Texture analysis on the fluence map to evaluate the degree of modulation for volumetric modulated arc therapy.

PubMed

Park, So-Yeon; Kim, Il Han; Ye, Sung-Joon; Carlson, Joel; Park, Jong Min

2014-11-01

Texture analysis on fluence maps was performed to evaluate the degree of modulation for volumetric modulated arc therapy (VMAT) plans. A total of six textural features including angular second moment, inverse difference moment, contrast, variance, correlation, and entropy were calculated for fluence maps generated from 20 prostate and 20 head and neck VMAT plans. For each of the textural features, particular displacement distances (d) of 1, 5, and 10 were adopted. To investigate the deliverability of each VMAT plan, gamma passing rates of pretreatment quality assurance, and differences in modulating parameters such as multileaf collimator (MLC) positions, gantry angles, and monitor units at each control point between VMAT plans and dynamic log files registered by the Linac control system during delivery were acquired. Furthermore, differences between the original VMAT plan and the plan reconstructed from the dynamic log files were also investigated. To test the performance of the textural features as indicators for the modulation degree of VMAT plans, Spearman's rank correlation coefficients (rs) with the plan deliverability were calculated. For comparison purposes, conventional modulation indices for VMAT including the modulation complexity score for VMAT, leaf travel modulation complexity score, and modulation index supporting station parameter optimized radiation therapy (MISPORT) were calculated, and their correlations were analyzed in the same way. There was no particular textural feature which always showed superior correlations with every type of plan deliverability. Considering the results comprehensively, contrast (d = 1) and variance (d = 1) generally showed considerable correlations with every type of plan deliverability. These textural features always showed higher correlations to the plan deliverability than did the conventional modulation indices, except in the case of modulating parameter differences. The rs values of contrast to the global gamma passing rates with criteria of 2%/2 mm, 2%/1 mm, and 1%/2 mm were 0.536, 0.473, and 0.718, respectively. The respective values for variance were 0.551, 0.481, and 0.688. In the case of local gamma passing rates, the rs values of contrast were 0.547, 0.578, and 0.620, respectively, and those of variance were 0.519, 0.527, and 0.569. All of the rs values in those cases were statistically significant (p < 0.003). In the cases of global and local gamma passing rates, MISPORT showed the highest correlations among the conventional modulation indices. For global passing rates, rs values of MISPORT were -0.420, -0.330, and -0.632, respectively, and those for local passing rates were -0.455, -0.490 and -0.502. The values of rs of contrast, variance, and MISPORT with the MLC errors were -0.863, -0.828, and 0.795, respectively, all with statistical significances (p < 0.001). The correlations with statistical significances between variance and dose-volumetric differences were observed more frequently than the others. The contrast (d = 1) and variance (d = 1) calculated from fluence maps of VMAT plans showed considerable correlations with the plan deliverability, indicating their potential use as indicators for assessing the degree of modulation of VMAT plans. Both contrast and variance consistently showed better performance than the conventional modulation indices for VMAT.

Poster - 52: Smoothing constraints in Modulated Photon Radiotherapy (XMRT) fluence map optimization

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

McGeachy, Philip; Villarreal-Barajas, Jose Eduardo

Purpose: Modulated Photon Radiotherapy (XMRT), which simultaneously optimizes photon beamlet energy (6 and 18 MV) and fluence, has recently shown dosimetric improvement in comparison to conventional IMRT. That said, the degree of smoothness of resulting fluence maps (FMs) has yet to be investigated and could impact the deliverability of XMRT. This study looks at investigating FM smoothness and imposing smoothing constraint in the fluence map optimization. Methods: Smoothing constraints were modeled in the XMRT algorithm with the sum of positive gradient (SPG) technique. XMRT solutions, with and without SPG constraints, were generated for a clinical prostate scan using standard dosimetricmore » prescriptions, constraints, and a seven coplanar beam arrangement. The smoothness, with and without SPG constraints, was assessed by looking at the absolute and relative maximum SPG scores for each fluence map. Dose volume histograms were utilized when evaluating impact on the dose distribution. Results: Imposing SPG constraints reduced the absolute and relative maximum SPG values by factors of up to 5 and 2, respectively, when compared with their non-SPG constrained counterparts. This leads to a more seamless conversion of FMS to their respective MLC sequences. This improved smoothness resulted in an increase to organ at risk (OAR) dose, however the increase is not clinically significant. Conclusions: For a clinical prostate case, there was a noticeable improvement in the smoothness of the XMRT FMs when SPG constraints were applied with a minor increase in dose to OARs. This increase in OAR dose is not clinically meaningful.« less

Commissioning and validation of fluence-based 3D VMAT dose reconstruction system using new transmission detector.

PubMed

Nakaguchi, Yuji; Oono, Takeshi; Maruyama, Masato; Shimohigashi, Yoshinobu; Kai, Yudai; Nakamura, Yuya

2018-06-01

In this study, we evaluated the basic performance of the three-dimensional dose verification system COMPASS (IBA Dosimetry). This system is capable of reconstructing 3D dose distributions on the patient anatomy based on the fluence measured using a new transmission detector (Dolphin, IBA Dosimetry) during treatment. The stability of the absolute dose and geometric calibrations of the COMPASS system with the Dolphin detector were investigated for fundamental validation. Furthermore, multileaf collimator (MLC) test patterns and a complicated volumetric modulated arc therapy (VMAT) plan were used to evaluate the accuracy of the reconstructed dose distributions determined by the COMPASS. The results from the COMPASS were compared with those of a Monte Carlo simulation (MC), EDR2 film measurement, and a treatment planning system (TPS). The maximum errors for the absolute dose and geometrical position were - 0.28% and 1.0 mm for 3 months, respectively. The Dolphin detector, which consists of ionization chamber detectors, was firmly mounted on the linear accelerator and was very stable. For the MLC test patterns, the TPS showed a > 5% difference at small fields, while the COMPASS showed good agreement with the MC simulation at small fields. However, the COMPASS produced a large error for complex small fields. For a clinical VMAT plan, COMPASS was more accurate than TPS. COMPASS showed real delivered-dose distributions because it uses the measured fluence, a high-resolution detector, and accurate beam modeling. We confirm here that the accuracy and detectability of the delivered dose of the COMPASS system are sufficient for clinical practice.

SU-E-T-195: Commissioning the Neutron Production of a Varian TrueBeam Linac

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

Irazola, L; Brualla, L; Rosello, J

2015-06-15

Purpose: The purpose of this work is the characterization of a new Varian TrueBeam™ facility in terms of neutron production, in order to estimate neutron equivalent dose in organs during radiotherapy treatments. Methods: The existing methodology [1] was used with the reference SRAMnd detector, calibrated in terms of thermal neutron fluence at the reference field operated by PTB (Physikalisch-Technische-Bundesanstalt) at the GeNF (Geesthacht-Neutron-Facility) with the GKSS reactor FRG-1 [2]. Thermal neutron fluence for the 5 available possibilities was evaluated: 15 MV and 10&6 MV with and without Flattening Filter (FF and FFF, respectively). Irradiation conditions are as described in [3].more » In addition, three different collimator-MLC configurations were studied for 15 MV: (a) collimator of 10×10 cm{sup 2} and MLC fully retracted (reference), (b) field sizes of 20×20 cm{sup 2} and 10×10 cm{sup 2} for collimator and MLC respectively, and (c) collimator and MLC aperture of 10×10 cm{sup 2}. Results: Thermal fluence rate at the “reference point” [3], as a consequence of the neutron production, obtained for (a) conformation in 15 MV is (1.45±0.11) x10{sup 4} n•cm{sup 2}/MU. Configurations (b) and (c) gave fluences of 96.6% and 97.8% of the reference (a). Neutron production decreases up to 8.6% and 5.7% for the 10 MV FF and FFF beams, respectively. Finally, it decreases up to 2.8% and 0.1% for the 6 MV FF and FFF modes, respectively. Conclusion: This work evaluates thermal neutron production of Varian TrueBeam™ system for organ equivalent dose estimation. The small difference in collimator-MLC configuration shows the universality of the methodology [3]. A decrease in this production is shown when decreasing energy from 15 to 10 MV and an almost negligible production was found for 6 MV. Moreover, a lower neutron contribution is observed for the FFF modes.[1]Phys Med Biol,2012;57:6167–6191.[2]Radiat Meas,2010;45:1513–1517.[3]Med Phys,2015;42:276–281.« less

SU-E-T-214: Intensity Modulated Proton Therapy (IMPT) Based On Passively Scattered Protons and Multi-Leaf Collimation: Prototype TPS and Dosimetry Study

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

Sanchez-Parcerisa, D; Carabe-Fernandez, A

2014-06-01

Purpose. Intensity-modulated proton therapy is usually implemented with multi-field optimization of pencil-beam scanning (PBS) proton fields. However, at the view of the experience with photon-IMRT, proton facilities equipped with double-scattering (DS) delivery and multi-leaf collimation (MLC) could produce highly conformal dose distributions (and possibly eliminate the need for patient-specific compensators) with a clever use of their MLC field shaping, provided that an optimal inverse TPS is developed. Methods. A prototype TPS was developed in MATLAB. The dose calculation process was based on a fluence-dose algorithm on an adaptive divergent grid. A database of dose kernels was precalculated in order tomore » allow for fast variations of the field range and modulation during optimization. The inverse planning process was based on the adaptive simulated annealing approach, with direct aperture optimization of the MLC leaves. A dosimetry study was performed on a phantom formed by three concentrical semicylinders separated by 5 mm, of which the inner-most and outer-most were regarded as organs at risk (OARs), and the middle one as the PTV. We chose a concave target (which is not treatable with conventional DS fields) to show the potential of our technique. The optimizer was configured to minimize the mean dose to the OARs while keeping a good coverage of the target. Results. The plan produced by the prototype TPS achieved a conformity index of 1.34, with the mean doses to the OARs below 78% of the prescribed dose. This Result is hardly achievable with traditional conformal DS technique with compensators, and it compares to what can be obtained with PBS. Conclusion. It is certainly feasible to produce IMPT fields with MLC passive scattering fields. With a fully developed treatment planning system, the produced plans can be superior to traditional DS plans in terms of plan conformity and dose to organs at risk.« less

Texture analysis on the fluence map to evaluate the degree of modulation for volumetric modulated arc therapy

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

Park, So-Yeon; Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul 110-744; Biomedical Research Institute, Seoul National University College of Medicine, Seoul 110-744

Purpose: Texture analysis on fluence maps was performed to evaluate the degree of modulation for volumetric modulated arc therapy (VMAT) plans. Methods: A total of six textural features including angular second moment, inverse difference moment, contrast, variance, correlation, and entropy were calculated for fluence maps generated from 20 prostate and 20 head and neck VMAT plans. For each of the textural features, particular displacement distances (d) of 1, 5, and 10 were adopted. To investigate the deliverability of each VMAT plan, gamma passing rates of pretreatment quality assurance, and differences in modulating parameters such as multileaf collimator (MLC) positions, gantrymore » angles, and monitor units at each control point between VMAT plans and dynamic log files registered by the Linac control system during delivery were acquired. Furthermore, differences between the original VMAT plan and the plan reconstructed from the dynamic log files were also investigated. To test the performance of the textural features as indicators for the modulation degree of VMAT plans, Spearman’s rank correlation coefficients (r{sub s}) with the plan deliverability were calculated. For comparison purposes, conventional modulation indices for VMAT including the modulation complexity score for VMAT, leaf travel modulation complexity score, and modulation index supporting station parameter optimized radiation therapy (MI{sub SPORT}) were calculated, and their correlations were analyzed in the same way. Results: There was no particular textural feature which always showed superior correlations with every type of plan deliverability. Considering the results comprehensively, contrast (d = 1) and variance (d = 1) generally showed considerable correlations with every type of plan deliverability. These textural features always showed higher correlations to the plan deliverability than did the conventional modulation indices, except in the case of modulating parameter differences. The r{sub s} values of contrast to the global gamma passing rates with criteria of 2%/2 mm, 2%/1 mm, and 1%/2 mm were 0.536, 0.473, and 0.718, respectively. The respective values for variance were 0.551, 0.481, and 0.688. In the case of local gamma passing rates, the r{sub s} values of contrast were 0.547, 0.578, and 0.620, respectively, and those of variance were 0.519, 0.527, and 0.569. All of the r{sub s} values in those cases were statistically significant (p < 0.003). In the cases of global and local gamma passing rates, MI{sub SPORT} showed the highest correlations among the conventional modulation indices. For global passing rates, r{sub s} values of MI{sub SPORT} were −0.420, −0.330, and −0.632, respectively, and those for local passing rates were −0.455, −0.490 and −0.502. The values of r{sub s} of contrast, variance, and MI{sub SPORT} with the MLC errors were −0.863, −0.828, and 0.795, respectively, all with statistical significances (p < 0.001). The correlations with statistical significances between variance and dose-volumetric differences were observed more frequently than the others. Conclusions: The contrast (d = 1) and variance (d = 1) calculated from fluence maps of VMAT plans showed considerable correlations with the plan deliverability, indicating their potential use as indicators for assessing the degree of modulation of VMAT plans. Both contrast and variance consistently showed better performance than the conventional modulation indices for VMAT.« less

Quality assurance for online adapted treatment plans: Benchmarking and delivery monitoring simulation

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

Li, Taoran, E-mail: taoran.li.duke@gmail.com; Wu, Qiuwen; Yang, Yun

Purpose: An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. Methods: The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system wasmore » designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system’s performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Results: Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system’s ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. Conclusions: The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.« less

Quality assurance for online adapted treatment plans: benchmarking and delivery monitoring simulation.

PubMed

Li, Taoran; Wu, Qiuwen; Yang, Yun; Rodrigues, Anna; Yin, Fang-Fang; Jackie Wu, Q

2015-01-01

An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system was designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system's performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system's ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.

SU-E-T-605: Performance Evaluation of MLC Leaf-Sequencing Algorithms in Head-And-Neck IMRT

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

Jing, J; Lin, H; Chow, J

2015-06-15

Purpose: To investigate the efficiency of three multileaf collimator (MLC) leaf-sequencing algorithms proposed by Galvin et al, Chen et al and Siochi et al using external beam treatment plans for head-and-neck intensity modulated radiation therapy (IMRT). Methods: IMRT plans for head-and-neck were created using the CORVUS treatment planning system. The plans were optimized and the fluence maps for all photon beams determined. Three different MLC leaf-sequencing algorithms based on Galvin et al, Chen et al and Siochi et al were used to calculate the final photon segmental fields and their monitor units in delivery. For comparison purpose, the maximum intensitymore » of fluence map was kept constant in different plans. The number of beam segments and total number of monitor units were calculated for the three algorithms. Results: From results of number of beam segments and total number of monitor units, we found that algorithm of Galvin et al had the largest number of monitor unit which was about 70% larger than the other two algorithms. Moreover, both algorithms of Galvin et al and Siochi et al have relatively lower number of beam segment compared to Chen et al. Although values of number of beam segment and total number of monitor unit calculated by different algorithms varied with the head-and-neck plans, it can be seen that algorithms of Galvin et al and Siochi et al performed well with a lower number of beam segment, though algorithm of Galvin et al had a larger total number of monitor units than Siochi et al. Conclusion: Although performance of the leaf-sequencing algorithm varied with different IMRT plans having different fluence maps, an evaluation is possible based on the calculated number of beam segment and monitor unit. In this study, algorithm by Siochi et al was found to be more efficient in the head-and-neck IMRT. The Project Sponsored by the Fundamental Research Funds for the Central Universities (J2014HGXJ0094) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.« less

Clinical validation of an in-house EPID dosimetry system for IMRT QA at the Prince of Wales Hospital

NASA Astrophysics Data System (ADS)

Tyler, M.; Vial, P.; Metcalfe, P.; Downes, S.

2013-06-01

In this study a simple method using standard flood-field corrected Electronic Portal Imaging Device (EPID) images for routine Intensity Modulated Radiation Therapy (IMRT) Quality Assurance (QA) was investigated. The EPID QA system was designed and tested on a Siemens Oncor Impression linear accelerator with an OptiVue 1000ST EPID panel (Siemens Medical Solutions USA, Inc, USA) and an Elekta Axesse linear accelerator with an iViewGT EPID (Elekta AB, Sweden) for 6 and 10 MV IMRT fields with Step-and-Shoot and dynamic-MLC delivery. Two different planning systems were used for patient IMRT field generation for comparison with the measured EPID fluences. All measured IMRT plans had >95% agreement to the planning fluences (using 3 cGy / 3 mm Gamma Criteria) and were comparable to the pass-rates calculated using a 2-D diode array dosimeter.

Towards real-time VMAT verification using a prototype, high-speed CMOS active pixel sensor.

PubMed

Zin, Hafiz M; Harris, Emma J; Osmond, John P F; Allinson, Nigel M; Evans, Philip M

2013-05-21

This work investigates the feasibility of using a prototype complementary metal oxide semiconductor active pixel sensor (CMOS APS) for real-time verification of volumetric modulated arc therapy (VMAT) treatment. The prototype CMOS APS used region of interest read out on the chip to allow fast imaging of up to 403.6 frames per second (f/s). The sensor was made larger (5.4 cm × 5.4 cm) using recent advances in photolithographic technique but retains fast imaging speed with the sensor's regional read out. There is a paradigm shift in radiotherapy treatment verification with the advent of advanced treatment techniques such as VMAT. This work has demonstrated that the APS can track multi leaf collimator (MLC) leaves moving at 18 mm s(-1) with an automatic edge tracking algorithm at accuracy better than 1.0 mm even at the fastest imaging speed. Evaluation of the measured fluence distribution for an example VMAT delivery sampled at 50.4 f/s was shown to agree well with the planned fluence distribution, with an average gamma pass rate of 96% at 3%/3 mm. The MLC leaves motion and linac pulse rate variation delivered throughout the VMAT treatment can also be measured. The results demonstrate the potential of CMOS APS technology as a real-time radiotherapy dosimeter for delivery of complex treatments such as VMAT.

Improvement of VMAT plan quality for head and neck cancer with high resolution fluences generated by couch shift between arcs.

PubMed

Park, Jong Min; Park, So-Yeon; Wu, Hong-Gyun; Kim, Jung-In

2018-02-01

To investigate the changes in quality of the volumetric modulated arc therapy (VMAT) plans with couch-shift between arcs by half of a multi-leaf collimator (MLC) leaf width. A total of 22 patients with head-and-neck cancer were retrospectively selected. Since the smallest MLC leaf width was 5 mm in this study, the couch was shifted by 2.5 mm in the longitudinal-direction between arcs to increase the resolution of fluence map. A total of three types of VMAT plans were generated for each patient; the three types of plans were a two-full-arc plan without couch-shift (NS plan), a two-half-arc-pair plan with couch-shift (HAS plan), and a two-full-arc pair plan with couch-shift (FAS plan). Changes in the dose-volumetric parameters were investigated. The FAS plan showed the best plan quality for the target volumes and organs at risk compared to the NS and HAS plans. However, the magnitudes of differences among the three types of plans were minimal, and every plan was clinically acceptable. The average integral doses of the NS, HAS, and FAS plans were 160,549 ± 37,600 Gy-cc, 147,828 ± 33,343 Gy-cc, and 156,030 ± 36,263 Gy-cc, respectively. The average monitor unit of the NS, HAS, and FAS plans were 717 ± 120 MU, 648 ± 100 MU, and 763 ± 158 MU, respectively. The HAS plan was better than the others in terms of normal tissue sparing and plan efficiency. By shifting the couch by half of the MLC leaf width in the longitudinal direction between arcs, the VMAT plan quality could be improved. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-F-T-527: A Novel Dynamic Multileaf Collimator Leaf-Sequencing Algorithm in Radiation Therapy

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

Jing, J; Lin, H; Chow, J

Purpose: A novel leaf-sequencing algorithm is developed for generating arbitrary beam intensity profiles in discrete levels using dynamic multileaf collimator (MLC). The efficiency of this dynamic MLC leaf-sequencing method was evaluated using external beam treatment plans delivered by intensity modulated radiation therapy technique. Methods: To qualify and validate this algorithm, integral test for the beam segment of MLC generated by the CORVUS treatment planning system was performed with clinical intensity map experiments. The treatment plans were optimized and the fluence maps for all photon beams were determined. This algorithm started with the algebraic expression for the area under the beammore » profile. The coefficients in the expression can be transformed into the specifications for the leaf-setting sequence. The leaf optimization procedure was then applied and analyzed for clinical relevant intensity profiles in cancer treatment. Results: The macrophysical effect of this method can be described by volumetric plan evaluation tools such as dose-volume histograms (DVHs). The DVH results are in good agreement compared to those from the CORVUS treatment planning system. Conclusion: We developed a dynamic MLC method to examine the stability of leaf speed including effects of acceleration and deceleration of leaf motion in order to make sure the stability of leaf speed did not affect the intensity profile generated. It was found that the mechanical requirements were better satisfied using this method. The Project is sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.« less

SU-E-T-01: 2-D Characterization of DLG Among All MLC Leaf Pairs

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

Kumaraswamy, L; Xu, Z; Podgorsak, M

Purpose: The aim of this study is to evaluate the variation of dosimetric leaf-gap (DLG) along the travel path of each MLC leaf pair. This study evaluates whether the spatial variations in DLG could cause dose differences between TPS-calculated and measured dose. Methods: The 6MV DLG values were measured for all leaf pairs in the direction of leaf motion using a 2-D diode array and 0.6cc ion chamber. These measurements were performed on two Varian Linacs, employing the Millennium 120-leaf MLC and a 2-D-DLG variation map was created via in-house software. Several test plans were created with sweeping MLC fieldsmore » using constant gaps from 2mm to 10mm and corrected for 2-D variation utilizing in-house software. Measurements were performed utilizing the MapCHECK at 5.0cm depth for plans with and without the 2-D DLG correction and compared to the TPS calculated dose via gamma analysis (3%/3mm). Results: The measured DLGs for the middle 40 MLC leaf pairs (0.5cm width) were very similar along the central superior-inferior axis, with maximum variation of 0.2mm. The outer 20 MLC leaf pairs (1.0cm width) have DLG values from 0.32mm (mean) to 0.65mm (maximum) lower than the central leaf-pair, depending on off-axis distance. Gamma pass rates for the 2mm, 4mm, and 6mm sweep plans increased by 23.2%, 28.7%, and 26.0% respectively using the 2-D-DLG correction. The most improved dose points occur in areas modulated by the 1.0cm leaf-pairs. The gamma pass rate for the 10mm sweep plan increased by only 7.7%, indicating that the 2D variation becomes less significant for dynamic plans with larger MLC gaps. Conclusion: Fluences residing significantly off-axis with narrow sweeping gaps may exhibit significant variations from planned dose due to large differences between the true DLG exhibited by the 1.0cm leaf-pairs versus the constant DLG value utilized by the TPS for dose calculation.« less

A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy

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

Nguyen, Dan; Ruan, Dan; O’Connor, Daniel

Purpose: To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. Methods: A total of seven patients—two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung—were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-basedmore » IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle–Pock algorithm, a first-order primal–dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. Results: Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and mean critical organ doses were reduced by 1.94% and 1.44% of the prescription dose. The average number of delivery segments was 12.68 segments per beam for both the RAO and DMS plans. The N = 2 and N = 4 SOC designs were, on average, 1.56 and 1.80 times more efficient than the N = 1 SOC design to deliver. The mean aperture size produced by the RAO plans was 3.9 times larger than that of the DMS plans. Conclusions: The DAO and dose domain optimization approach enabled high quality IMRT plans using a low-complexity collimator setup. The dosimetric quality is comparable or slightly superior to conventional MLC-based IMRT plans using the same number of delivery segments. The SOC IMRT delivery efficiency can be significantly improved by increasing the leaf numbers, but the number is still significantly lower than the number of leaves in a typical MLC.« less

A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy.

PubMed

Nguyen, Dan; Ruan, Dan; O'Connor, Daniel; Woods, Kaley; Low, Daniel A; Boucher, Salime; Sheng, Ke

2016-02-01

To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. A total of seven patients-two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung-were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-based IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle-Pock algorithm, a first-order primal-dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and mean critical organ doses were reduced by 1.94% and 1.44% of the prescription dose. The average number of delivery segments was 12.68 segments per beam for both the RAO and DMS plans. The N = 2 and N = 4 SOC designs were, on average, 1.56 and 1.80 times more efficient than the N = 1 SOC design to deliver. The mean aperture size produced by the RAO plans was 3.9 times larger than that of the DMS plans. The DAO and dose domain optimization approach enabled high quality IMRT plans using a low-complexity collimator setup. The dosimetric quality is comparable or slightly superior to conventional MLC-based IMRT plans using the same number of delivery segments. The SOC IMRT delivery efficiency can be significantly improved by increasing the leaf numbers, but the number is still significantly lower than the number of leaves in a typical MLC.

