4D dose calculation and delivery with interplay effects between respiratory motion and uniform scanning proton beam

NASA Astrophysics Data System (ADS)

Zhao, Qingya

2011-12-01

Proton radiotherapy has advantages to deliver accurate high conformal radiation dose to the tumor while sparing the surrounding healthy tissue and critical structures. However, the treatment effectiveness is degraded greatly due to patient free breathing during treatment delivery. Motion compensation for proton radiotherapy is especially challenging as proton beam is more sensitive to the density change along the beam path. Tumor respiratory motion during treatment delivery will affect the proton dose distribution and the selection of optimized parameters for treatment planning, which has not been fully addressed yet in the existing approaches for proton dose calculation. The purpose of this dissertation is to develop an approach for more accurate dose delivery to a moving tumor in proton radiotherapy, i.e., 4D proton dose calculation and delivery, for the uniform scanning proton beam. A three-step approach has been carried out to achieve this goal. First, a solution for the proton output factor calculation which will convert the prescribed dose to machine deliverable monitor unit for proton dose delivery has been proposed and implemented. The novel sector integration method is accurate and time saving, which considers the various beam scanning patterns and treatment field parameters, such as aperture shape, aperture size, measuring position, beam range, and beam modulation. Second, tumor respiratory motion behavior has been statistically characterized and the results have been applied to advanced image guided radiation treatment. Different statistical analysis and correlation discovery approaches have been investigated. The internal / external motion correlation patterns have been simulated, analyzed, and applied in a new hybrid gated treatment to improve the target coverage. Third, a dose calculation method has been developed for 4D proton treatment planning which integrates the interplay effects of tumor respiratory motion patterns and proton beam delivery

Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms.

PubMed

Genina, Natalja; Räikkönen, Heikki; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

2010-09-01

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

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

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens

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 doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposedmore » lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

PubMed Central

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

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 doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

PubMed

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

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. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability

Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

PubMed

Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout

Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

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

Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding

2012-08-15

Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receivingmore » a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.« less

Influence of beam efficiency through the patient-specific collimator on secondary neutron dose equivalent in double scattering and uniform scanning modes of proton therapy.

PubMed

Hecksel, D; Anferov, V; Fitzek, M; Shahnazi, K

2010-06-01

Conventional proton therapy facilities use double scattering nozzles, which are optimized for delivery of a few fixed field sizes. Similarly, uniform scanning nozzles are commissioned for a limited number of field sizes. However, cases invariably occur where the treatment field is significantly different from these fixed field sizes. The purpose of this work was to determine the impact of the radiation field conformity to the patient-specific collimator on the secondary neutron dose equivalent. Using a WENDI-II neutron detector, the authors experimentally investigated how the neutron dose equivalent at a particular point of interest varied with different collimator sizes, while the beam spreading was kept constant. The measurements were performed for different modes of dose delivery in proton therapy, all of which are available at the Midwest Proton Radiotherapy Institute (MPRI): Double scattering, uniform scanning delivering rectangular fields, and uniform scanning delivering circular fields. The authors also studied how the neutron dose equivalent changes when one changes the amplitudes of the scanned field for a fixed collimator size. The secondary neutron dose equivalent was found to decrease linearly with the collimator area for all methods of dose delivery. The relative values of the neutron dose equivalent for a collimator with a 5 cm diameter opening using 88 MeV protons were 1.0 for the double scattering field, 0.76 for rectangular uniform field, and 0.6 for the circular uniform field. Furthermore, when a single circle wobbling was optimized for delivery of a uniform field 5 cm in diameter, the secondary neutron dose equivalent was reduced by a factor of 6 compared to the double scattering nozzle. Additionally, when the collimator size was kept constant, the neutron dose equivalent at the given point of interest increased linearly with the area of the scanned proton beam. The results of these experiments suggest that the patient-specific collimator is a

Improvement of Predictive Ability by Uniform Coverage of the Target Genetic Space

PubMed Central

Bustos-Korts, Daniela; Malosetti, Marcos; Chapman, Scott; Biddulph, Ben; van Eeuwijk, Fred

2016-01-01

Genome-enabled prediction provides breeders with the means to increase the number of genotypes that can be evaluated for selection. One of the major challenges in genome-enabled prediction is how to construct a training set of genotypes from a calibration set that represents the target population of genotypes, where the calibration set is composed of a training and validation set. A random sampling protocol of genotypes from the calibration set will lead to low quality coverage of the total genetic space by the training set when the calibration set contains population structure. As a consequence, predictive ability will be affected negatively, because some parts of the genotypic diversity in the target population will be under-represented in the training set, whereas other parts will be over-represented. Therefore, we propose a training set construction method that uniformly samples the genetic space spanned by the target population of genotypes, thereby increasing predictive ability. To evaluate our method, we constructed training sets alongside with the identification of corresponding genomic prediction models for four genotype panels that differed in the amount of population structure they contained (maize Flint, maize Dent, wheat, and rice). Training sets were constructed using uniform sampling, stratified-uniform sampling, stratified sampling and random sampling. We compared these methods with a method that maximizes the generalized coefficient of determination (CD). Several training set sizes were considered. We investigated four genomic prediction models: multi-locus QTL models, GBLUP models, combinations of QTL and GBLUPs, and Reproducing Kernel Hilbert Space (RKHS) models. For the maize and wheat panels, construction of the training set under uniform sampling led to a larger predictive ability than under stratified and random sampling. The results of our methods were similar to those of the CD method. For the rice panel, all training set construction

Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

NASA Astrophysics Data System (ADS)

McCall, Keisha C.

Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

Non-uniform dose distributions in cranial radiation therapy

NASA Astrophysics Data System (ADS)

Bender, Edward T.

Radiation treatments are often delivered to patients with brain metastases. For those patients who receive radiation to the entire brain, there is a risk of long-term neuro-cognitive side effects, which may be due to damage to the hippocampus. In clinical MRI and CT scans it can be difficult to identify the hippocampus, but once identified it can be partially spared from radiation dose. Using deformable image registration we demonstrate a semi-automatic technique for obtaining an estimated location of this structure in a clinical MRI or CT scan. Deformable image registration is a useful tool in other areas such as adaptive radiotherapy, where the radiation oncology team monitors patients during the course of treatment and adjusts the radiation treatments if necessary when the patient anatomy changes. Deformable image registration is used in this setting, but there is a considerable level of uncertainty. This work represents one of many possible approaches at investigating the nature of these uncertainties utilizing consistency metrics. We will show that metrics such as the inverse consistency error correlate with actual registration uncertainties. Specifically relating to brain metastases, this work investigates where in the brain metastases are likely to form, and how the primary cancer site is related. We will show that the cerebellum is at high risk for metastases and that non-uniform dose distributions may be advantageous when delivering prophylactic cranial irradiation for patients with small cell lung cancer in complete remission.

Therapeutic analysis of high-dose-rate {sup 192}Ir vaginal cuff brachytherapy for endometrial cancer using a cylindrical target volume model and varied cancer cell distributions

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

Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu; Donnelly, Eric D.; Strauss, Jonathan B.

Purpose: To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model. Methods: A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model wasmore » used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution. Results: EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0){sup 4} to

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

PubMed

Dumas, J L; Lorchel, F; Perrot, Y; Aletti, P; Noel, A; Wolf, D; Courvoisier, P; Bosset, J F

2007-03-01

The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

Dose uniformity of loteprednol etabonate ophthalmic gel (0.5%) compared with branded and generic prednisolone acetate ophthalmic suspension (1%).

PubMed

Marlowe, Zora T; Davio, Stephen R

2014-01-01

Loteprednol etabonate (LE) ophthalmic gel 0.5% (Lotemax®) is a new polycarbophil-based, nonsettling topical ophthalmic formulation. The formulation is a semisolid gel at rest and a shear thinning fluid when expressed through a dropper tip. The present study was undertaken to determine how the nonsettling character of LE ophthalmic gel affects dose uniformity. Prednisolone acetate ophthalmic suspension 1% (Pred Forte®) and a generic prednisolone acetate suspension 1% were used as comparators. Drug concentrations of LE ophthalmic gel, Pred Forte, and a generic prednisolone acetate suspension were determined following simulated dosing - consisting of 2 drops, expressed four times daily for 2 weeks, with bottles that were shaken or not shaken immediately prior to expressing the drops. Drug concentrations were determined using a reverse-phase high-performance liquid chromatography (HPLC) method and reported as a percentage of the declared (labeled) concentration. Comparative kinetics of drug particle sedimentation were also determined for each formulation, using dispersion analysis under gravity. Mean drug concentrations in drops of all three formulations were within a few percentage points of the declared concentration when the bottles were shaken for 5 seconds prior to dispensing. Only LE ophthalmic gel showed consistent and on-target concentrations when the bottles were unshaken prior to dispensing, with a mean (standard deviation [SD]) percent declared concentration of 102% (1.92%) over the 2-week dosing regimen. Drug concentrations for the branded and generic prednisolone acetate suspensions following expression from unshaken bottles were highly variable (overall relative SDs of 16.8% and 20.3%, respectively), with mean concentrations for both falling significantly below the declared concentration for drops expressed at the beginning of the 2-week dosing regimen and significantly above the declared concentration for drops expressed near the end of the dosing

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

PubMed

Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

2018-02-01

To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Uniform magnetic targeting of magnetic particles attracted by a new ferromagnetic biological patch.

PubMed

Pei, Ning; Cai, Lanlan; Yang, Kai; Ma, Jiaqi; Gong, Yongyong; Wang, Qixin; Huang, Zheyong

2018-02-01

A new non-toxic ferromagnetic biological patch (MBP) was designed in this paper. The MBP consisted of two external layers that were made of transparent silicone, and an internal layer that was made of a mixture of pure iron powder and silicon rubber. Finite-element analysis showed that the local inhomogeneous magnetic field (MF) around the MBP was generated when MBP was placed in a uniform MF. The local MF near the MBP varied with the uniform MF and shape of the MBP. Therefore, not only could the accumulation of paramagnetic particles be adjusted by controlling the strength of the uniform MF, but also the distribution of the paramagnetic particles could be improved with the different shape of the MBP. The relationship of the accumulation of paramagnetic particles or cells, magnetic flux density, and fluid velocity were studied through in vitro experiments and theoretical considerations. The accumulation of paramagnetic particles first increased with increment in the magnetic flux density of the uniform MF. But when the magnetic flux density of the uniform MF exceeded a specific value, the magnetic flux density of the MBP reached saturation, causing the accumulation of paramagnetic particles to fall. In addition, the adsorption morphology of magnetic particles or cells could be improved and the uniform distribution of magnetic particles could be achieved by changing the shape of the MBP. Also, MBP may be used as a new implant to attract magnetic drug carrier particles in magnetic drug targeting. Bioelectromagnetics. 39:98-107, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

How do formulation and process parameters impact blend and unit dose uniformity? Further analysis of the product quality research institute blend uniformity working group industry survey.

PubMed

Hancock, Bruno C; Garcia-Munoz, Salvador

2013-03-01

Responses from the second Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) survey of industry have been reanalyzed to identify potential links between formulation and processing variables and the measured uniformity of blends and unit dosage forms. As expected, the variability of the blend potency and tablet potency data increased with a decrease in the loading of the active pharmaceutical ingredient (API). There was also an inverse relationship between the nominal strength of the unit dose and the blend uniformity data. The data from the PQRI industry survey do not support the commonly held viewpoint that granulation processes are necessary to create and sustain tablet and capsule formulations with a high degree of API uniformity. There was no correlation between the blend or tablet potency variability and the type of process used to manufacture the product. Although it is commonly believed that direct compression processes should be avoided for low API loading formulations because of blend and tablet content uniformity concerns, the data for direct compression processes reported by the respondents to the PQRI survey suggest that such processes are being used routinely to manufacture solid dosage forms of acceptable quality even when the drug loading is quite low. Copyright © 2012 Wiley Periodicals, Inc.

Glandular radiation dose in tomosynthesis of the breast using tungsten targets.

PubMed

Sechopoulos, Ioannis; D'Orsi, Carl J

2008-10-24

With the advent of new detector technology, digital tomosynthesis imaging of the breast has, in the past few years, become a technique intensely investigated as a replacement for planar mammography. As with all other x-ray-based imaging methods, radiation dose is of utmost concern in the development of this new imaging technology. For virtually all development and optimization studies, knowledge of the radiation dose involved in an imaging protocol is necessary. A previous study characterized the normalized glandular dose in tomosynthesis imaging and its variation with various breast and imaging system parameters. This characterization was performed with x-ray spectra generated by molybdenum and rhodium targets. In the recent past, many preliminary patient studies of tomosynthesis imaging have been reported in which the x-ray spectra were generated with x-ray tubes with tungsten targets. The differences in x-ray distribution among spectra from these target materials make the computation of new normalized glandular dose values for tungsten target spectra necessary. In this study we used previously obtained monochromatic normalized glandular dose results to obtain spectral results for twelve different tungsten target x-ray spectra. For each imaging condition, two separate values were computed: the normalized glandular dose for the zero degree projection angle (DgN0), and the ratio of the glandular dose for non-zero projection angles to the glandular dose for the zero degree projection (the relative glandular dose, RGD(alpha)). It was found that DgN0 is higher for tungsten target x-ray spectra when compared with DgN0 values for molybdenum and rhodium target spectra of both equivalent tube voltage and first half value layer. Therefore, the DgN0 for the twelve tungsten target x-ray spectra and different breast compositions and compressed breast thicknesses simulated are reported. The RGD(alpha) values for the tungsten spectra vary with the parameters studied in a

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

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

Papp, D; Unkelbach, J

2014-06-01

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

Enhanced retained dose uniformity in NiTi spinal correction rod treated by three-dimensional mesh-assisted nitrogen plasma immersion ion implantation

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

Lu, Q. Y.; Hu, T.; Kwok, Dixon T. K.

2010-05-15

Owing to the nonconformal plasma sheath in plasma immersion ion implantation of a rod sample, the retained dose can vary significantly. The authors propose to improve the implant uniformity by introducing a metal mesh. The depth profiles obtained with and without the mesh are compared and the implantation temperature at various locations is evaluated indirectly by differential scanning calorimeter. Our results reveal that by using the metal mesh, the retained dose uniformity along the length is greatly improved and the effects of the implantation temperature on the localized mechanical properties of the implanted NiTi shape memory alloy rod are nearlymore » negligible.« less

SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose-Range Dependency of Radio-Biological Parameters.

PubMed

Troeller, A; Soehn, M; Yan, D

2012-06-01

Introducing an extended, phenomenological, generalized equivalent uniform dose (eEUD) that incorporates multiple volume-effect parameters for different dose-ranges. The generalized EUD (gEUD) was introduced as an estimate of the EUD that incorporates a single, tissue-specific parameter - the volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its radio-biological equivalency to a given inhomogeneous dose distribution is not a priori clear and mechanistic models based on radio-biological parameters are assumed to better resemble the underlying biology. However, for normal organs mechanistic models are hard to derive, since the structural organization of the tissue plays a significant role. Consequently, phenomenological approaches might be especially useful in order to describe dose-response for normal tissues. However, the single parameter used to estimate the gEUD may not suffice in accurately representing more complex biological effects that have been discussed in the literature. For instance, radio-biological parameters and hence the effects of fractionation are known to be dose-range dependent. Therefore, we propose an extended phenomenological eEUD formula that incorporates multiple VEPs accounting for dose-range dependency. The eEUD introduced is a piecewise polynomial expansion of the gEUD formula. In general, it allows for an arbitrary number of VEPs, each valid for a certain dose-range. We proved that the formula fulfills required mathematical and physical criteria such as invertibility of the underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD as a special case, if all VEPs are equal to 'a' from the gEUD model. The eEUD is a concept that expands the gEUD such that it can theoretically represent dose-range dependent effects. Its practicality, however, remains to be shown. As a next step, this will be done by estimating the eEUD from patient data using maximum-likelihood based NTCP modelling in the same way

Dose-shaping using targeted sparse optimization

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

Sayre, George A.; Ruan, Dan

2013-07-15

Purpose: Dose volume histograms (DVHs) are common tools in radiation therapy treatment planning to characterize plan quality. As statistical metrics, DVHs provide a compact summary of the underlying plan at the cost of losing spatial information: the same or similar dose-volume histograms can arise from substantially different spatial dose maps. This is exactly the reason why physicians and physicists scrutinize dose maps even after they satisfy all DVH endpoints numerically. However, up to this point, little has been done to control spatial phenomena, such as the spatial distribution of hot spots, which has significant clinical implications. To this end, themore » authors propose a novel objective function that enables a more direct tradeoff between target coverage, organ-sparing, and planning target volume (PTV) homogeneity, and presents our findings from four prostate cases, a pancreas case, and a head-and-neck case to illustrate the advantages and general applicability of our method.Methods: In designing the energy minimization objective (E{sub tot}{sup sparse}), the authors utilized the following robust cost functions: (1) an asymmetric linear well function to allow differential penalties for underdose, relaxation of prescription dose, and overdose in the PTV; (2) a two-piece linear function to heavily penalize high dose and mildly penalize low and intermediate dose in organs-at risk (OARs); and (3) a total variation energy, i.e., the L{sub 1} norm applied to the first-order approximation of the dose gradient in the PTV. By minimizing a weighted sum of these robust costs, general conformity to dose prescription and dose-gradient prescription is achieved while encouraging prescription violations to follow a Laplace distribution. In contrast, conventional quadratic objectives are associated with a Gaussian distribution of violations, which is less forgiving to large violations of prescription than the Laplace distribution. As a result, the proposed objective E

Margin estimation and disturbances of irradiation field in layer-stacking carbon-ion beams for respiratory moving targets.

PubMed

Tajiri, Shinya; Tashiro, Mutsumi; Mizukami, Tomohiro; Tsukishima, Chihiro; Torikoshi, Masami; Kanai, Tatsuaki

2017-11-01

Carbon-ion therapy by layer-stacking irradiation for static targets has been practised in clinical treatments. In order to apply this technique to a moving target, disturbances of carbon-ion dose distributions due to respiratory motion have been studied based on the measurement using a respiratory motion phantom, and the margin estimation given by the square root of the summation Internal margin2+Setup margin2 has been assessed. We assessed the volume in which the variation in the ratio of the dose for a target moving due to respiration relative to the dose for a static target was within 5%. The margins were insufficient for use with layer-stacking irradiation of a moving target, and an additional margin was required. The lateral movement of a target converts to the range variation, as the thickness of the range compensator changes with the movement of the target. Although the additional margin changes according to the shape of the ridge filter, dose uniformity of 5% can be achieved for a spherical target 93 mm in diameter when the upward range variation is limited to 5 mm and the additional margin of 2.5 mm is applied in case of our ridge filter. Dose uniformity in a clinical target largely depends on the shape of the mini-peak as well as on the bolus shape. We have shown the relationship between range variation and dose uniformity. In actual therapy, the upper limit of target movement should be considered by assessing the bolus shape. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.

EPA Science Inventory

Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure...

Absorbed dose in target cell nuclei and dose conversion coefficient of radon progeny in the human lung.

PubMed

Nikezic, D; Lau, B M F; Stevanovic, N; Yu, K N

2006-01-01

To calculate the absorbed dose in the human lung due to inhaled radon progeny, ICRP focussed on the layers containing the target cells, i.e., the basal and secretory cells. Such an approach did not consider details of the sensitive cells in the layers. The present work uses the microdosimetric approach and determines the absorbed alpha-particle energy in non-spherical nuclei of target cells (basal and secretory cells). The absorbed energy for alpha particles emitted by radon progeny in the human respiratory tract was calculated in basal- and secretory-cell nuclei, assuming conical and ellipsoidal forms for these cells. Distributions of specific energy for different combinations of alpha-particle sources, energies and targets are calculated and shown. The dose conversion coefficient for radon progeny is reduced for about 2mSv/WLM when conical and ellipsoidal cell nuclei are considered instead of the layers. While changes in the geometry of secretory-cell nuclei do not have significant effects on their absorbed dose, changes from spherical to conical basal-cell nuclei have significantly reduced their absorbed dose from approximately 4 to approximately 3mGy/WLM. This is expected because basal cells are situated close to the end of the range of 6MeV alpha particles. This also underlines the significance of better and more precise information on targets in the T-B tree. A further change in the dose conversion coefficient can be achieved if a different weighting scheme is adopted for the doses for the cells. The results demonstrate the necessity for better information on the target cells for more accurate dosimetry for radon progeny.

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

PubMed

Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Low-dose fixed-target serial synchrotron crystallography.

PubMed

Owen, Robin L; Axford, Danny; Sherrell, Darren A; Kuo, Anling; Ernst, Oliver P; Schulz, Eike C; Miller, R J Dwayne; Mueller-Werkmeister, Henrike M

2017-04-01

The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption.

Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy.

PubMed

Corletto, Anna; Fröhlich, Hanna; Täger, Tobias; Hochadel, Matthias; Zahn, Ralf; Kilkowski, Caroline; Winkler, Ralph; Senges, Jochen; Katus, Hugo A; Frankenstein, Lutz

2018-05-17

Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69 bpm. All-cause mortality during the median follow-up of 42.8 months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p <  0.001). Survival for group A patients with a HR ≥ 70 bpm was 28.8% but 14.8% if HR was 50-70 bpm (p = 0.054). Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

PubMed

Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

2012-02-01

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Analytical dose modeling for preclinical proton irradiation of millimetric targets.

PubMed

Vanstalle, Marie; Constanzo, Julie; Karakaya, Yusuf; Finck, Christian; Rousseau, Marc; Brasse, David

2018-01-01

Due to the considerable development of proton radiotherapy, several proton platforms have emerged to irradiate small animals in order to study the biological effectiveness of proton radiation. A dedicated analytical treatment planning tool was developed in this study to accurately calculate the delivered dose given the specific constraints imposed by the small dimensions of the irradiated areas. The treatment planning system (TPS) developed in this study is based on an analytical formulation of the Bragg peak and uses experimental range values of protons. The method was validated after comparison with experimental data from the literature and then compared to Monte Carlo simulations conducted using Geant4. Three examples of treatment planning, performed with phantoms made of water targets and bone-slab insert, were generated with the analytical formulation and Geant4. Each treatment planning was evaluated using dose-volume histograms and gamma index maps. We demonstrate the value of the analytical function for mouse irradiation, which requires a targeting accuracy of 0.1 mm. Using the appropriate database, the analytical modeling limits the errors caused by misestimating the stopping power. For example, 99% of a 1-mm tumor irradiated with a 24-MeV beam receives the prescribed dose. The analytical dose deviations from the prescribed dose remain within the dose tolerances stated by report 62 of the International Commission on Radiation Units and Measurements for all tested configurations. In addition, the gamma index maps show that the highly constrained targeting accuracy of 0.1 mm for mouse irradiation leads to a significant disagreement between Geant4 and the reference. This simulated treatment planning is nevertheless compatible with a targeting accuracy exceeding 0.2 mm, corresponding to rat and rabbit irradiations. Good dose accuracy for millimetric tumors is achieved with the analytical calculation used in this work. These volume sizes are typical in mouse

Non-targeted effects of ionizing radiation–implications for low dose risk

PubMed Central

Kadhim, Munira; Salomaa, Sisko; Wright, Eric; Hildebrandt, Guido; Belyakov, Oleg V.; Prise, Kevin M.; Little, Mark P.

2014-01-01

Non-DNA targeted effects of ionizing radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionizing radiation. Other outstanding questions include links between the different non-targeted responses and the variations in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the Non-targeted effects of ionizing radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. PMID:23262375

A quality control method for intensity-modulated radiation therapy planning based on generalized equivalent uniform dose.

PubMed

Pang, Haowen; Sun, Xiaoyang; Yang, Bo; Wu, Jingbo

2018-05-01

To ensure good quality intensity-modulated radiation therapy (IMRT) planning, we proposed the use of a quality control method based on generalized equivalent uniform dose (gEUD) that predicts absorbed radiation doses in organs at risk (OAR). We conducted a retrospective analysis of patients who underwent IMRT for the treatment of cervical carcinoma, nasopharyngeal carcinoma (NPC), or non-small cell lung cancer (NSCLC). IMRT plans were randomly divided into data acquisition and data verification groups. OAR in the data acquisition group for cervical carcinoma and NPC were further classified as sub-organs at risk (sOAR). The normalized volume of sOAR and normalized gEUD (a = 1) were analyzed using multiple linear regression to establish a fitting formula. For NSCLC, the normalized intersection volume of the planning target volume (PTV) and lung, the maximum diameter of the PTV (left-right, anterior-posterior, and superior-inferior), and the normalized gEUD (a = 1) were analyzed using multiple linear regression to establish a fitting formula for the lung gEUD (a = 1). The r-squared and P values indicated that the fitting formula was a good fit. In the data verification group, IMRT plans verified the accuracy of the fitting formula, and compared the gEUD (a = 1) for each OAR between the subjective method and the gEUD-based method. In conclusion, the gEUD-based method can be used effectively for quality control and can reduce the influence of subjective factors on IMRT planning optimization. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

PubMed

Murthy, Kk; Shukeili, Ka; Kumar, Ss; Davis, Ca; Chandran, Rr; Namrata, S

2010-01-01

To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV(95), D(mean), uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, D(mean), D(max), dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p<0.001) with higher conformity index value of 0.81±0.07 compared to both the 3D-CRT plans. The doses to the liver and bowel reduced significantly (p<0.001) with IMRT plans compared to other 3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

A Monte Carlo study of I-125 prostate brachytherapy with gold nanoparticles: dose enhancement with simultaneous rectal dose sparing via radiation shielding.

PubMed

Brivio, D; Nguyen, P L; Sajo, E; Ngwa, W; Zygmanski, P

2017-03-07

We investigate via Monte Carlo simulations a new 125 I brachytherapy treatment technique for high-risk prostate cancer patients via injection of Au nanoparticle (AuNP) directly into the prostate. The purpose of using the nanoparticles is to increase the therapeutic index via two synergistic effects: enhanced energy deposition within the prostate and simultaneous shielding of organs at risk from radiation escaping from the prostate. Both uniform and non-uniform concentrations of AuNP are studied. The latter are modeled considering the possibility of AuNP diffusion after the injection using brachy needles. We study two extreme cases of coaxial AuNP concentrations: centered on brachy needles and centered half-way between them. Assuming uniform distribution of 30 mg g -1 of AuNP within the prostate, we obtain a dose enhancement larger than a factor of 2 to the prostate. Non-uniform concentration of AuNP ranging from 10 mg g -1 and 66 mg g -1 were studied. The higher the concentration in a given region of the prostate the greater is the enhancement therein. We obtain the highest dose enhancement when the brachytherapy needles are coincident with AuNP injection needles but, at the same time, the regions in the tail are colder (average dose ratio of 0.7). The best enhancement uniformity is obtained with the seeds in the tail of the AuNP distribution. In both uniform and non-uniform cases the urethra and rectum receive less than 1/3 dose compared to an analog treatment without AuNP. Remarkably, employing AuNP not only significantly increases dose to the target but also decreases dose to the neighboring rectum and even urethra, which is embedded within the prostate. These are mutually interdependent effects as more enhancement leads to more shielding and vice-versa. Caution must be paid since cold spot or hot spots may be created if the AuNP concentration versus seed position is not properly distributed respect to the seed locations.

A Monte Carlo study of I-125 prostate brachytherapy with gold nanoparticles: dose enhancement with simultaneous rectal dose sparing via radiation shielding

NASA Astrophysics Data System (ADS)

Brivio, D.; Nguyen, P. L.; Sajo, E.; Ngwa, W.; Zygmanski, P.

2017-03-01

We investigate via Monte Carlo simulations a new 125I brachytherapy treatment technique for high-risk prostate cancer patients via injection of Au nanoparticle (AuNP) directly into the prostate. The purpose of using the nanoparticles is to increase the therapeutic index via two synergistic effects: enhanced energy deposition within the prostate and simultaneous shielding of organs at risk from radiation escaping from the prostate. Both uniform and non-uniform concentrations of AuNP are studied. The latter are modeled considering the possibility of AuNP diffusion after the injection using brachy needles. We study two extreme cases of coaxial AuNP concentrations: centered on brachy needles and centered half-way between them. Assuming uniform distribution of 30 mg g-1 of AuNP within the prostate, we obtain a dose enhancement larger than a factor of 2 to the prostate. Non-uniform concentration of AuNP ranging from 10 mg g-1 and 66 mg g-1 were studied. The higher the concentration in a given region of the prostate the greater is the enhancement therein. We obtain the highest dose enhancement when the brachytherapy needles are coincident with AuNP injection needles but, at the same time, the regions in the tail are colder (average dose ratio of 0.7). The best enhancement uniformity is obtained with the seeds in the tail of the AuNP distribution. In both uniform and non-uniform cases the urethra and rectum receive less than 1/3 dose compared to an analog treatment without AuNP. Remarkably, employing AuNP not only significantly increases dose to the target but also decreases dose to the neighboring rectum and even urethra, which is embedded within the prostate. These are mutually interdependent effects as more enhancement leads to more shielding and vice-versa. Caution must be paid since cold spot or hot spots may be created if the AuNP concentration versus seed position is not properly distributed respect to the seed locations.

Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose–volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer

PubMed Central

Lee, T-F; Ting, H-M; Chao, P-J; Wang, H-Y; Shieh, C-S; Horng, M-F; Wu, J-M; Yeh, S-A; Cho, M-Y; Huang, E-Y; Huang, Y-J; Chen, H-C; Fang, F-M

2012-01-01

Objective We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose–volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose–volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan). Methods The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle3® system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2–T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V20 Gy and V30 Gy of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability. Results Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V20 Gy, and heart V30 Gy in the DV-gEUD plan were lower than those in the DV plan (p<0.05). Conclusions A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution. Advances to knowledge The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV. PMID:23091290

In vivo tumor targeting of gold nanoparticles: effect of particle type and dosing strategy.

PubMed

Puvanakrishnan, Priyaveena; Park, Jaesook; Chatterjee, Deyali; Krishnan, Sunil; Tunnell, James W

2012-01-01

Gold nanoparticles (GNPs) have gained significant interest as nanovectors for combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs preferentially accumulate at the tumor site via the enhanced permeability and retention effect, and when irradiated with near infrared light, produce sufficient heat to treat tumor tissue. The efficacy of this process strongly depends on the targeting ability of the GNPs, which is a function of the particle's geometric properties (eg, size) and dosing strategy (eg, number and amount of injections). The purpose of this study was to investigate the effect of GNP type and dosing strategy on in vivo tumor targeting. Specifically, we investigated the in vivo tumor-targeting efficiency of pegylated gold nanoshells (GNSs) and gold nanorods (GNRs) for single and multiple dosing. We used Swiss nu/nu mice with a subcutaneous tumor xenograft model that received intravenous administration for a single and multiple doses of GNS and GNR. We performed neutron activation analysis to quantify the gold present in the tumor and liver. We performed histology to determine if there was acute toxicity as a result of multiple dosing. Neutron activation analysis results showed that the smaller GNRs accumulated in higher concentrations in the tumor compared to the larger GNSs. We observed a significant increase in GNS and GNR accumulation in the liver for higher doses. However, multiple doses increased targeting efficiency with minimal effect beyond three doses of GNPs. These results suggest a significant effect of particle type and multiple doses on increasing particle accumulation and on tumor targeting ability.

A Monte Carlo study of the impact of the choice of rectum volume definition on estimates of equivalent uniform doses and the volume parameter

NASA Astrophysics Data System (ADS)

Kvinnsland, Yngve; Muren, Ludvig Paul; Dahl, Olav

2004-08-01

Calculations of normal tissue complication probability (NTCP) values for the rectum are difficult because it is a hollow, non-rigid, organ. Finding the true cumulative dose distribution for a number of treatment fractions requires a CT scan before each treatment fraction. This is labour intensive, and several surrogate distributions have therefore been suggested, such as dose wall histograms, dose surface histograms and histograms for the solid rectum, with and without margins. In this study, a Monte Carlo method is used to investigate the relationships between the cumulative dose distributions based on all treatment fractions and the above-mentioned histograms that are based on one CT scan only, in terms of equivalent uniform dose. Furthermore, the effect of a specific choice of histogram on estimates of the volume parameter of the probit NTCP model was investigated. It was found that the solid rectum and the rectum wall histograms (without margins) gave equivalent uniform doses with an expected value close to the values calculated from the cumulative dose distributions in the rectum wall. With the number of patients available in this study the standard deviations of the estimates of the volume parameter were large, and it was not possible to decide which volume gave the best estimates of the volume parameter, but there were distinct differences in the mean values of the values obtained.

Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation

NASA Technical Reports Server (NTRS)

Limoli, C. L.; Corcoran, J. J.; Milligan, J. R.; Ward, J. F.; Morgan, W. F.

1999-01-01

To investigate the critical target, dose response and dose-rate response for the induction of chromosomal instability by ionizing radiation, bromodeoxyuridine (BrdU)-substituted and unsubstituted GM10115 cells were exposed to a range of doses (0.1-10 Gy) and different dose rates (0.092-17.45 Gy min(-1)). The status of chromosomal stability was determined by fluorescence in situ hybridization approximately 20 generations after irradiation in clonal populations derived from single progenitor cells surviving acute exposure. Overall, nearly 700 individual clones representing over 140,000 metaphases were analyzed. In cells unsubstituted with BrdU, a dose response was found, where the probability of observing delayed chromosomal instability in any given clone was 3% per gray of X rays. For cells substituted with 25-66% BrdU, however, a dose response was observed only at low doses (<1.0 Gy); at higher doses (>1.0 Gy), the incidence of chromosomal instability leveled off. There was an increase in the frequency and complexity of chromosomal instability per unit dose compared to cells unsubstituted with BrdU. The frequency of chromosomal instability appeared to saturate around approximately 30%, an effect which occurred at much lower doses in the presence of BrdU. Changing the gamma-ray dose rate by a factor of 190 (0.092 to 17.45 Gy min(-1)) produced no significant differences in the frequency of chromosomal instability. The enhancement of chromosomal instability promoted by the presence of the BrdU argues that DNA comprises at least one of the critical targets important for the induction of this end point of genomic instability.

Poster - 36: Effect of Planning Target Volume Coverage on the Dose Delivered in Lung Radiotherapy

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

Dekker, Chris; Wierzbicki, Marcin

2016-08-15

Purpose: In lung radiotherapy, breathing motion may be encompassed by contouring the internal target volume (ITV). Remaining uncertainties are included in a geometrical expansion to the planning target volume (PTV). In IMRT, the treatment is then optimized until a desired PTV fraction is covered by the appropriate dose. The resulting beams often carry high fluence in the PTV margin to overcome low lung density and to generate steep dose gradients. During treatment, the high density tumour can enter the PTV margin, potentially increasing target dose. Thus, planning lung IMRT with a reduced PTV dose may still achieve the desired ITVmore » dose during treatment. Methods: A retrospective analysis was carried out with 25 IMRT plans prescribed to 63 Gy in 30 fractions. The plans were re-normalized to cover various fractions of the PTV by different isodose lines. For each case, the isocentre was moved using 125 shifts derived from all 3D combinations of 0 mm, (PTV margin - 1 mm), and PTV margin. After each shift, the dose was recomputed to approximate the delivered dose. Results and Conclusion: Our plans typically cover 95% of the PTV by 95% of the dose. Reducing the PTV covered to 94% did not significantly reduce the delivered ITV doses for (PTV margin - 1 mm) shifts. Target doses were reduced significantly for all other shifts and planning goals studied. Thus, a reduced planning goal will likely deliver the desired target dose as long as the ITV rarely enters the last mm of the PTV margin.« less

Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates.

PubMed

Hou, X; Tanguay, J; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2016-01-21

In response to the recognized fragility of reactor-produced (99)Mo supply, direct production of (99m)Tc via (100)Mo(p,2n)(99m)Tc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with (99m)Tc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical (99m)Tc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates

NASA Astrophysics Data System (ADS)

Hou, X.; Tanguay, J.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2016-01-01

In response to the recognized fragility of reactor-produced 99Mo supply, direct production of 99mTc via 100Mo(p,2n)99mTc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with 99mTc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical 99mTc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

PubMed

Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis

2011-08-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia

PubMed Central

Yadav, Manisha C.; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L.; Whyte, Michael P.; Crine, Philippe; Millán, José Luis

2011-01-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD10, renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2−/−) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2−/− mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2 mg/kg for 43 days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED80 (the dose prevents the bone defects in 80% of mice) was 3.2, 2.8 and 2.9 mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PPi concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. PMID:21458605

Helical Tomotherapy vs. Intensity-Modulated Proton Therapy for Whole Pelvis Irradiation in High-Risk Prostate Cancer Patients: Dosimetric, Normal Tissue Complication Probability, and Generalized Equivalent Uniform Dose Analysis

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

Widesott, Lamberto, E-mail: widesott@yahoo.it; Pierelli, Alessio; Fiorino, Claudio

2011-08-01

Purpose: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for high-risk prostate cancer (HRPCa) patients. Methods and Materials: The plans of 8 patients with HRPCa treated with HT were compared with IMPT plans with two quasilateral fields set up (-100{sup o}; 100{sup o}) and optimized with the Hyperion treatment planning system. Both techniques were optimized to simultaneously deliver 74.2 Gy/Gy relative biologic effectiveness (RBE) in 28 fractions on planning target volumes (PTVs)3-4 (P + proximal seminal vesicles), 65.5 Gy/Gy(RBE) on PTV2 (distal seminal vesicles and rectum/prostate overlapping), and 51.8 Gy/Gy(RBE) to PTV1 (pelvic lymph nodes). Normalmore » tissue calculation probability (NTCP) calculations were performed for the rectum, and generalized equivalent uniform dose (gEUD) was estimated for the bowel cavity, penile bulb and bladder. Results: A slightly better PTV coverage and homogeneity of target dose distribution with IMPT was found: the percentage of PTV volume receiving {>=}95% of the prescribed dose (V{sub 95%}) was on average >97% in HT and >99% in IMPT. The conformity indexes were significantly lower for protons than for photons, and there was a statistically significant reduction of the IMPT dosimetric parameters, up to 50 Gy/Gy(RBE) for the rectum and bowel and 60 Gy/Gy(RBE) for the bladder. The NTCP values for the rectum were higher in HT for all the sets of parameters, but the gain was small and in only a few cases statistically significant. Conclusions: Comparable PTV coverage was observed. Based on NTCP calculation, IMPT is expected to allow a small reduction in rectal toxicity, and a significant dosimetric gain with IMPT, both in medium-dose and in low-dose range in all OARs, was observed.« less

[EEG-adjusted target-controlled infusion : Propofol target concentration with different doses of remifentanil].

PubMed

Büttner, N; Schultz, B; Grouven, U; Schultz, A

2010-02-01

The aim of this study was to examine to what extent the use of electroencephalography (EEG) monitoring leads to an adaptation of the target-controlled infusion (TCI) concentration of propofol during propofol anaesthesia with different doses of remifentanil. With ethics committee approval 60 patients (27-69 years old) with American Society of Anesthesiologists classification (ASA) I-III received anaesthestics with propofol (TCI, Diprifusor, AstraZeneca, Wedel, Deutschland) and 0.2, 0.4, or 0.6 microg/kg body weight remifentanil, respectively (groups 1-3). Anaesthesia was maintained at a level of deep hypnosis (EEG stages D(2)/E(0), EEG monitor: Narcotrend, version 2.0/5.0, manufacturer: MT MonitorTechnik, Bad Bramstedt, Germany). During the steady state the propofol concentration in groups 1-3 was 3.02+/-0.86, 1.93+/-0.53 and 1.60+/-0.55 microg/ml, respectively (p<0.001). Women had a higher propofol consumption than men (p<0.05). Dreams during anaesthesia were more often reported by women than by men (p<0.05). The need for postoperative analgesia decreased with an increasing intraoperative remifentanil dose (p<0.05). The study demonstrates that remifentanil has both analgetic and hypnotic effects. With increasing remifentanil dose the propofol requirement decreased and in this context EEG monitoring is useful to adapt the target concentrations of propofol to the patients' age and gender.

Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

PubMed

Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

2013-09-01

The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect

Significance of including field non-uniformities such as the heel effect and beam scatter in the determination of the skin dose distribution during interventional fluoroscopic procedures

NASA Astrophysics Data System (ADS)

Rana, Vijay; Gill, Kamaljit; Rudin, Stephen; Bednarek, Daniel R.

2012-03-01

The current version of the real-time skin-dose-tracking system (DTS) we have developed assumes the exposure is contained within the collimated beam and is uniform except for inverse-square variation. This study investigates the significance of factors that contribute to beam non-uniformity such as the heel effect and backscatter from the patient to areas of the skin inside and outside the collimated beam. Dose-calibrated Gafchromic film (XR-RV3, ISP) was placed in the beam in the plane of the patient table at a position 15 cm tube-side of isocenter on a Toshiba Infinix C-Arm system. Separate exposures were made with the film in contact with a block of 20-cm solid water providing backscatter and with the film suspended in air without backscatter, both with and without the table in the beam. The film was scanned to obtain dose profiles and comparison of the profiles for the various conditions allowed a determination of field non-uniformity and backscatter contribution. With the solid-water phantom and with the collimator opened completely for the 20-cm mode, the dose profile decreased by about 40% on the anode side of the field. Backscatter falloff at the beam edge was about 10% from the center and extra-beam backscatter decreased slowly with distance from the field, being about 3% of the beam maximum at 6 cm from the edge. Determination of the magnitude of these factors will allow them to be included in the skin-dose-distribution calculation and should provide a more accurate determination of peak-skin dose for the DTS.

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

PubMed

Luxton, Gary; Keall, Paul J; King, Christopher R

2008-01-07

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

Autologous hematopoietic stem cell transplantation in peripheral T-cell lymphoma using a uniform high-dose regimen.

PubMed

Smith, S D; Bolwell, B J; Rybicki, L A; Brown, S; Dean, R; Kalaycio, M; Sobecks, R; Andresen, S; Hsi, E D; Pohlman, B; Sweetenham, J W

2007-08-01

The role of high-dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Some retrospective studies have found comparable survival rates for patients with T- and B-cell NHL. In this study, we report our single-center experience of ASCT over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell lymphoma (21 patients) underwent autologous stem cell transplant, mostly for relapsed or refractory disease. The preparative regimen consisted of busulfan, etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a poor outcome for patients with PTCL after ASCT, and new therapies for T-cell lymphoma are needed.

