aiming at in vivo treatment verification. This contribution will address the recent developments of the FLUKA MC code and its practical applications in this field. Refinements of the FLUKA nuclear models in the therapeutic energy interval lead to an improved description of the mixed radiation field as shown in the presented benchmarks against experimental data with both 4He and 12C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth–dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features. PMID:27242956

  19. The FLUKA Code: An Accurate Simulation Tool for Particle Therapy.

    PubMed

    Battistoni, Giuseppe; Bauer, Julia; Boehlen, Till T; Cerutti, Francesco; Chin, Mary P W; Dos Santos Augusto, Ricardo; Ferrari, Alfredo; Ortega, Pablo G; Kozłowska, Wioletta; Magro, Giuseppe; Mairani, Andrea; Parodi, Katia; Sala, Paola R; Schoofs, Philippe; Tessonnier, Thomas; Vlachoudis, Vasilis

    2016-01-01

    Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved. In addition, accurate prediction of emerging secondary radiation is of utmost importance in innovative areas of research aiming at in vivo treatment verification. This contribution will address the recent developments of the FLUKA MC code and its practical applications in this field. Refinements of the FLUKA nuclear models in the therapeutic energy interval lead to an improved description of the mixed radiation field as shown in the presented benchmarks against experimental data with both (4)He and (12)C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth-dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features. PMID:27242956

  20. Improving Dose Determination Accuracy in Nonstandard Fields of the Varian TrueBeam Accelerator

    NASA Astrophysics Data System (ADS)

    Hyun, Megan A.

    In recent years, the use of flattening-filter-free (FFF) linear accelerators in radiation-based cancer therapy has gained popularity, especially for hypofractionated treatments (high doses of radiation given in few sessions). However, significant challenges to accurate radiation dose determination remain. If physicists cannot accurately determine radiation dose in a clinical setting, cancer patients treated with these new machines will not receive safe, accurate and effective treatment. In this study, an extensive characterization of two commonly used clinical radiation detectors (ionization chambers and diodes) and several potential reference detectors (thermoluminescent dosimeters, plastic scintillation detectors, and alanine pellets) has been performed to investigate their use in these challenging, nonstandard fields. From this characterization, reference detectors were identified for multiple beam sizes, and correction factors were determined to improve dosimetric accuracy for ionization chambers and diodes. A validated computational (Monte Carlo) model of the TrueBeam(TM) accelerator, including FFF beam modes, was also used to calculate these correction factors, which compared favorably to measured results. Small-field corrections of up to 18 % were shown to be necessary for clinical detectors such as microionization chambers. Because the impact of these large effects on treatment delivery is not well known, a treatment planning study was completed using actual hypofractionated brain, spine, and lung treatments that were delivered at the UW Carbone Cancer Center. This study demonstrated that improperly applying these detector correction factors can have a substantial impact on patient treatments. This thesis work has taken important steps toward improving the accuracy of FFF dosimetry through rigorous experimentally and Monte-Carlo-determined correction factors, the validation of an important published protocol (TG-51) for use with FFF reference fields, and a

  1. Optimal oxygen titration in patients with chronic obstructive pulmonary disease: A role for automated oxygen delivery?

    PubMed Central

    Lellouche, François; Lipes, Jed; L’Her, Erwan

    2013-01-01

    Oxygen therapy can be life-saving for patients with chronic obstructive pulmonary disease (COPD) and is the backbone of any acute COPD treatment strategy. Although largely considered to be a benign drug, many publications have highlighted the need to accurately adjust oxygen delivery to avoid both hypoxemia and the problem of hyperoxia-induced hypercapnia. Recent clinical data have shown that the deleterious effects of excess oxygen treatment can not only alter carbon dioxide levels (which has been known for more than 60 years) but can also lead to an increase in mortality. Nevertheless, despite the extensive literature, the risks associated with hyperoxia are often overlooked and published clinical recommendations are largely ignored. This failure in knowledge translation has become increasingly important not only because of the desire to reduce medical error, but in a society with limited health care resources, the economic burden of COPD is such that it cannot afford to make preventable medical mistakes. Recently, novel devices have been developed to automatically adjust oxygen flow rates to maintain stable oxygen saturations. These closed-loop oxygen delivery systems have the potential to reduce medical error, improve morbidity and mortality, and reduce health care costs. Preliminary data in this field are promising and will require a significant amount of research in the coming years to determine the precise indications for these systems. The importance of appropriate oxygen dosing and the current literature regarding novel oxygen delivery systems are reviewed. PMID:23936881

  2. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  3. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  4. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  5. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  6. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  7. Analytic IMRT dose calculations utilizing Monte Carlo to predict MLC fluence modulation

    SciTech Connect

    Mihaylov, I.B.; Lerma, F.A.; Wu, Y.; Siebers, J.V.

    2006-04-15

    A hybrid dose-computation method is designed which accurately accounts for multileaf collimator (MLC)-induced intensity modulation in intensity modulated radiation therapy (IMRT) dose calculations. The method employs Monte Carlo (MC) modeling to determine the fluence modulation caused by the delivery of dynamic or multisegmental (step-and-shoot) MLC fields, and a conventional dose-computation algorithm to estimate the delivered dose to a phantom or a patient. Thus, it determines the IMRT fluence prediction accuracy achievable by analytic methods in the limit that the analytic method includes all details of the MLC leaf transport and scatter. The hybrid method is validated and benchmarked by comparison with in-phantom film dose measurements, as well as dose calculations from two in-house, and two commercial treatment planning system analytic fluence estimation methods. All computation methods utilize the same dose algorithm to calculate dose to a phantom, varying only in the estimation of the MLC modulation of the incident photon energy fluence. Gamma analysis, with respect to measured two-dimensional (2D) dose planes, is used to benchmark each algorithm's performance. The analyzed fields include static and dynamic test patterns, as well as fields from ten DMLC IMRT treatment plans (79 fields) and five SMLC treatment plans (29 fields). The test fields (fully closed MLC, picket fence, sliding windows of different size, and leaf-tip profiles) cover the extremes of MLC usage during IMRT, while the patient fields represent realistic clinical conditions. Of the methods tested, the hybrid method most accurately reproduces measurements. For the hybrid method, 79 of 79 DMLC field calculations have {gamma}{<=}1 (3%/3 mm) for more than 95% of the points (per field) while for SMLC fields, 27 of 29 pass the same criteria. The analytic energy fluence estimation methods show inferior pass rates, with 76 of 79 DMLC and 24 of 29 SMLC fields having more than 95% of the test points

  8. Ultrasound-Mediated Transdermal Protein Delivery

    NASA Astrophysics Data System (ADS)

    Mitragotri, Samir; Blankschtein, Daniel; Langer, Robert

    1995-08-01

    Transdermal drug delivery offers a potential method of drug administration. However, its application has been limited to a few low molecular weight compounds because of the extremely low permeability of human skin. Low-frequency ultrasound was shown to increase the permeability of human skin to many drugs, including high molecular weight proteins, by several orders of magnitude, thus making transdermal administration of these molecules potentially feasible. It was possible to deliver and control therapeutic doses of proteins such as insulin, interferon γ, and erythropoeitin across human skin. Low-frequency ultrasound is thus a potential noninvasive substitute for traditional methods of drug delivery, such as injections.

  9. Commissioning of the discrete spot scanning proton beam delivery system at University of Texas M.D. Anderson Cancer Center, Proton Therapy Center, Houston

    SciTech Connect

    Gillin, Michael T.; Sahoo, Narayan; Bues, Martin; Ciangaru, George; Sawakuchi, Gabriel; Poenisch, Falk; Arjomandy, Bijan; Martin, Craig; Titt, Uwe; Suzuki, Kazumichi; Smith, Alfred R.; Zhu, X. Ronald

    2010-01-15

    Purpose: To describe a summary of the clinical commissioning of the discrete spot scanning proton beam at the Proton Therapy Center, Houston (PTC-H). Methods: Discrete spot scanning system is composed of a delivery system (Hitachi ProBeat), an electronic medical record (Mosaiq V 1.5), and a treatment planning system (TPS) (Eclipse V 8.1). Discrete proton pencil beams (spots) are used to deposit dose spot by spot and layer by layer for the proton distal ranges spanning from 4.0 to 30.6 g/cm{sup 2} and over a maximum scan area at the isocenter of 30x30 cm{sup 2}. An arbitrarily chosen reference calibration condition has been selected to define the monitor units (MUs). Using radiochromic film and ion chambers, the authors have measured spot positions, the spot sizes in air, depth dose curves, and profiles for proton beams with various energies in water, and studied the linearity of the dose monitors. In addition to dosimetric measurements and TPS modeling, significant efforts were spent in testing information flow and recovery of the delivery system from treatment interruptions. Results: The main dose monitors have been adjusted such that a specific amount of charge is collected in the monitor chamber corresponding to a single MU, following the IAEA TRS 398 protocol under a specific reference condition. The dose monitor calibration method is based on the absolute dose per MU, which is equivalent to the absolute dose per particle, the approach used by other scanning beam institutions. The full width at half maximum for the spot size in air varies from approximately 1.2 cm for 221.8 MeV to 3.4 cm for 72.5 MeV. The measured versus requested 90% depth dose in water agrees to within 1 mm over ranges of 4.0-30.6 cm. The beam delivery interlocks perform as expected, guarantying the safe and accurate delivery of the planned dose. Conclusions: The dosimetric parameters of the discrete spot scanning proton beam have been measured as part of the clinical commissioning program

  10. Experimental verification of a Monte Carlo-based MLC simulation model for IMRT dose calculation

    SciTech Connect

    Tyagi, Neelam; Moran, Jean M.; Litzenberg, Dale W.; Bielajew, Alex F.; Fraass, Benedick A.; Chetty, Indrin J.

    2007-02-15

    Inter- and intra-leaf transmission and head scatter can play significant roles in intensity modulated radiation therapy (IMRT)-based treatment deliveries. In order to accurately calculate the dose in the IMRT planning process, it is therefore important that the detailed geometry of the multi-leaf collimator (MLC), in addition to other components in the accelerator treatment head, be accurately modeled. In this paper, we have used the Monte Carlo method (MC) to develop a comprehensive model of the Varian 120 leaf MLC and have compared it against measurements in homogeneous phantom geometries under different IMRT delivery circumstances. We have developed a geometry module within the DPM MC code to simulate the detailed MLC design and the collimating jaws. Tests consisting of leakage, leaf positioning and static MLC shapes were performed to verify the accuracy of transport within the MLC model. The calculations show agreement within 2% in the high dose region for both film and ion-chamber measurements for these static shapes. Clinical IMRT treatment plans for the breast [both segmental MLC (SMLC) and dynamic MLC (DMLC)], prostate (SMLC) and head and neck split fields (SMLC) were also calculated and compared with film measurements. Such a range of cases were chosen to investigate the accuracy of the model as a function of modulation in the beamlet pattern, beamlet width, and field size. The overall agreement is within 2%/2 mm of the film data for all IMRT beams except the head and neck split field, which showed differences up to 5% in the high dose regions. Various sources of uncertainties in these comparisons are discussed.

  11. Characterization of exposure and dose of man made vitreous fiber in experimental studies.

    PubMed Central

    Hamilton, R D; Miiller, W C; Christensen, D R; Anderson, R; Hesterberg, T W

    1994-01-01

    The use of fibrous test materials in in vivo experiments introduces a number of significant problems not associated with nonfibrous particulates. The key to all aspects of the experiment is the accurate characterization of the test material in terms of fiber length, diameter, particulate content, and chemistry. All data related to fiber properties must be collected in a statistically sound manner to eliminate potential bias. Procedures similar to those outlined by the National Institute of Occupational Safety and Health (NIOSH) or the World Health Organization (WHO) must be the basis of any fiber characterization. The test material to which the animal is exposed must be processed to maximize the amount of respirable fiber and to minimize particulate content. The complex relationship among the characteristics of the test material, the properties of the delivery system, and the actual dose that reaches the target tissue in the lung makes verification of dose essential. In the case of man-made vitreous fibers (MMVF), dose verification through recovery of fiber from exposed animals is a complex task. The potential for high fiber solubility makes many of the conventional techniques for tissue preservation and digestion inappropriate. Processes based on the minimum use of aggressive chemicals, such as cold storage and low temperature ashing, are potentially useful for a wide range of inorganic fibers. Any processes used to assess fiber exposure and dose must be carefully validated to establish that the chemical and physical characteristics of the fibers have not been changed and that the dose to the target tissue is completely and accurately described. PMID:7882912

  12. A Simple Low-dose X-ray CT Simulation from High-dose Scan

    PubMed Central

    Zeng, Dong; Huang, Jing; Bian, Zhaoying; Niu, Shanzhou; Zhang, Hua; Feng, Qianjin; Liang, Zhengrong

    2015-01-01

    Low-dose X-ray computed tomography (CT) simulation from high-dose scan is required in optimizing radiation dose to patients. In this study, we propose a simple low-dose CT simulation strategy in sinogram domain using the raw data from high-dose scan. Specially, a relationship between the incident fluxes of low- and high- dose scans is first determined according to the repeated projection measurements and analysis. Second, the incident flux level of the simulated low-dose scan is generated by properly scaling the incident flux level of high-dose scan via the determined relationship in the first step. Third, the low-dose CT transmission data by energy integrating detection is simulated by adding a statistically independent Poisson noise distribution plus a statistically independent Gaussian noise distribution. Finally, a filtered back-projection (FBP) algorithm is implemented to reconstruct the resultant low-dose CT images. The present low-dose simulation strategy is verified on the simulations and real scans by comparing it with the existing low-dose CT simulation tool. Experimental results demonstrated that the present low-dose CT simulation strategy can generate accurate low-dose CT sinogram data from high-dose scan in terms of qualitative and quantitative measurements. PMID:26543245

  13. SPE dose prediction using locally weighted regression.

    PubMed

    Hines, J W; Townsend, L W; Nichols, T F

    2005-01-01

    When astronauts are outside Earth's protective magnetosphere, they are subject to large radiation doses resulting from solar particle events. The total dose received from a major solar particle event in deep space could cause severe radiation poisoning. The dose is usually received over a 20-40 h time interval but the event's effects may be reduced with an early warning system. This paper presents a method to predict the total dose early in the event. It uses a locally weighted regression model, which is easier to train, and provides predictions as accurate as the neural network models that were used previously. PMID:16604613

  14. A machine learning approach to the accurate prediction of multi-leaf collimator positional errors

    NASA Astrophysics Data System (ADS)

    Carlson, Joel N. K.; Park, Jong Min; Park, So-Yeon; In Park, Jong; Choi, Yunseok; Ye, Sung-Joon

    2016-03-01

    Discrepancies between planned and delivered movements of multi-leaf collimators (MLCs) are an important source of errors in dose distributions during radiotherapy. In this work we used machine learning techniques to train models to predict these discrepancies, assessed the accuracy of the model predictions, and examined the impact these errors have on quality assurance (QA) procedures and dosimetry. Predictive leaf motion parameters for the models were calculated from the plan files, such as leaf position and velocity, whether the leaf was moving towards or away from the isocenter of the MLC, and many others. Differences in positions between synchronized DICOM-RT planning files and DynaLog files reported during QA delivery were used as a target response for training of the models. The final model is capable of predicting MLC positions during delivery to a high degree of accuracy. For moving MLC leaves, predicted positions were shown to be significantly closer to delivered positions than were planned positions. By incorporating predicted positions into dose calculations in the TPS, increases were shown in gamma passing rates against measured dose distributions recorded during QA delivery. For instance, head and neck plans with 1%/2 mm gamma criteria had an average increase in passing rate of 4.17% (SD  =  1.54%). This indicates that the inclusion of predictions during dose calculation leads to a more realistic representation of plan delivery. To assess impact on the patient, dose volumetric histograms (DVH) using delivered positions were calculated for comparison with planned and predicted DVHs. In all cases, predicted dose volumetric parameters were in closer agreement to the delivered parameters than were the planned parameters, particularly for organs at risk on the periphery of the treatment area. By incorporating the predicted positions into the TPS, the treatment planner is given a more realistic view of the dose distribution as it will truly be

  15. Pre-treatment radiotherapy dose verification using Monte Carlo doselet modulation in a spherical phantom

    NASA Astrophysics Data System (ADS)

    Townson, Reid W.; Zavgorodni, Sergei

    2014-04-01

    Due to the increasing complexity of radiotherapy delivery, accurate dose verification has become an essential part of the clinical treatment process. The purpose of this work was to develop a pre-treatment verification technique capable of quickly reconstructing 3D dose distributions from both coplanar and non-coplanar treatments. For each treatment field, electronic portal images were taken in non-transmission mode (with no patient in the beam) allowing the derivation of the delivered fluence maps. The dose reconstruction was then performed in a spherical water phantom by modulating and summing the Monte Carlo (MC) doselets, defined on a spherical co-ordinate system, and pre-calculated from azimuthally symmetric fluence above the jaws. The technique, called the spherical doselet modulation (SDM) method, essentially eliminates the statistical uncertainty of the MC dose calculations by exploiting the azimuthal symmetry in both a patient-independent phase-space and in a virtual spherical water phantom. For example, this symmetry allowed the number of doselets necessary for dose reconstruction to be reduced by a factor of ˜250. In this work, only 51 radially binned doselets were used (each generated from all particles in a given annulus of the phase-space, azimuthally redistributed into a small cylindrical sector). The SDM method mitigates the most computationally intensive part of this type of dose reconstruction--reading, weighting and summing dose matrices. The accuracy of the system was tested against MC calculations as well as our previously reported phase-space modulation method, using a series of open field and IMRT cases. The mean chi- and gamma-test 3%/3 mm success rates of the SDM method were 98.6% and 99.5%, respectively, when compared to full MC simulation. The total calculation time was 96 s per treatment field on a single processor core.

  16. Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan.

    PubMed

    Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

    2015-04-21

    At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy(-1) and β = 0.0615 Gy(-2) as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

  17. Sci—Sat AM: Stereo — 01: 3D Pre-treatment Dose Verification for Stereotactic Body Radiation Therapy Patients

    SciTech Connect

    Asuni, G; Beek, T van; Van Utyven, E; McCowan, P; McCurdy, B.M.C.

    2014-08-15

    Radical treatment techniques such as stereotactic body radiation therapy (SBRT) are becoming popular and they involve delivery of large doses in fewer fractions. Due to this feature of SBRT, a high-resolution, pre-treatment dose verification method that makes use of a 3D patient representation would be appropriate. Such a technique will provide additional information about dose delivered to the target volume(s) and organs-at-risk (OARs) in the patient volume compared to 2D verification methods. In this work, we investigate an electronic portal imaging device (EPID) based pre-treatment QA method which provides an accurate reconstruction of the 3D-dose distribution in the patient model. Customized patient plans are delivered ‘in air’ and the portal images are collected using the EPID in cine mode. The images are then analysed to determine an estimate of the incident energy fluence. This is then passed to a collapsed-cone convolution dose algorithm which reconstructs a 3D patient dose estimate on the CT imaging dataset. To date, the method has been applied to 5 SBRT patient plans. Reconstructed doses were compared to those calculated by the TPS. Reconstructed mean doses were mostly within 3% of those in the TPS. DVHs of target volumes and OARs compared well. The Chi pass rates using 3%/3mm in the high dose region are greater than 97% in all cases. These initial results demonstrate clinical feasibility and utility of a robust, efficient, effective and convenient pre-treatment QA method using EPID. Research sponsored in part by Varian Medical Systems.