SU-E-T-467: Implementation of Monte Carlo Dose Calculation for a Multileaf Collimator Equipped Robotic Radiotherapy System

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

Li, JS; Fan, J; Ma, C-M

Purpose: To improve the treatment efficiency and capabilities for full-body treatment, a robotic radiosurgery system has equipped with a multileaf collimator (MLC) to extend its accuracy and precision to radiation therapy. To model the MLC and include it in the Monte Carlo patient dose calculation is the goal of this work. Methods: The radiation source and the MLC were carefully modeled to consider the effects of the source size, collimator scattering, leaf transmission and leaf end shape. A source model was built based on the output factors, percentage depth dose curves and lateral dose profiles measured in a water phantom.more » MLC leaf shape, leaf end design and leaf tilt for minimizing the interleaf leakage and their effects on beam fluence and energy spectrum were all considered in the calculation. Transmission/leakage was added to the fluence based on the transmission factors of the leaf and the leaf end. The transmitted photon energy was tuned to consider the beam hardening effects. The calculated results with the Monte Carlo implementation was compared with measurements in homogeneous water phantom and inhomogeneous phantoms with slab lung or bone material for 4 square fields and 9 irregularly shaped fields. Results: The calculated output factors are compared with the measured ones and the difference is within 1% for different field sizes. The calculated dose distributions in the phantoms show good agreement with measurements using diode detector and films. The dose difference is within 2% inside the field and the distance to agreement is within 2mm in the penumbra region. The gamma passing rate is more than 95% with 2%/2mm criteria for all the test cases. Conclusion: Implementation of Monte Carlo dose calculation for a MLC equipped robotic radiosurgery system is completed successfully. The accuracy of Monte Carlo dose calculation with MLC is clinically acceptable. This work was supported by Accuray Inc.« less

A real-time dynamic-MLC control algorithm for delivering IMRT to targets undergoing 2D rigid motion in the beam's eye view.

PubMed

McMahon, Ryan; Berbeco, Ross; Nishioka, Seiko; Ishikawa, Masayori; Papiez, Lech

2008-09-01

An MLC control algorithm for delivering intensity modulated radiation therapy (IMRT) to targets that are undergoing two-dimensional (2D) rigid motion in the beam's eye view (BEV) is presented. The goal of this method is to deliver 3D-derived fluence maps over a moving patient anatomy. Target motion measured prior to delivery is first used to design a set of planned dynamic-MLC (DMLC) sliding-window leaf trajectories. During actual delivery, the algorithm relies on real-time feedback to compensate for target motion that does not agree with the motion measured during planning. The methodology is based on an existing one-dimensional (ID) algorithm that uses on-the-fly intensity calculations to appropriately adjust the DMLC leaf trajectories in real-time during exposure delivery [McMahon et al., Med. Phys. 34, 3211-3223 (2007)]. To extend the 1D algorithm's application to 2D target motion, a real-time leaf-pair shifting mechanism has been developed. Target motion that is orthogonal to leaf travel is tracked by appropriately shifting the positions of all MLC leaves. The performance of the tracking algorithm was tested for a single beam of a fractionated IMRT treatment, using a clinically derived intensity profile and a 2D target trajectory based on measured patient data. Comparisons were made between 2D tracking, 1D tracking, and no tracking. The impact of the tracking lag time and the frequency of real-time imaging were investigated. A study of the dependence of the algorithm's performance on the level of agreement between the motion measured during planning and delivery was also included. Results demonstrated that tracking both components of the 2D motion (i.e., parallel and orthogonal to leaf travel) results in delivered fluence profiles that are superior to those that track the component of motion that is parallel to leaf travel alone. Tracking lag time effects may lead to relatively large intensity delivery errors compared to the other sources of error investigated. However, the algorithm presented is robust in the sense that it does not rely on a high level of agreement between the target motion measured during treatment planning and delivery.

Poster — Thur Eve — 56: Design of Quality Assurance Methodology for VMAT system on Agility System equipped with CVDR

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

Thind, K; Tolakanahalli, R

2014-08-15

The aim of this study was to analyze the feasibility of designing comprehensive QA plans using iComCAT for Elekta machines equipped with Agility multileaf collimator and continuously variable dose rate. Test plans with varying MLC speed, gantry speed, and dose rate were created and delivered in a controlled manner. A strip test was designed with three 1 cm MLC positions and delivered using dynamic, StepNShoot and VMAT techniques. Plans were also designed to test error in MLC position with various gantry speeds and various MLC speeds. The delivery fluence was captured using the electronic portal-imaging device. Gantry speed was foundmore » to be within tolerance as per the Canadian standards. MLC positioning errors at higher MLC speed with gravity effects does add more than 2 mm discrepancy. More tests need to be performed to evaluate MLC performance using independent measurement systems. The treatment planning system with end-to-end testing necessary for commissioning was also investigated and found to have >95% passing rates within 3%/3mm gamma criteria. Future studies involve performing off-axis gantry starshot pattern and repeating the tests on three matched Elekta linear accelerators.« less

Maximizing the potential of direct aperture optimization through collimator rotation

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

Milette, Marie-Pierre; Otto, Karl; Medical Physics, BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia

Intensity-modulated radiation therapy (IMRT) treatment plans are conventionally produced by the optimization of fluence maps followed by a leaf sequencing step. An alternative to fluence based inverse planning is to optimize directly the leaf positions and field weights of multileaf collimator (MLC) apertures. This approach is typically referred to as direct aperture optimization (DAO). It has been shown that equivalent dose distributions may be generated that have substantially fewer monitor units (MU) and number of apertures compared to fluence based optimization techniques. Here we introduce a DAO technique with rotated apertures that we call rotating aperture optimization (RAO). The advantagesmore » of collimator rotation in IMRT have been shown previously and include higher fluence spatial resolution, increased flexibility in the generation of aperture shapes and less interleaf effects. We have tested our RAO algorithm on a complex C-shaped target, seven nasopharynx cancer recurrences, and one multitarget nasopharynx carcinoma patient. A study was performed in order to assess the capabilities of RAO as compared to fixed collimator angle DAO. The accuracy of fixed and rotated collimator aperture delivery was also verified. An analysis of the optimized treatment plans indicates that plans generated with RAO are as good as or better than DAO while maintaining a smaller number of apertures and MU than fluence based IMRT. Delivery verification results show that RAO is less sensitive to tongue and groove effects than DAO. Delivery time is currently increased due to the collimator rotation speed although this is a mechanical limitation that can be eliminated in the future.« less

Micro-Laser Range Finder Development: Using the Monolithic Approach

DTIC Science & Technology

1999-02-01

components can be joined together, optically aligned to form the laser cavity and then sliced to produce MLC modules . This batch process can greatly reduce...the overall fabrication costs of the µLRF system. The MLC module is ultra-compact. Its overall size is approximately 56 mm (L) x 3 mm (W) x 3 mm (H) as...MLC module is placed on a laser pallet for stiffness, mechanical stability. The laser pallet size is selected as part of the integration design

A clinically observed discrepancy between image-based and log-based MLC positions

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

Neal, Brian, E-mail: bpn2p@virginia.edu; Ahmed, Mahmoud; Kathuria, Kunal

2016-06-15

Purpose: To present a clinical case in which real-time intratreatment imaging identified an multileaf collimator (MLC) leaf to be consistently deviating from its programmed and logged position by >1 mm. Methods: An EPID-based exit-fluence dosimetry system designed to prevent gross delivery errors was used to capture cine during treatment images. The author serendipitously visually identified a suspected MLC leaf displacement that was not otherwise detected. The leaf position as recorded on the EPID images was measured and log-files were analyzed for the treatment in question, the prior day’s treatment, and for daily MLC test patterns acquired on those treatment days.more » Additional standard test patterns were used to quantify the leaf position. Results: Whereas the log-file reported no difference between planned and recorded positions, image-based measurements showed the leaf to be 1.3 ± 0.1 mm medial from the planned position. This offset was confirmed with the test pattern irradiations. Conclusions: It has been clinically observed that log-file derived leaf positions can differ from their actual position by >1 mm, and therefore cannot be considered to be the actual leaf positions. This cautions the use of log-based methods for MLC or patient quality assurance without independent confirmation of log integrity. Frequent verification of MLC positions through independent means is a necessary precondition to trust log-file records. Intratreatment EPID imaging provides a method to capture departures from MLC planned positions.« less

VMAT optimization with dynamic collimator rotation.

PubMed

Lyu, Qihui; O'Connor, Daniel; Ruan, Dan; Yu, Victoria; Nguyen, Dan; Sheng, Ke

2018-04-16

Although collimator rotation is an optimization variable that can be exploited for dosimetric advantages, existing Volumetric Modulated Arc Therapy (VMAT) optimization uses a fixed collimator angle in each arc and only rotates the collimator between arcs. In this study, we develop a novel integrated optimization method for VMAT, accounting for dynamic collimator angles during the arc motion. Direct Aperture Optimization (DAO) for Dynamic Collimator in VMAT (DC-VMAT) was achieved by adding to the existing dose fidelity objective an anisotropic total variation term for regulating the fluence smoothness, a binary variable for forming simple apertures, and a group sparsity term for controlling collimator rotation. The optimal collimator angle for each beam angle was selected using the Dijkstra's algorithm, where the node costs depend on the estimated fluence map at the current iteration and the edge costs account for the mechanical constraints of multi-leaf collimator (MLC). An alternating optimization strategy was implemented to solve the DAO and collimator angle selection (CAS). Feasibility of DC-VMAT using one full-arc with dynamic collimator rotation was tested on a phantom with two small spherical targets, a brain, a lung and a prostate cancer patient. The plan was compared against a static collimator VMAT (SC-VMAT) plan using three full arcs with 60 degrees of collimator angle separation in patient studies. With the same target coverage, DC-VMAT achieved 20.3% reduction of R50 in the phantom study, and reduced the average max and mean OAR dose by 4.49% and 2.53% of the prescription dose in patient studies, as compared with SC-VMAT. The collimator rotation co-ordinated with the gantry rotation in DC-VMAT plans for deliverability. There were 13 beam angles in the single-arc DC-VMAT plan in patient studies that requires slower gantry rotation to accommodate multiple collimator angles. The novel DC-VMAT approach utilizes the dynamic collimator rotation during arc delivery. In doing so, DC-VMAT affords more sophisticated intensity modulation, alleviating the limitation previously imposed by the square beamlet from the MLC leaf thickness and achieves higher effective modulation resolution. Consequently, DC-VMAT with a single arc manages to achieve superior dosimetry than SC-VMAT with three full arcs. © 2018 American Association of Physicists in Medicine.

Dosimetric effect of Elekta Beam Modulator micromultileaf in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer

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

Carosi, Alessandra, E-mail: alessandra.carosi@katamail.com; Ingrosso, Gianluca; Ponti, Elisabetta

2014-07-01

The purpose of this study is to analyze the dosimetric effect of Elekta Beam Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity-modulated radiation therapy (IMRT) for localized prostate cancer. We compared treatment plans developed with 2 different Elekta multileaf collimators (MLC): Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard MLC (10-mm leaf width at the isocenter). The comparison was performed for 15 patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60 treatment plans were processed. The dose-volume histograms were used to provide the quantitative comparison between plans. In particular,more » we analyzed differences between rectum and bladder sparing in terms of a set of appropriate Vx (percentage of organ at risk [OAR] volume receiving the x dose) and differences between target conformity and coverage in terms of coverage factor and conformation number. Our analysis demonstrates that in 3DCRT there is an advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in particular, a significant decrease in rectal V{sub 60} and V{sub 50} (p = 0.001) and in bladder V{sub 70} and V{sub 65} (p = 0.007 and 0.002, respectively) was found. Moreover, a better target dose conformity was obtained (p = 0.002). IMRT plans comparison demonstrated no significant differences between the use of the 4 or 10-mm MLCs. Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives a gain in target conformity and in OARs dose sparing whereas in IMRT plans there is no advantage.« less

Functional conservation between rodents and chicken of regulatory sequences driving skeletal muscle gene expression in transgenic chickens

PubMed Central

2010-01-01

Background Regulatory elements that control expression of specific genes during development have been shown in many cases to contain functionally-conserved modules that can be transferred between species and direct gene expression in a comparable developmental pattern. An example of such a module has been identified at the rat myosin light chain (MLC) 1/3 locus, which has been well characterised in transgenic mouse studies. This locus contains two promoters encoding two alternatively spliced isoforms of alkali myosin light chain. These promoters are differentially regulated during development through the activity of two enhancer elements. The MLC3 promoter alone has been shown to confer expression of a reporter gene in skeletal and cardiac muscle in transgenic mice and the addition of the downstream MLC enhancer increased expression levels in skeletal muscle. We asked whether this regulatory module, sufficient for striated muscle gene expression in the mouse, would drive expression in similar domains in the chicken. Results We have observed that a conserved downstream MLC enhancer is present in the chicken MLC locus. We found that the rat MLC1/3 regulatory elements were transcriptionally active in chick skeletal muscle primary cultures. We observed that a single copy lentiviral insert containing this regulatory cassette was able to drive expression of a lacZ reporter gene in the fast-fibres of skeletal muscle in chicken in three independent transgenic chicken lines in a pattern similar to the endogenous MLC locus. Reporter gene expression in cardiac muscle tissues was not observed for any of these lines. Conclusions From these results we conclude that skeletal expression from this regulatory module is conserved in a genomic context between rodents and chickens. This transgenic module will be useful in future investigations of muscle development in avian species. PMID:20184756

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

PubMed

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

2006-05-01

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

Dosimetric comparison using different multileaf collimeters in intensity-modulated radiotherapy for upper thoracic esophageal cancer.

PubMed

Gong, Youling; Wang, Shichao; Zhou, Lin; Liu, Yongmei; Xu, Yong; Lu, You; Bai, Sen; Fu, Yuchuan; Xu, Qingfeng; Jiang, Qingfeng

2010-07-15

To study the impacts of multileaf collimators (MLC) width [standard MLC width of 10 mm (sMLC) and micro-MLC width of 4 mm (mMLC)] in the intensity-modulated radiotherapy (IMRT) planning for the upper thoracic esophageal cancer (UTEC). 10 patients with UTEC were retrospectively planned with the sMLC and the mMLC. The monitor unites (MUs) and dose volume histogram-based parameters [conformity index (CI) and homogeneous index (HI)] were compared between the IMRT plans with sMLC and with mMLC. The IMRT plans with the mMLC were more efficient (average MUs: 703.1 +/- 68.3) than plans with the sMLC (average MUs: 833.4 +/- 73.8) (p < 0.05). Also, compared to plans with the sMLC, the plans with the mMLC showed advantages in dose coverage of the planning gross tumor volume (Pgtv) (CI 0.706 +/- 0.056/HI 1.093 +/- 0.021) and the planning target volume (PTV) (CI 0.707 +/- 0.029/HI 1.315 +/- 0.013) (p < 0.05). In addition, the significant dose sparing in the D5 (3260.3 +/- 374.0 vs 3404.5 +/- 374.4)/gEUD (1815.1 +/- 281.7 vs 1849.2 +/- 297.6) of the spinal cord, the V10 (33.2 +/- 6.5 vs 34.0 +/- 6.7), V20 (16.0 +/- 4.6 vs 16.6 +/- 4.7), MLD (866.2 +/- 174.1 vs 887.9 +/- 172.1) and gEUD (938.6 +/- 175.2 vs 956.8 +/- 171.0) of the lungs were observed in the plans with the mMLC, respectively (p < 0.05). Comparing to the sMLC, the mMLC not only demonstrated higher efficiencies and more optimal target coverage, but also considerably improved the dose sparing of OARs in the IMRT planning for UTEC.

Performance of a multi leaf collimator system for MR-guided radiation therapy.

PubMed

Cai, Bin; Li, Harold; Yang, Deshan; Rodriguez, Vivian; Curcuru, Austen; Wang, Yuhe; Wen, Jie; Kashani, Rojano; Mutic, Sasa; Green, Olga

2017-12-01

The purpose of this study was to investigate and characterize the performance of a Multi Leaf Collimator (MLC) designed for Cobalt-60 based MR-guided radiation therapy system in a 0.35 T magnetic field. The MLC design and unique assembly features in the ViewRay MRIdian system were first reviewed. The RF cage shielding of MLC motor and cables were evaluated using ACR phantoms with real-time imaging and quantified by signal-to-noise ratio. The dosimetric characterizations, including the leaf transmission, leaf penumbra, tongue-and-groove effect, were investigated using radiosensitive films. The output factor of MLC-defined fields was measured with ionization chambers for both symmetric fields from 2.1 × 2.1 cm 2 to 27.3 × 27.3 cm 2 and asymmetric fields from 10.5 × 10.5 cm 2 to 10.5 × 2.0 cm 2 . Multi leaf collimator (MLC) positional accuracy was assessed by delivering either a picket fence (PF) style pattern on radiochromic films with wire-jig phantom or double and triple-rectangular patterns on ArcCheck-MR (Sun Nuclear, Melbourne, FL, USA) with gamma analysis as the pass/fail indicator. Leaf speed tests were performed to assess the capability of full range leaf travel within manufacture's specifications. Multi leaf collimator plan delivery reproducibility was tested by repeatedly delivering both open fields and fields with irregular shaped segments over 1-month period. Comparable SNRs within 4% were observed for MLC moving and stationary plans on vendor-reconstructed images, and the direct k-space reconstructed images showed that the three SNRs are within 1%. The maximum leaf transmission for all three MLCs was less than 0.35% and the average leakage was 0.153 ± 0.006%, 0.151 ± 0.008%, and 0.159 ± 0.015% for head 1, 2, and 3, respectively. Both the leaf edge and leaf end penumbra showed comparable values within 0.05 cm, and the measured values are within 0.1 cm with TPS values. The leaf edge TG effect indicated 10% underdose and the leaf end TG showed a shifted dose distribution with 0.3 cm offset. The leaf positioning test showed a 0.2 cm accuracy in the PF style test, and a gamma passing rate above 96% was observed with a 3%/2 mm criteria when comparing the measured double/triple-rectangular pattern fluence with TPS calculated fluence. The average leaf speed when executing the test plan fell in a range from 1.86 to 1.95 cm/s. The measured and TPS calculated output factors were within 2% for squared fields and within 3% for rectangular fields. The reproducibility test showed the deviation of output factors were well within 2% for square fields and the gamma passing rate within 1.5% for fields with irregular segments. The Monte Carlo predicted output factors were within 2% compared to TPS values. 15 out of the 16 IMRT plans have gamma passing rate more than 98% compared to the TPS fluence with an average passing rate of 99.1 ± 0.6%. The MRIdian MLC has a good RF noise shielding design, low radiation leakage, good positioning accuracy, comparable TG effect, and can be modeled by an independent Monte Carlo calculation platform. © 2017 American Association of Physicists in Medicine.

SU-E-T-478: Sliding Window Multi-Criteria IMRT Optimization

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

Craft, D; Papp, D; Unkelbach, J

2014-06-01

Purpose: To demonstrate a method for what-you-see-is-what-you-get multi-criteria Pareto surface navigation for step and shoot IMRT treatment planning. Methods: We show mathematically how multiple sliding window treatment plans can be averaged to yield a single plan whose dose distribution is the dosimetric average of the averaged plans. This is incorporated into the Pareto surface navigation based approach to treatment planning in such a way that as the user navigates the surface, the plans he/she is viewing are ready to be delivered (i.e. there is no extra ‘segment the plans’ step that often leads to unacceptable plan degradation in step andmore » shoot Pareto surface navigation). We also describe how the technique can be applied to VMAT. Briefly, sliding window VMAT plans are created such that MLC leaves paint out fluence maps every 15 degrees or so. These fluence map leaf trajectories are averaged in the same way the static beam IMRT ones are. Results: We show mathematically that fluence maps are exactly averaged using our leaf sweep averaging algorithm. Leaf transmission and output factor corrections effects, which are ignored in this work, can lead to small errors in terms of the dose distributions not being exactly averaged even though the fluence maps are. However, our demonstrations show that the dose distributions are almost exactly averaged as well. We demonstrate the technique both for IMRT and VMAT. Conclusions: By turning to sliding window delivery, we show that the problem of losing plan fidelity during the conversion of an idealized fluence map plan into a deliverable plan is remedied. This will allow for multicriteria optimization that avoids the pitfall that the planning has to be redone after the conversion into MLC segments due to plan quality decline. David Craft partially funded by RaySearch Laboratories.« less

SU-F-T-233: Evaluation of Treatment Delivery Parameters Using High Resolution ELEKTA Log Files

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

Kabat, C; Defoor, D; Alexandrian, A

2016-06-15

Purpose: As modern linacs have become more technologically advanced with the implementation of IGRT and IMRT with HDMLCs, a requirement for more elaborate tracking techniques to monitor components’ integrity is paramount. ElektaLog files are generated every 40 milliseconds, which can be analyzed to track subtle changes and provide another aspect of quality assurance. This allows for constant monitoring of fraction consistency in addition to machine reliability. With this in mind, it was the aim of the study to evaluate if ElektaLog files can be utilized for linac consistency QA. Methods: ElektaLogs were reviewed for 16 IMRT patient plans with >16more » fractions. Logs were analyzed by creating fluence maps from recorded values of MLC locations, jaw locations, and dose per unit time. Fluence maps were then utilized to calculate a 2D gamma index with a 2%–2mm criteria for each fraction. ElektaLogs were also used to analyze positional errors for MLC leaves and jaws, which were used to compute an overall error for the MLC banks, Y-jaws, and X-jaws by taking the root-meansquare value of the individual recorded errors during treatment. Additionally, beam on time was calculated using the number of ElektaLog file entries within the file. Results: The average 2D gamma for all 16 patient plans was found to be 98.0±2.0%. Recorded gamma index values showed an acceptable correlation between fractions. Average RMS values for MLC leaves and the jaws resulted in a leaf variation of roughly 0.3±0.08 mm and jaw variation of about 0.15±0.04 mm, both of which fall within clinical tolerances. Conclusion: The use of ElektaLog files for day-to-day evaluation of linac integrity and patient QA can be utilized to allow for reliable analysis of system accuracy and performance.« less

SU-F-T-465: Two Years of Radiotherapy Treatments Analyzed Through MLC Log Files

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

Defoor, D; Kabat, C; Papanikolaou, N

Purpose: To present treatment statistics of a Varian Novalis Tx using more than 90,000 Varian Dynalog files collected over the past 2 years. Methods: Varian Dynalog files are recorded for every patient treated on our Varian Novalis Tx. The files are collected and analyzed daily to check interfraction agreement of treatment deliveries. This is accomplished by creating fluence maps from the data contained in the Dynalog files. From the Dynalog files we have also compiled statistics for treatment delivery times, MLC errors, gantry errors and collimator errors. Results: The mean treatment time for VMAT patients was 153 ± 86 secondsmore » while the mean treatment time for step & shoot was 256 ± 149 seconds. Patient’s treatment times showed a variation of 0.4% over there treatment course for VMAT and 0.5% for step & shoot. The average field sizes were 40 cm2 and 26 cm2 for VMAT and step & shoot respectively. VMAT beams contained and average overall leaf travel of 34.17 meters and step & shoot beams averaged less than half of that at 15.93 meters. When comparing planned and delivered fluence maps generated using the Dynalog files VMAT plans showed an average gamma passing percentage of 99.85 ± 0.47. Step & shoot plans showed an average gamma passing percentage of 97.04 ± 0.04. 5.3% of beams contained an MLC error greater than 1 mm and 2.4% had an error greater than 2mm. The mean gantry speed for VMAT plans was 1.01 degrees/s with a maximum of 6.5 degrees/s. Conclusion: Varian Dynalog files are useful for monitoring machine performance treatment parameters. The Dynalog files have shown that the performance of the Novalis Tx is consistent over the course of a patients treatment with only slight variations in patient treatment times and a low rate of MLC errors.« less

Evaluation of dosimetric effect caused by slowing with multi-leaf collimator (MLC) leaves for volumetric modulated arc therapy (VMAT)

PubMed Central

Wang, Iris Z.; Kumaraswamy, Lalith K.; Podgorsak, Matthew B.