Margin selection to compensate for loss of target dose coverage due to target motion during external‐beam radiation therapy of the lung

PubMed Central

Osei, Ernest; Barnett, Rob

2015-01-01

The aim of this study is to provide guidelines for the selection of external‐beam radiation therapy target margins to compensate for target motion in the lung during treatment planning. A convolution model was employed to predict the effect of target motion on the delivered dose distribution. The accuracy of the model was confirmed with radiochromic film measurements in both static and dynamic phantom modes. 502 unique patient breathing traces were recorded and used to simulate the effect of target motion on a dose distribution. A 1D probability density function (PDF) representing the position of the target throughout the breathing cycle was generated from each breathing trace obtained during 4D CT. Changes in the target D95 (the minimum dose received by 95% of the treatment target) due to target motion were analyzed and shown to correlate with the standard deviation of the PDF. Furthermore, the amount of target D95 recovered per millimeter of increased field width was also shown to correlate with the standard deviation of the PDF. The sensitivity of changes in dose coverage with respect to target size was also determined. Margin selection recommendations that can be used to compensate for loss of target D95 were generated based on the simulation results. These results are discussed in the context of clinical plans. We conclude that, for PDF standard deviations less than 0.4 cm with target sizes greater than 5 cm, little or no additional margins are required. Targets which are smaller than 5 cm with PDF standard deviations larger than 0.4 cm are most susceptible to loss of coverage. The largest additional required margin in this study was determined to be 8 mm. PACS numbers: 87.53.Bn, 87.53.Kn, 87.55.D‐, 87.55.Gh

SU-G-BRC-08: Evaluation of Dose Mass Histogram as a More Representative Dose Description Method Than Dose Volume Histogram in Lung Cancer Patients

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

Liu, J; Eldib, A; Ma, C

2016-06-15

Purpose: Dose-volume-histogram (DVH) is widely used for plan evaluation in radiation treatment. The concept of dose-mass-histogram (DMH) is expected to provide a more representative description as it accounts for heterogeneity in tissue density. This study is intended to assess the difference between DVH and DMH for evaluating treatment planning quality. Methods: 12 lung cancer treatment plans were exported from the treatment planning system. DVHs for the planning target volume (PTV), the normal lung and other structures of interest were calculated. DMHs were calculated in a similar way as DVHs expect that the voxel density converted from the CT number wasmore » used in tallying the dose histogram bins. The equivalent uniform dose (EUD) was calculated based on voxel volume and mass, respectively. The normal tissue complication probability (NTCP) in relation to the EUD was calculated for the normal lung to provide quantitative comparison of DVHs and DMHs for evaluating the radiobiological effect. Results: Large differences were observed between DVHs and DMHs for lungs and PTVs. For PTVs with dense tumor cores, DMHs are higher than DVHs due to larger mass weighing in the high dose conformal core regions. For the normal lungs, DMHs can either be higher or lower than DVHs depending on the target location within the lung. When the target is close to the lower lung, DMHs show higher values than DVHs because the lower lung has higher density than the central portion or the upper lung. DMHs are lower than DVHs for targets in the upper lung. The calculated NTCPs showed a large range of difference between DVHs and DMHs. Conclusion: The heterogeneity of lung can be well considered using DMH for evaluating target coverage and normal lung pneumonitis. Further studies are warranted to quantify the benefits of DMH over DVH for plan quality evaluation.« less

SU-F-T-568: QA of a Multi-Target Multi-Dose VMAT SRS

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

Roa, D; Kuo, J; Gonzales, A

2016-06-15

Purpose: To, experimentally, corroborated the prescribed doses utilizing dosimeters (e.g. films and TLDs) that can provide high spatial resolution, allow dose measurement of multiple targets at once, and provide accurate dosimetric results. Methods: A single-isocenter 6FFF SRS VMAT plan consisting of one 358° arc at 0° couch angle and four 179° arcs at 30°, 60°, 330° and 300° couch angles respectively, was generated in ECLIPSE v.11 using a Rando-Alderson anthropomorphic head phantom CT study. This plan was a reproduction of a clinical plan generated for a stage-IV melanoma patient diagnosed with 19 intracranial lesions. The phantom was loaded with axiallymore » mounted (between phantom slabs) Gafchromic EBT3 film and TLDs strategically positioned within various target volumes. Film and TLDS were calibrated according to established protocols. Target prescription doses were 16 Gy (3cc≤, 3 lesions), 18 Gy (∼1–3cc, 10 lesions) and 20 Gy (≤1cc, 6 lesions). Phantom setup was verified through CBCT imaging prior to irradiation. Gafchromic films were scanned in transmission mode and TLDs were read, respectively, ∼24 hrs after irradiation. Results: Dose calibrated Gafchromic film data were compared to the ECLIPSE calculated data using a 3% / 3mm gamma function analysis. Results for the gamma values were 96–99% in agreement with the calculated data and with 84–90% of the film pixels within the 3% dose difference. TLD data showed a dose difference of 0.4–8% while the film data for those same locations yielded a difference of 0.4–4%. It was observed that the highest dose discrepancies correlated with the location of the small volume targets. Conclusion: Overall this study corroborated that a VMAT SRS treatment, employing various treatment table rotations and arcs, to multiple intracranial lesions with multiple dose prescriptions can be delivered accurately with the existing radiotherapy technology.« less

MO-FG-CAMPUS-IeP1-04: Kerma Area Product Calculation for Non-Uniform X-Ray Fields Using a Skin Dose Tracking System

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

Vijayan, S; Xiong, Z; Rudin, S

Purpose: The functionality of the Dose-Tracking System (DTS) has been expanded to include the calculation of the Kerma-Area Product (KAP) for non-uniform x-ray fields such as result from the use of compensation filters during fluoroscopic procedures Methods: The DTS calculates skin dose during fluoroscopic interventions and provides a color-coded dose map on a patient-graphic model. The KAP is the integral of air kerma over the x-ray field and is usually measured with a transmission-ionization chamber that intercepts the entire x-ray beam. The DTS has been modified to determine KAP when there are beam non-uniformities that can be modeled. For example,more » the DTS includes models of the three compensation filters with tapered edges located in the collimator assembly of the Toshiba Infinix fluoroscopic C-Arm and can track their movement. To determine the air kerma after the filters, DTS includes transmission factors for the compensation filters as a function of kVp and beam filtration. A virtual KAP dosimeter is simulated in the DTS by an array of graphic vertices; the air kerma at each vertex is corrected by the field non-uniformity, which in this case is the attenuation factor for those rays which pass through the filter. The products of individual vertex air-kerma values for all vertices within the beam times the effective-area-per-vertex are summed for each x-ray pulse to yield the KAP per pulse and the cumulative KAP for the procedure is then calculated. Results: The KAP values estimated by DTS with the compensation filter inserted into the x-ray field agree within ± 6% with the values displayed on the fluoroscopy unit monitor, which are measured with a transmission chamber. Conclusion: The DTS can account for field non-uniformities such as result from the use of compensation filters in calculating KAP and can obviate the need for a KAP transmission ionization chamber. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.« less

Calculation of Absorbed Dose in Target Tissue and Equivalent Dose in Sensitive Tissues of Patients Treated by BNCT Using MCNP4C

NASA Astrophysics Data System (ADS)

Zamani, M.; Kasesaz, Y.; Khalafi, H.; Pooya, S. M. Hosseini

Boron Neutron Capture Therapy (BNCT) is used for treatment of many diseases, including brain tumors, in many medical centers. In this method, a target area (e.g., head of patient) is irradiated by some optimized and suitable neutron fields such as research nuclear reactors. Aiming at protection of healthy tissues which are located in the vicinity of irradiated tissue, and based on the ALARA principle, it is required to prevent unnecessary exposure of these vital organs. In this study, by using numerical simulation method (MCNP4C Code), the absorbed dose in target tissue and the equiavalent dose in different sensitive tissues of a patiant treated by BNCT, are calculated. For this purpose, we have used the parameters of MIRD Standard Phantom. Equiavelent dose in 11 sensitive organs, located in the vicinity of target, and total equivalent dose in whole body, have been calculated. The results show that the absorbed dose in tumor and normal tissue of brain equal to 30.35 Gy and 0.19 Gy, respectively. Also, total equivalent dose in 11 sensitive organs, other than tumor and normal tissue of brain, is equal to 14 mGy. The maximum equivalent doses in organs, other than brain and tumor, appear to the tissues of lungs and thyroid and are equal to 7.35 mSv and 3.00 mSv, respectively.

Modeling the target dose fall-off in IMRT and VMAT planning techniques for cervical SBRT.

PubMed

Brito Delgado, A; Cohen, D; Eng, T Y; Stanley, D N; Shi, Z; Charlton, M; Gutiérrez, A N

2018-01-01

There has been growing interest in the use of stereotactic body radiotherapy (SBRT) technique for the treatment of cervical cancer. The purpose of this study was to characterize dose distributions as well as model the target dose fall-off for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) delivery techniques using 6 and 10 MV photon beam energies. Fifteen (n = 15) patients with non-bulky cervical tumors were planned in Pinnacle 3 with a Varian Novalis Tx (HD120 MLC) using 6 and 10 MV photons with the following techniques: (1) IMRT with 10 non-coplanar beams (2) dual, coplanar 358° VMAT arcs (4° spacing), and (3) triple, non-coplanar VMAT arcs. Treatment volumes and dose prescriptions were segmented according to University of Texas Southwestern (UTSW) Phase II study. All plans were normalized such that 98% of the planning target volume (PTV) received 28 Gy (4 fractions). For the PTV, the following metrics were evaluated: homogeneity index, conformity index, D 2cc , D mean , D max , and dose fall-off parameters. For the organs at risk (OARs), D 2cc , D 15cc , D 0.01cc , V 20 , V 40 , V 50 , V 60 , and V 80 were evaluated for the bladder, bowel, femoral heads, rectum, and sigmoid. Statistical differences were evaluated using a Friedman test with a significance level of 0.05. To model dose fall-off, expanding 2-mm-thick concentric rings were created around the PTV, and doses were recorded. Statistically significant differences (p < 0.05) were noted in the dose fall-off when using 10 MV and VMAT 3-arc , as compared with IMRT. VMAT 3-arc improved the bladder V 40 , V 50 , and V 60 , and the bowel V 20 and V 50 . All fitted regressions had an R 2  ≥ 0.98. For cervical SBRT plans, a VMAT 3-arc approach offers a steeper dose fall-off outside of the target volume. Faster dose fall-off was observed in smaller targets as opposed to medium and large targets, denoting that OAR sparing is dependent on target size. These

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

10 CFR 835.205 - Determination of compliance for non-uniform exposure of the skin.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 100 cm 2 or more. The non-uniform equivalent dose received during the year shall be averaged over the... irradiated is 10 cm 2 or more, but is less than 100 cm 2. The non-uniform equivalent dose (H) to the... less than 0.1 be used. (3) Area of skin irradiated is less than 10 cm 2. The non-uniform equivalent...

CD uniformity control for thick resist process

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Influence of process parameters on content uniformity of a low dose active pharmaceutical ingredient in a tablet formulation according to GMP.

PubMed

Muselík, Jan; Franc, Aleš; Doležel, Petr; Goněc, Roman; Krondlová, Anna; Lukášová, Ivana

2014-09-01

The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler particle size and the time of lubricant addition during mixing on content uniformity according to the Good Manufacturing Practice (GMP) process validation requirements. Processes are regulated by complex directives, forcing the producers to validate, using sophisticated methods, the content uniformity of intermediates as well as final products. Cutting down of production time and material, shortening of analyses, and fast and reliable statistic evaluation of results can reduce the final price without affecting product quality. The manufacturing process of directly compressed tablets containing the low dose active pharmaceutical ingredient (API) warfarin, with content uniformity passing validation criteria, is used as a model example. Statistic methods have proved that the manufacturing process is reproducible. Methods suitable for elucidation of various properties of the final blend, e.g., measurement of electrostatic charge by Faraday pail and evaluation of mutual influences of researched variables by partial least square (PLS) regression, were used. Using these methods, it was proved that the filler with higher particle size increased the content uniformity of both blends and the ensuing tablets. Addition of the lubricant, magnesium stearate, during the blending process improved the content uniformity of blends containing the filler with larger particles. This seems to be caused by reduced sampling error due to the suppression of electrostatic charge.

Three-dimensional radiotherapy of head and neck and esophageal carcinomas: a monoisocentric treatment technique to achieve improved dose distributions.

PubMed

Ahmad, M; Nath, R

2001-02-20

The specific aim of three-dimensional conformal radiotherapy is to deliver adequate therapeutic radiation dose to the target volume while concomitantly keeping the dose to surrounding and intervening normal tissues to a minimum. The objective of this study is to examine dose distributions produced by various radiotherapy techniques used in managing head and neck tumors when the upper part of the esophagus is also involved. Treatment planning was performed with a three-dimensional (3-D) treatment planning system. Computerized tomographic (CT) scans used by this system to generate isodose distributions and dose-volume histograms were obtained directly from the CT scanner, which is connected via ethernet cabling to the 3-D planning system. These are useful clinical tools for evaluating the dose distribution to the treatment volume, clinical target volume, gross tumor volume, and certain critical organs. Using 6 and 18 MV photon beams, different configurations of standard treatment techniques for head and neck and esophageal carcinoma were studied and the resulting dose distributions were analyzed. Film validation dosimetry in solid-water phantom was performed to assess the magnitude of dose inhomogeneity at the field junction. Real-time dose measurements on patients using diode dosimetry were made and compared with computed dose values. With regard to minimizing radiation dose to surrounding structures (i.e., lung, spinal cord, etc.), the monoisocentric technique gave the best isodose distributions in terms of dose uniformity. The mini-mantle anterior-posterior/posterior-anterior (AP/PA) technique produced grossly non-uniform dose distribution with excessive hot spots. The dose measured on the patient during the treatment agrees to within +/- 5 % with the computed dose. The protocols presented in this work for simulation, immobilization and treatment planning of patients with head and neck and esophageal tumors provide the optimum dose distributions in the target

SU-E-T-232: Custom High-Dose-Rate Brachytherapy Surface Mold Applicators: The Importance Source to Skin Distance

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

Park, S; Demanes, J; Kamrava, M

2015-06-15

Purpose: Surface mold applicators can be customized to fit irregular skin surfaces that are difficult to treat with other radiation therapy techniques. Optimal design of customized HDR skin brachytherapy is not well-established. We evaluated the impact of applicator thickness (source to skin distance) on target dosimetry. Methods: 27 patients had 34 treated sites: scalp 4, face 13, extremity 13, and torso 4. Custom applicators were constructed from 5–15 mm thick thermoplastic bolus molded over the skin lesion. A planar array of plastic brachytherapy catheters spaced 5–10 mm apart was affixed to the bolus. CT simulation was used to contour themore » target volume and to determine the prescription depth. Inverse planning simulated annealing followed by graphical optimization was used to plan and deliver 40–56 Gy in 8–16 fractions. Target coverage parameters (D90, Dmean, and V100) and dose uniformity (V110–200, D0.1cc, D1cc, and D2cc) were studied according to target depth (<5mm vs. ≥5mm) and applicator thickness (5–10mm vs. ≥10mm). Results: The average prescription depth was 4.2±1.5mm. The average bolus thickness was 9.2±2.4mm. The median CTV volume was 10.0 cc (0.2–212.4 cc). Similar target coverage was achieved with prescription depths of <5mm and ≥5mm (Dmean = 113.8% vs. 112.4% and D90 = 100.2% vs. 98.3%). The <5mm prescription depth plans were more uniform (D0.1cc = 131.8% vs. 151.8%). Bolus thickness <10mm vs. ≥10mm plans also had similar target coverage (Dmean = 118.2% vs. 110.7% and D90 = 100.1% vs. 99.0%). Applicators ≥10mm thick, however, provide more uniform target dosimetry (D0.1cc = 146.9% vs. 139.5%). Conclusion: Prescription depth is based upon the thickness of the lesion and upon the clinical needs of the patient. Applicators ≥10mm thick provide more dose uniformity than 5–10mm thick applicators. Applicator thickness is an important variable that should be considered during treatment planning to achieve optimal dose

Pellicle transmission uniformity requirements

NASA Astrophysics Data System (ADS)

Brown, Thomas L.; Ito, Kunihiro

1998-12-01

Controlling critical dimensions of devices is a constant battle for the photolithography engineer. Current DUV lithographic process exposure latitude is typically 12 to 15% of the total dose. A third of this exposure latitude budget may be used up by a variable related to masking that has not previously received much attention. The emphasis on pellicle transmission has been focused on increasing the average transmission. Much less, attention has been paid to transmission uniformity. This paper explores the total demand on the photospeed latitude budget, the causes of pellicle transmission nonuniformity and examines reasonable expectations for pellicle performance. Modeling is used to examine how the two primary errors in pellicle manufacturing contribute to nonuniformity in transmission. World-class pellicle transmission uniformity standards are discussed and a comparison made between specifications of other components in the photolithographic process. Specifications for other materials or parameters are used as benchmarks to develop a proposed industry standard for pellicle transmission uniformity.

Online compensation for target motion with scanned particle beams: simulation environment.

PubMed

Li, Qiang; Groezinger, Sven Oliver; Haberer, Thomas; Rietzel, Eike; Kraft, Gerhard

2004-07-21

Target motion is one of the major limitations of each high precision radiation therapy. Using advanced active beam delivery techniques, such as the magnetic raster scanning system for particle irradiation, the interplay between time-dependent beam and target position heavily distorts the applied dose distribution. This paper presents a simulation environment in which the time-dependent effect of target motion on heavy-ion irradiation can be calculated with dynamically scanned ion beams. In an extension of the existing treatment planning software for ion irradiation of static targets (TRiP) at GSI, the expected dose distribution is calculated as the sum of several sub-distributions for single target motion states. To investigate active compensation for target motion by adapting the position of the therapeutic beam during irradiation, the planned beam positions can be altered during the calculation. Applying realistic parameters to the planned motion-compensation methods at GSI, the effect of target motion on the expected dose uniformity can be simulated for different target configurations and motion conditions. For the dynamic dose calculation, experimentally measured profiles of the beam extraction in time were used. Initial simulations show the feasibility and consistency of an active motion compensation with the magnetic scanning system and reveal some strategies to improve the dose homogeneity inside the moving target. The simulation environment presented here provides an effective means for evaluating the dose distribution for a moving target volume with and without motion compensation. It contributes a substantial basis for the experimental research on the irradiation of moving target volumes with scanned ion beams at GSI which will be presented in upcoming papers.

The effect of uterine motion and uterine margins on target and normal tissue doses in intensity modulated radiation therapy of cervical cancer

NASA Astrophysics Data System (ADS)

Gordon, J. J.; Weiss, E.; Abayomi, O. K.; Siebers, J. V.; Dogan, N.

2011-05-01

In intensity modulated radiation therapy (IMRT) of cervical cancer, uterine motion can be larger than cervix motion, requiring a larger clinical target volume to planning target volume (CTV-to-PTV) margin around the uterine fundus. This work simulates different motion models and margins to estimate the dosimetric consequences. A virtual study used image sets from ten patients. Plans were created with uniform margins of 1 cm (PTVA) and 2.4 cm (PTVC), and a margin tapering from 2.4 cm at the fundus to 1 cm at the cervix (PTVB). Three inter-fraction motion models (MM) were simulated. In MM1, all structures moved with normally distributed rigid body translations. In MM2, CTV motion was progressively magnified as one moved superiorly from the cervix to the fundus. In MM3, both CTV and normal tissue motion were magnified as in MM2, modeling the scenario where normal tissues move into the void left by the mobile uterus. Plans were evaluated using static and percentile DVHs. For a conventional margin (PTVA), quasi-realistic uterine motion (MM3) reduces fundus dose by about 5 Gy and increases normal tissue volumes receiving 30-50 Gy by ~5%. A tapered CTV-to-PTV margin can restore fundus and CTV doses, but will increase normal tissue volumes receiving 30-50 Gy by a further ~5%.

Intensity-Modulated Radiotherapy for Craniospinal Irradiation: Target Volume Considerations, Dose Constraints, and Competing Risks

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

Parker, William; Filion, Edith; Roberge, David

2007-09-01

Purpose: To report the results of an analysis of dose received to tissues and organs outside the target volume, in the setting of spinal axis irradiation for the treatment of medulloblastoma, using three treatment techniques. Methods and Materials: Treatment plans (total dose, 23.4 Gy) for a standard two-dimensional (2D) technique, a three-dimensional (3D) technique using a 3D imaging-based target volume, and an intensity-modulated radiotherapy (IMRT) technique, were compared for 3 patients in terms of dose-volume statistics for target coverage, as well as organ at risk (OAR) and overall tissue sparing. Results: Planning target volume coverage and dose homogeneity was superiormore » for the IMRT plans for V{sub 95%} (IMRT, 100%; 3D, 96%; 2D, 98%) and V{sub 107%} (IMRT, 3%; 3D, 38%; 2D, 37%). In terms of OAR sparing, the IMRT plan was better for all organs and whole-body contour when comparing V{sub 10Gy}, V{sub 15Gy}, and V{sub 20Gy}. The 3D plan was superior for V{sub 5Gy} and below. For the heart and liver in particular, the IMRT plans provided considerable sparing in terms of V{sub 10Gy} and above. In terms of the integral dose, the IMRT plans were superior for liver (IMRT, 21.9 J; 3D, 28.6 J; 2D, 38.6 J) and heart (IMRT, 9 J; 3D, 14.1J; 2D, 19.4 J), the 3D plan for the body contour (IMRT, 349 J; 3D, 337 J; 2D, 555 J). Conclusions: Intensity-modulated radiotherapy is a valid treatment option for spinal axis irradiation. We have shown that IMRT results in sparing of organs at risk without a significant increase in integral dose.« less

Keeping an eye on the ring: COMS plaque loading optimization for improved dose conformity and homogeneity.

PubMed

Gagne, Nolan L; Cutright, Daniel R; Rivard, Mark J

2012-09-01

To improve tumor dose conformity and homogeneity for COMS plaque brachytherapy by investigating the dosimetric effects of varying component source ring radionuclides and source strengths. The MCNP5 Monte Carlo (MC) radiation transport code was used to simulate plaque heterogeneity-corrected dose distributions for individually-activated source rings of 14, 16 and 18 mm diameter COMS plaques, populated with (103)Pd, (125)I and (131)Cs sources. Ellipsoidal tumors were contoured for each plaque size and MATLAB programming was developed to generate tumor dose distributions for all possible ring weighting and radionuclide permutations for a given plaque size and source strength resolution, assuming a 75 Gy apical prescription dose. These dose distributions were analyzed for conformity and homogeneity and compared to reference dose distributions from uniformly-loaded (125)I plaques. The most conformal and homogeneous dose distributions were reproduced within a reference eye environment to assess organ-at-risk (OAR) doses in the Pinnacle(3) treatment planning system (TPS). The gamma-index analysis method was used to quantitatively compare MC and TPS-generated dose distributions. Concentrating > 97% of the total source strength in a single or pair of central (103)Pd seeds produced the most conformal dose distributions, with tumor basal doses a factor of 2-3 higher and OAR doses a factor of 2-3 lower than those of corresponding uniformly-loaded (125)I plaques. Concentrating 82-86% of the total source strength in peripherally-loaded (131)Cs seeds produced the most homogeneous dose distributions, with tumor basal doses 17-25% lower and OAR doses typically 20% higher than those of corresponding uniformly-loaded (125)I plaques. Gamma-index analysis found > 99% agreement between MC and TPS dose distributions. A method was developed to select intra-plaque ring radionuclide compositions and source strengths to deliver more conformal and homogeneous tumor dose distributions than

Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

PubMed

Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

2008-06-01

Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

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

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

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

Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael

2008-06-01

Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm{sup 3} before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapymore » with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm{sup 3} subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon {alpha}) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm{sup 3}. More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.« less

SU-E-T-278: Dose Conformity Index for the Target in a Multitarget Environment

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

Harikrishnaperumal, Sudahar

2015-06-15

Purpose: The existing conformity index formulations are failing when multiple targets present outside the target of interest with same or different dose prescriptions. In the present study a novel methodology is introduced to solve this issue. Methods: The conformity index used by Nakamura et al (Int J Radiat Oncol Biol Phys 2001; 51(5):1313–1319) is taken as the base for this methodology. In this proposal, the prescription isodose volume (PIV) which normally includes the normal tissue and other target regions is restricted as PIV in annular regions of different thickness around the target of interest. The graphical line plotted between themore » thickness of annular region and the corresponding conformity index, will increase in the beginning and will reach a flat region, then it will increase again. The second increase in the conformity index depends basically on the distance between the targets, dose prescriptions, and size of the targets. The conformity index in the flat region should be the conformity index of the target of interest. This methodology was validated on dual target environment on a skull phantom in Multiplan planning system (Accuray Inc. Sunnyvale, USA) Results: When the surrounding target’s (sphere) size is changed from 1.5cm to 6cm diameter, the conformity index of the target of interest (3cm diameter) changed from 1.09 to 1.25. When the distance between the targets changed from 7.5cm to 2.5cm, the conformity index changed from 1.10 to 1.17. Similarly, when the prescribed dose changed from 25Gy to 50Gy the conformity index changed from 1.09 to 1.42. These values were above 2.0 when Nakamura et al formula was used. Conclusion: The proposed conformity index methodology eliminates the influence of surrounding targets to a greater extend. However, the limitations of this method should be studied further. Application of this method in clinical situations is the future scope.« less

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

NASA Technical Reports Server (NTRS)

Chappelli, Lori J.; Cucinotta, Francis A.

2010-01-01

BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data

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

NASA Astrophysics Data System (ADS)

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

2008-03-01

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

Dose-finding designs for trials of molecularly targeted agents and immunotherapies

PubMed Central

Chiuzan, Cody; Shtaynberger, Jonathan; Manji, Gulam A.; Duong, Jimmy K.; Schwartz, Gary K.; Ivanova, Anastasia; Lee, Shing M.

2017-01-01

Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, only 7.1% of trials use novel designs. PMID:28166468

Adaptive Dose Painting by Numbers for Head-and-Neck Cancer

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

Duprez, Frederic, E-mail: frederic.duprez@ugent.be; De Neve, Wilfried; De Gersem, Werner

Purpose: To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials: Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography [{sup 18}F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment {sup 18}F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a {sup 18}F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gymore » to the high-dose clinical target volume (CTV{sub highdose}) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. Results: All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second {sup 18}F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV{sub highdose} (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV{sub highdose} and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. Conclusion: To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.« less

Changes in the planning target volume and liver volume dose based on the selected respiratory phase in respiratory-gated radiation therapy for a hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Baek, Seong-Min

2013-11-01

The aim of this study was to quantitatively analyze the changes in the planning target volume (PTV) and liver volume dose based on the respiratory phase to identify the optimal respiratory phase for respiratory-gated radiation therapy for a hepatocellular carcinoma (HCC). Based on the standardized procedure for respiratory-gated radiation therapy, we performed a 4-dimensional computed tomography simulation for 0 ˜ 90%, 30 ˜ 70%, and 40 ˜ 60% respiratory phases to assess the respiratory stability (S R ) and the defined PTV i for each respiratory phase i. A treatment plan was established, and the changes in the PTV i and dose volume of the liver were quantitatively analyzed. Most patients (91.5%) passed the respiratory stability test (S R = 0.111 ± 0.015). With standardized respiration training exercises, we were able to minimize the overall systematic error caused by irregular respiration. Furthermore, a quantitative analysis to identify the optimal respiratory phase revealed that when a short respiratory phase (40 ˜ 60%) was used, the changes in the PTV were concentrated inside the center line; thus, we were able to obtain both a PTV margin accounting for respiration and a uniform radiation dose within the PTV.

Low dose megavoltage cone beam computed tomography with an unflattened 4 MV beam from a carbon target

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

Faddegon, Bruce A.; Wu, Vincent; Pouliot, Jean

2008-12-15

Megavoltage cone beam computed tomography (MVCBCT) is routinely used for visualizing anatomical structures and implanted fiducials for patient positioning in radiotherapy. MVCBCT using a 6 MV treatment beam with high atomic number (Z) target and flattening filter in the beamline, as done conventionally, has lower image quality than can be achieved with a MV beam due to heavy filtration of the low-energy bremsstrahlung. The unflattened beam of a low Z target has an abundance of diagnostic energy photons, detected with modern flat panel detectors with much higher efficiency given the same dose to the patient. This principle guided the developmentmore » of a new megavoltage imaging beamline (IBL) for a commercial radiotherapy linear accelerator. A carbon target was placed in one of the electron primary scattering foil slots on the target-foil slide. A PROM on a function controller board was programed to put the carbon target in place for MVCBCT. A low accelerating potential of 4.2 MV was used for the IBL to restrict leakage of primary electrons through the target such that dose from x rays dominated the signal in the monitor chamber and the patient surface dose. Results from phantom and cadaver images demonstrated that the IBL had much improved image quality over the treatment beam. For similar imaging dose, the IBL improved the contrast-to-noise ratio by as much as a factor of 3 in soft tissue over that of the treatment beam. The IBL increased the spatial resolution by about a factor of 2, allowing the visualization of finer anatomical details. Images of the cadaver contained useful information with doses as low as 1 cGy. The IBL may be installed on certain models of linear accelerators without mechanical modification and results in significant improvement in the image quality with the same dose, or images of the same quality with less than one-third of the dose.« less

Dose painting to treat single-lobe prostate cancer with hypofractionated high-dose radiation using targeted external beam radiation: Is it feasible?

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

Amini, Arya; Westerly, David C.; Waxweiler, Timothy V.

Targeted focal therapy strategies for treating single-lobe prostate cancer are under investigation. In this planning study, we investigate the feasibility of treating a portion of the prostate to full-dose external beam radiation with reduced dose to the opposite lobe, compared with full-dose radiation delivered to the entire gland using hypofractionated radiation. For 10 consecutive patients with low- to intermediate-risk prostate cancer, 2 hypofractionated, single-arc volumetric-modulated arc therapy (VMAT) plans were designed. The first plan (standard hypofractionation regimen [STD]) included the entire prostate gland, treated to 70 Gy delivered in 28 fractions. The second dose painting plan (DP) encompassed the involvedmore » lobe treated to 70 Gy delivered in 28 fractions, whereas the opposing, uninvolved lobe received 50.4 Gy in 28 fractions. Mean dose to the opposing neurovascular bundle (NVB) was considerably lower for DP vs STD, with a mean dose of 53.9 vs 72.3 Gy (p < 0.001). Mean penile bulb dose was 18.6 Gy for DP vs 19.2 Gy for STD (p = 0.880). Mean rectal dose was 21.0 Gy for DP vs 22.8 Gy for STD (p = 0.356). Rectum V{sub 70} (the volume receiving ≥70 Gy) was 2.01% for DP vs 2.74% for STD (p = 0.328). Bladder V{sub 70} was 1.69% for DP vs 2.78% for STD (p = 0.232). Planning target volume (PTV) maximum dose points were 76.5 and 76.3 Gy for DP and STD, respectively (p = 0.760). This study demonstrates the feasibility of using VMAT for partial-lobe prostate radiation in patients with prostate cancer involving 1 lobe. Partial-lobe prostate plans appeared to spare adjacent critical structures including the opposite NVB.« less

Radionuclide production and dose rate estimation during the commissioning of the W-Ta spallation target

NASA Astrophysics Data System (ADS)

Yu, Q. Z.; Liang, T. J.

2018-06-01

China Spallation Neutron Source (CSNS) is intended to begin operation in 2018. CSNS is an accelerator-base multidisciplinary user facility. The pulsed neutrons are produced by a 1.6GeV short-pulsed proton beam impinging on a W-Ta spallation target, at a beam power of100 kW and a repetition rate of 25 Hz. 20 neutron beam lines are extracted for the neutron scattering and neutron irradiation research. During the commissioning and maintenance scenarios, the gamma rays induced from the W-Ta target can cause the dose threat to the personal and the environment. In this paper, the gamma dose rate distributions for the W-Ta spallation are calculated, based on the engineering model of the target-moderator-reflector system. The shipping cask is analyzed to satisfy the dose rate limit that less than 2 mSv/h at the surface of the shipping cask. All calculations are performed by the Monte carlo code MCNPX2.5 and the activation code CINDER’90.

Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

DTIC Science & Technology

2008-06-01

brachytherapy treatment planning has been demonstrated. Using the inverse planning program IPSA , dose escalation of target regions with a higher tumor...algorithm (called IPSA ) was used to generate dose distributions for five different levels of DIL- boost, at least 110%, 120%, 130%, 140% and 150...and LDR, VI Last Generation Radiotherapy Course, São Paulo, Brazil, Oct. 19, 2006. Principles and Clinical Applications of IPSA ; Nucletron

A comparison of foveated acquisition and tracking performance relative to uniform resolution approaches

NASA Astrophysics Data System (ADS)

Dubuque, Shaun; Coffman, Thayne; McCarley, Paul; Bovik, A. C.; Thomas, C. William

2009-05-01

Foveated imaging has been explored for compression and tele-presence, but gaps exist in the study of foveated imaging applied to acquisition and tracking systems. Results are presented from two sets of experiments comparing simple foveated and uniform resolution targeting (acquisition and tracking) algorithms. The first experiments measure acquisition performance when locating Gabor wavelet targets in noise, with fovea placement driven by a mutual information measure. The foveated approach is shown to have lower detection delay than a notional uniform resolution approach when using video that consumes equivalent bandwidth. The second experiments compare the accuracy of target position estimates from foveated and uniform resolution tracking algorithms. A technique is developed to select foveation parameters that minimize error in Kalman filter state estimates. Foveated tracking is shown to consistently outperform uniform resolution tracking on an abstract multiple target task when using video that consumes equivalent bandwidth. Performance is also compared to uniform resolution processing without bandwidth limitations. In both experiments, superior performance is achieved at a given bandwidth by foveated processing because limited resources are allocated intelligently to maximize operational performance. These findings indicate the potential for operational performance improvements over uniform resolution systems in both acquisition and tracking tasks.

Effect of lung and target density on small-field dose coverage and PTV definition

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

Higgins, Patrick D., E-mail: higgi010@umn.edu; Ehler, Eric D.; Cho, Lawrence C.

We have studied the effect of target and lung density on block margin for small stereotactic body radiotherapy (SBRT) targets. A phantom (50 × 50 × 50 cm{sup 3}) was created in the Pinnacle (V9.2) planning system with a 23-cm diameter lung region of interest insert. Diameter targets of 1.6, 2.0, 3.0, and 4.0 cm were placed in the lung region of interest and centered at a physical depth of 15 cm. Target densities evaluated were 0.1 to 1.0 g/cm{sup 3}, whereas the surrounding lung density was varied between 0.05 and 0.6 g/cm{sup 3}. A dose of 100 cGy wasmore » delivered to the isocenter via a single 6-MV field, and the ratio of the average dose to points defining the lateral edges of the target to the isocenter dose was recorded for each combination. Field margins were varied from none to 1.5 cm in 0.25-cm steps. Data obtained in the phantom study were used to predict planning treatment volume (PTV) margins that would match the clinical PTV and isodose prescription for a clinical set of 39 SBRT cases. The average internal target volume (ITV) density was 0.73 ± 0.17, average local lung density was 0.33 ± 0.16, and average ITV diameter was 2.16 ± 0.8 cm. The phantom results initially underpredicted PTV margins by 0.35 cm. With this offset included in the model, the ratio of predicted-to-clinical PTVs was 1.05 ± 0.32. For a given target and lung density, it was found that treatment margin was insensitive to target diameter, except for the smallest (1.6-cm diameter) target, for which the treatment margin was more sensitive to density changes than the larger targets. We have developed a graphical relationship for block margin as a function of target and lung density, which should save time in the planning phase by shortening the design of PTV margins that can satisfy Radiation Therapy Oncology Group mandated treatment volume ratios.« less

Nonimaging solar concentrator with uniform irradiance

NASA Astrophysics Data System (ADS)

Winston, Roland; O'Gallagher, Joseph J.; Gee, Randy C.

2004-09-01

We report results of a study our group has undertaken under NREL/DOE auspices to design a solar concentrator with uniform irradiance on a planar target. This attribute is especially important for photovoltaic concentrators.

A trichrome beam model for biological dose calculation in scanned carbon-ion radiotherapy treatment planning.

PubMed

Inaniwa, T; Kanematsu, N

2015-01-07

In scanned carbon-ion (C-ion) radiotherapy, some primary C-ions undergo nuclear reactions before reaching the target and the resulting particles deliver doses to regions at a significant distance from the central axis of the beam. The effects of these particles on physical dose distribution are accounted for in treatment planning by representing the transverse profile of the scanned C-ion beam as the superposition of three Gaussian distributions. In the calculation of biological dose distribution, however, the radiation quality of the scanned C-ion beam has been assumed to be uniform over its cross-section, taking the average value over the plane at a given depth (monochrome model). Since these particles, which have relatively low radiation quality, spread widely compared to the primary C-ions, the radiation quality of the beam should vary with radial distance from the central beam axis. To represent its transverse distribution, we propose a trichrome beam model in which primary C-ions, heavy fragments with atomic number Z ≥ 3, and light fragments with Z ≤ 2 are assigned to the first, second, and third Gaussian components, respectively. Assuming a realistic beam-delivery system, we performed computer simulations using Geant4 Monte Carlo code for analytical beam modeling of the monochrome and trichrome models. The analytical beam models were integrated into a treatment planning system for scanned C-ion radiotherapy. A target volume of 20  ×  20  ×  40 mm(3) was defined within a water phantom. A uniform biological dose of 2.65 Gy (RBE) was planned for the target with the two beam models based on the microdosimetric kinetic model (MKM). The plans were recalculated with Geant4, and the recalculated biological dose distributions were compared with the planned distributions. The mean target dose of the recalculated distribution with the monochrome model was 2.72 Gy (RBE), while the dose with the trichrome model was 2.64 Gy (RBE). The monochrome

A trichrome beam model for biological dose calculation in scanned carbon-ion radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Inaniwa, T.; Kanematsu, N.

2015-01-01

In scanned carbon-ion (C-ion) radiotherapy, some primary C-ions undergo nuclear reactions before reaching the target and the resulting particles deliver doses to regions at a significant distance from the central axis of the beam. The effects of these particles on physical dose distribution are accounted for in treatment planning by representing the transverse profile of the scanned C-ion beam as the superposition of three Gaussian distributions. In the calculation of biological dose distribution, however, the radiation quality of the scanned C-ion beam has been assumed to be uniform over its cross-section, taking the average value over the plane at a given depth (monochrome model). Since these particles, which have relatively low radiation quality, spread widely compared to the primary C-ions, the radiation quality of the beam should vary with radial distance from the central beam axis. To represent its transverse distribution, we propose a trichrome beam model in which primary C-ions, heavy fragments with atomic number Z ≥ 3, and light fragments with Z ≤ 2 are assigned to the first, second, and third Gaussian components, respectively. Assuming a realistic beam-delivery system, we performed computer simulations using Geant4 Monte Carlo code for analytical beam modeling of the monochrome and trichrome models. The analytical beam models were integrated into a treatment planning system for scanned C-ion radiotherapy. A target volume of 20  ×  20  ×  40 mm3 was defined within a water phantom. A uniform biological dose of 2.65 Gy (RBE) was planned for the target with the two beam models based on the microdosimetric kinetic model (MKM). The plans were recalculated with Geant4, and the recalculated biological dose distributions were compared with the planned distributions. The mean target dose of the recalculated distribution with the monochrome model was 2.72 Gy (RBE), while the dose with the trichrome model was 2.64 Gy (RBE). The monochrome model

Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

PubMed

Wheldon, T E; O'Donoghue, J A; Hilditch, T E; Barrett, A

1988-02-01

A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to

Optical design for uniform scanning in MEMS-based 3D imaging lidar.

PubMed

Lee, Xiaobao; Wang, Chunhui

2015-03-20

This paper proposes a method for the optical system design of uniform scanning in a larger scan field of view (FOV) in 3D imaging lidar. The theoretical formulas are derived for the design scheme. By employing the optical design software ZEMAX, a foldaway uniform scanning optical system based on MEMS has been designed, and the scanning uniformity and spot size of the system on the target plane, perpendicular to optical axis, are analyzed and discussed. Results show that the designed system can scan uniformly within the FOV of 40°×40° with small spot size for the target at distance of about 100 m.

Water-filled balloon in the postoperative resection cavity improves dose distribution to target volumes in radiotherapy of maxillary sinus carcinoma.

PubMed

Zhang, Qun; Lin, Shi-Rong; He, Fang; Kang, De-Hua; Chen, Guo-Zhang; Luo, Wei

2011-11-01

Postoperative radiotherapy is a major treatment for patients with maxillary sinus carcinoma. However, the irregular resection cavity poses a technical difficulty for this treatment, causing uneven dose distribution to target volumes. In this study, we evaluated the dose distribution to target volumes and normal tissues in postoperative intensity-modulated radiotherapy (IMRT) after placing a water-filled balloon into the resection cavity. Three postoperative patients with advanced maxillary sinus carcinoma were selected in this trial. Water-filled balloons and supporting dental stents were fabricated according to the size of the maxillary resection cavity. Simulation CT scans were performed with or without water-filled balloons, IMRT treatment plans were established, and dose distribution to target volumes and organs at risk were evaluated. Compared to those in the treatment plan without balloons, the dose (D98) delivered to 98% of the gross tumor volume (GTV) increased by 2.1 Gy (P = 0.009), homogeneity index (HI) improved by 2.3% (P = 0.001), and target volume conformity index (TCI) of 68 Gy increased by 18.5% (P = 0.011) in the plan with balloons. Dosimetry endpoints of normal tissues around target regions in both plans were not significantly different (P > 0.05) except for the optic chiasm. In the plan without balloons, 68 Gy high-dose regions did not entirely cover target volumes in the ethmoid sinus, posteromedial wall of the maxillary sinus, or surgical margin of the hard palate. In contrast, 68 Gy high-dose regions entirely covered the GTV in the plan with balloons. These results suggest that placing a water-filled balloon in the resection cavity for postoperative IMRT of maxillary sinus carcinoma can reduce low-dose regions and markedly and simultaneously increase dose homogeneity and conformity of target volumes.

Use of radiation protraction to escalate biologically effective dose to the treatment target

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

Kuperman, V. Y.; Spradlin, G. S.; Department of Mathematics, Embry-Riddle University, Daytona Beach, Florida 32114

2011-12-15

Purpose: The aim of this study is to evaluate how simultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target (BED{sub tar}) while biologically effective dose for the normal tissue (BED{sub nt}) is fixed. Methods: In this investigation, BED{sub tar} and BED{sub nt} were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results: Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BED{sub tar} while BED{sub nt} is fixed. The dependence of biologically effective dose on fraction time is influenced bymore » the dose rate. In this investigation we analytically determined time-varying dose rate R-tilde which minimizes BED. Changes in BED with fraction time were compared for constant dose rate and for R-tilde. Conclusions: A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.« less

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy

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

Berbeco, Ross I., E-mail: rberbeco@partners.org; Detappe, Alexandre; Tsiamas, Panogiotis

2016-01-15

Purpose: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. Methods: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam,more » (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. Results: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. Conclusions: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.« less

TU-H-BRC-06: Temperature Simulation of Tungsten and W25Re Targets to Deliver High Dose Rate 10 MV Photons

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

Wang, J; Trovati, S; Loo, B

Purpose: To study the impact of electron beam size, target thickness, and target temperature on the ability of the flattening filter-free mode (FFF) treatment head to deliver high-dose-rate irradiations. Methods: The dose distribution and transient temperature of the X-ray target under 10 MeV electron beam with pulse length of 5 microseconds, and repetition rate of 1000 Hz was studied. A MCNP model was built to calculate the percentage depth dose (PPD) distribution in a water phantom at a distance of 100 cm. ANSYS software was used to run heat transfer simulations. The PPD and temperature for both tungsten and W25Remore » targets for different electron beam sizes (FHWM 0.2, 0.5, 1 and 2 mm) and target thickness (0.2 to 2 mm) were studied. Results: Decreasing the target thickness from 1 mm to 0.5 mm, caused a surface dose increase about 10 percent. For both target materials, the peak temperature was about 1.6 times higher for 0.5 mm electron beam compared to the 1 mm beam after reaching their equilibrium. For increasing target thicknesses, the temperature rise caused by the first pulse is similar for all thicknesses, however the temperature difference for subsequent pulses becomes larger until a constant ratio is reached. The target peak temperature after reaching equilibrium can be calculated by adding the steady state temperature and the amplitude of the temperature oscillation. Conclusion: This work indicates the potential to obtain high dose rate irradiation by selecting target material, geometry and electron beam parameters. W25Re may not outperformed tungsten when the target is thick due to its relatively low thermal conductivity. The electron beam size only affects the target temperature but not the PPD. Thin target is preferred to obtain high dose rate and low target temperature, however, the resulting high surface dose is a major concern. NIH funding:R21 EB015957-01; DOD funding:W81XWH-13-1-0165 BL, PM, PB, and RF are founders of TibaRay, Inc. BL is also

Ignition of deuterium-trtium fuel targets

DOEpatents

Musinski, Donald L.; Mruzek, Michael T.