  18. Transdermal delivery of contraceptives.

    PubMed

    Friend, D R

    1990-01-01

    Contraceptive agents are administered to the body through a variety of routes. Research has recently been directed at examining the transdermal route for systemic delivery of contraceptive agents, including estrogens and progestins. The transdermal route has several potential advantages over the other routes of administration: (1) improved compliance, (2) once-weekly administration, (3) delivery is easily terminated, and (4) some side effects can be alleviated based on more constant delivery rates. This article reviews the permeability of skin toward contraceptive steroids and how skin permeability is evaluated. The metabolism of contraceptive steroids is also considered. Transdermal delivery systems used to deliver contraceptives are presented, followed by a detailed discussion of several delivery systems for specific contraceptive agents such as levonorgestrel and estradiol. The potential problem of skin irritation is presented as it relates to transdermal contraceptive delivery systems, all of which will be worn chronically. PMID:2272099

  19. Technical basis for dose reconstruction

    SciTech Connect

    Anspaugh, L.R.

    1996-01-31

    The purpose of this paper is to consider two general topics: technical considerations of why dose-reconstruction studies should or should not be performed and methods of dose reconstruction. The first topic is of general and growing interest as the number of dose-reconstruction studies increases, and one asks the question whether it is necessary to perform a dose reconstruction for virtually every site at which, for example, the Department of Energy (DOE) has operated a nuclear-related facility. And there is the broader question of how one might logically draw the line at performing or not performing dose-reconstruction (radiological and chemical) studies for virtually every industrial complex in the entire country. The second question is also of general interest. There is no single correct way to perform a dose-reconstruction study, and it is important not to follow blindly a single method to the point that cheaper, faster, more accurate, and more transparent methods might not be developed and applied.

  20. A silicon strip detector dose magnifying glass for IMRT dosimetry

    SciTech Connect

    Wong, J. H. D.; Carolan, M.; Lerch, M. L. F.; Petasecca, M.; Khanna, S.; Perevertaylo, V. L.; Metcalfe, P.; Rosenfeld, A. B.

    2010-02-15

    Purpose: Intensity modulated radiation therapy (IMRT) allows the delivery of escalated radiation dose to tumor while sparing adjacent critical organs. In doing so, IMRT plans tend to incorporate steep dose gradients at interfaces between the target and the organs at risk. Current quality assurance (QA) verification tools such as 2D diode arrays, are limited by their spatial resolution and conventional films are nonreal time. In this article, the authors describe a novel silicon strip detector (CMRP DMG) of high spatial resolution (200 {mu}m) suitable for measuring the high dose gradients in an IMRT delivery. Methods: A full characterization of the detector was performed, including dose per pulse effect, percent depth dose comparison with Farmer ion chamber measurements, stem effect, dose linearity, uniformity, energy response, angular response, and penumbra measurements. They also present the application of the CMRP DMG in the dosimetric verification of a clinical IMRT plan. Results: The detector response changed by 23% for a 390-fold change in the dose per pulse. A correction function is derived to correct for this effect. The strip detector depth dose curve agrees with the Farmer ion chamber within 0.8%. The stem effect was negligible (0.2%). The dose linearity was excellent for the dose range of 3-300 cGy. A uniformity correction method is described to correct for variations in the individual detector pixel responses. The detector showed an over-response relative to tissue dose at lower photon energies with the maximum dose response at 75 kVp nominal photon energy. Penumbra studies using a Varian Clinac 21EX at 1.5 and 10.0 cm depths were measured to be 2.77 and 3.94 mm for the secondary collimators, 3.52 and 5.60 mm for the multileaf collimator rounded leaf ends, respectively. Point doses measured with the strip detector were compared to doses measured with EBT film and doses predicted by the Philips Pinnacle treatment planning system. The differences were 1

  1. Pathophysiological and disease constraints on aerosol delivery

    SciTech Connect

    Gerrity, T.R.

    1989-01-01

    The dose of inhaled particles to the respiratory tract depends upon many factors. These factors include the size of the particles, the pattern of breathing (flow and tidal volume), the physical properties of the articles (hygroscopic or non-hygroscopic), anatomy of the respiratory tract, and the pathophysiologic status of the respiratory tract. In addition to these factors, which are primarily related to the deposition of particles, the rate of particle clearance from the respiratory tract also influences the dose of particles. The paper is a review of the various factors influencing dose of inhaled particles to the respiratory tract. The emphasis of the paper is on therapeutic aerosol particles, though the principals discussed also apply to toxic particles as well. An important area of consideration is the influence of disease on the delivery of particle dose. From the point of view of toxic particles this is important when considering potential susceptible populations.

  2. Optimizing portal dose calculation for an amorphous silicon detector using Swiss Monte Carlo Plan

    NASA Astrophysics Data System (ADS)

    Frauchiger, D.; Fix, M. K.; Frei, D.; Volken, W.; Mini, R.; Manser, P.

    2007-06-01

    Purpose: Modern treatment planning systems (TPS) are able to calculate doses within the patient for numerous delivery techniques as e. g. intensity modulated radiation therapy (IMRT). Even dose predictions to an electronic portal image device (EPID) are available in some TPS, but with limitations in accuracy. With the steadily increasing number of facilities using EPIDs for pre-treatment and treatment verification, the desire of calculating accurate EPID dose distributions is growing. A solution for this problem is the use of Monte Carlo (MC) methods. Aims of this study were firstly to implement geometries of an amorphous silicon based EPID with varying levels of geometry complexity. Secondly to analyze the differences between simulation results and measurements for each geometry. Thirdly, to compare different transport algorithms within all EPID geometries in a flexible C++ MC environment. Materials and Methods: In this work three geometry sets, representing the EPID, are implemented and investigated. To gain flexibility in the MC environment geometry and particle transport code are independent. That allows the user to select between the transport algorithms EGSnrc, VMC++ and PIN (an in-house developed transport code) while using one of the implemented geometries of the EPID. For all implemented EPID geometries dose distributions were calculated for 6 MV and 15 MV beams using different transport algorithms and are then compared with measurements. Results: A very simple geometry, consisting of a water slab, is not capable to reproduce measurements, whereas 8 material layers perform well. The more layers with different materials are used, the longer last the calculations. EGSnrc and VMC++ lead to dosimetrically equal results. Gamma analysis between calculated and measured EPID dose distributions, using a dose difference criterion of ± 3% and a distance to agreement criterion of ± 3 mm, revealed a gamma value < 1 within more than 95% of all pixels, that have a

  3. Experimental verification of a real-time compensation functionality for dose changes due to target motion in scanned particle therapy

    SciTech Connect

    Luechtenborg, Robert; Saito, Nami; Durante, Marco; Bert, Christoph

    2011-10-15

    Purpose: Implementation and experimental assessment of a real-time dose compensation system for beam tracking in scanned carbon beam therapy of intrafractionally moving targets. Methods: A real-time dose compensation functionality has been developed and implemented at the experimental branch of the beam tracking system at GSI Helmholtzzentrum fuer Schwerionenforschung (GSI). Treatment plans for different target geometries have been optimized. They have been delivered using scanned carbon ions with beam tracking (BT) and real-time dose compensation combined with beam tracking (RDBT), respectively. Target motion was introduced by a rotating table. Dose distributions were assessed by ionization chamber measurements and dose reconstructions. These distributions have been compared to stationary delivery for BT as well as RDBT. Additionally simulations have been performed to investigate the dependence of delivered dose distributions on varying motion starting phases for BT and RDBT, respectively. Results: Average measured dose differences between static delivery and motion influenced delivery could be reduced from 27-68 mGy when BT was used to 12-37 mGy when RDBT was used. Nominal dose was 1000 mGy. Simulated dose deliveries showed improvements in dose delivery and robustness against varying starting motion phases when RDBT was used. Conclusions: A real-time dose compensation functionality extending the existing beam tracking functionality has been implemented and verified by measurements. Measurements and simulated dose deliveries show that real-time dose compensation can substantially improve delivered dose distributions for large rotational target motion compared to beam tracking alone.

  4. Barriers to drug delivery in solid tumors.

    PubMed

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  5. Barriers to drug delivery in solid tumors

    PubMed Central

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  6. Confectionery-based dose forms.

    PubMed

    Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

    2015-01-01

    Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations. PMID:25146440

  7. Peripheral doses from pediatric IMRT

    SciTech Connect

    Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David

    2006-07-15

    Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 to 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged

  8. A dosimetric phantom study of dose accuracy and build-up effects using IMRT and RapidArc in stereotactic irradiation of lung tumours

    PubMed Central

    2012-01-01

    Background and purpose Stereotactic lung radiotherapy (SLRT) has emerged as a curative treatment for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC) and the use of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc treatments (VMAT) have been proposed as the best practical approaches for the delivery of SLRT. However, a large number of narrow field shapes are needed in the dose delivery of intensity-modulated techniques and the probability of underdosing the tumour periphery increases as the effective field size is decreased. The purpose of this study was to evaluate small lung tumour doses irradiated by intensity-modulated techniques to understand the risk for dose calculation errors in precision radiotherapy such as SLRT. Materials and methods The study was executed with two heterogeneous phantoms with targets of Ø1.5 and Ø4.0 cm. Dose distributions in the simulated tumours delivered by small sliding window apertures (SWAs), IMRT and RapidArc treatment plans were measured with radiochromic film. Calculation algorithms of pencil beam convolution (PBC) and anisotropic analytic algorithm (AAA) were used to calculate the corresponding dose distributions. Results Peripheral doses of the tumours were decreased as SWA decreased, which was not modelled by the calculation algorithms. The smallest SWA studied was 2 mm, which reduced the 90% isodose line width by 4.2 mm with the Ø4.0 cm tumour as compared to open field irradiation. PBC was not able to predict the dose accurately as the gamma evaluation failed to meet the criteria of ±3%/±1 mm on average in 61% of the defined volume with the smaller tumour. With AAA the corresponding value was 16%. The dosimetric inaccuracy of AAA was within ±3% with the optimized treatment plans of IMRT and RapidArc. The exception was the clinical RapidArc plan with dose overestimation of 4%. Conclusions Overall, the peripheral doses of the simulated lung tumours were

  9. Octavius 4D characterization for flattened and flattening filter free rotational deliveries

    SciTech Connect

    McGarry, Conor K.; Hounsell, Alan R.; O’Connell, Barry F.; Grattan, Mark W. D.; Agnew, Christina E.; Irvine, Denise M.

    2013-09-15

    Purpose: In this study the Octavius detector 729 ionization chamber (IC) array with the Octavius 4D phantom was characterized for flattening filter (FF) and flattening filter free (FFF) static and rotational beams. The device was assessed for verification with FF and FFF RapidArc treatment plans.Methods: The response of the detectors to field size, dose linearity, and dose rate were assessed for 6 MV FF beams and also 6 and 10 MV FFF beams. Dosimetric and mechanical accuracy of the detector array within the Octavius 4D rotational phantom was evaluated against measurements made using semiflex and pinpoint ionization chambers, and radiochromic film. Verification FF and FFF RapidArc plans were assessed using a gamma function with 3%/3 mm tolerances and 2%/2 mm tolerances and further analysis of these plans was undertaken using film and a second detector array with higher spatial resolution.Results: A warm-up dose of >6 Gy was required for detector stability. Dose-rate measurements were stable across a range from 0.26 to 15 Gy/min and dose response was linear, although the device overestimated small doses compared with pinpoint ionization chamber measurements. Output factors agreed with ionization chamber measurements to within 0.6% for square fields of side between 3 and 25 cm and within 1.2% for 2 × 2 cm{sup 2} fields. The Octavius 4D phantom was found to be consistent with measurements made with radiochromic film, where the gantry angle was found to be within 0.4° of that expected during rotational deliveries. RapidArc FF and FFF beams were found to have an accuracy of >97.9% and >90% of pixels passing 3%/3 mm and 2%/2 mm, respectively. Detector spatial resolution was observed to be a factor in determining the accurate delivery of each plan, particularly at steep dose gradients. This was confirmed using data from a second detector array with higher spatial resolution and with radiochromic film.Conclusions: The Octavius 4D phantom with associated Octavius detector

  10. Design of Drug Delivery Methods for the Brain and Central Nervous System

    NASA Astrophysics Data System (ADS)

    Lueshen, Eric

    Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection

  11. Dose and Position Measurements using a Novel Four-Dimensional In Vivo Dosimetry System

    NASA Astrophysics Data System (ADS)

    Cherpak, Amanda

    agreement between dose measurements and treatment plan calculations was within 5% for both free breathing and adaptive treatment deliveries and position measurements were accurate and consistent between the CT and treatment delivery rooms. The two clinical trials demonstrated that the RADPOS system can be used during daily treatments without any disruption to the treatment schedule or discomfort to patients. The lung patient study found significant deviations in external surface motion which emphasize a need for continued position monitoring. Average measured dose values were in agreement with treatment plan dose calculations for the majority of points. The second clinical trial highlighted deviations from calculated treatment plan values as well as changes in position due to needle placement, swelling, and other internal motion as well as changes due to the TRUS probe. These changes were found to be significant in several cases and should therefore be quantified to evaluate influence on dose distributions.

  12. Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

    SciTech Connect

    Sha, Rajib Lochan; Reddy, Palreddy Yadagiri; Rao, Ramakrishna; Muralidhar, Kanaparthy R.; Kudchadker, Rajat J.

    2011-01-01

    High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm{sup 3}) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5-10% in 26 patients, and 10-14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

  13. Dose Imprecision and Resistance: Free-Choice Medicated Feeds in Industrial Food Animal Production in the United States

    PubMed Central

    Love, David C.; Davis, Meghan F.; Bassett, Anna; Gunther, Andrew; Nachman, Keeve E.

    2011-01-01

    Background Industrial food animal production employs many of the same antibiotics or classes of antibiotics that are used in human medicine. These drugs can be administered to food animals in the form of free-choice medicated feeds (FCMF), where animals choose how much feed to consume. Routine administration of these drugs to livestock selects for microorganisms that are resistant to medications critical to the treatment of clinical infections in humans. Objectives In this commentary, we discuss the history of medicated feeds, the nature of FCMF use with regard to dose delivery, and U.S. policies that address antimicrobial drug use in food animals. Discussion FCMF makes delivering a predictable, accurate, and intended dose difficult. Overdosing can lead to animal toxicity; underdosing or inconsistent dosing can result in a failure to resolve animal diseases and in the development of antimicrobial-resistant microorganisms. Conclusions The delivery of antibiotics to food animals for reasons other than the treatment of clinically diagnosed disease, especially via free-choice feeding methods, should be reconsidered. PMID:21030337

  14. Targeted Lung Delivery of Nasally Administered Aerosols

    PubMed Central

    Tian, Geng; Hindle, Michael; Longest, P. Worth

    2014-01-01

    Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages including co-administration during non-invasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1–2.6x, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35x. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions. PMID:24932058

  15. Systemic delivery of artemether by dissolving microneedles.

    PubMed

    Qiu, Yuqin; Li, Chun; Zhang, Suohui; Yang, Guozhong; He, Meilin; Gao, Yunhua

    2016-07-11

    Dissolving microneedles (DMNs) based transdermal delivery is an attractive drug delivery approach with minimal invasion. However, it is still challenging to load poorly water-soluble drugs in DMNs for systemic delivery. The aim of the study was to develop DMNs loaded with artemether (ARM) as a model drug, to enable efficient drug penetration through skin for systemic absorption and distribution. The micro-conduits created by microneedles were imaged by confocal laser scanning microscopy (CLSM), and the insertion depth was suggested to be about 270μm. The maximum amount of ARM delivered into skin was 72.67±2.69% of the initial dose loaded on DMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma ARM concentrations, after ARM-loaded DMNs treatment. In contrast to intramuscular injection, DMNs application resulted in lower peak plasma levels, but higher plasma ARM concentration at 8h after administration. There were no significant difference in area under the curve and bioavailability between DMNs group and intramuscular group (P>0.05). Pharmacodynamics studies performed in collagen-induced arthritis (CIA) rats showed that ARM-loaded DMNs could reverse paw edema, similar to ARM intramuscular injection. In conclusion, developed DMNs provided a potential minimally invasive route for systemic delivery of poorly water-soluble drugs. PMID:27150946

  16. Tomotherapy and other innovative IMRT delivery systems.

    PubMed

    Fenwick, John D; Tomé, Wolfgang A; Soisson, Emilie T; Mehta, Minesh P; Rock Mackie, T

    2006-10-01

    Fixed-field treatments, delivered using conventional clinical linear accelerators fitted with multileaf collimators, have rapidly become the standard form of intensity-modulated radiotherapy (IMRT). Several innovative nonstandard alternatives also exist, for which delivery and treatment planning systems are now commercially available. Three of these nonstandard IMRT approaches are reviewed here: tomotherapy, robotic linear accelerators (CyberKnife, Accuray Inc., Sunnyvale, CA), and standard linear accelerators modulated by jaws alone or by their jaws acting together with a tertiary beam-masking device. Rationales for the nonstandard IMRT approaches are discussed, and elements of their delivery system designs are briefly described. Differences between fixed-field IMRT dose distributions and the distributions that can be delivered by using the nonstandard technologies are outlined. Because conventional linear accelerators are finely honed machines, innovative design enhancement of one aspect of system performance often limits another facet of machine capability. Consequently the various delivery systems may prove optimal for different types of treatment, with specific machine designs excelling for disease sites with specific target volume and normal structure topologies. However it is likely that the delivery systems will be distinguished not just by the optimality of the dose distributions they deliver, but also by factors such as the efficiency of their treatment process, the integration of their onboard imaging systems into that process, and their ability to measure and minimize or compensate for target movement, including the effects of respiratory motion.

  17. Fast Arc Delivery for Stereotactic Body Radiotherapy of Vertebral and Lung Tumors

    SciTech Connect

    Ong, Chin Loon; Verbakel, Wilko F.A.R.; Dahele, Max; Cuijpers, Johan P.; Slotman, Ben J.; Senan, Suresh

    2012-05-01

    Purpose: Flattening filter-free (FFF) beams with higher dose rates and faster delivery are now clinically available. The purpose of this planning study was to compare optimized non-FFF and FFF RapidArc plans for stereotactic body radiotherapy (SBRT) and to validate the accuracy of fast arc delivery. Methods and Material: Ten patients with peripheral lung tumors and 10 with vertebral metastases were planned using RapidArc with a flattened 6-MV photon beam and a 10-MV FFF beam for fraction doses of 7.5-18 Gy. Dosimetry of the target and organs at risk (OAR), number of monitor units (MU), and beam delivery times were assessed. GafChromic EBT2 film measurements of FFF plans were performed to compare calculated and delivered dose distributions. Results: No major dosimetric differences were seen between the two delivery techniques. For lung SBRT plans, conformity indices and OAR doses were similar, although the average MU required were higher with FFF plans. For vertebral SBRT, FFF plans provided comparable PTV coverage, with no significant differences in OAR doses. Average beam delivery times were reduced by a factor of up to 2.5, with all FFF fractions deliverable within 4 min. Measured FFF plans showed high agreement with calculated plans, with more than 99% of the area within the region of interest fulfilling the acceptance criterion. Conclusion: The higher dose rate of FFF RapidArc reduces delivery times significantly, without compromising plan quality or accuracy of dose delivery.