2016-01-01

Background This study is to report 1) the sensitivity of intensity modulated radiation therapy (IMRT) QA method for clinical volumetric modulated arc therapy (VMAT) plans with multi-leaf collimator (MLC) leaf errors that will not trigger MLC interlock during beam delivery; 2) the effect of non-beam-hold MLC leaf errors on the quality of VMAT plan dose delivery. Materials and methods. Eleven VMAT plans were selected and modified using an in-house developed software. For each control point of a VMAT arc, MLC leaves with the highest speed (1.87-1.95 cm/s) were set to move at the maximal allowable speed (2.3 cm/s), which resulted in a leaf position difference of less than 2 mm. The modified plans were considered as ‘standard’ plans, and the original plans were treated as the ‘slowing MLC’ plans for simulating ‘standard’ plans with leaves moving at relatively lower speed. The measurement of each ‘slowing MLC’ plan using MapCHECK®2 was compared with calculated planar dose of the ‘standard’ plan with respect to absolute dose Van Dyk distance-to-agreement (DTA) comparisons using 3%/3 mm and 2%/2 mm criteria. Results All ‘slowing MLC’ plans passed the 90% pass rate threshold using 3%/3 mm criteria while one brain and three anal VMAT cases were below 90% with 2%/2 mm criteria. For ten out of eleven cases, DVH comparisons between ‘standard’ and ‘slowing MLC’ plans demonstrated minimal dosimetric changes in targets and organs-at-risk. Conclusions For highly modulated VMAT plans, pass rate threshold (90%) using 3%/3mm criteria is not sensitive in detecting MLC leaf errors that will not trigger the MLC leaf interlock. However, the consequential effects of non-beam hold MLC errors on target and OAR doses are negligible, which supports the reliability of current patient-specific IMRT quality assurance (QA) method for VMAT plans. PMID:27069458

SU-F-T-469: A Clinically Observed Discrepancy Between Image-Based and Log- Based MLC Position

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

Neal, B; Ahmed, M; Siebers, J

2016-06-15

Purpose: To present a clinical case which challenges the base assumption of log-file based QA, by showing that the actual position of a MLC leaf can suddenly deviate from its programmed and logged position by >1 mm as observed with real-time imaging. Methods: An EPID-based exit-fluence dosimetry system designed to prevent gross delivery errors was used in cine mode to capture portal images during treatment. Visual monitoring identified an anomalous MLC leaf pair gap not otherwise detected by the automatic position verification. The position of the erred leaf was measured on EPID images and log files were analyzed for themore » treatment in question, the prior day’s treatment, and for daily MLC test patterns acquired on those treatment days. Additional standard test patterns were used to quantify the leaf position. Results: Whereas the log file reported no difference between planned and recorded positions, image-based measurements showed the leaf to be 1.3±0.1 mm medial from the planned position. This offset was confirmed with the test pattern irradiations. Conclusion: It has been clinically observed that log-file derived leaf positions can differ from their actual positions by >1 mm, and therefore cannot be considered to be the actual leaf positions. This cautions the use of log-based methods for MLC or patient quality assurance without independent confirmation of log integrity. Frequent verification of MLC positions through independent means is a necessary precondition to trusting log file records. Intra-treatment EPID imaging provides a method to capture departures from MLC planned positions. Work was supported in part by Varian Medical Systems.« less

The dosimetric impact of inversely optimized arc radiotherapy plan modulation for real-time dynamic MLC tracking delivery.

PubMed

Falk, Marianne; Larsson, Tobias; Keall, Paul; Chul Cho, Byung; Aznar, Marianne; Korreman, Stine; Poulsen, Per; Munck Af Rosenschold, Per

2012-03-01

Real-time dynamic multileaf collimator (MLC) tracking for management of intrafraction tumor motion can be challenging for highly modulated beams, as the leaves need to travel far to adjust for target motion perpendicular to the leaf travel direction. The plan modulation can be reduced by using a leaf position constraint (LPC) that reduces the difference in the position of adjacent MLC leaves in the plan. The purpose of this study was to investigate the impact of the LPC on the quality of inversely optimized arc radiotherapy plans and the effect of the MLC motion pattern on the dosimetric accuracy of MLC tracking delivery. Specifically, the possibility of predicting the accuracy of MLC tracking delivery based on the plan modulation was investigated. Inversely optimized arc radiotherapy plans were created on CT-data of three lung cancer patients. For each case, five plans with a single 358° arc were generated with LPC priorities of 0 (no LPC), 0.25, 0.5, 0.75, and 1 (highest possible LPC), respectively. All the plans had a prescribed dose of 2 Gy × 30, used 6 MV, a maximum dose rate of 600 MU/min and a collimator angle of 45° or 315°. To quantify the plan modulation, an average adjacent leaf distance (ALD) was calculated by averaging the mean adjacent leaf distance for each control point. The linear relationship between the plan quality [i.e., the calculated dose distributions and the number of monitor units (MU)] and the LPC was investigated, and the linear regression coefficient as well as a two tailed confidence level of 95% was used in the evaluation. The effect of the plan modulation on the performance of MLC tracking was tested by delivering the plans to a cylindrical diode array phantom moving with sinusoidal motion in the superior-inferior direction with a peak-to-peak displacement of 2 cm and a cycle time of 6 s. The delivery was adjusted to the target motion using MLC tracking, guided in real-time by an infrared optical system. The dosimetric results were evaluated using gamma index evaluation with static target measurements as reference. The plan quality parameters did not depend significantly on the LPC (p ≥ 0.066), whereas the ALD depended significantly on the LPC (p < 0.001). The gamma index failure rate depended significantly on the ALD, weighted to the percentage of the beam delivered in each control point of the plan (ALD(w)) when MLC tracking was used (p < 0.001), but not for delivery without MLC tracking (p ≥ 0.342). The gamma index failure rate with the criteria of 2% and 2 mm was decreased from > 33.9% without MLC tracking to <31.4% (LPC 0) and <2.2% (LPC 1) with MLC tracking. The results indicate that the dosimetric robustness of MLC tracking delivery of an inversely optimized arc radiotherapy plan can be improved by incorporating leaf position constraints in the objective function without otherwise affecting the plan quality. The dosimetric robustness may be estimated prior to delivery by evaluating the ALD(w) of the plan.

Effect of MLC leaf position, collimator rotation angle, and gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma

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

Bai, Sen; Li, Guangjun; Wang, Maojie

The purpose of this study was to investigate the effect of multileaf collimator (MLC) leaf position, collimator rotation angle, and accelerator gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma. To compare dosimetric differences between the simulating plans and the clinical plans with evaluation parameters, 6 patients with nasopharyngeal carcinoma were selected for simulation of systematic and random MLC leaf position errors, collimator rotation angle errors, and accelerator gantry rotation angle errors. There was a high sensitivity to dose distribution for systematic MLC leaf position errors in response to field size. When the systematic MLC position errors weremore » 0.5, 1, and 2 mm, respectively, the maximum values of the mean dose deviation, observed in parotid glands, were 4.63%, 8.69%, and 18.32%, respectively. The dosimetric effect was comparatively small for systematic MLC shift errors. For random MLC errors up to 2 mm and collimator and gantry rotation angle errors up to 0.5°, the dosimetric effect was negligible. We suggest that quality control be regularly conducted for MLC leaves, so as to ensure that systematic MLC leaf position errors are within 0.5 mm. Because the dosimetric effect of 0.5° collimator and gantry rotation angle errors is negligible, it can be concluded that setting a proper threshold for allowed errors of collimator and gantry rotation angle may increase treatment efficacy and reduce treatment time.« less

Experimental investigation of the response of an amorphous silicon EPID to intensity modulated radiotherapy beams.

PubMed

Greer, Peter B; Vial, Philip; Oliver, Lyn; Baldock, Clive

2007-11-01

The aim of this work was to experimentally determine the difference in response of an amorphous silicon (a-Si) electronic portal imaging device (EPID) to the open and multileaf collimator (MLC) transmitted beam components of intensity modulated radiation therapy (IMRT) beams. EPID dose response curves were measured for open and MLC transmitted (MLCtr) 10 x 10 cm2 beams at central axis and with off axis distance using a shifting field technique. The EPID signal was obtained by replacing the flood-field correction with a pixel sensitivity variation matrix correction. This signal, which includes energy-dependent response, was then compared to ion-chamber measurements. An EPID calibration method to remove the effect of beam energy variations on EPID response was developed for IMRT beams. This method uses the component of open and MLCtr fluence to an EPID pixel calculated from the MLC delivery file and applies separate radially dependent calibration factors for each component. The calibration procedure does not correct for scatter differences between ion chamber in water measurements and EPID response; these must be accounted for separately with a kernel-based approach or similar method. The EPID response at central axis for the open beam was found to be 1.28 +/- 0.03 of the response for the MLCtr beam, with the ratio increasing to 1.39 at 12.5 cm off axis. The EPID response to MLCtr radiation did not change with off-axis distance. Filtering the beam with copper plates to reduce the beam energy difference between open and MLCtr beams was investigated; however, these were not effective at reducing EPID response differences. The change in EPID response for uniform sliding window IMRT beams with MLCtr dose components from 0.3% to 69% was predicted to within 2.3% using the separate EPID response calibration factors for each dose component. A clinical IMRT image calibrated with this method differed by nearly 30% in high MLCtr regions from an image calibrated with an open beam calibration factor only. Accounting for the difference in EPID response to open and MLCtr radiation should improve IMRT dosimetry with a-Si EPIDs.

Rate adaptive multilevel coded modulation with high coding gain in intensity modulation direct detection optical communication

NASA Astrophysics Data System (ADS)

Xiao, Fei; Liu, Bo; Zhang, Lijia; Xin, Xiangjun; Zhang, Qi; Tian, Qinghua; Tian, Feng; Wang, Yongjun; Rao, Lan; Ullah, Rahat; Zhao, Feng; Li, Deng'ao

2018-02-01

A rate-adaptive multilevel coded modulation (RA-MLC) scheme based on fixed code length and a corresponding decoding scheme is proposed. RA-MLC scheme combines the multilevel coded and modulation technology with the binary linear block code at the transmitter. Bits division, coding, optional interleaving, and modulation are carried out by the preset rule, then transmitted through standard single mode fiber span equal to 100 km. The receiver improves the accuracy of decoding by means of soft information passing through different layers, which enhances the performance. Simulations are carried out in an intensity modulation-direct detection optical communication system using MATLAB®. Results show that the RA-MLC scheme can achieve bit error rate of 1E-5 when optical signal-to-noise ratio is 20.7 dB. It also reduced the number of decoders by 72% and realized 22 rate adaptation without significantly increasing the computing time. The coding gain is increased by 7.3 dB at BER=1E-3.

Improving IMRT delivery efficiency with reweighted L1-minimization for inverse planning

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

Kim, Hojin; Becker, Stephen; Lee, Rena

2013-07-15

Purpose: This study presents an improved technique to further simplify the fluence-map in intensity modulated radiation therapy (IMRT) inverse planning, thereby reducing plan complexity and improving delivery efficiency, while maintaining the plan quality.Methods: First-order total-variation (TV) minimization (min.) based on L1-norm has been proposed to reduce the complexity of fluence-map in IMRT by generating sparse fluence-map variations. However, with stronger dose sparing to the critical structures, the inevitable increase in the fluence-map complexity can lead to inefficient dose delivery. Theoretically, L0-min. is the ideal solution for the sparse signal recovery problem, yet practically intractable due to its nonconvexity of themore » objective function. As an alternative, the authors use the iteratively reweighted L1-min. technique to incorporate the benefits of the L0-norm into the tractability of L1-min. The weight multiplied to each element is inversely related to the magnitude of the corresponding element, which is iteratively updated by the reweighting process. The proposed penalizing process combined with TV min. further improves sparsity in the fluence-map variations, hence ultimately enhancing the delivery efficiency. To validate the proposed method, this work compares three treatment plans obtained from quadratic min. (generally used in clinic IMRT), conventional TV min., and our proposed reweighted TV min. techniques, implemented by a large-scale L1-solver (template for first-order conic solver), for five patient clinical data. Criteria such as conformation number (CN), modulation index (MI), and estimated treatment time are employed to assess the relationship between the plan quality and delivery efficiency.Results: The proposed method yields simpler fluence-maps than the quadratic and conventional TV based techniques. To attain a given CN and dose sparing to the critical organs for 5 clinical cases, the proposed method reduces the number of segments by 10-15 and 30-35, relative to TV min. and quadratic min. based plans, while MIs decreases by about 20%-30% and 40%-60% over the plans by two existing techniques, respectively. With such conditions, the total treatment time of the plans obtained from our proposed method can be reduced by 12-30 s and 30-80 s mainly due to greatly shorter multileaf collimator (MLC) traveling time in IMRT step-and-shoot delivery.Conclusions: The reweighted L1-minimization technique provides a promising solution to simplify the fluence-map variations in IMRT inverse planning. It improves the delivery efficiency by reducing the entire segments and treatment time, while maintaining the plan quality in terms of target conformity and critical structure sparing.« less

Mlc Is a Transcriptional Activator with a Key Role in Integrating Cyclic AMP Receptor Protein and Integration Host Factor Regulation of Leukotoxin RNA Synthesis in Aggregatibacter actinomycetemcomitans

PubMed Central

Childress, Catherine; Feuerbacher, Leigh A.; Phillips, Linda; Burgum, Alex

2013-01-01

Aggregatibacter actinomycetemcomitans, a periodontal pathogen, synthesizes leukotoxin (LtxA), a protein that helps the bacterium evade the host immune response. Transcription of the ltxA operon is induced during anaerobic growth. The cyclic AMP (cAMP) receptor protein (CRP) indirectly increases ltxA expression, but the intermediary regulator is unknown. Integration host factor (IHF) binds to and represses the leukotoxin promoter, but neither CRP nor IHF is responsible for the anaerobic induction of ltxA RNA synthesis. Thus, we have undertaken studies to identify other regulators of leukotoxin transcription and to demonstrate how these proteins work together to modulate leukotoxin synthesis. First, analyses of ltxA RNA expression from defined leukotoxin promoter mutations in the chromosome identify positions −69 to −35 as the key control region and indicate that an activator protein modulates leukotoxin transcription. We show that Mlc, which is a repressor in Escherichia coli, functions as a direct transcriptional activator in A. actinomycetemcomitans; an mlc deletion mutant reduces leukotoxin RNA synthesis, and recombinant Mlc protein binds specifically at the −68 to −40 region of the leukotoxin promoter. Furthermore, we show that CRP activates ltxA expression indirectly by increasing the levels of Mlc. Analyses of Δmlc, Δihf, and Δihf Δmlc strains demonstrate that Mlc can increase RNA polymerase (RNAP) activity directly and that IHF represses ltxA RNA synthesis mainly by blocking Mlc binding. Finally, a Δihf Δmlc mutant still induces ltxA during anaerobic growth, indicating that there are additional factors involved in leukotoxin transcriptional regulation. A model for the coordinated regulation of leukotoxin transcription is presented. PMID:23475968

Modeling of a multileaf collimator

NASA Astrophysics Data System (ADS)

Kim, Siyong

A comprehensive physics model of a multileaf collimator (MLC) field for treatment planning was developed. Specifically, an MLC user interface module that includes a geometric optimization tool and a general method of in- air output factor calculation were developed. An automatic tool for optimization of MLC conformation is needed to realize the potential benefits of MLC. It is also necessary that a radiation therapy treatment planning (RTTP) system is capable of modeling MLC completely. An MLC geometric optimization and user interface module was developed. The planning time has been reduced significantly by incorporating the MLC module into the main RTTP system, Radiation Oncology Computer System (ROCS). The dosimetric parameter that has the most profound effect on the accuracy of the dose delivered with an MLC is the change in the in-air output factor that occurs with field shaping. It has been reported that the conventional method of calculating an in-air output factor cannot be used for MLC shaped fields accurately. Therefore, it is necessary to develop algorithms that allow accurate calculation of the in-air output factor. A generalized solution for an in-air output factor calculation was developed. Three major contributors of scatter to the in-air output-flattening filter, wedge, and tertiary collimator-were considered separately. By virtue of a field mapping method, in which a source plane field determined by detector's eye view is mapped into a detector plane field, no additional dosimetric data acquisition other than the standard data set for a range of square fields is required for the calculation of head scatter. Comparisons of in-air output factors between calculated and measured values show a good agreement for both open and wedge fields. For rectangular fields, a simple equivalent square formula was derived based on the configuration of a linear accelerator treatment head. This method predicts in-air output to within 1% accuracy. A two-effective-source algorithm was developed to account for the effect of source to detector distance on in-air output for wedge fields. Two effective sources, one for head scatter and the other for wedge scatter, were dealt with independently. Calculations provided less than 1% difference of in-air output factors from measurements. This approach offers the best comprehensive accuracy in radiation delivery with field shapes defined using MLC. This generalized model works equally well with fields shaped by any type of tertiary collimator and have the necessary framework to extend its application to intensity modulated radiation therapy.

SU-E-T-624: Quantitative Evaluation of 2D Versus 3D Dosimetry for Stereotactic Volumetric Modulated Arc Delivery Using COMPASS

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

Vikraman, S; Karrthick, K; Rajesh, T

2014-06-15

Purpose: The purpose of this study was to evaluate quantitatively 2D versus 3D dosimetry for stereotactic volumetric modulated arc delivery using COMPASS with 2D array. Methods: Twenty-five patients CT images and RT structures of different sites like brain, head and neck, thorax, abdomen and spine were taken from Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in Cyberknife. For each patient, linac based VMAT stereotactic plans were generated in Monaco TPS v 3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5-20Gy/fraction.TPS calculated VMAT plan delivery accuracy was quantitatively evaluated withmore » COMPASS measured dose and calculated dose based on DVH metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using Multicube. Results: For each site, D{sub 9} {sub 5} was achieved with 100% of prescription dose with maximum 0.05SD. Conformity index (CI) was observed closer to 1.15 in all cases. Maximum deviation of 2.62 % was observed for D{sub 9} {sub 5} when compared TPS versus COMPASS measured. Considerable deviations were observed in head and neck cases compare to other sites. The maximum mean and standard deviation for D{sub 9} {sub 5}, average target dose and average gamma were -0.78±1.72, -1.10±1.373 and 0.39±0.086 respectively. Numbers of pixels passing 2D fluence verification were observed as a mean of 99.36% ±0.455 SD with 3% dose difference and 3mm DTA. For critical organs in head and neck cases, significant dose differences were observed in 3D dosimetry while the target doses were matched well within limit in both 2D and 3D dosimetry. Conclusion: The quantitative evaluations of 2D versus 3D dosimetry for stereotactic volumetric modulated plans showed the potential of highlighting the delivery errors. This study reveals that COMPASS 3D dosimetry is an effective tool for patient specific quality assurance compared to 2D fluence verification.« less

Multileaf collimator characteristics and reliability requirements for IMRT Elekta system.

PubMed

Liu, Chihray; Simon, Thomas A; Fox, Christopher; Li, Jonathan; Palta, Jatinder R

2008-01-01

Understanding the characteristics of a multileaf collimator (MLC) system, modeling MLC in a treatment planning system, and maintaining the mechanical accuracy of the linear accelerator gantry head system are important factors in the safe implementation of an intensity-modulated radiotherapy program. We review the characteristics of an Elekta MLC system, discuss the necessary MLC modeling parameters for a treatment planning system, and provide a novel method to establish an MLC leaf position quality assurance program. To perform quality assurance on 40 pairs of individual MLC leaves is a time-consuming and difficult task. In this report, an effective routine MLC quality assurance method based on the field edge of a backup jaw as referenced in conjunction with a diode array as a radiation detector system is discussed. The sensitivity of this test for determining the relative leaf positions was observed to be better than 0.1 mm. The Elekta MLC leaf position accuracy measured with this system has been better than 0.3 mm.

Development and evaluation of aperture-based complexity metrics using film and EPID measurements of static MLC openings

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

Götstedt, Julia; Karlsson Hauer, Anna; Bäck, Anna, E-mail: anna.back@vgregion.se

Purpose: Complexity metrics have been suggested as a complement to measurement-based quality assurance for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). However, these metrics have not yet been sufficiently validated. This study develops and evaluates new aperture-based complexity metrics in the context of static multileaf collimator (MLC) openings and compares them to previously published metrics. Methods: This study develops the converted aperture metric and the edge area metric. The converted aperture metric is based on small and irregular parts within the MLC opening that are quantified as measured distances between MLC leaves. The edge area metricmore » is based on the relative size of the region around the edges defined by the MLC. Another metric suggested in this study is the circumference/area ratio. Earlier defined aperture-based complexity metrics—the modulation complexity score, the edge metric, the ratio monitor units (MU)/Gy, the aperture area, and the aperture irregularity—are compared to the newly proposed metrics. A set of small and irregular static MLC openings are created which simulate individual IMRT/VMAT control points of various complexities. These are measured with both an amorphous silicon electronic portal imaging device and EBT3 film. The differences between calculated and measured dose distributions are evaluated using a pixel-by-pixel comparison with two global dose difference criteria of 3% and 5%. The extent of the dose differences, expressed in terms of pass rate, is used as a measure of the complexity of the MLC openings and used for the evaluation of the metrics compared in this study. The different complexity scores are calculated for each created static MLC opening. The correlation between the calculated complexity scores and the extent of the dose differences (pass rate) are analyzed in scatter plots and using Pearson’s r-values. Results: The complexity scores calculated by the edge area metric, converted aperture metric, circumference/area ratio, edge metric, and MU/Gy ratio show good linear correlation to the complexity of the MLC openings, expressed as the 5% dose difference pass rate, with Pearson’s r-values of −0.94, −0.88, −0.84, −0.89, and −0.82, respectively. The overall trends for the 3% and 5% dose difference evaluations are similar. Conclusions: New complexity metrics are developed. The calculated scores correlate to the complexity of the created static MLC openings. The complexity of the MLC opening is dependent on the penumbra region relative to the area of the opening. The aperture-based complexity metrics that combined either the distances between the MLC leaves or the MLC opening circumference with the aperture area show the best correlation with the complexity of the static MLC openings.« less

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

PubMed

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

2016-07-08

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

SU-E-T-67: A Quality Assurance Procedure for VMAT Delivery Technique with Multiple Verification Metric Using TG-119 Protocol

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

Katsuta, Y; Kadoya, N; Shimizu, E

2015-06-15

Purpose: A successful VMAT plan delivery includes precise modulations of dose rate, gantry rotational and multi-leaf collimator shapes. The purpose of this research is to construct routine QA protocol which focuses on VMAT delivery technique and to obtain a baseline including dose error, fluence distribution and mechanical accuracy during VMAT. Methods: The mock prostate, head and neck (HN) cases supplied from AAPM were used in this study. A VMAT plans were generated in Monaco TPS according to TG-119 protocol. Plans were created using 6 MV and 10 MV photon beams for each case. The phantom based measurement, fluence measurement andmore » log files analysis were performed. The dose measurement was performed using 0.6 cc ion chamber, which located at isocenter. The fluence distribution were acquired using the MapCHECK2 mounted in the MapPHAN. The trajectory log files recorded inner 20 leaf pairs and gantry angle positions at every 0.25 sec interval were exported to in-house software developed by MATLAB and determined those RMS values. Results: The dose difference is expressed as a ratio of the difference between measured and planned doses. The dose difference for 6 MV was 0.91%, for 10 MV was 0.67%. In turn, the fluence distribution using gamma criteria of 2%/2 mm with a 50% minimum dose threshold for 6 MV was 98.8%, for 10 MV was 97.5%, respectively. The RMS values of MLC for 6 MV and 10 MV were 0.32 mm and 0.37 mm, of gantry were 0.33 degree and 0.31 degree. Conclusion: In this study, QA protocol to assess VMAT delivery accuracy is constructed and results acquired in this study are used as a baseline of VMAT delivery performance verification.« less

Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

NASA Astrophysics Data System (ADS)

Weinberg, Rebecca

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity.