1991-01-01

A method of igniting a deuterium-tritium ICF fuel target to obtain fuel burn in which the fuel target initially includes a hollow spherical shell having a frozen layer of DT material at substantially uniform thickness and cryogenic temperature around the interior surface of the shell. The target is permitted to free-fall through a target chamber having walls heated by successive target ignitions, so that the target is uniformly heated during free-fall to at least partially melt the frozen fuel layer and form a liquid single-phase layer or a mixed liquid/solid bi-phase layer of substantially uniform thickness around the interior shell surface. The falling target is then illuminated from exteriorly of the chamber while the fuel layer is at substantially uniformly single or bi-phase so as to ignite the fuel layer and release energy therefrom.

The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens.

PubMed

Haeseker, Michiel; Stolk, Leo; Nieman, Fred; Hoebe, Christian; Neef, Cees; Bruggeman, Cathrien; Verbon, Annelies

2013-01-01

The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\\PHARM 3.60). A two compartment open model was used. Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively. A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery.

PubMed

Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A; Sahgal, Arjun

2011-11-21

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R² = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A.; Sahgal, Arjun

2011-11-01

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R2 = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

Ignition of deuterium-tritium fuel targets

DOEpatents

Musinski, D.L.; Mruzek, M.T.

1991-08-27

Disclosed is a method of igniting a deuterium-tritium ICF fuel target to obtain fuel burn in which the fuel target initially includes a hollow spherical shell having a frozen layer of DT material at substantially uniform thickness and cryogenic temperature around the interior surface of the shell. The target is permitted to free-fall through a target chamber having walls heated by successive target ignitions, so that the target is uniformly heated during free-fall to at least partially melt the frozen fuel layer and form a liquid single-phase layer or a mixed liquid/solid bi-phase layer of substantially uniform thickness around the interior shell surface. The falling target is then illuminated from exteriorly of the chamber while the fuel layer is at substantially uniformly single or bi-phase so as to ignite the fuel layer and release energy therefrom. 5 figures.

Dose uniformity analysis among ten 16-slice same-model CT scanners.

PubMed

Erdi, Yusuf Emre

2012-01-01

With the introduction of multislice scanners, computed tomographic (CT) dose optimization has become important. The patient-absorbed dose may differ among the scanners although they are the same type and model. To investigate the dose output variation of the CT scanners, we designed the study to analyze dose outputs of 10 same-model CT scanners using 3 clinical protocols. Ten GE Lightspeed (GE Healthcare, Waukesha, Wis) 16-slice scanners located at main campus and various satellite locations of our institution have been included in this study. All dose measurements were performed using poly (methyl methacrylate) (PMMA) head (diameter, 16 cm) and body (diameter, 32 cm) phantoms manufactured by Radcal (RadCal Corp, Monrovia, Calif) using a 9095 multipurpose analyzer with 10 × 9-3CT ion chamber both from the same manufacturer. Ion chamber is inserted into the peripheral and central axis locations and volume CT dose index (CTDIvol) is calculated as weighted average of doses at those locations. Three clinical protocol settings for adult head, high-resolution chest, and adult abdomen are used for dose measurements. We have observed up to 9.4% CTDIvol variation for the adult head protocol in which the largest variation occurred among the protocols. However, head protocol uses higher milliampere second values than the other 2 protocols. Most of the measured values were less than the system-stored CTDIvol values. It is important to note that reduction in dose output from tubes as they age is expected in addition to the intrinsic radiation output fluctuations of the same scanner. Although the same model CT scanners were used in this study, it is possible to see CTDIvol variation in standard patient scanning protocols of head, chest, and abdomen. The compound effect of the dose variation may be larger with higher milliampere and multiphase and multilocation CT scans.

Ion Implantation Doping of Inertial Confinement Fusion Targets

DOE PAGES

Shin, S. J.; Lee, J. R. I.; van Buuren, T.; ...

2017-12-19

Controlled doping of inertial confinement fusion (ICF) targets is needed to enable nuclear diagnostics of implosions. Here in this study, we demonstrate that ion implantation with a custom-designed carousel holder can be used for azimuthally uniform doping of ICF fuel capsules made from a glow discharge polymer (GDP). Particular emphasis is given to the selection of the initial wall thickness of GDP capsules as well as implantation and postimplantation annealing parameters in order to minimize capsule deformation during a postimplantation thermal treatment step. In contrast to GDP, ion-implanted high-density carbon exhibits excellent thermal stability and ~100% implantation efficiency for themore » entire range of ion doses studied (2 × 10 14 to 1 × 10 16 cm -2) and for annealing temperatures up to 700°C. Lastly, we demonstrate a successful doping of planar Al targets with isotopes of Kr and Xe to doses of ~10 17 cm -2.« less

Ion Implantation Doping of Inertial Confinement Fusion Targets

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

Shin, S. J.; Lee, J. R. I.; van Buuren, T.

Controlled doping of inertial confinement fusion (ICF) targets is needed to enable nuclear diagnostics of implosions. Here in this study, we demonstrate that ion implantation with a custom-designed carousel holder can be used for azimuthally uniform doping of ICF fuel capsules made from a glow discharge polymer (GDP). Particular emphasis is given to the selection of the initial wall thickness of GDP capsules as well as implantation and postimplantation annealing parameters in order to minimize capsule deformation during a postimplantation thermal treatment step. In contrast to GDP, ion-implanted high-density carbon exhibits excellent thermal stability and ~100% implantation efficiency for themore » entire range of ion doses studied (2 × 10 14 to 1 × 10 16 cm -2) and for annealing temperatures up to 700°C. Lastly, we demonstrate a successful doping of planar Al targets with isotopes of Kr and Xe to doses of ~10 17 cm -2.« less

Quantification of residual dose estimation error on log file-based patient dose calculation.

PubMed

Katsuta, Yoshiyuki; Kadoya, Noriyuki; Fujita, Yukio; Shimizu, Eiji; Matsunaga, Kenichi; Matsushita, Haruo; Majima, Kazuhiro; Jingu, Keiichi

2016-05-01

The log file-based patient dose estimation includes a residual dose estimation error caused by leaf miscalibration, which cannot be reflected on the estimated dose. The purpose of this study is to determine this residual dose estimation error. Modified log files for seven head-and-neck and prostate volumetric modulated arc therapy (VMAT) plans simulating leaf miscalibration were generated by shifting both leaf banks (systematic leaf gap errors: ±2.0, ±1.0, and ±0.5mm in opposite directions and systematic leaf shifts: ±1.0mm in the same direction) using MATLAB-based (MathWorks, Natick, MA) in-house software. The generated modified and non-modified log files were imported back into the treatment planning system and recalculated. Subsequently, the generalized equivalent uniform dose (gEUD) was quantified for the definition of the planning target volume (PTV) and organs at risks. For MLC leaves calibrated within ±0.5mm, the quantified residual dose estimation errors that obtained from the slope of the linear regression of gEUD changes between non- and modified log file doses per leaf gap are in head-and-neck plans 1.32±0.27% and 0.82±0.17Gy for PTV and spinal cord, respectively, and in prostate plans 1.22±0.36%, 0.95±0.14Gy, and 0.45±0.08Gy for PTV, rectum, and bladder, respectively. In this work, we determine the residual dose estimation errors for VMAT delivery using the log file-based patient dose calculation according to the MLC calibration accuracy. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-C-BRA-05: Delineating High-Dose Clinical Target Volumes for Head and Neck Tumors Using Machine Learning Algorithms

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

Cardenas, C; The University of Texas Graduate School of Biomedical Sciences, Houston, TX; Wong, A

Purpose: To develop and test population-based machine learning algorithms for delineating high-dose clinical target volumes (CTVs) in H&N tumors. Automating and standardizing the contouring of CTVs can reduce both physician contouring time and inter-physician variability, which is one of the largest sources of uncertainty in H&N radiotherapy. Methods: Twenty-five node-negative patients treated with definitive radiotherapy were selected (6 right base of tongue, 11 left and 9 right tonsil). All patients had GTV and CTVs manually contoured by an experienced radiation oncologist prior to treatment. This contouring process, which is driven by anatomical, pathological, and patient specific information, typically results inmore » non-uniform margin expansions about the GTV. Therefore, we tested two methods to delineate high-dose CTV given a manually-contoured GTV: (1) regression-support vector machines(SVM) and (2) classification-SVM. These models were trained and tested on each patient group using leave-one-out cross-validation. The volume difference(VD) and Dice similarity coefficient(DSC) between the manual and auto-contoured CTV were calculated to evaluate the results. Distances from GTV-to-CTV were computed about each patient’s GTV and these distances, in addition to distances from GTV to surrounding anatomy in the expansion direction, were utilized in the regression-SVM method. The classification-SVM method used categorical voxel-information (GTV, selected anatomical structures, else) from a 3×3×3cm3 ROI centered about the voxel to classify voxels as CTV. Results: Volumes for the auto-contoured CTVs ranged from 17.1 to 149.1cc and 17.4 to 151.9cc; the average(range) VD between manual and auto-contoured CTV were 0.93 (0.48–1.59) and 1.16(0.48–1.97); while average(range) DSC values were 0.75(0.59–0.88) and 0.74(0.59–0.81) for the regression-SVM and classification-SVM methods, respectively. Conclusion: We developed two novel machine learning methods to

Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring.

PubMed

Vassal, G; Michel, G; Espérou, H; Gentet, J C; Valteau-Couanet, D; Doz, F; Mechinaud, F; Galambrun, C; Neven, B; Zouabi, H; Nguyen, L; Puozzo, C

2008-01-01

Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated. Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16-23 kg; 0.95 mg/kg for >23-34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3-17.2 years (median 5.6 years). No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window.

Sci—Fri PM: Topics — 04: What if bystander effects influence cell kill within a target volume? Potential consequences of dose heterogeneity on TCP and EUD on intermediate risk prostate patients

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

Balderson, M.J.; Kirkby, C.; Department of Medical Physics, Tom Baker Cancer Centre, Calgary, Alberta

In vitro evidence has suggested that radiation induced bystander effects may enhance non-local cell killing which may influence radiotherapy treatment planning paradigms. This work applies a bystander effect model, which has been derived from published in vitro data, to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) and compare them with predictions from standard linear quadratic (LQ) models that assume a response due only to local absorbed dose. Comparisons between the models were made under increasing dose heterogeneity scenarios. Dose throughout the CTV was modeled with normal distributions, where the degree of heterogeneity was then dictated by changingmore » the standard deviation (SD). The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. The bystander model suggests a moderate degree of dose heterogeneity yields as good or better outcome compared to a uniform dose in terms of EUD and TCP. Intermediate risk prostate prescriptions of 78 Gy over 39 fractions had maximum EUD and TCP values at SD of around 5Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. The bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV is varies. The results suggest the potential for allowing some degree of dose heterogeneity within a CTV, although further investigations of the assumptions of the bystander model are warranted.« less

Radar Imaging of Non-Uniformly Rotating Targets via a Novel Approach for Multi-Component AM-FM Signal Parameter Estimation

PubMed Central

Wang, Yong

2015-01-01

A novel radar imaging approach for non-uniformly rotating targets is proposed in this study. It is assumed that the maneuverability of the non-cooperative target is severe, and the received signal in a range cell can be modeled as multi-component amplitude-modulated and frequency-modulated (AM-FM) signals after motion compensation. Then, the modified version of Chirplet decomposition (MCD) based on the integrated high order ambiguity function (IHAF) is presented for the parameter estimation of AM-FM signals, and the corresponding high quality instantaneous ISAR images can be obtained from the estimated parameters. Compared with the MCD algorithm based on the generalized cubic phase function (GCPF) in the authors’ previous paper, the novel algorithm presented in this paper is more accurate and efficient, and the results with simulated and real data demonstrate the superiority of the proposed method. PMID:25806870

Managing toxicities and optimal dosing of targeted drugs in advanced kidney cancer

PubMed Central

Seruga, B.; Gan, H.K.; Knox, J.J.

2009-01-01

The toxicities of new, targeted drugs may diminish their effectiveness in advanced kidney cancer if those toxicities are not recognized and properly addressed early in patient treatment. Most of the drug-related toxicities in advanced kidney cancer are manageable with supportive care, obviating a need for long interruptions, dose reductions, or permanent discontinuation of the treatment. PMID:19478903

The photon fluence non-uniformity correction for air kerma near Cs-137 brachytherapy sources.

PubMed

Rodríguez, M L; deAlmeida, C E

2004-05-07

The use of brachytherapy sources in radiation oncology requires their proper calibration to guarantee the correctness of the dose delivered to the treatment volume of a patient. One of the elements to take into account in the dose calculation formalism is the non-uniformity of the photon fluence due to the beam divergence that causes a steep dose gradient near the source. The correction factors for this phenomenon have been usually evaluated by the two theories available, both of which were conceived only for point sources. This work presents the Monte Carlo assessment of the non-uniformity correction factors for a Cs-137 linear source and a Farmer-type ionization chamber. The results have clearly demonstrated that for linear sources there are some important differences among the values obtained from different calculation models, especially at short distances from the source. The use of experimental values for each specific source geometry is recommended in order to assess the non-uniformity factors for linear sources in clinical situations that require special dose calculations or when the correctness of treatment planning software is verified during the acceptance tests.

Nonimaging solar concentrator with near-uniform irradiance for photovoltaic arrays

NASA Astrophysics Data System (ADS)

O'Gallagher, Joseph J.; Winston, Roland; Gee, Randy

2001-11-01

We report results of a study our group has undertaken to design a solar concentrator with uniform irradiance on a planar target. This attribute is especially important for photovoltaic concentrators. We find that a variety of optical mixers, some incorporating a moderate level of concentration, can be quite effective in achieving near uniform irradiance.

Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions.

PubMed

Inaniwa, Taku; Kohno, Toshiyuki; Tomitani, Takehiro; Urakabe, Eriko; Sato, Shinji; Kanazawa, Mitsutaka; Kanai, Tatsuaki

2006-09-07

In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an

SU-E-T-397: Evaluation of Planned Dose Distributions by Monte Carlo (0.5%) and Ray Tracing Algorithm for the Spinal Tumors with CyberKnife

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

Cho, H; Brindle, J; Hepel, J

2015-06-15

Purpose: To analyze and evaluate dose distribution between Ray Tracing (RT) and Monte Carlo (MC) algorithms of 0.5% uncertainty on a critical structure of spinal cord and gross target volume and planning target volume. Methods: Twenty four spinal tumor patients were treated with stereotactic body radiotherapy (SBRT) by CyberKnife in 2013 and 2014. The MC algorithm with 0.5% of uncertainty is used to recalculate the dose distribution for the treatment plan of the patients using the same beams, beam directions, and monitor units (MUs). Results: The prescription doses are uniformly larger for MC plans than RT except one case. Upmore » to a factor of 1.19 for 0.25cc threshold volume and 1.14 for 1.2cc threshold volume of dose differences are observed for the spinal cord. Conclusion: The MC recalculated dose distributions are larger than the original MC calculations for the spinal tumor cases. Based on the accuracy of the MC calculations, more radiation dose might be delivered to the tumor targets and spinal cords with the increase prescription dose.« less

Two-dimensional particle-in-cell plasma source ion implantation of a prolate spheroid target

NASA Astrophysics Data System (ADS)

Liu, Cheng-Sen; Han, Hong-Ying; Peng, Xiao-Qing; Chang, Ye; Wang, De-Zhen

2010-03-01

A two-dimensional particle-in-cell simulation is used to study the time-dependent evolution of the sheath surrounding a prolate spheroid target during a high voltage pulse in plasma source ion implantation. Our study shows that the potential contour lines pack more closely in the plasma sheath near the vertex of the major axis, i.e. where a thinner sheath is formed, and a non-uniform total ion dose distribution is incident along the surface of the prolate spheroid target due to the focusing of ions by the potential structure. Ion focusing takes place not only at the vertex of the major axis, where dense potential contour lines exist, but also at the vertex of the minor axis, where sparse contour lines exist. This results in two peaks of the received ion dose, locating at the vertices of the major and minor axes of the prolate spheroid target, and an ion dose valley, staying always between the vertices, rather than at the vertex of the minor axis.

Haploidentical HCT using an αβ T-cell-depleted graft with targeted αβ(+) cells by add-back after a reduced intensity preparative regimen containing low-dose TBI.

PubMed

Im, H J; Koh, K N; Suh, J K; Lee, S W; Choi, E S; Jang, S; Kwon, S W; Park, C-J; Seo, J J

2016-09-01

Between 2012 and 2015, 42 pediatric patients underwent haploidentical hematopoietic cell transplantation using an αβ(+) T-cell-depleted graft with targeted αβ cells at 1-5 × 10(5)/kg by add-back; 31 had hematologic malignancy (HM), 8 had non-malignant disease (NM) and 3 had solid tumors. All patients received uniform reduced-intensity conditioning with fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and low-dose TBI. All 42 patients achieved neutrophil engraftment at a median of 10 days. The cumulative incidences (CIs) of ⩾grade II and ⩾grade III acute GvHD were 31±7.1% (SE) and 12±5.0%, respectively, and 1-year CI of chronic GvHD was 15±5.8%. One patient died of CMV pneumonia, leading to transplant-related mortality (TRM) of 2.6±2.5%. Sixteen patients relapsed and 11 died of disease. At a median follow-up of 19 months (range, 5-43 months), the estimated 2-year event-free survival for NM and HM were 88±11.7 and 50±10.1%, respectively. Our study demonstrated that haploidentical hematopoietic cell transplantation after ex vivo depletion of αβ(+) T cells with targeted dose noticeably reduced the graft failure rate and TRM in pediatric patients and could be applied to patients lacking a suitable related or unrelated donor.

A Science and Risk-Based Pragmatic Methodology for Blend and Content Uniformity Assessment.

PubMed

Sayeed-Desta, Naheed; Pazhayattil, Ajay Babu; Collins, Jordan; Doshi, Chetan

2018-04-01

This paper describes a pragmatic approach that can be applied in assessing powder blend and unit dosage uniformity of solid dose products at Process Design, Process Performance Qualification, and Continued/Ongoing Process Verification stages of the Process Validation lifecycle. The statistically based sampling, testing, and assessment plan was developed due to the withdrawal of the FDA draft guidance for industry "Powder Blends and Finished Dosage Units-Stratified In-Process Dosage Unit Sampling and Assessment." This paper compares the proposed Grouped Area Variance Estimate (GAVE) method with an alternate approach outlining the practicality and statistical rationalization using traditional sampling and analytical methods. The approach is designed to fit solid dose processes assuring high statistical confidence in both powder blend uniformity and dosage unit uniformity during all three stages of the lifecycle complying with ASTM standards as recommended by the US FDA.

Using Generalized Equivalent Uniform Dose Atlases to Combine and Analyze Prospective Dosimetric and Radiation Pneumonitis Data From 2 Non-Small Cell Lung Cancer Dose Escalation Protocols

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

Liu Fan; Yorke, Ellen D.; Belderbos, Jose S.A.

2013-01-01

Purpose: To demonstrate the use of generalized equivalent uniform dose (gEUD) atlas for data pooling in radiation pneumonitis (RP) modeling, to determine the dependence of RP on gEUD, to study the consistency between data sets, and to verify the increased statistical power of the combination. Methods and Materials: Patients enrolled in prospective phase I/II dose escalation studies of radiation therapy of non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) (78 pts) and the Netherlands Cancer Institute (NKI) (86 pts) were included; 10 (13%) and 14 (17%) experienced RP requiring steroids (RPS) within 6 months after treatment. gEUD wasmore » calculated from dose-volume histograms. Atlases for each data set were created using 1-Gy steps from exact gEUDs and RPS data. The Lyman-Kutcher-Burman model was fit to the atlas and exact gEUD data. Heterogeneity and inconsistency statistics for the fitted parameters were computed. gEUD maps of the probability of RPS rate {>=}20% were plotted. Results: The 2 data sets were homogeneous and consistent. The best fit values of the volume effect parameter a were small, with upper 95% confidence limit around 1.0 in the joint data. The likelihood profiles around the best fit a values were flat in all cases, making determination of the best fit a weak. All confidence intervals (CIs) were narrower in the joint than in the individual data sets. The minimum P value for correlations of gEUD with RPS in the joint data was .002, compared with P=.01 and .05 for MSKCC and NKI data sets, respectively. gEUD maps showed that at small a, RPS risk increases with gEUD. Conclusions: The atlas can be used to combine gEUD and RPS information from different institutions and model gEUD dependence of RPS. RPS has a large volume effect with the mean dose model barely included in the 95% CI. Data pooling increased statistical power.« less

Dose gradient curve: A new tool for evaluating dose gradient.

PubMed

Sung, KiHoon; Choi, Young Eun

2018-01-01

Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

Dose gradient curve: A new tool for evaluating dose gradient

PubMed Central

Choi, Young Eun

2018-01-01

Purpose Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. Methods The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Results Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. Conclusions The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice. PMID:29698471

Comparison of pencil beam–based homogeneous vs inhomogeneous target dose planning for stereotactic body radiotherapy of peripheral lung tumors through Monte Carlo–based recalculation

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

Ohtakara, Kazuhiro, E-mail: ohtakara@murakami.asahi-u.ac.jp; Hoshi, Hiroaki

2015-10-01

This study was conducted to ascertain whether homogeneous target dose planning is suitable for stereotactic body radiotherapy (SBRT) of peripheral lung cancer under appropriate breath-holding. For 20 peripheral lung tumors, paired dynamic conformal arc plans were generated by only adjusting the leaf margin to the planning target volume (PTV) edge for fulfilling the conditions such that the prescription isodose surface (IDS) encompassing exactly 95% of the PTV (PTV D{sub 95}) corresponds to 95% and 80% IDS, normalized to 100% at the PTV isocenter under a pencil beam (PB) algorithm with radiologic path length correction. These plans were recalculated using themore » x-ray voxel Monte Carlo (XVMC) algorithm under otherwise identical conditions, and then compared. Lesions abutting the parietal pleura or not were defined as edge or island tumors, respectively, and the influences of the target volume and its location relative to the chest wall on the target dose were examined. The median (range) leaf margin required for the 95% and 80% plans was 3.9 mm (1.3 to 5.0) and −1.2 mm (−1.8 to 0.1), respectively. Notably, the latter was significantly correlated negatively with PTV. In the 80% plans, the PTV D{sub 95} was slightly higher under XVMC, whereas the PTV D{sub 98} was significantly lower, irrespective of the dose calculation algorithm used. Other PTV and all gross tumor volume doses were significantly higher, while the lung doses outside the PTV were slightly lower. The target doses increased as a function of PTV and were significantly lower for island tumors than for edge tumors. In conclusion, inhomogeneous target dose planning using smaller leaf margin for a larger tumor volume was deemed suitable in ensuring more sufficient target dose while slightly reducing lung dose. In addition, more inhomogeneous target dose planning using <80% IDS (e.g., 70%) for PTV covering would be preferable for island tumors.« less

Multi-axis dose accumulation of noninvasive image-guided breast brachytherapy through biomechanical modeling of tissue deformation using the finite element method

PubMed Central

Ghadyani, Hamid R.; Bastien, Adam D.; Lutz, Nicholas N.; Hepel, Jaroslaw T.

2015-01-01

Purpose Noninvasive image-guided breast brachytherapy delivers conformal HDR 192Ir brachytherapy treatments with the breast compressed, and treated in the cranial-caudal and medial-lateral directions. This technique subjects breast tissue to extreme deformations not observed for other disease sites. Given that, commercially-available software for deformable image registration cannot accurately co-register image sets obtained in these two states, a finite element analysis based on a biomechanical model was developed to deform dose distributions for each compression circumstance for dose summation. Material and methods The model assumed the breast was under planar stress with values of 30 kPa for Young's modulus and 0.3 for Poisson's ratio. Dose distributions from round and skin-dose optimized applicators in cranial-caudal and medial-lateral compressions were deformed using 0.1 cm planar resolution. Dose distributions, skin doses, and dose-volume histograms were generated. Results were examined as a function of breast thickness, applicator size, target size, and offset distance from the center. Results Over the range of examined thicknesses, target size increased several millimeters as compression thickness decreased. This trend increased with increasing offset distances. Applicator size minimally affected target coverage, until applicator size was less than the compressed target size. In all cases, with an applicator larger or equal to the compressed target size, > 90% of the target covered by > 90% of the prescription dose. In all cases, dose coverage became less uniform as offset distance increased and average dose increased. This effect was more pronounced for smaller target–applicator combinations. Conclusions The model exhibited skin dose trends that matched MC-generated benchmarking results within 2% and clinical observations over a similar range of breast thicknesses and target sizes. The model provided quantitative insight on dosimetric treatment variables

INFLUENCE OF TABLET SPLITTING ON CONTENT UNIFORMITY OF LISINOPRIL/ HYDROCHLORTHIAZIDE TABLETS

PubMed Central

Vranić, Edina; Uzunović, Alija

2007-01-01

Dose-related adverse effects of medications are a major problem in modern medical practice. The “correct” dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, two batches of lisinopril-hydrochlorothiazide scored tablets labeled to contain 20/12,5 mg were used. The aim of this study was to establish possible influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Determination of the content uniformity of lisinopril and hydrochlorthiazide in our batches, was carried out by HPLC method. The results of content uniformity studies for halves of tablets containing combination of lisinopril-hydrochlorthiazide (supposed to contain 50% of stated 20/12,5 mg in the whole tablet) were: 49,60 ±3,29% and 49,29±0,60 % (lisinopril); 50,33±3,50% and 50,69±1,95% (hydrochlorthiazide) for batch I and II, respectively. We can conclude that the results obtained in this study support an option of tablet splitting, which is very important for obtaining the required dosage when a dosage form of the required strength is unavailable, and for better individualization of the therapy PMID:18039191

Shading correction for cone-beam CT in radiotherapy: validation of dose calculation accuracy using clinical images

NASA Astrophysics Data System (ADS)

Marchant, T. E.; Joshi, K. D.; Moore, C. J.

2017-03-01

Cone-beam CT (CBCT) images are routinely acquired to verify patient position in radiotherapy (RT), but are typically not calibrated in Hounsfield Units (HU) and feature non-uniformity due to X-ray scatter and detector persistence effects. This prevents direct use of CBCT for re-calculation of RT delivered dose. We previously developed a prior-image based correction method to restore HU values and improve uniformity of CBCT images. Here we validate the accuracy with which corrected CBCT can be used for dosimetric assessment of RT delivery, using CBCT images and RT plans for 45 patients including pelvis, lung and head sites. Dose distributions were calculated based on each patient's original RT plan and using CBCT image values for tissue heterogeneity correction. Clinically relevant dose metrics were calculated (e.g. median and minimum target dose, maximum organ at risk dose). Accuracy of CBCT based dose metrics was determined using an "override ratio" method where the ratio of the dose metric to that calculated on a bulk-density assigned version of the image is assumed to be constant for each patient, allowing comparison to "gold standard" CT. For pelvis and head images the proportion of dose errors >2% was reduced from 40% to 1.3% after applying shading correction. For lung images the proportion of dose errors >3% was reduced from 66% to 2.2%. Application of shading correction to CBCT images greatly improves their utility for dosimetric assessment of RT delivery, allowing high confidence that CBCT dose calculations are accurate within 2-3%.

Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation.

PubMed

van den Bosch, Sven; Vogel, Wouter V; Raaijmakers, Cornelis P; Dijkema, Tim; Terhaard, Chris H J; Al-Mamgani, Abrahim; Kaanders, Johannes H A M

2018-05-03

Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Dose enhancement effects of gold nanoparticles specifically targeting RNA in breast cancer cells

PubMed Central

Metzler, Philipp; Pilarczyk, Götz; Bobu, Vladimir; Kriz, Wilhelm; Hosser, Hiltraud; Fleckenstein, Jens; Krufczik, Matthias; Bestvater, Felix; Wenz, Frederik; Hausmann, Michael

2018-01-01

Localization microscopy has shown to be capable of systematic investigations on the arrangement and counting of cellular uptake of gold nanoparticles (GNP) with nanometer resolution. In this article, we show that the application of specially modified RNA targeting gold nanoparticles (“SmartFlares”) can result in ring like shaped GNP arrangements around the cell nucleus. Transmission electron microscopy revealed GNP accumulation in vicinity to the intracellular membrane structures including them of the endoplasmatic reticulum. A quantification of the radio therapeutic dose enhancement as a proof of principle was conducted with γH2AX foci analysis: The application of both—SmartFlares and unmodified GNPs—lead to a significant dose enhancement with a factor of up to 1.2 times the dose deposition compared to non-treated breast cancer cells. This enhancement effect was even more pronounced for SmartFlares. Furthermore, it was shown that a magnetic field of 1 Tesla simultaneously applied during irradiation has no detectable influence on neither the structure nor the dose enhancement dealt by gold nanoparticles. PMID:29346397

SU-E-T-495: Influence of Reduced Target-To-Nozzle Distance On Secondary Neutron Dose Equivalent in Proton and Carbon Ion Radiotherapy

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

Sheng, Y; Shahnazi, K; Wang, W

Purpose: Ion beams have an unavoidable lateral spread due to nuclear interactions interacting with the air and monitoring systems. To minimize this spread, the distance between the nozzle and the patient should be kept as small as possible.The purpose of this work was to determine the impact of the target-to-nozzle distance reduction on the secondary neutron dose equivalent in proton and carbon ion radiotherapy. Methods: In this study, abdominal and head phantoms were scanned with our CT scanner. Cubical targets with side lengths of 3 cm to 10 cm and 1 cm to 5 cm were drawn in the abdominalmore » and head phantoms respectively. Two intensity-modulated plans were made for each phantom and ion. The first of these plans placed the target at the isocenter while the other shifted the phantom 30 cm towards the nozzle. The plans at both phantom locations were optimized to provide identical dose coverage to the PTVs.Secondary neutron dose equivalent at 50 cm lateral to the center of target. Results: The neutron dose equivalent was higher for the larger field size from 0.25µSv per Gy (RBE) to 72µSv per Gy (RBE). The neutron dose equivalent was smaller when the phantom was placed at the upstream target location versus at the isocenter location by 8.9% to 10.4% and 11.0% to 22.1% for proton plans of the abdominal and head phantoms respectively. Differences for carbon plans with different target-to-nozzle locations were less than 3% for both phantoms. Conclusion: A reduction of target-to-nozzle distance can lead to benefits for proton radiotherapy. In this study, a reduction of secondary neutron dose equivalent was found for proton plans with a smaller target-to-nozzle distance. A greater impact was found for a head phantom with a smaller field size; however, a reduction of the target-to-nozzle distance had little effect for carbon therapy.« less

SU-F-T-563: Delivered Dose Reconstruction of Moving Targets for Gated Volumetric Modulated Arc Therapy (VMAT)

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

Chung, H; Cho, S; Jeong, C

2016-06-15

Purpose: Actual delivered dose of moving tumors treated with gated volumetric arc therapy (VMAT) may significantly differ from the planned dose assuming static target. In this study, we developed a method which reconstructs actual delivered dose distribution of moving target by taking into account both tumor motion and dynamic beam delivery of gated VMAT, and applied to abdominal tumors. Methods: Fifteen dual-arc VMAT plans (Eclipse, Varian Medical Systems) for 5 lung, 5 pancreatic, and 5 liver cancer patients treated with gated VMAT stereotactic body radiotherapy (SBRT) were studied. For reconstruction of the delivered dose distribution, we divided each original arcmore » beam into control-point-wise sub-beams, and applied beam isocenter shifting to each sub-beam to reflect the tumor motion. The tumor positions as a function of beam delivery were estimated by synchronizing the beam delivery with the respiratory signal which acquired during treatment. For this purpose, an in-house program (MATLAB, Mathworks) was developed to convert the original DICOM plan data into motion-involved treatment plan. The motion-involved DICOM plan was imported into Eclipse for dose calculation. The reconstructed delivered dose was compared to the plan dose using the dose coverage of gross tumor volume (GTV) and dose distribution of organs at risk (OAR). Results: The mean GTV dose coverage difference between the reconstructed delivered dose and the plan dose was 0.2 % in lung and pancreas cases, and no difference in liver cases. Mean D1000cc of ipsilateral lungs was reduced (0.8 ± 1.4cGy). Conclusion: We successfully developed a method of delivered dose reconstruction taking into account both respiratory tumor motion and dynamic beam delivery, and applied it to abdominal tumors treated with gated VAMT. No significant deterioration of delivered dose distribution indicates that interplay effect would be minimal even in the case of gated SBRT. This work was supported by the National

WE-EF-BRA-07: High Performance Preclinical Irradiation Through Optimized Dual Focal Spot Dose Painting and Online Virtual Isocenter Radiation Field Targeting

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

Stewart, J; Princess Margaret Cancer Centre, University Health Network, Toronto, CA; Lindsay, P

Purpose: Advances in radiotherapy practice facilitated by collimation systems to shape radiation fields and image guidance to target these conformal beams have motivated proposals for more complex dose patterns to improve the therapeutic ratio. Recent progress in small animal radiotherapy platforms has provided the foundation to validate the efficacy of such interventions, but robustly delivering heterogeneous dose distributions at the scale and accuracy demanded by preclinical studies remains challenging. This work proposes a dual focal spot optimization method to paint spatially heterogeneous dose regions and an online virtual isocenter targeting method to accurately target the dose distributions. Methods: Two-dimensional dosemore » kernels were empirically measured for the 1 mm diameter circular collimator with radiochromic film in a solid water phantom for the small and large x-ray focal spots on the X-RAD 225Cx microirradiator. These kernels were used in an optimization framework which determined a set of animal stage positions, beam-on times, and focal spot settings to optimally deliver a given desired dose distribution. An online method was developed which defined a virtual treatment isocenter based on a single image projection of the collimated radiation field. The method was demonstrated by optimization of a 6 mm circular 2 Gy target adjoining a 4 mm semicircular avoidance region. Results: The dual focal spot technique improved the optimized dose distribution with the proportion of avoidance region receiving more than 0.5 Gy reduced by 40% compared to the large focal spot technique. Targeting tests performed by irradiating ball bearing targets on radiochromic film pieced revealed the online targeting method improved the three-dimensional accuracy from 0.48 mm to 0.15 mm. Conclusion: The dual focal spot optimization and online virtual isocenter targeting framework is a robust option for delivering dose at the preclinical level and provides a new

Ultralow dose computed tomography attenuation correction for pediatric PET CT using adaptive statistical iterative reconstruction

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

Brady, Samuel L., E-mail: samuel.brady@stjude.org; Shulkin, Barry L.

2015-02-15

Purpose: To develop ultralow dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultralow doses (10–35 mA s). CT quantitation: noise, low-contrast resolution, and CT numbers for 11 tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% volume computed tomography dose index (0.39/3.64; mGy) from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET imagesmore » were reconstructed with the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUV{sub bw}) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative dose reduction and noise control. Results: CT numbers were constant to within 10% from the nondose reduced CTAC image for 90% dose reduction. No change in SUV{sub bw}, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols was found down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62% and 86% (3.2/8.3–0.9/6.2). Noise magnitude in dose-reduced patient images increased but was not statistically different from predose-reduced patient images. Conclusions: Using ASiR allowed for aggressive reduction in CT dose with no change in PET reconstructed images while maintaining sufficient image quality for colocalization of hybrid CT anatomy and PET radioisotope uptake.« less

SU-E-T-133: Dosimetric Impact of Scan Orientation Relative to Target Motion During Spot Scanning Proton Therapy

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

Stoker, J; Summers, P; Li, X

2014-06-01

Purpose: This study seeks to evaluate the dosimetric effects of intra-fraction motion during spot scanning proton beam therapy as a function of beam-scan orientation and target motion amplitude. Method: Multiple 4DCT scans were collected of a dynamic anthropomorphic phantom mimicking respiration amplitudes of 0 (static), 0.5, 1.0, and 1.5 cm. A spot-scanning treatment plan was developed on the maximum intensity projection image set, using an inverse-planning approach. Dynamic phantom motion was continuous throughout treatment plan delivery.The target nodule was designed to accommodate film and thermoluminescent dosimeters (TLD). Film and TLDs were uniquely labeled by location within the target. The phantommore » was localized on the treatment table using the clinically available orthogonal kV on-board imaging device. Film inserts provided data for dose uniformity; TLDs provided a 3% precision estimate of absolute dose. An inhouse script was developed to modify the delivery order of the beam spots, to orient the scanning direction parallel or perpendicular to target motion.TLD detector characterization and analysis was performed by the Imaging and Radiation Oncology Core group (IROC)-Houston. Film inserts, exhibiting a spatial resolution of 1mm, were analyzed to determine dose homogeneity within the radiation target. Results: Parallel scanning and target motions exhibited reduced target dose heterogeneity, relative to perpendicular scanning orientation. The average percent deviation in absolute dose for the motion deliveries relative to the static delivery was 4.9±1.1% for parallel scanning, and 11.7±3.5% (p<<0.05) for perpendicularly oriented scanning. Individual delivery dose deviations were not necessarily correlated to amplitude of motion for either scan orientation. Conclusions: Results demonstrate a quantifiable difference in dose heterogeneity as a function of scan orientation, more so than target amplitude. Comparison to the analyzed planar dose of a

Luminescence imaging of water during uniform-field irradiation by spot scanning proton beams

NASA Astrophysics Data System (ADS)

Komori, Masataka; Sekihara, Eri; Yabe, Takuya; Horita, Ryo; Toshito, Toshiyuki; Yamamoto, Seiichi

2018-06-01

Luminescence was found during pencil-beam proton irradiation to water phantom and range could be estimated from the luminescence images. However, it is not yet clear whether the luminescence imaging is applied to the uniform fields made of spot-scanning proton-beam irradiations. For this purpose, imaging was conducted for the uniform fields having spread out Bragg peak (SOBP) made by spot scanning proton beams. We designed six types of the uniform fields with different ranges, SOBP widths and irradiation fields. One of the designed fields was irradiated to water phantom and a cooled charge coupled device camera was used to measure the luminescence image during irradiations. We estimated the ranges, field widths, and luminescence intensities from the luminescence images and compared those with the dose distribution calculated by a treatment planning system. For all types of uniform fields, we could obtain clear images of the luminescence showing the SOBPs. The ranges and field widths evaluated from the luminescence were consistent with those of the dose distribution calculated by a treatment planning system within the differences of  ‑4 mm and  ‑11 mm, respectively. Luminescence intensities were almost proportional to the SOBP widths perpendicular to the beam direction. The luminescence imaging could be applied to uniform fields made of spot scanning proton beam irradiations. Ranges and widths of the uniform fields with SOBP could be estimated from the images. The luminescence imaging is promising for the range and field width estimations in proton therapy.

Corneal targeted nanoparticles for sustained natamycin delivery and their PK/PD indices: an approach to reduce dose and dosing frequency.

PubMed

Chandasana, Hardik; Prasad, Yarra Durga; Chhonker, Yashpal S; Chaitanya, Telaprolu K; Mishra, Nripendra N; Mitra, Kalyan; Shukla, Praveen K; Bhatta, Rabi S

2014-12-30

Natamycin is the only approved medication for the treatment of mycotic keratitis. Current dosage regimen include one drop of natamycin suspension (5% w/v) instilled in the conjunctival sac at hourly or two hourly intervals for several days which has poor patient compliance. The purpose of the present study was to design a corneal targeted nanoformulation in order to reduce dose and dosing frequency of natamycin and evaluate its pharmacokinetic/pharmacodynamic indices in comparison with clinical marketed preparation. The nanoparticles prepared by nanoprecipitation method were in nanometer size range with high entrapment efficiency and positive surface charge. In-vitro release studies indicated prolonged release of natamycin up to 8h. In-vitro antifungal activity was comparable with marketed preparation. The performance of nanoformulations was evaluated in rabbit eyes. The concentration of natamycin in tear fluid was determined by using LC-MS/MS. The pharmacokinetic parameters such as area under the curve, t½ and mean residence time were significantly higher and clearance was significantly lower for nanoformulations with that of marketed preparation. The optimized dosing schedule to maintain natamycin concentration above tenfold of MIC90 was one instillation in every 5h. Moreover, 1/5th dose reduction of nanoformulation was also effective. Copyright © 2014 Elsevier B.V. All rights reserved.

Pulsed-coil magnet systems for applying uniform 10-30 T fields to centimeter-scale targets on Sandia's Z facility

NASA Astrophysics Data System (ADS)

Rovang, D. C.; Lamppa, D. C.; Cuneo, M. E.; Owen, A. C.; McKenney, J.; Johnson, D. W.; Radovich, S.; Kaye, R. J.; McBride, R. D.; Alexander, C. S.; Awe, T. J.; Slutz, S. A.; Sefkow, A. B.; Haill, T. A.; Jones, P. A.; Argo, J. W.; Dalton, D. G.; Robertson, G. K.; Waisman, E. M.; Sinars, D. B.; Meissner, J.; Milhous, M.; Nguyen, D. N.; Mielke, C. H.

2014-12-01

Sandia has successfully integrated the capability to apply uniform, high magnetic fields (10-30 T) to high energy density experiments on the Z facility. This system uses an 8-mF, 15-kV capacitor bank to drive large-bore (5 cm diameter), high-inductance (1-3 mH) multi-turn, multi-layer electromagnets that slowly magnetize the conductive targets used on Z over several milliseconds (time to peak field of 2-7 ms). This system was commissioned in February 2013 and has been used successfully to magnetize more than 30 experiments up to 10 T that have produced exciting and surprising physics results. These experiments used split-magnet topologies to maintain diagnostic lines of sight to the target. We describe the design, integration, and operation of the pulsed coil system into the challenging and harsh environment of the Z Machine. We also describe our plans and designs for achieving fields up to 20 T with a reduced-gap split-magnet configuration, and up to 30 T with a solid magnet configuration in pursuit of the Magnetized Liner Inertial Fusion concept.