  18. Evaluation of Aerosol Delivery of Nanosuspension for Pre-clinical Pulmonary Drug Delivery

    NASA Astrophysics Data System (ADS)

    Chiang, Po-Chang; Alsup, Jason W.; Lai, Yurong; Hu, Yiding; Heyde, Bruce R.; Tung, David

    2009-03-01

    Asthma and chronic obstructive pulmonary disease (COPD) are pulmonary diseases that are characterized by inflammatory cell infiltration, cytokine production, and airway hyper-reactivity. Most of the effector cells responsible for these pathologies reside in the lungs. One of the most direct ways to deliver drugs to the target cells is via the trachea. In a pre-clinical setting, this can be achieved via intratracheal (IT), intranasal (IN), or aerosol delivery in the desired animal model. In this study, we pioneered the aerosol delivery of a nanosuspension formulation in a rodent model. The efficiency of different dosing techniques and formulations to target the lungs were compared, and fluticasone was used as the model compound. For the aerosol particle size determination, a ten-stage cascade impactor was used. The mass median aerodynamic diameter (MMAD) was calculated based on the percent cumulative accumulation at each stage. Formulations with different particle size of fluticasone were made for evaluation. The compatibility of regular fluticasone suspension and nanosuspension for aerosol delivery was also investigated. The in vivo studies were conducted on mice with optimized setting. It was found that the aerosol delivery of fluticasone with nanosuspension was as efficient as intranasal (IN) dosing, and was able to achieve dose dependent lung deposition.

  19. Automated administration of intermittent intravenous doses.

    PubMed

    Lutomski, D M; Schwartz-Fulton, J; Rivera, J O

    1985-11-01

    The cost difference of administering cimetidine 300 mg via intravenous piggyback (IVPB) every six hours by a conventional separate container system versus using an automated intermittent i.v. administration system was evaluated. The study was conducted in two phases. Phase 1 documented the amount of drug waste with the two systems, and phase 2 examined the practical use of the IVAC Multi Dose System. Nurses who administered the medication using the multiple-dose system completed a questionnaire on its operation. A materials cost analysis was performed to compare the two methods. The two systems were found to have approximately equivalent amounts of drug waste over the 30-day evaluation period of phase 1. The mean percentage of doses wasted was 12.2% with the conventional single-dose minibag method and 12.7% with the automated multiple-dose method. The multiple-dose system had a lower cost per dose of cimetidine ($2.25 versus $3.47). These savings appear to outweigh the cost of the additional equipment necessary for the automated system. The majority of nurses preferred the multiple-dose system. Potential problems encountered in accurately delivering doses with the multiple-dose automated system were identified, and possible solutions are suggested. The use of an automated multiple-dose i.v. administration system can potentially decrease the materials cost portion of drug administration. The total impact on hospital costs needs to be evaluated, and other comparisons with alternative administration systems need to be performed.

  20. Optical delivery and monitoring of photodynamic therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Weersink, Robert A.; Bogaards, Arjun; Gertner, Mark; Davidson, Sean; Zhang, Kai; Netchev, George; Giewercer, David J.; Trachtenberg, John; Wilson, Brian C.

    2004-10-01

    Photodynamic therapy of recurrent prostate cancer is currently undergoing Phase II clinical trials with the vascular targeting drug TOOKAD. Proper PDT dosage requires sound estimates of the light fluence and drug concentration throughout the organ. The treatment requires multiple diffusing light delivery fibers placed in position according to a light dose treatment plan under ultrasound guidance. Fluence rate is monitored by multiple sensor fibers placed throughout the organ and in sensitive organs near the prostate. The combination of multiple light delivery and fluence sensor fibers is used to estimate the optical properties of the tissue and to provide a general fluence map throughout the organ. This fluence map is then used to estimate extent of photodynamic dose. Optical spectroscopy is used to monitor drug pharmacokinetics in the organ and blood hemodynamics within the organ. Further development of these delivery and monitoring techniques will permit full online monitoring of the treatment that will enable real-time patient-specific delivery of photodynamic therapy.

  1. Low Dose Suppression of Neoplastic Transformation in Vitro

    SciTech Connect

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  2. [The moon and delivery].

    PubMed

    Romero Martínez, Jorge; Guerrero Guijo, Inmaculada; Artura Serrano, Antonio

    2004-11-01

    In different cultures and mythologies, the moon is related with fertility, pregnancy and delivery. Professional obstetricians also notice an increase in care demands on the days when the moon is full. Many studies have been made which try to correlate delivery processes to the phases of the moon with contradictory results. The authors plan to try to find any basis in fact which support these popular beliefs and to discover if lunar phases bear an influence on the distribution of deliveries. They carried out a descriptive transversal study on a total of 1715 unassisted deliveries over the course of ten complete lunar cycles. The authors have carried out a descriptive and inferential analysis, a one way ANOVA and a Kruskal Wallis test on their three data bases which are general, primipara and multipara in which they contemplated the total number of deliveries per phase, the mean of each phase, as well as the central day in each phase of the lunar cycle. The differences found in the distribution of deliveries over the four lunar phases, along with the comparison of the means and the comparison of the number of deliveries on the central day in each phase are not statistically significant. The different phases in the lunar cycle and especially the full moon do not appear to have any influence over the distribution of deliveries in this study.

  3. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

  4. Document Delivery Update.

    ERIC Educational Resources Information Center

    Computers in Libraries, 1992

    1992-01-01

    Describes new products that relate to document delivery, including a wireless electronic mail connection; multivendor office integration software to exchange electronic mail; analog film recorders; an electronic messaging system for personal computer local area networks; software for transferring data files; voice message delivery systems; and…

  5. Staff Development Content Delivery.

    ERIC Educational Resources Information Center

    Dillon, Elizabeth A.

    1979-01-01

    Question clusters related to staff development content delivery are used to develop programs that will result in more productive professional development. The questions determine the focus of programs, analyze the target audience, discuss the selection of delivery modes, and identify future directions. (JMF)

  6. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.

  7. Delivery system for molten salt oxidation of solid waste

    DOEpatents

    Brummond, William A.; Squire, Dwight V.; Robinson, Jeffrey A.; House, Palmer A.

    2002-01-01

    The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a temperature below incineration temperature while entering the molten salt reactor.

  8. Tumour dose estimation using automated TLD techniques.

    PubMed

    Ferguson, H M; Lambert, G D; Gustard, D; Harrison, R M

    1998-01-01

    Lithium fluoride (TLD-700) dosimeters were used to measure exit surface absorbed doses in external beam radiotherapy using an automated TLD reader. Delivered tumour absorbed doses were derived from these measurements for head and neck, pelvis and breast treatments. For the head and neck treatments (first fraction only), the mean percentage difference between prescribed and delivered tumour absorbed doses was -0.15 +/- 3.0% (+/- 1 SD), for the pelvic treatments -0.83 +/- 2.8% and for the breast treatments +0.26 +/- 2.9%. The spread of results is approximately +/- 3% (+/- 1 SD). This is comparable with the estimated uncertainty in a single TLD absorbed dose measurement in phantom (+/- 2%; +/- 1 SD). Thus, ICRU recommended tolerances for absorbed dose delivery of +/- 5% may not be unequivocally detectable using this method. An action level of +/- 10% is suggested, allowing investigation of possible gross errors in treatment delivery at an early stage, before the course of treatment has progressed to a point at which absorbed dose compensation is impossible.

  9. Imaging method for monitoring delivery of high dose rate brachytherapy

    DOEpatents

    Weisenberger, Andrew G; Majewski, Stanislaw

    2012-10-23

    A method for in-situ monitoring both the balloon/cavity and the radioactive source in brachytherapy treatment utilizing using at least one pair of miniature gamma cameras to acquire separate images of: 1) the radioactive source as it is moved in the tumor volume during brachytherapy; and 2) a relatively low intensity radiation source produced by either an injected radiopharmaceutical rendering cancerous tissue visible or from a radioactive solution filling a balloon surgically implanted into the cavity formed by the surgical resection of a tumor.

  10. Characterization of differences in calculated and actual measured skin doses to canine limbs during stereotactic radiosurgery using Gafchromic film

    SciTech Connect

    Walters, Jerri; Ryan, Stewart; Harmon, Joseph F.

    2012-07-01

    Accurate calculation of absorbed dose to the skin, especially the superficial and radiosensitive basal cell layer, is difficult for many reasons including, but not limited to, the build-up effect of megavoltage photons, tangential beam effects, mixed energy scatter from support devices, and dose interpolation caused by a finite resolution calculation matrix. Stereotactic body radiotherapy (SBRT) has been developed as an alternative limb salvage treatment option at Colorado State University Veterinary Teaching Hospital for dogs with extremity bone tumors. Optimal dose delivery to the tumor during SBRT treatment can be limited by uncertainty in skin dose calculation. The aim of this study was to characterize the difference between measured and calculated radiation dose by the Varian Eclipse (Varian Medical Systems, Palo Alto, CA) AAA treatment planning algorithm (for 1-mm, 2-mm, and 5-mm calculation voxel dimensions) as a function of distance from the skin surface. The study used Gafchromic EBT film (International Specialty Products, Wayne, NJ), FilmQA analysis software, a limb phantom constructed from plastic water Trade-Mark-Sign (fluke Biomedical, Everett, WA) and a canine cadaver forelimb. The limb phantom was exposed to 6-MV treatments consisting of a single-beam, a pair of parallel opposed beams, and a 7-beam coplanar treatment plan. The canine forelimb was exposed to the 7-beam coplanar plan. Radiation dose to the forelimb skin at the surface and at depths of 1.65 mm and 1.35 mm below the skin surface were also measured with the Gafchromic film. The calculation algorithm estimated the dose well at depths beyond buildup for all calculation voxel sizes. The calculation algorithm underestimated the dose in portions of the buildup region of tissue for all comparisons, with the most significant differences observed in the 5-mm calculation voxel and the least difference in the 1-mm voxel. Results indicate a significant difference between measured and calculated data

  11. Nanocarriers for Nitric Oxide Delivery

    PubMed Central

    Saraiva, Juliana; Marotta-Oliveira, Samantha S.; Cicillini, Simone Aparecida; Eloy, Josimar de Oliveira; Marchetti, Juliana Maldonado

    2011-01-01

    Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes) have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology. PMID:21869934

  12. Transdermal Delivery of Nisoldipine: Refinement of Vehicles.

    PubMed

    El Maghraby, Gamal M; Ahmed, Amal A; Osman, Mohamed A

    2015-01-01

    Nisoldipine is used for the treatment of hypertension and angina pectoris. However, it has very low bioavailabil-ty, which is attributed to extensive pre-systemic metabolism. In addition, nisol-ipine is highly potent (used at a low dose). Taking into consideration the fact that transdermal delivery avoids the pre-systemic metabolism and is only suit-ble for potent drugs, nisoldipine can be considered as an excellent candidate for transdermal delivery. Accordingly, the purpose of this study was to optimize nisoldipine transdermal delivery. That was achieved initially by investigating the effect of vehicles on skin penetration. The tested vehicles were ranked with respect to transdermal flux of nisoldipine as isopropyl myristate > oleic acid > propylene glycol > water > polyethylene glycol 400. A combination of oleic acid with propylene glycol was synergistic with a ratio of 1:2 w/w being the best. These results were taken further to develop microemulsion systems using either oleic acid or isopropyl myristate as the oil phase. Both cases employed polyoxy-thylene sorbitan monooleate as a surfactant with propylene glycol being uti-ized as a cosurfactant in the case of oleic acid and ethanol in the case of isopropyl myristate. The developed microemulsions produced significant enhancement in nisoldipine transdermal delivery with the flux being even greater than that obtained from the corresponding pure vehicles. This achieve-ent was recorded in optimum microemulsion formulations which contained a cosurfactant. The study provided stepwise optimization of a vehicle for trans-ermal delivery of nisoldipine.

  13. Transdermal Delivery of Nisoldipine: Refinement of Vehicles.

    PubMed

    El Maghraby, Gamal M; Ahmed, Amal A; Osman, Mohamed A

    2015-01-01

    Nisoldipine is used for the treatment of hypertension and angina pectoris. However, it has very low bioavailabil-ty, which is attributed to extensive pre-systemic metabolism. In addition, nisol-ipine is highly potent (used at a low dose). Taking into consideration the fact that transdermal delivery avoids the pre-systemic metabolism and is only suit-ble for potent drugs, nisoldipine can be considered as an excellent candidate for transdermal delivery. Accordingly, the purpose of this study was to optimize nisoldipine transdermal delivery. That was achieved initially by investigating the effect of vehicles on skin penetration. The tested vehicles were ranked with respect to transdermal flux of nisoldipine as isopropyl myristate > oleic acid > propylene glycol > water > polyethylene glycol 400. A combination of oleic acid with propylene glycol was synergistic with a ratio of 1:2 w/w being the best. These results were taken further to develop microemulsion systems using either oleic acid or isopropyl myristate as the oil phase. Both cases employed polyoxy-thylene sorbitan monooleate as a surfactant with propylene glycol being uti-ized as a cosurfactant in the case of oleic acid and ethanol in the case of isopropyl myristate. The developed microemulsions produced significant enhancement in nisoldipine transdermal delivery with the flux being even greater than that obtained from the corresponding pure vehicles. This achieve-ent was recorded in optimum microemulsion formulations which contained a cosurfactant. The study provided stepwise optimization of a vehicle for trans-ermal delivery of nisoldipine. PMID:26685495

  14. Methods of Drug Delivery in Neurotrauma.

    PubMed

    Deng-Bryant, Ying; Readnower, Ryan; Leung, Lai Yee; Tortella, Frank; Shear, Deborah

    2016-01-01

    The central nervous system (CNS) is protected by blood-brain barrier (BBB) and blood-cerebrospinal-fluid (CSF) barrier that limit toxic agents and most molecules from penetrating the brain and spinal cord. However, these barriers also prevent most pharmaceuticals from entering into the CNS. Drug delivery to the CNS following neurotrauma is complicated. Although studies have shown BBB permeability increases in various TBI models, it remains as the key mitigating factor for delivering drugs into the CNS. The commonly used methods for drug delivery in preclinical neurotrauma studies include intraperitoneal, subcutaneous, intravenous, and intracerebroventricular delivery. It should be noted that for a drug to be successfully translated into the clinic, it needs to be administered preclinically as it would be anticipated to be administered to patients. And this likely leads to better dose selection of the drug, as well as recognition of any possible side effects, prior to transition into a clinical trial. Additionally, novel approach that is noninvasive and yet circumvents BBB, such as drug delivery through nerve pathways innervating the nasal passages, needs to be investigated in animal models, as it may provide a viable drug delivery method for patients who sustain mild CNS injury or require chronic treatments. Therefore, the focus of this chapter is to present rationales and methods for delivering drugs by IV infusion via the jugular vein, and intranasally in preclinical studies. PMID:27604714

  15. SU-E-J-17: Intra-Fractional Prostate Movement Correction During Treatment Delivery Period for Prostate Cancer Using the Intra-Fractional Orthogonal KV-MV Image Pairs

    SciTech Connect

    Zhang, J; Azawi, S; Cho-Lim, J; Wei, R; Williams, R; Frank, E

    2015-06-15

    Purpose: To evaluate the intra-fractional prostate movement range during the beam delivery and implement new IGRT method to correct the prostate movement during the hypofractionated prostate treatment delivery. Methods: To evaluate the prostate internal motion range during the beam delivery, 11 conventional treatments were utilized. Two-arc RapidArc plans were used for the treatment delivery. Orthogonal KV imaging is performed in the middle of the treatment to correct intra-fractional prostate movement. However, it takes gantry-mounted on-board imaging system relative long time to finish the orthogonal KV imaging because of gantry rotation. To avoid gantry movement and accelerate the IGRT processing time, orthogonal KV-MV image pair is tested using the OBI daily QA Cube phantom. Results: The average prostate movement between two orthogonal KV image pairs was 0.38cm (0.20cm ∼ 0.85cm). And the interval time between them was 6.71 min (4.64min ∼ 9.22 min). 2-arc beam delivery time is within 3 minutes for conventional RapidArc treatment delivery. Hypofractionated treatment or SBRT need 4 partial arc and possible non-coplanar technology, which need much longer beam delivery time. Therefore prostate movement might be larger. New orthogonal KV-MV image pair is a new method to correct the prostate movement in the middle of the beam delivery if real time tracking method is not available. Orthogonal KV-MV image pair doesn’t need gantry rotation. Images were acquired quickly which minimized possible new prostate movement. Therefore orthogonal KV-MV image pair is feasible for IGRT. Conclusion: Hypofractionated prostate treatment with less PTV margin always needs longer beam delivery time. Therefore prostate movement correction during the treatment delivery is critical. Orthogonal KV-MV imaging pair is efficient and accurate to correct the prostate movement during treatment beam delivery. Due to limited fraction number and high dose per fraction, the MV imaging dose is

  16. Elective Delivery Before 39 Weeks

    MedlinePlus

    ... Delivery, and Postpartum Care Elective Delivery Before 39 Weeks • What is a “medically indicated” delivery? • What is ... the baby grow and develop during the last weeks of pregnancy? • What are the risks for babies ...

  17. Impact of geometric uncertainties on dose calculations for intensity modulated radiation therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Jiang, Runqing

    Intensity-modulated radiation therapy (IMRT) uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI) during treatment delivery, a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or "blurred" dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). A Gaussian probability density function (PDF) is reasonable for modeling geometric uncertainties as indicated by the 118 patients group. The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. In addition, individual SD should not be determined or predicted from small imaging samples because of random nature of the fluctuations. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. Cumulative PDF data can be used for re-planning to assess accuracy of delivered dose. Group data is useful for determining worst case discrepancy between planned and delivered dose. The margins for the PTV should ideally represent true geometric uncertainties. The measured geometric uncertainties were used in this thesis to assess PTV coverage, dose to OAR, equivalent

  18. Convection-enhanced delivery to the central nervous system.

    PubMed

    Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

    2015-03-01

    Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

  19. Implantable microchip: the futuristic controlled drug delivery system.

    PubMed

    Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta

    2016-01-01

    There is no doubt that controlled and pulsatile drug delivery system is an important challenge in medicine over the conventional drug delivery system in case of therapeutic efficacy. However, the conventional drug delivery systems often offer a limited by their inability to drug delivery which consists of systemic toxicity, narrow therapeutic window, complex dosing schedule for long term treatment etc. Therefore, there has been a search for the drug delivery system that exhibit broad enhancing activity for more drugs with less complication. More recently, some elegant study has noted that, a new type of micro-electrochemical system or MEMS-based drug delivery systems called microchip has been improved to overcome the problems related to conventional drug delivery. Moreover, micro-fabrication technology has enabled to develop the implantable controlled released microchip devices with improved drug administration and patient compliance. In this article, we have presented an overview of the investigations on the feasibility and application of microchip as an advanced drug delivery system. Commercial manufacturing materials and methods, related other research works and current advancement of the microchips for controlled drug delivery have also been summarized.