SU-F-T-402: The Effect of Extremely Narrow MLC Leaf Width On the Plan Quality of VMAT for Prostate Cancer

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

Kim, J; Park, S; Kim, J

2016-06-15

Purpose: To investigate the effect of multi-leaf collimators (MLCs) with leaf width of 1.25 mm on the plan quality of volumetric modulated arc therapy (VMAT) for prostate cancer. Methods: A total of 20 patients with prostate cancer were retrospectively selected. Using a high definition MLC (HD MLC), primary and boost VMAT plans with two full arcs were generated for each patient (original plan). After that, by shifting patient CT images by 1.25 mm in the cranio-caudal direction between the 1st and the 2nd arc, we simulated fluences made with MLCs with leaf width of 1.25 mm. After shifting, primary andmore » boost plans were generated for each patient (shifted plan). A sum plan was generated by summation of the primary and boost plan for each patient. Dose-volumetric parameters were calculated and compared. Results: Both homogeneity index (HI) and conformity index (CI) of the shifted plans were better than those of the original plans in primary plans (HI = 0.044 vs. 0.040 with p < 0.001 and CI = 1.056 vs. 1.044 with p = 0.006). Similarly, the shifted plans for boost target volume showed better homogeneity and conformity than did the original plans (HI = 0.042 vs. 0.037 with p = 0.006 and CI = 1.015 vs. 1.009 with p < 0.001). The total body volumes of the original plans irradiated by the prescription dose were larger than those of the shifted plans in sum plans (60.9 cc vs. 49.0 cc with p = 0.007). Conclusion: Use of extremely narrow MLCs could increase dose homogeneity and conformity of the target volume for prostate VMAT. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A02036331).« less

Electromagnetic guided couch and multileaf collimator tracking on a TrueBeam accelerator

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

Hansen, Rune; Ravkilde, Thomas; Worm, Esben Schjødt

2016-05-15

Purpose: Couch and MLC tracking are two promising methods for real-time motion compensation during radiation therapy. So far, couch and MLC tracking experiments have mainly been performed by different research groups, and no direct comparison of couch and MLC tracking of volumetric modulated arc therapy (VMAT) plans has been published. The Varian TrueBeam 2.0 accelerator includes a prototype tracking system with selectable couch or MLC compensation. This study provides a direct comparison of the two tracking types with an otherwise identical setup. Methods: Several experiments were performed to characterize the geometric and dosimetric performance of electromagnetic guided couch and MLCmore » tracking on a TrueBeam accelerator equipped with a Millennium MLC. The tracking system latency was determined without motion prediction as the time lag between sinusoidal target motion and the compensating motion of the couch or MLC as recorded by continuous MV portal imaging. The geometric and dosimetric tracking accuracies were measured in tracking experiments with motion phantoms that reproduced four prostate and four lung tumor trajectories. The geometric tracking error in beam’s eye view was determined as the distance between an embedded gold marker and a circular MLC aperture in continuous MV images. The dosimetric tracking error was quantified as the measured 2%/2 mm gamma failure rate of a low and a high modulation VMAT plan delivered with the eight motion trajectories using a static dose distribution as reference. Results: The MLC tracking latency was approximately 146 ms for all sinusoidal period lengths while the couch tracking latency increased from 187 to 246 ms with decreasing period length due to limitations in the couch acceleration. The mean root-mean-square geometric error was 0.80 mm (couch tracking), 0.52 mm (MLC tracking), and 2.75 mm (no tracking) parallel to the MLC leaves and 0.66 mm (couch), 1.14 mm (MLC), and 2.41 mm (no tracking) perpendicular to the leaves. The motion-induced gamma failure rate was in mean 0.1% (couch tracking), 8.1% (MLC tracking), and 30.4% (no tracking) for prostate motion and 2.9% (couch), 2.4% (MLC), and 41.2% (no tracking) for lung tumor motion. The residual tracking errors were mainly caused by inadequate adaptation to fast lung tumor motion for couch tracking and to prostate motion perpendicular to the MLC leaves for MLC tracking. Conclusions: Couch and MLC tracking markedly improved the geometric and dosimetric accuracies of VMAT delivery. However, the two tracking types have different strengths and weaknesses. While couch tracking can correct perfectly for slowly moving targets such as the prostate, MLC tracking may have considerably larger dose errors for persistent target shift perpendicular to the MLC leaves. Advantages of MLC tracking include faster dynamics with better adaptation to fast moving targets, the avoidance of moving the patient, and the potential to track target rotations and deformations.« less

Monte Carlo design and simulation of a grid-type multi-layer pixel collimator for radiotherapy: Feasibility study

NASA Astrophysics Data System (ADS)

Yoon, Do-Kun; Jung, Joo-Young; Suh, Tae Suk

2014-05-01

In order to confirm the possibility of field application of a different type collimator with a multileaf collimator (MLC), we constructed a grid-type multi-layer pixel collimator (GTPC) by using a Monte Carlo n-particle simulation (MCNPX). In this research, a number of factors related to the performance of the GPTC were evaluated using simulated output data of a basic MLC model. A layer was comprised of a 1024-pixel collimator (5.0 × 5.0 mm2) which could operate individually as a grid-type collimator (32 × 32). A 30-layer collimator was constructed for a specific portal form to pass radiation through the opening and closing of each pixel cover. The radiation attenuation level and the leakage were compared between the GTPC modality simulation and MLC modeling (tungsten, 17.50 g/cm3, 5.0 × 70.0 × 160.0 mm3) currently used for a radiation field. Comparisons of the portal imaging, the lateral dose profile from a virtual water phantom, the dependence of the performance on the increase in the number of layers, the radiation intensity modulation verification, and the geometric error between the GTPC and the MLC were done using the MCNPX simulation data. From the simulation data, the intensity modulation of the GTPC showed a faster response than the MLC's (29.6%). In addition, the agreement between the doses that should be delivered to the target region was measured as 97.0%, and the GTPC system had an error below 0.01%, which is identical to that of MLC. A Monte Carlo simulation of the GTPC could be useful for verification of application possibilities. Because the line artifact is caused by the grid frame and the folded cover, a lineal dose transfer type is chosen for the operation of this system. However, the result of GTPC's performance showed that the methods of effective intensity modulation and the specific geometric beam shaping differed with the MLC modality.

Experimental evaluation of dual multiple aperture devices for fluence field modulated x-ray computed tomography

NASA Astrophysics Data System (ADS)

Mathews, A. J.; Gang, G.; Levinson, R.; Zbijewski, W.; Kawamoto, S.; Siewerdsen, J. H.; Stayman, J. W.

2017-03-01

Acquisition of CT images with comparable diagnostic power can potentially be achieved with lower radiation exposure than the current standard of care through the adoption of hardware-based fluence-field modulation (e.g. dynamic bowtie filters). While modern CT scanners employ elements such as static bowtie filters and tube-current modulation, such solutions are limited in the fluence patterns that they can achieve, and thus are limited in their ability to adapt to broad classes of patient morphology. Fluence-field modulation also enables new applications such as region-of-interest imaging, task specific imaging, reducing measurement noise or improving image quality. The work presented in this paper leverages a novel fluence modulation strategy that uses "Multiple Aperture Devices" (MADs) which are, in essence, binary filters, blocking or passing x-rays on a fine scale. Utilizing two MAD devices in series provides the capability of generating a large number of fluence patterns via small relative motions between the MAD filters. We present the first experimental evaluation of fluence-field modulation using a dual-MAD system, and demonstrate the efficacy of this technique with a characterization of achievable fluence patterns and an investigation of experimental projection data.

Radio frequency noise from an MLC: a feasibility study of the use of an MLC for linac-MR systems.

PubMed

Lamey, M; Yun, J; Burke, B; Rathee, S; Fallone, B G

2010-02-21

Currently several groups are actively researching the integration of a megavoltage teletherapy unit with magnetic resonance (MR) imaging for real-time image-guided radiotherapy. The use of a multileaf collimator (MLC) for intensity-modulated radiotherapy for linac-MR units must be investigated. The MLC itself will likely reside in the fringe field of the MR and the motors will produce radio frequency (RF) noise. The RF noise power spectral density from a Varian 52-leaf MLC motor, a Varian Millennium MLC motor and a brushless fan motor has been measured as a function of the applied magnetic field using a near field probe set. For the Varian 52-leaf MLC system, the RF noise produced by 13 of 52 motors is studied as a function of distance from the MLC. Data are reported in the frequency range suitable for 0.2-1.5 T linac-MR systems. Below 40 MHz the Millennium MLC motor tested showed more noise than the Varian 52-leaf motor or the brushless fan motor. The brushless motor showed a small dependence on the applied magnetic field. Images of a phantom were taken by the prototype linac-MR system with the MLC placed in close proximity to the magnet. Several orientations of the MLC in both shielded and non-shielded configurations were studied. For the case of a non-shielded MLC and associated cables, the signal-to-noise ratio (SNR) was reduced when 13 of 52 MLC leaves were moved during imaging. When the MLC and associated cables were shielded, the measured SNR of the images with 13 MLC leaves moving was experimentally the same as the SNR of the stationary MLC image. When the MLC and cables are shielded, subtraction images acquired with and without MLC motion contains no systematic signal. This study illustrates that the small RF noise produced by functioning MLC motors can be effectively shielded to avoid SNR degradation. A functioning MLC can be incorporated into a linac-MR unit.

Radio frequency noise from an MLC: a feasibility study of the use of an MLC for linac-MR systems

PubMed Central

Lamey, M; Yun, J; Burke, B; Rathee, S; Fallone, B G

2010-01-01

Currently several groups are actively researching the integration of a megavoltage teletherapy unit with magnetic resonance (MR) imaging for real-time image-guided radiotherapy. The use of a multileaf collimator (MLC) for intensity-modulated radiotherapy for linac-MR units must be investigated. The MLC itself will likely reside in the fringe field of the MR and the motors will produce radio frequency (RF) noise. The RF noise power spectral density from a Varian 52-leaf MLC motor, a Varian Millennium MLC motor and a brushless fan motor has been measured as a function of the applied magnetic field using a near field probe set. For the Varian 52-leaf MLC system, the RF noise produced by 13 of 52 motors is studied as a function of distance from the MLC. Data are reported in the frequency range suitable for 0.2–1.5 T linac-MR systems. Below 40 MHz the Millennium MLC motor tested showed more noise than the Varian 52-leaf motor or the brushless fan motor. The brushless motor showed a small dependence on the applied magnetic field. Images of a phantom were taken by the prototype linac-MR system with the MLC placed in close proximity to the magnet. Several orientations of the MLC in both shielded and non-shielded configurations were studied. For the case of a non-shielded MLC and associated cables, the signal-to-noise ratio (SNR) was reduced when 13 of 52 MLC leaves were moved during imaging. When the MLC and associated cables were shielded, the measured SNR of the images with 13 MLC leaves moving was experimentally the same as the SNR of the stationary MLC image. When the MLC and cables are shielded, subtraction images acquired with and without MLC motion contains no systematic signal. This study illustrates that the small RF noise produced by functioning MLC motors can be effectively shielded to avoid SNR degradation. A functioning MLC can be incorporated into a linac-MR unit. PMID:20090187

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

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

Yang, D; Li, X; Li, H

2014-06-15

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

Technology assessment of multileaf collimation: a North American users survey.

PubMed

Klein, E E; Tepper, J; Sontag, M; Franklin, M; Ling, C; Kubo, D

1999-06-01

The American Association of Physicists in Medicine (AAPM) initiated an Assessment of Technology Subcommittee (ATS) to help the radiotherapy community evaluate emerging technologies. The ATS decided to first address multileaf collimation (MLC) by means of a North American users survey. The survey attempted to address issues such as MLC utility, efficacy, cost-effectiveness, and customer satisfaction. The survey was designed with 38 questions, with cross-tabulation set up to decipher a particular clinic's perception of MLC. The surveys were coded according to MLC types, which were narrowed to four: Elekta, Siemens, Varian 52-leaf, and Varian 80-leaf. A 40% return rate was desired. A 44% (108 of 250) return was achieved. On an MLC machine, 76.5% of photon patients are being treated with MLC. The main reasons for not using MLC were stair stepping, field size limitation, and physician objection. The most common sites in which MLC is being used are lung, pelvis, and prostate. The least used sites are head & neck and mantle fields. Of the facilities, 31% claimed an increase in number of patients being treated since MLC was installed, and 44% claimed an increase in the number of fields. Though the staffing for block cutting has decreased, therapist staffing has not. However, 91% of the facilities claimed a decreased workload for the therapists, despite the increase in daily treated patients and fields. Of the facilities that justified MLC purchase for more daily patients, 63% are actually treating more patients. Only 26% of the facilities that justified an MLC purchase for intensity-modulated radiotherapy (IMRT) are currently using it for that purpose. The satisfaction rating (1 = low to 5 = high) for department groups averaged 4.0. Therapists ranked MLC as 4.6. Our survey shows that most users have successfully introduced MLC into the clinic as a block replacement. Most have found MLC to be cost-effective and efficient. The use of MLC for IMRT has progressed slower, but users anticipate escalated use.

Quantitative evaluation of 3D dosimetry for stereotactic volumetric‐modulated arc delivery using COMPASS

PubMed Central

Manigandan, Durai; Karrthick, Karukkupalayam Palaniappan; Sambasivaselli, Raju; Senniandavar, Vellaingiri; Ramu, Mahendran; Rajesh, Thiyagarajan; Lutz, Muller; Muthukumaran, Manavalan; Karthikeyan, Nithyanantham; Tejinder, Kataria

2014-01-01

The purpose of this study was to evaluate quantitatively the patient‐specific 3D dosimetry tool COMPASS with 2D array MatriXX detector for stereotactic volumetric‐modulated arc delivery. Twenty‐five patients CT images and RT structures from different sites (brain, head & neck, thorax, abdomen, and spine) were taken from CyberKnife Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in CyberKnife. For each patient, linac based volumetric‐modulated arc therapy (VMAT) stereotactic plans were generated in Monaco TPS v3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5–20 Gy per fraction. Target prescription and critical organ constraints were tried to match the delivered treatment plans. Each plan quality was analyzed using conformity index (CI), conformity number (CN), gradient Index (GI), target coverage (TC), and dose to 95% of volume (D95). Monaco Monte Carlo (MC)‐calculated treatment plan delivery accuracy was quantitatively evaluated with COMPASS‐calculated (CCA) dose and COMPASS indirectly measured (CME) dose based on dose‐volume histogram metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using MultiCube phantom. Routine quality assurance of absolute point dose verification was performed to check the overall delivery accuracy. Quantitative analyses of dose delivery verification were compared with pass and fail criteria of 3 mm and 3% distance to agreement and dose differences. Gamma passing rate was compared with 2D fluence verification from MatriXX with MultiCube. Comparison of COMPASS reconstructed dose from measured fluence and COMPASS computed dose has shown a very good agreement with TPS calculated dose. Each plan was evaluated based on dose volume parameters for target volumes such as dose at 95% of volume (D95) and average dose. For critical organs dose at 20% of volume (D20), dose at 50% of volume (D50), and maximum point doses were evaluated. Comparison was carried out using gamma analysis with passing criteria of 3 mm and 3%. Mean deviation of 1.9%±1% was observed for dose at 95% of volume (D95) of target volumes, whereas much less difference was noticed for critical organs. However, significant dose difference was noticed in two cases due to the smaller tumor size. Evaluation of this study revealed that the COMPASS 3D dosimetry is efficient and easy to use for patient‐specific QA of VMAT stereotactic delivery. 3D dosimetric QA with COMPASS provides additional degrees of freedom to check the high‐dose modulated stereotactic delivery with very high precision on patient CT images. PACS numbers: 87.55.Qr, 87.56.Fc PMID:25679152

A Rapidly Deployable Bridge System

DTIC Science & Technology

2013-01-15

17 - 4PH SS H1150 Hinge Pins 30x106 psi (2) 143 ksi (4) 157 ksi (4) - 104.7 ksi SS T316 Cables 30x106 psi - 116 ksi - 77.3 ksi The stress...CLASSIFICATION OF: 17 . LIMITATION OF ABSTRACT Public Release 18. NUMBER OF PAGES 12 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b...an MLC30/12m configuration. The MLC50/20m system uses 17 modules in a 9/8 configuration. The connection of the modules to each other is by means of

VMAT testing for an Elekta accelerator

PubMed Central

Sweeney, Larry E.; Marshall, Edward I.; Mahendra, Saikanth

2012-01-01

Volumetric‐modulated arc therapy (VMAT) has been shown to be able to deliver plans equivalent to intensity‐modulated radiation therapy (IMRT) in a fraction of the treatment time. This improvement is important for patient immobilization/ localization compliance due to comfort and treatment duration, as well as patient throughput. Previous authors have suggested commissioning methods for this modality. Here, we extend the methods reported for the Varian RapidArc system (which tested individual system components) to the Elekta linear accelerator, using custom files built using the Elekta iComCAT software. We also extend the method reported for VMAT commissioning of the Elekta accelerator by verifying maximum values of parameters (gantry speed, multileaf collimator (MLC) speed, and backup jaw speed), investigating: 1) beam profiles as a function of dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3) over/under dosing at changing dose rate junctions. Equations for construction of the iComCAT files are given. Results indicate that the beam profile for lower dose rates varies less than 3% from that of the maximum dose rate, with no difference during an arc. The gantry, MLC, and backup jaw maximum speed are internally consistent. The monitor unit chamber is stable over the MUs and gantry movement conditions expected. MLC movement and position during VMAT delivery are within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately controlled. Over/under dosing at junctions of MLC reversals or dose rate changes are within clinical acceptability. PACS numbers: 87.55.de, 87.55.Qr, 87.56.bd PMID:22402389

A stochastic convolution/superposition method with isocenter sampling to evaluate intrafraction motion effects in IMRT.

PubMed

Naqvi, Shahid A; D'Souza, Warren D

2005-04-01

Current methods to calculate dose distributions with organ motion can be broadly classified as "dose convolution" and "fluence convolution" methods. In the former, a static dose distribution is convolved with the probability distribution function (PDF) that characterizes the motion. However, artifacts are produced near the surface and around inhomogeneities because the method assumes shift invariance. Fluence convolution avoids these artifacts by convolving the PDF with the incident fluence instead of the patient dose. In this paper we present an alternative method that improves the accuracy, generality as well as the speed of dose calculation with organ motion. The algorithm starts by sampling an isocenter point from a parametrically defined space curve corresponding to the patient-specific motion trajectory. Then a photon is sampled in the linac head and propagated through the three-dimensional (3-D) collimator structure corresponding to a particular MLC segment chosen randomly from the planned IMRT leaf sequence. The photon is then made to interact at a point in the CT-based simulation phantom. Randomly sampled monoenergetic kernel rays issued from this point are then made to deposit energy in the voxels. Our method explicitly accounts for MLC-specific effects (spectral hardening, tongue-and-groove, head scatter) as well as changes in SSD with isocentric displacement, assuming that the body moves rigidly with the isocenter. Since the positions are randomly sampled from a continuum, there is no motion discretization, and the computation takes no more time than a static calculation. To validate our method, we obtained ten separate film measurements of an IMRT plan delivered on a phantom moving sinusoidally, with each fraction starting with a random phase. For 2 cm motion amplitude, we found that a ten-fraction average of the film measurements gave an agreement with the calculated infinite fraction average to within 2 mm in the isodose curves. The results also corroborate the existing notion that the interfraction dose variability due to the interplay between the MLC motion and breathing motion averages out over typical multifraction treatments. Simulation with motion waveforms more representative of real breathing indicate that the motion can produce penumbral spreading asymmetric about the static dose distributions. Such calculations can help a clinician decide to use, for example, a larger margin in the superior direction than in the inferior direction. In the paper we demonstrate that a 15 min run on a single CPU can readily illustrate the effect of a patient-specific breathing waveform, and can guide the physician in making informed decisions about margin expansion and dose escalation.

WE-AB-209-10: Optimizing the Delivery of Sequential Fluence Maps for Efficient VMAT Delivery

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

Craft, D; Balvert, M

2016-06-15

Purpose: To develop an optimization model and solution approach for computing MLC leaf trajectories and dose rates for high quality matching of a set of optimized fluence maps to be delivered sequentially around a patient in a VMAT treatment. Methods: We formulate the fluence map matching problem as a nonlinear optimization problem where time is discretized but dose rates and leaf positions are continuous variables. For a given allotted time, which is allocated across the fluence maps based on the complexity of each fluence map, the optimization problem searches for the best leaf trajectories and dose rates such that themore » original fluence maps are closely recreated. Constraints include maximum leaf speed, maximum dose rate, and leaf collision avoidance, as well as the constraint that the ending leaf positions for one map are the starting leaf positions for the next map. The resulting model is non-convex but smooth, and therefore we solve it by local searches from a variety of starting positions. We improve solution time by a custom decomposition approach which allows us to decouple the rows of the fluence maps and solve each leaf pair individually. This decomposition also makes the problem easily parallelized. Results: We demonstrate method on a prostate case and a head-and-neck case and show that one can recreate fluence maps to high degree of fidelity in modest total delivery time (minutes). Conclusion: We present a VMAT sequencing method that reproduces optimal fluence maps by searching over a vast number of possible leaf trajectories. By varying the total allotted time given, this approach is the first of its kind to allow users to produce VMAT solutions that span the range of wide-field coarse VMAT deliveries to narrow-field high-MU sliding window-like approaches.« less

Measurement and Monte Carlo simulation for energy- and intensity-modulated electron radiotherapy delivered by a computer-controlled electron multileaf collimator.

PubMed

Jin, Lihui; Eldib, Ahmed; Li, Jinsheng; Emam, Ismail; Fan, Jiajin; Wang, Lu; Ma, C-M

2014-01-06

The dosimetric advantage of modulated electron radiotherapy (MERT) has been explored by many investigators and is considered to be an advanced radiation therapy technique in the utilization of electrons. A computer-controlled electron multileaf collimator (MLC) prototype, newly designed to be added onto a Varian linac to deliver MERT, was investigated both experimentally and by Monte Carlo simulations. Four different electron energies, 6, 9, 12, and 15 MeV, were employed for this investigation. To ensure that this device was capable of delivering the electron beams properly, measurements were performed to examine the electron MLC (eMLC) leaf leakage and to determine the appropriate jaw positioning for an eMLC-shaped field in order to eliminate a secondary radiation peak that could otherwise appear outside of an intended radiation field in the case of inappropriate jaw positioning due to insufficient radiation blockage from the jaws. Phase space data were obtained by Monte Carlo (MC) simulation and recorded at the plane just above the jaws for each of the energies (6, 9, 12, and 15 MeV). As an input source, phase space data were used in MC dose calculations for various sizes of the eMLC shaped field (10 × 10 cm2, 3.4 × 3.4 cm2, and 2 × 2 cm2) with respect to a water phantom at source-to-surface distance (SSD) = 94 cm, while the jaws, eMLC leaves, and some accessories associated with the eMLC assembly as well were modeled as modifiers in the calculations. The calculated results were then compared with measurements from a water scanning system. The results showed that jaw settings with 5 mm margins beyond the field shaped by the eMLC were appropriate to eliminate the secondary radiation peak while not widening the beam penumbra; the eMLC leaf leakage measurements ranged from 0.3% to 1.8% for different energies based on in-phantom measurements, which should be quite acceptable for MERT. Comparisons between MC dose calculations and measurements showed agreement within 1%/1 mm based on percentage depth doses (PDDs) and off-axis dose profiles for a range of field sizes for each of the electron energies. Our current work has demonstrated that the eMLC and other relevant components in the linac were correctly modeled and simulated via our in-house MC codes, and the eMLC is capable of accurately delivering electron beams for various eMLC-shaped field sizes with appropriate jaw settings. In the next stage, patient-specific verification with a full MERT plan should be performed.

Technical Note: A novel leaf sequencing optimization algorithm which considers previous underdose and overdose events for MLC tracking radiotherapy

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

Wisotzky, Eric, E-mail: eric.wisotzky@charite.de, E-mail: eric.wisotzky@ipk.fraunhofer.de; O’Brien, Ricky; Keall, Paul J., E-mail: paul.keall@sydney.edu.au

2016-01-15

Purpose: Multileaf collimator (MLC) tracking radiotherapy is complex as the beam pattern needs to be modified due to the planned intensity modulation as well as the real-time target motion. The target motion cannot be planned; therefore, the modified beam pattern differs from the original plan and the MLC sequence needs to be recomputed online. Current MLC tracking algorithms use a greedy heuristic in that they optimize for a given time, but ignore past errors. To overcome this problem, the authors have developed and improved an algorithm that minimizes large underdose and overdose regions. Additionally, previous underdose and overdose events aremore » taken into account to avoid regions with high quantity of dose events. Methods: The authors improved the existing MLC motion control algorithm by introducing a cumulative underdose/overdose map. This map represents the actual projection of the planned tumor shape and logs occurring dose events at each specific regions. These events have an impact on the dose cost calculation and reduce recurrence of dose events at each region. The authors studied the improvement of the new temporal optimization algorithm in terms of the L1-norm minimization of the sum of overdose and underdose compared to not accounting for previous dose events. For evaluation, the authors simulated the delivery of 5 conformal and 14 intensity-modulated radiotherapy (IMRT)-plans with 7 3D patient measured tumor motion traces. Results: Simulations with conformal shapes showed an improvement of L1-norm up to 8.5% after 100 MLC modification steps. Experiments showed comparable improvements with the same type of treatment plans. Conclusions: A novel leaf sequencing optimization algorithm which considers previous dose events for MLC tracking radiotherapy has been developed and investigated. Reductions in underdose/overdose are observed for conformal and IMRT delivery.« less

Comparision of beam data requirements for MLC commissioning on a TPS

NASA Astrophysics Data System (ADS)

Solaiappan, Gopi; Singaravelu, Ganesan; Prakasarao, Aruna; Supe, Sanjay S.