Uniform hydrogen fuel layers for inertial fusion targets by microgravity

NASA Technical Reports Server (NTRS)

Parks, P. B.; Fagaly, Robert L.

1994-01-01

A critical concern in the fabrication of targets for inertial confinement fusion (ICF) is ensuring that the hydrogenic (D(sub 2) or DT) fuel layer maintains spherical symmetry. Solid layered targets have structural integrity, but lack the needed surface smoothness. Liquid targets are inherently smooth, but suffer from gravitationally induced sagging. One method to reduce the effective gravitational field environment is freefall insertion into the target chamber. Another method to counterbalance field gravitational force is to use an applied magnetic field combined with a gradient field to induce a magnetic dipole force on the liquid fuel layer. Based on time dependent calculations of the dynamics of the liquid fuel layer in microgravity environments, we show that it may be possible to produce a liquid layered ICF target that satisfies both smoothness and symmetry requirements.

Angular distributions of absorbed dose of Bremsstrahlung and secondary electrons induced by 18-, 28- and 38-MeV electron beams in thick targets.

PubMed

Takada, Masashi; Kosako, Kazuaki; Oishi, Koji; Nakamura, Takashi; Sato, Kouichi; Kamiyama, Takashi; Kiyanagi, Yoshiaki

2013-03-01

Angular distributions of absorbed dose of Bremsstrahlung photons and secondary electrons at a wide range of emission angles from 0 to 135°, were experimentally obtained using an ion chamber with a 0.6 cm(3) air volume covered with or without a build-up cap. The Bremsstrahlung photons and electrons were produced by 18-, 28- and 38-MeV electron beams bombarding tungsten, copper, aluminium and carbon targets. The absorbed doses were also calculated from simulated photon and electron energy spectra by multiplying simulated response functions of the ion chambers, simulated with the MCNPX code. Calculated-to-experimental (C/E) dose ratios obtained are from 0.70 to 1.57 for high-Z targets of W and Cu, from 15 to 135° and the C/E range from 0.6 to 1.4 at 0°; however, the values of C/E for low-Z targets of Al and C are from 0.5 to 1.8 from 0 to 135°. Angular distributions at the forward angles decrease with increasing angles; on the other hand, the angular distributions at the backward angles depend on the target species. The dependences of absorbed doses on electron energy and target thickness were compared between the measured and simulated results. The attenuation profiles of absorbed doses of Bremsstrahlung beams at 0, 30 and 135° were also measured.

SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

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

Gong, Y; Yu, J; Xiao, Y

Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

The segmented non-uniform dielectric module design for uniformity control of plasma profile in a capacitively coupled plasma chamber

NASA Astrophysics Data System (ADS)

Xia, Huanxiong; Xiang, Dong; Yang, Wang; Mou, Peng

2014-12-01

Low-temperature plasma technique is one of the critical techniques in IC manufacturing process, such as etching and thin-film deposition, and the uniformity greatly impacts the process quality, so the design for the plasma uniformity control is very important but difficult. It is hard to finely and flexibly regulate the spatial distribution of the plasma in the chamber via controlling the discharge parameters or modifying the structure in zero-dimensional space, and it just can adjust the overall level of the process factors. In the view of this problem, a segmented non-uniform dielectric module design solution is proposed for the regulation of the plasma profile in a CCP chamber. The solution achieves refined and flexible regulation of the plasma profile in the radial direction via configuring the relative permittivity and the width of each segment. In order to solve this design problem, a novel simulation-based auto-design approach is proposed, which can automatically design the positional sequence with multi independent variables to make the output target profile in the parameterized simulation model approximate the one that users preset. This approach employs an idea of quasi-closed-loop control system, and works in an iterative mode. It starts from initial values of the design variable sequences, and predicts better sequences via the feedback of the profile error between the output target profile and the expected one. It never stops until the profile error is narrowed in the preset tolerance.

The effects of small field dosimetry on the biological models used in evaluating IMRT dose distributions

NASA Astrophysics Data System (ADS)

Cardarelli, Gene A.

The primary goal in radiation oncology is to deliver lethal radiation doses to tumors, while minimizing dose to normal tissue. IMRT has the capability to increase the dose to the targets and decrease the dose to normal tissue, increasing local control, decrease toxicity and allow for effective dose escalation. This advanced technology does present complex dose distributions that are not easily verified. Furthermore, the dose inhomogeneity caused by non-uniform dose distributions seen in IMRT treatments has caused the development of biological models attempting to characterize the dose-volume effect in the response of organized tissues to radiation. Dosimetry of small fields can be quite challenging when measuring dose distributions for high-energy X-ray beams used in IMRT. The proper modeling of these small field distributions is essential in reproducing accurate dose for IMRT. This evaluation was conducted to quantify the effects of small field dosimetry on IMRT plan dose distributions and the effects on four biological model parameters. The four biological models evaluated were: (1) the generalized Equivalent Uniform Dose (gEUD), (2) the Tumor Control Probability (TCP), (3) the Normal Tissue Complication Probability (NTCP) and (4) the Probability of uncomplicated Tumor Control (P+). These models are used to estimate local control, survival, complications and uncomplicated tumor control. This investigation compares three distinct small field dose algorithms. Dose algorithms were created using film, small ion chamber, and a combination of ion chamber measurements and small field fitting parameters. Due to the nature of uncertainties in small field dosimetry and the dependence of biological models on dose volume information, this examination quantifies the effects of small field dosimetry techniques on radiobiological models and recommends pathways to reduce the errors in using these models to evaluate IMRT dose distributions. This study demonstrates the importance

Restoration of non-uniform exposure motion blurred image

NASA Astrophysics Data System (ADS)

Luo, Yuanhong; Xu, Tingfa; Wang, Ningming; Liu, Feng

2014-11-01

Restoring motion-blurred image is the key technologies in the opto-electronic detection system. The imaging sensors such as CCD and infrared imaging sensor, which are mounted on the motion platforms, quickly move together with the platforms of high speed. As a result, the images become blur. The image degradation will cause great trouble for the succeeding jobs such as objects detection, target recognition and tracking. So the motion-blurred images must be restoration before detecting motion targets in the subsequent images. On the demand of the real weapon task, in order to deal with targets in the complex background, this dissertation uses the new theories in the field of image processing and computer vision to research the new technology of motion deblurring and motion detection. The principle content is as follows: 1) When the prior knowledge about degradation function is unknown, the uniform motion blurred images are restored. At first, the blur parameters, including the motion blur extent and direction of PSF(point spread function), are estimated individually in domain of logarithmic frequency. The direction of PSF is calculated by extracting the central light line of the spectrum, and the extent is computed by minimizing the correction between the fourier spectrum of the blurred image and a detecting function. Moreover, in order to remove the strip in the deblurred image, windows technique is employed in the algorithm, which makes the deblurred image clear. 2) According to the principle of infrared image non-uniform exposure, a new restoration model for infrared blurred images is developed. The fitting of infrared image non-uniform exposure curve is performed by experiment data. The blurred images are restored by the fitting curve.

Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model.

PubMed

Malhotra, Meenakshi; Sekar, Thillai Veerapazham; Ananta, Jeyarama S; Devulapally, Rammohan; Afjei, Rayhaneh; Babikir, Husam A; Paulmurugan, Ramasamy; Massoud, Tarik F

2018-04-20

Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with consequent efficient therapeutic response and increased sensitivity of GBM cells to lower doses of TMZ. We synthesized both targeted and non-targeted nanoparticles, and characterized them for size, surface charge and encapsulation efficiency of antagomiRs. When using targeted nanoparticles in U87MG and Ln229 GBM cells, we showed higher uptake-associated improvement in sensitivity of these cells to lower concentrations of TMZ in medium. Co-inhibition of microRNA-21 and microRNA-10b reduced the number of viable cells and increased cell cycle arrest at G2/M phase upon TMZ treatment. We found a significant increase in expression of key target genes for microRNA-21 and microRNA-10b upon using targeted versus non-targeted nanoparticles. There was also significant reduction in tumor volume when using TMZ after pre-treatment with loaded nanoparticles in human GBM cell xenografts in mice. In vivo targeted nanoparticles plus different doses of TMZ showed a significant therapeutic response even at the lowest dose of TMZ, indicating that preloading cells with antagomiR-21 and antagomiR-10b increases cellular chemosensitivity towards lower TMZ doses. Future clinical applications of this combination therapy may result in improved GBM response by using lower doses of TMZ and reducing nonspecific treatment side effects.

The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

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

Liebl, Jakob, E-mail: jakob.liebl@medaustron.at; Francis H. Burr Proton Therapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Therapeutic Radiology and Oncology, Medical University of Graz, 8036 Graz

2014-09-15

Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patientmore » positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R{sup 2} < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small

The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

PubMed Central

Liebl, Jakob; Paganetti, Harald; Zhu, Mingyao; Winey, Brian A.

2014-01-01

Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patient positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R2 < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small lesions in the

Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators.

PubMed

Belley, Matthew D; Wang, Chu; Nguyen, Giao; Gunasingha, Rathnayaka; Chao, Nelson J; Chen, Benny J; Dewhirst, Mark W; Yoshizumi, Terry T

2014-03-01

Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. Organ doses were simulated in the Geant4 application for tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. Average doses in soft-tissue organs were found to vary by as much as 23%-32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigninga single dose value for irradiation of mice to a more comprehensive approach of characterizing individual organ doses to minimize the error and uncertainty. In human radiation therapy, clinical treatment planning establishes the target dose as well as the dose distribution, however, this has generally not been done in small animal research. These results suggest that organ dose errors will be minimized by calibrating the dose rates for all filters, and using different dose rates for different organs.

Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators

PubMed Central

Belley, Matthew D.; Wang, Chu; Nguyen, Giao; Gunasingha, Rathnayaka; Chao, Nelson J.; Chen, Benny J.; Dewhirst, Mark W.; Yoshizumi, Terry T.

2014-01-01

Purpose: Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. Methods: Organ doses were simulated in the Geant4 application for tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. Results: Average doses in soft-tissue organs were found to vary by as much as 23%–32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. Conclusions: This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigning a single dose value for irradiation of mice to a more comprehensive approach of characterizing individual organ doses to minimize the error and uncertainty. In human radiation therapy, clinical treatment planning establishes the target dose as well as the dose distribution, however, this has generally not been done in small animal research. These results suggest that organ dose errors will be minimized by calibrating the dose rates for all filters, and using different dose rates for different organs. PMID:24593746

Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators

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

Belley, Matthew D.; Wang, Chu; Nguyen, Giao

2014-03-15

Purpose: Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. Methods: Organ doses were simulated in the Geant4 application formore » tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. Results: Average doses in soft-tissue organs were found to vary by as much as 23%–32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. Conclusions: This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigninga single dose value for irradiation of mice to a more comprehensive approach of characterizing individual organ doses to minimize the error and uncertainty. In human radiation therapy, clinical treatment planning establishes the target dose as well as the dose distribution, however, this has generally not been done in small animal research. These results suggest that organ dose errors will be minimized by calibrating the dose rates for all filters, and using different dose rates for different organs.« less

Impact of Node Negative Target Volume Delineation on Contralateral Parotid Gland Dose Sparing Using IMRT in Head and Neck Cancer.

PubMed

Magnuson, William J; Urban, Erich; Bayliss, R Adam; Harari, Paul M

2015-06-01

There is considerable practice variation in treatment of the node negative (N0) contralateral neck in patients with head and neck cancer. In this study, we examined the impact of N0 neck target delineation volume on radiation dose to the contralateral parotid gland. Following institutional review board approval, 12 patients with head and neck cancer were studied. All had indications for treatment of the N0 neck, such as midline base of tongue or soft palate extension or advanced ipsilateral nodal disease. The N0 neck volumes were created using the Radiation Therapy Oncology Group head and neck contouring atlas. The physician-drawn N0 neck clinical target volume (CTV) was expanded by 25% to 200% to generate volume variation, followed by a 3-mm planning target volume (PTV) expansion. Surrounding organs at risk were contoured and complete intensity-modulated radiation therapy plans were generated for each N0 volume expansion. The median N0 target volume drawn by the radiation oncologist measured 93 cm(3) (range 71-145). Volumetric expansion of the N0 CTV by 25% to 200% increased the resultant mean dose to the contralateral parotid gland by 1.4 to 8.5 Gray (Gy). For example, a 4.1-mm increase in the N0 neck CTV translated to a 2.0-Gy dose increase to the parotid, 7.4 mm to a 4.5 Gy dose increase, and 12.5 mm to an 8.5 Gy dose increase, respectively. The treatment volume designated for the N0 neck has profound impact on resultant dose to the contralateral parotid gland. Variations of up to 15 mm are routine across physicians in target contouring, reflecting individual preference and training expertise. Depending on the availability of immobilization and image guidance techniques, experts commonly recommend 3 to 10 mm margin expansions to generate the PTV. Careful attention to the original volume of the N0 neck CTV, as well as expansion margins, is important in achieving effective contralateral gland sparing to reduce the resultant xerostomia and dysguesia that may ensue

Calibration of EBT2 film by the PDD method with scanner non-uniformity correction.

PubMed

Chang, Liyun; Chui, Chen-Shou; Ding, Hueisch-Jy; Hwang, Ing-Ming; Ho, Sheng-Yow

2012-09-21

The EBT2 film together with a flatbed scanner is a convenient dosimetry QA tool for verification of clinical radiotherapy treatments. However, it suffers from a relatively high degree of uncertainty and a tedious film calibration process for every new lot of films, including cutting the films into several small pieces, exposing with different doses, restoring them back and selecting the proper region of interest (ROI) for each piece for curve fitting. In this work, we present a percentage depth dose (PDD) method that can accurately calibrate the EBT2 film together with the scanner non-uniformity correction and provide an easy way to perform film dosimetry. All films were scanned before and after the irradiation in one of the two homemade 2 mm thick acrylic frames (one portrait and the other landscape), which was located at a fixed position on the scan bed of an Epson 10 000XL scanner. After the pre-irradiated scan, the film was placed parallel to the beam central axis and sandwiched between six polystyrene plates (5 cm thick each), followed by irradiation of a 20 × 20 cm² 6 MV photon beam. Two different beams on times were used on two different films to deliver a dose to the film ranging from 32 to 320 cGy. After the post-irradiated scan, the net optical densities for a total of 235 points on the beam central axis on the films were auto-extracted and compared with the corresponding depth doses that were calculated through the measurement of a 0.6 cc farmer chamber and the related PDD table to perform the curve fitting. The portrait film location was selected for routine calibration, since the central beam axis on the film is parallel to the scanning direction, where non-uniformity correction is not needed (Ferreira et al 2009 Phys. Med. Biol. 54 1073-85). To perform the scanner non-uniformity calibration, the cross-beam profiles of the film were analysed by referencing the measured profiles from a Profiler™. Finally, to verify our method, the films were

Gamma-H2AX-based dose estimation for whole and partial body radiation exposure.

PubMed

Horn, Simon; Barnard, Stephen; Rothkamm, Kai

2011-01-01

Most human exposures to ionising radiation are partial body exposures. However, to date only limited tools are available for rapid and accurate estimation of the dose distribution and the extent of the body spared from the exposure. These parameters are of great importance for emergency triage and clinical management of exposed individuals. Here, measurements of γ-H2AX immunofluorescence by microscopy and flow cytometry were compared as rapid biodosimetric tools for whole and partial body exposures. Ex vivo uniformly X-irradiated blood lymphocytes from one donor were used to generate a universal biexponential calibration function for γ-H2AX foci/intensity yields per unit dose for time points up to 96 hours post exposure. Foci--but not intensity--levels remained significantly above background for 96 hours for doses of 0.5 Gy or more. Foci-based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers were in excellent agreement with the actual dose delivered to the targeted samples. Flow cytometric dose estimates for X-irradiated blood samples from 8 volunteers were in excellent agreement with the actual dose delivered at 1 hour post exposure but less so at 24 hours post exposure. In partial body exposures, simulated by mixing ex vivo irradiated and unirradiated lymphocytes, foci/intensity distributions were significantly over-dispersed compared to uniformly irradiated lymphocytes. For both methods and in all cases the estimated fraction of irradiated lymphocytes and dose to that fraction, calculated using the zero contaminated Poisson test and γ-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, γ-H2AX analysis of irradiated lymphocytes enables rapid and accurate assessment of whole body doses while dispersion analysis of foci or intensity distributions helps determine partial body doses and the irradiated fraction size in cases of partial body exposures.

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

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

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.

2014-01-15

and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.« less

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

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

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.

and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.« less

Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy. Addendum

DTIC Science & Technology

2009-06-01

imagining) into the HDR brachytherapy treatment planning has been demonstrated. Using the inverse planning program IPSA , dose escalation of target...Principles and Clinical Applications of IPSA ; Nucletron International Physics Seminar, Vaals, Netherlands, Sept 13-16, 2006. 7 IPSA ...experience with IPSA for prostate cancer treatment in HDR Brachytherapy, 4ième séminaire francophone de curiethérapie, Arcachon, France, June 15, 2006

Development and Validation of a Novel Vancomycin Dosing Nomogram for Achieving High-Target Trough Levels at 2 Canadian Teaching Hospitals

PubMed Central

Thalakada, Rosanne; Legal, Michael; Lau, Tim T Y; Luey, Tiffany; Batterink, Josh; Ensom, Mary H H

2012-01-01

Background: Recent guidelines recommend a vancomycin trough (predose) level between 15 and 20 mg/L in the treatment of invasive gram-positive infections, but most initial dosing nomograms are designed to achieve lower targets (5–15 mg/L). Clinicians need guidance about appropriate initial dosing to achieve the higher target. Objective: To develop and validate a high-target vancomycin dosing nomogram to achieve trough levels of 15–20 mg/L. Methods: A retrospective study was conducted at 2 teaching hospitals, St Paul’s Hospital and Vancouver General Hospital in Vancouver, British Columbia. Patients who were treated with vancomycin between January 2008 and June 2010 and who had achieved a trough level of 14.5–20.5 mg/L were identified. Demographic and clinical data were collected. Multiple linear regression was used to develop a vancomycin dosing nomogram for each hospital site. An integrated nomogram was constructed by merging the data from the 2 hospitals. A unique set of patients at each institution was used for validating their respective nomograms and a pooled group of patients for validating the integrated nomogram. Predictive success was evaluated, and a nomogram was deemed significantly different from another nomogram if p < 0.05 via “χ2 testing. Results: Data from 78 patients at one hospital and 91 patients at the other were used in developing the respective institutional nomograms. For each hospital’s data set, both age and initial serum creatinine were significantly associated with the predicted dosing interval (p < 0.001). Validation in a total of 105 test patients showed that the integrated nomogram had a predictive success rate of 56%. Conclusions: A novel vancomycin dosing nomogram was developed and validated at 2 Canadian teaching hospitals. This integrated nomogram is a tool that clinicians can use in selecting appropriate initial vancomycin regimens on the basis of age and serum creatinine, to achieve high-target levels of 15–20 mg

Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy

DTIC Science & Technology

2008-08-01

AD_________________ Award Number: W81XWH-04-1-0697 TITLE: Alpha -v Integrin Targeted PET Imaging of...SUBTITLE 5a. CONTRACT NUMBER Alpha -v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low- Dose Metronomic Anti-Angiogenic...Evaluation of biodistribution and anti-tumor effect of a dimeric RGD peptide-paclitaxel conjugate in mice with breast cancer” was published in Eur J Nucl

TH-E-BRE-09: TrueBeam Monte Carlo Absolute Dose Calculations Using Monitor Chamber Backscatter Simulations and Linac-Logged Target Current

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

A, Popescu I; Lobo, J; Sawkey, D

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 simulationsmore » 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

Method to produce large, uniform hollow spherical shells

DOEpatents

Hendricks, C.D.

1983-09-26

The invention is a method to produce large uniform hollow spherical shells by (1) forming uniform size drops of heat decomposable or vaporizable material, (2) evaporating the drops to form dried particles, (3) coating the dried particles with a layer of shell forming material and (4) heating the composite particles to melt the outer layer and to decompose or vaporize the inner particle to form an expanding inner gas bubble. The expanding gas bubble forms the molten outer layer into a shell of relatively large diameter. By cycling the temperature and pressure on the molten shell, nonuniformities in wall thickness can be reduced. The method of the invention is utilized to produce large uniform spherical shells, in the millimeter to centimeter diameter size range, from a variety of materials and of high quality, including sphericity, concentricity and surface smoothness, for use as laser fusion or other inertial confinement fusion targets as well as other applications.

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

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

Ding, C; Hrycushko, B; Jiang, S

2014-06-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan,more » the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.« less

Generalized Tumor Dose for Treatment Planning Decision Support

NASA Astrophysics Data System (ADS)

Zuniga, Areli A.

Modern radiation therapy techniques allow for improved target conformity and normal tissue sparing. These highly conformal treatment plans have allowed dose escalation techniques increasing the probability of tumor control. At the same time this conformation has introduced inhomogeneous dose distributions, making delivered dose characterizations more difficult. The concept of equivalent uniform dose (EUD) characterizes a heterogeneous dose distribution within irradiated structures as a single value and has been used in biologically based treatment planning (BBTP); however, there are no substantial validation studies on clinical outcome data supporting EUD's use and therefore has not been widely adopted as decision-making support. These highly conformal treatment plans have also introduced the need for safety margins around the target volume. These margins are designed to minimize geometrical misses, and to compensate for dosimetric and treatment delivery uncertainties. The margin's purpose is to reduce the chance of tumor recurrence. This dissertation introduces a new EUD formulation designed especially for tumor volumes, called generalized Tumor Dose (gTD). It also investigates, as a second objective, margins extensions for potential improvements in local control while maintaining or minimizing toxicity. The suitability of gTD to rank LC was assessed by means of retrospective studies in a head and neck (HN) squamous cell carcinoma (SCC) and non-small cell lung cancer (NSCLC) cohorts. The formulation was optimized based on two datasets (one of each type) and then, model validation was assessed on independent cohorts. The second objective of this dissertation was investigated by ranking the probability of LC of the primary disease adding different margin sizes. In order to do so, an already published EUD formula was used retrospectively in a HN and a NSCLC datasets. Finally, recommendations for the viability to implement this new formulation into a routine treatment

Risk-targeted maps for Romania

NASA Astrophysics Data System (ADS)

Vacareanu, Radu; Pavel, Florin; Craciun, Ionut; Coliba, Veronica; Arion, Cristian; Aldea, Alexandru; Neagu, Cristian

2018-03-01

Romania has one of the highest seismic hazard levels in Europe. The seismic hazard is due to a combination of local crustal seismic sources, situated mainly in the western part of the country and the Vrancea intermediate-depth seismic source, which can be found at the bend of the Carpathian Mountains. Recent seismic hazard studies have shown that there are consistent differences between the slopes of the seismic hazard curves for sites situated in the fore-arc and back-arc of the Carpathian Mountains. Consequently, in this study we extend this finding to the evaluation of the probability of collapse of buildings and finally to the development of uniform risk-targeted maps. The main advantage of uniform risk approach is that the target probability of collapse will be uniform throughout the country. Finally, the results obtained are discussed in the light of a recent study with the same focus performed at European level using the hazard data from SHARE project. The analyses performed in this study have pointed out to a dominant influence of the quantile of peak ground acceleration used for anchoring the fragility function. This parameter basically alters the shape of the risk-targeted maps shifting the areas which have higher collapse probabilities from eastern Romania to western Romania, as its exceedance probability increases. Consequently, a uniform procedure for deriving risk-targeted maps appears as more than necessary.

Four-dimensional dose evaluation using deformable image registration in radiotherapy for liver cancer

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

Hoon Jung, Sang; Min Yoon, Sang; Ho Park, Sung

2013-01-15

Purpose: In order to evaluate the dosimetric impact of respiratory motion on the dose delivered to the target volume and critical organs during free-breathing radiotherapy, a four-dimensional dose was evaluated using deformable image registration (DIR). Methods: Four-dimensional computed tomography (4DCT) images were acquired for 11 patients who were treated for liver cancer. Internal target volume-based treatment planning and dose calculation (3D dose) were performed using the end-exhalation phase images. The four-dimensional dose (4D dose) was calculated based on DIR of all phase images from 4DCT to the planned image. Dosimetric parameters from the 4D dose, were calculated and compared withmore » those from the 3D dose. Results: There was no significant change of the dosimetric parameters for gross tumor volume (p > 0.05). The increase D{sub mean} and generalized equivalent uniform dose (gEUD) for liver were by 3.1%{+-} 3.3% (p= 0.003) and 2.8%{+-} 3.3% (p= 0.008), respectively, and for duodenum, they were decreased by 15.7%{+-} 11.2% (p= 0.003) and 15.1%{+-} 11.0% (p= 0.003), respectively. The D{sub max} and gEUD for stomach was decreased by 5.3%{+-} 5.8% (p= 0.003) and 9.7%{+-} 8.7% (p= 0.003), respectively. The D{sub max} and gEUD for right kidney was decreased by 11.2%{+-} 16.2% (p= 0.003) and 14.9%{+-} 16.8% (p= 0.005), respectively. For left kidney, D{sub max} and gEUD were decreased by 11.4%{+-} 11.0% (p= 0.003) and 12.8%{+-} 12.1% (p= 0.005), respectively. The NTCP values for duodenum and stomach were decreased by 8.4%{+-} 5.8% (p= 0.003) and 17.2%{+-} 13.7% (p= 0.003), respectively. Conclusions: The four-dimensional dose with a more realistic dose calculation accounting for respiratory motion revealed no significant difference in target coverage and potentially significant change in the physical and biological dosimetric parameters in normal organs during free-breathing treatment.« less

Isospectrals of non-uniform Rayleigh beams with respect to their uniform counterparts

PubMed Central

Ganguli, Ranjan

2018-01-01

In this paper, we look for non-uniform Rayleigh beams isospectral to a given uniform Rayleigh beam. Isospectral systems are those that have the same spectral properties, i.e. the same free vibration natural frequencies for a given boundary condition. A transformation is proposed that converts the fourth-order governing differential equation of non-uniform Rayleigh beam into a uniform Rayleigh beam. If the coefficients of the transformed equation match with those of the uniform beam equation, then the non-uniform beam is isospectral to the given uniform beam. The boundary-condition configuration should be preserved under this transformation. We present the constraints under which the boundary configurations will remain unchanged. Frequency equivalence of the non-uniform beams and the uniform beam is confirmed by the finite-element method. For the considered cases, examples of beams having a rectangular cross section are presented to show the application of our analysis. PMID:29515879

Study of Fricke-gel dosimeter calibration for attaining precise measurements of the absorbed dose

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

Liosi, Giulia Maria; Benedini, Sara; Giacobbo, Francesca

2015-07-01

A method has been studied for attaining, with good precision, absolute measurements of the spatial distribution of the absorbed dose by means of the Fricke gelatin Xylenol Orange dosimetric system. With this aim, the dose response to subsequent irradiations was analyzed. In fact, the proposed modality is based on a pre-irradiation of each single dosimeter in a uniform field with a known dose, in order to extrapolate a calibration image for a subsequent non-uniform irradiation with an un-known dose to be measured. (authors)

Forming Uniform Deuterium-Ice Layers in Cryogenic Targets: Experiences Using the OMEGA Cryogenic Target Handling System

NASA Astrophysics Data System (ADS)

Harding, D. R.; Wittman, M. D.; Elasky, L.; Iwan, L. S.; Lund, L.

2001-10-01

The OMEGA Cryogenic Target Handling System (OCTHS) allows variable-thickness ice layers (nominal 100-μm) to be formed inside OMEGA-size (1-mm-diam., 3-μm-wall) plastic shells. The OCTHS design provides the most straightforward thermal environment for layering targets: permeation filled spherical targets are in a spherical isothermal environment. The layered target can be rotated 360^o to acquire multiple views of the ice layer. However, the capability of providing cryogenic targets for implosion experiments imposes constraints that do not exist in test systems dedicated to ice-layering studies. Most affected is the ability to characterize the target: space constraints and the need for multiple sets of windows limit the viewing access to f/5 optics, which affects the image quality. With these features, the OCTS provides the most relevant test system, to date, for layering targets and quantifying the overall ice roughness. No single layering protocol provides repeatable ice smoothness. All techniques require extensive operator interaction, and the layering process is lengthy. Typical ice rms smoothness varied from 5 to 10 μm for all targets studied. Characterizing the ice layer from different views shows a ~30% variation in the ice rms smoothness and a greater difference in the power spectra, depending on the view axis. This work was supported by the U.S. DOE Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460.

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

PubMed

Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

2017-06-01

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

PubMed Central

Palmer, Brian C.; DeLouise, Lisa A.

2017-01-01

Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

PubMed

Palmer, Brian C; DeLouise, Lisa A

2016-12-15

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

Students Wearing Police Uniforms Exhibit Biased Attention toward Individuals Wearing Hoodies.

PubMed

Civile, Ciro; Obhi, Sukhvinder S

2017-01-01

Police provide an essential public service and they often operate in difficult circumstances, requiring high-speed cognition. Recent incidents involving apparent profiling and aggressive behavior have led to accusations that the police are sometimes biased. Given that previous research has shown a link between clothing and cognition, we investigated the question of whether the police uniform itself might induce a bias in social attention. To address this question, and using a Canadian university student sample, we assessed whether wearing a police uniform biases attention toward black faces compared to white faces, and low-status individuals compared to high-status individuals. In Experiment 1 ( n = 28), participants wore either a police-style uniform or mechanic overalls, and performed a shape categorization task in the presence of a distractor that could be either: a black face, a white face, a person wearing a hoodie (whom we propose will be associated with low SES), or a person wearing a suit (whom we propose will be associated with high SES). Participants wearing the police-style uniform exhibited biased attention, indexed by slower reaction times (RTs), in the presence of low-SES images. In Experiment 2 ( n = 28), we confirmed this bias using a modified Dot-Probe task - an alternate measure of attentional bias in which we observed faster RTs to a dot probe that was spatially aligned with a low SES image. Experiment 3 ( n = 56) demonstrated that attentional bias toward low-SES targets appears only when participants wear the police-style uniform, and not when they are simply exposed to it - by having it placed on the desk in front of them. Our results demonstrate that wearing a police-style uniform biases attention toward low-SES targets. Thus, wearing a police-style uniform may induce a kind of "status-profiling" in which individuals from low-status groups become salient and capture attention. We note that our results are limited to university students and

Students Wearing Police Uniforms Exhibit Biased Attention toward Individuals Wearing Hoodies

PubMed Central

Civile, Ciro; Obhi, Sukhvinder S.

2017-01-01

Police provide an essential public service and they often operate in difficult circumstances, requiring high-speed cognition. Recent incidents involving apparent profiling and aggressive behavior have led to accusations that the police are sometimes biased. Given that previous research has shown a link between clothing and cognition, we investigated the question of whether the police uniform itself might induce a bias in social attention. To address this question, and using a Canadian university student sample, we assessed whether wearing a police uniform biases attention toward black faces compared to white faces, and low-status individuals compared to high-status individuals. In Experiment 1 (n = 28), participants wore either a police-style uniform or mechanic overalls, and performed a shape categorization task in the presence of a distractor that could be either: a black face, a white face, a person wearing a hoodie (whom we propose will be associated with low SES), or a person wearing a suit (whom we propose will be associated with high SES). Participants wearing the police-style uniform exhibited biased attention, indexed by slower reaction times (RTs), in the presence of low-SES images. In Experiment 2 (n = 28), we confirmed this bias using a modified Dot-Probe task – an alternate measure of attentional bias in which we observed faster RTs to a dot probe that was spatially aligned with a low SES image. Experiment 3 (n = 56) demonstrated that attentional bias toward low-SES targets appears only when participants wear the police-style uniform, and not when they are simply exposed to it – by having it placed on the desk in front of them. Our results demonstrate that wearing a police-style uniform biases attention toward low-SES targets. Thus, wearing a police-style uniform may induce a kind of “status-profiling” in which individuals from low-status groups become salient and capture attention. We note that our results are limited to university students

SU-F-T-669: Commissioning of An Electronic Brachytherapy System for Targeted Mouse Irradiation

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

Culberson, W; Micka, J; Carchman, E

Purpose: The aim of this study was to commission the Xoft Axxent™ electronic brachytherapy (eBT) source and 10 mm diameter surface applicator with NIST traceability for targeted irradiations of mouse anal carcinomas. Methods: The Xoft Axxent™ electronic brachytherapy (eBT) and 10 mm diameter surface applicator was chosen by the collaborating physician as a radiation delivery mechanism for mouse anal carcinomas. The target dose was 2 Gy at a depth of 3 mm in tissue to be delivered in a single fraction. To implement an accurate and reliable irradiation plan, the system was commissioned by first determining the eBT source outputmore » and corresponding dose rate at a depth of 3 mm in tissue. This was determined through parallel-plate ion chamber measurements and published conversion factors. Well-type ionization chamber measurements were used to determine a transfer coefficient, which correlates the measured dose rate at 3 mm to the NIST-traceable quantity, air-kerma rate at 50 cm in air, for eBT sources. By correlating these two quantities, daily monitoring in the well chamber becomes an accurate and efficient quality assurance technique. Once the dose-rate was determined, a treatment recipe was developed and confirmed with chamber measurements to deliver the requested dose. Radiochromic film was used to verify the dose distribution across the field. Results: Dose rates at 3 mm depth in tissue were determined for two different Xoft Axxent™ sources and correlated with NIST-traceable well-type ionization chamber measurements. Unique transfer coefficients were determined for each source and the treatment recipe was validated by measurements. Film profiles showed a uniform dose distribution across the field. Conclusion: A Xoft Axxent™ eBT system was successfully commissioned for use in the irradiation of mouse rectal tumors. Dose rates in tissue were determined as well as other pertinent parameters to ensure accurate delivery of dose to the target region.« less

Influence of eye size and beam entry angle on dose to non-targeted tissues of the eye during stereotactic x-ray radiosurgery of AMD

NASA Astrophysics Data System (ADS)

Cantley, Justin L.; Hanlon, Justin; Chell, Erik; Lee, Choonsik; Smith, W. Clay; Bolch, Wesley E.

2013-10-01

Age-related macular degeneration is a leading cause of vision loss for the elderly population of industrialized nations. The IRay® Radiotherapy System, developed by Oraya® Therapeutics, Inc., is a stereotactic low-voltage irradiation system designed to treat the wet form of the disease. The IRay System uses three robotically positioned 100 kVp collimated photon beams to deliver an absorbed dose of up to 24 Gy to the macula. The present study uses the Monte Carlo radiation transport code MCNPX to assess absorbed dose to six non-targeted tissues within the eye—total lens, radiosensitive tissues of the lens, optic nerve, distal tip of the central retinal artery, non-targeted portion of the retina, and the ciliary body--all as a function of eye size and beam entry angle. The ocular axial length was ranged from 20 to 28 mm in 2 mm increments, with the polar entry angle of the delivery system varied from 18° to 34° in 2° increments. The resulting data showed insignificant variations in dose for all eye sizes. Slight variations in the dose to the optic nerve and the distal tip of the central retinal artery were noted as the polar beam angle changed. An increase in non-targeted retinal dose was noted as the entry angle increased, while the dose to the lens, sensitive volume of the lens, and ciliary body decreased as the treatment polar angle increased. Polar angles of 26° or greater resulted in no portion of the sensitive volume of the lens receiving an absorbed dose of 0.5 Gy or greater. All doses to non-targeted structures reported in this study were less than accepted thresholds for post-procedure complications.

Covariant Uniform Acceleration

NASA Astrophysics Data System (ADS)

Friedman, Yaakov; Scarr, Tzvi

2013-04-01

We derive a 4D covariant Relativistic Dynamics Equation. This equation canonically extends the 3D relativistic dynamics equation , where F is the 3D force and p = m0γv is the 3D relativistic momentum. The standard 4D equation is only partially covariant. To achieve full Lorentz covariance, we replace the four-force F by a rank 2 antisymmetric tensor acting on the four-velocity. By taking this tensor to be constant, we obtain a covariant definition of uniformly accelerated motion. This solves a problem of Einstein and Planck. We compute explicit solutions for uniformly accelerated motion. The solutions are divided into four Lorentz-invariant types: null, linear, rotational, and general. For null acceleration, the worldline is cubic in the time. Linear acceleration covariantly extends 1D hyperbolic motion, while rotational acceleration covariantly extends pure rotational motion. We use Generalized Fermi-Walker transport to construct a uniformly accelerated family of inertial frames which are instantaneously comoving to a uniformly accelerated observer. We explain the connection between our approach and that of Mashhoon. We show that our solutions of uniformly accelerated motion have constant acceleration in the comoving frame. Assuming the Weak Hypothesis of Locality, we obtain local spacetime transformations from a uniformly accelerated frame K' to an inertial frame K. The spacetime transformations between two uniformly accelerated frames with the same acceleration are Lorentz. We compute the metric at an arbitrary point of a uniformly accelerated frame. We obtain velocity and acceleration transformations from a uniformly accelerated system K' to an inertial frame K. We introduce the 4D velocity, an adaptation of Horwitz and Piron s notion of "off-shell." We derive the general formula for the time dilation between accelerated clocks. We obtain a formula for the angular velocity of a uniformly accelerated object. Every rest point of K' is uniformly accelerated, and

Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study.

PubMed

Ehmann, Lisa; Zoller, Michael; Minichmayr, Iris K; Scharf, Christina; Maier, Barbara; Schmitt, Maximilian V; Hartung, Niklas; Huisinga, Wilhelm; Vogeser, Michael; Frey, Lorenz; Zander, Johannes; Kloft, Charlotte

2017-10-21

Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCR CG ). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T >MIC , 50%T >4×MIC ) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCR CG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T >MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T >4×MIC . A hyperbolic relationship between CLCR CG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C 8h ) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was

A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

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

Yao Rui; Bernard, Damian; Turian, Julius

2012-04-15

Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lungmore » dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.« less

Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.

PubMed

Postel-Vinay, Sophie; Collette, Laurence; Paoletti, Xavier; Rizzo, Elisa; Massard, Christophe; Olmos, David; Fowst, Camilla; Levy, Bernard; Mancini, Pierre; Lacombe, Denis; Ivy, Percy; Seymour, Lesley; Le Tourneau, Christophe; Siu, Lillian L; Kaye, Stan B; Verweij, Jaap; Soria, Jean-Charles

2014-08-01

Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention. In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded. The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G ⩾ 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G⩾3 toxicity occurring after C1 in 18.6% of patients. Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI. Copyright © 2014 Elsevier Ltd. All rights reserved.

On the relationship of minimum detectable contrast to dose and lesion size in abdominal CT

NASA Astrophysics Data System (ADS)

Zhou, Yifang; Scott, Alexander, II; Allahverdian, Janet; Lee, Christina; Kightlinger, Blake; Azizyan, Avetis; Miller, Joseph

2015-10-01

CT dose optimization is typically guided by pixel noise or contrast-to-noise ratio that does not delineate low contrast details adequately. We utilized the statistically defined low contrast detectability to study its relationship to dose and lesion size in abdominal CT. A realistically shaped medium sized abdomen phantom was customized to contain a cylindrical void of 4 cm diameter. The void was filled with a low contrast (1% and 2%) insert containing six groups of cylindrical targets ranging from 1.2 mm to 7 mm in size. Helical CT scans were performed using a Siemens 64-slice mCT and a GE Discovery 750 HD at various doses. After the subtractions between adjacent slices, the uniform sections of the filtered backprojection reconstructed images were partitioned to matrices of square elements matching the sizes of the targets. It was verified that the mean values from all the elements in each matrix follow a Gaussian distribution. The minimum detectable contrast (MDC), quantified by the mean signal to background difference equal to the distribution’s standard deviation multiplied by 3.29, corresponding to 95% confidence level, was found to be related to the phantom specific dose and the element size by a power law (R^2  >  0.990). Independent readings on the 5 mm and 7 mm targets were compared to the measured contrast to the MDC ratios. The results showed that 93% of the cases were detectable when the measured contrast exceeds the MDC. The correlation of the MDC to the pixel noise and target size was also identified and the relationship was found to be the same for the scanners in the study. To quantify the impact of iterative reconstructions to the low contrast detectability, the noise structure was studied in a similar manner at different doses and with different ASIR blending fractions. The relationship of the dose to the blending fraction and low contrast detectability is presented.

The Nike KrF laser facility: Performance and initial target experiments

NASA Astrophysics Data System (ADS)

Obenschain, S. P.; Bodner, S. E.; Colombant, D.; Gerber, K.; Lehmberg, R. H.; McLean, E. A.; Mostovych, A. N.; Pronko, M. S.; Pawley, C. J.; Schmitt, A. J.; Sethian, J. D.; Serlin, V.; Stamper, J. A.; Sullivan, C. A.; Dahlburg, J. P.; Gardner, J. H.; Chan, Y.; Deniz, A. V.; Hardgrove, J.; Lehecka, T.; Klapisch, M.

1996-05-01

Krypton-fluoride (KrF) lasers are of interest to laser fusion because they have both the large bandwidth capability (≳THz) desired for rapid beam smoothing and the short laser wavelength (1/4 μm) needed for good laser-target coupling. Nike is a recently completed 56-beam KrF laser and target facility at the Naval Research Laboratory. Because of its bandwidth of 1 THz FWHM (full width at half-maximum), Nike produces more uniform focal distributions than any other high-energy ultraviolet laser. Nike was designed to study the hydrodynamic instability of ablatively accelerated planar targets. First results show that Nike has spatially uniform ablation pressures (Δp/p<2%). Targets have been accelerated for distances sufficient to study hydrodynamic instability while maintaining good planarity. In this review we present the performance of the Nike laser in producing uniform illumination, and its performance in correspondingly uniform acceleration of targets.

Consequences of additional use of PET information for target volume delineation and radiotherapy dose distribution for esophageal cancer.

PubMed

Muijs, Christina T; Schreurs, Liesbeth M; Busz, Dianne M; Beukema, Jannet C; van der Borden, Arnout J; Pruim, Jan; Van der Jagt, Eric J; Plukker, John Th; Langendijk, Johannes A

2009-12-01

To determine the consequences of target volume (TV) modifications, based on the additional use of PET information, on radiation planning, assuming PET/CT-imaging represents the true extent of the tumour. For 21 patients with esophageal cancer, two separate TV's were retrospectively defined based on CT (CT-TV) and co-registered PET/CT images (PET/CT-TV). Two 3D-CRT plans (prescribed dose 50.4 Gy) were constructed to cover the corresponding TV's. Subsequently, these plans were compared for target coverage, normal tissue dose-volume histograms and the corresponding normal tissue complication probability (NTCP) values. The addition of PET led to the modification of CT-TV with at least 10% in 12 of 21 patients (57%) (reduction in 9, enlargement in 3). PET/CT-TV was inadequately covered by the CT-based treatment plan in 8 patients (36%). Treatment plan modifications resulted in significant changes (p<0.05) in dose distributions to heart and lungs. Corresponding changes in NTCP values ranged from -3% to +2% for radiation pneumonitis and from -0.2% to +1.2% for cardiac mortality. This study demonstrated that TV's based on CT might exclude PET-avid disease. Consequences are under dosing and thereby possibly ineffective treatment. Moreover, the addition of PET in radiation planning might result in clinical important changes in NTCP.