  20. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug

  1. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

    Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

    2012-01-01

    This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

  2. Investigation of simple IMRT delivery techniques for non-small cell lung cancer patients with respiratory motion using 4DCT.

    PubMed

    Reitz, Bodo; Parda, David S; Colonias, Athanasios; Lee, Vincent; Miften, Moyed

    2009-01-01

    Techniques for generating simplified IMRT treatment plans for treating non-small cell lung cancer (NSCLC) patients with respiratory motion were investigated. To estimate and account for respiratory motion, 4-dimensional computed tomography (4DCT) datasets from 5 patients were used to design 5-field 6-MV ungated step-and-shoot intensity modulated radiotherapy (IMRT) plans delivering a dose of 66 Gy to the planning target volume (PTV). For each patient, 2 plans were generated using the mean intensity and the maximum intensity of 10 CT datasets from different breathing phases. The plans also utilized different margins around the clinical target volume/internal target volume (CTV/ITV) to account for tumor motion. To reduce the treatment time and ensure accurate dose delivery to moving targets, the number of intensity levels was minimized while maintaining dose coverage to PTV and minimizing dose to organs at risk (OARs). Dose-volume histograms (DVHs), dosimetric metrics, and outcome probabilities were evaluated for all plans. Plans using the averaged CT image dataset were inferior, requiring larger margins around the PTV, with a maximum of 1.5 cm, to ensure coverage of the tumor, and therefore increased the dose to OARs located in proximity of the tumor. The plans based on superimposed CT image datasets achieved full coverage of the tumor, while allowing tight margins around the PTV and minimizing the dose to OARs. A small number of intensity-levels (3 to 5), resulting in IMRT plans with a total of 13 to 30 segments, were sufficient for homogeneous PTV coverage, without affecting the sparing of OARs. In conclusion, a technique involving treatment planning with the superimposed CT scans of all respiratory phases, and the application of IMRT with only a small number of segments was feasible despite significant tumor motion; however, greater patient numbers are needed to support the statistical significance of the results presented in this work.

  3. Investigation of simple IMRT delivery techniques for non-small cell lung cancer patients with respiratory motion using 4DCT.

    PubMed

    Reitz, Bodo; Parda, David S; Colonias, Athanasios; Lee, Vincent; Miften, Moyed

    2009-01-01

    Techniques for generating simplified IMRT treatment plans for treating non-small cell lung cancer (NSCLC) patients with respiratory motion were investigated. To estimate and account for respiratory motion, 4-dimensional computed tomography (4DCT) datasets from 5 patients were used to design 5-field 6-MV ungated step-and-shoot intensity modulated radiotherapy (IMRT) plans delivering a dose of 66 Gy to the planning target volume (PTV). For each patient, 2 plans were generated using the mean intensity and the maximum intensity of 10 CT datasets from different breathing phases. The plans also utilized different margins around the clinical target volume/internal target volume (CTV/ITV) to account for tumor motion. To reduce the treatment time and ensure accurate dose delivery to moving targets, the number of intensity levels was minimized while maintaining dose coverage to PTV and minimizing dose to organs at risk (OARs). Dose-volume histograms (DVHs), dosimetric metrics, and outcome probabilities were evaluated for all plans. Plans using the averaged CT image dataset were inferior, requiring larger margins around the PTV, with a maximum of 1.5 cm, to ensure coverage of the tumor, and therefore increased the dose to OARs located in proximity of the tumor. The plans based on superimposed CT image datasets achieved full coverage of the tumor, while allowing tight margins around the PTV and minimizing the dose to OARs. A small number of intensity-levels (3 to 5), resulting in IMRT plans with a total of 13 to 30 segments, were sufficient for homogeneous PTV coverage, without affecting the sparing of OARs. In conclusion, a technique involving treatment planning with the superimposed CT scans of all respiratory phases, and the application of IMRT with only a small number of segments was feasible despite significant tumor motion; however, greater patient numbers are needed to support the statistical significance of the results presented in this work. PMID:19410146

  4. Dose characterization in the near-source region for two high dose rate brachytherapy sources.

    PubMed

    Wang, Ruqing; Li, X Allen

    2002-08-01

    High dose rate (HDR) 192Ir sources are currently used in intravascular brachytherapy (IVB) for the peripheral arterial system. This poses a demand on evaluating accurate dose parameters in the near-source region for such sources. The purpose of this work is to calculate the dose parameters for the old VariSource HDR 192Ir source and the new microSelectron HDR 192Ir source, using Monte Carlo electron and photon transport simulation. The two-dimensional (2D) dose rate distributions and the air kerma strengths for the two HDR sources were calculated by EGSnrc and EGS4 Monte Carlo codes. Based on these data, the dose parameters proposed in the AAPM TG-60 protocol were derived. The dose rate constants obtained are 13.119+/-0.028 cGy h(-1) U(-1) for the old VariSource source, and 22.751+/-0.031 cGy h(-1) U(-1) for the new microSelectron source at the reference point (r0 = 2 mm, theta = pi/2). The 2D dose rate distributions, the radial dose functions, and the anisotropy functions presented for the two sources cover radial distances ranging from 0.5 to 10 mm. In the near-source region on the transverse plane, the dose effects of the charged particle nonequilibrium and the beta-particle dose contribution were studied. It is found that at radial distances ranging from 0.5 to 2 mm, these effects increase the calculated dose rates by up to 29% for the old VariSource source, and by up to 12% for the new microSelectron source, which, in turn, change values of the radial dose function and the anisotropy function. The present dose parameters, which account for the charged particle nonequilibrium and the beta particle contribution, may be used for accurate IVB dose calculation. PMID:12201413

  5. Mill profiler machines soft materials accurately

    NASA Technical Reports Server (NTRS)

    Rauschl, J. A.

    1966-01-01

    Mill profiler machines bevels, slots, and grooves in soft materials, such as styrofoam phenolic-filled cores, to any desired thickness. A single operator can accurately control cutting depths in contour or straight line work.

  6. Using In-Service and Coaching to Increase Kindergarten Teachers' Accurate Delivery of Group Instructional Units

    ERIC Educational Resources Information Center

    Kretlow, Allison G.; Wood, Charles L.; Cooke, Nancy L.

    2011-01-01

    Early intervention is key to preventing academic failure and referral to special education. General educators are responsible for providing primary instruction for students at risk for failure; however, the training they receive related to specific instructional strategies for these students is often insufficient (e.g., 1-day workshops).…

  7. Midline Dose Verification with Diode In Vivo Dosimetry for External Photon Therapy of Head and Neck and Pelvis Cancers During Initial Large-Field Treatments

    SciTech Connect

    Tung, Chuan-Jong; Yu, Pei-Chieh; Chiu, Min-Chi; Yeh, Chi-Yuan; Lee, Chung-Chi; Chao, Tsi-Chian

    2010-01-01

    During radiotherapy treatments, quality assurance/control is essential, particularly dose delivery to patients. This study was designed to verify midline doses with diode in vivo dosimetry. Dosimetry was studied for 6-MV bilateral fields in head and neck cancer treatments and 10-MV bilateral and anteroposterior/posteroanterior (AP/PA) fields in pelvic cancer treatments. Calibrations with corrections of diodes were performed using plastic water phantoms; 190 and 100 portals were studied for head and neck and pelvis treatments, respectively. Calculations of midline doses were made using the midline transmission, arithmetic mean, and geometric mean algorithms. These midline doses were compared with the treatment planning system target doses for lateral or AP (PA) portals and paired opposed portals. For head and neck treatments, all 3 algorithms were satisfactory, although the geometric mean algorithm was less accurate and more uncertain. For pelvis treatments, the arithmetic mean algorithm seemed unacceptable, whereas the other algorithms were satisfactory. The random error was reduced by using averaged midline doses of paired opposed portals because the asymmetric effect was averaged out. Considering the simplicity of in vivo dosimetry, the arithmetic mean and geometric mean algorithm should be adopted for head/neck and pelvis treatments, respectively.

  8. Evaluation of absorbed dose in Gadolinium neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Abdullaeva, Gayane; Djuraeva, Gulnara; Kim, Andrey; Koblik, Yuriy; Kulabdullaev, Gairatulla; Rakhmonov, Turdimukhammad; Saytjanov, Shavkat

    2015-02-01

    Gadolinium neutron capture therapy (GdNCT) is used for treatment of radioresistant malignant tumors. The absorbed dose in GdNCT can be divided into four primary dose components: thermal neutron, fast neutron, photon and natural gadolinium doses. The most significant is the dose created by natural gadolinium. The amount of gadolinium at the irradiated region is changeable and depends on the gadolinium delivery agent and on the structure of the location where the agent is injected. To de- fine the time dependence of the gadolinium concentration ρ(t) in the irradiated region the pharmacokinetics of gadolinium delivery agent (Magnevist) was studied at intratumoral injection in mice and intramuscular injection in rats. A polynomial approximation was applied to the experimental data and the influence of ρ(t) on the relative change of the absorbed dose of gadolinium was studied.

  9. Project Delivery Methods.

    ERIC Educational Resources Information Center

    Dolan, Thomas G.

    2003-01-01

    Describes project delivery methods that are replacing the traditional Design/Bid/Build linear approach to the management, design, and construction of new facilities. These variations can enhance construction management and teamwork. (SLD)

  10. Assisted Vaginal Delivery

    MedlinePlus

    ... having a repeat assisted vaginal delivery in a future pregnancy? If you have had one assisted vaginal ... a vacuum device. Vacuum Device: A metal or plastic cup that is applied to the fetus’ head ...

  11. Absorbed Dose and Dose Equivalent Calculations for Modeling Effective Dose

    NASA Technical Reports Server (NTRS)

    Welton, Andrew; Lee, Kerry

    2010-01-01

    While in orbit, Astronauts are exposed to a much higher dose of ionizing radiation than when on the ground. It is important to model how shielding designs on spacecraft reduce radiation effective dose pre-flight, and determine whether or not a danger to humans is presented. However, in order to calculate effective dose, dose equivalent calculations are needed. Dose equivalent takes into account an absorbed dose of radiation and the biological effectiveness of ionizing radiation. This is important in preventing long-term, stochastic radiation effects in humans spending time in space. Monte carlo simulations run with the particle transport code FLUKA, give absorbed and equivalent dose data for relevant shielding. The shielding geometry used in the dose calculations is a layered slab design, consisting of aluminum, polyethylene, and water. Water is used to simulate the soft tissues that compose the human body. The results obtained will provide information on how the shielding performs with many thicknesses of each material in the slab. This allows them to be directly applicable to modern spacecraft shielding geometries.

  12. Robotic Delivery of Complex Radiation Volumes for Small Animal Research

    PubMed Central

    Matinfar, Mohammad; Iordachita, Iulian; Wong, John; Kazanzides, Peter

    2011-01-01

    The Small Animal Radiation Research Platform (SARRP) is a novel and complete system capable of delivering multidirectional (focal), kilo-voltage radiation fields to targets in small animals under robotic control using cone-beam CT (CBCT) image guidance. The capability of the SARRP to deliver highly focused beams to multiple animal models provides new research opportunities that more realistically bridge laboratory research and clinical translation. This paper describes the design and operation of the SARRP for precise radiation delivery. Different delivery procedures are presented which enable the system to radiate through a series of points, representative of a complex shape. A particularly interesting case is shell dose irradiation, where the goal is to deliver a high dose of radiation to the shape surface, with minimal dose to the shape interior. The ability to deliver a dose shell allows mechanistic research of how a tumor interacts with its microenvironment to sustain its growth and lead to its resistance or recurrence. PMID:21643448

  13. Robotic Delivery of Complex Radiation Volumes for Small Animal Research.

    PubMed

    Matinfar, Mohammad; Iordachita, Iulian; Wong, John; Kazanzides, Peter

    2010-07-15

    The Small Animal Radiation Research Platform (SARRP) is a novel and complete system capable of delivering multidirectional (focal), kilo-voltage radiation fields to targets in small animals under robotic control using cone-beam CT (CBCT) image guidance. The capability of the SARRP to deliver highly focused beams to multiple animal models provides new research opportunities that more realistically bridge laboratory research and clinical translation. This paper describes the design and operation of the SARRP for precise radiation delivery. Different delivery procedures are presented which enable the system to radiate through a series of points, representative of a complex shape. A particularly interesting case is shell dose irradiation, where the goal is to deliver a high dose of radiation to the shape surface, with minimal dose to the shape interior. The ability to deliver a dose shell allows mechanistic research of how a tumor interacts with its microenvironment to sustain its growth and lead to its resistance or recurrence.

  14. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter.

  15. Validation of a method for in vivo 3D dose reconstruction for IMRT and VMAT treatments using on-treatment EPID images and a model-based forward-calculation algorithm

    SciTech Connect

    Van Uytven, Eric Van Beek, Timothy; McCowan, Peter M.; Chytyk-Praznik, Krista; Greer, Peter B.; McCurdy, Boyd M. C.

    2015-12-15

    Purpose: Radiation treatments are trending toward delivering higher doses per fraction under stereotactic radiosurgery and hypofractionated treatment regimens. There is a need for accurate 3D in vivo patient dose verification using electronic portal imaging device (EPID) measurements. This work presents a model-based technique to compute full three-dimensional patient dose reconstructed from on-treatment EPID portal images (i.e., transmission images). Methods: EPID dose is converted to incident fluence entering the patient using a series of steps which include converting measured EPID dose to fluence at the detector plane and then back-projecting the primary source component of the EPID fluence upstream of the patient. Incident fluence is then recombined with predicted extra-focal fluence and used to calculate 3D patient dose via a collapsed-cone convolution method. This method is implemented in an iterative manner, although in practice it provides accurate results in a single iteration. The robustness of the dose reconstruction technique is demonstrated with several simple slab phantom and nine anthropomorphic phantom cases. Prostate, head and neck, and lung treatments are all included as well as a range of delivery techniques including VMAT and dynamic intensity modulated radiation therapy (IMRT). Results: Results indicate that the patient dose reconstruction algorithm compares well with treatment planning system computed doses for controlled test situations. For simple phantom and square field tests, agreement was excellent with a 2%/2 mm 3D chi pass rate ≥98.9%. On anthropomorphic phantoms, the 2%/2 mm 3D chi pass rates ranged from 79.9% to 99.9% in the planning target volume (PTV) region and 96.5% to 100% in the low dose region (>20% of prescription, excluding PTV and skin build-up region). Conclusions: An algorithm to reconstruct delivered patient 3D doses from EPID exit dosimetry measurements was presented. The method was applied to phantom and patient

  16. Development of the premature infant nose throat-model (PrINT-Model): an upper airway replica of a premature neonate for the study of aerosol delivery.

    PubMed

    Minocchieri, Stefan; Burren, Juerg Martin; Bachmann, Marc Aurel; Stern, Georgette; Wildhaber, Johannes; Buob, Stefan; Schindel, Ralf; Kraemer, Richard; Frey, Urs Peter; Nelle, Mathias

    2008-08-01

    Clinical efficacy of aerosol therapy in premature newborns depends on the efficiency of delivery of aerosolized drug to the bronchial tree. To study the influence of various anatomical, physical, and physiological factors on aerosol delivery in preterm newborns, it is crucial to have appropriate in vitro models, which are currently not available. We therefore constructed the premature infant nose throat-model (PrINT-Model), an upper airway model corresponding to a premature infant of 32-wk gestational age by three-dimensional (3D) reconstruction of a three-planar magnetic resonance imaging scan and subsequent 3D-printing. Validation was realized by visual comparison and comparison of total airway volume. To study the feasibility of measuring aerosol deposition, budesonide was aerosolized through the cast and lung dose was expressed as percentage of nominal dose. The airway volumes of the initial magnetic resonance imaging and validation computed tomography scan showed a relative deviation of 0.94%. Lung dose at low flow (1 L/min) was 61.84% and 9.00% at high flow (10 L/min), p < 0.0001. 3D-reconstruction provided an anatomically accurate surrogate of the upper airways of a 32-wk-old premature infant, making the model suitable for future in vitro testing.

  17. Fast Monte Carlo Electron-Photon Transport Method and Application in Accurate Radiotherapy

    NASA Astrophysics Data System (ADS)

    Hao, Lijuan; Sun, Guangyao; Zheng, Huaqing; Song, Jing; Chen, Zhenping; Li, Gui

    2014-06-01

    Monte Carlo (MC) method is the most accurate computational method for dose calculation, but its wide application on clinical accurate radiotherapy is hindered due to its poor speed of converging and long computation time. In the MC dose calculation research, the main task is to speed up computation while high precision is maintained. The purpose of this paper is to enhance the calculation speed of MC method for electron-photon transport with high precision and ultimately to reduce the accurate radiotherapy dose calculation time based on normal computer to the level of several hours, which meets the requirement of clinical dose verification. Based on the existing Super Monte Carlo Simulation Program (SuperMC), developed by FDS Team, a fast MC method for electron-photon coupled transport was presented with focus on two aspects: firstly, through simplifying and optimizing the physical model of the electron-photon transport, the calculation speed was increased with slightly reduction of calculation accuracy; secondly, using a variety of MC calculation acceleration methods, for example, taking use of obtained information in previous calculations to avoid repeat simulation of particles with identical history; applying proper variance reduction techniques to accelerate MC method convergence rate, etc. The fast MC method was tested by a lot of simple physical models and clinical cases included nasopharyngeal carcinoma, peripheral lung tumor, cervical carcinoma, etc. The result shows that the fast MC method for electron-photon transport was fast enough to meet the requirement of clinical accurate radiotherapy dose verification. Later, the method will be applied to the Accurate/Advanced Radiation Therapy System ARTS as a MC dose verification module.

  18. Telerobotic system concept for real-time soft-tissue imaging during radiotherapy beam delivery

    SciTech Connect

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2010-12-15

    Purpose: The curative potential of external beam radiation therapy is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. However, existing technologies are incapable of real-time, volumetric, soft-tissue imaging during radiation beam delivery, when accurate target tracking is most critical. The authors address this challenge in the development and evaluation of a novel, minimally interfering, telerobotic ultrasound (U.S.) imaging system that can be integrated with existing medical linear accelerators (LINACs) for therapy guidance. Methods: A customized human-safe robotic manipulator was designed and built to control the pressure and pitch of an abdominal U.S. transducer while avoiding LINAC gantry collisions. A haptic device was integrated to remotely control the robotic manipulator motion and U.S. image acquisition outside the LINAC room. The ability of the system to continuously maintain high quality prostate images was evaluated in volunteers over extended time periods. Treatment feasibility was assessed by comparing a clinically deployed prostate treatment plan to an alternative plan in which beam directions were restricted to sectors that did not interfere with the transabdominal U.S. transducer. To demonstrate imaging capability concurrent with delivery, robot performance and U.S. target tracking in a phantom were tested with a 15 MV radiation beam active. Results: Remote image acquisition and maintenance of image quality with the haptic interface was successfully demonstrated over 10 min periods in representative treatment setups of volunteers. Furthermore, the robot's ability to maintain a constant probe force and desired pitch angle was unaffected by the LINAC beam. For a representative prostate patient, the dose-volume histogram (DVH) for a plan with restricted sectors remained virtually identical to the DVH of a clinically deployed plan. With reduced margins, as

  19. Characterizing a proton beam scanning system for Monte Carlo dose calculation in patients.

    PubMed

    Grassberger, C; Lomax, Anthony; Paganetti, H

    2015-01-21

    The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations.