2008-01-01

The treatment planning system (TPS) has become a key element in the radiotherapy process with the introduction of computer tomography (CT) based 3D conformal treatment planning. Commissioning of a MLC on a TPS either for conformal radiotherapy or intensity modulated radiation therapy (IMRT) requires beam data to be generated on a linear accelerator. Most of the TPS require these beam data to be generated with routine collimator jaws. However some TPS demand the data to be provided for MLC shaped fields. This prompted us to investigate whether beam data with jaws differ than that with MLC and whether the jaw based beam data would suffice for the commissioning of a MLC on a TPS. Beam data like percentage depth dose (PDD), cross beam profiles and output factors was acquired for jaws and MLC defined square fields for 6, 10 and 23 MV photon beams. Percentage depth dose and cross beam profiles were acquired with a radiation field analyzer RFA-200, CC13-S ion chambers with active volume of 0.13 cm3 and OmniPro-Accept software from Scanditronix-Wellhofer. A Medtec-TG51 water tank with Max-4000 electrometer and 0.6 cc PTW ionization chamber and a mini phantom from Standard Imaging was utilized for output measurements for millennium-120 MLC (Varian Medical Systems) and SRS diode detector (Scanditronix-Wellhofer) of 0.6 mm diameter of active area and 0.3 mm of active volume thickness for micro-MLC (BrainLab). The difference in PDD in the build-up region for millennium MLC was ±1.0% for 6 MV photons. For 10 MV photons the PDD difference was within ±4.0%. The difference in PDD for 23 MV photons ranged from 0% to 40.0%. PDD difference from build-up depth to about 28 cm was within ±1.0%. Difference in PDD crossed ±1.0% at 30 cm depth for 6 MV photons. The difference in PDD in the build-up region for mMLC was ±8.0% for 6 MV photons. For the smallest field size studied with micro-MLC i.e. 0.6 × 0.6 cm2 difference in PDD was more than ±1.0% in the build-up region and beyond a depth of 8.0 cm. The profiles for jaws and MLC agreed within the umbra region. However in the penumbra region small differences in doses were observed. The collimator scatter factor (Sc), phantom scatter factor (Sp) and output factor values for MLC were different that those for jaws. The differences in beam characteristics could have implication for intensity modulated radiation therapy and stereotactic radiosurgery in terms of dose in the build up region, exit dose, dose to the planning target volume (PTV) and organ at risk (OAR). Impact of these dosimetric differences between jaw and MLC needs to be further studied in terms of dose volume histograms for PTV and OAR and its further impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).

A method for photon beam Monte Carlo multileaf collimator particle transport

NASA Astrophysics Data System (ADS)

Siebers, Jeffrey V.; Keall, Paul J.; Kim, Jong Oh; Mohan, Radhe

2002-09-01

Monte Carlo (MC) algorithms are recognized as the most accurate methodology for patient dose assessment. For intensity-modulated radiation therapy (IMRT) delivered with dynamic multileaf collimators (DMLCs), accurate dose calculation, even with MC, is challenging. Accurate IMRT MC dose calculations require inclusion of the moving MLC in the MC simulation. Due to its complex geometry, full transport through the MLC can be time consuming. The aim of this work was to develop an MLC model for photon beam MC IMRT dose computations. The basis of the MC MLC model is that the complex MLC geometry can be separated into simple geometric regions, each of which readily lends itself to simplified radiation transport. For photons, only attenuation and first Compton scatter interactions are considered. The amount of attenuation material an individual particle encounters while traversing the entire MLC is determined by adding the individual amounts from each of the simplified geometric regions. Compton scatter is sampled based upon the total thickness traversed. Pair production and electron interactions (scattering and bremsstrahlung) within the MLC are ignored. The MLC model was tested for 6 MV and 18 MV photon beams by comparing it with measurements and MC simulations that incorporate the full physics and geometry for fields blocked by the MLC and with measurements for fields with the maximum possible tongue-and-groove and tongue-or-groove effects, for static test cases and for sliding windows of various widths. The MLC model predicts the field size dependence of the MLC leakage radiation within 0.1% of the open-field dose. The entrance dose and beam hardening behind a closed MLC are predicted within +/-1% or 1 mm. Dose undulations due to differences in inter- and intra-leaf leakage are also correctly predicted. The MC MLC model predicts leaf-edge tongue-and-groove dose effect within +/-1% or 1 mm for 95% of the points compared at 6 MV and 88% of the points compared at 18 MV. The dose through a static leaf tip is also predicted generally within +/-1% or 1 mm. Tests with sliding windows of various widths confirm the accuracy of the MLC model for dynamic delivery and indicate that accounting for a slight leaf position error (0.008 cm for our MLC) will improve the accuracy of the model. The MLC model developed is applicable to both dynamic MLC and segmental MLC IMRT beam delivery and will be useful for patient IMRT dose calculations, pre-treatment verification of IMRT delivery and IMRT portal dose transmission dosimetry.

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

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

Nguyen, D; Thomas, D; Cao, M

2016-06-15

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

Electromagnetic-Guided MLC Tracking Radiation Therapy for Prostate Cancer Patients: Prospective Clinical Trial Results.

PubMed

Keall, Paul J; Colvill, Emma; O'Brien, Ricky; Caillet, Vincent; Eade, Thomas; Kneebone, Andrew; Hruby, George; Poulsen, Per R; Zwan, Benjamin; Greer, Peter B; Booth, Jeremy

2018-06-01

To report on the primary and secondary outcomes of a prospective clinical trial of electromagnetic-guided multileaf collimator (MLC) tracking radiation therapy for prostate cancer. Twenty-eight men with prostate cancer were treated with electromagnetic-guided MLC tracking with volumetric modulated arc therapy. A total of 858 fractions were delivered, with the dose per fraction ranging from 2 to 13.75 Gy. The primary outcome was feasibility, with success determined if >95% of fractions were successfully delivered. The secondary outcomes were (1) the improvement in beam-target geometric alignment, (2) the improvement in dosimetric coverage of the prostate and avoidance of critical structures, and (3) no acute grade ≥3 genitourinary or gastrointestinal toxicity. All 858 planned fractions were successfully delivered with MLC tracking, demonstrating the primary outcome of feasibility (P < .001). MLC tracking improved the beam-target geometric alignment from 1.4 to 0.90 mm (root-mean-square error). MLC tracking improved the dosimetric coverage of the prostate and reduced the daily variation in dose to critical structures. No acute grade ≥3 genitourinary or gastrointestinal toxicity was observed. Electromagnetic-guided MLC tracking radiation therapy for prostate cancer is feasible. The patients received improved geometric targeting and delivered dose distributions that were closer to those planned than they would have received without electromagnetic-guided MLC tracking. No significant acute toxicity was observed. Copyright © 2018 Elsevier Inc. All rights reserved.

Development and validation of a BEAMnrc component module for a miniature multileaf collimator.

PubMed

Doerner, E; Hartmann, G H

2012-05-21

A new component module (CM) named mini multileaf collimator (mMLC) was developed for the Monte Carlo code BEAMnrc. It models the geometry of the add-on miniature multileaf collimator ModuLeaf (MRC Systems GmbH, Heidelberg, Germany, now part of Siemens, Erlangen, Germany). The new CM is partly based on the existing CM called DYNVMLC. The development was performed using a modified EGSnrc platform which enables us to work in the Microsoft Visual Studio environment. In order to validate the new CM, the PRIMUS linac with 6 MV x-rays (Siemens OCS, Concord, CA, USA) equipped with the ModuLeaf mMLC was modelled. Validation was performed by two methods: (a) a ray-tracing method to check the correct geometry of the multileaf collimator (MLC) and (b) a comparison of calculated and measured results of the following dosimetrical parameters: output factors, dose profiles, field edge position penumbra, MLC interleaf leakage and transmission values. Excellent agreement was found for all parameters. It was, in particular, found that the relationship between leaf position and field edge depending on the shape of the leaf ends can be investigated with a higher accuracy by this new CM than by measurements demonstrating the usefulness of the new CM.

Development and validation of a BEAMnrc component module for a miniature multileaf collimator

NASA Astrophysics Data System (ADS)

Doerner, E.; Hartmann, G. H.

2012-05-01

A new component module (CM) named mini multileaf collimator (mMLC) was developed for the Monte Carlo code BEAMnrc. It models the geometry of the add-on miniature multileaf collimator ModuLeaf (MRC Systems GmbH, Heidelberg, Germany, now part of Siemens, Erlangen, Germany). The new CM is partly based on the existing CM called DYNVMLC. The development was performed using a modified EGSnrc platform which enables us to work in the Microsoft Visual Studio environment. In order to validate the new CM, the PRIMUS linac with 6 MV x-rays (Siemens OCS, Concord, CA, USA) equipped with the ModuLeaf mMLC was modelled. Validation was performed by two methods: (a) a ray-tracing method to check the correct geometry of the multileaf collimator (MLC) and (b) a comparison of calculated and measured results of the following dosimetrical parameters: output factors, dose profiles, field edge position penumbra, MLC interleaf leakage and transmission values. Excellent agreement was found for all parameters. It was, in particular, found that the relationship between leaf position and field edge depending on the shape of the leaf ends can be investigated with a higher accuracy by this new CM than by measurements demonstrating the usefulness of the new CM.

SU-E-T-430: Modeling MLC Leaf End in 2D for Sliding Window IMRT and Arc Therapy

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

Liang, X; Zhu, T

2014-06-01

Purpose: To develop a 2D geometric model for MLC accounting for leaf end dose leakage for dynamic IMRT and Rapidarc therapy. Methods: Leaf-end dose leakage is one of the problems for MLC dose calculation and modeling. Dosimetric leaf gap used to model the MLC and to count for leakage in dose calculation, but may not be accurate for smaller leaf gaps. We propose another geometric modeling method to compensate for the MLC round-shape leaf ends dose leakage, and improve the accuracy of dose calculation and dose verification. A triangular function is used to geometrically model the MLC leaf end leakagemore » in the leaf motion direction, and a step function is used in the perpendicular direction. Dose measurements with different leaf gap, different window width, and different window height were conducted, and the results were used to fit the analytical model to get the model parameters. Results: Analytical models have been obtained for stop-and-shoot and dynamic modes for MLC motion. Parameters a=0.4, lw'=5.0 mm for 6X and a=0.54, lw'=4.1 mm for 15x were obtained from the fitting process. The proposed MLC leaf end model improves the dose profile at the two ends of the sliding window opening. This improvement is especially significant for smaller sliding window openings, which are commonly used for highly modulated IMRT plans and arc therapy plans. Conclusion: This work models the MLC round leaf end shape and movement pattern for IMRT dose calculation. The theory, as well as the results in this work provides a useful tool for photon beam IMRT dose calculation and verification.« less

Fast regional readout CMOS Image Sensor for dynamic MLC tracking

NASA Astrophysics Data System (ADS)

Zin, H.; Harris, E.; Osmond, J.; Evans, P.

2014-03-01

Advanced radiotherapy techniques such as volumetric modulated arc therapy (VMAT) require verification of the complex beam delivery including tracking of multileaf collimators (MLC) and monitoring the dose rate. This work explores the feasibility of a prototype Complementary metal-oxide semiconductor Image Sensor (CIS) for tracking these complex treatments by utilising fast, region of interest (ROI) read out functionality. An automatic edge tracking algorithm was used to locate the MLC leaves edges moving at various speeds (from a moving triangle field shape) and imaged with various sensor frame rates. The CIS demonstrates successful edge detection of the dynamic MLC motion within accuracy of 1.0 mm. This demonstrates the feasibility of the sensor to verify treatment delivery involving dynamic MLC up to ~400 frames per second (equivalent to the linac pulse rate), which is superior to any current techniques such as using electronic portal imaging devices (EPID). CIS provides the basis to an essential real-time verification tool, useful in accessing accurate delivery of complex high energy radiation to the tumour and ultimately to achieve better cure rates for cancer patients.

Design of dual multiple aperture devices for dynamical fluence field modulated CT.

PubMed

Mathews, Aswin John; Tilley, Steven; Gang, Grace; Kawamoto, Satomi; Zbijewski, Wojciech; Siewerdsen, Jeffrey H; Levinson, Reuven; Webster Stayman, J

2016-07-01

A Multiple Aperture Device (MAD) is a novel x-ray beam modulator that uses binary filtration on a fine scale to spatially modulate an x-ray beam. Using two MADs in series enables a large variety of fluence profiles by shifting the MADS relative to each other. This work details the design and control of dual MADs for a specific class of desired fluence patterns. Specifically, models of MAD operation are integrated into a best fit objective followed by CMA-ES optimization. To illustrate this framework we demonstrate the design process for an abdominal phantom with the goal of uniform detected signal. Achievable fluence profiles show good agreement with target fluence profiles, and the ability to flatten projections when a phantom is scanned is demonstrated. Simulated data reconstruction using traditional tube current modulation (TCM) and MAD filtering with TCM are investigated with the dual MAD system demonstrating more uniformity in noise and illustrating the potential for dose reduction under a maximum noise level constraint.

Measurement and Monte Carlo simulation for energy‐ and intensity‐modulated electron radiotherapy delivered by a computer‐controlled electron multileaf collimator

PubMed Central

Eldib, Ahmed; Li, Jinsheng; Emam, Ismail; Fan, Jiajin; Wang, Lu; Ma, C‐M

2014-01-01

The dosimetric advantage of modulated electron radiotherapy (MERT) has been explored by many investigators and is considered to be an advanced radiation therapy technique in the utilization of electrons. A computer‐controlled electron multileaf collimator (MLC) prototype, newly designed to be added onto a Varian linac to deliver MERT, was investigated both experimentally and by Monte Carlo simulations. Four different electron energies, 6, 9, 12, and 15 MeV, were employed for this investigation. To ensure that this device was capable of delivering the electron beams properly, measurements were performed to examine the electron MLC (eMLC) leaf leakage and to determine the appropriate jaw positioning for an eMLC‐shaped field in order to eliminate a secondary radiation peak that could otherwise appear outside of an intended radiation field in the case of inappropriate jaw positioning due to insufficient radiation blockage from the jaws. Phase space data were obtained by Monte Carlo (MC) simulation and recorded at the plane just above the jaws for each of the energies (6, 9, 12, and 15 MeV). As an input source, phase space data were used in MC dose calculations for various sizes of the eMLC shaped field (10×10 cm2, 3.4×3.4 cm2, and 2×2 cm2) with respect to a water phantom at source‐to‐surface distance (SSD)=94cm, while the jaws, eMLC leaves, and some accessories associated with the eMLC assembly as well were modeled as modifiers in the calculations. The calculated results were then compared with measurements from a water scanning system. The results showed that jaw settings with 5 mm margins beyond the field shaped by the eMLC were appropriate to eliminate the secondary radiation peak while not widening the beam penumbra; the eMLC leaf leakage measurements ranged from 0.3% to 1.8% for different energies based on in‐phantom measurements, which should be quite acceptable for MERT. Comparisons between MC dose calculations and measurements showed agreement within 1%/1mm based on percentage depth doses (PDDs) and off‐axis dose profiles for a range of field sizes for each of the electron energies. Our current work has demonstrated that the eMLC and other relevant components in the linac were correctly modeled and simulated via our in‐house MC codes, and the eMLC is capable of accurately delivering electron beams for various eMLC‐shaped field sizes with appropriate jaw settings. In the next stage, patient‐specific verification with a full MERT plan should be performed. PACS number: 87.55.ne PMID:24423848

Intercultural Learning--An Undergraduate Module Supporting the Development of Students' Cultural Awareness in International Settings

ERIC Educational Resources Information Center

Colaiacomo, Silvia; Puntil, Donata

2018-01-01

This report illustrates the context and development of the Intercultural Learning module, provided by the Modern Language Centre (MLC), King's College London. The Intercultural Learning Module is a one semester undergraduate course mostly attended by visiting study abroad students. The module aims to enhance students' intercultural awareness and…

A Varian DynaLog file-based procedure for patient dose-volume histogram-based IMRT QA.

PubMed

Calvo-Ortega, Juan F; Teke, Tony; Moragues, Sandra; Pozo, Miquel; Casals-Farran, Joan

2014-03-06

In the present study, we describe a method based on the analysis of the dynamic MLC log files (DynaLog) generated by the controller of a Varian linear accelerator in order to perform patient-specific IMRT QA. The DynaLog files of a Varian Millennium MLC, recorded during an IMRT treatment, can be processed using a MATLAB-based code in order to generate the actual fluence for each beam and so recalculate the actual patient dose distribution using the Eclipse treatment planning system. The accuracy of the DynaLog-based dose reconstruction procedure was assessed by introducing ten intended errors to perturb the fluence of the beams of a reference plan such that ten subsequent erroneous plans were generated. In-phantom measurements with an ionization chamber (ion chamber) and planar dose measurements using an EPID system were performed to investigate the correlation between the measured dose changes and the expected ones detected by the reconstructed plans for the ten intended erroneous cases. Moreover, the method was applied to 20 cases of clinical plans for different locations (prostate, lung, breast, and head and neck). A dose-volume histogram (DVH) metric was used to evaluate the impact of the delivery errors in terms of dose to the patient. The ionometric measurements revealed a significant positive correlation (R² = 0.9993) between the variations of the dose induced in the erroneous plans with respect to the reference plan and the corresponding changes indicated by the DynaLog-based reconstructed plans. The EPID measurements showed that the accuracy of the DynaLog-based method to reconstruct the beam fluence was comparable with the dosimetric resolution of the portal dosimetry used in this work (3%/3 mm). The DynaLog-based reconstruction method described in this study is a suitable tool to perform a patient-specific IMRT QA. This method allows us to perform patient-specific IMRT QA by evaluating the result based on the DVH metric of the planning CT image (patient DVH-based IMRT QA).

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

Liu, S; Mazur, T; Li, H

Purpose: The aim of this paper was to demonstrate the feasibility and creditability of computing and verifying 3D fluencies to assure IMRT and VMAT treatment deliveries, by correlating the passing rates of the 3D fluence-based QA (P(ά)) to the passing rates of 2D dose measurementbased QA (P(Dm)). Methods: 3D volumetric primary fluencies are calculated by forward-projecting the beam apertures and modulated by beam MU values at all gantry angles. We first introduce simulated machine parameter errors (MU, MLC positions, jaw, gantry and collimator) to the plan. Using passing rates of voxel intensity differences (P(Ir)) and 3D gamma analysis (P(γ)), calculatedmore » 3D fluencies, calculated 3D delivered dose, and measured 2D planar dose in phantom from the original plan are then compared with those from corresponding plans with errors, respectively. The correlations of these three groups of resultant passing rates, i.e. 3D fluence-based QA (P(ά,Ir) and P(ά,γ)), calculated 3D dose (P(Dc,Ir) and P(Dc,γ)), and 2D dose measurement-based QA (P(Dm,Ir) and P(Dm,γ)), will be investigated. Results: 20 treatment plans with 5 different types of errors were tested. Spearman’s correlations were found between P(ά,Ir) and P(Dc,Ir), and also between P(ά,γ) and P(Dc,γ), with averaged p-value 0.037, 0.065, and averaged correlation coefficient ρ-value 0.942, 0.871 respectively. Using Matrixx QA for IMRT plans, Spearman’s correlations were also obtained between P(ά,Ir) and P(Dm,Ir) and also between P(ά,γ) and P(Dm,γ), with p-value being 0.048, 0.071 and ρ-value being 0.897, 0.779 respectively. Conclusion: The demonstrated correlations improve the creditability of using 3D fluence-based QA for assuring treatment deliveries for IMRT/VMAT plans. Together with advantages of high detection sensitivity and better visualization of machine parameter errors, this study further demonstrates the accuracy and feasibility of 3D fluence based-QA in pre-treatment QA and daily QA. Research reported in this study is supported by the Agency for Healthcare Research and Quality (AHRQ) under award 1R01HS0222888. The senior author received research grants from ViewRay Inc. and Varian Medical System.« less

Heavy Ion and Proton-Induced Single Event Upset Characteristics of a 3D NAND Flash Memory

NASA Technical Reports Server (NTRS)

Chen, Dakai; Wilcox, Edward; Ladbury, Raymond; Seidleck, Christina; Kim, Hak; Phan, Anthony; Label, Kenneth

2017-01-01

We evaluated the effects of heavy ion and proton irradiation for a 3D NAND flash. The 3D NAND showed similar single-event upset (SEU) sensitivity to a planar NAND of identical density in the multiple-cell level (MLC) storage mode. The 3D NAND showed significantly reduced SEU susceptibility in single-level-cell (SLC) storage mode. Additionally, the 3D NAND showed less multiple-bit upset susceptibility than the planar NAND, with fewer number of upset bits per byte and smaller cross sections overall. However, the 3D architecture exhibited angular sensitivities for both base and face angles, reflecting the anisotropic nature of the SEU vulnerability in space. Furthermore, the SEU cross section decreased with increasing fluence for both the 3D NAND and the Micron 16 nm planar NAND, which suggests that typical heavy ion test fluences will underestimate the upset rate during a space mission. These unique characteristics introduce complexity to traditional ground irradiation test procedures.

Poster - 22: Retrospective analysis of portal dosimetry based QA of Prostate VMAT Plans

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

Badu, Shyam; Darko, Johnson; Fleck, Andre

2016-08-15

Purpose: The purpose of this study is to retrospectively analyze the portal dosimetry based quality assurance of prostate VMAT plans. Methods: Our standard quality assurance of VMAT treatment plans are performed using EPID installed on Varian TrueBeam Linac. In our current study we analyzed 84 prostate pretreatment VMAT plans. All plans consisted of two arcs, 7800cGy in 39 fractions with a 6MV beam. For each of these VMAT plans, the measured fluence for each arc is compared with the reference fluence using gamma index analysis. Results: We have compared the gamma passing rates for three criteria; 3%/3mm, 2%/2mm and 1%/1mm.more » Out of 168 arcs measured, the number below the gamma passing rate 95% using the area, Field+1cm, are 0, 2, and 124 for 3%/3mm, 2%/2mm and 1%/1mm criteria respectively. Corresponding numbers for MLC CIAO are 0, 2, and 139 respectively. The average gamma passing rate for all arcs measured using Field+1cm are 99.9±0.4, 99.6±1.2, and 90.9±6.5 for 3%/3mm, 2%/2mm and 1%/1mm respectively. Similarly if the MLC CIAO area is analyzed, a passing rate of 99.9±0.2, 99.2±1.2 and 87.2±8.5 respectively was observed. The average of the maximum gamma was also found to increase with tighter criteria. Conclusion: Analysis of prostate VMAT quality assurance plans indicate that the gamma passing rate is sensitive to the criteria and the area analyzed.« less

Quality assurance of dynamic parameters in volumetric modulated arc therapy.

PubMed

Manikandan, A; Sarkar, B; Holla, R; Vivek, T R; Sujatha, N

2012-07-01

The purpose of this study was to demonstrate quality assurance checks for accuracy of gantry speed and position, dose rate and multileaf collimator (MLC) speed and position for a volumetric modulated arc treatment (VMAT) modality (Synergy S; Elekta, Stockholm, Sweden), and to check that all the necessary variables and parameters were synchronous. Three tests (for gantry position-dose delivery synchronisation, gantry speed-dose delivery synchronisation and MLC leaf speed and positions) were performed. The average error in gantry position was 0.5° and the average difference was 3 MU for a linear and a parabolic relationship between gantry position and delivered dose. In the third part of this test (sawtooth variation), the maximum difference was 9.3 MU, with a gantry position difference of 1.2°. In the sweeping field method test, a linear relationship was observed between recorded doses and distance from the central axis, as expected. In the open field method, errors were encountered at the beginning and at the end of the delivery arc, termed the "beginning" and "end" errors. For MLC position verification, the maximum error was -2.46 mm and the mean error was 0.0153 ±0.4668 mm, and 3.4% of leaves analysed showed errors of >±1 mm. This experiment demonstrates that the variables and parameters of the Synergy S are synchronous and that the system is suitable for delivering VMAT using a dynamic MLC.

A novel method for dose distribution registration using fiducial marks made by a megavoltage beam in film dosimetry for intensity-modulated radiation therapy quality assurance.