Uniformity testing: assessment of a centralized web-based uniformity analysis system.

PubMed

Klempa, Meaghan C

2011-06-01

Uniformity testing is performed daily to ensure adequate camera performance before clinical use. The aim of this study is to assess the reliability of Beth Israel Deaconess Medical Center's locally built, centralized, Web-based uniformity analysis system by examining the differences between manufacturer and Web-based National Electrical Manufacturers Association integral uniformity calculations measured in the useful field of view (FOV) and the central FOV. Manufacturer and Web-based integral uniformity calculations measured in the useful FOV and the central FOV were recorded over a 30-d period for 4 cameras from 3 different manufacturers. These data were then statistically analyzed. The differences between the uniformity calculations were computed, in addition to the means and the SDs of these differences for each head of each camera. There was a correlation between the manufacturer and Web-based integral uniformity calculations in the useful FOV and the central FOV over the 30-d period. The average differences between the manufacturer and Web-based useful FOV calculations ranged from -0.30 to 0.099, with SD ranging from 0.092 to 0.32. For the central FOV calculations, the average differences ranged from -0.163 to 0.055, with SD ranging from 0.074 to 0.24. Most of the uniformity calculations computed by this centralized Web-based uniformity analysis system are comparable to the manufacturers' calculations, suggesting that this system is reasonably reliable and effective. This finding is important because centralized Web-based uniformity analysis systems are advantageous in that they test camera performance in the same manner regardless of the manufacturer.

Impact of temporal probability in 4D dose calculation for lung tumors.

PubMed

Rouabhi, Ouided; Ma, Mingyu; Bayouth, John; Xia, Junyi

2015-11-08

The purpose of this study was to evaluate the dosimetric uncertainty in 4D dose calculation using three temporal probability distributions: uniform distribution, sinusoidal distribution, and patient-specific distribution derived from the patient respiratory trace. Temporal probability, defined as the fraction of time a patient spends in each respiratory amplitude, was evaluated in nine lung cancer patients. Four-dimensional computed tomography (4D CT), along with deformable image registration, was used to compute 4D dose incorporating the patient's respiratory motion. First, the dose of each of 10 phase CTs was computed using the same planning parameters as those used in 3D treatment planning based on the breath-hold CT. Next, deformable image registration was used to deform the dose of each phase CT to the breath-hold CT using the deformation map between the phase CT and the breath-hold CT. Finally, the 4D dose was computed by summing the deformed phase doses using their corresponding temporal probabilities. In this study, 4D dose calculated from the patient-specific temporal probability distribution was used as the ground truth. The dosimetric evaluation matrix included: 1) 3D gamma analysis, 2) mean tumor dose (MTD), 3) mean lung dose (MLD), and 4) lung V20. For seven out of nine patients, both uniform and sinusoidal temporal probability dose distributions were found to have an average gamma passing rate > 95% for both the lung and PTV regions. Compared with 4D dose calculated using the patient respiratory trace, doses using uniform and sinusoidal distribution showed a percentage difference on average of -0.1% ± 0.6% and -0.2% ± 0.4% in MTD, -0.2% ± 1.9% and -0.2% ± 1.3% in MLD, 0.09% ± 2.8% and -0.07% ± 1.8% in lung V20, -0.1% ± 2.0% and 0.08% ± 1.34% in lung V10, 0.47% ± 1.8% and 0.19% ± 1.3% in lung V5, respectively. We concluded that four-dimensional dose computed using either a uniform or sinusoidal temporal probability distribution can

Mandatory School Uniforms.

ERIC Educational Resources Information Center

Cohn, Carl A.

1996-01-01

Shortly after implementing a mandatory school uniform policy, the Long Beach (California) Public Schools can boast 99% compliance and a substantial reduction in school crime. The uniforms can't be confused with gang colors, save parents money, and help identify outsiders. A sidebar lists ingredients for a mandatory uniform policy. (MLH)

WE-AB-207B-09: Margin Reduction for Planning Target Volume (PTV) in Patients with Localized Prostate Cancer: Impact On Delivered Dose and Quality of Life

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

Kumarasiri, A; Liu, C; Brown, S

Purpose: To estimate the delivered (cumulative) dose to targets and organs at risk for localized prostate cancer patients treated with reduced PTV margins and to evaluate preliminary patient reported quality-of-life (QOL). Methods: Under an IRB-approved protocol, 20 prostate cancer patients (including 11 control patients) were treated with reduced planning margins (5 mm uniform with 4 mm at prostate/rectum interface). Control patients had standard margin (10/6 mm)-based treatments. A parameter-optimized Elastix algorithm along with energy-mass mapping was used to deform and resample dose of the day onto the planning CT for each fraction to estimate the delivered dose over all fractions.more » QOL data were collected via Expanded Prostate cancer Index Composite (EPIC-26) questionnaires at time points pre-treatment, post-treatment, and at 2, 6, 12, 18 month follow-ups. Standardized QOL scores [range: 0–100] were determined and baseline-corrected by subtracting pre-treatment QOL data. Mean QOL differences between the margin reduced group and control group (QOLmr-QOLcontrol) were calculated for first 18 months. Results: The difference between the cumulative mean dose (Dmean) and the planned mean dose (±SD) for PTV, prostate, bladder, and rectum were −2.2±1.0, 0.3±0.5, −0.7±2.6, and −2.1±1.3 Gy respectively for the margin-reduced group, and −0.8±2.0, 0.9±1.4, - 0.7±3.1 and −1.0±2.4 Gy for the control group. Difference between the two groups was statistically insignificant (p=0.1). Standardized and baseline corrected QOLmr-QOLcontrol for EPIC domains categorized as “Urinary Incontinence”, “Urinary Irritative/Obstructive”, “Bowel”, “Sexual”, and “Hormonal” were 0.6, 12.1, 9.1, 13.3, and −0.9 for the 18 months following radiation therapy (higher values better). Delivered dose to rectum showed a weak correlation to “Bowel” domain (Pearson’s coefficient −0.24, p<0.001), while bladder dose did not correlate to Urinary

Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

PubMed

Durand, Cheryl; Bylo, Mary; Howard, Brian; Belliveau, Paul

2018-06-01

To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

Low-Dose Irradiation Enhances Gene Targeting in Human Pluripotent Stem Cells.

PubMed

Hatada, Seigo; Subramanian, Aparna; Mandefro, Berhan; Ren, Songyang; Kim, Ho Won; Tang, Jie; Funari, Vincent; Baloh, Robert H; Sareen, Dhruv; Arumugaswami, Vaithilingaraja; Svendsen, Clive N

2015-09-01

Human pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy; however, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. We showed that limited low-dose irradiation (LDI) using either γ-ray or x-ray exposure (0.4 Gy) significantly enhanced HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by more than 30-fold when combined with the targeting tools zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats. Whole-exome sequencing confirmed that the LDI administered to hPSCs did not induce gross genomic alterations or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new, targeted hPSC lines that are crucial to expand the use of disease modeling and to develop novel avenues of cell therapy. The simple and relevant technique described in this report uses a low level of radiation to increase desired gene modifications in human pluripotent stem cells by an order of magnitude. This higher efficiency permits greater throughput with reduced time and cost. The low level of radiation also greatly increased the recombination frequency when combined with developed engineered nucleases. Critically, the radiation did not lead to increases in DNA mutations or to reductions in overall cellular viability. This novel technique enables not only the rapid production of disease models using human stem cells but also the possibility of treating genetically based diseases by correcting patient-derived cells. ©AlphaMed Press.

Permethrin exposure from fabric-treated military uniforms under different wear-time scenarios.

PubMed

Proctor, Susan P; Maule, Alexis L; Heaton, Kristin J; Adam, Gina E

2014-11-01

The objective of the project was to ascertain whether urinary biomarkers of permethrin exposure are detected after wearing post-tailored, fabric-treated military uniforms under two different wear-time exposure scenarios. Study A occurred over 3.5 days and involved six participants wearing treated uniforms continuously for 30-32 h. Urine collection occurred at scheduled time points before, during, and after wearing the uniform. Study B, conducted over 19 days, included 11 participants wearing treated uniforms for 3 consecutive days, 8 h each day (with urine collection before, during, and after wear). Urinary biomarkers of permethrin (3-phenoxybenzoic acid (3PBA), cis- 2,2-(dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cDCCA), trans- 2,2-(dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (tDCCA)) were detected during and after wear. Biomarker detection generally occurred over the 10- to 12-h period after putting on the uniform and subsided 24 h following uniform removal (in both Study A and B scenarios). Those wearing permethrin-treated uniforms under the longer wear-time scenario (Study A) excreted significantly higher cumulative mean levels compared with those in Study B (3.29 times higher for 3PBA and 2.23 times higher for the sum of c/tDCCA (P≤0.001)). Findings suggest that wearing permethrin-treated clothing does increase absorbed, internal dose levels of permethrin above population levels and is significantly related to wear-time duration.

SU-E-T-318: The Effect of Patient Positioning Errors On Target Coverage and Cochlear Dose in Stereotactic Radiosurgery Treatment of Acoustic Neuromas

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

Dellamonica, D.; Luo, G.; Ding, G.

Purpose: Setup errors on the order of millimeters may cause under-dosing of targets and significant changes in dose to critical structures especially when planning with tight margins in stereotactic radiosurgery. This study evaluates the effects of these types of patient positioning uncertainties on planning target volume (PTV) coverage and cochlear dose for stereotactic treatments of acoustic neuromas. Methods: Twelve acoustic neuroma patient treatment plans were retrospectively evaluated in Brainlab iPlan RT Dose 4.1.3. All treatment beams were shaped by HDMLC from a Varian TX machine. Seven patients had planning margins of 2mm, five had 1–1.5mm. Six treatment plans were createdmore » for each patient simulating a 1mm setup error in six possible directions: anterior-posterior, lateral, and superiorinferior. The arcs and HDMLC shapes were kept the same for each plan. Change in PTV coverage and mean dose to the cochlea was evaluated for each plan. Results: The average change in PTV coverage for the 72 simulated plans was −1.7% (range: −5 to +1.1%). The largest average change in coverage was observed for shifts in the patient's superior direction (−2.9%). The change in mean cochlear dose was highly dependent upon the direction of the shift. Shifts in the anterior and superior direction resulted in an average increase in dose of 13.5 and 3.8%, respectively, while shifts in the posterior and inferior direction resulted in an average decrease in dose of 17.9 and 10.2%. The average change in dose to the cochlea was 13.9% (range: 1.4 to 48.6%). No difference was observed based on the size of the planning margin. Conclusion: This study indicates that if the positioning uncertainty is kept within 1mm the setup errors may not result in significant under-dosing of the acoustic neuroma target volumes. However, the change in mean cochlear dose is highly dependent upon the direction of the shift.« less

Modelling of the reactive sputtering process with non-uniform discharge current density and different temperature conditions

NASA Astrophysics Data System (ADS)

Vašina, P; Hytková, T; Eliáš, M

2009-05-01

The majority of current models of the reactive magnetron sputtering assume a uniform shape of the discharge current density and the same temperature near the target and the substrate. However, in the real experimental set-up, the presence of the magnetic field causes high density plasma to form in front of the cathode in the shape of a toroid. Consequently, the discharge current density is laterally non-uniform. In addition to this, the heating of the background gas by sputtered particles, which is usually referred to as the gas rarefaction, plays an important role. This paper presents an extended model of the reactive magnetron sputtering that assumes the non-uniform discharge current density and which accommodates the gas rarefaction effect. It is devoted mainly to the study of the behaviour of the reactive sputtering rather that to the prediction of the coating properties. Outputs of this model are compared with those that assume uniform discharge current density and uniform temperature profile in the deposition chamber. Particular attention is paid to the modelling of the radial variation of the target composition near transitions from the metallic to the compound mode and vice versa. A study of the target utilization in the metallic and compound mode is performed for two different discharge current density profiles corresponding to typical two pole and multipole magnetics available on the market now. Different shapes of the discharge current density were tested. Finally, hysteresis curves are plotted for various temperature conditions in the reactor.

School Uniforms Redux.

ERIC Educational Resources Information Center

Dowling-Sendor, Benjamin

2002-01-01

Reviews a recent decision in "Littlefield" by the 5th Circuit upholding a school uniform policy. Advises board member who wish to adopt a school uniform policy to solicit input from parents and students, research the experiences of other school districts with uniform policies, and articulate the interests they wish to promote through uniform…

An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug

PubMed Central

Alyami, Hamad; Dahmash, Eman; Bowen, James

2017-01-01

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation. PMID:28609454

An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug.

PubMed

Alyami, Hamad; Dahmash, Eman; Bowen, James; Mohammed, Afzal R

2017-01-01

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation.

Evaluation of Mean Glandular Dose and Modulation Transfer Function for Different Tube Potentials and Target-Filter Combinations in Computed Radiography Mammography

PubMed Central

Abdul Aziz,, Siti Aishah; Mohd Saparudin, Abdul Khaliq; Harun, Ahmad Zaky

2013-01-01

Background: Different target-filter combinations in computed radiography have different impacts on the dose and image quality in digital radiography. This study aims to evaluate the mean glandular dose (MGD) and modulation transfer function (MTF) of various target-filter combinations by investigating the signal intensities of X-ray beams. Methods: General Electric (GE) Senographe DMR Plus mammography unit was used for MGD and MTF evaluation. The measured MGD was compared with the dose reference level (DRL), whereas the MTF was evaluated using ImageJ 1.46o software. A modified Mammography Accreditation Phantom RMI 156 was exposed using different target-filter combinations of molybdenum-molybdenum (Mo-Mo), molybdenum-rhodium (Mo-Rh) and rhodium-rhodium (Rh-Rh) at two different tube voltages, 26 kV and 32 kV with 50 mAs. Results: In the MGD evaluations, all target-filters gave an MGD value of < 1.5 mGy. The one-way ANOVA test showed a highly significant interaction between the MGD and the kilovoltage and target-filter material used (26 kV: F (2,12) = 49,234, P = 0.001;32 kV: F (2,12) = 89,972, P = 0.001). A Tukey post-hoc test revealed that the MGD for 26 kV and 32 kV was highly affected by the target-filter combinations. The test of homogeneity of variances indicates that the MGD varies significantly for 26 kV and 32 kV images (0.045 and 0.030 (P < 0.05), respectively). However, the one-way ANOVA for the MTF shows that no significant difference exists between the target-filter combinations used with 26 kV and 32 kV images either in parallel or perpendicular to the chest wall side F (2,189) = 0.26, P > 0.05). Conclusion: Higher tube voltage and atomic number target-filter yield higher MGD values. However, the MTF is independent of the X-ray energy and the type of target-filter combinations used. PMID:23966821

Skin dose mapping for non-uniform x-ray fields using a backscatter point spread function

NASA Astrophysics Data System (ADS)

Vijayan, Sarath; Xiong, Zhenyu; Shankar, Alok; Rudin, Stephen; Bednarek, Daniel R.

2017-03-01

Beam shaping devices like ROI attenuators and compensation filters modulate the intensity distribution of the xray beam incident on the patient. This results in a spatial variation of skin dose due to the variation of primary radiation and also a variation in backscattered radiation from the patient. To determine the backscatter component, backscatter point spread functions (PSF) are generated using EGS Monte-Carlo software. For this study, PSF's were determined by simulating a 1 mm beam incident on the lateral surface of an anthropomorphic head phantom and a 20 cm thick PMMA block phantom. The backscatter PSF's for the head phantom and PMMA phantom are curve fit with a Lorentzian function after being normalized to the primary dose intensity (PSFn). PSFn is convolved with the primary dose distribution to generate the scatter dose distribution, which is added to the primary to obtain the total dose distribution. The backscatter convolution technique is incorporated in the dose tracking system (DTS), which tracks skin dose during fluoroscopic procedures and provides a color map of the dose distribution on a 3D patient graphic model. A convolution technique is developed for the backscatter dose determination for the nonuniformly spaced graphic-model surface vertices. A Gafchromic film validation was performed for shaped x-ray beams generated with an ROI attenuator and with two compensation filters inserted into the field. The total dose distribution calculated by the backscatter convolution technique closely agreed with that measured with the film.

Quantitative multi-pinhole small-animal SPECT: uniform versus non-uniform Chang attenuation correction.

PubMed

Wu, C; de Jong, J R; Gratama van Andel, H A; van der Have, F; Vastenhouw, B; Laverman, P; Boerman, O C; Dierckx, R A J O; Beekman, F J

2011-09-21

Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. We propose a Chang-based non-uniform attenuation correction (NUA-CT) for small-animal SPECT/CT with focusing pinhole collimation, and compare the quantitative accuracy with uniform Chang correction based on (i) body outlines extracted from x-ray CT (UA-CT) and (ii) on hand drawn body contours on the images obtained with three integrated optical cameras (UA-BC). Measurements in phantoms and rats containing known activities of isotopes were conducted for evaluation. In (125)I, (201)Tl, (99m)Tc and (111)In phantom experiments, average relative errors comparing to the gold standards measured in a dose calibrator were reduced to 5.5%, 6.8%, 4.9% and 2.8%, respectively, with NUA-CT. In animal studies, these errors were 2.1%, 3.3%, 2.0% and 2.0%, respectively. Differences in accuracy on average between results of NUA-CT, UA-CT and UA-BC were less than 2.3% in phantom studies and 3.1% in animal studies except for (125)I (3.6% and 5.1%, respectively). All methods tested provide reasonable attenuation correction and result in high quantitative accuracy. NUA-CT shows superior accuracy except for (125)I, where other factors may have more impact on the quantitative accuracy than the selected attenuation correction.

Plasma Doping—Enabling Technology for High Dose Logic and Memory Applications

NASA Astrophysics Data System (ADS)

Miller, T.; Godet, L.; Papasouliotis, G. D.; Singh, V.

2008-11-01

As logic and memory device dimensions shrink with each generation, there are more high dose implants at lower energies. Examples include dual poly gate (also referred to as counter-doped poly), elevated source drain and contact plug implants. Plasma Doping technology throughput and dopant profile benefits at these ultra high dose and lower energy conditions have been well established [1,2,3]. For the first time a production-worthy plasma doping implanter, the VIISta PLAD tool, has been developed with unique architecture suited for precise and repeatable dopant placement. Critical elements of the architecture include pulsed DC wafer bias, closed-loop dosimetry and a uniform low energy, high density plasma source. In this paper key performance metrics such as dose uniformity, dose repeatability and dopant profile control will be presented that demonstrate the production-worthiness of the VIISta PLAD tool for several high dose applications.

SU-F-J-133: Adaptive Radiation Therapy with a Four-Dimensional Dose Calculation Algorithm That Optimizes Dose Distribution Considering Breathing Motion

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

Ali, I; Algan, O; Ahmad, S

Purpose: To model patient motion and produce four-dimensional (4D) optimized dose distributions that consider motion-artifacts in the dose calculation during the treatment planning process. Methods: An algorithm for dose calculation is developed where patient motion is considered in dose calculation at the stage of the treatment planning. First, optimal dose distributions are calculated for the stationary target volume where the dose distributions are optimized considering intensity-modulated radiation therapy (IMRT). Second, a convolution-kernel is produced from the best-fitting curve which matches the motion trajectory of the patient. Third, the motion kernel is deconvolved with the initial dose distribution optimized for themore » stationary target to produce a dose distribution that is optimized in four-dimensions. This algorithm is tested with measured doses using a mobile phantom that moves with controlled motion patterns. Results: A motion-optimized dose distribution is obtained from the initial dose distribution of the stationary target by deconvolution with the motion-kernel of the mobile target. This motion-optimized dose distribution is equivalent to that optimized for the stationary target using IMRT. The motion-optimized and measured dose distributions are tested with the gamma index with a passing rate of >95% considering 3% dose-difference and 3mm distance-to-agreement. If the dose delivery per beam takes place over several respiratory cycles, then the spread-out of the dose distributions is only dependent on the motion amplitude and not affected by motion frequency and phase. This algorithm is limited to motion amplitudes that are smaller than the length of the target along the direction of motion. Conclusion: An algorithm is developed to optimize dose in 4D. Besides IMRT that provides optimal dose coverage for a stationary target, it extends dose optimization to 4D considering target motion. This algorithm provides alternative to motion

Analysis of FET-PET imaging for target volume definition in patients with gliomas treated with conformal radiotherapy.

PubMed

Rieken, Stefan; Habermehl, Daniel; Giesel, Frederik L; Hoffmann, Christoph; Burger, Ute; Rief, Harald; Welzel, Thomas; Haberkorn, Uwe; Debus, Jürgen; Combs, Stephanie E

2013-12-01

Modern radiotherapy (RT) techniques such as stereotactic RT, intensity-modulated RT, or particle irradiation allow local dose escalation with simultaneous sparing of critical organs. Several trials are currently investigating their benefit in glioma reirradiation and boost irradiation. Target volume definition is of critical importance especially when steep dose gradient techniques are employed. In this manuscript we investigate the impact of O-(2-(F-18)fluoroethyl)-l-tyrosine-positron emission tomography/computer tomography (FET-PET/CT) on target volume definition in low and high grade glioma patients undergoing either first or re-irradiation with particles. We investigated volumetric size and uniformity of magnetic resonance imaging (MRI)- vs. FET-PET/CT-derived gross tumor volumes (GTVs) and planning target volumes (PTVs) of 41 glioma patients. Clinical cases are presented to demonstrate potential benefits of integrating FET-PET/CT-planning into daily routine. Integrating FET-uptake into the delineation of GTVs yields larger volumes. Combined modality-derived PTVs are significantly enlarged in high grade glioma patients and in case of primary RT. The congruence of MRI and FET signals for the identification of glioma GTVs is poor with mean uniformity indices of 0.39. MRI-based PTVs miss 17% of FET-PET/CT-based GTVs. Non significant alterations were detected in low grade glioma patients and in those undergoing reirradiation. Target volume definition for malignant gliomas during initial RT may yield significantly differing results depending upon the imaging modality, which the contouring process is based upon. The integration of both MRI and FET-PET/CT may help to improve GTV coverage by avoiding larger incongruences between physical and biological imaging techniques. In low grade gliomas and in cases of reirradiation, more studies are needed in order to investigate a potential benefit of FET-PET/CT for planning of RT. Copyright © 2013 Elsevier Ireland Ltd. All

Real-time intraoperative evaluation of implant quality and dose correction during prostate brachytherapy consistently improves target coverage using a novel image fusion and optimization program.

PubMed

Zelefsky, Michael J; Cohen, Gilad N; Taggar, Amandeep S; Kollmeier, Marisa; McBride, Sean; Mageras, Gig; Zaider, Marco

Our purpose was to describe the process and outcome of performing postimplantation dosimetric assessment and intraoperative dose correction during prostate brachytherapy using a novel image fusion-based treatment-planning program. Twenty-six consecutive patients underwent intraoperative real-time corrections of their dose distributions at the end of their permanent seed interstitial procedures. After intraoperatively planned seeds were implanted and while the patient remained in the lithotomy position, a cone beam computed tomography scan was obtained to assess adequacy of the prescription dose coverage. The implanted seed positions were automatically segmented from the cone-beam images, fused onto a new set of acquired ultrasound images, reimported into the planning system, and recontoured. Dose distributions were recalculated based upon actual implanted seed coordinates and recontoured ultrasound images and were reviewed. If any dose deficiencies within the prostate target were identified, additional needles and seeds were added. Once an implant was deemed acceptable, the procedure was completed, and anesthesia was reversed. When the intraoperative ultrasound-based quality assurance assessment was performed after seed placement, the median volume receiving 100% of the dose (V100) was 93% (range, 74% to 98%). Before seed correction, 23% (6/26) of cases were noted to have V100 <90%. Based on this intraoperative assessment and replanning, additional seeds were placed into dose-deficient regions within the target to improve target dose distributions. Postcorrection, the median V100 was 97% (range, 93% to 99%). Following intraoperative dose corrections, all implants achieved V100 >90%. In these patients, postimplantation evaluation during the actual prostate seed implant procedure was successfully applied to determine the need for additional seeds to correct dose deficiencies before anesthesia reversal. When applied, this approach should significantly reduce

Computation of mean and variance of the radiotherapy dose for PCA-modeled random shape and position variations of the target.

PubMed

Budiarto, E; Keijzer, M; Storchi, P R M; Heemink, A W; Breedveld, S; Heijmen, B J M

2014-01-20

Radiotherapy dose delivery in the tumor and surrounding healthy tissues is affected by movements and deformations of the corresponding organs between fractions. The random variations may be characterized by non-rigid, anisotropic principal component analysis (PCA) modes. In this article new dynamic dose deposition matrices, based on established PCA modes, are introduced as a tool to evaluate the mean and the variance of the dose at each target point resulting from any given set of fluence profiles. The method is tested for a simple cubic geometry and for a prostate case. The movements spread out the distributions of the mean dose and cause the variance of the dose to be highest near the edges of the beams. The non-rigidity and anisotropy of the movements are reflected in both quantities. The dynamic dose deposition matrices facilitate the inclusion of the mean and the variance of the dose in the existing fluence-profile optimizer for radiotherapy planning, to ensure robust plans with respect to the movements.

Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts.

PubMed

O'Donnell, Robert T; Ma, Yunpeng; McKnight, Hayes C; Pearson, David; Tuscano, Joseph M

2009-12-01

CD22 is a cell-surface adhesion molecule on most B-cell NHL, so it is a promising target for immunotherapy. HB22.7 is an anti-CD22 mAb that binds the two NH(2)-terminal immunoglobulin domains and specifically blocks the interaction of CD22 with its ligand. CD22-blocking mAbs induce apoptosis in neoplastic B-cells and are functionally distinguishable from other anti-CD22 mAbs. This study assessed the optimal dose, route, schedule, and the targeted CD22 epitope. Raji NHL-bearing nude mice were studied. A non-blocking anti-CD22 mAb (HB22.27) was used as a control. HB22.27 had minimal effect, whereas HB22.7 improved survival and shrank tumors substantially. HB22.7 doses greater than 1.4 mg/week did not further increase efficacy (or toxicity). Tumors less than 200 mm(3) had a higher response rate than did larger tumors. Various schedules of HB22.7 administration were tested; one dose every other week was more effective than more or less frequent dosing. Pharmacokinetic studies revealed that the half-life of HB22.7 was 28 days; this correlated with the time needed to re-populate cell-surface CD22 after treatment with HB22.7. Immuno-PET showed that NHL was rapidly and specifically targeted by copper-64-labeled-HB22.7. This study provided data as to an optimal dose, route, schedule and interval between doses of HB22.7.

Uniform heating of materials into the warm dense matter regime with laser-driven quasimonoenergetic ion beams

NASA Astrophysics Data System (ADS)

Bang, W.; Albright, B. J.; Bradley, P. A.; Vold, E. L.; Boettger, J. C.; Fernández, J. C.

2015-12-01

In a recent experiment at the Trident laser facility, a laser-driven beam of quasimonoenergetic aluminum ions was used to heat solid gold and diamond foils isochorically to 5.5 and 1.7 eV, respectively. Here theoretical calculations are presented that suggest the gold and diamond were heated uniformly by these laser-driven ion beams. According to calculations and SESAME equation-of-state tables, laser-driven aluminum ion beams achievable at Trident, with a finite energy spread of ΔE /E ˜20 %, are expected to heat the targets more uniformly than a beam of 140-MeV aluminum ions with zero energy spread. The robustness of the expected heating uniformity relative to the changes in the incident ion energy spectra is evaluated, and expected plasma temperatures of various target materials achievable with the current experimental platform are presented.

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

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

Bender, Edward T.

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

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

PubMed

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

SU-E-CAMPUS-I-06: Y90 PET/CT for the Instantaneous Determination of Both Target and Non-Target Absorbed Doses Following Hepatic Radioembolization

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

Pasciak, A; Kao, J

2014-06-15

Purpose The process of converting Yttrium-90 (Y90) PET/CT images into 3D absorbed dose maps will be explained. The simple methods presented will allow the medical physicst to analyze Y90 PET images following radioembolization and determine the absorbed dose to tumor, normal liver parenchyma and other areas of interest, without application of Monte-Carlo radiation transport or dose-point-kernel (DPK) convolution. Methods Absorbed dose can be computed from Y90 PET/CT images based on the premise that radioembolization is a permanent implant with a constant relative activity distribution after infusion. Many Y90 PET/CT publications have used DPK convolution to obtain 3D absorbed dose maps.more » However, this method requires specialized software limiting clinical utility. The Local Deposition method, an alternative to DPK convolution, can be used to obtain absorbed dose and requires no additional computer processing. Pixel values from regions of interest drawn on Y90 PET/CT images can be converted to absorbed dose (Gy) by multiplication with a scalar constant. Results There is evidence that suggests the Local Deposition method may actually be more accurate than DPK convolution and it has been successfully used in a recent Y90 PET/CT publication. We have analytically compared dose-volume-histograms (DVH) for phantom hot-spheres to determine the difference between the DPK and Local Deposition methods, as a function of PET scanner point-spread-function for Y90. We have found that for PET/CT systems with a FWHM greater than 3.0 mm when imaging Y90, the Local Deposition Method provides a more accurate representation of DVH, regardless of target size than DPK convolution. Conclusion Using the Local Deposition Method, post-radioembolization Y90 PET/CT images can be transformed into 3D absorbed dose maps of the liver. An interventional radiologist or a Medical Physicist can perform this transformation in a clinical setting, allowing for rapid prediction of treatment efficacy

Impact of Uniform Methods on Interlaboratory Antibody Titration Variability: Antibody Titration and Uniform Methods.

PubMed

Bachegowda, Lohith S; Cheng, Yan H; Long, Thomas; Shaz, Beth H

2017-01-01

-Substantial variability between different antibody titration methods prompted development and introduction of uniform methods in 2008. -To determine whether uniform methods consistently decrease interlaboratory variation in proficiency testing. -Proficiency testing data for antibody titration between 2009 and 2013 were obtained from the College of American Pathologists. Each laboratory was supplied plasma and red cells to determine anti-A and anti-D antibody titers by their standard method: gel or tube by uniform or other methods at different testing phases (immediate spin and/or room temperature [anti-A], and/or anti-human globulin [AHG: anti-A and anti-D]) with different additives. Interlaboratory variations were compared by analyzing the distribution of titer results by method and phase. -A median of 574 and 1100 responses were reported for anti-A and anti-D antibody titers, respectively, during a 5-year period. The 3 most frequent (median) methods performed for anti-A antibody were uniform tube room temperature (147.5; range, 119-159), uniform tube AHG (143.5; range, 134-150), and other tube AHG (97; range, 82-116); for anti-D antibody, the methods were other tube (451; range, 431-465), uniform tube (404; range, 382-462), and uniform gel (137; range, 121-153). Of the larger reported methods, uniform gel AHG phase for anti-A and anti-D antibodies had the most participants with the same result (mode). For anti-A antibody, 0 of 8 (uniform versus other tube room temperature) and 1 of 8 (uniform versus other tube AHG), and for anti-D antibody, 0 of 8 (uniform versus other tube) and 0 of 8 (uniform versus other gel) proficiency tests showed significant titer variability reduction. -Uniform methods harmonize laboratory techniques but rarely reduce interlaboratory titer variance in comparison with other methods.

A tuneable approach to uniform light distribution for artificial daylight photodynamic therapy.

PubMed

O'Mahoney, Paul; Haigh, Neil; Wood, Kenny; Brown, C Tom A; Ibbotson, Sally; Eadie, Ewan

2018-06-16

Implementation of daylight photodynamic therapy (dPDT) is somewhat limited by variable weather conditions. Light sources have been employed to provide artificial dPDT indoors, with low irradiances and longer treatment times. Uniform light distribution across the target area is key to ensuring effective treatment, particularly for large areas. A novel light source is developed with tuneable direction of light emission in order to meet this challenge. Wavelength composition of the novel light source is controlled such that the protoporphyrin-IX (PpIX) weighed spectra of both the light source and daylight match. The uniformity of the light source is characterised on a flat surface, a model head and a model leg. For context, a typical conventional PDT light source is also characterised. Additionally, the wavelength uniformity across the treatment site is characterised. The PpIX-weighted spectrum of the novel light source matches with PpIX-weighted daylight spectrum, with irradiance values within the bounds for effective dPDT. By tuning the direction of light emission, improvements are seen in the uniformity across large anatomical surfaces. Wavelength uniformity is discussed. We have developed a light source that addresses the challenges in uniform, multiwavelength light distribution for large area artificial dPDT across curved anatomical surfaces. Copyright © 2018. Published by Elsevier B.V.

Feasibility study on inverse four-dimensional dose reconstruction using the continuous dose-image of EPID

PubMed Central

Yeo, Inhwan Jason; Jung, Jae Won; Yi, Byong Yong; Kim, Jong Oh

2013-01-01

Purpose: When an intensity-modulated radiation beam is delivered to a moving target, the interplay effect between dynamic beam delivery and the target motion due to miss-synchronization can cause unpredictable dose delivery. The portal dose image in electronic portal imaging device (EPID) represents radiation attenuated and scattered through target media. Thus, it may possess information about delivered radiation to the target. Using a continuous scan (cine) mode of EPID, which provides temporal dose images related to target and beam movements, the authors’ goal is to perform four-dimensional (4D) dose reconstruction. Methods: To evaluate this hypothesis, first, the authors have derived and subsequently validated a fast method of dose reconstruction based on virtual beamlet calculations of dose responses using a test intensity-modulated beam. This method was necessary for processing a large number of EPID images pertinent for four-dimensional reconstruction. Second, cine mode acquisition after summation over all images was validated through comparison with integration mode acquisition on EPID (IAS3 and aS1000) for the test beam. This was to confirm the agreement of the cine mode with the integrated mode, specifically for the test beam, which is an accepted mode of image acquisition for dosimetry with EPID. Third, in-phantom film and exit EPID dosimetry was performed on a moving platform using the same beam. Heterogeneous as well as homogeneous phantoms were used. The cine images were temporally sorted at 10% interval. The authors have performed dose reconstruction to the in-phantom plane from the sorted cine images using the above validated method of dose reconstruction. The reconstructed dose from each cine image was summed to compose a total reconstructed dose from the test beam delivery, and was compared with film measurements. Results: The new method of dose reconstruction was validated showing greater than 95.3% pass rates of the gamma test with the criteria

Nonimaging reflectors for efficient uniform illumination.

PubMed

Gordon, J M; Kashin, P; Rabl, A

1992-10-01

Nonimaging reflectors that are an extension of the design principle that was developed for compound parabolic concentrator type devices are proposed for illumination applications. The optical designs presented offer maximal lighting efficiency while they retain sharp angular control of the radiation and highly uniform flux densities on distant target planes. Our results are presented for symmetrical configurations in two dimensions (troughlike reflectors) for flat and for tubular sources. For fields of view of practical interest (half-angle in the 30-60 degrees range), these devices can achieve minimum-tomaximum intensity ratios of 0.7, while they remain compact and incur low reflective losses.

Comparison of Kodak EDR2 and Gafchromic EBT film for intensity-modulated radiation therapy dose distribution verification.

PubMed

Sankar, A; Ayyangar, Komanduri M; Nehru, R Mothilal; Kurup, P G Gopalakrishna; Murali, V; Enke, Charles A; Velmurugan, J

2006-01-01

The quantitative dose validation of intensity-modulated radiation therapy (IMRT) plans require 2-dimensional (2D) high-resolution dosimetry systems with uniform response over its sensitive region. The present work deals with clinical use of commercially available self-developing Radio Chromic Film, Gafchromic EBT film, for IMRT dose verification. Dose response curves were generated for the films using a VXR-16 film scanner. The results obtained with EBT films were compared with the results of Kodak extended dose range 2 (EDR2) films. The EBT film had a linear response between the dose range of 0 to 600 cGy. The dose-related characteristics of the EBT film, such as post irradiation color growth with time, film uniformity, and effect of scanning orientation, were studied. There was up to 8.6% increase in the color density between 2 to 40 hours after irradiation. There was a considerable variation, up to 8.5%, in the film uniformity over its sensitive region. The quantitative differences between calculated and measured dose distributions were analyzed using DTA and Gamma index with the tolerance of 3% dose difference and 3-mm distance agreement. The EDR2 films showed consistent results with the calculated dose distributions, whereas the results obtained using EBT were inconsistent. The variation in the film uniformity limits the use of EBT film for conventional large-field IMRT verification. For IMRT of smaller field sizes (4.5 x 4.5 cm), the results obtained with EBT were comparable with results of EDR2 films.

SU-E-T-486: Effect of the Normalized Prescription Isodose Line On Target Dose Deficiency in Lung SBRT Based On Monte Carlo Calculation

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

Zheng, D; Zhang, Q; Zhou, S

Purpose: To investigate the impact of normalized prescription isodose line on target dose deficiency calculated with Monte Carlo (MC) vs. pencil Beam (PB) in lung SBRT. RTOG guidelines recommend prescription lines between 60% and 90% for lung SBRT. How this affects the magnitude of MC-calculated target dose deficiency has never been studied. Methods: Under an IRB-approved protocol, four lung SBRT patients were replanned following RTOG0813 by a single physicist. For each patient, four alternative plans were generated based on PB calculation prescribing to 60–90% isodose lines, respectively. Each plan consisted of 360o coplanar dynamic conformal arcs with beam apertures manuallymore » optimized to achieve similar dose coverage and conformity for all plans of the same patient. Dose distribution was calculated with MC and compared to that with PB. PTV dose-volume endpoints were compared, including Dmin, D5, Dmean, D95, and Dmax. PTV V100 coverage, conformity index (CI), and heterogeneity index (HI) were also evaluated. Results: For all 16 plans, median (range) PTV V100 and CI were 99.7% (97.5–100%) and 1.27 (1.20–1.41), respectively. As expected, lower prescription line resulted in higher target dose heterogeneity, yielding median (range) HI of 1.26 (1.05–1.51) for all plans. Comparing MC to PB, median (range) D95, Dmean, D5 PTV dose deficiency were 18.9% (11.2–23.2%), 15.6% (10.0–22.7%), and 9.4%(5.5–13.6%) of the prescription dose, respectively. The Dmean, D5, and Dmax deficiency was found to monotonically increase with decreasing prescription line from 90% to 60%, while the Dmin deficiency monotonically decreased. D95 deficiency exhibited more complex trend, reaching the largest deficiency at 80% for all patients. Conclusion: Dependence on prescription isodose line was found for MC-calculated PTV dose deficiency of lung SBRT. When comparing reported MC dose deficiency values from different institutions, their individual selections of prescription

Multiple anatomy optimization of accumulated dose

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

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

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

The application of polymer gel dosimeters to dosimetry for targeted radionuclide therapy

NASA Astrophysics Data System (ADS)

Gear, J. I.; Flux, G. D.; Charles-Edwards, E.; Partridge, M.; Cook, G.; Ott, R. J.

2006-07-01

There is a lack of standardized methodology to perform dose calculations for targeted radionuclide therapy and at present no method exists to objectively evaluate the various approaches employed. The aim of the work described here was to investigate the practicality and accuracy of calibrating polymer gel dosimeters such that dose measurements resulting from complex activity distributions can be verified. Twelve vials of the polymer gel dosimeter, 'MAGIC', were uniformly mixed with varying concentrations of P-32 such that absorbed doses ranged from 0 to 30 Gy after a period of 360 h before being imaged on a magnetic resonance scanner. In addition, nine vials were prepared and irradiated using an external 6 MV x-ray beam. Magnetic resonance transverse relaxation time, T2, maps were obtained using a multi-echo spin echo sequence and converted to R2 maps (where T2 = 1/R2). Absorbed doses for P-32 irradiated gel were calculated according to the medical internal radiation dose schema using EGSnrc Monte Carlo simulations. Here the energy deposited in cylinders representing the irradiated vials was scored. A relationship between dose and R2 was determined. Effects from oxygen contamination were present in the internally irradiated vials. An increase in O2 sensitivity over those gels irradiated externally was thought to be a result of the longer irradiation period. However, below the region of contamination dose response appeared homogenous. Due do a drop-off of dose at the periphery of the internally irradiated vials, magnetic resonance ringing artefacts were observed. The ringing did not greatly affect the accuracy of calibration, which was comparable for both methods. The largest errors in calculated dose originated from the initial activity measurements, and were approximately 10%. Measured R2 values ranged from 5-35 s-1 with an average standard deviation of 1%. A clear relationship between R2 and dose was observed, with up to 40% increased sensitivity for internally

Planning magnetic resonance imaging for prostate cancer intensity-modulated radiation therapy: Impact on target volumes, radiotherapy dose and androgen deprivation administration.

PubMed

Horsley, Patrick J; Aherne, Noel J; Edwards, Grace V; Benjamin, Linus C; Wilcox, Shea W; McLachlan, Craig S; Assareh, Hassan; Welshman, Richard; McKay, Michael J; Shakespeare, Thomas P

2015-03-01

Magnetic resonance imaging (MRI) scans are increasingly utilized for radiotherapy planning to contour the primary tumors of patients undergoing intensity-modulated radiation therapy (IMRT). These scans may also demonstrate cancer extent and may affect the treatment plan. We assessed the impact of planning MRI detection of extracapsular extension, seminal vesicle invasion, or adjacent organ invasion on the staging, target volume delineation, doses, and hormonal therapy of patients with prostate cancer undergoing IMRT. The records of 509 consecutive patients with planning MRI scans being treated with IMRT for prostate cancer between January 2010 and July 2012 were retrospectively reviewed. Tumor staging and treatment plans before and after MRI were compared. Of the 509 patients, 103 (20%) were upstaged and 44 (9%) were migrated to a higher risk category as a result of findings at MRI. In 94 of 509 patients (18%), the MRI findings altered management. Ninety-four of 509 patients (18%) had a change to their clinical target volume (CTV) or treatment technique, and in 41 of 509 patients (8%) the duration of hormone therapy was changed because of MRI findings. The use of radiotherapy planning MRI altered CTV design, dose and/or duration of androgen deprivation in 18% of patients in this large, single institution series of men planned for dose-escalated prostate IMRT. This has substantial implications for radiotherapy target volumes and doses, as well as duration of androgen deprivation. Further research is required to investigate whether newer MRI techniques can simultaneously fulfill staging and radiotherapy contouring roles. © 2014 Wiley Publishing Asia Pty Ltd.

Uniform amplification of phage display libraries in monodisperse emulsions.

PubMed

Matochko, Wadim L; Ng, Simon; Jafari, Mohammad R; Romaniuk, Joseph; Tang, Sindy K Y; Derda, Ratmir

2012-09-01

In this paper, we describe a complete experimental setup for the uniform amplification of libraries of phage. Uniform amplification, which multiplies every phage clone by the same amount irrespective of the growth rate of the clone is essential for phage-display screening. Amplification of phage libraries in a common solution is often non-uniform: it favors fast-growing clones and eliminates those that grow slower. This competition leads to elimination of many useful binding clones, and it is a major barrier to identification of ligands for targets with multiple binding sites such as cells, tissues, or mixtures of proteins. Uniform amplification is achieved by encapsulating individual phage clones into isolated compartments (droplets) of identical volume. Each droplet contains culture medium and an excess of host (Escherichia coli). Here, we describe microfluidics devices that generate mono-disperse droplet-based compartments, and optimal conditions for amplification of libraries of different size. We also describe the detailed synthesis of a perfluoro surfactant, which gives droplets exceptional stability. Droplets stabilized by this compound do not coalesce after many hours in shaking culture. We identified a commercially available compound (Krytox), which destabilizes these droplets to recover the amplified libraries. Overall, uniform amplification is a sequence of three simple steps: (1) encapsulation of mixture of phage and bacteria in droplets using microfluidics; (2) incubation of droplets in a shaking culture; (3) destabilization of droplets to harvest the amplified phage. We anticipate that this procedure can be easily adapted in any academic or industrial laboratory that uses phage display. Copyright © 2012 Elsevier Inc. All rights reserved.