  20. Characterizing a proton beam scanning system for Monte Carlo dose calculation in patients

    NASA Astrophysics Data System (ADS)

    Grassberger, C.; Lomax, Anthony; Paganetti, H.

    2015-01-01

    The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations.

  1. Characterizing a Proton Beam Scanning System for Monte Carlo Dose Calculation in Patients

    PubMed Central

    Grassberger, C; Lomax, Tony; Paganetti, H

    2015-01-01

    The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low–energy electrons (<0.6MeV for 230MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations. PMID:25549079

  2. Effect of dosimeter type for commissioning small photon beams on calculated dose distribution in stereotactic radiosurgery

    SciTech Connect

    García-Garduño, O. A. E-mail: amanda.garcia.g@gmail.com; Rodríguez-Ponce, M.; Gamboa-deBuen, I.; Rodríguez-Villafuerte, M.; Galván de la Cruz, O. O.; and others

    2014-09-15

    . Finally, the dose volume histogram results were independent of the size of the calculation grid used. Conclusions: The results of this study showed that all of the studied detectors produced similar commissioned data sets for the TPS dose calculations. However, this result only validated the dose distribution calculation in the TPS and could not be used to assess the dose delivery to the target in which the TFS data were used to calculate the monitor units (the TFS data were not used in the TPS dose distribution calculation). Therefore, this study could not be used to determine the most accurate detector commissioning data set; however, all of the detectors exhibited superior performance for the relative dosimetry of small photon beams.

  3. Fast and accurate sensitivity analysis of IMPT treatment plans using Polynomial Chaos Expansion

    NASA Astrophysics Data System (ADS)

    Perkó, Zoltán; van der Voort, Sebastian R.; van de Water, Steven; Hartman, Charlotte M. H.; Hoogeman, Mischa; Lathouwers, Danny

    2016-06-01

    The highly conformal planned dose distribution achievable in intensity modulated proton therapy (IMPT) can severely be compromised by uncertainties in patient setup and proton range. While several robust optimization approaches have been presented to address this issue, appropriate methods to accurately estimate the robustness of treatment plans are still lacking. To fill this gap we present Polynomial Chaos Expansion (PCE) techniques which are easily applicable and create a meta-model of the dose engine by approximating the dose in every voxel with multidimensional polynomials. This Polynomial Chaos (PC) model can be built in an automated fashion relatively cheaply and subsequently it can be used to perform comprehensive robustness analysis. We adapted PC to provide among others the expected dose, the dose variance, accurate probability distribution of dose-volume histogram (DVH) metrics (e.g. minimum tumor or maximum organ dose), exact bandwidths of DVHs, and to separate the effects of random and systematic errors. We present the outcome of our verification experiments based on 6 head-and-neck (HN) patients, and exemplify the usefulness of PCE by comparing a robust and a non-robust treatment plan for a selected HN case. The results suggest that PCE is highly valuable for both research and clinical applications.

  4. Trans-ungual iontophoretic delivery of terbinafine.

    PubMed

    Nair, Anroop B; Vaka, Siva Ram K; Sammeta, Srinivasa M; Kim, Hyun D; Friden, Phillip M; Chakraborty, Bireswar; Murthy, S Narasimha

    2009-05-01

    Successful treatment of deep-seated nail infections remains elusive as the delivery of efficacious levels of antifungal drug to the site of action is very difficult. The aim of the present study was to attain rapid trans-ungual delivery of an antifungal agent, terbinafine, via the topical route using iontophoresis. Initial studies revealed that application of current (0.5 mA/cm(2)) could significantly enhance the trans-ungual delivery of terbinafine. An increase in the applied current or duration of current application enhanced the trans-ungual delivery of terbinafine. Permeation of terbinafine through the nail and drug load in the nail correlated well with the applied electrical dose. Release of drug from nails loaded using iontophoresis followed a two-phase release profile. Light microscopy studies substantiated the capability of iontophoresis to drive a charged molecule across the nail plate. The results of these studies indicate that iontophoresis could be developed as a potential technique for onychomycosis therapy. PMID:18781625

  5. Trans-ungual iontophoretic delivery of terbinafine.

    PubMed

    Nair, Anroop B; Vaka, Siva Ram K; Sammeta, Srinivasa M; Kim, Hyun D; Friden, Phillip M; Chakraborty, Bireswar; Murthy, S Narasimha

    2009-05-01

    Successful treatment of deep-seated nail infections remains elusive as the delivery of efficacious levels of antifungal drug to the site of action is very difficult. The aim of the present study was to attain rapid trans-ungual delivery of an antifungal agent, terbinafine, via the topical route using iontophoresis. Initial studies revealed that application of current (0.5 mA/cm(2)) could significantly enhance the trans-ungual delivery of terbinafine. An increase in the applied current or duration of current application enhanced the trans-ungual delivery of terbinafine. Permeation of terbinafine through the nail and drug load in the nail correlated well with the applied electrical dose. Release of drug from nails loaded using iontophoresis followed a two-phase release profile. Light microscopy studies substantiated the capability of iontophoresis to drive a charged molecule across the nail plate. The results of these studies indicate that iontophoresis could be developed as a potential technique for onychomycosis therapy.

  6. Inhaled nano- and microparticles for drug delivery

    PubMed Central

    El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

    2015-01-01

    The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

  7. Modified chemiluminescent NO analyzer accurately measures NOX

    NASA Technical Reports Server (NTRS)

    Summers, R. L.

    1978-01-01

    Installation of molybdenum nitric oxide (NO)-to-higher oxides of nitrogen (NOx) converter in chemiluminescent gas analyzer and use of air purge allow accurate measurements of NOx in exhaust gases containing as much as thirty percent carbon monoxide (CO). Measurements using conventional analyzer are highly inaccurate for NOx if as little as five percent CO is present. In modified analyzer, molybdenum has high tolerance to CO, and air purge substantially quenches NOx destruction. In test, modified chemiluminescent analyzer accurately measured NO and NOx concentrations for over 4 months with no denegration in performance.

  8. Simulating total-dose and dose-rate effects on digital microelectronics timing delays using VHDL

    SciTech Connect

    Brothers, C.P. Jr.; Pugh, R.D.

    1995-12-01

    This paper describes a fast timing simulator based on Very High Speed Integrated Circuit (VHSIC) Hardware Description Language (VHDL) for simulating the timing of digital microelectronics in pre-irradiation, total dose, and dose-rate radiation environments. The goal of this research is the rapid and accurate timing simulation of radiation-hardened microelectronic circuits before, during, and after exposure to ionizing radiation. The results of this research effort were the development of VHDL compatible models capable of rapid and accurate simulation of the effect of radiation on the timing performance of microelectronic circuits. The effects of radiation for total dose at 1 Mrad(Si) and dose rates up to 2 {times} 10{sup 12} rads(Si) per second were modeled for a variety of Separation by IMplantion of OXygen (SIMOX) circuits. In all cases tested, the VHDL simulations ran at least 600 times faster than SPICE while maintaining a timing accuracy to within 15% of SPICE values.

  9. Mouse model for efficacy testing of antituberculosis agents via intrapulmonary delivery.

    PubMed

    Gonzalez-Juarrero, Mercedes; Woolhiser, Lisa K; Brooks, Elizabeth; DeGroote, Mary Ann; Lenaerts, Anne J

    2012-07-01

    Here we describe an experimental murine model that allows for aerosolized antituberculosis drug efficacy testing. Intrapulmonary aerosol delivery of isoniazid, capreomycin, and amikacin to mice with pulmonary infection of Mycobacterium tuberculosis demonstrated efficacy in reducing pulmonary bacterial loads similar to that seen by standard drug delivery methods, even when lower concentrations of drugs and fewer doses were used in the aerosolized drug regimens. Interestingly, intrapulmonary delivery of isoniazid also reduced the bacterial load in the spleen. PMID:22547626

  10. Hydrofluoroalkane-beclomethasone versus chlorofluorocarbon-beclomethasone delivery in neonatal models.

    PubMed

    Cole, C H; Mitchell, J P; Foley, M P; Nagel, M W

    2004-09-01

    Dose delivery of hydrofluoroalkane-beclomethasone and chlorofluorocarbon-beclomethasone was compared during in vitro neonatal simulations: mechanical ventilation with 40% and 100% relative humidity + Neonatal Chamber-Ventilator System/endotracheal tube; manual ventilation + Neonatal Chamber/endotracheal tube; "spontaneous breathing" + Neonatal Chamber/face mask without/with manual assistance. The delivery of hydrofluoroalkane-beclomethasone was significantly greater in each simulation.

  11. Nanofibers based antibacterial drug design, delivery and applications.

    PubMed

    Ulubayram, Kezban; Calamak, Semih; Shahbazi, Reza; Eroglu, Ipek

    2015-01-01

    Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications.

  12. Nanofibers based antibacterial drug design, delivery and applications.

    PubMed

    Ulubayram, Kezban; Calamak, Semih; Shahbazi, Reza; Eroglu, Ipek

    2015-01-01

    Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications. PMID:25732666

  13. Nanocarriers for delivery of platinum anticancer drugs.

    PubMed

    Oberoi, Hardeep S; Nukolova, Natalia V; Kabanov, Alexander V; Bronich, Tatiana K

    2013-11-01

    Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum-polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs.

  14. Nanocarriers for delivery of platinum anticancer drugs☆

    PubMed Central

    Oberoi, Hardeep S.; Nukolova, Natalia V.; Kabanov, Alexander V.; Bronich, Tatiana K.

    2014-01-01

    Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs. PMID:24113520

  15. From cellular doses to average lung dose.

    PubMed

    Hofmann, W; Winkler-Heil, R

    2015-11-01

    Sensitive basal and secretory cells receive a wide range of doses in human bronchial and bronchiolar airways. Variations of cellular doses arise from the location of target cells in the bronchial epithelium of a given airway and the asymmetry and variability of airway dimensions of the lung among airways in a given airway generation and among bronchial and bronchiolar airway generations. To derive a single value for the average lung dose which can be related to epidemiologically observed lung cancer risk, appropriate weighting scenarios have to be applied. Potential biological weighting parameters are the relative frequency of target cells, the number of progenitor cells, the contribution of dose enhancement at airway bifurcations, the promotional effect of cigarette smoking and, finally, the application of appropriate regional apportionment factors. Depending on the choice of weighting parameters, detriment-weighted average lung doses can vary by a factor of up to 4 for given radon progeny exposure conditions.

  16. Can Appraisers Rate Work Performance Accurately?

    ERIC Educational Resources Information Center

    Hedge, Jerry W.; Laue, Frances J.

    The ability of individuals to make accurate judgments about others is examined and literature on this subject is reviewed. A wide variety of situational factors affects the appraisal of performance. It is generally accepted that the purpose of the appraisal influences the accuracy of the appraiser. The instrumentation, or tools, available to the…

  17. Accurate pointing of tungsten welding electrodes

    NASA Technical Reports Server (NTRS)

    Ziegelmeier, P.

    1971-01-01

    Thoriated-tungsten is pointed accurately and quickly by using sodium nitrite. Point produced is smooth and no effort is necessary to hold the tungsten rod concentric. The chemically produced point can be used several times longer than ground points. This method reduces time and cost of preparing tungsten electrodes.

  18. Controlled Delivery of Zoledronate Improved Bone Formation Locally In Vivo

    PubMed Central

    Peng, Jiang; Lu, Qiang; Wang, Yu; Wang, Aiyuan; Guo, Quanyi; Gao, Xupeng; Xu, Wenjing; Lu, Shibi

    2014-01-01

    Bisphosphonates (BPs) have been widely used in clinical treatment of bone diseases with increased bone resorption because of their strong affinity for bone and their inhibition of bone resorption. Recently, there has been growing interest in their improvement of bone formation. However, the effect of local controlled delivery of BPs is unclear. We used polylactide acid-glycolic acid copolymer (PLGA) as a drug carrier to deliver various doses of the bisphosphonate zoledronate (Zol) into the distal femur of 8-week-old Sprague-Dawley rats. After 6 weeks, samples were harvested and analyzed by micro-CT and histology. The average bone mineral density and mineralized bone volume fraction were higher with medium- and high-dose PLGA-Zol (30 and 300 µg Zol, respectively) than control and low-dose Zol (3 µg PLGA-Zol; p<0.05). Local controlled delivery of Zol decreased the numbers of osteoclast and increased the numbers of osteoblast. Moreover, local controlled delivery of medium- and high-dose Zol accelerated the expression of bone-formation markers. PLGA used as a drug carrier for controlled delivery of Zol may promote local bone formation. PMID:24618585

  19. Drug delivery systems improve pharmaceutical profile and facilitate medication adherence.

    PubMed

    Wertheimer, Albert I; Santella, Thomas M; Finestone, Albert J; Levy, Richard A

    2005-01-01

    Innovations in dosage forms and dose delivery systems across a wide range of medications offer substantial clinical advantages, including reduced dosing frequency and improved patient adherence; minimized fluctuation of drug concentrations and maintenance of blood levels within a desired range; localized drug delivery; and the potential for reduced adverse effects and increased safety. The advent of new large-molecule drugs for previously untreatable or only partially treatable diseases is stimulating the development of suitable delivery systems for these agents. Although advanced formulations may be more expensive than conventional dosage forms, they often have a more favorable pharmacologic profile and can be cost-effective. Inclusion of these dosage forms on drug formulary lists may help patients remain on therapy and reduce the economic and social burden of care.

  20. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  1. How to calculate the dose of chemotherapy

    PubMed Central

    Gurney, H

    2002-01-01

    Body surface area-dosing does not account for the complex processes of cytotoxic drug elimination. This leads to an unpredictable variation in effect. Overdosing is easily recognised but it is possible that unrecognised underdosing is more common and may occur in 30% or more of patients receiving standard regimen. Those patients who are inadvertently underdosed are at risk of a significantly reduced anticancer effect. Using published data, it can be calculated that there is an almost 20% relative reduction in survival for women receiving adjuvant chemotherapy for breast cancer as a result of unrecognised underdosing. Similarly, the cure rate of cisplatin-based chemotherapy for advanced testicular cancer may be reduced by as much as 10%. The inaccuracy of body surface area-dosing is more than an inconvenience and it is important that methods for more accurate dose calculation are determined, based on the known drug elimination processes for cytotoxic chemotherapy. Twelve rules for dose calculation of chemotherapy are given that can be used as a guideline until better dose-calculation methods become available. Consideration should be given to using fixed dose guidelines independent of body surface area and based on drug elimination capability, both as a starting dose and for dose adjustment, which may have accuracy, safety and financial advantages. British Journal of Cancer (2002) 86, 1297–1302. DOI: 10.1038/sj/bjc/6600139 www.bjcancer.com © 2002 Cancer Research UK PMID:11953888

  2. The Adaptive Aerosol Delivery (AAD) technology: Past, present, and future.

    PubMed

    Denyer, John; Dyche, Tony

    2010-04-01

    Conventional aerosol delivery systems and the availability of new technologies have led to the development of "intelligent" nebulizers such as the I-neb Adaptive Aerosol Delivery (AAD) System. Based on the AAD technology, the I-neb AAD System has been designed to continuously adapt to changes in the patient's breathing pattern, and to pulse aerosol only during the inspiratory part of the breathing cycle. This eliminates waste of aerosol during exhalation, and creates a foundation for precise aerosol (dose) delivery. To facilitate the delivery of precise metered doses of aerosol to the patient, a unique metering chamber design has been developed. Through the vibrating mesh technology, the metering chamber design, and the AAD Disc function, the aerosol output rate and metered (delivered) dose can be tailored to the demands of the specific drug to be delivered. In the I-neb AAD System, aerosol delivery is guided through two algorithms, one for the Tidal Breathing Mode (TBM), and one for slow and deep inhalations, the Target Inhalation Mode (TIM). The aim of TIM is to reduce the treatment time by increasing the total inhalation time per minute, and to increase lung deposition by reducing impaction in the upper airways through slow and deep inhalations. A key feature of the AAD technology is the patient feedback mechanisms that are provided to guide the patient on delivery performance. These feedback signals, which include visual, audible, and tactile forms, are configured in a feedback cascade that leads to a high level of compliance with the use of the I-neb AAD System. The I-neb Insight and the Patient Logging System facilitate a further degree of sophistication to the feedback mechanisms, by providing information on long term adherence and compliance data. These can be assessed by patients and clinicians via a Web-based delivery of information in the form of customized graphical analyses.

  3. The Adaptive Aerosol Delivery (AAD) Technology: Past, Present, and Future

    PubMed Central

    Dyche, Tony

    2010-01-01

    Abstract Conventional aerosol delivery systems and the availability of new technologies have led to the development of “intelligent” nebulizers such as the I-neb Adaptive Aerosol Delivery (AAD) System. Based on the AAD technology, the I-neb AAD System has been designed to continuously adapt to changes in the patient's breathing pattern, and to pulse aerosol only during the inspiratory part of the breathing cycle. This eliminates waste of aerosol during exhalation, and creates a foundation for precise aerosol (dose) delivery. To facilitate the delivery of precise metered doses of aerosol to the patient, a unique metering chamber design has been developed. Through the vibrating mesh technology, the metering chamber design, and the AAD Disc function, the aerosol output rate and metered (delivered) dose can be tailored to the demands of the specific drug to be delivered. In the I-neb AAD System, aerosol delivery is guided through two algorithms, one for the Tidal Breathing Mode (TBM), and one for slow and deep inhalations, the Target Inhalation Mode (TIM). The aim of TIM is to reduce the treatment time by increasing the total inhalation time per minute, and to increase lung deposition by reducing impaction in the upper airways through slow and deep inhalations. A key feature of the AAD technology is the patient feedback mechanisms that are provided to guide the patient on delivery performance. These feedback signals, which include visual, audible, and tactile forms, are configured in a feedback cascade that leads to a high level of compliance with the use of the I-neb AAD System. The I-neb Insight and the Patient Logging System facilitate a further degree of sophistication to the feedback mechanisms, by providing information on long term adherence and compliance data. These can be assessed by patients and clinicians via a Web-based delivery of information in the form of customized graphical analyses. PMID:20373904

  4. MO-G-BRE-01: A Real-Time Virtual Delivery System for Photon Radiotherapy Delivery Monitoring

    SciTech Connect

    Shi, F; Gu, X; Jiang, S; Jia, X; Graves, Y

    2014-06-15

    Purpose: Treatment delivery monitoring is important for radiotherapy, which enables catching dosimetric error at the earliest possible opportunity. This project develops a virtual delivery system to monitor the dose delivery process of photon radiotherapy in real-time using GPU-based Monte Carlo (MC) method. Methods: The simulation process consists of 3 parallel CPU threads. A thread T1 is responsible for communication with a linac, which acquires a set of linac status parameters, e.g. gantry angles, MLC configurations, and beam MUs every 20 ms. Since linac vendors currently do not offer interface to acquire data in real time, we mimic this process by fetching information from a linac dynalog file at the set frequency. Instantaneous beam fluence map (FM) is calculated. A FM buffer is also created in T1 and the instantaneous FM is accumulated to it. This process continues, until a ready signal is received from thread T2 on which an inhouse developed MC dose engine executes on GPU. At that moment, the accumulated FM is transferred to T2 for dose calculations, and the FM buffer in T1 is cleared. Once the calculation finishes, the resulting 3D dose distribution is directed to thread T3, which displays it in three orthogonal planes overlaid on the CT image for treatment monitoring. This process continues to monitor the 3D dose distribution in real-time. Results: An IMRT and a VMAT cases used in our patient-specific QA are studied. Maximum dose differences between our system and treatment planning system are 0.98% and 1.58% for the two cases, respectively. The average time per MC calculation is 0.1sec with <2% relative uncertainty. The update frequency of ∼10Hz is considered as real time. Conclusion: By embedding a GPU-based MC code in a novel data/work flow, it is possible to achieve real-time MC dose calculations to monitor delivery process.