PubMed

Nakayama, Shinichi; Monzen, Hajime; Oonishi, Yuuichi; Mizote, Rika; Iramina, Hiraku; Kaneshige, Souichirou; Mizowaki, Takashi

2015-06-01

Photographic film is widely used for the dose distribution verification of intensity-modulated radiation therapy (IMRT). However, analysis for verification of the results is subjective. We present a novel method for marking the isocenter using irradiation from a megavoltage (MV) beam transmitted through slits in a multi-leaf collimator (MLC). We evaluated the effect of the marking irradiation at 500 monitor units (MU) on the total transmission through the MLC using an ionization chamber and Radiochromic Film. Film dosimetry was performed for quality assurance (QA) of IMRT plans. Three methods of registration were used for each film: marking by irradiating with an MV beam through slits in the MLC (MLC-IC); marking with a fabricated phantom (Phantom-IC); and a subjective method based on isodose lines (Manual). Each method was subjected to local γ-analysis. The effect of the marking irradiation on the total transmission was 0.16%, as measured by a ionization chamber at a 10-cm depth in a solid phantom, while the inter-leaf transmission was 0.3%, determined from the film. The mean pass rates for each registration method agreed within ± 1% when the criteria used were a distance-to-agreement (DTA) of 3 mm and a dose difference (DD) of 3%. For DTA/DD criteria of 2mm/3%, the pass rates in the sagittal plane were 96.09 ± 0.631% (MLC-IC), 96.27 ± 0.399% (Phantom-IC), and 95.62 ± 0.988% (Manual). The present method is a versatile and useful method of improving the objectivity of film dosimetry for IMRT QA. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A dosimetric evaluation of the Eclipse AAA algorithm and Millennium 120 MLC for cranial intensity-modulated radiosurgery

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

Calvo Ortega, Juan Francisco, E-mail: jfcdrr@yahoo.es; Moragues, Sandra; Pozo, Miquel

2014-07-01

The aim of this study is to assess the accuracy of a convolution-based algorithm (anisotropic analytical algorithm [AAA]) implemented in the Eclipse planning system for intensity-modulated radiosurgery (IMRS) planning of small cranial targets by using a 5-mm leaf-width multileaf collimator (MLC). Overall, 24 patient-based IMRS plans for cranial lesions of variable size (0.3 to 15.1 cc) were planned (Eclipse, AAA, version 10.0.28) using fixed field-based IMRS produced by a Varian linear accelerator equipped with a 120 MLC (5-mm width on central leaves). Plan accuracy was evaluated according to phantom-based measurements performed with radiochromic film (EBT2, ISP, Wayne, NJ). Film 2Dmore » dose distributions were performed with the FilmQA Pro software (version 2011, Ashland, OH) by using the triple-channel dosimetry method. Comparison between computed and measured 2D dose distributions was performed using the gamma method (3%/1 mm). Performance of the MLC was checked by inspection of the DynaLog files created by the linear accelerator during the delivery of each dynamic field. The absolute difference between the calculated and measured isocenter doses for all the IMRS plans was 2.5% ± 2.1%. The gamma evaluation method resulted in high average passing rates of 98.9% ± 1.4% (red channel) and 98.9% ± 1.5% (blue and green channels). DynaLog file analysis revealed a maximum root mean square error of 0.46 mm. According to our results, we conclude that the Eclipse/AAA algorithm provides accurate cranial IMRS dose distributions that may be accurately delivered by a Varian linac equipped with a Millennium 120 MLC.« less

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 05: A novel respiratory motion simulation program for VMAT treatment plans: a phantom validation study

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

Hubley, Emily; Pierce, Greg; Ploquin, Nicolas

Purpose: To develop and validate a computational method to simulate craniocaudal respiratory motion in a VMAT treatment plan. Methods: Three 4DCTs of the QUASAR respiratory motion phantom were acquired with a 2cm water-density spherical tumour embedded in cedar to simulate lung. The phantom was oscillating sinusoidally with an amplitude of 2cm and periods of 3, 4, and 5 seconds. An ITV was contoured and 5mm PTV margin was added. High and a low modulation factor VMAT plans were created for each scan. An in-house program was developed to simulate respiratory motion in the treatment plans by shifting the MLC leafmore » positions relative to the phantom. Each plan was delivered to the phantom and the dose was measured using Gafchromic film. The measured and calculated plans were compared using an absolute dose gamma analysis (3%/3mm). Results: The average gamma pass rate for the low modulation plan and high modulation plans were 91.1% and 51.4% respectively. The difference between the high and low modulation plans gamma pass rates is likely related to the different sampling frequency of the respiratory curve and the higher MLC leaf speeds in the high modulation plan. A high modulation plan has a slower gantry speed and therefore samples the breathing cycle at a coarser frequency leading to inaccuracies between the measured and planned doses. Conclusion: A simple program, including a novel method for increasing sampling frequency beyond the control point frequency, has been developed to simulate respiratory motion in VMAT plans by shifting the MLC leaf positions.« less

SU-F-BRE-16: VMAT Commissioning and Quality Assurance (QA) of An Elekta Synergy-STM Linac Using ICOM Test HarnessTM

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

Nguyen, A; Ironwood CRC, Phoenix, AZ; Rajaguru, P

2014-06-15

Purpose: To establish a set of tests based on the iCOM software that can be used to commission and perform periodic QA of VMAT delivery on the Elekta Synergy-S, commonly known as the Beam Modulator (BM). Methods: iCOM is used to create and deliver customized treatment fields to characterize the system in terms of 1) MLC positioning accuracy under static and dynamic delivery with full gantry rotation, 2) MLC positioning with known errors, 3) Maximum dose rate, 4) Maximum MLC speed, 5) Maximum gantry speed, 6) Synchronization: gantry speed versus dose rate, and 7) Synchronization: MLC speed versus dose rate.more » The resulting images were captured on the iView GT and exported in DICOM format to Dosimetry Check™ system for visual and quantitative analysis. For the initial commissioning phase, the system tests described should be supplemented with extensive patient QAs covering all clinically relevant treatment sites. Results: The system performance test suite showed that on our Synergy-S, MLC positioning was accurate under both static and dynamic deliveries. Intentional errors of 1 mm were also easily identified on both static and dynamic picket fence tests. Maximum dose rate was verified with stop watch to be consistently between 475-480 MU/min. Maximum gantry speed and MLC speed were 5.5 degree/s and 2.5 cm/s respectively. After accounting for beam flatness, both synchronization tests, gantry versus dose rate and MLC speed versus dose rate, were successful as the fields were uniform across the strips and there were no obvious cold/hot spots. Conclusion: VMAT commissioning and quality assurance should include machine characterization tests in addition to patient QAs. Elekta iCOM is a valuable tool for the design of customized VMAT field with specific MU, MLC leaf positions, dose rate, and indirect control of MLC and gantry speed at each of its control points.« less

SU-F-T-429: Craniospinal Irradiation by VMAT Technique: Impact of FFF Beam and High Resolution MLC On Plan Quality

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

Ganesh, T; Sarkar, B; Munshi, A

2016-06-15

Purpose: Objective of this study was to evaluate the impact of using flattening filter free (FFF) beam with 0.5 cm multileaf collimator (MLC) leaves over conventional flattened beam with 1 cm leaf width MLC on the treatment plan quality in cranio-spinal irradiation (CSI). Methods: For five medulloblastoma cases (3 males and 2 females), who were previously treated by volumetric modulated arc therapy (VMAT) technique using conventional flattened beam shaped by 1 cm width MLC leaves, four test plans were generated and compared against the delivered plan. These retrospective plans consisted of four different combinations of flattened and FFF beams frommore » Elekta’s Agility treatment head with 0.5 cm width MLC leaves. Sparing of organs at risks (OAR) in terms of dose to 5%, 50%, 75% and 90% volumes, mean and maximum dose were evaluated. Results: All plans satisfied the planning objective of covering 95% of PTV by at least 95% of prescription dose. Marginal variation of dose spillage was observed between different VMAT plans at very low dose range (1–5 Gy). Variation in dose statistics for PTVs and OARs were within 1% or 1 Gy. Amongst the five plans, the plan with flattened beam with 1 cm MLC had the highest number of MUs, 2.13 times higher than the plan with Agility MLC with FFF beam that had the least number of MUs. No statistically significant difference (p≥0.05) was observed between the reference plan and the retrospectively generated plans in terms of PTV coverage, cold spot, hot spot and organ at risk doses. Conclusion: In the treatment of CSI cases by VMAT technique, FFF beams and/or finer width MLC did not exhibit advantage over the flattened beams or wider MLC in terms of plan quality except for reduction in MUs.« less

SU-F-T-366: Dosimetric Parameters Enhancement of 120-Leaf Millennium MLC Using EGSnrc and IAEA Phase-Space Data

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

Haddad, K; Alopoor, H

Purpose: Recently, the multileaf collimators (MLC) have become an important part of any LINAC collimation systems because they reduce the treatment planning time and improves the conformity. Important factors that affects the MLCs collimation performance are leaves material composition and their thickness. In this study, we investigate the main dosimetric parameters of 120-leaf Millennium MLC including dose in the buildup point, physical penumbra as well as average and end leaf leakages. Effects of the leaves geometry and density on these parameters are evaluated Methods: From EGSnrc Monte Carlo code, BEAMnrc and DOSXYZnrc modules are used to evaluate the dosimetric parametersmore » of a water phantom exposed to a Varian xi for 100cm SSD. Using IAEA phasespace data just above MLC (Z=46cm) and BEAMnrc, for the modified 120-leaf Millennium MLC a new phase space data at Z=52cm is produces. The MLC is modified both in leaf thickness and material composition. EGSgui code generates 521ICRU library for tungsten alloys. DOSXYZnrc with the new phase space evaluates the dose distribution in a water phantom of 60×60×20 cm3 with voxel size of 4×4×2 mm3. Using DOSXYZnrc dose distributions for open beam and closed beam as well as the leakages definition, end leakage, average leakage and physical penumbra are evaluated. Results: A new MLC with improved dosimetric parameters is proposed. The physical penumbra for proposed MLC is 4.7mm compared to 5.16 mm for Millennium. Average leakage in our design is reduced to 1.16% compared to 1.73% for Millennium, the end leaf leakage suggested design is also reduced to 4.86% compared to 7.26% of Millennium. Conclusion: The results show that the proposed MLC with enhanced dosimetric parameters could improve the conformity of treatment planning.« less

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

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

Colvill, Emma; Northern Sydney Cancer Centre, Royal North Shore Hospital, St. Leonards, NSW; Booth, Jeremy T.

2015-08-01

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

TH-AB-202-05: BEST IN PHYSICS (JOINT IMAGING-THERAPY): First Online Ultrasound-Guided MLC Tracking for Real-Time Motion Compensation in Radiotherapy

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

Ipsen, S; Bruder, R; Schweikard, A

Purpose: While MLC tracking has been successfully used for motion compensation of moving targets, current real-time target localization methods rely on correlation models with x-ray imaging or implanted electromagnetic transponders rather than direct target visualization. In contrast, ultrasound imaging yields volumetric data in real-time (4D) without ionizing radiation. We report the first results of online 4D ultrasound-guided MLC tracking in a phantom. Methods: A real-time tracking framework was installed on a 4D ultrasound station (Vivid7 dimension, GE) and used to detect a 2mm spherical lead marker inside a water tank. The volumetric frame rate was 21.3Hz (47ms). The marker wasmore » rigidly attached to a motion stage programmed to reproduce nine tumor trajectories (five prostate, four lung). The 3D marker position from ultrasound was used for real-time MLC aperture adaption. The tracking system latency was measured and compensated by prediction for lung trajectories. To measure geometric accuracy, anterior and lateral conformal fields with 10cm circular aperture were delivered for each trajectory. The tracking error was measured as the difference between marker position and MLC aperture in continuous portal imaging. For dosimetric evaluation, 358° VMAT fields were delivered to a biplanar diode array dosimeter using the same trajectories. Dose measurements with and without MLC tracking were compared to a static reference dose using a 3%/3 mm γ-test. Results: The tracking system latency was 170ms. The mean root-mean-square tracking error was 1.01mm (0.75mm prostate, 1.33mm lung). Tracking reduced the mean γ-failure rate from 13.9% to 4.6% for prostate and from 21.8% to 0.6% for lung with high-modulation VMAT plans and from 5% (prostate) and 18% (lung) to 0% with low modulation. Conclusion: Real-time ultrasound tracking was successfully integrated with MLC tracking for the first time and showed similar accuracy and latency as other methods while holding the potential to measure target motion non-invasively. SI was supported by the Graduate School for Computing in Medicine and Life Science, German Excellence Initiative [grant DFG GSC 235/1].« less

SU-E-T-178: Clinical Feasibility of Multi-Leaf Collimator Based Dynamic Wedge

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

Jeong, C; Kwak, J; Ahn, S

2015-06-15

Purpose: A multi-leaf collimator (MLC) based dynamic wedge (MDW), which provide similar dose profile of physical wedge (PW) along x-jaw direction while significant monitor unit (MU) reduction, was developed and investigated for clinical use. Methods: A novel technique was used to create the wedge profile using MLC. A modification was applied to the DICOM-RT format file of the plan made with the PW to replace PW with MDW. The Varian enhanced dynamic wedge profile was used to produce MLC sequence, while the MU of the wedged field was recalculated using PW factor and fluence map. The profiles for all possiblemore » MDWs to substitute PWs were verified in 6/15 MV x-ray irradiations. New plans with MDWs were compared with the original plans in 5 rectal, 5 RT breast and 5 liver cases. Results: The wedge profile of the MDW fields were well matched with those of PWs inside the fields while less scatter than PW out of the fields. For plan comparisons of the clinical cases no significant dose discrepancy was observed between MDW plan and PW’s with the dose volume histograms. The maximum and mean doses in PTVs are agreed within 1.0%. The Result of OARs of MDW plans are slightly improved in the maximum doses (3.22 ∼ 150.4 cGy) and the mean doses (17.18 ∼ 85.52 cGy) on average for all cases while the prescribed doses are 45 Gy for rectal cases, 40 or 45 Gy for liver cases and 50 Gy for breast cases. The MUs of the fields which replace PW with MDW are reduced to 68% of those of PW. Conclusion: We developed a novel dynamic wedge technique with MLC that shows clinical advantage compared to PW.« less

Quality assurance of dynamic parameters in volumetric modulated arc therapy

PubMed Central

Manikandan, A; Sarkar, B; Holla, R; Vivek, T R; Sujatha, N

2012-01-01

Objectives The purpose of this study was to demonstrate quality assurance checks for accuracy of gantry speed and position, dose rate and multileaf collimator (MLC) speed and position for a volumetric modulated arc treatment (VMAT) modality (Synergy® S; Elekta, Stockholm, Sweden), and to check that all the necessary variables and parameters were synchronous. Methods Three tests (for gantry position–dose delivery synchronisation, gantry speed–dose delivery synchronisation and MLC leaf speed and positions) were performed. Results The average error in gantry position was 0.5° and the average difference was 3 MU for a linear and a parabolic relationship between gantry position and delivered dose. In the third part of this test (sawtooth variation), the maximum difference was 9.3 MU, with a gantry position difference of 1.2°. In the sweeping field method test, a linear relationship was observed between recorded doses and distance from the central axis, as expected. In the open field method, errors were encountered at the beginning and at the end of the delivery arc, termed the “beginning” and “end” errors. For MLC position verification, the maximum error was −2.46 mm and the mean error was 0.0153 ±0.4668 mm, and 3.4% of leaves analysed showed errors of >±1 mm. Conclusion This experiment demonstrates that the variables and parameters of the Synergy® S are synchronous and that the system is suitable for delivering VMAT using a dynamic MLC. PMID:22745206

SU-F-T-384: Step and Shoot IMRT, VMAT and Autoplan VMAT Nasopharnyx Plan Robustness to Linear Accelerator Delivery Errors

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

Pogson, EM; Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW; Ingham Institute for Applied Medical Research, Sydney, NSW

Purpose: To identify the robustness of different treatment techniques in respect to simulated linac errors on the dose distribution to the target volume and organs at risk for step and shoot IMRT (ssIMRT), VMAT and Autoplan generated VMAT nasopharynx plans. Methods: A nasopharynx patient dataset was retrospectively replanned with three different techniques: 7 beam ssIMRT, one arc manual generated VMAT and one arc automatically generated VMAT. Treatment simulated uncertainties: gantry, collimator, MLC field size and MLC shifts, were introduced into these plans at increments of 5,2,1,−1,−2 and −5 (degrees or mm) and recalculated in Pinnacle. The mean and maximum dosesmore » were calculated for the high dose PTV, parotids, brainstem, and spinal cord and then compared to the original baseline plan. Results: Simulated gantry angle errors have <1% effect on the PTV, ssIMRT is most sensitive. The small collimator errors (±1 and ±2 degrees) impacted the mean PTV dose by <2% for all techniques, however for the ±5 degree errors mean target varied by up to 7% for the Autoplan VMAT and 10% for the max dose to the spinal cord and brain stem, seen in all techniques. The simulated MLC shifts introduced the largest errors for the Autoplan VMAT, with the larger MLC modulation presumably being the cause. The most critical error observed, was the MLC field size error, where even small errors of 1 mm, caused significant changes to both the PTV and the OAR. The ssIMRT is the least sensitive and the Autoplan the most sensitive, with target errors of up to 20% over and under dosages observed. Conclusion: For a nasopharynx patient the plan robustness observed is highest for the ssIMRT plan and lowest for the Autoplan generated VMAT plan. This could be caused by the more complex MLC modulation seen for the VMAT plans. This project is supported by a grant from NSW Cancer Council.« less

The sensitivity of patient specific IMRT QC to systematic MLC leaf bank offset errors.

PubMed

Rangel, Alejandra; Palte, Gesa; Dunscombe, Peter

2010-07-01

Patient specific IMRT QC is performed routinely in many clinics as a safeguard against errors and inaccuracies which may be introduced during the complex planning, data transfer, and delivery phases of this type of treatment. The purpose of this work is to evaluate the feasibility of detecting systematic errors in MLC leaf bank position with patient specific checks. 9 head and neck (H&N) and 14 prostate IMRT beams were delivered using MLC files containing systematic offsets (+/- 1 mm in two banks, +/- 0.5 mm in two banks, and 1 mm in one bank of leaves). The beams were measured using both MAPCHECK (Sun Nuclear Corp., Melbourne, FL) and the aS1000 electronic portal imaging device (Varian Medical Systems, Palo Alto, CA). Comparisons with calculated fields, without offsets, were made using commonly adopted criteria including absolute dose (AD) difference, relative dose difference, distance to agreement (DTA), and the gamma index. The criteria most sensitive to systematic leaf bank offsets were the 3% AD, 3 mm DTA for MAPCHECK and the gamma index with 2% AD and 2 mm DTA for the EPID. The criterion based on the relative dose measurements was the least sensitive to MLC offsets. More highly modulated fields, i.e., H&N, showed greater changes in the percentage of passing points due to systematic MLC inaccuracy than prostate fields. None of the techniques or criteria tested is sufficiently sensitive, with the population of IMRT fields, to detect a systematic MLC offset at a clinically significant level on an individual field. Patient specific QC cannot, therefore, substitute for routine QC of the MLC itself.

LETTER TO THE EDITOR: Comments on 'The influence of a novel transmission detector on 6 MV x-ray beam characteristics'

NASA Astrophysics Data System (ADS)

Harder, Dietrich

2010-02-01

In their recent paper (Venkataraman et al 2009 Phys. Med. Biol. 54 3173-83) the authors reported on photon beam attenuation and secondary electron production in the novel transmission detector COMPASS, to be placed in the accessory holder of the linac treatment head. In the interest of IMRT patient safety, space-resolved measurements by transmission detectors analysing the MLC-shaped photon fluence pattern in real time are in fact an urgent item for equipment designers. However, there are some constraints for the construction of such devices. The COMPASS system, at its present stage of development, has difficulties in complying with the constraints that the spatial sampling rate should fit the desired task and that the enhanced secondary electron contamination of the photon beam due to the presence of the device should be minimized. The authors also missed to mention a forerunner in this field, the DAVID transmission detector (Poppe et al 2006 Phys. Med. Biol. 51 1237-48), serving for the real-time supervision of the MLC aperture during patient treatment and ever since proven in clinical practice. The DAVID system, a transparent multiwire ionization chamber placed in the accessory holder, will be shortly described.

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

Otageri, P; Grant, E; Maricle, S

Purpose: To evaluate the effects of MLC modeling after commissioning the Varian TrueBeam LINAC in Pinnacle version 9.2. Methods: Stepand-shoot IMRT QAs were investigated when we observed our measured absolute dose results using ion chamber (Capintec PR-05P) were uncharacteristically low; about 4–5% compared to doses calculated by Pinnacle{sup 3} (Phillips, Madison, WI). This problem was predominant for large and highly modulated head and neck (HN) treatments. Intuitively we knew this had to be related to shortcomings in the MLC modeling in Pinnacle. Using film QA we were able to iteratively adjust the MLC parameters. We confirmed results by re-testing fivemore » failed IMRT QA patients; and ion chamber measurements were verified in Quasar anthropomorphic phantom. Results: After commissioning the LINAC in Pinnacle version 9.2, the MLC transmission for 6X, 10X and 15X were 2.0%, 1.7% and 2.0%, respectively, and additional Interleaf leakage for all three energies was 0.5%. These parameters were obtained from profiles scanned with an Edge detector (Sun Nuclear, Melbourne, FL) during machine commissioning. A Verification testing with radiographic EDR2 film (Kodak, Rochester, NY) measurement was performed by creating a closed MLC leaf pattern and analyzing using RIT software (RIT, Colorado Springs, CO). This reduced MLC transmission for 6X, 10X and 15X to 0.7%, 0.9% and 0.9%, respectively; while increasing additional Interleaf leakage for all three energies to 1.0%. Conclusion: Radiographic film measurements were used to correct MLC transmission values for step and shoot IMRT fields used in Pinnacle version 9.2. After adjusting the MLC parameters to correlate with the film QA, there was still very good agreement between the Pinnacle model and commissioning data. Using the same QA methodology, we were also able to improve the beam models for the Varian C-series linacs, Novalis-Tx, and TrueBeam M-120 linacs.« less

Electron beam collimation with a photon MLC for standard electron treatments

NASA Astrophysics Data System (ADS)

Mueller, S.; Fix, M. K.; Henzen, D.; Frei, D.; Frauchiger, D.; Loessl, K.; Stampanoni, M. F. M.; Manser, P.

2018-01-01

Standard electron treatments are currently still performed using standard or molded patient-specific cut-outs placed in the electron applicator. Replacing cut-outs and electron applicators with a photon multileaf collimator (pMLC) for electron beam collimation would make standard electron treatments more efficient and would facilitate advanced treatment techniques like modulated electron radiotherapy (MERT) and mixed beam radiotherapy (MBRT). In this work, a multiple source Monte Carlo beam model for pMLC shaped electron beams commissioned at a source-to-surface distance (SSD) of 70 cm is extended for SSDs of up to 100 cm and validated for several Varian treatment units with field sizes typically used for standard electron treatments. Measurements and dose calculations agree generally within 3% of the maximal dose or 2 mm distance to agreement. To evaluate the dosimetric consequences of using pMLC collimated electron beams for standard electron treatments, pMLC-based and cut-out-based treatment plans are created for a left and a right breast boost, a sternum, a testis and a parotid gland case. The treatment plans consist of a single electron field, either alone (1E) or in combination with two 3D conformal tangential photon fields (1E2X). For each case, a pMLC plan with similar treatment plan quality in terms of dose homogeneity to the target and absolute mean dose values to the organs at risk (OARs) compared to a cut-out plan is found. The absolute mean dose to an OAR is slightly increased for pMLC-based compared to cut-out-based 1E plans if the OAR is located laterally close to the target with respect to beam direction, or if a 6 MeV electron beam is used at an extended SSD. In conclusion, treatment plans using cut-out collimation can be replaced by plans of similar treatment plan quality using pMLC collimation with accurately calculated dose distributions.

Dosimetric evaluation of the clinical implementation of the first commercial IMRT Monte Carlo treatment planning system at 6 MV

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

Heath, Emily; Seuntjens, Jan; Sheikh-Bagheri, Daryoush

2004-10-01

In this work we dosimetrically evaluated the clinical implementation of a commercial Monte Carlo treatment planning software (PEREGRINE, North American Scientific, Cranberry Township, PA) intended for quality assurance (QA) of intensity modulated radiation therapy treatment plans. Dose profiles calculated in homogeneous and heterogeneous phantoms using this system were compared to both measurements and simulations using the EGSnrc Monte Carlo code for the 6 MV beam of a Varian CL21EX linear accelerator. For simple jaw-defined fields, calculations agree within 2% of the dose at d{sub max} with measurements in homogeneous phantoms with the exception of the buildup region where the calculationsmore » overestimate the dose by up to 8%. In heterogeneous lung and bone phantoms the agreement is within 3%, on average, up to 5% for a 1x1 cm{sup 2} field. We tested two consecutive implementations of the MLC model. After matching the calculated and measured MLC leakage, simulations of static and dynamic MLC-defined fields using the most recent MLC model agreed to within 2% with measurements.« less

Modulation indices for volumetric modulated arc therapy.