Uniform heating of materials into the warm dense matter regime with laser-driven quasimonoenergetic ion beams

DOE PAGES

Bang, W.; Albright, B. J.; Bradley, P. A.; ...

2015-12-01

In a recent experiment at the Trident laser facility, a laser-driven beam of quasimonoenergetic aluminum ions was used to heat solid gold and diamond foils isochorically to 5.5 and 1.7 eV, respectively. Here theoretical calculations are presented that suggest the gold and diamond were heated uniformly by these laser-driven ion beams. According to calculations and SESAME equation-of-state tables, laser-driven aluminum ion beams achievable at Trident, with a finite energy spread of ΔE/E~20%, are expected to heat the targets more uniformly than a beam of 140-MeV aluminum ions with zero energy spread. As a result, the robustness of the expected heatingmore » uniformity relative to the changes in the incident ion energy spectra is evaluated, and expected plasma temperatures of various target materials achievable with the current experimental platform are presented.« less

Do School Uniforms Fit?

ERIC Educational Resources Information Center

White, Kerry A.

2000-01-01

In 1994, Long Beach (California) Unified School District began requiring uniforms in all elementary and middle schools. Now, half of all urban school systems and many suburban schools have uniform policies. Research on uniforms' effectiveness is mixed. Tightened dress codes may be just as effective and less litigious. (MLH)

Method and apparatus for uniformly concentrating solar flux for photovoltaic applications

DOEpatents

Jorgensen, Gary J.; Carasso, Meir; Wendelin, Timothy J.; Lewandowski, Allan A.

1992-01-01

A dish reflector and method for concentrating moderate solar flux uniformly on a target plane on a solar cell array, the dish having a stepped reflective surface that is characterized by a plurality of ring-like segments arranged about a common axis, and each segment having a concave spherical configuration.

Potential for intensity-modulated radiation therapy to permit dose escalation for canine nasal cancer.

PubMed

Vaudaux, Catherine; Schneider, Uwe; Kaser-Hotz, Barbara

2007-01-01

We evaluated the impact of inverse planned intensity-modulated radiation therapy (IMRT) on the dose-volume histograms (DVHs) and on the normal tissue complication probabilities (NTCPs) of brain and eyes in dogs with nasal tumors. Nine dogs with large, caudally located nasal tumors were planned using conventional techniques and inverse planned IMRT for a total prescribed dose of 52.5 Gy in 3.5 Gy fractions. The equivalent uniform dose for brain and eyes was calculated to estimate the normal tissue complication probability (NTCP) of these organs. The NTCP values as well as the DVHs were used to compare the treatment plans. The dose distribution in IMRT plans was more conformal than in conventional plans. The average dose delivered to one-third of the brain was 10 Gy lower with the IMRT plan compared with conventional planning. The mean partial brain volume receiving 43.6 Gy or more was reduced by 25.6% with IMRT. As a consequence, the NTCPs were also significantly lower in the IMRT plans. The mean NTCP of brain was two times lower and at least one eye could be saved in all patients planed with IMRT. Another possibility with IMRT is dose escalation in the target to improve tumor control while keeping the NTCPs at the same level as for conventional planning. Veterinary

SU-E-T-287: Dose Verification On the Variation of Target Volume and Organ at Risk in Preradiation Chemotherapy IMRT for Nasopharyngeal Cancer

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

Zhang, X; Kong, L; Wang, J

2015-06-15

Purpose: To quantify the target volume and organ at risk of nasopharyngeal carcinoma (NPC) patients with preradiation chemotherapy based on CT scanned during intensity-modulated radiotherapy (IMRT), and recalculate the dose distribution. Methods: Seven patients with NPC and preradiation chemotherapy, treated with IMRT (35 to 37 fractions) were reviewed. Repeat CT scanning was required to all of the patients during the radiotherapy, and the number of repeat CTs varies from 2 to 6. The plan CT and repeat CT were generated by different CT scanner. To ensure crespectively on the same IMPT plan. The real dose distribution was calculated by deformablemore » registration and weighted method in Raystation (v 4.5.1). The fraction of each dose is based on radiotherapy record. The volumetric and dose differences among these images were calculated for nascIpharyngeal tumor and retro-pharyngeal lymph nodes (GTV-NX), neck lymph nodes(GTV-ND), and parotid glands. Results: The volume variation in GTV-NX from CT1 to CT2 was 1.15±3.79%, and in GTV-LN −0.23±4.93%. The volume variation in left parotid from CT1 to CT2 was −6.79±11.91%, and in right parotid −3.92±8.80%. In patient 2, the left parotid volume were decreased remarkably, as a Result, the V30 and V40 of it were increased as well. Conclusion: The target volume of patients with NPC varied lightly during IMRT. It shows that preradiation chemotherapy can control the target volume variation and perform a good dose repeatability. Also, the decreasing volume of parotid in some patient might increase the dose of it, which might course potential complications.« less

Scalable uniform construction of highly conditional quantum gates

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

Ivanov, Svetoslav S.; Vitanov, Nikolay V.

2011-08-15

We present a scalable uniform technique for the construction of highly conditional multiply-controlled-not quantum gates of trapped ion qubits, such as the Toffoli gate, without using ancilla states and circuits of an exorbitant number of concatenated one- and two-qubit gates. Apart from the initial dressing of the internal qubit states with vibrational phonons and the final restoration of the phonon ground state, our technique requires the application of just a single composite pulse on the target qubit and is applicable both in and outside the Lamb-Dicke regime. We design special narrowband composite pulses, which suppress all transitions but the conditionalmore » transition of the target qubit; moreover, these composite pulses significantly improve the spatial addressing selectivity.« less

Human target acquisition performance

NASA Astrophysics Data System (ADS)

Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

2012-06-01

The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

Natural healing-inspired collagen-targeting surgical protein glue for accelerated scarless skin regeneration.

PubMed

Jeon, Eun Young; Choi, Bong-Hyuk; Jung, Dooyup; Hwang, Byeong Hee; Cha, Hyung Joon

2017-07-01

Skin scarring after deep dermal injuries is a major clinical problem due to the current therapies limited to established scars with poor understanding of healing mechanisms. From investigation of aberrations within the extracellular matrix involved in pathophysiologic scarring, it was revealed that one of the main factors responsible for impaired healing is abnormal collagen reorganization. Here, inspired by the fundamental roles of decorin, a collagen-targeting proteoglycan, in collagen remodeling, we created a scar-preventive collagen-targeting glue consisting of a newly designed collagen-binding mussel adhesive protein and a specific glycosaminoglycan. The collagen-targeting glue specifically bound to type I collagen in a dose-dependent manner and regulated the rate and the degree of fibrillogenesis. In a rat skin excisional model, the collagen-targeting glue successfully accelerated initial wound regeneration as defined by effective reepithelialization, neovascularization, and rapid collagen synthesis. Moreover, the improved dermal collagen architecture was demonstrated by uniform size of collagen fibrils, their regular packing, and a restoration of healthy tissue component. Collectively, our natural healing-inspired collagen-targeting glue may be a promising therapeutic option for improving the healing rate with high-quality and effective scar inhibition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pesticide Dose - A Parameter with Many Implications

USDA-ARS?s Scientific Manuscript database

Like pharmaceuticals, pesticides can have unintended effects, even when used at the proper dose. For pesticides, the possible effects are even more diverse, because the chemicals are released immediately into the environment and the dose reaching the intended target(s) and unintended targets can var...

Moderate-dose sedation and analgesia during targeted temperature management after cardiac arrest.

PubMed

May, Teresa L; Seder, David B; Fraser, Gilles L; Stone, Philip; McCrum, Barbara; Riker, Richard R

2015-02-01

Sedation and analgesia regimens during targeted temperature management (TTM), after cardiac arrest varies widely, are poorly described in the literature and may have a negative impact on outcome. Since implementing TTM in 2005, we have used moderate-dose sedation and describe our experience with this approach. In this retrospective review, we included patients treated with TTM for cardiac arrest at our institution for 2008-2012. Patients received TTM if they did not follow verbal commands following cardiac arrest, regardless of place of arrest or rhythm. Utstein-compatible data were prospectively entered into the International Cardiac Arrest Registry, supplemented by review of nursing, pharmacy, and physical therapy records. We report analgesic and sedative medications and doses during the 24 h of active TTM at 33 °C, resource utilization, and important clinical events. 166 patients treated with TTM after in- and out-of-hospital cardiac arrest with complete data were included. Overall survival was 42 %, median time to following commands was 3 h after rewarming (-6, 14), time to spontaneous breathing trial was 19 h (5-35), time to extubation was 28 h (9-60), and 59 % of survivors were discharged directly home at 13 (10-20) days. The incidence of seizure was 6 %, septic shock 4 %, and pneumonia 32 %. Four survivors required tracheostomy at 8, 8, 12, and 16 days. A moderate-dose sedation and analgesia regimen was well tolerated and effective during therapeutic hypothermia after cardiac arrest and is an effective alternative to very deep sedation. We recommend more complete description of sedation and analgesia protocols in future studies, including expanded outcome reporting to include variables affected by sedation therapy. Further study is required to define which sedation approach for TTM may be best.

Development and validation of an UPLC method for determination of content uniformity in low-dose solid drugs products using the design space approach.

PubMed

Oliva, Alexis; Fariña, José B; Llabrés, Matías

2013-10-15

A simple and reproducible UPLC method was developed and validated for the quantitative analysis of finasteride in low-dose drug products. Method validation demonstrated the reliability and consistency of analytical results. Due to the regulatory requirements of pharmaceutical analysis in particular, evaluation of robustness is vital to predict how small variations in operating conditions affect the responses. Response surface methodology as an optimization technique was used to evaluate the robustness. For this, a central composite design was implemented around the nominal conditions. Statistical treatment of the responses (retention factor and drug concentrations expressed as percentage of label claim) showed that methanol content in mobile-phase and flow rate were the most influential factors. In the optimization process, the compromise decision support problem (cDSP) strategy was used. Construction of the robust domain from response-surfaces provided tolerance windows for the factors affecting the effectiveness of the method. The specified limits for the USP uniformity of dosage units assay (98.5-101.5%) and the purely experimental variations based on the repeatability test for center points (nominal conditions repetitions) were used as criteria to establish the tolerance windows, which allowed definition design space (DS) of analytical method. Thus, the acceptance criteria values (AV) proposed by the USP-uniformity of assay only depend on the sampling error. If the variation in the responses corresponded to approximately twice the repeatability standard deviation, individual values for percentage label claim (%LC) response may lie outside the specified limits; this implies the data are not centered between the specified limits, and that this term plus the sampling error affects the AV value. To avoid this fact, the limits specified by the Uniformity of Dosage Form assay (i.e., 98.5-101.5%) must be taken into consideration to fix the tolerance windows for each

The influence of non-DNA-targeted effects on carbon ion–induced low-dose hyper-radiosensitivity in MRC-5 cells

PubMed Central

Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

2016-01-01

Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation–induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion–induced LDHRS. PMID:26559335

Edema worsens target coverage in high-dose-rate interstitial brachytherapy of mobile tongue cancer: a report of two cases.

PubMed

Yoshida, Ken; Yamazaki, Hideya; Kotsuma, Tadayuki; Akiyama, Hironori; Takenaka, Tadashi; Masui, Koji; Yoshioka, Yasuo; Uesugi, Yasuo; Shimbo, Taiju; Yoshikawa, Nobuhiko; Yoshioka, Hiroto; Arika, Takumi; Tanaka, Eiichi; Narumi, Yoshifumi

2017-02-01

We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. To treat the lateral side of the CTV, flexible applicator tubes were implanted on the mouth floor. Two-dimensional planning was performed using X-ray images for Case 1, and three-dimensional (3D) planning was performed using computed tomography (CT) for Case 2. Prescribed doses for both cases were 54 Gy in nine fractions. Case 1 was treated for cancer of the right lateral border of the tongue in 2005. Tongue edema occurred after implantation, and part of the lateral border of the tongue protruded between the applicator tubes. Acute mucosal reaction abated in the protruded area earlier than in the other parts of the CTV. In this case, the tumor recurred in this area 5 months after the treatment. Case 2 was treated for cancer of the left lateral border of the tongue. Because tongue edema occurred in this case also, plastic splints were inserted between the applicator tubes to push the edematous region into the irradiated area. The mucosal surface of the CTV was covered by the 70% isodose, and 100% isodose line for before and after splint insertion. Local control of the tumor was achieved 4 years after treatment. To ensure sufficient target coverage, 3D image-based planning using CT should be performed, followed by re-planning using repeated CT as needed. Also, the development of devices to prevent protrusion of the edematous tissue outside the target area will help to ensure the full dosing of CTV.

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

Multicentre dose audit for clinical trials of radiation therapy in Asia

PubMed Central

Fukuda, Shigekazu; Fukumura, Akifumi; Nakamura, Yuzuru-Kutsutani; Jianping, Cao; Cho, Chul-Koo; Supriana, Nana; Dung, To Anh; Calaguas, Miriam Joy; Devi, C.R. Beena; Chansilpa, Yaowalak; Banu, Parvin Akhter; Riaz, Masooma; Esentayeva, Surya; Kato, Shingo; Karasawa, Kumiko; Tsujii, Hirohiko

2017-01-01

Abstract A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy. PMID:27864507

Dose Titration Algorithm Tuning (DTAT) should supersede 'the' Maximum Tolerated Dose (MTD) in oncology dose-finding trials.

PubMed

Norris, David C

2017-01-01

Background . Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent 'confirmatory' Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of 'the' maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as 'dose-finding', but as dose titration algorithm (DTA) -finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug's population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace 'the' MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically in relation to

Evaluation of various boluses in dose distribution for electron therapy of the chest wall with an inward defect

PubMed Central

Mahdavi, Hoda; Jabbari, Keyvan; Roayaei, Mahnaz

2016-01-01

Delivering radiotherapy to the postmastectomy chest wall can be achieved using matched electron fields. Surgical defects of the chest wall change the dose distribution of electrons. In this study, the improvement of dose homogeneity using simple, nonconformal techniques of thermoplastic bolus application on a defect is evaluated. The proposed phantom design improves the capability of film dosimetry for obtaining dose profiles of a patient's anatomical condition. A modeled electron field of a patient with a postmastectomy inward surgical defect was planned. High energy electrons were delivered to the phantom in various settings, including no bolus, a bolus that filled the inward defect (PB0), a uniform thickness bolus of 5 mm (PB1), and two 5 mm boluses (PB2). A reduction of mean doses at the base of the defect was observed by any bolus application. PB0 increased the dose at central parts of the defect, reduced hot areas at the base of steep edges, and reduced dose to the lung and heart. Thermoplastic boluses that compensate a defect (PB0) increased the homogeneity of dose in a fixed depth from the surface; adversely, PB2 increased the dose heterogeneity. This study shows that it is practical to investigate dose homogeneity profiles inside a target volume for various techniques of electron therapy. PMID:27051169

Theoretical impact of insecticide-impregnated school uniforms on dengue incidence in Thai children.

PubMed

Massad, Eduardo; Amaku, Marcos; Coutinho, Francisco Antonio Bezerra; Kittayapong, Pattamaporn; Wilder-Smith, Annelies

2013-03-28

Children carry the main burden of morbidity and mortality caused by dengue. Children spend a considerable amount of their day at school; hence strategies that reduce human-mosquito contact to protect against the day-biting habits of Aedes mosquitoes at schools, such as insecticide-impregnated uniforms, could be an effective prevention strategy. We used mathematical models to calculate the risk of dengue infection based on force of infection taking into account the estimated proportion of mosquito bites that occur in school and the proportion of school time that children wear the impregnated uniforms. The use of insecticide-impregnated uniforms has efficacy varying from around 6% in the most pessimistic estimations, to 55% in the most optimistic scenarios simulated. Reducing contact between mosquito bites and human hosts via insecticide-treated uniforms during school time is theoretically effective in reducing dengue incidence and may be a valuable additional tool for dengue control in school-aged children. The efficacy of this strategy, however, is dependent on the compliance of the target population in terms of proper and consistent wearing of uniforms and, perhaps more importantly, the proportion of bites inflicted by the Aedes population during school time.

Feasibility study of stereotactic body radiotherapy for peripheral lung tumors with a maximum dose of 100 Gy in five fractions and a heterogeneous dose distribution in the planning target volume.

PubMed

Takeda, Atsuya; Oku, Yohei; Sanuki, Naoko; Eriguchi, Takahisa; Aoki, Yousuke; Enomoto, Tatsuji; Kaneko, Takeshi; Nishimura, Shuichi; Kunieda, Etsuo

2014-09-01

We evaluated toxicity and outcomes for patients with peripheral lung tumors treated with stereotactic body radiation therapy (SBRT) in a dose-escalation and dose-convergence study. A total of 15 patients were enrolled. SBRT was performed with 60 Gy in 5 fractions (fr.) prescribed to the 60% isodose line of maximum dose, which was 100 Gy in 5 fr., covering the planning target volume (PTV) surface (60 Gy/5 fr. - (60%-isodose)) using dynamic conformal multiple arc therapy (DCMAT). The primary endpoint was radiation pneumonitis (RP) ≥ Grade 2 within 6 months. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Using dose-volumetric analysis, the trial regimen of 60 Gy/5 fr. - (60%-isodose) was compared with our institutional conventional regimen of 50 Gy/5 fr. - (80%-isodose). The enrolled consecutive patients had either a solitary peripheral tumor or two ipsilateral tumors. The median follow-up duration was 22.0 (12.0-27.0) months. After 6 months post-SBRT, the respective number of RP Grade 0, 1 and 2 cases was 5, 9 and 1. In the Grade 2 RP patient, the image showed an organizing pneumonia pattern at 6.0 months post-SBRT. No other toxicity was found. At last follow-up, there was no evidence of recurrence of the treated tumors. The target volumes of 60 Gy/ 5 fr. - (60%-isodose) were irradiated with a significantly higher dose than those of 50 Gy/5 fr. - (80%-isodose), while the former dosimetric parameters of normal lung were almost equivalent to the latter. SBRT with 60 Gy/5 fr. - (60%-isodose) using DCMAT allowed the delivery of very high and convergent doses to peripheral lung tumors with feasibility in the acute and subacute phases. Further follow-up is required to assess for late toxicity. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Uniform Sampling Table Method and its Applications II--Evaluating the Uniform Sampling by Experiment.

PubMed

Chen, Yibin; Chen, Jiaxi; Chen, Xuan; Wang, Min; Wang, Wei

2015-01-01

A new method of uniform sampling is evaluated in this paper. The items and indexes were adopted to evaluate the rationality of the uniform sampling. The evaluation items included convenience of operation, uniformity of sampling site distribution, and accuracy and precision of measured results. The evaluation indexes included operational complexity, occupation rate of sampling site in a row and column, relative accuracy of pill weight, and relative deviation of pill weight. They were obtained from three kinds of drugs with different shape and size by four kinds of sampling methods. Gray correlation analysis was adopted to make the comprehensive evaluation by comparing it with the standard method. The experimental results showed that the convenience of uniform sampling method was 1 (100%), odds ratio of occupation rate in a row and column was infinity, relative accuracy was 99.50-99.89%, reproducibility RSD was 0.45-0.89%, and weighted incidence degree exceeded the standard method. Hence, the uniform sampling method was easy to operate, and the selected samples were distributed uniformly. The experimental results demonstrated that the uniform sampling method has good accuracy and reproducibility, which can be put into use in drugs analysis.

Non-Target Effect for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Doses of High LET Radiation

NASA Technical Reports Server (NTRS)

Hada, Megumi; George, Kerry A.; Cucinotta, F. A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (.01 - 0.2 Gy) of 170 MeV/u Si-28-ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The curves for doses above 0.1 Gy were more than one ion traverses a cell showed linear dose responses. However, for doses less than 0.1 Gy, Si-28-ions showed no dose response, suggesting a non-targeted effect when less than one ion traversal occurs. Additional findings for Fe-56 will be discussed.

Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model?☆

PubMed Central

Little, M.P.

2011-01-01

In this paper we review the evidence for departure from linearity for malignant and non-malignant disease and in the light of this assess likely mechanisms, and in particular the potential role for non-targeted effects. Excess cancer risks observed in the Japanese atomic bomb survivors and in many medically and occupationally exposed groups exposed at low or moderate doses are generally statistically compatible. For most cancer sites the dose–response in these groups is compatible with linearity over the range observed. The available data on biological mechanisms do not provide general support for the idea of a low dose threshold or hormesis. This large body of evidence does not suggest, indeed is not statistically compatible with, any very large threshold in dose for cancer, or with possible hormetic effects, and there is little evidence of the sorts of non-linearity in response implied by non-DNA-targeted effects. There are also excess risks of various types of non-malignant disease in the Japanese atomic bomb survivors and in other groups. In particular, elevated risks of cardiovascular disease, respiratory disease and digestive disease are observed in the A-bomb data. In contrast with cancer, there is much less consistency in the patterns of risk between the various exposed groups; for example, radiation-associated respiratory and digestive diseases have not been seen in these other (non-A-bomb) groups. Cardiovascular risks have been seen in many exposed populations, particularly in medically exposed groups, but in contrast with cancer there is much less consistency in risk between studies: risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well known (but unobserved) risk factors. In the absence of a convincing mechanistic explanation of epidemiological evidence that is, at present, less than persuasive, a cause-and-effect interpretation of the reported

A systematic review of dosing frequency with bone-targeted agents for patients with bone metastases from breast cancer

PubMed Central

Hutton, Brian; Addison, Christina L.; Campbell, Kaitryn; Fergusson, Dean; Mazarello, Sasha; Clemons, Mark

2013-01-01

Background Bone-targeted agents are usually administered to breast cancer patients with bone metastases every 3–4 weeks. Less frequent (‘de-escalated’) treatment may provide similar benefits with improved safety and reduced cost. Methods To systematically review randomised trials comparing de-escalated treatment with bone-targeted agents (i.e. every 12–16 weeks) to standard treatment (i.e. every 3–4 weeks), a formal systematic review of the literature was performed. Two individuals independently screened citations and full text articles. Random effects meta-analyses of clinically important outcomes were planned provided homogeneous studies were identified. Results Five relevant studies (n=1287 patients) were identified. Sample size ranged from 38 to 425. Information on outcomes including occurrence of SREs, bone pain, urinary N-telopeptide concentrations, serum C-telopeptide concentrations, pain medication use and safety outcomes was not consistently available. Two trials were non-inferiority studies, two dose-response evaluations and one was a pilot study. Bone-targeted agents use varied between studies, as did duration of prior therapy. Patient populations were considered heterogeneous in several ways, and thus no meta-analyses were performed. Observations from the included studies suggest there is potential that 3 month de-escalated treatment may provide similar benefits compared to 3–4 weekly treatment and that lower doses of zoledronic acid and denosumab might be equally effective. Conclusions Studies comparing standard and de-escalated treatment with bone-targeted agents in breast cancer are rare. The benefits of standard treatment compared to de-escalated therapy on important clinical outcomes remain unclear. Future pragmatic studies must be conducted to determine the merits of this approach. PMID:26909282

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

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

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi

2012-09-15

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase weremore » extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10

Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

NASA Astrophysics Data System (ADS)

Dant, James T.; Richardson, Richard B.; Nie, Linda H.

2013-05-01

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions

PubMed Central

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René

2015-01-01

Abstract Background: Spiromax® is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide–formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Methods: Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Results: Mean values for both budesonide and formoterol were within 85%–115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. Conclusions: DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions.

PubMed

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René; Chrystyn, Henry

2015-10-01

Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment.

A global, comprehensive review of literature related to paper recycling: A pressing need for a uniform system of terms and definitions.

PubMed

Ervasti, Ilpo; Miranda, Ruben; Kauranen, Ilkka

2016-02-01

A global, comprehensive review of terms and definitions related to paper recycling was conducted in this article. Terms and definitions related to paper recycling have varied in the course of time. Different terms and different definitions for the same thing are being used in different geographical regions and by different organizations. Definitions are different based on varying conceptions of waste paper as a raw material. Definitions of how to make various calculations related to paper recycling activity are inconsistent. Even such fundamental basic definitions like how to calculate recycling rate and paper consumption are not uniform. It could be concluded that there is no uniform system of terms and definitions related to paper recycling and the implications of this deficiency are profound. For example, it is difficult to reliably compare with each other statistics from different times and from different geographical regions. It is not possible to measure if targets for recycling activities are met if the terms describing the targets are not uniformly defined. In cases of reporting data for recycling targets, the lack of uniform terminology can, for example, impede the necessary transparency between different stakeholders and may allow for deception. The authors conclude there is a pressing need to develop a uniform system of terms and definition for terms related to paper recycling. Copyright © 2015 Elsevier Ltd. All rights reserved.

UNIFORMLY MOST POWERFUL BAYESIAN TESTS

PubMed Central

Johnson, Valen E.

2014-01-01

Uniformly most powerful tests are statistical hypothesis tests that provide the greatest power against a fixed null hypothesis among all tests of a given size. In this article, the notion of uniformly most powerful tests is extended to the Bayesian setting by defining uniformly most powerful Bayesian tests to be tests that maximize the probability that the Bayes factor, in favor of the alternative hypothesis, exceeds a specified threshold. Like their classical counterpart, uniformly most powerful Bayesian tests are most easily defined in one-parameter exponential family models, although extensions outside of this class are possible. The connection between uniformly most powerful tests and uniformly most powerful Bayesian tests can be used to provide an approximate calibration between p-values and Bayes factors. Finally, issues regarding the strong dependence of resulting Bayes factors and p-values on sample size are discussed. PMID:24659829

Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials

PubMed Central

Norris, David C.

2017-01-01

Background. Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent ‘confirmatory’ Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of ‘the’ maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as ‘dose-finding’, but as dose titration algorithm (DTA)-finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug’s population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace ‘the’ MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically

Enhancement of thickness uniformity of thin films grown by pulsed laser deposition

NASA Technical Reports Server (NTRS)

Fernandez, Felix E.

1995-01-01

A peculiarity of the pulsed laser deposition technique of thin-film growth which limits its applicability is the very rapid drop of resulting film thickness as a function of distance from the deposition axis. This is due to the narrow forward peaking of the emission plume characteristic of the laser ablation process. The plume is usually modeled by a cos(sup n) theta function with n greater, and in some cases, much higher, than 1. Based on this behavior, a method is presented to substantially enhance coverage uniformity in substrate zones of the order of the target-substrate distance h, and to within a specified thickness tolerance. Essentially, target irradiation is caused to form an annular emission source instead of the usual spot. By calculating the resulting thickness profiles, an optimum radius s is found for the annular source, corresponding to a given power in the emission characteristic and a given value of h. The radius of this annulus scales with h. Calculated numerical results for optimal s/h ratios corresponding to a wide range of values for n are provided for the case of +/- 1% tolerance in deviation from the thickness at deposition axis. Manners of producing annular illumination of the target by means of conic optics are presented for the case of a laser beam with radially symmetric profile. The region of uniform coverage at the substrate can be further augmented by extension of the method to multiple concentric annular sources. By using a conic optic of novel design, it is shown also how a single-laser beam can be focused onto a target in the required manner. Applicability of the method would be limited in practice by the available laser power. On the other hand, the effective emitting area can be large, which favors extremely high growth rates, and since growth can occur uniformly over the whole substrate for each laser pulse, single-shot depositions with substantial thicknesses are possible. In addition, the simultaneity of growth over the

Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor.

PubMed

Yoon, Hong Yeol; Shin, Min Lee; Shim, Man Kyu; Lee, Sangmin; Na, Jin Hee; Koo, Heebeom; Lee, Hyukjin; Kim, Jong-Ho; Lee, Kuen Yong; Kim, Kwangmeyung; Kwon, Ick Chan

2017-05-01

Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-CNPs) and integrin α v β 3 with cyclic RGD-conjugated CNPs (cRGD-CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN-CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD-CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN-CNPs could bind artificial azide reporters on tumor cells more uniformly (∼92.9%) compared to cRGD-CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy.

Method for mounting laser fusion targets for irradiation

DOEpatents

Fries, R. Jay; Farnum, Eugene H.; McCall, Gene H.

1977-07-26

Methods for preparing laser fusion targets of the ball-and-disk type are disclosed. Such targets are suitable for irradiation with one or two laser beams to produce the requisite uniform compression of the fuel material.

Target dose conformity in 3-dimensional conformal radiotherapy and intensity modulated radiotherapy.

PubMed

Wu, Vincent W C; Kwong, Dora L W; Sham, Jonathan S T

2004-05-01

Dose conformity to the planning target volume is an important criterion in radiotherapy treatment planning, for which the conformity index is a useful assessment tool. The purpose of this study is to compare the differences in CI for the treatment planning of four cancers including the nasopharynx, oesophagus, lung and prostate. Seventy patients with cancers of nasopharynx (30), oesophagus (15), lung (15) and prostate (10) were recruited. Each of these patients was planned with three sets of treatment plans using the FOCUS treatment planning system: the forward and inverse 3DCRT plans and the IMRT plan. The CI was generated for each treatment plan. The mean CI from each cancer patient group was calculated and compared with the other three cancer groups. The mean value of CI was also compared among the three planning methods. The oesophageal and lung cancers demonstrated relatively higher overall mean CI values (0.64 and 0.62, respectively), whereas that of the nasopharynx and prostate were lower (0.54 and 0.50, respectively). With regards to the planning method groups, the IMRT plans produced the highest overall mean CI (0.62), while those for the forward and inverse 3DCRT were similar (0.57 and 0.55, respectively). For the four selected cancers, oesophageal and lung cancers were easier to conform than the nasopharyngeal and prostate cancers. The IMRT plans were more effective in achieving better dose conformity than that of the 3DCRT.

Factor analysis in optimization of formulation of high content uniformity tablets containing low dose active substance.

PubMed

Lukášová, Ivana; Muselík, Jan; Franc, Aleš; Goněc, Roman; Mika, Filip; Vetchý, David

2017-11-15

Warfarin is intensively discussed drug with narrow therapeutic range. There have been cases of bleeding attributed to varying content or altered quality of the active substance. Factor analysis is useful for finding suitable technological parameters leading to high content uniformity of tablets containing low amount of active substance. The composition of tabletting blend and technological procedure were set with respect to factor analysis of previously published results. The correctness of set parameters was checked by manufacturing and evaluation of tablets containing 1-10mg of warfarin sodium. The robustness of suggested technology was checked by using "worst case scenario" and statistical evaluation of European Pharmacopoeia (EP) content uniformity limits with respect to Bergum division and process capability index (Cpk). To evaluate the quality of active substance and tablets, dissolution method was developed (water; EP apparatus II; 25rpm), allowing for statistical comparison of dissolution profiles. Obtained results prove the suitability of factor analysis to optimize the composition with respect to batches manufactured previously and thus the use of metaanalysis under industrial conditions is feasible. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation of a novel fixed dose combination of salmeterol xinafoate and mometasone furoate for inhaled drug delivery.

PubMed

Liu, Sha; Watts, Alan B; Du, Ju; Bui, Amanda; Hengsawas, Soraya; Peters, Jay I; Williams, Robert O

2015-10-01

Co-administration of an inhaled corticosteroid and long acting beta agonist for chronic obstructive pulmonary disease has reduced mortality compared to either drug alone. This combination reduces exacerbations, hospitalization, emergency department visits and health care costs. A novel fixed-dose combination of the long acting beta-2 agonist salmeterol xinafoate (SX) and the corticosteroid mometasone furoate (MF) were prepared in a composite particle formulation as brittle matrix powder (BMP) and investigated for suitability as an inhaled combination product. In this study, BMP fixed dose combinations of SX and MF with or without stabilizing excipients (lactose, mannitol, glycine and trehalose) were prepared and characterized with respect to their thermal properties, morphology, aerodynamic performance and physical stability. BMP combination formulations of SX and MF exhibited improved aerodynamic properties when delivered by dry powder inhalation as compared to the micronized blends of the same substances. Aerodynamic evaluation was carried out by next generation pharmaceutical impactor (NGI) with a marketed DPI device. Results demonstrated that co-deposition occurred when SX and MF were formulated together as composite particles in a BMP, while physical blends resulted in inconsistent deposition and dose uniformity. As a result of the bottom-up particle engineering approach, combination BMP formulations allow for dual API composite formulations to be dispersed as aerosolized particles. Aerosolized BMP combination formulations resulted in delivered dose uniformity and co-deposition of each API. Further, an excipient-free formulation, BMP SXMF, delivered approximately 50% of the loaded dose in the respirable range and demonstrated stability at ambient conditions for 6months. Single dose 24-h pharmacokinetic studies in rats demonstrated that lung tissue deposition and blood circulation (AUC0-24h) of two APIs were higher for the BMP combination group exhibiting a

Impact of tumour motion compensation and delineation methods on FDG PET-based dose painting plan quality for NSCLC radiation therapy.

PubMed

Thomas, Hannah Mary; Kinahan, Paul E; Samuel, James Jebaseelan E; Bowen, Stephen R

2018-02-01

To quantitatively estimate the impact of different methods for both boost volume delineation and respiratory motion compensation of [18F] FDG PET/CT images on the fidelity of planned non-uniform 'dose painting' plans to the prescribed boost dose distribution. Six locally advanced non-small cell lung cancer (NSCLC) patients were retrospectively reviewed. To assess the impact of respiratory motion, time-averaged (3D AVG), respiratory phase-gated (4D GATED) and motion-encompassing (4D MIP) PET images were used. The boost volumes were defined using manual contour (MANUAL), fixed threshold (FIXED) and gradient search algorithm (GRADIENT). The dose painting prescription of 60 Gy base dose to the planning target volume and an integral dose of 14 Gy (total 74 Gy) was discretized into seven treatment planning substructures and linearly redistributed according to the relative SUV at every voxel in the boost volume. Fifty-four dose painting plan combinations were generated and conformity was evaluated using quality index VQ0.95-1.05, which represents the sum of planned dose voxels within 5% deviation from the prescribed dose. Trends in plan quality and magnitude of achievable dose escalation were recorded. Different segmentation techniques produced statistically significant variations in maximum planned dose (P < 0.02), as well as plan quality between segmentation methods for 4D GATED and 4D MIP PET images (P < 0.05). No statistically significant differences in plan quality and maximum dose were observed between motion-compensated PET-based plans (P > 0.75). Low variability in plan quality was observed for FIXED threshold plans, while MANUAL and GRADIENT plans achieved higher dose with lower plan quality indices. The dose painting plans were more sensitive to segmentation of boost volumes than PET motion compensation in this study sample. Careful consideration of boost target delineation and motion compensation strategies should guide the design of NSCLC dose

Sensitivity of postplanning target and OAR coverage estimates to dosimetric margin distribution sampling parameters.

PubMed

Xu, Huijun; Gordon, J James; Siebers, Jeffrey V

2011-02-01

A dosimetric margin (DM) is the margin in a specified direction between a structure and a specified isodose surface, corresponding to a prescription or tolerance dose. The dosimetric margin distribution (DMD) is the distribution of DMs over all directions. Given a geometric uncertainty model, representing inter- or intrafraction setup uncertainties or internal organ motion, the DMD can be used to calculate coverage Q, which is the probability that a realized target or organ-at-risk (OAR) dose metric D, exceeds the corresponding prescription or tolerance dose. Postplanning coverage evaluation quantifies the percentage of uncertainties for which target and OAR structures meet their intended dose constraints. The goal of the present work is to evaluate coverage probabilities for 28 prostate treatment plans to determine DMD sampling parameters that ensure adequate accuracy for postplanning coverage estimates. Normally distributed interfraction setup uncertainties were applied to 28 plans for localized prostate cancer, with prescribed dose of 79.2 Gy and 10 mm clinical target volume to planning target volume (CTV-to-PTV) margins. Using angular or isotropic sampling techniques, dosimetric margins were determined for the CTV, bladder and rectum, assuming shift invariance of the dose distribution. For angular sampling, DMDs were sampled at fixed angular intervals w (e.g., w = 1 degree, 2 degrees, 5 degrees, 10 degrees, 20 degrees). Isotropic samples were uniformly distributed on the unit sphere resulting in variable angular increments, but were calculated for the same number of sampling directions as angular DMDs, and accordingly characterized by the effective angular increment omega eff. In each direction, the DM was calculated by moving the structure in radial steps of size delta (=0.1, 0.2, 0.5, 1 mm) until the specified isodose was crossed. Coverage estimation accuracy deltaQ was quantified as a function of the sampling parameters omega or omega eff and delta. The

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

NASA Astrophysics Data System (ADS)

Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.

2008-05-01

The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients

Theoretical impact of insecticide-impregnated school uniforms on dengue incidence in Thai children

PubMed Central

Massad, Eduardo; Amaku, Marcos; Coutinho, Francisco Antonio Bezerra; Kittayapong, Pattamaporn; Wilder-Smith, Annelies

2013-01-01

Background Children carry the main burden of morbidity and mortality caused by dengue. Children spend a considerable amount of their day at school; hence strategies that reduce human–mosquito contact to protect against the day-biting habits of Aedes mosquitoes at schools, such as insecticide-impregnated uniforms, could be an effective prevention strategy. Methodology We used mathematical models to calculate the risk of dengue infection based on force of infection taking into account the estimated proportion of mosquito bites that occur in school and the proportion of school time that children wear the impregnated uniforms. Principal findings The use of insecticide-impregnated uniforms has efficacy varying from around 6% in the most pessimistic estimations, to 55% in the most optimistic scenarios simulated. Conclusions Reducing contact between mosquito bites and human hosts via insecticide-treated uniforms during school time is theoretically effective in reducing dengue incidence and may be a valuable additional tool for dengue control in school-aged children. The efficacy of this strategy, however, is dependent on the compliance of the target population in terms of proper and consistent wearing of uniforms and, perhaps more importantly, the proportion of bites inflicted by the Aedes population during school time. PMID:23541045

Feasibility and Initial Dosimetric Findings for a Randomized Trial Using Dose-Painted Multiparametric Magnetic Resonance Imaging–Defined Targets in Prostate Cancer

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

Bossart, Elizabeth L., E-mail: EBossart@med.miami.edu; Stoyanova, Radka; Sandler, Kiri

2016-06-01

Purpose: To compare dosimetric characteristics with multiparametric magnetic resonance imaging–identified imaging tumor volume (gross tumor volume, GTV), prostate clinical target volume and planning target volume, and organs at risk (OARs) for 2 treatment techniques representing 2 arms of an institutional phase 3 randomized trial of hypofractionated external beam image guided highly targeted radiation therapy. Methods and Materials: Group 1 (n=20) patients were treated before the trial inception with the standard dose prescription. Each patient had an additional treatment plan generated per the experimental arm. A total of 40 treatment plans were compared (20 plans for each technique). Group 2 (n=15)more » consists of patients currently accrued to the hypofractionated external beam image guided highly targeted radiation therapy trial. Plans were created as per the treatment arm, with additional plans for 5 of the group 2 experimental arm with a 3-mm expansion in the imaging GTV. Results: For all plans in both patient groups, planning target volume coverage ranged from 95% to 100%; GTV coverage of 89.3 Gy for the experimental treatment plans ranged from 95.2% to 99.8%. For both groups 1 and 2, the percent volumes of rectum/anus and bladder receiving 40 Gy, 65 Gy, and 80 Gy were smaller in the experimental plans than in the standard plans. The percent volume at 1 Gy per fraction and 1.625 Gy per fraction were compared between the standard and the experimental arms, and these were found to be equivalent. Conclusions: The dose per fraction to the OARs can be made equal even when giving a large simultaneous integrated boost to the GTV. The data suggest that a GTV margin may be added without significant dose effects on the OARs.« less

Automated optimization of an aspheric light-emitting diode lens for uniform illumination.

PubMed

Luo, Xiaoxia; Liu, Hua; Lu, Zhenwu; Wang, Yao

2011-07-10

In this paper, an automated optimization method in the sequential mode of ZEMAX is proposed in the design of an aspheric lens with uniform illuminance for an LED source. A feedback modification is introduced in the design for the LED extended source. The user-defined merit function is written out by using ZEMAX programming language macros language and, as an example, optimum parameters of an aspheric lens are obtained via running an optimization. The optical simulation results show that the illumination efficiency and uniformity can reach 83% and 90%, respectively, on a target surface of 40 mm diameter and at 60 mm away for a 1×1 mm LED source. © 2011 Optical Society of America

46 CFR 310.11 - Cadet uniforms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... for State, Territorial or Regional Maritime Academies and Colleges § 310.11 Cadet uniforms. Cadet uniforms shall be supplied at the school in accordance with the uniform regulations of the School. Those... 46 Shipping 8 2010-10-01 2010-10-01 false Cadet uniforms. 310.11 Section 310.11 Shipping MARITIME...

46 CFR 310.11 - Cadet uniforms.

Code of Federal Regulations, 2011 CFR

2011-10-01

... for State, Territorial or Regional Maritime Academies and Colleges § 310.11 Cadet uniforms. Cadet uniforms shall be supplied at the school in accordance with the uniform regulations of the School. Those... 46 Shipping 8 2011-10-01 2011-10-01 false Cadet uniforms. 310.11 Section 310.11 Shipping MARITIME...

46 CFR 310.11 - Cadet uniforms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... for State, Territorial or Regional Maritime Academies and Colleges § 310.11 Cadet uniforms. Cadet uniforms shall be supplied at the school in accordance with the uniform regulations of the School. Those... 46 Shipping 8 2013-10-01 2013-10-01 false Cadet uniforms. 310.11 Section 310.11 Shipping MARITIME...

46 CFR 310.11 - Cadet uniforms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... for State, Territorial or Regional Maritime Academies and Colleges § 310.11 Cadet uniforms. Cadet uniforms shall be supplied at the school in accordance with the uniform regulations of the School. Those... 46 Shipping 8 2012-10-01 2012-10-01 false Cadet uniforms. 310.11 Section 310.11 Shipping MARITIME...

46 CFR 310.11 - Cadet uniforms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... for State, Territorial or Regional Maritime Academies and Colleges § 310.11 Cadet uniforms. Cadet uniforms shall be supplied at the school in accordance with the uniform regulations of the School. Those... 46 Shipping 8 2014-10-01 2014-10-01 false Cadet uniforms. 310.11 Section 310.11 Shipping MARITIME...

Comparison of two leading uniform theories of edge diffraction with the exact uniform asymptotic solution

NASA Technical Reports Server (NTRS)

Boersma, J.; Rahmat-Samii, Y.