  5. 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

    SciTech Connect

    Park, J; Park, H; Lee, J; Kang, S; Lee, M; Suh, T; Lee, B

    2014-06-01

    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 the 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

  6. Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

    PubMed Central

    Shrivastav, Anupama; Kim, Hae-Yeong; Kim, Young-Rok

    2013-01-01

    Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system. PMID:23984383

  7. Dosimetric verification and clinical evaluation of a new commercially available Monte Carlo-based dose algorithm for application in stereotactic body radiation therapy (SBRT) treatment planning

    NASA Astrophysics Data System (ADS)

    Fragoso, Margarida; Wen, Ning; Kumar, Sanath; Liu, Dezhi; Ryu, Samuel; Movsas, Benjamin; Munther, Ajlouni; Chetty, Indrin J.

    2010-08-01

    Modern cancer treatment techniques, such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT), have greatly increased the demand for more accurate treatment planning (structure definition, dose calculation, etc) and dose delivery. The ability to use fast and accurate Monte Carlo (MC)-based dose calculations within a commercial treatment planning system (TPS) in the clinical setting is now becoming more of a reality. This study describes the dosimetric verification and initial clinical evaluation of a new commercial MC-based photon beam dose calculation algorithm, within the iPlan v.4.1 TPS (BrainLAB AG, Feldkirchen, Germany). Experimental verification of the MC photon beam model was performed with film and ionization chambers in water phantoms and in heterogeneous solid-water slabs containing bone and lung-equivalent materials for a 6 MV photon beam from a Novalis (BrainLAB) linear accelerator (linac) with a micro-multileaf collimator (m3 MLC). The agreement between calculated and measured dose distributions in the water phantom verification tests was, on average, within 2%/1 mm (high dose/high gradient) and was within ±4%/2 mm in the heterogeneous slab geometries. Example treatment plans in the lung show significant differences between the MC and one-dimensional pencil beam (PB) algorithms within iPlan, especially for small lesions in the lung, where electronic disequilibrium effects are emphasized. Other user-specific features in the iPlan system, such as options to select dose to water or dose to medium, and the mean variance level, have been investigated. Timing results for typical lung treatment plans show the total computation time (including that for processing and I/O) to be less than 10 min for 1-2% mean variance (running on a single PC with 8 Intel Xeon X5355 CPUs, 2.66 GHz). Overall, the iPlan MC algorithm is demonstrated to be an accurate and efficient dose algorithm, incorporating robust tools for MC

  8. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

    PubMed Central

    Madry, Henning

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair. PMID:27642587

  9. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair.

    PubMed

    Rey-Rico, Ana; Madry, Henning; Cucchiarini, Magali

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair. PMID:27642587

  10. Targeted Delivery Systems for Molecular Therapy in Skeletal Disorders

    PubMed Central

    Dang, Lei; Liu, Jin; Li, Fangfei; Wang, Luyao; Li, Defang; Guo, Baosheng; He, Xiaojuan; Jiang, Feng; Liang, Chao; Liu, Biao; Badshah, Shaikh Atik; He, Bing; Lu, Jun; Lu, Cheng; Lu, Aiping; Zhang, Ge

    2016-01-01

    Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk of toxic effects in non-skeletal tissues, which remain clinical challenges in the treatment of skeletal disorders. Thus, targeted delivery systems are urgently needed to achieve higher drug delivery efficiency, improve therapeutic efficacy in the targeted cells/tissues, and minimize toxicities in non-targeted cells/tissues. In this review, we summarize recent progress in the application of different targeting moieties and nanoparticles for targeted drug delivery in skeletal disorders, and also discuss the advantages, challenges and perspectives in their clinical translation. PMID:27011176

  11. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

    PubMed Central

    Madry, Henning

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair.

  12. Feedback about More Accurate versus Less Accurate Trials: Differential Effects on Self-Confidence and Activation

    ERIC Educational Resources Information Center

    Badami, Rokhsareh; VaezMousavi, Mohammad; Wulf, Gabriele; Namazizadeh, Mahdi

    2012-01-01

    One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected by feedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On Day 1, participants performed a golf putting task under one of…

  13. Systems and Components Fuel Delivery System, Water Delivery System, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

  14. Feedback about more accurate versus less accurate trials: differential effects on self-confidence and activation.

    PubMed

    Badami, Rokhsareh; VaezMousavi, Mohammad; Wulf, Gabriele; Namazizadeh, Mahdi

    2012-06-01

    One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected byfeedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On day 1, participants performed a golf putting task under one of two conditions: one group received feedback on the most accurate trials, whereas another group received feedback on the least accurate trials. On day 2, participants completed an anxiety questionnaire and performed a retention test. Shin conductance level, as a measure of arousal, was determined. The results indicated that feedback about more accurate trials resulted in more effective learning as well as increased self-confidence. Also, activation was a predictor of performance. PMID:22808705

  15. The spatial and energy dependence of gold nanoparticle dose enhancement using deterministic computations

    NASA Astrophysics Data System (ADS)

    Cifter, Fulya

    The main objective of this work is to investigate the detailed dose enhancement characteristics of Gold Nanoparticle Aided Radiotherapy using deterministic computations, which offer several advantages over Monte Carlo simulations. In the first chapter, computations were preformed to obtain the parametric representation of gold nanoparticle (GNP) dose enhancement as function of space and incident photon energy, which can be regarded as the Green's function of GNP aided radiotherapy. The Green's function describes the spatial distribution of dose response in water due to a specific photon energy incident on single or clustered GNPs of defined size, located at a given depth in the phantom. In this way, using convolution-superposition, the dose enhancement may be determined for any incident photon spectrum and combinations of GNP sizes and depths. In obtaining the parameterized Green's function, dose enhancement as function of incident energy, GNP size, and GNP depth was calculated at nanometric spatial resolution for a series of monoenergetic beams. In addition, the dose enhancement was also determined for clinical beams in which the incident photon spectra were obtained using Monte Carlo. Based on the systematic computations of DER as function of x-ray energy and GNP size, optimal photon energies and optimal GNP sizes were determined. In the second chapter, dosimetric properties of GNP-laden target volumes (TV) embedded in a water phantom were investigated as a function of GNP concentration, geometry, and volume. In addition, the characteristics of GNP dose enhancement due to clustering versus homogeneous concentrations are studied. These parameters have importance in today's sophisticated beam delivery techniques, when modifying the beam intensity and direction provides a conformal dose delivery during treatment. Coupled electron-photon radiation transport computations were performed in high spatial resolution (1 nm -- 10 mum mesh sizes) using the CEPXS/ONEDANT code

  16. On the use of pulsed reduced dose rate for improvement of the therapeutic ratio

    NASA Astrophysics Data System (ADS)

    Rasmussen, Karl H., V.

    This work demonstrates three related aspects of the efficacy, delivery, and verification of pulsed reduced dose rate radiotherapy (PRDR). PRDR is a method of irradiation designed to minimize radiation-related toxicities in patients undergoing reirradiation for loco-regional reoccurrence of glioblastoma. PRDR uses 0.2GyX10fx daily doses delivered over a 30-minute time span. Under PRDR treatments, a subset of patients have had an unexpectedly positive response to treatment. It was a primary goal of this project to determine if low-dose hyper-radiosensitivity was a contributor to the increased radio-response from these patients. This was done through the use of human T98G glioma and HT29 colorectal cells, and V79.379-A Chinese hamster fibroblasts with drug inhibition of the p53 and PI3K pathways. Radiation was delivered with a medical linear accelerator in either 2Gy acute doses or through PRDR. Methods used to analyze the effect of these techniques included clonogenic assay, flow cytometry, and western blots. Comparison of survival ratios demonstrated no decrease in efficacy for either the standard T98G or HT29 cell lines when using PRDR as compared to an acute dose. T98G with PI3K inhibition and V79.397-A cells demonstrated a decreased efficacy of treatment using PRDR relative to an acute dose. These results suggest an equivalency in tumor treatment with a possible improvement in normal tissue toxicities for the PRDR method. An additional method of delivering PRDR through the use of Tomotherapy was proposed and demonstrated to be accurate. Tomotherapy planning forces the short leaf open times for individual MLC projections from low dose fractionation closed, resulting in an undeliverable plan due to the loss of a large number of usable projections. Application of a virtual grid with directional blocking allows for the output from useable segments to be above this threshold, resulting in a deliverable treatment plan. Finally, analysis was performed on a proposed QA

  17. Comparison of Elekta VMAT with helical tomotherapy and fixed field IMRT: Plan quality, delivery efficiency and accuracy

    SciTech Connect

    Rao Min; Yang Wensha; Chen Fan; Sheng Ke; Ye Jinsong; Mehta, Vivek; Shepard, David; Cao Daliang

    2010-03-15

    Purpose: Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are arc-based approaches to IMRT delivery. The objective of this study is to compare VMAT to both HT and fixed field IMRT in terms of plan quality, delivery efficiency, and accuracy. Methods: Eighteen cases including six prostate, six head-and-neck, and six lung cases were selected for this study. IMRT plans were developed using direct machine parameter optimization in the Pinnacle{sup 3} treatment planning system. HT plans were developed using a Hi-Art II planning station. VMAT plans were generated using both the Pinnacle{sup 3} SmartArc IMRT module and a home-grown arc sequencing algorithm. VMAT and HT plans were delivered using Elekta's PreciseBeam VMAT linac control system (Elekta AB, Stockholm, Sweden) and a TomoTherapy Hi-Art II system (TomoTherapy Inc., Madison, WI), respectively. Treatment plan quality assurance (QA) for VMAT was performed using the IBA MatriXX system while an ion chamber and films were used for HT plan QA. Results: The results demonstrate that both VMAT and HT are capable of providing more uniform target doses and improved normal tissue sparing as compared with fixed field IMRT. In terms of delivery efficiency, VMAT plan deliveries on average took 2.2 min for prostate and lung cases and 4.6 min for head-and-neck cases. These values increased to 4.7 and 7.0 min for HT plans. Conclusions: Both VMAT and HT plans can be delivered accurately based on their own QA standards. Overall, VMAT was able to provide approximately a 40% reduction in treatment time while maintaining comparable plan quality to that of HT.

  18. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

  19. Microencapsulation: A promising technique for controlled drug delivery

    PubMed Central

    Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

    2010-01-01

    Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

  20. Two highly accurate methods for pitch calibration

    NASA Astrophysics Data System (ADS)

    Kniel, K.; Härtig, F.; Osawa, S.; Sato, O.

    2009-11-01

    Among profiles, helix and tooth thickness pitch is one of the most important parameters of an involute gear measurement evaluation. In principle, coordinate measuring machines (CMM) and CNC-controlled gear measuring machines as a variant of a CMM are suited for these kinds of gear measurements. Now the Japan National Institute of Advanced Industrial Science and Technology (NMIJ/AIST) and the German national metrology institute the Physikalisch-Technische Bundesanstalt (PTB) have each developed independently highly accurate pitch calibration methods applicable to CMM or gear measuring machines. Both calibration methods are based on the so-called closure technique which allows the separation of the systematic errors of the measurement device and the errors of the gear. For the verification of both calibration methods, NMIJ/AIST and PTB performed measurements on a specially designed pitch artifact. The comparison of the results shows that both methods can be used for highly accurate calibrations of pitch standards.

  1. Accurate guitar tuning by cochlear implant musicians.

    PubMed

    Lu, Thomas; Huang, Juan; Zeng, Fan-Gang

    2014-01-01

    Modern cochlear implant (CI) users understand speech but find difficulty in music appreciation due to poor pitch perception. Still, some deaf musicians continue to perform with their CI. Here we show unexpected results that CI musicians can reliably tune a guitar by CI alone and, under controlled conditions, match simultaneously presented tones to <0.5 Hz. One subject had normal contralateral hearing and produced more accurate tuning with CI than his normal ear. To understand these counterintuitive findings, we presented tones sequentially and found that tuning error was larger at ∼ 30 Hz for both subjects. A third subject, a non-musician CI user with normal contralateral hearing, showed similar trends in performance between CI and normal hearing ears but with less precision. This difference, along with electric analysis, showed that accurate tuning was achieved by listening to beats rather than discriminating pitch, effectively turning a spectral task into a temporal discrimination task. PMID:24651081

  2. Accurate Guitar Tuning by Cochlear Implant Musicians

    PubMed Central

    Lu, Thomas; Huang, Juan; Zeng, Fan-Gang

    2014-01-01

    Modern cochlear implant (CI) users understand speech but find difficulty in music appreciation due to poor pitch perception. Still, some deaf musicians continue to perform with their CI. Here we show unexpected results that CI musicians can reliably tune a guitar by CI alone and, under controlled conditions, match simultaneously presented tones to <0.5 Hz. One subject had normal contralateral hearing and produced more accurate tuning with CI than his normal ear. To understand these counterintuitive findings, we presented tones sequentially and found that tuning error was larger at ∼30 Hz for both subjects. A third subject, a non-musician CI user with normal contralateral hearing, showed similar trends in performance between CI and normal hearing ears but with less precision. This difference, along with electric analysis, showed that accurate tuning was achieved by listening to beats rather than discriminating pitch, effectively turning a spectral task into a temporal discrimination task. PMID:24651081

  3. Preparation and accurate measurement of pure ozone.

    PubMed

    Janssen, Christof; Simone, Daniela; Guinet, Mickaël

    2011-03-01

    Preparation of high purity ozone as well as precise and accurate measurement of its pressure are metrological requirements that are difficult to meet due to ozone decomposition occurring in pressure sensors. The most stable and precise transducer heads are heated and, therefore, prone to accelerated ozone decomposition, limiting measurement accuracy and compromising purity. Here, we describe a vacuum system and a method for ozone production, suitable to accurately determine the pressure of pure ozone by avoiding the problem of decomposition. We use an inert gas in a particularly designed buffer volume and can thus achieve high measurement accuracy and negligible degradation of ozone with purities of 99.8% or better. The high degree of purity is ensured by comprehensive compositional analyses of ozone samples. The method may also be applied to other reactive gases. PMID:21456766

  4. Accurate guitar tuning by cochlear implant musicians.

    PubMed

    Lu, Thomas; Huang, Juan; Zeng, Fan-Gang

    2014-01-01

    Modern cochlear implant (CI) users understand speech but find difficulty in music appreciation due to poor pitch perception. Still, some deaf musicians continue to perform with their CI. Here we show unexpected results that CI musicians can reliably tune a guitar by CI alone and, under controlled conditions, match simultaneously presented tones to <0.5 Hz. One subject had normal contralateral hearing and produced more accurate tuning with CI than his normal ear. To understand these counterintuitive findings, we presented tones sequentially and found that tuning error was larger at ∼ 30 Hz for both subjects. A third subject, a non-musician CI user with normal contralateral hearing, showed similar trends in performance between CI and normal hearing ears but with less precision. This difference, along with electric analysis, showed that accurate tuning was achieved by listening to beats rather than discriminating pitch, effectively turning a spectral task into a temporal discrimination task.

  5. Accurate modeling of parallel scientific computations

    NASA Technical Reports Server (NTRS)

    Nicol, David M.; Townsend, James C.

    1988-01-01

    Scientific codes are usually parallelized by partitioning a grid among processors. To achieve top performance it is necessary to partition the grid so as to balance workload and minimize communication/synchronization costs. This problem is particularly acute when the grid is irregular, changes over the course of the computation, and is not known until load time. Critical mapping and remapping decisions rest on the ability to accurately predict performance, given a description of a grid and its partition. This paper discusses one approach to this problem, and illustrates its use on a one-dimensional fluids code. The models constructed are shown to be accurate, and are used to find optimal remapping schedules.

  6. Line gas sampling system ensures accurate analysis

    SciTech Connect

    Not Available

    1992-06-01

    Tremendous changes in the natural gas business have resulted in new approaches to the way natural gas is measured. Electronic flow measurement has altered the business forever, with developments in instrumentation and a new sensitivity to the importance of proper natural gas sampling techniques. This paper reports that YZ Industries Inc., Snyder, Texas, combined its 40 years of sampling experience with the latest in microprocessor-based technology to develop the KynaPak 2000 series, the first on-line natural gas sampling system that is both compact and extremely accurate. This means the composition of the sampled gas must be representative of the whole and related to flow. If so, relative measurement and sampling techniques are married, gas volumes are accurately accounted for and adjustments to composition can be made.

  7. Accurate mask model for advanced nodes

    NASA Astrophysics Data System (ADS)

    Zine El Abidine, Nacer; Sundermann, Frank; Yesilada, Emek; Ndiaye, El Hadji Omar; Mishra, Kushlendra; Paninjath, Sankaranarayanan; Bork, Ingo; Buck, Peter; Toublan, Olivier; Schanen, Isabelle

    2014-07-01

    Standard OPC models consist of a physical optical model and an empirical resist model. The resist model compensates the optical model imprecision on top of modeling resist development. The optical model imprecision may result from mask topography effects and real mask information including mask ebeam writing and mask process contributions. For advanced technology nodes, significant progress has been made to model mask topography to improve optical model accuracy. However, mask information is difficult to decorrelate from standard OPC model. Our goal is to establish an accurate mask model through a dedicated calibration exercise. In this paper, we present a flow to calibrate an accurate mask enabling its implementation. The study covers the different effects that should be embedded in the mask model as well as the experiment required to model them.