PubMed

Park, Jong Min; Park, So-Yeon; Kim, Hyoungnyoun; Kim, Jin Ho; Carlson, Joel; Ye, Sung-Joon

2014-12-07

The aim of this study is to present a modulation index (MI) for volumetric modulated arc therapy (VMAT) based on the speed and acceleration analysis of modulating-parameters such as multi-leaf collimator (MLC) movements, gantry rotation and dose-rate, comprehensively. The performance of the presented MI (MIt) was evaluated with correlation analyses to the pre-treatment quality assurance (QA) results, differences in modulating-parameters between VMAT plans versus dynamic log files, and differences in dose-volumetric parameters between VMAT plans versus reconstructed plans using dynamic log files. For comparison, the same correlation analyses were performed for the previously suggested modulation complexity score (MCS(v)), leaf travel modulation complexity score (LTMCS) and MI by Li and Xing (MI Li&Xing). In the two-tailed unpaired parameter condition, p values were acquired. The Spearman's rho (r(s)) values of MIt, MCSv, LTMCS and MI Li&Xing to the local gamma passing rate with 2%/2 mm criterion were -0.658 (p < 0.001), 0.186 (p = 0.251), 0.312 (p = 0.05) and -0.455 (p = 0.003), respectively. The values of rs to the modulating-parameter (MLC positions) differences were 0.917, -0.635, -0.857 and 0.795, respectively (p < 0.001). For dose-volumetric parameters, MIt showed higher statistically significant correlations than the conventional MIs. The MIt showed good performance for the evaluation of the modulation-degree of VMAT plans.

Commissioning of the tongue-and-groove modelling in treatment planning systems: from static fields to VMAT treatments

NASA Astrophysics Data System (ADS)

Hernandez, Victor; Vera-Sánchez, Juan Antonio; Vieillevigne, Laure; Saez, Jordi

2017-08-01

Adequate modelling of the multi-leaf collimator (MLC) by treatment planning systems (TPS) is essential for accurate dose calculations in intensity-modulated radiation-therapy. For this reason modern TPSs incorporate MLC characteristics such as the leaf end curvature, MLC transmission and the tongue-and-groove. However, the modelling of the tongue-and-groove is often neglected during TPS commissioning and it is not known how accurate it is. This study evaluates the dosimetric consequences of the tongue-and-groove effect for two different MLC models using both film dosimetry and ionisation chambers. A set of comprehensive tests are presented that evaluate the ability of TPSs to accurately model this effect in (a) static fields, (b) sliding window beams and (c) VMAT arcs. The tests proposed are useful for the commissioning of TPSs and for the validation of major upgrades. With the ECLIPSE TPS, relevant differences were found between calculations and measurements for beams with dynamic MLCs in the presence of the TG effect, especially for the High Definition MLC, small gap sizes and the 1 mm calculation grid. For this combination, dose differences as high as 10% and 7% were obtained for dynamic MLC gaps of 5 mm and 10 mm, respectively. These differences indicate inadequate modelling of the tongue-and-groove effect, which might not be identified without the proposed tests. In particular, the TPS tended to underestimate the calculated dose, which may require tuning of other configuration parameters in the TPS (such as the dosimetric leaf gap) in order to maximise the agreement between calculations and measurements in clinical plans. In conclusion, a need for better modelling of the MLC by TPSs is demonstrated, one of the relevant aspects being the tongue-and-groove effect. This would improve the accuracy of TPS calculations, especially for plans using small MLC gaps, such as plans with small target volumes or high complexities. Improved modelling of the MLC would also reduce the need for tuning parameters in the TPS, facilitating a more comprehensive configuration and commissioning of TPSs.

Dose-to-water conversion for the backscatter-shielded EPID: A frame-based method to correct for EPID energy response to MLC transmitted radiation

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

Zwan, Benjamin J., E-mail: benjamin.zwan@uon.edu.au; O’Connor, Daryl J.; King, Brian W.

2014-08-15

Purpose: To develop a frame-by-frame correction for the energy response of amorphous silicon electronic portal imaging devices (a-Si EPIDs) to radiation that has transmitted through the multileaf collimator (MLC) and to integrate this correction into the backscatter shielded EPID (BSS-EPID) dose-to-water conversion model. Methods: Individual EPID frames were acquired using a Varian frame grabber and iTools acquisition software then processed using in-house software developed inMATLAB. For each EPID image frame, the region below the MLC leaves was identified and all pixels in this region were multiplied by a factor of 1.3 to correct for the under-response of the imager tomore » MLC transmitted radiation. The corrected frames were then summed to form a corrected integrated EPID image. This correction was implemented as an initial step in the BSS-EPID dose-to-water conversion model which was then used to compute dose planes in a water phantom for 35 IMRT fields. The calculated dose planes, with and without the proposed MLC transmission correction, were compared to measurements in solid water using a two-dimensional diode array. Results: It was observed that the integration of the MLC transmission correction into the BSS-EPID dose model improved agreement between modeled and measured dose planes. In particular, the MLC correction produced higher pass rates for almost all Head and Neck fields tested, yielding an average pass rate of 99.8% for 2%/2 mm criteria. A two-sample independentt-test and fisher F-test were used to show that the MLC transmission correction resulted in a statistically significant reduction in the mean and the standard deviation of the gamma values, respectively, to give a more accurate and consistent dose-to-water conversion. Conclusions: The frame-by-frame MLC transmission response correction was shown to improve the accuracy and reduce the variability of the BSS-EPID dose-to-water conversion model. The correction may be applied as a preprocessing step in any pretreatment portal dosimetry calculation and has been shown to be beneficial for highly modulated IMRT fields.« less

SU-E-T-550: Modulation Index for VMAT

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

Park, J; Park, S; Kim, J

2015-06-15

Purpose: To present modulation indices (MIs) for volumetric modulated arc therapy (VMAT). Methods: A total of 40 VMAT plans were retrospectively selected. To investigate the delivery accuracy of each VMAT plan, gamma passing rates, differences in modulating parameters between plans and log files, and differences between the original plans and the plans reconstructed with the log files were acquired. A modulation index (MIt) was designed by multiplications of the weighted quantifications of MLC speeds, MLC accelerations, gantry accelerations and dose-rate variations. Textural features including angular second moment, inverse difference moment, contrast, variance, correlation and entropy were calculated from the fluencesmore » of each VMAT plan. To test the performance of suggested MIs, Spearman’s rank correlation coefficients (r) with the plan delivery accuracy were calculated. Conventional modulation indices for VMAT including the modulation complexity score for VMAT (MCSv), leaf travel modulation complexity score (LTMCS) and MI by Li & Xing were calculated, and their correlations were also analyzed in the same way. Results: The r values of contrast (particular displacement distance, d = 1), variance (d = 1), MIt, MCSv, LTMCS and MI by Li&Xing to the local gamma passing rates with 2%/2 mm were 0.547 (p < 0.001), 0.519 (p < 0.001), −0.658 (p < 0.001), 0.186 (p = 0.251), 0.312 (p = 0.05) and −0.455 (p = 0.003), respectively. The r values of those to the MLC errors were −0.863, −0.828, 0.917, −0.635, − 0.857 and 0.795, respectively (p < 0.001). For dose-volumetric parameters, MIt showed higher statistically significant correlations than did the conventional modulation indices. Conclusion: The MIt, contrast (d = 1) and variance (d = 1) showed good performance to predict the VMAT delivery accuracy showing higher correlations to the results of various types of verification methods for VMAT. This work was in part supported by the National Research Foundation of Korea (NRF) grant (no. 490-20140029 and no. 490-20130047) funded by the Korea government.« less

Direct aperture optimization using an inverse form of back-projection.

PubMed

Zhu, Xiaofeng; Cullip, Timothy; Tracton, Gregg; Tang, Xiaoli; Lian, Jun; Dooley, John; Chang, Sha X

2014-03-06

Direct aperture optimization (DAO) has been used to produce high dosimetric quality intensity-modulated radiotherapy (IMRT) treatment plans with fast treatment delivery by directly modeling the multileaf collimator segment shapes and weights. To improve plan quality and reduce treatment time for our in-house treatment planning system, we implemented a new DAO approach without using a global objective function (GFO). An index concept is introduced as an inverse form of back-projection used in the CT multiplicative algebraic reconstruction technique (MART). The index, introduced for IMRT optimization in this work, is analogous to the multiplicand in MART. The index is defined as the ratio of the optima over the current. It is assigned to each voxel and beamlet to optimize the fluence map. The indices for beamlets and segments are used to optimize multileaf collimator (MLC) segment shapes and segment weights, respectively. Preliminary data show that without sacrificing dosimetric quality, the implementation of the DAO reduced average IMRT treatment time from 13 min to 8 min for the prostate, and from 15 min to 9 min for the head and neck using our in-house treatment planning system PlanUNC. The DAO approach has also shown promise in optimizing rotational IMRT with burst mode in a head and neck test case.

Flip-chip replacement within the constraints imposed by multilayer ceramic (MLC) modules

NASA Astrophysics Data System (ADS)

Puttlitz, Karl J.

1984-01-01

Economics often dictates that suitable module rework procedures be established to replace solder bump devices (flip chips) reflowed to multichip carriers. These operations are complicated, owing to various constraints such as the substrate's physical and mechanical properties, close proximity of surface features, etc. This paper describes the constraints and the methods to circumvent them. An order of preference based upon the degree of constraint is recommended to achieve device removal and subsequent site dress of the residual solder left on the substrate. It has been determined that rework (device replacement) can be successfully achieved in even highly constricted situations. This is illustrated by the example of utilizing a localized heating technique, hot gas, to remove solder from microsockets from which chips were previously removed. Microsockets are areas to which chips are reflowed to the top surface of IBM's densely populated multilayer ceramic (MLC) modules, thus forming the so-called controlled collapse chip connection or C-4. The microsocket patterns are thus identical to the chip footprint.

Incorporating geometric ray tracing to generate initial conditions for intensity modulated arc therapy optimization

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

Oliver, Mike; Gladwish, Adam; Craig, Jeff

2008-07-15

Purpose and background: Intensity modulated arc therapy (IMAT) is a rotational variant of Intensity modulated radiation therapy (IMRT) that is achieved by allowing the multileaf collimator (MLC) positions to vary as the gantry rotates around the patient. This work describes a method to generate an IMAT plan through the use of a fast ray tracing technique based on dosimetric and geometric information for setting initial MLC leaf positions prior to final IMAT optimization. Methods and materials: Three steps were used to generate an IMAT plan. The first step was to generate arcs based on anatomical contours. The second step wasmore » to generate ray importance factor (RIF) maps by ray tracing the dose distribution inside the planning target volume (PTV) to modify the MLC leaf positions of the anatomical arcs to reduce the maximum dose inside the PTV. The RIF maps were also segmented to create a new set of arcs to improve the dose to low dose voxels within the PTV. In the third step, the MLC leaf positions from all arcs were put through a leaf position optimization (LPO) algorithm and brought into a fast Monte Carlo dose calculation engine for a final dose calculation. The method was applied to two phantom cases, a clinical prostate case and the Radiological Physics Center (RPC)'s head and neck phantom. The authors assessed the plan improvements achieved by each step and compared plans with and without using RIF. They also compared the IMAT plan with an IMRT plan for the RPC phantom. Results: All plans that incorporated RIF and LPO had lower objective function values than those that incorporated LPO only. The objective function value was reduced by about 15% after the generation of RIF arcs and 52% after generation of RIF arcs and leaf position optimization. The IMAT plan for the RPC phantom had similar dose coverage for PTV1 and PTV2 (the same dose volume histogram curves), however, slightly lower dose to the normal tissues compared to a six-field IMRT plan. Conclusion: The use of a ray importance factor can generate initial IMAT arcs efficiently for further MLC leaf position optimization to obtain more favorable IMAT plan.« less

Role of Rac1 in Escherichia coli K1 invasion of human brain microvascular endothelial cells.

PubMed

Rudrabhatla, Rajyalakshmi S; Selvaraj, Suresh K; Prasadarao, Nemani V

2006-02-01

Escherichia coli K1 invasion of human brain microvascular endothelial cells (HBMEC) requires the reorganization of host cytoskeleton at the sites of bacterial entry. Both actin and myosin constitute the cytoskeletal architecture. We have previously shown that myosin light chain (MLC) phosphorylation by MLC kinase is regulated during E. coli invasion by an upstream kinase, p21-activated kinase 1 (PAK1), which is an effector protein of Rac and Cdc42 GTPases, but not of RhoA. Here, we report that the binding of only Rac1 to PAK1 decreases in HBMEC upon infection with E. coli K1, which resulted in increased phosphorylation of MLC. Overexpression of a constitutively active (cAc) form of Rac1 in HBMEC blocked the E. coli invasion significantly, whereas overexpression of a dominant negative form had no effect. Increased PAK1 phosphorylation was observed in HBMEC expressing cAc-Rac1 with a concomitant reduction in the phosphorylation of MLC. Immunocytochemistry studies demonstrated that the inhibition of E. coli invasion into cAc-Rac1/HBMEC is due to lack of phospho-MLC recruitment to the sites of E. coli entry. Taken together the data suggest that E. coli modulates the binding of Rac1, but not Cdc42, to PAK1 during the invasion of HBMEC.

Effects of prostaglandin F2alpha and latanoprost on phosphoinositide turnover, myosin light chain phosphorylation and contraction in cat iris sphincter.

PubMed

Ansari, Habib R; Davis, Angela M; Kaddour-Djebbar, Ismail; Abdel-Latif, Ata A

2003-06-01

The effects of the ocular hypotensive agents prostaglandin F(2alpha) (PGF(2alpha)) and its analog latanoprost on intraocular pressure (IOP) in both animals and human have been investigated extensively in the last two decades. While there is general agreement that application of these PGs to the eye alters IOP by altering the aqueous humor outflow of the eye via the uveoscleral and trabecular meshwork pathways, the mechanism of action of these agents on IOP lowering remains unclear. There is evidence which suggests that myosin light kinase (MLC kinase) may be involved in the IOP-lowering effects of these agents. Thus, the purpose of the present work was to investigate in cat iris sphincter the effects of these PGs on the MLC kinase signaling pathway, inositol phosphates production, MLC phosphorylation and contraction, in order to gain more information about the mechanism through which these agents modulate smooth muscle function and lower IOP. [(3)H]myo-inositol phosphates production was measured by ion-exchange chromatography, MLC kinase activity was measured by incorporation of (32)Pi into MLC, and changes in muscle tension were recorded isometrically. PGF(2alpha) and latanoprost induced contraction in a concentration-dependent manner with EC(50) values of 18.6 and 29.9 nM, respectively, and increased inositol phosphates production in a concentration-dependent manner. At 1 microM, PGF(2alpha) and latanoprost increased inositol phosphates formation by 125 and 102% over basal, respectively. PGF(2alpha) and latanoprost increased MLC phosphorylation in a concentration- and time-dependent manner, at 1 microM and 5 min incubation, the PGs increased the MLC response by 181 and 176% over basal, respectively. In general, PGF(2alpha) was slightly more potent in inducing the biochemical and pharmacological responses. Wortmannin, ML-7 and ML-9, selective inhibitors of MLC kinase, inhibited significantly PGF(2alpha)- and latanoprost-induced MLC phosphorylation and contraction. These results demonstrate for the first time involvement of the MLC kinase pathway in the FP receptor function of this ocular tissue. Contraction-relaxation of smooth muscle alters the shape and stiffness of smooth muscle cells and MLC kinase, through myosin phosphorylation and dephosphorylation, has been shown to be involved in cytoskeletal remodeling, cytoskeletal alterations, and IOP lowering. In light of these reports and the findings presented here we suggest that alterations in the MLC kinase signaling pathway and its derived second messengers, which leads to changes in contraction-relaxation of the smooth muscles of the anterior segment, could facilitate aqueous humor outflow and thus contribute to the IOP-lowering effects of the FP-class PGs.

[Investigation of Elekta linac characteristics for VMAT].

PubMed

Luo, Guangwen; Zhang, Kunyi

2012-01-01

The aim of this study is to investigate the characteristics of Elekta delivery system for volumetric modulated arc therapy (VMAT). Five VMAT plans were delivered in service mode and dose rates, and speed of gantry and MLC leaves were analyzed by log files. Results showed that dose rates varied between 6 dose rates. Gantry and MLC leaf speed dynamically varied during delivery. The technique of VMAT requires linac to dynamically control more parameters, and these key dynamic variables during VMAT delivery can be checked by log files. Quality assurance procedure should be carried out for VMAT related parameter.

A software tool to automatically assure and report daily treatment deliveries by a cobalt‐60 radiation therapy device

PubMed Central

Wooten, H. Omar; Green, Olga; Li, Harold H.; Liu, Shi; Li, Xiaoling; Rodriguez, Vivian; Mutic, Sasa; Kashani, Rojano

2016-01-01

The aims of this study were to develop a method for automatic and immediate verification of treatment delivery after each treatment fraction in order to detect and correct errors, and to develop a comprehensive daily report which includes delivery verification results, daily image‐guided radiation therapy (IGRT) review, and information for weekly physics reviews. After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a commercial MRI‐guided radiotherapy treatment machine, we designed a procedure to use 1) treatment plan files, 2) delivery log files, and 3) beam output information to verify the accuracy and completeness of each daily treatment delivery. The procedure verifies the correctness of delivered treatment plan parameters including beams, beam segments and, for each segment, the beam‐on time and MLC leaf positions. For each beam, composite primary fluence maps are calculated from the MLC leaf positions and segment beam‐on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. A daily treatment delivery report is designed to include all required information for IGRT and weekly physics reviews including the plan and treatment fraction information, daily beam output information, and the treatment delivery verification results. A computer program was developed to implement the proposed procedure of the automatic delivery verification and daily report generation for an MRI guided radiation therapy system. The program was clinically commissioned. Sensitivity was measured with simulated errors. The final version has been integrated into the commercial version of the treatment delivery system. The method automatically verifies the EBRT treatment deliveries and generates the daily treatment reports. Already in clinical use for over one year, it is useful to facilitate delivery error detection, and to expedite physician daily IGRT review and physicist weekly chart review. PACS number(s): 87.55.km PMID:27167269

Analysis of Neutron Production in Passively Scattered Ion-Beam Therapy.

PubMed

Heo, Seunguk; Yoo, Seunghoon; Song, Yongkeun; Kim, Eunho; Shin, Jaeik; Han, Soorim; Jung, Wongyun; Nam, Sanghee; Lee, Rena; Lee, Kitae; Cho, Sungho

2017-07-01

A new treatment facility for heavy ion therapy since 2010 was constructed. In the broad beam, a range shifter, ridge filter and multi leaf collimator (MLC) for the generation of the spread-out Bragg peak is used. In this case, secondary neutrons produced by the interactions of the ion field with beam-modifying devices (e.g. double-scattering system, beam shaping collimators and range compensators) are very important for patient safety. Therefore, these components must be carefully examined in the context of secondary neutron yield and associated secondary cancer risk. In this article, Monte Carlo simulation has been carried out with the FLUktuierende KAskade particle transport code, the fluence and distribution of neutron generation and the neutron dose equivalent from the broad beam components are compared using carbon and proton beams. As a result, it is confirmed that the yield of neutron production using a carbon beam from all components of the broad beam was higher than using a proton beam. The ambient dose by neutrons per heavy ion and proton ion from the MLC surface was 0.12-0.18 and 0.0067-0.0087 pSv, respectively, which shows that heavy ions generate more neutrons than protons. However, ambient dose per treatment 2 Gy, which means physical dose during treatment by ion beam, is higher than carbon beam because proton therapy needs more beam flux to make 2-Gy prescription dose. Therefore, the neutron production from the MLC, which is closed to the patient, is a very important parameter for patient safety. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Do technological advances in linear accelerators improve dosimetric outcomes in stereotaxy? A head-on comparison of seven linear accelerators using volumetric modulated arc therapy-based stereotactic planning.

PubMed

Sarkar, B; Pradhan, A; Munshi, A

2016-01-01

Linear accelerator (Linac) based stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) using volumetric modulated arc therapy (VMAT) has been used for treating small intracranial lesions. Recent development in the Linacs such as inbuilt micro multileaf collimator (MLC) and flattening filter free (FFF) beam are intended to provide a better dose conformity and faster delivery when using VMAT technique. This study was aimed to compare the dosimetric outcomes and monitor units (MUs) of the stereotactic treatment plans for different commercially available MLC models and beam profiles. Ten patients having 12 planning target volume (PTV)/gross target volume's (GTVs) who received the SRS/SRT treatment in our clinic using Axesse Linac (considered reference arm gold standard) were considered for this study. The test arms comprised of plans using Elekta Agility with FFF, Elekta Agility with the plane beam, Elekta APEX, Varian Millennium 120, Varian Millennium 120HD, and Elekta Synergy in Monaco treatment planning system. Planning constraints and calculation grid spacing were not altered in the test plans. To objectively evaluate the efficacy of MLC-beam model, the resultant dosimetric outcomes were subtracted from the reference arm parameters. V95%, V100%, V105%, D1%, maximum dose, and mean dose of PTV/GTV showed a maximum inter MLC - beam model variation of 1.5% and 2% for PTV and GTV, respectively. Average PTV conformity index and heterogeneity index shows a variation in the range 0.56-0.63 and 1.08-1.11, respectively. Mean dose difference (excluding Axesse) for all organs varied between 1.1 cGy and 74.8 cGy (mean dose = 6.1 cGy standard deviation [SD] = 26.9 cGy) and 1.7 cGy-194.5 cGy (mean dose 16.1 cGy SD = 57.2 cGy) for single and multiple fraction, respectively. The dosimetry of VMAT-based SRS/SRT treatment plan had minimal dependence on MLC and beam model variations. All tested MLC and beam model could fulfil the desired PTV coverage and organs at risk dose constraints. The only notable difference was the halving of the MU for FFF beam as compared to the plane beam. This has the potential to reduce the total patient on couch time by 15% (approximately 2 min).

Effect of MLC leaf width on treatment adaptation and accuracy for concurrent irradiation of prostate and pelvic lymph nodes

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

Shang Qingyang; Qi Peng; Ferjani, Samah

2013-06-15

Purpose: The aim of the study was to evaluate the impact of multileaf collimator (MLC) leaf width on treatment adaptation and delivery accuracy for concurrent treatment of the prostate and pelvic lymph nodes with intensity modulated radiation therapy (IMRT). Methods: Seventy-five kilovoltage cone beam CTs (KV-CBCT) from six patients were included for this retrospective study. For each patient, three different IMRT plans were created based on a planning CT using three different MLC leaf widths of 2.5, 5, and 10 mm, respectively. For each CBCT, the prostate displacement was determined by a dual image registration. Adaptive plans were created bymore » shifting selected MLC leaf pairs to compensate for daily prostate movements. To evaluate the impact of MLC leaf width on the adaptive plan for each daily CBCT, three MLC shifted plans were created using three different leaf widths of MLCs (a total of 225 adaptive treatment plans). Selective dosimetric endpoints for the tumor volumes and organs at risk (OARs) were evaluated for these adaptive plans. Using the planning CT from a selected patient, MLC shifted plans for three hypothetical longitudinal shifts of 2, 4, and 8 mm were delivered on the three linear accelerators to test the deliverability of the shifted plans and to compare the dose accuracy of the shifted plans with the original IMRT plans. Results: Adaptive plans from 2.5 and 5 mm MLCs had inadequate dose coverage to the prostate (D99 < 97%, or D{sub mean} < 99% of the planned dose) in 6%-8% of the fractions, while adaptive plans from 10 mm MLC led to inadequate dose coverage to the prostate in 25.3% of the fractions. The average V{sub 56Gy} of the prostate over the six patients was improved by 6.4% (1.6%-32.7%) and 5.8% (1.5%-35.7%) with adaptive plans from 2.5 and 5 mm MLCs, respectively, when compared with adaptive plans from 10 mm MLC. Pelvic lymph nodes were well covered for all MLC adaptive plans, as small differences were observed for D99, D{sub mean}, and V{sub 50.4Gy}. Similar OAR sparing could be achieved for the bladder and rectum with all three MLCs for treatment adaptation. The MLC shifted plans can be accurately delivered on all three linear accelerators with accuracy similar to their original IMRT plans, where gamma (3%/3 mm) passing rates were 99.6%, 93.0%, and 92.1% for 2.5, 5, and 10 mm MLCs, respectively. The percentages of pixels with dose differences between the measurement and calculation being less than 3% of the maximum dose were 85.9%, 82.5%, and 70.5% for the original IMRT plans from the three MLCs, respectively. Conclusions: Dosimetric advantages associated with smaller MLC leaves were observed in terms of the coverage to the prostate, when the treatment was adapted to account for daily prostate movement for concurrent irradiation of the prostate and pelvic lymph nodes. The benefit of switching the MLC from 10 to 5 mm was significant (p Much-Less-Than 0.01); however, switching the MLC from 5 to 2.5 mm would not gain significant (p= 0.15) improvement. IMRT plans with smaller MLC leaf widths achieved more accurate dose delivery.« less

Evaluation of MLC leaf transmission on IMRT treatment plan quality of patients with advanced lung cancer.