1980-01-01

The diffraction of an arbitrary cylindrical wave by a half-plane has been treated by Rahmat-Samii and Mittra who used a spectral domain approach. In this paper, their exact solution for the total field is expressed in terms of a new integral representation. For large wave number k, two rigorous procedures are described for the exact uniform asymptotic expansion of the total field solution. The uniform expansions obtained are valid in the entire space, including transition regions around the shadow boundaries. The final results are compared with the formulations of two leading uniform theories of edge diffraction, namely, the uniform asymptotic theory and the uniform theory of diffraction. Some unique observations and conclusions are made in relating the two theories.

Gliding Motility of Mycoplasma mobile on Uniform Oligosaccharides.

PubMed

Kasai, Taishi; Hamaguchi, Tasuku; Miyata, Makoto

2015-09-01

The binding and gliding of Mycoplasma mobile on a plastic plate covered by 53 uniform oligosaccharides were analyzed. Mycoplasmas bound to and glided on only 21 of the fixed sialylated oligosaccharides (SOs), showing that sialic acid is essential as the binding target. The affinities were mostly consistent with our previous results on the inhibitory effects of free SOs and suggested that M. mobile recognizes SOs from the nonreducing end with four continuous sites as follows. (i and ii) A sialic acid at the nonreducing end is tightly recognized by tandemly connected two sites. (iii) The third site is recognized by a loose groove that may be affected by branches. (iv) The fourth site is recognized by a large groove that may be enhanced by branches, especially those with a negative charge. The cells glided on uniform SOs in manners apparently similar to those of the gliding on mixed SOs. The gliding speed was related inversely to the mycoplasma's affinity for SO, suggesting that the detaching step may be one of the speed determinants. The cells glided faster and with smaller fluctuations on the uniform SOs than on the mixtures, suggesting that the drag caused by the variation in SOs influences gliding behaviors. Mycoplasma is a group of bacteria generally parasitic to animals and plants. Some Mycoplasma species form a protrusion at a pole, bind to solid surfaces, and glide in the direction of the protrusion. These procedures are essential for parasitism. Usually, mycoplasmas glide on mixed sialylated oligosaccharides (SOs) derived from glycoprotein and glycolipid. Since gliding motility on uniform oligosaccharides has never been observed, this study gives critical information about recognition and interaction between receptors and SOs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

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

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

Purpose: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. Methods: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTV{sub PET}) was calculated from {sup 18}FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number ofmore » fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTV{sub PET} inevitably leads to overdosing, which was compared for both optimization schemes. Results: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTV{sub PET} (worst

Should School Nurses Wear Uniforms?

ERIC Educational Resources Information Center

Journal of School Health, 2001

2001-01-01

This 1958 paper questions whether school nurses should wear uniforms (specifically, white uniforms). It concludes that white uniforms are often associated with the treatment of ill people, and since many people have a fear reaction to them, they are not necessary and are even undesirable. Since school nurses are school staff members, they should…

Arc-based smoothing of ion beam intensity on targets

DOE PAGES

Friedman, Alex

2012-06-20

Manipulating a set of ion beams upstream of a target, makes it possible to arrange a smoother deposition pattern, so as to achieve more uniform illumination of the target. A uniform energy deposition pattern is important for applications including ion-beam-driven high energy density physics and heavy-ion beam-driven inertial fusion energy (“heavy-ion fusion”). Here, we consider an approach to such smoothing that is based on rapidly “wobbling” each of the beams back and forth along a short arc-shaped path, via oscillating fields applied upstream of the final pulse compression. In this technique, uniformity is achieved in the time-averaged sense; this ismore » sufficient provided the beam oscillation timescale is short relative to the hydrodynamic timescale of the target implosion. This work builds on two earlier concepts: elliptical beams applied to a distributed-radiator target [D. A. Callahan and M. Tabak, Phys. Plasmas 7, 2083 (2000)] and beams that are wobbled so as to trace a number of full rotations around a circular or elliptical path [R. C. Arnold et al., Nucl. Instrum. Methods 199, 557 (1982)]. Here, we describe the arc-based smoothing approach and compare it to results obtainable using an elliptical-beam prescription. In particular, we assess the potential of these approaches for minimization of azimuthal asymmetry, for the case of a ring of beams arranged on a cone. We also found that, for small numbers of beams on the ring, the arc-based smoothing approach offers superior uniformity. In contrast with the full-rotation approach, arc-based smoothing remains usable when the geometry precludes wobbling the beams around a full circle, e.g., for the X-target [E. Henestroza, B. G. Logan, and L. J. Perkins, Phys. Plasmas 18, 032702 (2011)] and some classes of distributed-radiator targets.« less

Helical tomotherapy for radiotherapy in esophageal cancer: a preferred plan with better conformal target coverage and more homogeneous dose distribution.

PubMed

Chen, Yi-Jen; Liu, An; Han, Chunhui; Tsai, Peter T; Schultheiss, Timothy E; Pezner, Richard D; Vora, Nilesh; Lim, Dean; Shibata, Stephen; Kernstine, Kemp H; Wong, Jeffrey Y C

2007-01-01

We compare different radiotherapy techniques-helical tomotherapy (tomotherapy), step-and-shoot IMRT (IMRT), and 3-dimensional conformal radiotherapy (3DCRT)-for patients with mid-distal esophageal carcinoma on the basis of dosimetric analysis. Six patients with locally advanced mid-distal esophageal carcinoma were treated with neoadjuvant chemoradiation followed by surgery. Radiotherapy included 50 Gy to gross planning target volume (PTV) and 45 Gy to elective PTV in 25 fractions. Tomotherapy, IMRT, and 3DCRT plans were generated. Dose-volume histograms (DVHs), homogeneity index (HI), volumes of lung receiving more than 10, 15, or 20 Gy (V(10), V(15), V(20)), and volumes of heart receiving more than 30 or 45 Gy (V(30), V(45)) were determined. Statistical analysis was performed by paired t-tests. By isodose distributions and DVHs, tomotherapy plans showed sharper dose gradients, more conformal coverage, and better HI for both gross and elective PTVs compared with IMRT or 3DCRT plans. Mean V(20) of lung was significantly reduced in tomotherapy plans. However, tomotherapy and IMRT plans resulted in larger V(10) of lung compared to 3DCRT plans. The heart was significantly spared in tomotherapy and IMRT plans compared to 3DCRT plans in terms of V(30) and V(45). We conclude that tomotherapy plans are superior in terms of target conformity, dose homogeneity, and V(20) of lung.

Less is more: Patient-level meta-analysis reveals paradoxical dose-response effects of a computer-based social anxiety intervention targeting attentional bias.

PubMed

Price, Rebecca B; Kuckertz, Jennie M; Amir, Nader; Bar-Haim, Yair; Carlbring, Per; Wallace, Meredith L

2017-12-01

The past decade of research has seen considerable interest in computer-based approaches designed to directly target cognitive mechanisms of anxiety, such as attention bias modification (ABM). By pooling patient-level datasets from randomized controlled trials of ABM that utilized a dot-probe training procedure, we assessed the impact of training "dose" on relevant outcomes among a pooled sample of 693 socially anxious adults. A paradoxical effect of the number of training trials administered was observed for both posttraining social anxiety symptoms and behavioral attentional bias (AB) toward threat (the target mechanism of ABM). Studies administering a large (>1,280) number of training trials showed no benefit of ABM over control conditions, while those administering fewer training trials showed significant benefit for ABM in reducing social anxiety (P = .02). These moderating effects of dose were not better explained by other examined variables and previously identified moderators, including patient age, training setting (laboratory vs. home), or type of anxiety assessment (clinician vs. self-report). Findings inform the optimal dosing for future dot-probe style ABM applications in both research and clinical settings, and suggest several novel avenues for further research. © 2017 Wiley Periodicals, Inc.

Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

PubMed Central

2014-01-01

Introduction The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response. Methods The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L). Results Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5). Conclusions This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in

Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements

PubMed Central

Whitaker, May

2016-01-01

Purpose Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. Material and methods This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. Results The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. Conclusions The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected. PMID:27504129

Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements.

PubMed

Poder, Joel; Whitaker, May

2016-06-01

Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected.

Whole-body voxel-based personalized dosimetry: Multiple voxel S-value approach for heterogeneous media with non-uniform activity distributions.

PubMed

Lee, Min Sun; Kim, Joong Hyun; Paeng, Jin Chul; Kang, Keon Wook; Jeong, Jae Min; Lee, Dong Soo; Lee, Jae Sung

2017-12-14

Personalized dosimetry with high accuracy is becoming more important because of the growing interests in personalized medicine and targeted radionuclide therapy. Voxel-based dosimetry using dose point kernel or voxel S-value (VSV) convolution is available. However, these approaches do not consider medium heterogeneity. Here, we propose a new method for whole-body voxel-based personalized dosimetry for heterogeneous media with non-uniform activity distributions, which is referred to as the multiple VSV approach. Methods: The multiple numbers (N) of VSVs for media with different densities covering the whole-body density ranges were used instead of using only a single VSV for water. The VSVs were pre-calculated using GATE Monte Carlo simulation; those were convoluted with the time-integrated activity to generate density-specific dose maps. Computed tomography-based segmentation was conducted to generate binary maps for each density region. The final dose map was acquired by the summation of N segmented density-specific dose maps. We tested several sets of VSVs with different densities: N = 1 (single water VSV), 4, 6, 8, 10, and 20. To validate the proposed method, phantom and patient studies were conducted and compared with direct Monte Carlo, which was considered the ground truth. Finally, patient dosimetry (10 subjects) was conducted using the multiple VSV approach and compared with the single VSV and organ-based dosimetry approaches. Errors at the voxel- and organ-levels were reported for eight organs. Results: In the phantom and patient studies, the multiple VSV approach showed significant improvements regarding voxel-level errors, especially for the lung and bone regions. As N increased, voxel-level errors decreased, although some overestimations were observed at lung boundaries. In the case of multiple VSVs ( N = 8), we achieved voxel-level errors of 2.06%. In the dosimetry study, our proposed method showed much improved results compared to the single VSV and

Does partial titin degradation affect sarcomere length non-uniformities and force in active and passive myofibrils?

PubMed

Joumaa, Venus; Bertrand, Fanny; Liu, Shuyue; Poscente, Sophia; Herzog, Walter

2018-05-16

The aim of this study was to determine the role of titin in preventing the development of sarcomere length non-uniformities following activation and after active and passive stretch, by determining the effect of partial titin degradation on sarcomere length non-uniformities and force in passive and active myofibrils. Selective partial titin degradation was performed using a low dose of trypsin. Myofibrils were set at a sarcomere length of 2.4 µm and then passively stretched to sarcomere lengths of 3.4 µm and 4.4 µm. In the active condition, myofibrils were set at a sarcomere length of 2.8µm, activated and actively stretched by 1 µm/sarcomere. The extent of sarcomere length non-uniformities was calculated for each sarcomere as the absolute difference between sarcomere length and the mean sarcomere length of the myofibril. Our main finding is that partial titin degradation does not increase sarcomere length non-uniformities after passive stretch and activation compared to when titin is intact, but increases the extent of sarcomere length non-uniformities after active stretch. Furthermore, when titin was partially degraded, active and passive stresses were substantially reduced. These results suggest that titin plays a crucial role in actively stretched myofibrils and is likely involved in active and passive force production.

Uniform Media Effects and Uniform Audience Responses.

ERIC Educational Resources Information Center

Perry, David K.

The idea that mass communication effects may decrease diversity among people or societies exposed to it arises constantly. However, discussions of mass media effects do not highlight differences between mass communications that "affect" people uniformly and messages that members of audiences "respond to" in similar ways. A…

Multicentre dose audit for clinical trials of radiation therapy in Asia.

PubMed

Mizuno, Hideyuki; Fukuda, Shigekazu; Fukumura, Akifumi; Nakamura, Yuzuru-Kutsutani; Jianping, Cao; Cho, Chul-Koo; Supriana, Nana; Dung, To Anh; Calaguas, Miriam Joy; Devi, C R Beena; Chansilpa, Yaowalak; Banu, Parvin Akhter; Riaz, Masooma; Esentayeva, Surya; Kato, Shingo; Karasawa, Kumiko; Tsujii, Hirohiko

2017-05-01

A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

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

An efficient shutter-less non-uniformity correction method for infrared focal plane arrays

NASA Astrophysics Data System (ADS)

Huang, Xiyan; Sui, Xiubao; Zhao, Yao

2017-02-01

The non-uniformity response in infrared focal plane array (IRFPA) detectors has a bad effect on images with fixed pattern noise. At present, it is common to use shutter to prevent from radiation of target and to update the parameters of non-uniformity correction in the infrared imaging system. The use of shutter causes "freezing" image. And inevitably, there exists the problems of the instability and reliability of system, power consumption, and concealment of infrared detection. In this paper, we present an efficient shutter-less non-uniformity correction (NUC) method for infrared focal plane arrays. The infrared imaging system can use the data gaining in thermostat to calculate the incident infrared radiation by shell real-timely. And the primary output of detector except the shell radiation can be corrected by the gain coefficient. This method has been tested in real infrared imaging system, reaching high correction level, reducing fixed pattern noise, adapting wide temperature range.

Evaluation of Dose Uncertainty to the Target Associated With Real-Time Tracking Intensity-Modulated Radiation Therapy Using the CyberKnife Synchrony System.

PubMed

Iwata, Hiromitsu; Inoue, Mitsuhiro; Shiomi, Hiroya; Murai, Taro; Tatewaki, Koshi; Ohta, Seiji; Okawa, Kohei; Yokota, Naoki; Shibamoto, Yuta

2016-02-01

We investigated the dose uncertainty caused by errors in real-time tracking intensity-modulated radiation therapy (IMRT) using the CyberKnife Synchrony Respiratory Tracking System (SRTS). Twenty lung tumors that had been treated with non-IMRT real-time tracking using CyberKnife SRTS were used for this study. After validating the tracking error in each case, we did 40 IMRT planning using 8 different collimator sizes for the 20 patients. The collimator size was determined for each planning target volume (PTV); smaller ones were one-half, and larger ones three-quarters, of the PTV diameter. The planned dose was 45 Gy in 4 fractions prescribed at 95% volume border of the PTV. Thereafter, the tracking error in each case was substituted into calculation software developed in house and randomly added in the setting of each beam. The IMRT planning incorporating tracking errors was simulated 1000 times, and various dose data on the clinical target volume (CTV) were compared with the original data. The same simulation was carried out by changing the fraction number from 1 to 6 in each IMRT plan. Finally, a total of 240 000 plans were analyzed. With 4 fractions, the change in the CTV maximum and minimum doses was within 3.0% (median) for each collimator. The change in D99 and D95 was within 2.0%. With decreases in the fraction number, the CTV coverage rate and the minimum dose decreased and varied greatly. The accuracy of real-time tracking IMRT delivered in 4 fractions using CyberKnife SRTS was considered to be clinically acceptable. © The Author(s) 2014.

Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

PubMed

Sedel, Frédéric; Bernard, Delphine; Mock, Donald M; Tourbah, Ayman

2016-11-01

Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Total skin electron irradiation: evaluation of dose uniformity throughout the skin surface.

PubMed

Anacak, Yavuz; Arican, Zumre; Bar-Deroma, Raquel; Tamir, Ada; Kuten, Abraham

2003-01-01

In this study, in vivo dosimetic data of 67 total skin electron irradiation (TSEI) treatments were analyzed. Thermoluminescent dosimetry (TLD) measurements were made at 10 different body points for every patient. The results demonstrated that the dose inhomogeneity throughout the skin surface is around 15%. The homogeneity was better at the trunk than at the extratrunk points, and was worse when a degrader was used. There was minimal improvement of homogeneity in subsequent days of treatment.

SU-E-T-513: Investigating Dose of Internal Target Volume After Correcting for Tissue Heterogeneity in SBRT Lung Plans with Homogeneity Calculation

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

Qi, P; Zhuang, T; Magnelli, A

2015-06-15

Purpose It was recommended to use the prescription of 54 Gy/3 with heterogeneity corrections for previously established dose scheme of 60 Gy/3 with homogeneity calculation. This study is to investigate dose coverage for the internal target volume (ITV) with and without heterogeneity correction. Methods Thirty patients who received stereotactic body radiotherapy (SBRT) to a dose of 60 Gy in 3 fractions with homogeneous planning for early stage non-small-cell lung cancer (NSCLC) were selected. ITV was created either from 4DCT scans or a fusion of multi-phase respiratory scans. Planning target volume (PTV) was a 5 mm expansion of the ITV. Formore » this study, we recalculated homogeneous clinical plans using heterogeneity corrections with monitor units set as clinically delivered. All plans were calculated with 3 mm dose grids and collapsed cone convolution algorithm. To account for uncertainties from tumor delineation and image-guided radiotherapy, a structure ITV2mm was created by expanding ITV with 2 mm margins. Dose coverage to the PTV, ITV and ITV2mm were compared with a student paired t-test. Results With heterogeneity corrections, the PTV V60Gy decreased by 10.1% ± 18.4% (p<0.01) while the maximum dose to the PTV increased by 3.7 ± 4.3% (p<0.01). With and without corrections, D99% was 65.8 ± 4.0 Gy and 66.7 ± 4.8 Gy (p=0.15) for the ITV, and 63.9 ± 3.4 Gy and 62.9 ± 4.6 Gy for the ITV2mm (p=0.22), respectively. The mean dose to the ITV and ITV2mm increased 3.6% ± 4.7% (p<0.01) and 2.3% ± 5.2% (p=0.01) with heterogeneity corrections. Conclusion After heterogeneity correction, the peripheral coverage of the PTV decreased to approximately 54 Gy, but D99% of the ITV and ITV2mm was unchanged and the mean dose to the ITV and ITV2mm was increased. Clinical implication of these results requires more investigation.« less

Dedicated high dose rate 192Ir brachytherapy radiation fields for in vitro cell exposures at variable source-target cell distances: killing of mammalian cells depends on temporal dose rate fluctuation

NASA Astrophysics Data System (ADS)

Veigel, Cornelia; Hartmann, Günther H.; Fritz, Peter; Debus, Jürgen; Weber, Klaus-Josef

2017-02-01

Afterloading brachytherapy is conducted by the stepwise movement of a radioactive source through surgically implanted applicator tubes where at predefined dwell positions calculated dwell times optimize spatial dose delivery with respect to a planned dose level. The temporal exposure pattern exhibits drastic fluctuations in dose rate at a given coordinate and within a single treatment session because of the discontinuous and repeated source movement into the target volume. This could potentially affect biological response. Therefore, mammalian cells were exposed as monolayers to a high dose rate 192Ir source by utilizing a dedicated irradiation device where the distance between a planar array of radioactive source positions and the plane of the cell monolayer could be varied from 2.5 mm to 40 mm, thus varying dose rate pattern for any chosen total dose. The Gammamed IIi afterloading system equipped with a nominal 370 GBq (10 Ci) 192-Ir source was used to irradiate V79 Chinese hamster lung fibroblasts from both confluent and from exponential growth phase with dose up to 12 Gy (at room temperature, total exposure not exceeding 1 h). For comparison, V79 cells were also exposed to 6 MV x-rays from a clinical linear accelerator (dose rate of 2.5 Gy min-1). As biological endpoint, cell survival was determined by standard colony forming assay. Dose measurements were conducted with a diamond detector (sensitive area 7.3 mm2), calibrated by means of 60Co radiation. Additionally, dose delivery was simulated by Monte Carlo calculations using the EGSnrc code system. The calculated secondary electron fluence spectra at the cell location did not indicate a significant change of radiation quality (i.e. higher linear energy transfer) at the lower distances. Clonogenic cell survival curves obtained after brachytherapy exhibited an altered biological response compared to x-rays which was characterized by a significant reduction of the survival curve shoulder when dose rate

Assessment and quantification of patient set-up errors in nasopharyngeal cancer patients and their biological and dosimetric impact in terms of generalized equivalent uniform dose (gEUD), tumour control probability (TCP) and normal tissue complication probability (NTCP).

PubMed

Boughalia, A; Marcie, S; Fellah, M; Chami, S; Mekki, F

2015-06-01

The aim of this study is to assess and quantify patients' set-up errors using an electronic portal imaging device and to evaluate their dosimetric and biological impact in terms of generalized equivalent uniform dose (gEUD) on predictive models, such as the tumour control probability (TCP) and the normal tissue complication probability (NTCP). 20 patients treated for nasopharyngeal cancer were enrolled in the radiotherapy-oncology department of HCA. Systematic and random errors were quantified. The dosimetric and biological impact of these set-up errors on the target volume and the organ at risk (OARs) coverage were assessed using calculation of dose-volume histogram, gEUD, TCP and NTCP. For this purpose, an in-house software was developed and used. The standard deviations (1SDs) of the systematic set-up and random set-up errors were calculated for the lateral and subclavicular fields and gave the following results: ∑ = 0.63 ± (0.42) mm and σ = 3.75 ± (0.79) mm, respectively. Thus a planning organ at risk volume (PRV) margin of 3 mm was defined around the OARs, and a 5-mm margin used around the clinical target volume. The gEUD, TCP and NTCP calculations obtained with and without set-up errors have shown increased values for tumour, where ΔgEUD (tumour) = 1.94% Gy (p = 0.00721) and ΔTCP = 2.03%. The toxicity of OARs was quantified using gEUD and NTCP. The values of ΔgEUD (OARs) vary from 0.78% to 5.95% in the case of the brainstem and the optic chiasm, respectively. The corresponding ΔNTCP varies from 0.15% to 0.53%, respectively. The quantification of set-up errors has a dosimetric and biological impact on the tumour and on the OARs. The developed in-house software using the concept of gEUD, TCP and NTCP biological models has been successfully used in this study. It can be used also to optimize the treatment plan established for our patients. The gEUD, TCP and NTCP may be more suitable tools to assess the treatment plans

Recent developments in human biomonitoring: non-invasive assessment of target tissue dose and effects of pneumotoxic metals.

PubMed

Mutti, A; Corradi, M

2006-01-01

Tobacco smoke and polluted environments substantially increase the lung burden of pneumotoxic chemicals, particularly pneumotoxic metallic elements. To achieve a better understanding of the early events between exposure to inhaled toxicants and the onset of adverse effects on the lung, the characterization of dose at the target organ would be extremely useful. Exhaled breath condensate (EBC), obtained by cooling exhaled air under conditions of spontaneous breathing, is a novel technique that could provide a non-invasive assessment of pulmonary pathobiology. Considering that EBC is water practically free of interfering solutes, it represents an ideal biological matrix for elemental characterization. Published data show that several toxic metals and trace elements are detectable in EBC, raising the possibility of using this medium to quantify the lung tissue dose of pneumotoxic substances. This novel approach may represent a significant advance over the analysis of alternative media (blood, serum, urine, hair), which are not as reliable (owing to interfering substances in the complex matrix) and reflect systemic rather than lung (target tissue) levels of both toxic metals and essential trace elements. Data obtained among workers occupationally exposed to either hard metals or chromium (VI) and in smokers with or without chronic obstructive pulmonary disease (COPD) are reviewed to show that--together with biomarkers of exposure--EBC also allows the simultaneous quantification of biomarkers of effect directly sampled from the epithelial lining fluid, thus providing novel insights on both kinetic and dynamic aspects of metal toxicology.

Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

PubMed

Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

2016-10-01

In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001). In PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Sensitivity of postplanning target and OAR coverage estimates to dosimetric margin distribution sampling parameters

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

Xu Huijun; Gordon, J. James; Siebers, Jeffrey V.

2011-02-15

Purpose: A dosimetric margin (DM) is the margin in a specified direction between a structure and a specified isodose surface, corresponding to a prescription or tolerance dose. The dosimetric margin distribution (DMD) is the distribution of DMs over all directions. Given a geometric uncertainty model, representing inter- or intrafraction setup uncertainties or internal organ motion, the DMD can be used to calculate coverage Q, which is the probability that a realized target or organ-at-risk (OAR) dose metric D{sub v} exceeds the corresponding prescription or tolerance dose. Postplanning coverage evaluation quantifies the percentage of uncertainties for which target and OAR structuresmore » meet their intended dose constraints. The goal of the present work is to evaluate coverage probabilities for 28 prostate treatment plans to determine DMD sampling parameters that ensure adequate accuracy for postplanning coverage estimates. Methods: Normally distributed interfraction setup uncertainties were applied to 28 plans for localized prostate cancer, with prescribed dose of 79.2 Gy and 10 mm clinical target volume to planning target volume (CTV-to-PTV) margins. Using angular or isotropic sampling techniques, dosimetric margins were determined for the CTV, bladder and rectum, assuming shift invariance of the dose distribution. For angular sampling, DMDs were sampled at fixed angular intervals {omega} (e.g., {omega}=1 deg., 2 deg., 5 deg., 10 deg., 20 deg.). Isotropic samples were uniformly distributed on the unit sphere resulting in variable angular increments, but were calculated for the same number of sampling directions as angular DMDs, and accordingly characterized by the effective angular increment {omega}{sub eff}. In each direction, the DM was calculated by moving the structure in radial steps of size {delta}(=0.1,0.2,0.5,1 mm) until the specified isodose was crossed. Coverage estimation accuracy {Delta}Q was quantified as a function of the sampling parameters

Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11-vascular-targeted photodynamic (VTP) therapy.

PubMed

Moore, Caroline M; Azzouzi, Abel-Rahmene; Barret, Eric; Villers, Arnauld; Muir, Gordon H; Barber, Neil J; Bott, Simon; Trachtenberg, John; Arumainayagam, Nimalan; Gaillac, Bertrand; Allen, Clare; Schertz, Avigdor; Emberton, Mark

2015-12-01

To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer. In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months. In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP. Treatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%). © 2014 The Authors BJU International © 2014 BJU

Dress Codes and Uniforms.

ERIC Educational Resources Information Center

Lumsden, Linda; Miller, Gabriel

2002-01-01

Students do not always make choices that adults agree with in their choice of school dress. Dress-code issues are explored in this Research Roundup, and guidance is offered to principals seeking to maintain a positive school climate. In "Do School Uniforms Fit?" Kerry White discusses arguments for and against school uniforms and summarizes the…

School Uniforms. Research Brief

ERIC Educational Resources Information Center

Walker, Karen

2007-01-01

Does clothing make the person or does the person make the clothing? How does what attire a student wears to school affect their academic achievement? In 1996, President Clinton cited examples of school violence and discipline issues that might have been avoided had the students been wearing uniforms ("School uniforms: Prevention or suppression?").…

Dose properties of a laser accelerated electron beam and prospects for clinical application.

PubMed

Kainz, K K; Hogstrom, K R; Antolak, J A; Almond, P R; Bloch, C D; Chiu, C; Fomytskyi, M; Raischel, F; Downer, M; Tajima, T

2004-07-01

Laser wakefield acceleration (LWFA) technology has evolved to where it should be evaluated for its potential as a future competitor to existing technology that produces electron and x-ray beams. The purpose of the present work is to investigate the dosimetric properties of an electron beam that should be achievable using existing LWFA technology, and to document the necessary improvements to make radiotherapy application for LWFA viable. This paper first qualitatively reviews the fundamental principles of LWFA and describes a potential design for a 30 cm accelerator chamber containing a gas target. Electron beam energy spectra, upon which our dose calculations are based, were obtained from a uniform energy distribution and from two-dimensional particle-in-cell (2D PIC) simulations. The 2D PIC simulation parameters are consistent with those reported by a previous LWFA experiment. According to the 2D PIC simulations, only approximately 0.3% of the LWFA electrons are emitted with an energy greater than 1 MeV. We studied only the high-energy electrons to determine their potential for clinical electron beams of central energy from 9 to 21 MeV. Each electron beam was broadened and flattened by designing a dual scattering foil system to produce a uniform beam (103%>off-axis ratio>95%) over a 25 x 25 cm2 field. An energy window (deltaE) ranging from 0.5 to 6.5 MeV was selected to study central-axis depth dose, beam flatness, and dose rate. Dose was calculated in water at a 100 cm source-to-surface distance using the EGS/BEAM Monte Carlo algorithm. Calculations showed that the beam flatness was fairly insensitive to deltaE. However, since the falloff of the depth-dose curve (R10-R90) and the dose rate both increase with deltaE, a tradeoff between minimizing (R10-R90) and maximizing dose rate is implied. If deltaE is constrained so that R10-R90 is within 0.5 cm of its value for a monoenergetic beam, the maximum practical dose rate based on 2D PIC is approximately 0.1 Gy min

Voluntary Deep Inspiration Breath-hold Reduces the Heart Dose Without Compromising the Target Volume Coverage During Radiotherapy for Left-sided Breast Cancer.

PubMed

Al-Hammadi, Noora; Caparrotti, Palmira; Naim, Carole; Hayes, Jillian; Rebecca Benson, Katherine; Vasic, Ana; Al-Abdulla, Hissa; Hammoud, Rabih; Divakar, Saju; Petric, Primoz

2018-03-01

During radiotherapy of left-sided breast cancer, parts of the heart are irradiated, which may lead to late toxicity. We report on the experience of single institution with cardiac-sparing radiotherapy using voluntary deep inspiration breath hold (V-DIBH) and compare its dosimetric outcome with free breathing (FB) technique. Left-sided breast cancer patients, treated at our department with postoperative radiotherapy of breast/chest wall +/- regional lymph nodes between May 2015 and January 2017, were considered for inclusion. FB-computed tomography (CT) was obtained and dose-planning performed. Cases with cardiac V25Gy ≥ 5% or risk factors for heart disease were coached for V-DIBH. Compliant patients were included. They underwent additional CT in V-DIBH for planning, followed by V-DIBH radiotherapy. Dose volume histogram parameters for heart, lung and optimized planning target volume (OPTV) were compared between FB and BH. Treatment setup shifts and systematic and random errors for V-DIBH technique were compared with FB historic control. Sixty-three patients were considered for V-DIBH. Nine (14.3%) were non-compliant at coaching, leaving 54 cases for analysis. When compared with FB, V-DIBH resulted in a significant reduction of mean cardiac dose from 6.1 +/- 2.5 to 3.2 +/- 1.4 Gy (p < 0.001), maximum cardiac dose from 51.1 +/- 1.4 to 48.5 +/- 6.8 Gy (p = 0.005) and cardiac V25Gy from 8.5 +/- 4.2 to 3.2 +/- 2.5% (p < 0.001). Heart volumes receiving low (10-20 Gy) and high (30-50 Gy) doses were also significantly reduced. Mean dose to the left anterior coronary artery was 23.0 (+/- 6.7) Gy and 14.8 (+/- 7.6) Gy on FB and V-DIBH, respectively (p < 0.001). Differences between FB- and V-DIBH-derived mean lung dose (11.3 +/- 3.2 vs. 10.6 +/- 2.6 Gy), lung V20Gy (20.5 +/- 7 vs. 19.5 +/- 5.1 Gy) and V95% for the OPTV (95.6 +/- 4.1 vs. 95.2 +/- 6.3%) were non-significant. V-DIBH-derived mean shifts for initial patient setup were ≤ 2.7 mm. Random and systematic errors

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

PubMed

Wilkowski, Ralf; Thoma, Martin; Weingandt, Helmut; Dühmke, Eckhart; Heinemann, Volker

2005-05-10

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

Isoniazid, Pyrazinamide and Rifampicin Content Variation in Split Fixed-Dose Combination Tablets

PubMed Central

Pouplin, Thomas; Phuong, Pham Nguyen; Toi, Pham Van; Nguyen Pouplin, Julie; Farrar, Jeremy

2014-01-01

Setting In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. Objective To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. Design Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. Results All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. Conclusion In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis. PMID:25004128

Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets.

PubMed

Pouplin, Thomas; Phuong, Pham Nguyen; Toi, Pham Van; Nguyen Pouplin, Julie; Farrar, Jeremy

2014-01-01

In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.

Electrostatic lens to focus an ion beam to uniform density

DOEpatents

Johnson, Cleland H.

1977-01-11

A focusing lens for an ion beam having a gaussian or similar density profile is provided. The lens is constructed to provide an inner zero electrostatic field, and an outer electrostatic field such that ions entering this outer field are deflected by an amount that is a function of their distance from the edge of the inner field. The result is a beam that focuses to a uniform density in a manner analogous to that of an optical ring lens. In one embodiment, a conically-shaped network of fine wires is enclosed within a cylindrical anode. The wire net together with the anode produces a voltage field that re-directs the outer particles of the beam while the axial particles pass undeflected through a zero field inside the wire net. The result is a focused beam having a uniform intensity over a given target area and at a given distance from the lens.

Wave modeling in a cylindrical non-uniform helicon discharge

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

Chang, L.; Hole, M. J.; Caneses, J. F.

2012-08-15

A radio frequency field solver based on Maxwell's equations and a cold plasma dielectric tensor is employed to describe wave phenomena observed in a cylindrical non-uniform helicon discharge. The experiment is carried out on a recently built linear plasma-material interaction machine: The magnetized plasma interaction experiment [Blackwell et al., Plasma Sources Sci. Technol. (submitted)], in which both plasma density and static magnetic field are functions of axial position. The field strength increases by a factor of 15 from source to target plate, and the plasma density and electron temperature are radially non-uniform. With an enhancement factor of 9.5 to themore » electron-ion Coulomb collision frequency, a 12% reduction in the antenna radius, and the same other conditions as employed in the experiment, the solver produces axial and radial profiles of wave amplitude and phase that are consistent with measurements. A numerical study on the effects of axial gradient in plasma density and static magnetic field on wave propagations is performed, revealing that the helicon wave has weaker attenuation away from the antenna in a focused field compared to a uniform field. This may be consistent with observations of increased ionization efficiency and plasma production in a non-uniform field. We find that the relationship between plasma density, static magnetic field strength, and axial wavelength agrees well with a simple theory developed previously. A numerical scan of the enhancement factor to the electron-ion Coulomb collision frequency from 1 to 15 shows that the wave amplitude is lowered and the power deposited into the core plasma decreases as the enhancement factor increases, possibly due to the stronger edge heating for higher collision frequencies.« less

Methods and computer executable instructions for rapidly calculating simulated particle transport through geometrically modeled treatment volumes having uniform volume elements for use in radiotherapy

DOEpatents

Frandsen, Michael W.; Wessol, Daniel E.; Wheeler, Floyd J.

2001-01-16

Methods and computer executable instructions are disclosed for ultimately developing a dosimetry plan for a treatment volume targeted for irradiation during cancer therapy. The dosimetry plan is available in "real-time" which especially enhances clinical use for in vivo applications. The real-time is achieved because of the novel geometric model constructed for the planned treatment volume which, in turn, allows for rapid calculations to be performed for simulated movements of particles along particle tracks there through. The particles are exemplary representations of neutrons emanating from a neutron source during BNCT. In a preferred embodiment, a medical image having a plurality of pixels of information representative of a treatment volume is obtained. The pixels are: (i) converted into a plurality of substantially uniform volume elements having substantially the same shape and volume of the pixels; and (ii) arranged into a geometric model of the treatment volume. An anatomical material associated with each uniform volume element is defined and stored. Thereafter, a movement of a particle along a particle track is defined through the geometric model along a primary direction of movement that begins in a starting element of the uniform volume elements and traverses to a next element of the uniform volume elements. The particle movement along the particle track is effectuated in integer based increments along the primary direction of movement until a position of intersection occurs that represents a condition where the anatomical material of the next element is substantially different from the anatomical material of the starting element. This position of intersection is then useful for indicating whether a neutron has been captured, scattered or exited from the geometric model. From this intersection, a distribution of radiation doses can be computed for use in the cancer therapy. The foregoing represents an advance in computational times by multiple factors of

[The Dose Effect of Isocenter Selection during IMRT Dose Verification with the 2D Chamber Array].

PubMed

Xie, Chuanbin; Cong, Xiaohu; Xu, Shouping; Dai, Xiangkun; Wang, Yunlai; Han, Lu; Gong, Hanshun; Ju, Zhongjian; Ge, Ruigang; Ma, Lin

2015-03-01

To investigate the dose effect of isocenter difference during IMRT dose verification with the 2D chamber array. The samples collected from 10 patients were respectively designed for IMRT plans, the isocenter of which was independently defined as P(o), P(x) and P(y). P(o) was fixed on the target center and the other points shifted 8cm from the target center in the orientation of x/y. The PTW729 was used for 2D dose verification in the 3 groups which beams of plans were set to 0 degrees. The γ-analysis passing rates for the whole plan and each beam were gotten using the different standards in the 3 groups, The results showed the mean passing rate of γ-analysis was highest in the P(o) group, and the mean passing rate of the whole plan was better than that of each beam. In addition, it became worse with the increase of dose leakage between the leaves in P(y) group. Therefore, the determination of isocenter has a visible effect for IMRT dose verification of the 2D chamber array, The isocenter of the planning design should be close to the geometric center of target.

Helical tomotherapy significantly reduces dose to normal tissues when compared to 3D-CRT for locally advanced rectal cancer.

PubMed

Jhaveri, Pavan M; Teh, Bin S; Paulino, Arnold C; Smiedala, Mindy J; Fahy, Bridget; Grant, Walter; McGary, John; Butler, E Brian

2009-10-01

Combined modality treatment (neoadjuvant chemoradiotherapy followed by surgery) for locally advanced rectal cancer requires special attention to various organs at risk (OAR). As a result, the use of conformal dose delivery methods has become more common in this disease setting. Helical tomotherapy is an image-guided intensity modulated delivery system that delivers dose in a fan-beam manner at 7 degree intervals around the patient and can potentially limit normal tissue from high dose radiation while adequately treating targets. In this study we dosimetrically compare helical tomotherapy to 3D-CRT for stage T3 rectal cancer. The helical tomotherapy plans were optimized in the TomoPlan system to achieve an equivalent uniform dose of 45 Gy for 10 patients with T3N0M0 disease that was at least 5cm from the anal verge. The GTV included the rectal thickening and mass evident on colonoscopy and CT scan as well as with the help of a colorectal surgeon. The CTV included the internal iliac, obturator, and pre-sacral lymphatic chains. The OAR that were outlined included the small bowel, pelvic bone marrow, femoral heads, and bladder. Anatom-e system was used to assist in delineating GTV, CTV and OAR. These 10 plans were then duplicated and optimized into 3-field 3D-CRT plans within the Pinnacle planning system.The V[45], V[40], V[30], V[20], V[10], and mean dose to the OAR were compared between the helical tomotherapy and 3D-CRT plans. Statistically significant differences were achieved in the doses to all OAR, including all volumes and means except for V[10] for the small bowel and the femoral heads. Adequate dosimetric coverage of targets were achieved with both helical tomotherapy and 3D-CRT. Helical tomotherapy reduces the volume of normal tissue receiving high-dose RT when compared to 3D-CRT treatment. Both modalities adequately dose the tumor. Clinical studies addressing the dosimetric benefits are on-going.

Dose calculations accounting for breathing motion in stereotactic lung radiotherapy based on 4D-CT and the internal target volume.

PubMed

Admiraal, Marjan A; Schuring, Danny; Hurkmans, Coen W

2008-01-01

The purpose of this study was to determine the 4D accumulated dose delivered to the CTV in stereotactic radiotherapy of lung tumours, for treatments planned on an average CT using an ITV derived from the Maximum Intensity Projection (MIP) CT. For 10 stage I lung cancer patients, treatment plans were generated based on 4D-CT images. From the 4D-CT scan, 10 time-sorted breathing phases were derived, along with the average CT and the MIP. The ITV with a margin of 0mm was used as a PTV to study a worst case scenario in which the differences between 3D planning and 4D dose accumulation will be largest. Dose calculations were performed on the average CT. Dose prescription was 60Gy to 95% of the PTV, and at least 54Gy should be received by 99% of the PTV. Plans were generated using the inverse planning module of the Pinnacle(3) treatment planning system. The plans consisted of nine coplanar beams with two segments each. After optimisation, the treatment plan was transferred to all breathing phases and the delivered dose per phase was calculated using an elastic body spline model available in our research version of Pinnacle (8.1r). Then, the cumulative dose to the CTV over all breathing phases was calculated and compared to the dose distribution of the original treatment plan. Although location, tumour size and breathing-induced tumour movement varied widely between patients, the PTV planning criteria could always be achieved without compromising organs at risk criteria. After 4D dose calculations, only very small differences between the initial planned PTV coverage and resulting CTV coverage were observed. For all patients, the dose delivered to 99% of the CTV exceeded 54Gy. For nine out of 10 patients also the criterion was met that the volume of the CTV receiving at least the prescribed dose was more than 95%. When the target dose is prescribed to the ITV (PTV=ITV) and dose calculations are performed on the average CT, the cumulative CTV dose compares well to the

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

2012-01-01

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

A novel dose-based positioning method for CT image-guided proton therapy

PubMed Central

Cheung, Joey P.; Park, Peter C.; Court, Laurence E.; Ronald Zhu, X.; Kudchadker, Rajat J.; Frank, Steven J.; Dong, Lei

2013-01-01

Purpose: Proton dose distributions can potentially be altered by anatomical changes in the beam path despite perfect target alignment using traditional image guidance methods. In this simulation study, the authors explored the use of dosimetric factors instead of only anatomy to set up patients for proton therapy using in-room volumetric computed tomographic (CT) images. Methods: To simulate patient anatomy in a free-breathing treatment condition, weekly time-averaged four-dimensional CT data near the end of treatment for 15 lung cancer patients were used in this study for a dose-based isocenter shift method to correct dosimetric deviations without replanning. The isocenter shift was obtained using the traditional anatomy-based image guidance method as the starting position. Subsequent isocenter shifts were established based on dosimetric criteria using a fast dose approximation method. For each isocenter shift, doses were calculated every 2 mm up to ±8 mm in each direction. The optimal dose alignment was obtained by imposing a target coverage constraint that at least 99% of the target would receive at least 95% of the prescribed dose and by minimizing the mean dose to the ipsilateral lung. Results: The authors found that 7 of 15 plans did not meet the target coverage constraint when using only the anatomy-based alignment. After the authors applied dose-based alignment, all met the target coverage constraint. For all but one case in which the target dose was met using both anatomy-based and dose-based alignment, the latter method was able to improve normal tissue sparing. Conclusions: The authors demonstrated that a dose-based adjustment to the isocenter can improve target coverage and/or reduce dose to nearby normal tissue. PMID:23635262

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

Shusharina, N; Khan, F; Sharp, G

Purpose: To determine the dose level and timing of the boost in locally advanced lung cancer patients with confirmed tumor recurrence by comparing different boosting strategies by an impact of dose escalation in improvement of the therapeutic ratio. Methods: We selected eighteen patients with advanced NSCLC and confirmed recurrence. For each patient, a base IMRT plan to 60 Gy prescribed to PTV was created. Then we compared three dose escalation strategies: a uniform escalation to the original PTV, an escalation to a PET-defined target planned sequentially and concurrently. The PET-defined targets were delineated by biologically-weighed regions on a pre-treatment 18F-FDGmore » PET. The maximal achievable dose, without violating the OAR constraints, was identified for each boosting method. The EUD for the target, spinal cord, combined lung, and esophagus was compared for each plan. Results: The average prescribed dose was 70.4±13.9 Gy for the uniform boost, 88.5±15.9 Gy for the sequential boost and 89.1±16.5 Gy for concurrent boost. The size of the boost planning volume was 12.8% (range: 1.4 – 27.9%) of the PTV. The most prescription-limiting dose constraints was the V70 of the esophagus. The EUD within the target increased by 10.6 Gy for the uniform boost, by 31.4 Gy for the sequential boost and by 38.2 for the concurrent boost. The EUD for OARs increased by the following amounts: spinal cord, 3.1 Gy for uniform boost, 2.8 Gy for sequential boost, 5.8 Gy for concurrent boost; combined lung, 1.6 Gy for uniform, 1.1 Gy for sequential, 2.8 Gy for concurrent; esophagus, 4.2 Gy for uniform, 1.3 Gy for sequential, 5.6 Gy for concurrent. Conclusion: Dose escalation to a biologically-weighed gross tumor volume defined on a pre-treatment 18F-FDG PET may provide improved therapeutic ratio without breaching predefined OAR constraints. Sequential boost provides better sparing of OARs as compared with concurrent boost.« less

Design and analysis of reflector for uniform light-emitting diode illuminance.