  8. New delivery systems and propellants.

    PubMed

    Dolovich, M

    1999-01-01

    The removal of chlorofluorocarbon (CFC) propellants from industrial and household products has been agreed to by over 165 countries of which more than 135 are developing countries. The timetable for this process is outlined in the Montreal Protocol on Substances that Deplete the Ozone Layer document and in several subsequent amendments. Pressured metered dose inhalers (pMDIs) for medical use have been granted temporary exemptions until replacement formulations, providing the same medication via the same route, and with the same efficacy and safety profiles, are approved for human use. Hydrofluoroalkanes (HFAs) are the alternative propellants for CFCs-12 and -114. Their potential for damage to the ozone layer is nonexistent, and while they are greenhouse gases, their global warming potential is a fraction (one-tenth) of that of CFCs. Replacement formulations for almost all inhalant respiratory medications have been or are being produced and tested; in Canada, it is anticipated that the transition to these HFA or CFC-free pMDIs will be complete by the year 2005. Initially, an HFA pMDI was to be equivalent to the CFC pMDI being replaced, in terms of aerosol properties and effective clinical dose. However, this will not necessarily be the situation, particularly for some corticosteroid products. Currently, only one CFC-free formulation is available in Canada - Airomir, a HFA salbutamol pMDI. This paper discusses the in vitro aerosol characteristics, in vivo deposition and clinical data for several HFA pMDIs for which there are data available in the literature. Alternative delivery systems to the pMDI, namely, dry powder inhalers and nebulizers, are briefly reviewed.

  9. Document Delivery Update.

    ERIC Educational Resources Information Center

    Nelson, Nancy Melin

    1992-01-01

    Presents highlights of research that used industrywide surveys, focus groups, personal interviews, and industry-published data to explore the future of electronic information delivery in libraries. Topics discussed include CD-ROMs; prices; full-text products; magnetic tape leasing; engineering and technical literature; connections between online…

  10. Fluid delivery control system

    DOEpatents

    Hoff, Brian D.; Johnson, Kris William; Algrain, Marcelo C.; Akasam, Sivaprasad

    2006-06-06

    A method of controlling the delivery of fluid to an engine includes receiving a fuel flow rate signal. An electric pump is arranged to deliver fluid to the engine. The speed of the electric pump is controlled based on the fuel flow rate signal.

  11. Vaccine delivery using nanoparticles

    PubMed Central

    Gregory, Anthony E.; Titball, Richard; Williamson, Diane

    2013-01-01

    Vaccination has had a major impact on the control of infectious diseases. However, there are still many infectious diseases for which the development of an effective vaccine has been elusive. In many cases the failure to devise vaccines is a consequence of the inability of vaccine candidates to evoke appropriate immune responses. This is especially true where cellular immunity is required for protective immunity and this problem is compounded by the move toward devising sub-unit vaccines. Over the past decade nanoscale size (<1000 nm) materials such as virus-like particles, liposomes, ISCOMs, polymeric, and non-degradable nanospheres have received attention as potential delivery vehicles for vaccine antigens which can both stabilize vaccine antigens and act as adjuvants. Importantly, some of these nanoparticles (NPs) are able to enter antigen-presenting cells by different pathways, thereby modulating the immune response to the antigen. This may be critical for the induction of protective Th1-type immune responses to intracellular pathogens. Their properties also make them suitable for the delivery of antigens at mucosal surfaces and for intradermal administration. In this review we compare the utilities of different NP systems for the delivery of sub-unit vaccines and evaluate the potential of these delivery systems for the development of new vaccines against a range of pathogens. PMID:23532930

  12. Caesarean delivery: conflicting interests.

    PubMed

    Osuna, Eduardo; Pérez Cárceles, Maria Dolores; Sánchez Ferrer, Maria Luisa; Machado, Francisco

    2015-12-01

    Within the maternal-fetal relationship, interests may sometimes diverge. In this paper, a pregnant woman's refusal to undergo a caesarean delivery, which was recommended both to save the life of the fetus and to minimize risks to her, is described. The legal aspects involved in the conflict between maternal autonomy and fetal well-being are analysed. The patient requested an abortion because of the poor condition of the fetus; however, according to Spanish legislation, the possibility of abortion was rejected as the pregnancy was in its 27th week. The woman still persisted in her refusal to accept a caesarian delivery. After the medical team sought guidance on the course to follow, the Duty Court authorized a caesarean delivery against the wishes of the patient. From a legal point of view, at stake were the freedom of the woman - expressed by the decision to reject a caesarean delivery - and the life of the unborn child. In clinical treatment, the interests of the fetus are generally aligned with those of the pregnant woman. When they are not, it is the pregnant woman's autonomy that should be respected, and coercion should form no part of treatment, contrary to the decision of this court.

  13. Educational Telecommunications Delivery Systems.

    ERIC Educational Resources Information Center

    Curtis, John A., Ed.; Biedenbach, Joseph M., Ed.

    This monograph is a single volume reference manual providing an overall review of the current status and likely near future application of six major educational telecommunications delivery technologies. The introduction provides an overview to the usage and potential for these systems in the context of the major educational issues involved. Each…

  14. Integral dose: Comparison between four techniques for prostate radiotherapy

    PubMed Central

    Ślosarek, Krzysztof; Osewski, Wojciech; Grządziel, Aleksandra; Radwan, Michał; Dolla, Łukasz; Szlag, Marta; Stąpór-Fudzińska, Małgorzata

    2014-01-01

    Aim Comparisons of integral dose delivered to the treatment planning volume and to the whole patient body during stereotactic, helical and intensity modulated radiotherapy of prostate. Background Multifield techniques produce large volumes of low dose inside the patient body. Delivered dose could be the result of the cytotoxic injuries of the cells even away from the treatment field. We calculated the total dose absorbed in the patient body for four radiotherapy techniques to investigate whether some methods have a potential to reduce the exposure to the patient. Materials and methods We analyzed CyberKnife plans for 10 patients with localized prostate cancer. Five alternative plans for each patient were calculated with the VMAT, IMRT and TomoTherapy techniques. Alternative dose distributions were calculated to achieve the same coverage for PTV. Integral Dose formula was used to calculate the total dose delivered to the PTV and whole patient body. Results Analysis showed that the same amount of dose was deposited to the treated volume despite different methods of treatment delivery. The mean values of total dose delivered to the whole patient body differed significantly for each treatment technique. The highest integral dose in the patient's body was at the TomoTherapy and CyberKnife treatment session. VMAT was characterized by the lowest integral dose deposited in the patient body. Conclusions The highest total dose absorbed in normal tissue was observed with the use of a robotic radiosurgery system and TomoTherapy. These results demonstrate that the exposure of healthy tissue is a dosimetric factor which differentiates the dose delivery methods. PMID:25859398

  15. The KFM, A Homemade Yet Accurate and Dependable Fallout Meter

    SciTech Connect

    Kearny, C.H.

    2001-11-20

    The KFM is a homemade fallout meter that can be made using only materials, tools, and skills found in millions of American homes. It is an accurate and dependable electroscope-capacitor. The KFM, in conjunction with its attached table and a watch, is designed for use as a rate meter. Its attached table relates observed differences in the separations of its two leaves (before and after exposures at the listed time intervals) to the dose rates during exposures of these time intervals. In this manner dose rates from 30 mR/hr up to 43 R/hr can be determined with an accuracy of {+-}25%. A KFM can be charged with any one of the three expedient electrostatic charging devices described. Due to the use of anhydrite (made by heating gypsum from wallboard) inside a KFM and the expedient ''dry-bucket'' in which it can be charged when the air is very humid, this instrument always can be charged and used to obtain accurate measurements of gamma radiation no matter how high the relative humidity. The heart of this report is the step-by-step illustrated instructions for making and using a KFM. These instructions have been improved after each successive field test. The majority of the untrained test families, adequately motivated by cash bonuses offered for success and guided only by these written instructions, have succeeded in making and using a KFM. NOTE: ''The KFM, A Homemade Yet Accurate and Dependable Fallout Meter'', was published by Oak Ridge National Laboratory report in1979. Some of the materials originally suggested for suspending the leaves of the Kearny Fallout Meter (KFM) are no longer available. Because of changes in the manufacturing process, other materials (e.g., sewing thread, unwaxed dental floss) may not have the insulating capability to work properly. Oak Ridge National Laboratory has not tested any of the suggestions provided in the preface of the report, but they have been used by other groups. When using these instructions, the builder can verify the

  16. Accurate maser positions for MALT-45

    NASA Astrophysics Data System (ADS)

    Jordan, Christopher; Bains, Indra; Voronkov, Maxim; Lo, Nadia; Jones, Paul; Muller, Erik; Cunningham, Maria; Burton, Michael; Brooks, Kate; Green, James; Fuller, Gary; Barnes, Peter; Ellingsen, Simon; Urquhart, James; Morgan, Larry; Rowell, Gavin; Walsh, Andrew; Loenen, Edo; Baan, Willem; Hill, Tracey; Purcell, Cormac; Breen, Shari; Peretto, Nicolas; Jackson, James; Lowe, Vicki; Longmore, Steven

    2013-10-01

    MALT-45 is an untargeted survey, mapping the Galactic plane in CS (1-0), Class I methanol masers, SiO masers and thermal emission, and high frequency continuum emission. After obtaining images from the survey, a number of masers were detected, but without accurate positions. This project seeks to resolve each maser and its environment, with the ultimate goal of placing the Class I methanol maser into a timeline of high mass star formation.

  17. Accurate maser positions for MALT-45

    NASA Astrophysics Data System (ADS)

    Jordan, Christopher; Bains, Indra; Voronkov, Maxim; Lo, Nadia; Jones, Paul; Muller, Erik; Cunningham, Maria; Burton, Michael; Brooks, Kate; Green, James; Fuller, Gary; Barnes, Peter; Ellingsen, Simon; Urquhart, James; Morgan, Larry; Rowell, Gavin; Walsh, Andrew; Loenen, Edo; Baan, Willem; Hill, Tracey; Purcell, Cormac; Breen, Shari; Peretto, Nicolas; Jackson, James; Lowe, Vicki; Longmore, Steven

    2013-04-01

    MALT-45 is an untargeted survey, mapping the Galactic plane in CS (1-0), Class I methanol masers, SiO masers and thermal emission, and high frequency continuum emission. After obtaining images from the survey, a number of masers were detected, but without accurate positions. This project seeks to resolve each maser and its environment, with the ultimate goal of placing the Class I methanol maser into a timeline of high mass star formation.

  18. Verification of IMRT dose calculations using AAA and PBC algorithms in dose buildup regions.

    PubMed

    Oinam, Arun S; Singh, Lakhwant

    2010-08-26

    The purpose of this comparative study was to test the accuracy of anisotropic analytical algorithm (AAA) and pencil beam convolution (PBC) algorithms of Eclipse treatment planning system (TPS) for dose calculations in the low- and high-dose buildup regions. AAA and PBC algorithms were used to create two intensity-modulated radiotherapy (IMRT) plans of the same optimal fluence generated from a clinically simulated oropharynx case in an in-house fabricated head and neck phantom. The TPS computed buildup doses were compared with the corresponding measured doses in the phantom using thermoluminescence dosimeters (TLD 100). Analysis of dose distribution calculated using PBC and AAA shows an increase in gamma value in the dose buildup region indicating large dose deviation. For the surface areas of 1, 50 and 100 cm2, PBC overestimates doses as compared to AAA calculated value in the range of 1.34%-3.62% at 0.6 cm depth, 1.74%-2.96% at 0.4 cm depth, and 1.96%-4.06% at 0.2 cm depth, respectively. In high-dose buildup region, AAA calculated doses were lower by an average of -7.56% (SD = 4.73%), while PBC was overestimated by 3.75% (SD = 5.70%) as compared to TLD measured doses at 0.2 cm depth. However, at 0.4 and 0.6 cm depth, PBC overestimated TLD measured doses by 5.84% (SD = 4.38%) and 2.40% (SD = 4.63%), respectively, while AAA underestimated the TLD measured doses by -0.82% (SD = 4.24%) and -1.10% (SD = 4.14%) at the same respective depth. In low-dose buildup region, both AAA and PBC overestimated the TLD measured doses at all depths except -2.05% (SD = 10.21%) by AAA at 0.2 cm depth. The differences between AAA and PBC at all depths were statistically significant (p < 0.05) in high-dose buildup region, whereas it is not statistically significant in low-dose buildup region. In conclusion, AAA calculated the dose more accurately than PBC in clinically important high-dose buildup region at 0.4 cm and 0.6 cm depths. The use of an orfit cast increases the dose buildup

  19. Accurate Molecular Polarizabilities Based on Continuum Electrostatics

    PubMed Central

    Truchon, Jean-François; Nicholls, Anthony; Iftimie, Radu I.; Roux, Benoît; Bayly, Christopher I.

    2013-01-01

    A novel approach for representing the intramolecular polarizability as a continuum dielectric is introduced to account for molecular electronic polarization. It is shown, using a finite-difference solution to the Poisson equation, that the Electronic Polarization from Internal Continuum (EPIC) model yields accurate gas-phase molecular polarizability tensors for a test set of 98 challenging molecules composed of heteroaromatics, alkanes and diatomics. The electronic polarization originates from a high intramolecular dielectric that produces polarizabilities consistent with B3LYP/aug-cc-pVTZ and experimental values when surrounded by vacuum dielectric. In contrast to other approaches to model electronic polarization, this simple model avoids the polarizability catastrophe and accurately calculates molecular anisotropy with the use of very few fitted parameters and without resorting to auxiliary sites or anisotropic atomic centers. On average, the unsigned error in the average polarizability and anisotropy compared to B3LYP are 2% and 5%, respectively. The correlation between the polarizability components from B3LYP and this approach lead to a R2 of 0.990 and a slope of 0.999. Even the F2 anisotropy, shown to be a difficult case for existing polarizability models, can be reproduced within 2% error. In addition to providing new parameters for a rapid method directly applicable to the calculation of polarizabilities, this work extends the widely used Poisson equation to areas where accurate molecular polarizabilities matter. PMID:23646034

  20. Accurate phase-shift velocimetry in rock.

    PubMed

    Shukla, Matsyendra Nath; Vallatos, Antoine; Phoenix, Vernon R; Holmes, William M

    2016-06-01

    Spatially resolved Pulsed Field Gradient (PFG) velocimetry techniques can provide precious information concerning flow through opaque systems, including rocks. This velocimetry data is used to enhance flow models in a wide range of systems, from oil behaviour in reservoir rocks to contaminant transport in aquifers. Phase-shift velocimetry is the fastest way to produce velocity maps but critical issues have been reported when studying flow through rocks and porous media, leading to inaccurate results. Combining PFG measurements for flow through Bentheimer sandstone with simulations, we demonstrate that asymmetries in the molecular displacement distributions within each voxel are the main source of phase-shift velocimetry errors. We show that when flow-related average molecular displacements are negligible compared to self-diffusion ones, symmetric displacement distributions can be obtained while phase measurement noise is minimised. We elaborate a complete method for the production of accurate phase-shift velocimetry maps in rocks and low porosity media and demonstrate its validity for a range of flow rates. This development of accurate phase-shift velocimetry now enables more rapid and accurate velocity analysis, potentially helping to inform both industrial applications and theoretical models. PMID:27111139

  1. Accurate phase-shift velocimetry in rock

    NASA Astrophysics Data System (ADS)

    Shukla, Matsyendra Nath; Vallatos, Antoine; Phoenix, Vernon R.; Holmes, William M.

    2016-06-01

    Spatially resolved Pulsed Field Gradient (PFG) velocimetry techniques can provide precious information concerning flow through opaque systems, including rocks. This velocimetry data is used to enhance flow models in a wide range of systems, from oil behaviour in reservoir rocks to contaminant transport in aquifers. Phase-shift velocimetry is the fastest way to produce velocity maps but critical issues have been reported when studying flow through rocks and porous media, leading to inaccurate results. Combining PFG measurements for flow through Bentheimer sandstone with simulations, we demonstrate that asymmetries in the molecular displacement distributions within each voxel are the main source of phase-shift velocimetry errors. We show that when flow-related average molecular displacements are negligible compared to self-diffusion ones, symmetric displacement distributions can be obtained while phase measurement noise is minimised. We elaborate a complete method for the production of accurate phase-shift velocimetry maps in rocks and low porosity media and demonstrate its validity for a range of flow rates. This development of accurate phase-shift velocimetry now enables more rapid and accurate velocity analysis, potentially helping to inform both industrial applications and theoretical models.

  2. Accurate phase-shift velocimetry in rock.

    PubMed

    Shukla, Matsyendra Nath; Vallatos, Antoine; Phoenix, Vernon R; Holmes, William M

    2016-06-01

    Spatially resolved Pulsed Field Gradient (PFG) velocimetry techniques can provide precious information concerning flow through opaque systems, including rocks. This velocimetry data is used to enhance flow models in a wide range of systems, from oil behaviour in reservoir rocks to contaminant transport in aquifers. Phase-shift velocimetry is the fastest way to produce velocity maps but critical issues have been reported when studying flow through rocks and porous media, leading to inaccurate results. Combining PFG measurements for flow through Bentheimer sandstone with simulations, we demonstrate that asymmetries in the molecular displacement distributions within each voxel are the main source of phase-shift velocimetry errors. We show that when flow-related average molecular displacements are negligible compared to self-diffusion ones, symmetric displacement distributions can be obtained while phase measurement noise is minimised. We elaborate a complete method for the production of accurate phase-shift velocimetry maps in rocks and low porosity media and demonstrate its validity for a range of flow rates. This development of accurate phase-shift velocimetry now enables more rapid and accurate velocity analysis, potentially helping to inform both industrial applications and theoretical models.

  3. Tolerance doses for treatment planning

    SciTech Connect

    Lyman, J.T.

    1985-10-01

    Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD/sub 5/) or 50% (TD/sub 50/) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs.

  4. Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications

    PubMed Central

    Labiris, N R; Dolovich, M B

    2003-01-01

    Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally. PMID:14616419

  5. Novel delivery systems for improving the clinical use of peptides.

    PubMed

    Kovalainen, Miia; Mönkäre, Juha; Riikonen, Joakim; Pesonen, Ullamari; Vlasova, Maria; Salonen, Jarno; Lehto, Vesa-Pekka; Järvinen, Kristiina; Herzig, Karl-Heinz

    2015-07-01

    Peptides have long been recognized as a promising group of therapeutic substances to treat various diseases. Delivery systems for peptides have been under development since the discovery of insulin for the treatment of diabetes. The challenge of using peptides as drugs arises from their poor bioavailability resulting from the low permeability of biological membranes and their instability. Currently, subcutaneous injection is clinically the most common administration route for peptides. This route is cost-effective and suitable for self-administration, and the development of appropriate dosing equipment has made performing the repeated injections relatively easy; however, only few clinical subcutaneous peptide delivery systems provide sustained peptide release. As a result, frequent injections are needed, which may cause discomfort and additional risks resulting from a poor administration technique. Controlled peptide delivery systems, able to provide required therapeutic plasma concentrations over an extended period, are needed to increase peptide safety and patient compliancy. In this review, we summarize the current peptidergic drugs, future developments, and parenteral peptide delivery systems. Special emphasis is given to porous silicon, a novel material in peptide delivery. Biodegradable and biocompatible porous silicon possesses some unique properties, such as the ability to carry exceptional high peptide payloads and to modify peptide release extensively. We have successfully developed porous silicon as a carrier material for improved parenteral peptide delivery. Nanotechnology, with its different delivery systems, will enable better use of peptides in several therapeutic applications in the near future. PMID:26023145

  6. Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery.

    PubMed

    Wing Moon Lam, Raymond; Abbah, Sunny Akogwu; Ming, Wang; Naidu, Mathanapriya; Ng, Felly; Tao, Hu; Goh Cho Hong, James; Ting, Kang; Hee Kit, Wong

    2016-01-01

    During reconstructive bone surgeries, supraphysiological amounts of growth factors are empirically loaded onto scaffolds to promote successful bone fusion. Large doses of highly potent biological agents are required due to growth factor instability as a result of rapid enzymatic degradation as well as carrier inefficiencies in localizing sufficient amounts of growth factor at implant sites. Hence, strategies that prolong the stability of growth factors such as BMP-2/NELL-1, and control their release could actually lower their efficacious dose and thus reduce the need for larger doses during future bone regeneration surgeries. This in turn will reduce side effects and growth factor costs. Self-assembled PECs have been fabricated to provide better control of BMP-2/NELL-1 delivery via heparin binding and further potentiate growth factor bioactivity by enhancing in vivo stability. Here we illustrate the simplicity of PEC fabrication which aids in the delivery of a variety of growth factors during reconstructive bone surgeries. PMID:27585207

  7. Use of effective dose.

    PubMed

    Harrison, J D; Balonov, M; Martin, C J; Ortiz Lopez, P; Menzel, H-G; Simmonds, J R; Smith-Bindman, R; Wakeford, R

    2016-06-01

    International Commission on Radiological Protection (ICRP) Publication 103 provided a detailed explanation of the purpose and use of effective dose and equivalent dose to individual organs and tissues. Effective dose has proven to be a valuable and robust quantity for use in the implementation of protection principles. However, questions have arisen regarding practical applications, and a Task Group has been set up to consider issues of concern. This paper focusses on two key proposals developed by the Task Group that are under consideration by ICRP: (1) confusion will be avoided if equivalent dose is no longer used as a protection quantity, but regarded as an intermediate step in the calculation of effective dose. It would be more appropriate for limits for the avoidance of deterministic effects to the hands and feet, lens of the eye, and skin, to be set in terms of the quantity, absorbed dose (Gy) rather than equivalent dose (Sv). (2) Effective dose is in widespread use in medical practice as a measure of risk, thereby going beyond its intended purpose. While doses incurred at low levels of exposure may be measured or assessed with reasonable reliability, health effects have not been demonstrated reliably at such levels but are inferred. However, bearing in mind the uncertainties associated with risk projection to low doses or low dose rates, it may be considered reasonable to use effective dose as a rough indicator of possible risk, with the additional consideration of variation in risk with age, sex and population group. PMID:26980800

  8. Use of effective dose.

    PubMed

    Harrison, J D; Balonov, M; Martin, C J; Ortiz Lopez, P; Menzel, H-G; Simmonds, J R; Smith-Bindman, R; Wakeford, R

    2016-06-01

    International Commission on Radiological Protection (ICRP) Publication 103 provided a detailed explanation of the purpose and use of effective dose and equivalent dose to individual organs and tissues. Effective dose has proven to be a valuable and robust quantity for use in the implementation of protection principles. However, questions have arisen regarding practical applications, and a Task Group has been set up to consider issues of concern. This paper focusses on two key proposals developed by the Task Group that are under consideration by ICRP: (1) confusion will be avoided if equivalent dose is no longer used as a protection quantity, but regarded as an intermediate step in the calculation of effective dose. It would be more appropriate for limits for the avoidance of deterministic effects to the hands and feet, lens of the eye, and skin, to be set in terms of the quantity, absorbed dose (Gy) rather than equivalent dose (Sv). (2) Effective dose is in widespread use in medical practice as a measure of risk, thereby going beyond its intended purpose. While doses incurred at low levels of exposure may be measured or assessed with reasonable reliability, health effects have not been demonstrated reliably at such levels but are inferred. However, bearing in mind the uncertainties associated with risk projection to low doses or low dose rates, it may be considered reasonable to use effective dose as a rough indicator of possible risk, with the additional consideration of variation in risk with age, sex and population group.

  9. SU-C-BRD-07: Three-Dimensional Dose Reconstruction in the Presence of Inhomogeneities Using Fast EPID-Based Back-Projection Method

    SciTech Connect

    Ren, Q; Cao, R; Pei, X; Wang, H; Hu, L

    2015-06-15

    Purpose: Three-dimensional dose verification can detect errors introduced by the treatment planning system (TPS) or differences between planned and delivered dose distribution during the treatment. The aim of the study is to extend a previous in-house developed three-dimensional dose reconstructed model in homogeneous phantom to situtions in which tissue inhomogeneities are present. Methods: The method was based on the portal grey images from an electronic portal imaging device (EPID) and the relationship between beamlets and grey-scoring voxels at the position of the EPID. The relationship was expressed in the form of grey response matrix that was quantified using thickness-dependence scatter kernels determined by series of experiments. From the portal grey-value distribution information measured by the EPID the two-dimensional incident fluence distribution was reconstructed based on the grey response matrix using a fast iterative algorithm. The accuracy of this approach was verified using a four-field intensity-modulated radiotherapy (IMRT) plan for the treatment of lung cancer in anthopomorphic phantom. Each field had between twenty and twenty-eight segments and was evaluated by comparing the reconstructed dose distribution with the measured dose. Results: The gamma-evaluation method was used with various evaluation criteria of dose difference and distance-to-agreement: 3%/3mm and 2%/2 mm. The dose comparison for all irradiated fields showed a pass rate of 100% with the criterion of 3%/3mm, and a pass rate of higher than 92% with the criterion of 2%/2mm. Conclusion: Our experimental results demonstrate that our method is capable of accurately reconstructing three-dimensional dose distribution in the presence of inhomogeneities. Using the method, the combined planning and treatment delivery process is verified, offing an easy-to-use tool for the verification of complex treatments.

  10. Monte Carlo simulations of patient dose perturbations in rotational-type radiotherapy due to a transverse magnetic field: A tomotherapy investigation

    SciTech Connect

    Yang, Y. M.; Geurts, M.; Smilowitz, J. B.; Bednarz, B. P.; Sterpin, E.

    2015-02-15

    Purpose: Several groups are exploring the integration of magnetic resonance (MR) image guidance with radiotherapy to reduce tumor position uncertainty during photon radiotherapy. The therapeutic gain from reducing tumor position uncertainty using intrafraction MR imaging during radiotherapy could be partially offset if the negative effects of magnetic field-induced dose perturbations are not appreciated or accounted for. The authors hypothesize that a more rotationally symmetric modality such as helical tomotherapy will permit a systematic mediation of these dose perturbations. This investigation offers a unique look at the dose perturbations due to homogeneous transverse magnetic field during the delivery of Tomotherapy{sup ®} Treatment System plans under varying degrees of rotational beamlet symmetry. Methods: The authors accurately reproduced treatment plan beamlet and patient configurations using the Monte Carlo code GEANT4. This code has a thoroughly benchmarked electromagnetic particle transport physics package well-suited for the radiotherapy energy regime. The three approved clinical treatment plans for this study were for a prostate, head and neck, and lung treatment. The dose heterogeneity index metric was used to quantify the effect of the dose perturbations to the target volumes. Results: The authors demonstrate the ability to reproduce the clinical dose–volume histograms (DVH) to within 4% dose agreement at each DVH point for the target volumes and most planning structures, and therefore, are able to confidently examine the effects of transverse magnetic fields on the plans. The authors investigated field strengths of 0.35, 0.7, 1, 1.5, and 3 T. Changes to the dose heterogeneity index of 0.1% were seen in the prostate and head and neck case, reflecting negligible dose perturbations to the target volumes, a change from 5.5% to 20.1% was observed with the lung case. Conclusions: This study demonstrated that the effect of external magnetic fields can

  11. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Arenare, Brian; Poulin, Gregory; Moser, Daniel R.; Delgado, Reynolds

    2005-01-01

    High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing

  12. Transorbital therapy delivery: phantom testing

    NASA Astrophysics Data System (ADS)

    Ingram, Martha-Conley; Atuegwu, Nkiruka; Mawn, Louise; Galloway, Robert L.

    2011-03-01

    We have developed a combined image-guided and minimally invasive system for the delivery of therapy to the back of the eye. It is composed of a short 4.5 mm diameter endoscope with a magnetic tracker embedded in the tip. In previous work we have defined an optimized fiducial placement for accurate guidance to the back of the eye and are now moving to system testing. The fundamental difficulty in testing performance is establishing a target in a manner which closely mimics the physiological task. We have to have a penetrable material which obscures line of sight, similar to the orbital fat. In addition we need to have some independent measure of knowing when a target has been reached to compare to the ideal performance. Lastly, the target cannot be rigidly attached to the skull phantom since the optic nerve lies buried in the orbital fat. We have developed a skull phantom with white cloth stellate balls supporting a correctly sized globe. Placed in the white balls are red, blue, orange and yellow balls. One of the colored balls has been soaked in barium to make it bright on CT. The user guides the tracked endoscope to the target as defined by the images and tells us its color. We record task accuracy and time to target. We have tested this with 28 residents, fellows and attending physicians. Each physician performs the task twice guided and twice unguided. Results will be presented.

  13. Poster — Thur Eve — 30: 4D VMAT dose calculation methodology to investigate the interplay effect: experimental validation using TrueBeam Developer Mode and Gafchromic film

    SciTech Connect

    Teke, T; Milette, MP; Huang, V; Thomas, SD

    2014-08-15

    The interplay effect between the tumor motion and the radiation beam modulation during a VMAT treatment delivery alters the delivered dose distribution from the planned one. This work present and validate a method to accurately calculate the dose distribution in 4D taking into account the tumor motion, the field modulation and the treatment starting phase. A QUASAR™ respiratory motion phantom was 4D scanned with motion amplitude of 3 cm and with a 3 second period. A static scan was also acquired with the lung insert and the tumor contained in it centered. A VMAT plan with a 6XFFF beam was created on the averaged CT and delivered on a Varian TrueBeam and the trajectory log file was saved. From the trajectory log file 10 VMAT plans (one for each breathing phase) and a developer mode XML file were created. For the 10 VMAT plans, the tumor motion was modeled by moving the isocentre on the static scan, the plans were re-calculated and summed in the treatment planning system. In the developer mode, the tumor motion was simulated by moving the couch dynamically during the treatment. Gafchromic films were placed in the QUASAR phantom static and irradiated using the developer mode. Different treatment starting phase were investigated (no phase shift, maximum inhalation and maximum exhalation). Calculated and measured isodose lines and profiles are in very good agreement. For each starting phase, the dose distribution exhibit significant differences but are accurately calculated with the methodology presented in this work.

  14. Delivery of testosterone replacement therapy.

    PubMed

    Hameed, Asjad; Brothwood, Theresa; Bouloux, Pierre

    2003-10-01

    Optimal testosterone replacement therapy remains a considerable challenge for the estimated five out of 1000 men in the general community with androgen deficiency. Oral delivery is not possible due to rapid first pass metabolism and short half-life. Testosterone derivatives have been developed to enhance intrinsic androgenic potency, prolong duration of action, or improve oral bioavailability of synthetic androgens. Structural modification of testosterone include 17 beta-esterification, 17 alpha-alkylation, 1-methylation, addition of a 19-normethyl group, and 7 alpha-methylation. Currently, oral (testosterone undecanoate), transcutaneous (Andropatch, Virormone, Testoderm (ALZA Corp), Testogel), sublingual (testosterone cyclodextrin), intramuscular (Sustanon, Primoteston Depot), and fused crystalline testosterone pellet preparations are available for clinical use. Transbuccal testosterone systems have also been developed for clinical use and require twice daily application. Suspensions of biodegradable microspheres consisting of a polyglycolide-lactide matrix laden with testosterone can deliver stable, physiological levels of testosterone for 2 to 3 months. Micronized testosterone has low oral bioavailability requiring high daily doses. 7 alpha-Methyl 19-nortestosterone, a potent, synthetic androgen free of hepatotoxicity, has tissue-specific selectivity, being susceptible to aromatization but not 5 alpha-reduction, thereby potentially avoiding intraprostatic androgen amplification. PMID:14649214

  15. Protease-mediated drug delivery

    NASA Astrophysics Data System (ADS)

    Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.

    2003-12-01

    Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drug delivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.

  16. VirtualDose: a software for reporting organ doses from CT for adult and pediatric patients.

    PubMed

    Ding, Aiping; Gao, Yiming; Liu, Haikuan; Caracappa, Peter F; Long, Daniel J; Bolch, Wesley E; Liu, Bob; Xu, X George

    2015-07-21

    This paper describes the development and testing of VirtualDose--a software for reporting organ doses for adult and pediatric patients who undergo x-ray computed tomography (CT) examinations. The software is based on a comprehensive database of organ doses derived from Monte Carlo (MC) simulations involving a library of 25 anatomically realistic phantoms that represent patients of different ages, body sizes, body masses, and pregnant stages. Models of GE Lightspeed Pro 16 and Siemens SOMATOM Sensation 16 scanners were carefully validated for use in MC dose calculations. The software framework is designed with the 'software as a service (SaaS)' delivery concept under which multiple clients can access the web-based interface simultaneously from any computer without having to install software locally. The RESTful web service API also allows a third-party picture archiving and communication system software package to seamlessly integrate with VirtualDose's functions. Software testing showed that VirtualDose was compatible with numerous operating systems including Windows, Linux, Apple OS X, and mobile and portable devices. The organ doses from VirtualDose were compared against those reported by CT-Expo and ImPACT-two dosimetry tools that were based on the stylized pediatric and adult patient models that were known to be anatomically simple. The organ doses reported by VirtualDose differed from those reported by CT-Expo and ImPACT by as much as 300% in some of the patient models. These results confirm the conclusion from past studies that differences in anatomical realism offered by stylized and voxel phantoms have caused significant discrepancies in CT dose estimations.

  17. VirtualDose: a software for reporting organ doses from CT for adult and pediatric patients.

    PubMed

    Ding, Aiping; Gao, Yiming; Liu, Haikuan; Caracappa, Peter F; Long, Daniel J; Bolch, Wesley E; Liu, Bob; Xu, X George

    2015-07-21

    This paper describes the development and testing of VirtualDose--a software for reporting organ doses for adult and pediatric patients who undergo x-ray computed tomography (CT) examinations. The software is based on a comprehensive database of organ doses derived from Monte Carlo (MC) simulations involving a library of 25 anatomically realistic phantoms that represent patients of different ages, body sizes, body masses, and pregnant stages. Models of GE Lightspeed Pro 16 and Siemens SOMATOM Sensation 16 scanners were carefully validated for use in MC dose calculations. The software framework is designed with the 'software as a service (SaaS)' delivery concept under which multiple clients can access the web-based interface simultaneously from any computer without having to install software locally. The RESTful web service API also allows a third-party picture archiving and communication system software package to seamlessly integrate with VirtualDose's functions. Software testing showed that VirtualDose was compatible with numerous operating systems including Windows, Linux, Apple OS X, and mobile and portable devices. The organ doses from VirtualDose were compared against those reported by CT-Expo and ImPACT-two dosimetry tools that were based on the stylized pediatric and adult patient models that were known to be anatomically simple. The organ doses reported by VirtualDose differed from those reported by CT-Expo and ImPACT by as much as 300% in some of the patient models. These results confirm the conclusion from past studies that differences in anatomical realism offered by stylized and voxel phantoms have caused significant discrepancies in CT dose estimations. PMID:26134511

  18. Microprocessor controlled transdermal drug delivery.

    PubMed

    Subramony, J Anand; Sharma, Ashutosh; Phipps, J B

    2006-07-01

    Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly.

  19. The image quality of ion computed tomography at clinical imaging dose levels

    SciTech Connect

    Hansen, David C.; Bassler, Niels; Sørensen, Thomas Sangild; Seco, Joao

    2014-11-01

    Purpose: Accurately predicting the range of radiotherapy ions in vivo is important for the precise delivery of dose in particle therapy. Range uncertainty is currently the single largest contribution to the dose margins used in planning and leads to a higher dose to normal tissue. The use of ion CT has been proposed as a method to improve the range uncertainty and thereby reduce dose to normal tissue of the patient. A wide variety of ions have been proposed and studied for this purpose, but no studies evaluate the image quality obtained with different ions in a consistent manner. However, imaging doses ion CT is a concern which may limit the obtainable image quality. In addition, the imaging doses reported have not been directly comparable with x-ray CT doses due to the different biological impacts of ion radiation. The purpose of this work is to develop a robust methodology for comparing the image quality of ion CT with respect to particle therapy, taking into account different reconstruction methods and ion species. Methods: A comparison of different ions and energies was made. Ion CT projections were simulated for five different scenarios: Protons at 230 and 330 MeV, helium ions at 230 MeV/u, and carbon ions at 430 MeV/u. Maps of the water equivalent stopping power were reconstructed using a weighted least squares method. The dose was evaluated via a quality factor weighted CT dose index called the CT dose equivalent index (CTDEI). Spatial resolution was measured by the modulation transfer function. This was done by a noise-robust fit to the edge spread function. Second, the image quality as a function of the number of scanning angles was evaluated for protons at 230 MeV. In the resolution study, the CTDEI was fixed to 10 mSv, similar to a typical x-ray CT scan. Finally, scans at a range of CTDEI’s were done, to evaluate dose influence on reconstruction error. Results: All ions yielded accurate stopping power estimates, none of which were statistically

  20. TH-E-BRE-09: TrueBeam Monte Carlo Absolute Dose Calculations Using Monitor Chamber Backscatter Simulations and Linac-Logged Target Current

    SciTech Connect

    A, Popescu I; Lobo, J; Sawkey, D; Svatos, M

    2014-06-15

    Purpose: To simulate and measure radiation backscattered into the monitor chamber of a TrueBeam linac; establish a rigorous framework for absolute dose calculations for TrueBeam Monte Carlo (MC) simulations through a novel approach, taking into account the backscattered radiation and the actual machine output during beam delivery; improve agreement between measured and simulated relative output factors. Methods: The ‘monitor backscatter factor’ is an essential ingredient of a well-established MC absolute dose formalism (the MC equivalent of the TG-51 protocol). This quantity was determined for the 6 MV, 6X FFF, and 10X FFF beams by two independent Methods: (1) MC simulations in the monitor chamber of the TrueBeam linac; (2) linac-generated beam record data for target current, logged for each beam delivery. Upper head MC simulations used a freelyavailable manufacturer-provided interface to a cloud-based platform, allowing use of the same head model as that used to generate the publicly-available TrueBeam phase spaces, without revealing the upper head design. The MC absolute dose formalism was expanded to allow direct use of target current data. Results: The relation between backscatter, number of electrons incident on the target for one monitor unit, and MC absolute dose was analyzed for open fields, as well as a jaw-tracking VMAT plan. The agreement between the two methods was better than 0.15%. It was demonstrated that the agreement between measured and simulated relative output factors improves across all field sizes when backscatter is taken into account. Conclusion: For the first time, simulated monitor chamber dose and measured target current for an actual TrueBeam linac were incorporated in the MC absolute dose formalism. In conjunction with the use of MC inputs generated from post-delivery trajectory-log files, the present method allows accurate MC dose calculations, without resorting to any of the simplifying assumptions previously made in the True

  1. Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

    SciTech Connect

    Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

    2013-05-15

    Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All d