PubMed

Tsai, Chung-Yu

2013-05-01

A light-emitting diode (LED) projection system is proposed, composed of an LED chip and a variable-focus-parabolic (VFP) reflector, in which the focal length varies as a function of the vertical displacement of the incidence point relative to the horizontal centerline of the LED chip. The light-ray paths within the projection system are analyzed using an exact analytical model and a skew-ray tracing approach. The profile of the proposed VFP reflector and the position of the LED chip are then optimized in such a way as to enhance the uniformity of the illuminance distribution on the target region of the image plane. The validity of the optimized design is demonstrated by means of ZEMAX simulations. It is shown that the optimized VFP projector system yields a significant improvement in illuminance uniformity compared to conventional spherical and parabolic projectors and therefore minimizes the glare effect.

Single line source with and without vaginal loading and the impact on target coverage and organ at risk doses for cervix cancer Stages IB, II, and IIIB: treatment planning simulation in patients treated with MRI-guided adaptive brachytherapy in a multicentre study (EMBRACE).

PubMed

Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian

2013-01-01

Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2015-04-01

physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ±1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

[Labour factors associated with post-traumatic stress in uniformed workers in Medellín].

PubMed

González-Penagos, Catalina; Moreno-Bedoya, Juan P; Berbesi-Fernández, Dedsy Y; Segura-Cardona, Angela M

2013-01-01

Determining the labor factors associated with post-traumatic stress in uniformed workers in Medellin. A cross-sectional study was made of 124 uniformed workers aged 20 to 48 years-old. A survey was made using an adults' post-traumatic stress instrument which had been validated in Medellin. Statistical analysis was carried out. Post-traumatic stress disorder risk prevalence was 52.2 %. Multivariate analysis showed that the highest risk situations were those related to previous mental health diagnosis (PR=7.67), working schedule (4.24), violent episodes (PR=3.59) and community relationships (PR=2.73). A person's current labor situation seemed to be a risk factor for developing post-traumatic stress in the target population.

SU-F-T-70: A High Dose Rate Total Skin Electron Irradiation Technique with A Specific Inter-Film Variation Correction Method for Very Large Electron Beam Fields

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

Yang, X; Rosenfield, J; Dong, X

2016-06-15

Purpose: Rotational total skin electron irradiation (RTSEI) is used in the treatment of cutaneous T-cell lymphoma. Due to inter-film uniformity variations the dosimetry measurement of a large electron beam of a very low energy is challenging. This work provides a method to improve the accuracy of flatness and symmetry for a very large treatment field of low electron energy used in dual beam RTSEI. Methods: RTSEI is delivered by dual angles field a gantry of ±20 degrees of 270 to cover the upper and the lower halves of the patient body with acceptable beam uniformity. The field size is inmore » the order of 230cm in vertical height and 120 cm in horizontal width and beam energy is a degraded 6 MeV (6 mm of PMMA spoiler). We utilized parallel plate chambers, Gafchromic films and OSLDs as a measuring devices for absolute dose, B-Factor, stationary and rotational percent depth dose and beam uniformity. To reduce inter-film dosimetric variation we introduced a new specific correction method to analyze beam uniformity. This correction method uses some image processing techniques combining film value before and after radiation dose to compensate the inter-variation dose response differences among films. Results: Stationary and rotational depth of dose demonstrated that the Rp is 2 cm for rotational and the maximum dose is shifted toward the surface (3mm). The dosimetry for the phantom showed that dose uniformity reduced to 3.01% for the vertical flatness and 2.35% for horizontal flatness after correction thus achieving better flatness and uniformity. The absolute dose readings of calibrated films after our correction matched with the readings from OSLD. Conclusion: The proposed correction method for Gafchromic films will be a useful tool to correct inter-film dosimetric variation for the future clinical film dosimetry verification in very large fields, allowing the optimizations of other parameters.« less

Dosimetric quality endpoints for low-dose-rate prostate brachytherapy using biological effective dose (bed) vs. conventional dose

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

Singh, Rachana; Al-Hallaq, Hania; Pelizzari, Charles A.

2003-12-31

The purpose of this study was to compare conventional low-dose-rate prostate brachytherapy dosimetric quality parameters with their biological effective dose (BED) counterparts. To validate a model for transformation from conventional dose to BED, the postimplant plans of 31 prostate brachytherapy patients were evaluated using conventional dose-volume histogram (DVH) quality endpoints and analogous BED-DVH endpoints. Based on CT scans obtained 4 weeks after implantation, DVHs were computed and standard dosimetric endpoints V100 (volume receiving 100% of the prescribed dose), V150, V200, HI (1-[V150/V100]), and D90 (dose that 90% of the target volume received) were obtained for quality analysis. Using known andmore » reported transformations, dose grids were transformed to BED-early ({alpha}/{beta} = 10 Gy) and BED-late ({alpha}/{beta} = 3 Gy) grids, and the same dosimetric endpoints were analyzed. For conventional, BED-early and BED-late DVHs, no differences in V100 were seen (0.896, 0.893, and 0.894, respectively). However, V150 and V200 were significantly higher for both BED-early (0.582 and 0.316) and BED-late (0.595 and 0.337), compared with the conventional (0.539 and 0.255) DVHs. D90 was significantly lower for the BED-early (103.1 Gy) and BED-late transformations (106.9 Gy) as compared with the conventional (119.5 Gy) DVHs. The conventional prescription parameter V100 is the same for the corresponding BED-early and BED-late transformed DVHs. The toxicity parameters V150 and V200 are slightly higher using the BED transformations, suggesting that the BED doses are somewhat higher than predicted using conventional DVHs. The prescription/quality parameter D90 is slightly lower, implying that target coverage is lower than predicted using conventional DVHs. This methodology can be applied to analyze BED dosimetric endpoints to improve clinical outcome and reduce complications of prostate brachytherapy.« less

Comparison of Turbulent Heat-Transfer Results for Uniform Wall Heat Flux and Uniform Wall Temperature

NASA Technical Reports Server (NTRS)

Siegel, R.; Sparrow, E. M.

1960-01-01

The purpose of this note is to examine in a more precise way how the Nusselt numbers for turbulent heat transfer in both the fully developed and thermal entrance regions of a circular tube are affected by two different wall boundary conditions. The comparisons are made for: (a) Uniform wall temperature (UWT); and (b) uniform wall heat flux (UHF). Several papers which have been concerned with the turbulent thermal entrance region problem are given. 1 Although these analyses have all utilized an eigenvalue formulation for the thermal entrance region there were differences in the choices of eddy diffusivity expressions, velocity distributions, and methods for carrying out the numerical solutions. These differences were also found in the fully developed analyses. Hence when making a comparison of the analytical results for uniform wall temperature and uniform wall heat flux, it was not known if differences in the Nusselt numbers could be wholly attributed to the difference in wall boundary conditions, since all the analytical results were not obtained in a consistent way. To have results which could be directly compared, computations were carried out for the uniform wall temperature case, using the same eddy diffusivity, velocity distribution, and digital computer program employed for uniform wall heat flux. In addition, the previous work was extended to a lower Reynolds number range so that comparisons could be made over a wide range of both Reynolds and Prandtl numbers.

7 CFR 1006.61 - Computation of uniform prices.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., the market administrator shall compute a uniform butterfat price, a uniform skim milk price, and a... section. (b) Uniform skim milk price. The uniform skim milk price per hundredweight, rounded to the... paragraph (a) of this section times 3.5 pounds of butterfat; and (2) Multiply the uniform skim milk price...

7 CFR 1007.61 - Computation of uniform prices.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., the market administrator shall compute a uniform butterfat price, a uniform skim milk price, and a... section. (b) Uniform skim milk price. The uniform skim milk price per hundredweight, rounded to the... paragraph (a) of this section times 3.5 pounds of butterfat; and (2) Multiply the uniform skim milk price...

7 CFR 1131.61 - Computation of uniform prices.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., the market administrator shall compute a uniform butterfat price, a uniform skim milk price, and a... section. (b) Uniform skim milk price. The uniform skim milk price per hundredweight, rounded to the... paragraph (a) of this section times 3.5 pounds of butterfat; and (2) Multiply the uniform skim milk price...

The influence of physical wedges on penumbra and in-field dose uniformity in ocular proton beams.

PubMed

Baker, Colin; Kacperek, Andrzej

2016-04-01

A physical wedge may be partially introduced into a proton beam when treating ocular tumours in order to improve dose conformity to the distal border of the tumour and spare the optic nerve. Two unwanted effects of this are observed: a predictable broadening of the beam penumbra on the wedged side of the field and, less predictably, an increase in dose within the field along a relatively narrow volume beneath the edge (toe) of the wedge, as a result of small-angle proton scatter. Monte Carlo simulations using MCNPX and direct measurements with radiochromic (GAFCHROMIC(®) EBT2) film were performed to quantify these effects for aluminium wedges in a 60 MeV proton beam as a function of wedge angle and position of the wedge relative to the patient. For extreme wedge angles (60° in eye tissue) and large wedge-to-patient distances (70 mm in this context), the 90-10% beam penumbra increased from 1.9 mm to 9.1 mm. In-field dose increases from small-angle proton scatter were found to contribute up to 21% additional dose, persisting along almost the full depth of the spread-out-Bragg peak. Profile broadening and in-field dose enhancement are both minimised by placing the wedge as close as possible to the patient. Use of lower atomic number wedge materials such as PMMA reduce the magnitude of both effects as a result of a reduced mean scattering angle per unit energy loss; however, their larger physical size and greater variation in density are undesirable. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

7 CFR 1005.61 - Computation of uniform prices.

Code of Federal Regulations, 2010 CFR

2010-01-01

... month, the market administrator shall compute a uniform butterfat price, a uniform skim milk price, and...) and (a)(2) of this section. (b) Uniform skim milk price. The uniform skim milk price per hundredweight... paragraph (a) of this section times 3.5 pounds of butterfat; and (2) Multiply the uniform skim milk price...

High-NA optical CD metrology on small in-cell targets enabling improved higher order dose control and process control for logic

NASA Astrophysics Data System (ADS)

Cramer, Hugo; Mc Namara, Elliott; van Laarhoven, Rik; Jaganatharaja, Ram; de la Fuente, Isabel; Hsu, Sharon; Belletti, Filippo; Popadic, Milos; Tu, Ward; Huang, Wade

2017-03-01

The logic manufacturing process requires small in-device metrology targets to exploit the full dose correction potential of the modern scanners and process tools. A high-NA angular resolved scatterometer (YieldStar S-1250D) was modified to demonstrate the possibility of OCD measurements on 5x5µm2 targets. The results obtained on test wafers in a logic manufacturing environment, measured after litho and after core etch, showed a good correlation to larger reference targets and AEI to ADI intra-field CDU correlation, thereby demonstrating the feasibility of OCD on such small targets. The data was used to determine a reduction potential of 55% for the intra-field CD variation, using 145 points per field on a few inner fields, and 33% of the process induced across wafer CD variation using 16 points per field full wafer. In addition, the OCD measurements reveal valuable information on wafer-to-wafer layer height variations within a lot.

Antibiotic Dosing in Continuous Renal Replacement Therapy.

PubMed

Shaw, Alexander R; Mueller, Bruce A

2017-07-01

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Reading sentences of uniform word length: Evidence for the adaptation of the preferred saccade length during reading.

PubMed

Cutter, Michael G; Drieghe, Denis; Liversedge, Simon P

2017-11-01

In the current study, the effect of removing word length variability within sentences on spatial aspects of eye movements during reading was investigated. Participants read sentences that were uniform in terms of word length, with each sentence consisting entirely of three-, four-, or five-letter words, or a combination of these word lengths. Several interesting findings emerged. Adaptation of the preferred saccade length occurred for sentences with different uniform word length; participants would be more accurate at making short saccades while reading uniform sentences of three-letter words, while they would be more accurate at making long saccades while reading uniform sentences of five-letter words. Furthermore, word skipping was affected such that three- and four-letter words were more likely, and five-letter words less likely, to be directly fixated in uniform compared to non-uniform sentences. It is argued that saccadic targeting during reading is highly adaptable and flexible toward the characteristics of the text currently being read, as opposed to the idea implemented in most current models of eye movement control during reading that readers develop a preference for making saccades of a certain length across a lifetime of experience with a given language. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Apparatus for producing cryogenic inertially driven fusion targets

DOEpatents

Miller, John R.

1981-01-01

A new technique for producing uniform layers of solid DT on microballoon surfaces. Local heating of the target, typically by means of a focused laser, within an isothermal freezing cell containing a low pressure cryogenic exchange gas such as helium, vaporizes the DT fuel contained within the microballoon. Removal of the laser heating source causes the DT gas to rapidly condense and freeze in a layer which exhibits a good degree of uniformity.

Ultrasonic backscatter imaging by shear-wave-induced echo phase encoding of target locations.

PubMed

McAleavey, Stephen

2011-01-01

We present a novel method for ultrasound backscatter image formation wherein lateral resolution of the target is obtained by using traveling shear waves to encode the lateral position of targets in the phase of the received echo. We demonstrate that the phase modulation as a function of shear wavenumber can be expressed in terms of a Fourier transform of the lateral component of the target echogenicity. The inverse transform, obtained by measurements of the phase modulation over a range of shear wave spatial frequencies, yields the lateral scatterer distribution. Range data are recovered from time of flight as in conventional ultrasound, yielding a B-mode-like image. In contrast to conventional ultrasound imaging, where mechanical or electronic focusing is used and lateral resolution is determined by aperture size and wavelength, we demonstrate that lateral resolution using the proposed method is independent of the properties of the aperture. Lateral resolution of the target is achieved using a stationary, unfocused, single-element transducer. We present simulated images of targets of uniform and non-uniform shear modulus. Compounding for speckle reduction is demonstrated. Finally, we demonstrate image formation with an unfocused transducer in gelatin phantoms of uniform shear modulus.

Surface dose measurement for helical tomotherapy.

PubMed

Snir, Jonatan A; Mosalaei, Homeira; Jordan, Kevin; Yartsev, Slav

2011-06-01

To compare the surface dose measurements made by different dosimeters for the helical tomotherapy (HT) plan in the case of the target close to the surface. Surface dose measurements in different points for the HT plan to deliver 2 Gy to the planning target volume (PTV) at 5 mm below the surface of the cylindrical phantom were performed by radiochromic films, single use metal oxide semiconductor field-effect transistor (MOSFET) dosimeters, silicon IVD QED diode, and optically stimulated luminescence (OSL) dosimeters. The measured doses by all dosimeters were within 12 +/- 8% difference of each other. Radiochromic films, EBT, and EBT2, provide high spatial resolution, although it is difficult to get accurate measurements of dose. Both the OSL and QED measured similar dose to that of the MOSFET detectors. The QED dosimeter is promising as a reusable on-line wireless dosimeter, while the OSL dosimeters are easier to use, require minimum setup time and are very precise.

Logical optimization for database uniformization

NASA Technical Reports Server (NTRS)

Grant, J.

1984-01-01

Data base uniformization refers to the building of a common user interface facility to support uniform access to any or all of a collection of distributed heterogeneous data bases. Such a system should enable a user, situated anywhere along a set of distributed data bases, to access all of the information in the data bases without having to learn the various data manipulation languages. Furthermore, such a system should leave intact the component data bases, and in particular, their already existing software. A survey of various aspects of the data bases uniformization problem and a proposed solution are presented.

General route to multifunctional uniform yolk/mesoporous silica shell nanocapsules: a platform for simultaneous cancer-targeted imaging and magnetically guided drug delivery.

PubMed

Zhang, Lingyu; Wang, Tingting; Yang, Lei; Liu, Cong; Wang, Chungang; Liu, Haiyan; Wang, Y Andrew; Su, Zhongmin

2012-09-24

Hollow mesoporous SiO(2) (mSiO(2)) nanostructures with movable nanoparticles (NPs) as cores, so-called yolk-shell nanocapsules (NCs), have attracted great research interest. However, a highly efficient, simple and general way to produce yolk-mSiO(2) shell NCs with tunable functional cores and shell compositions is still a great challenge. A facile, general and reproducible strategy has been developed for fabricating discrete, monodisperse and highly uniform yolk-shell NCs under mild conditions, composed of mSiO(2) shells and diverse functional NP cores with different compositions and shapes. These NPs can be Fe(3)O(4) NPs, gold nanorods (GNRs), and rare-earth upconversion NRs, endowing the yolk-mSiO(2) shell NCs with magnetic, plasmonic, and upconversion fluorescent properties. In addition, multifunctional yolk-shell NCs with tunable interior hollow spaces and mSiO(2) shell thickness can be precisely controlled. More importantly, fluorescent-magnetic-biotargeting multifunctional polyethyleneimine (PEI)-modified fluorescent Fe(3)O(4)@mSiO(2) yolk-shell nanobioprobes as an example for simultaneous targeted fluorescence imaging and magnetically guided drug delivery to liver cancer cells is also demonstrated. This synthetic approach can be easily extended to the fabrication of multifunctional yolk@mSiO(2) shell nanostructures that encapsulate various functional movable NP cores, which construct a potential platform for the simultaneous targeted delivery of drug/gene/DNA/siRNA and bio-imaging. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Off-axis dose equivalent due to secondary neutrons from uniform scanning proton beams during proton radiotherapy

NASA Astrophysics Data System (ADS)

Islam, M. R.; Collums, T. L.; Zheng, Y.; Monson, J.; Benton, E. R.

2013-11-01

The production of secondary neutrons is an undesirable byproduct of proton therapy and it is important to quantify the contribution from secondary neutrons to patient dose received outside the treatment volume. The purpose of this study is to investigate the off-axis dose equivalent from secondary neutrons experimentally using CR-39 plastic nuclear track detectors (PNTD) at ProCure Proton Therapy Center, Oklahoma City, OK. In this experiment, we placed several layers of CR-39 PNTD laterally outside the treatment volume inside a phantom and in air at various depths and angles with respect to the primary beam axis. Three different proton beams with max energies of 78, 162 and 226 MeV and 4 cm modulation width, a 5 cm diameter brass aperture, and a small snout located 38 cm from isocenter were used for the entire experiment. Monte Carlo simulations were also performed based on the experimental setup using a simplified snout configuration and the FLUKA Monte Carlo radiation transport code. The measured ratio of secondary neutron dose equivalent to therapeutic primary proton dose (H/D) ranged from 0.3 ± 0.08 mSv Gy-1 for 78 MeV proton beam to 37.4 ± 2.42 mSv Gy-1 for 226 MeV proton beam. Both experiment and simulation showed a similar decreasing trend in dose equivalent with distance to the central axis and the magnitude varied by a factor of about 2 in most locations. H/D was found to increase as the energy of the primary proton beam increased and higher H/D was observed at 135° compared to 45° and 90°. The overall higher H/D in air indicates the predominance of external neutrons produced in the nozzle rather than inside the body.

Foam shell cryogenic ICF target

DOEpatents

Darling, Dale H.

1987-01-01

A uniform cryogenic layer of DT fuel is maintained in a fusion target having a low density, small pore size, low Z rigid foam shell saturated with liquid DT fuel. Capillary action prevents gravitational slumping of the fuel layer. The saturated shell may be cooled to produce a solid fuel layer.

In vivo dose verification method in catheter based high dose rate brachytherapy.

PubMed

Jaselskė, Evelina; Adlienė, Diana; Rudžianskas, Viktoras; Urbonavičius, Benas Gabrielis; Inčiūra, Arturas

2017-12-01

In vivo dosimetry is a powerful tool for dose verification in radiotherapy. Its application in high dose rate (HDR) brachytherapy is usually limited to the estimation of gross errors, due to inability of the dosimetry system/ method to record non-uniform dose distribution in steep dose gradient fields close to the radioactive source. In vivo dose verification in interstitial catheter based HDR brachytherapy is crucial since the treatment is performed inserting radioactive source at the certain positions within the catheters that are pre-implanted into the tumour. We propose in vivo dose verification method for this type of brachytherapy treatment which is based on the comparison between experimentally measured and theoretical dose values calculated at well-defined locations corresponding dosemeter positions in the catheter. Dose measurements were performed using TLD 100-H rods (6 mm long, 1 mm diameter) inserted in a certain sequences into additionally pre-implanted dosimetry catheter. The adjustment of dosemeter positioning in the catheter was performed using reconstructed CT scans of patient with pre-implanted catheters. Doses to three Head&Neck and one Breast cancer patient have been measured during several randomly selected treatment fractions. It was found that the average experimental dose error varied from 4.02% to 12.93% during independent in vivo dosimetry control measurements for selected Head&Neck cancer patients and from 7.17% to 8.63% - for Breast cancer patient. Average experimental dose error was below the AAPM recommended margin of 20% and did not exceed the measurement uncertainty of 17.87% estimated for this type of dosemeters. Tendency of slightly increasing average dose error was observed in every following treatment fraction of the same patient. It was linked to the changes of theoretically estimated dosemeter positions due to the possible patient's organ movement between different treatment fractions, since catheter reconstruction was

Impact of grid size on uniform scanning and IMPT plans in XiO treatment planning system for brain cancer

PubMed Central

Zheng, Yuanshui

2015-01-01

The main purposes of this study are to: 1) evaluate the accuracy of XiO treatment planning system (TPS) for different dose calculation grid size based on head phantom measurements in uniform scanning proton therapy (USPT); and 2) compare the dosimetric results for various dose calculation grid sizes based on real computed tomography (CT) dataset of pediatric brain cancer treatment plans generated by USPT and intensity‐modulated proton therapy (IMPT) techniques. For phantom study, we have utilized the anthropomorphic head proton phantom provided by Imaging and Radiation Oncology Core (IROC). The imaging, treatment planning, and beam delivery were carried out following the guidelines provided by the IROC. The USPT proton plan was generated in the XiO TPS, and dose calculations were performed for grid size ranged from 1 to 3 mm. The phantom containing thermoluminescent dosimeter (TLDs) and films was irradiated using uniform scanning proton beam. The irradiated TLDs were read by the IROC. The calculated doses from the XiO for different grid sizes were compared to the measured TLD doses provided by the IROC. Gamma evaluation was done by comparing calculated planar dose distribution of 3 mm grid size with measured planar dose distribution. Additionally, IMPT plan was generated based on the same CT dataset of the IROC phantom, and IMPT dose calculations were performed for grid size ranged from 1 to 3 mm. For comparative purpose, additional gamma analysis was done by comparing the planar dose distributions of standard grid size (3 mm) with that of other grid sizes (1, 1.5, 2, and 2.5 mm) for both the USPT and IMPT plans. For patient study, USPT plans of three pediatric brain cancer cases were selected. IMPT plans were generated for each of three pediatric cases. All patient treatment plans (USPT and IMPT) were generated in the XiO TPS for a total dose of 54 Gy (relative biological effectiveness [RBE]). Treatment plans (USPT and IMPT) of each case was recalculated for

Choosing a therapy electron accelerator target.

PubMed

Hutcheon, R M; Schriber, S O; Funk, L W; Sherman, N K

1979-01-01

Angular distributions of photon depth dose produced by 25-MeV electrons incident on several fully stopping single-element targets (C, Al, Cu, Mo, Ta, Pb) and two composite layered targets (Ni-Al, W-Al) were studied. Depth-dose curves measured using TLD-700 (thermoluminescent dosimeter) chips embedded in lucite phantoms. Several useful therapy electron accelerator design curves were determined, including relative flattener thickness as a function of target atomic number, "effective" bremsstrahlung endpoint energy or beam "hardness" as a function of target atomic number and photon emission angle, and estimates of shielding thickness as a function of angle required to reduce the radiation outside the treatment cone to required levels.

Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA

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

Han, Eun Young, E-mail: eyhan@uams.edu; Kim, Dong-Wook; Zhang, Xin

It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics—target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose—were compared for each case. Consequently,more » the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy.« less

High-dose MVCT image guidance for stereotactic body radiation therapy.

PubMed

Westerly, David C; Schefter, Tracey E; Kavanagh, Brian D; Chao, Edward; Lucas, Dan; Flynn, Ryan T; Miften, Moyed

2012-08-01

Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp∕mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. High-dose imaging modes are made possible on a clinical tomotherapy machine by

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

PubMed Central

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

2012-01-01

Purpose: The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique’s sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved. Methods: They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans’ sensitivity to uncertainties. Results: With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies. Conclusions: IMPT’s sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the

[A practical procedure to improve the accuracy of radiochromic film dosimetry: a integration with a correction method of uniformity correction and a red/blue correction method].

PubMed

Uehara, Ryuzo; Tachibana, Hidenobu; Ito, Yasushi; Yoshino, Shinichi; Matsubayashi, Fumiyasu; Sato, Tomoharu

2013-06-01

It has been reported that the light scattering could worsen the accuracy of dose distribution measurement using a radiochromic film. The purpose of this study was to investigate the accuracy of two different films, EDR2 and EBT2, as film dosimetry tools. The effectiveness of a correction method for the non-uniformity caused from EBT2 film and the light scattering was also evaluated. In addition the efficacy of this correction method integrated with the red/blue correction method was assessed. EDR2 and EBT2 films were read using a flatbed charge-coupled device scanner (EPSON 10000G). Dose differences on the axis perpendicular to the scanner lamp movement axis were within 1% with EDR2, but exceeded 3% (Maximum: +8%) with EBT2. The non-uniformity correction method, after a single film exposure, was applied to the readout of the films. A corrected dose distribution data was subsequently created. The correction method showed more than 10%-better pass ratios in dose difference evaluation than when the correction method was not applied. The red/blue correction method resulted in 5%-improvement compared with the standard procedure that employed red color only. The correction method with EBT2 proved to be able to rapidly correct non-uniformity, and has potential for routine clinical IMRT dose verification if the accuracy of EBT2 is required to be similar to that of EDR2. The use of red/blue correction method may improve the accuracy, but we recommend we should use the red/blue correction method carefully and understand the characteristics of EBT2 for red color only and the red/blue correction method.

24 CFR 5.801 - Uniform financial reporting standards.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Uniform financial reporting... and Urban Development GENERAL HUD PROGRAM REQUIREMENTS; WAIVERS Uniform Financial Reporting Standards § 5.801 Uniform financial reporting standards. (a) Applicability. This subpart H implements uniform...

24 CFR 5.801 - Uniform financial reporting standards.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Uniform financial reporting... and Urban Development GENERAL HUD PROGRAM REQUIREMENTS; WAIVERS Uniform Financial Reporting Standards § 5.801 Uniform financial reporting standards. (a) Applicability. This subpart H implements uniform...

TU-D-209-02: A Backscatter Point Spread Function for Entrance Skin Dose Determination

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

Vijayan, S; Xiong, Z; Shankar, A

Purpose: To determine the distribution of backscattered radiation to the skin resulting from a non-uniform distribution of primary radiation through convolution with a backscatter point spread function (PSF). Methods: A backscatter PSF is determined using Monte Carlo simulation of a 1 mm primary beam incident on a 30 × 30 cm × 20 cm thick PMMA phantom using EGSnrc software. A primary profile is similarly obtained without the phantom and the difference from the total provides the backscatter profile. This scatter PSF characterizes the backscatter spread for a “point” primary interaction and can be convolved with the entrance primary dosemore » distribution to obtain the total entrance skin dose. The backscatter PSF was integrated into the skin dose tracking system (DTS), a graphical utility for displaying the color-coded skin dose distribution on a 3D graphic of the patient during interventional fluoroscopic procedures. The backscatter convolution method was validated for the non-uniform beam resulting from the use of an ROI attenuator. The ROI attenuator is a copper sheet with about 20% primary transmission (0.7 mm thick) containing a circular aperture; this attenuator is placed in the beam to reduce dose in the periphery while maintaining full dose in the region of interest. The DTS calculated primary plus backscatter distribution is compared to that measured with GafChromic film and that calculated using EGSnrc Monte-Carlo software. Results: The PSF convolution method used in the DTS software was able to account for the spread of backscatter from the ROI region to the region under the attenuator. The skin dose distribution determined using DTS with the ROI attenuator was in good agreement with the distributions measured with Gafchromic film and determined by Monte Carlo simulation Conclusion: The PSF convolution technique provides an accurate alternative for entrance skin dose determination with non-uniform primary x-ray beams. Partial support from NIH

Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats.

PubMed

López de las Hazas, Maria-Carmen; Rubió, Laura; Kotronoulas, Aristotelis; de la Torre, Rafael; Solà, Rosa; Motilva, Maria-José

2015-07-01

Hydroxytyrosol (HT) is the most prominent phenolic compound of virgin olive oil and due to its scientifically validated biological activities it is entering to the market as a potentially useful supplement for cardiovascular disease prevention. The aim of the present study was to investigate the relationship between the HT dose intake and its tissue uptake in rats, and thus, providing complementary information in relation to the target-dose relationship. Rats were given a refined olive oil enriched with HT at different doses (1, 10, and 100 mg/kg) and they were sacrificed after 5 h to ensure the cell tissue uptake of HT and its metabolites. Plasma samples and different organs as liver, kidney, heart and brain were obtained, and HT metabolites were analyzed by UPLC-MS/MS. The results showed that HT and its metabolites could be accumulated in a dose-dependent manner basically in the liver, kidney, and brain and were detected in these tissues even at nutritionally relevant human doses. The detection of free HT in liver and kidney was noteworthy. To date, this appears to be the only biologically active form, and thus, it provides relevant information for optimizing the potential applications of HT to prevent certain hepatic and renal diseases. In recent years, HT and its derivatives have led to a great interest from the virgin olive oil producers and manufacturers of nutraceutical supplements. The increasing interest in HT is mainly due to the European Food Safety Agency (EFSA) Panel on Dietetic Products, Nutrition, and Allergies (NDA) scientific opinion that established a cause-and-effect relationship between the consumption of olive oil polyphenols and protection of LDL particles from oxidative damage . Based on this positive opinion, the health claim "Olive oil polyphenols contribute to the protection of blood lipids from oxidative stress" was included in the list of health claims , being the only authorized health claim in the European Union regarding polyphenols

7 CFR 51.2085 - Fairly uniform color.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Fairly uniform color. 51.2085 Section 51.2085... Definitions § 51.2085 Fairly uniform color. Fairly uniform color means that the shells do not show excessive variation in color, whether bleached or natural. ...

7 CFR 51.2085 - Fairly uniform color.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Fairly uniform color. 51.2085 Section 51.2085... Definitions § 51.2085 Fairly uniform color. Fairly uniform color means that the shells do not show excessive variation in color, whether bleached or natural. ...

A method for real time detecting of non-uniform magnetic field

NASA Astrophysics Data System (ADS)

Marusenkov, Andriy

2015-04-01

The principle of measuring magnetic signatures for observing diverse objects is widely used in Near Surface work (unexploded ordnance (UXO); engineering & environmental; archaeology) and security and vehicle detection systems as well. As a rule, the magnitude of the signals to be measured is much lower than that of the quasi-uniform Earth magnetic field. Usually magnetometers for these purposes contain two or more spatially separated sensors to estimate the full tensor gradient of the magnetic field or, more frequently, only partial gradient components. The both types (scalar and vector) of magnetic sensors could be used. The identity of the scale factors and proper alignment of the sensitivity axes of the vector sensors are very important for deep suppression of the ambient field and detection of weak target signals. As a rule, the periodical calibration procedure is used to keep matching sensors' parameters as close as possible. In the present report we propose the technique for detection magnetic anomalies, which is almost insensitive to imperfect matching of the sensors. This method based on the idea that the difference signals between two sensors are considerably different when the instrument is rotated or moved in uniform and non-uniform fields. Due to the misfit of calibration parameters the difference signal observed at the rotation in the uniform field is similar to the total signal - the sum of the signals of both sensors. Zero change of the difference and total signals is expected, if the instrument moves in the uniform field along a straight line. In contrast, the same move in the non-uniform field produces some response of each of the sensors. In case one measures dB/dx and moves along x direction, the sensors signals is shifted in time with the lag proportional to the distance between sensors and the speed of move. It means that the difference signal looks like derivative of the total signal at move in the non-uniform field. So, using quite simple

Limitations of contrast enhancement for infrared target identification

NASA Astrophysics Data System (ADS)

Du Bosq, Todd W.; Fanning, Jonathan D.

2009-05-01

Contrast enhancement and dynamic range compression are currently being used to improve the performance of infrared imagers by increasing the contrast between the target and the scene content. Automatic contrast enhancement techniques do not always achieve this improvement. In some cases, the contrast can increase to a level of target saturation. This paper assesses the range-performance effects of contrast enhancement for target identification as a function of image saturation. Human perception experiments were performed to determine field performance using contrast enhancement on the U.S. Army RDECOM CERDEC NVESD standard military eight target set using an un-cooled LWIR camera. The experiments compare the identification performance of observers viewing contrast enhancement processed images at various levels of saturation. Contrast enhancement is modeled in the U.S. Army thermal target acquisition model (NVThermIP) by changing the scene contrast temperature. The model predicts improved performance based on any improved target contrast, regardless of specific feature saturation or enhancement. The measured results follow the predicted performance based on the target task difficulty metric used in NVThermIP for the non-saturated cases. The saturated images reduce the information contained in the target and performance suffers. The model treats the contrast of the target as uniform over spatial frequency. As the contrast is enhanced, the model assumes that the contrast is enhanced uniformly over the spatial frequencies. After saturation, the spatial cues that differentiate one tank from another are located in a limited band of spatial frequencies. A frequency dependent treatment of target contrast is needed to predict performance of over-processed images.

Effects of broiler breeder management on pullet body weight and carcass uniformity.

PubMed

Zuidhof, M J; Holm, D E; Renema, R A; Jalal, M A; Robinson, F E

2015-06-01

An experiment was conducted to study the effect of broiler breeder feeding management practices on pullet performance, BW uniformity, and carcass traits during rearing (to 22 wk of age). At 3 wk of age, 1,200 Ross 308 breeder pullets were assigned to one of 5 treatments: 1) control: standard mash diet, fed daily; 2) high fiber: mash diet containing 25% lower nutrient density, fed daily; 3) scatter: standard diet in pellet form scattered on litter, fed daily; 4) skip-a-day: standard mash diet, fed on alternate days; or 5) grading: standard mash diet, fed daily (birds sorted into low, average, and high BW groups every 4 wk). Birds on the high fiber treatment consumed more feed (P<0.0001) and had the highest feed conversion ratio (FCR; P<0.004) but the lowest ME to gain and CP to gain ratios (P≤0.002). Skip-a-day treatment pullets consumed more ME and CP than birds in any other treatment (P<0.001). Grading yielded the highest BW uniformity at 22 wk of age (CV=6.2%), while control and high fiber treatment groups were least uniform (CV>15%; P<0.0001). Skip-a-day feed restriction produced birds with the significantly lowest breast muscle and highest liver weight compared to all other treatments (P<0.05). Variation in shank length, chest width, and breast muscle was lowest in the grading treatment, whereas the CV for fat pad and liver was lowest in the skip-a-day treatment. In this trial, broiler breeder target BW profiles were achieved using combinations of quantitative and qualitative feed restriction, or preemptive management practices. Qualitative diet dilution and skip-a-day management did little to increase flock uniformity relative to the control during the most intense period of feed restriction (7 to 19 wk). Scatter feeding increased flock uniformity to a small degree, whereas grading yielded the highest increase in BW and carcass trait uniformity. © 2015 Poultry Science Association Inc.

Uniform-related infection control practices of dental students

PubMed Central

Aljohani, Yazan; Almutadares, Mohammed; Alfaifi, Khalid; El Madhoun, Mona; Albahiti, Maysoon H; Al-Hazmi, Nadia

2017-01-01

Background Uniform-related infection control practices are sometimes overlooked and underemphasized. In Saudi Arabia, personal protective equipment must meet global standards for infection control, but the country’s Islamic legislature also needs to be taken into account. Aim To assess uniform-related infection control practices of a group of dental students in a dental school in Saudi Arabia and compare the results with existing literature related to cross-contamination through uniforms in the dental field. Method A questionnaire was formulated and distributed to dental students at King Abdulaziz University Faculty of Dentistry in Jeddah, Saudi Arabia, which queried the students about their uniform-related infection control practices and their methods and frequency of laundering and sanitizing their uniforms, footwear, and name tags. Results There is a significant difference between genders with regard to daily uniform habits. The frequency of uniform washing was below the standard and almost 30% of students were not aware of how their uniforms are washed. Added to this, there is no consensus on a unified uniform for male and female students. Conclusion Information on preventing cross-contamination through wearing uniforms must be supplied, reinforced, and emphasized while taking into consideration the cultural needs of the Saudi society. PMID:28490894

School Uniforms: Esprit de Corps.

ERIC Educational Resources Information Center

Ryan, Rosemary P.; Ryan, Thomas E.

1998-01-01

The benefits of school uniforms far outweigh their short-term costs. School uniforms not only keep students safe, but they increase their self-esteem, promote a more positive attitude toward school, lead to improved student behavior, and help blur social-class distinctions. Students are allowed to wear their own political or religious messages,…

Collimated proton pencil-beam scanning for superficial targets: impact of the order of range shifter and aperture

NASA Astrophysics Data System (ADS)

Bäumer, C.; Janson, M.; Timmermann, B.; Wulff, J.

2018-04-01

To assess if apertures shall be mounted upstream or downstream of a range shifting block if these field-shaping devices are combined with the pencil-beam scanning delivery technique (PBS). The lateral dose fall-off served as a benchmark parameter. Both options realizing PBS-with-apertures were compared to the uniform scanning mode. We also evaluated the difference regarding the out-of-field dose caused by interactions of protons in beam-shaping devices. The potential benefit of the downstream configuration over the upstream configuration was estimated analytically. Guided by this theoretical evaluation a mechanical adapter was developed which transforms the upstream configuration provided by the proton machine vendor to a downstream configuration. Transversal dose profiles were calculated with the Monte-Carlo based dose engine of the commercial treatment planning system RayStation 6. Two-dimensional dose planes were measured with an ionization chamber array and a scintillation detector at different depths and compared to the calculation. Additionally, a clinical example for the irradiation of the orbit was compared for both PBS options and a uniform scanning treatment plan. Assuming the same air gap the lateral dose fall-off at the field edge at a few centimeter depth is 20% smaller for the aperture-downstream configuration than for the upstream one. For both options of PBS-with-apertures the dose fall-off is larger than in uniform scanning delivery mode if the minimum accelerator energy is 100 MeV. The RayStation treatment planning system calculated the width of the lateral dose fall-off with an accuracy of typically 0.1 mm–0.3 mm. Although experiments and calculations indicate a ranking of the three delivery options regarding lateral dose fall-off, there seems to be a limited impact on a multi-field treatment plan.

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

NASA Technical Reports Server (NTRS)

Chappell, Lori J.; Cucinotta, Francis A.

2010-01-01

There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies.

7 CFR 1425.13 - Uniform marketing agreement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Uniform marketing agreement. 1425.13 Section 1425.13... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.13 Uniform marketing agreement. (a) A CMA must enter into a uniform marketing agreement with each member who...

7 CFR 1425.13 - Uniform marketing agreement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Uniform marketing agreement. 1425.13 Section 1425.13... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.13 Uniform marketing agreement. (a) A CMA must enter into a uniform marketing agreement with each member who...

7 CFR 1425.13 - Uniform marketing agreement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Uniform marketing agreement. 1425.13 Section 1425.13... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.13 Uniform marketing agreement. (a) A CMA must enter into a uniform marketing agreement with each member who...

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

SU-F-19A-10: Recalculation and Reporting Clinical HDR 192-Ir Head and Neck Dose Distributions Using Model Based Dose Calculation

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

Carlsson Tedgren, A; Persson, M; Nilsson, J

Purpose: To retrospectively re-calculate dose distributions for selected head and neck cancer patients, earlier treated with HDR 192Ir brachytherapy, using Monte Carlo (MC) simulations and compare results to distributions from the planning system derived using TG43 formalism. To study differences between dose to medium (as obtained with the MC code) and dose to water in medium as obtained through (1) ratios of stopping powers and (2) ratios of mass energy absorption coefficients between water and medium. Methods: The MC code Algebra was used to calculate dose distributions according to earlier actual treatment plans using anonymized plan data and CT imagesmore » in DICOM format. Ratios of stopping power and mass energy absorption coefficients for water with various media obtained from 192-Ir spectra were used in toggling between dose to water and dose to media. Results: Differences between initial planned TG43 dose distributions and the doses to media calculated by MC are insignificant in the target volume. Differences are moderate (within 4–5 % at distances of 3–4 cm) but increase with distance and are most notable in bone and at the patient surface. Differences between dose to water and dose to medium are within 1-2% when using mass energy absorption coefficients to toggle between the two quantities but increase to above 10% for bone using stopping power ratios. Conclusion: MC predicts target doses for head and neck cancer patients in close agreement with TG43. MC yields improved dose estimations outside the target where a larger fraction of dose is from scattered photons. It is important with awareness and a clear reporting of absorbed dose values in using model based algorithms. Differences in bone media can exceed 10% depending on how dose to water in medium is defined.« less

A robust close-range photogrammetric target extraction algorithm for size and type variant targets

NASA Astrophysics Data System (ADS)

Nyarko, Kofi; Thomas, Clayton; Torres, Gilbert

2016-05-01

The Photo-G program conducted by Naval Air Systems Command at the Atlantic Test Range in Patuxent River, Maryland, uses photogrammetric analysis of large amounts of real-world imagery to characterize the motion of objects in a 3-D scene. Current approaches involve several independent processes including target acquisition, target identification, 2-D tracking of image features, and 3-D kinematic state estimation. Each process has its own inherent complications and corresponding degrees of both human intervention and computational complexity. One approach being explored for automated target acquisition relies on exploiting the pixel intensity distributions of photogrammetric targets, which tend to be patterns with bimodal intensity distributions. The bimodal distribution partitioning algorithm utilizes this distribution to automatically deconstruct a video frame into regions of interest (ROI) that are merged and expanded to target boundaries, from which ROI centroids are extracted to mark target acquisition points. This process has proved to be scale, position and orientation invariant, as well as fairly insensitive to global uniform intensity disparities.

Investigation of effective decision criteria for multiobjective optimization in IMRT.