PubMed

Chen, Jiayun; Fu, Guishan; Li, Minghui; Song, Yixin; Dai, Jianrong; Miao, Junjie; Liu, Zhiqiang; Li, Yexiong

2017-12-14

The purpose of this paper was to evaluate the impact of leaf treatment of multileaf collimator (MLC) in plan quality of intensity-modulated radiotherapy (IMRT) of patients with advanced lung cancer. Five MLCs with different leaf transmissions (0.01%, 0.5%, 1.2%, 1.8%, and 3%) were configured for an accelerator in a treatment planning system. Correspondingly, 5 treatment plans with the same optimization setting were created and evaluated quantitatively for each patient (11 patients total) who was diagnosed with advanced lung cancer. All of the 5 plans for each patient met the dose requirement for the planning treatment volumes (PTVs) and had similar target dose homogeneity and conformity. On average, the doses to selected organs were as follows: (1) V 5 , V 20 , and the mean dose of total lung; (2) the maximum and mean dose to spinal cord planning organ-at-risk volume (PRV); and (3) V 30 and V 40 of heart, decreased slightly when MLC transmission was decreased, but with no statistical differences. There is a clear grouping of plans having total quality score (S D ) value, which is used to evaluate plan quality: (1) more than 1 (patient nos. 1 to 3, 5, and 8), and more than 2.5 (patient no. 6); (2) less than 1 (patient nos. 7 and 10); (3) around 1 (patient nos. 4, 9, and 11). As MLC transmission increased, overall S D values increased as well and plan dose requirement was harder to meet. The clinical requirements were violated increasingly as MLC transmission became large. Total S D with and without normal tissue (NT) showed similar results, with no statistically significant differences. Therefore, decrease of MLC transmission did have minimum impact on plan, and it improved target coverage and reduced normal tissue radiation slightly, with no statistical significance. Plan quality could not be significantly improved by MLC transmission reduction. However, lower MLC transmission may have advantages on lung sparing to low- and intermediate-dose exposure. Besides conventional fraction, hyperfraction, or stereotactic body radiotherapy (SBRT), the reduction on lung sparing is still essential because it is highly relevant to radiation pneumonitis (RP). It has potential to diminish incidence of RP and improve patient's quality of life after irradiation with lowered MLC transmission. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-E-T-268: Differences in Treatment Plan Quality and Delivery Between Two Commercial Treatment Planning Systems for Volumetric Arc-Based Radiation Therapy

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

Chen, S; Zhang, H; Zhang, B

2015-06-15

Purpose: To clinically evaluate the differences in volumetric modulated arc therapy (VMAT) treatment plan and delivery between two commercial treatment planning systems. Methods: Two commercial VMAT treatment planning systems with different VMAT optimization algorithms and delivery approaches were evaluated. This study included 16 clinical VMAT plans performed with the first system: 2 spine, 4 head and neck (HN), 2 brain, 4 pancreas, and 4 pelvis plans. These 16 plans were then re-optimized with the same number of arcs using the second treatment planning system. Planning goals were invariant between the two systems. Gantry speed, dose rate modulation, MLC modulation, planmore » quality, number of monitor units (MUs), VMAT quality assurance (QA) results, and treatment delivery time were compared between the 2 systems. VMAT QA results were performed using Mapcheck2 and analyzed with gamma analysis (3mm/3% and 2mm/2%). Results: Similar plan quality was achieved with each VMAT optimization algorithm, and the difference in delivery time was minimal. Algorithm 1 achieved planning goals by highly modulating the MLC (total distance traveled by leaves (TL) = 193 cm average over control points per plan), while maintaining a relatively constant dose rate (dose-rate change <100 MU/min). Algorithm 2 involved less MLC modulation (TL = 143 cm per plan), but greater dose-rate modulation (range = 0-600 MU/min). The average number of MUs was 20% less for algorithm 2 (ratio of MUs for algorithms 2 and 1 ranged from 0.5-1). VMAT QA results were similar for all disease sites except HN plans. For HN plans, the average gamma passing rates were 88.5% (2mm/2%) and 96.9% (3mm/3%) for algorithm 1 and 97.9% (2mm/2%) and 99.6% (3mm/3%) for algorithm 2. Conclusion: Both VMAT optimization algorithms achieved comparable plan quality; however, fewer MUs were needed and QA results were more robust for Algorithm 2, which more highly modulated dose rate.« less

Monte Carlo modeling and simulations of the High Definition (HD120) micro MLC and validation against measurements for a 6 MV beam

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

Borges, C.; Zarza-Moreno, M.; Heath, E.

2012-01-15

Purpose: The most recent Varian micro multileaf collimator (MLC), the High Definition (HD120) MLC, was modeled using the BEAMNRC Monte Carlo code. This model was incorporated into a Varian medical linear accelerator, for a 6 MV beam, in static and dynamic mode. The model was validated by comparing simulated profiles with measurements. Methods: The Varian Trilogy (2300C/D) accelerator model was accurately implemented using the state-of-the-art Monte Carlo simulation program BEAMNRC and validated against off-axis and depth dose profiles measured using ionization chambers, by adjusting the energy and the full width at half maximum (FWHM) of the initial electron beam. Themore » HD120 MLC was modeled by developing a new BEAMNRC component module (CM), designated HDMLC, adapting the available DYNVMLC CM and incorporating the specific characteristics of this new micro MLC. The leaf dimensions were provided by the manufacturer. The geometry was visualized by tracing particles through the CM and recording their position when a leaf boundary is crossed. The leaf material density and abutting air gap between leaves were adjusted in order to obtain a good agreement between the simulated leakage profiles and EBT2 film measurements performed in a solid water phantom. To validate the HDMLC implementation, additional MLC static patterns were also simulated and compared to additional measurements. Furthermore, the ability to simulate dynamic MLC fields was implemented in the HDMLC CM. The simulation results of these fields were compared with EBT2 film measurements performed in a solid water phantom. Results: Overall, the discrepancies, with and without MLC, between the opened field simulations and the measurements using ionization chambers in a water phantom, for the off-axis profiles are below 2% and in depth-dose profiles are below 2% after the maximum dose depth and below 4% in the build-up region. On the conditions of these simulations, this tungsten-based MLC has a density of 18.7 g cm{sup -3} and an overall leakage of about 1.1 {+-} 0.03%. The discrepancies between the film measured and simulated closed and blocked fields are below 2% and 8%, respectively. Other measurements were performed for alternated leaf patterns and the agreement is satisfactory (to within 4%). The dynamic mode for this MLC was implemented and the discrepancies between film measurements and simulations are within 4%. Conclusions: The Varian Trilogy (2300 C/D) linear accelerator including the HD120 MLC was successfully modeled and simulated using the Monte Carlo BEAMNRC code by developing an independent CM, the HDMLC CM, either in static and dynamic modes.« less

Improvement of multi-level resistive switching characteristics in solution-processed AlO x -based non-volatile resistive memory using microwave irradiation

NASA Astrophysics Data System (ADS)

Kim, Seung-Tae; Cho, Won-Ju

2018-01-01

We fabricated a resistive random access memory (ReRAM) device on a Ti/AlO x /Pt structure with solution-processed AlO x switching layer using microwave irradiation (MWI), and demonstrated multi-level cell (MLC) operation. To investigate the effect of MWI power on the MLC characteristics, post-deposition annealing was performed at 600-3000 W after AlO x switching layer deposition, and the MLC operation was compared with as-deposited (as-dep) and conventional thermally annealing (CTA) treated devices. All solution-processed AlO x -based ReRAM devices exhibited bipolar resistive switching (BRS) behavior. We found that these devices have four-resistance states (2 bits) of MLC operation according to the modulation of the high-resistance state (HRSs) through reset voltage control. Particularly, compared to the as-dep and CTA ReRAM devices, the MWI-treated ReRAM devices showed a significant increase in the memory window and stable endurance for multi-level operation. Moreover, as the MWI power increased, excellent MLC characteristics were exhibited because the resistance ratio between each resistance state was increased. In addition, it exhibited reliable retention characteristics without deterioration at 25 °C and 85 °C for 10 000 s. Finally, the relationship between the chemical characteristics of the solution-processed AlO x switching layer and BRS-based multi-level operation according to the annealing method and MWI power was investigated using x-ray photoelectron spectroscopy.

New method for estimation of fluence complexity in IMRT fields and correlation with gamma analysis

NASA Astrophysics Data System (ADS)

Hanušová, T.; Vondráček, V.; Badraoui-Čuprová, K.; Horáková, I.; Koniarová, I.

2015-01-01

A new method for estimation of fluence complexity in Intensity Modulated Radiation Therapy (IMRT) fields is proposed. Unlike other previously published works, it is based on portal images calculated by the Portal Dose Calculation algorithm in Eclipse (version 8.6, Varian Medical Systems) in the plane of the EPID aS500 detector (Varian Medical Systems). Fluence complexity is given by the number and the amplitudes of dose gradients in these matrices. Our method is validated using a set of clinical plans where fluence has been smoothed manually so that each plan has a different level of complexity. Fluence complexity calculated with our tool is in accordance with the different levels of smoothing as well as results of gamma analysis, when calculated and measured dose matrices are compared. Thus, it is possible to estimate plan complexity before carrying out the measurement. If appropriate thresholds are determined which would distinguish between acceptably and overly modulated plans, this might save time in the re-planning and re-measuring process.

Rounded leaf end modeling in Pinnacle VMAT treatment planning for fixed jaw linacs

PubMed Central

Yang, Fei; Cao, Ning; Meyer, Juergen

2016-01-01

During volume‐modulated arc therapies (VMAT), dosimetric errors are introduced by multiple open dynamic leaf gaps that are present in fixed diaphragm linear accelerators. The purpose of this work was to develop a methodology for adjusting the rounded leaf end modeling parameters to improve out‐of‐field dose agreement in SmartArc VMAT treatment plans delivered by fixed jaw linacs where leaf gap dose is not negligible. Leaf gap doses were measured for an Elekta beam modulator linac with 0.4 cm micro‐multileaf collimators (MLC) using an A16 micro‐ionization chamber, a MatriXX ion chamber detector array, and Kodak EDR2 film dosimetry in a solid water phantom. The MLC offset and rounded end tip radius were adjusted in the Pinnacle treatment planning system (TPS) to iteratively arrive at the optimal configuration for 6 MV and 10 MV photon energies. Improvements in gamma index with a 3%/3 mm acceptance criteria and an inclusion threshold of 5% of maximum dose were measured, analyzed, and validated using an ArcCHECK diode detector array for field sizes ranging from 1.6 to 14 cm square field arcs and Task Group (TG) 119 VMAT test cases. The best results were achieved for a rounded leaf tip radius of 13 cm with a 0.1 cm MLC offset. With the optimized MLC model, measured gamma indices ranged between 99.9% and 91.7% for square field arcs with sizes between 3.6 cm and 1.6 cm, with a maximum improvement of 42.7% for the 1.6 cm square field size. Gamma indices improved up to 2.8% in TG‐119 VMAT treatment plans. Imaging and Radiation Oncology Core (IROC) credentialing of a VMAT plan with the head and neck phantom passed with a gamma index of 100%. Fine‐tune adjustments to MLC rounded leaf ends may improve patient‐specific QA pass rates and provide more accurate predictions of dose deposition to avoidance structures. PACS number(s): 87.55.D‐, 87.55.kd, 87.55.kh PMID:27929490

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

Ureba, A.; Salguero, F. J.; Barbeiro, A. R.

Purpose: The authors present a hybrid direct multileaf collimator (MLC) aperture optimization model exclusively based on sequencing of patient imaging data to be implemented on a Monte Carlo treatment planning system (MC-TPS) to allow the explicit radiation transport simulation of advanced radiotherapy treatments with optimal results in efficient times for clinical practice. Methods: The planning system (called CARMEN) is a full MC-TPS, controlled through aMATLAB interface, which is based on the sequencing of a novel map, called “biophysical” map, which is generated from enhanced image data of patients to achieve a set of segments actually deliverable. In order to reducemore » the required computation time, the conventional fluence map has been replaced by the biophysical map which is sequenced to provide direct apertures that will later be weighted by means of an optimization algorithm based on linear programming. A ray-casting algorithm throughout the patient CT assembles information about the found structures, the mass thickness crossed, as well as PET values. Data are recorded to generate a biophysical map for each gantry angle. These maps are the input files for a home-made sequencer developed to take into account the interactions of photons and electrons with the MLC. For each linac (Axesse of Elekta and Primus of Siemens) and energy beam studied (6, 9, 12, 15 MeV and 6 MV), phase space files were simulated with the EGSnrc/BEAMnrc code. The dose calculation in patient was carried out with the BEAMDOSE code. This code is a modified version of EGSnrc/DOSXYZnrc able to calculate the beamlet dose in order to combine them with different weights during the optimization process. Results: Three complex radiotherapy treatments were selected to check the reliability of CARMEN in situations where the MC calculation can offer an added value: A head-and-neck case (Case I) with three targets delineated on PET/CT images and a demanding dose-escalation; a partial breast irradiation case (Case II) solved with photon and electron modulated beams (IMRT + MERT); and a prostatic bed case (Case III) with a pronounced concave-shaped PTV by using volumetric modulated arc therapy. In the three cases, the required target prescription doses and constraints on organs at risk were fulfilled in a short enough time to allow routine clinical implementation. The quality assurance protocol followed to check CARMEN system showed a high agreement with the experimental measurements. Conclusions: A Monte Carlo treatment planning model exclusively based on maps performed from patient imaging data has been presented. The sequencing of these maps allows obtaining deliverable apertures which are weighted for modulation under a linear programming formulation. The model is able to solve complex radiotherapy treatments with high accuracy in an efficient computation time.« less

MCTP system model based on linear programming optimization of apertures obtained from sequencing patient image data maps.

PubMed

Ureba, A; Salguero, F J; Barbeiro, A R; Jimenez-Ortega, E; Baeza, J A; Miras, H; Linares, R; Perucha, M; Leal, A

2014-08-01

The authors present a hybrid direct multileaf collimator (MLC) aperture optimization model exclusively based on sequencing of patient imaging data to be implemented on a Monte Carlo treatment planning system (MC-TPS) to allow the explicit radiation transport simulation of advanced radiotherapy treatments with optimal results in efficient times for clinical practice. The planning system (called CARMEN) is a full MC-TPS, controlled through aMATLAB interface, which is based on the sequencing of a novel map, called "biophysical" map, which is generated from enhanced image data of patients to achieve a set of segments actually deliverable. In order to reduce the required computation time, the conventional fluence map has been replaced by the biophysical map which is sequenced to provide direct apertures that will later be weighted by means of an optimization algorithm based on linear programming. A ray-casting algorithm throughout the patient CT assembles information about the found structures, the mass thickness crossed, as well as PET values. Data are recorded to generate a biophysical map for each gantry angle. These maps are the input files for a home-made sequencer developed to take into account the interactions of photons and electrons with the MLC. For each linac (Axesse of Elekta and Primus of Siemens) and energy beam studied (6, 9, 12, 15 MeV and 6 MV), phase space files were simulated with the EGSnrc/BEAMnrc code. The dose calculation in patient was carried out with the BEAMDOSE code. This code is a modified version of EGSnrc/DOSXYZnrc able to calculate the beamlet dose in order to combine them with different weights during the optimization process. Three complex radiotherapy treatments were selected to check the reliability of CARMEN in situations where the MC calculation can offer an added value: A head-and-neck case (Case I) with three targets delineated on PET/CT images and a demanding dose-escalation; a partial breast irradiation case (Case II) solved with photon and electron modulated beams (IMRT + MERT); and a prostatic bed case (Case III) with a pronounced concave-shaped PTV by using volumetric modulated arc therapy. In the three cases, the required target prescription doses and constraints on organs at risk were fulfilled in a short enough time to allow routine clinical implementation. The quality assurance protocol followed to check CARMEN system showed a high agreement with the experimental measurements. A Monte Carlo treatment planning model exclusively based on maps performed from patient imaging data has been presented. The sequencing of these maps allows obtaining deliverable apertures which are weighted for modulation under a linear programming formulation. The model is able to solve complex radiotherapy treatments with high accuracy in an efficient computation time.

Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments.

PubMed

Tyler, Madelaine K

2016-01-08

This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5-30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ± 2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ± 15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ± 3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI.

Monte Carlo evaluation of RapidArc™ oropharynx treatment planning strategies for sparing of midline structures

NASA Astrophysics Data System (ADS)

Bush, K.; Zavgorodni, S.; Gagne, I.; Townson, R.; Ansbacher, W.; Beckham, W.

2010-08-01

The aim of the study was to perform the Monte Carlo (MC) evaluation of RapidArc™ (Varian Medical Systems, Palo Alto, CA) dose calculations for four oropharynx midline sparing planning strategies. Six patients with squamous cell cancer of the oropharynx were each planned with four RapidArc head and neck treatment strategies consisting of single and double photon arcs. In each case, RTOG0522 protocol objectives were used during planning optimization. Dose calculations performed with the analytical anisotropic algorithm (AAA) are compared against BEAMnrc/DOSXYZnrc dose calculations for the 24-plan dataset. Mean dose and dose-to-98%-of-structure-volume (D98%) were used as metrics in the evaluation of dose to planning target volumes (PTVs). Mean dose and dose-to-2%-of-structure-volume (D2%) were used to evaluate dose differences within organs at risk (OAR). Differences in the conformity index (CI) and the homogeneity index (HI) as well as 3D dose distributions were also observed. AAA calculated PTV mean dose, D98%, and HIs showed very good agreement with MC dose calculations within the 0.8% MC (statistical) calculation uncertainty. Regional node volume (PTV-80%) mean dose and D98% were found to be overestimated (1.3%, σ = 0.8% and 2.3%, σ = 0.8%, respectively) by the AAA with respect to MC calculations. Mean dose and D2% to OAR were also observed to be consistently overestimated by the AAA. Increasing dose calculation differences were found in planning strategies exhibiting a higher overall fluence modulation. From the plan dataset, the largest local dose differences were observed in heavily shielded regions and within the esophageal and sinus cavities. AAA dose calculations as implemented in RapidArc™ demonstrate excellent agreement with MC calculations in unshielded regions containing moderate inhomogeneities. Acceptable agreement is achieved in regions of increased MLC shielding. Differences in dose are attributed to inaccuracies in the AAA-modulated fluence modeling, modeling of material inhomogeneities and dose deposition within low-density materials. The use of MC dose calculations leads to the same general conclusion as using AAA that a two arc delivery with limited collimator opening can provide the greatest amount of midline sparing compared to the other techniques investigated.

TU-AB-BRC-04: Commissioning of a New MLC Model for the GEPTS Monte Carlo System: A Model Based On the Leaf and Interleaf Effective Density

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

Chibani, O; Tahanout, F; Ma, C

2016-06-15

Purpose: To commission a new MLC model for the GEPTS Monte Carlo system. The model is based on the concept of leaves and interleaves effective densities Methods: GEPTS is a Monte Carlo system to be used for external beam planning verification. GEPTS incorporates detailed photon and electron transport algorithms (Med.Phys. 29, 2002, 835). A new GEPTS model for the Varian Millennium MLC is presented. The model accounts for: 1) thick (1 cm) and thin (0.5 cm) leaves, 2) tongue-and-groove design, 3) High-Transmission (HT) and Low-Transmission (LT) interleaves, and 4) rounded leaf end. Leaf (and interleaf) height is set equal tomore » 6 cm. Instead of modeling air gaps, screw holes, and complex leaf heads, “effective densities” are assigned to: 1) thin leaves, 2) thick leaves, 3) HT-, and 4) LT-interleaves. Results: The new MLC model is used to calculate dose profiles for Closed-MLC and Tongue-and-Groove fields at 5 cm depth for 6, 10 and 15 MV Varian beams. Calculations are compared with 1) Pin-point ionization chamber transmission ratios and 2) EBT3 Radiochromic films. Pinpoint readings were acquired beneath thick and thin leaves, and HT and LT interleaves. The best fit of measured dose profiles was obtained for the following parameters: Thick-leaf density = 16.1 g/cc, Thin-leaf density = 17.2 g/cc; HT Interleaf density = 12.4 g/cc, LT Interleaf density = 14.3 g/cc; Interleaf thickness = 1.1 mm. Attached figures show comparison of calculated and measured transmission ratios for the 3 energies. Note this is the only study where transmission profiles are compared with measurements for 3 different energies. Conclusion: The new MLC model reproduces transmission measurements within 0.1%. The next step is to implement the MLC model for real plans and quantify the improvement in dose calculation accuracy gained using this model for IMRT plans with high modulation factors.« less

Intensity- and energy-modulated electron radiotherapy by means of an xMLC for head and neck shallow tumors

NASA Astrophysics Data System (ADS)

Salguero, Francisco Javier; Arráns, Rafael; Atriana Palma, Bianey; Leal, Antonio

2010-03-01

The purpose of this paper is to assess the feasibility of delivering intensity- and energy-modulated electron radiation treatment (MERT) by a photon multileaf collimator (xMLC) and to evaluate the improvements obtained in shallow head and neck (HN) tumors. Four HN patient cases covering different clinical situations were planned by MERT, which used an in-house treatment planning system that utilized Monte Carlo dose calculation. The cases included one oronasal, two parotid and one middle ear tumors. The resulting dose-volume histograms were compared with those obtained from conventional photon and electron treatment techniques in our clinic, which included IMRT, electron beam and mixed beams, most of them using fixed-thickness bolus. Experimental verification was performed with plane-parallel ionization chambers for absolute dose verification, and a PTW ionization chamber array and radiochromic film for relative dosimetry. A MC-based treatment planning system for target with compromised volumes in depth and laterally has been validated. A quality assurance protocol for individual MERT plans was launched. Relative MC dose distributions showed a high agreement with film measurements and absolute ion chamber dose measurements performed at a reference point agreed with MC calculations within 2% in all cases. Clinically acceptable PTV coverage and organ-at-risk sparing were achieved by using the proposed MERT approach. MERT treatment plans, based on delivery of intensity-modulated electron beam using the xMLC, for superficial head and neck tumors, demonstrated comparable or improved PTV dose homogeneity with significantly lower dose to normal tissues. The clinical implementation of this technique will be able to offer a viable alternative for the treatment of shallow head and neck tumors.

Automatic online adaptive radiation therapy techniques for targets with significant shape change: a feasibility study.

PubMed

Court, Laurence E; Tishler, Roy B; Petit, Joshua; Cormack, Robert; Chin, Lee

2006-05-21

This work looks at the feasibility of an online adaptive radiation therapy concept that would detect the daily position and shape of the patient, and would then correct the daily treatment to account for any changes compared with planning position. In particular, it looks at the possibility of developing algorithms to correct for large complicated shape change. For co-planar beams, the dose in an axial plane is approximately associated with the positions of a single multi-leaf collimator (MLC) pair. We start with a primary plan, and automatically generate several secondary plans with gantry angles offset by regular increments. MLC sequences for each plan are calculated keeping monitor units (MUs) and number of segments constant for a given beam (fluences are different). Bulk registration (3D) of planning and daily CT images gives global shifts. Slice-by-slice (2D) registration gives local shifts and rotations about the longitudinal axis for each axial slice. The daily MLC sequence is then created for each axial slice/MLC leaf pair combination, by taking the MLC positions from the pre-calculated plan with the nearest rotation, and shifting using a beam's-eye-view calculation to account for local linear shifts. A planning study was carried out using two head and neck region MR images of a healthy volunteer which were contoured to simulate a base-of-tongue treatment: one with the head straight (used to simulate the planning image) and the other with the head tilted to the left (the daily image). Head and neck treatment was chosen to evaluate this technique because of its challenging nature, with varying internal and external contours, and multiple degrees of freedom. Shape change was significant: on a slice-by-slice basis, local rotations in the daily image varied from 2 to 31 degrees, and local shifts ranged from -0.2 to 0.5 cm and -0.4 to 0.0 cm in right-left and posterior-anterior directions, respectively. The adapted treatment gave reasonable target coverage (100%, 90% and 80% of the base-of-tongue, left nodes and right nodes, respectively, receiving the daily prescription dose), and kept the daily cord dose below the limit used in the original plan (65%, equivalent to 46 Gy over 35 fractions). Most of the loss of coverage was due to one shoulder being raised more superior relative to the other shoulder compared with the plan. This type of skew-like motion is not accounted for by the proposed ART technique. In conclusion, this technique has potential to correct for fairly extreme daily changes in patient setup, but some control of the daily position would still be necessary. Importantly, it was possible to combine treatments from different plans (MLC sequences) to correct for position and shape change.

SU-E-T-179: Clinical Impact of IMRT Failure Modes at Or Near TG-142 Tolerance Criteria Levels

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

Faught, J Tonigan; Balter, P; Johnson, J

2015-06-15

Purpose: Quantitatively assess the clinical impact of 11 critical IMRT dose delivery failure modes. Methods: Eleven step-and-shoot IMRT failure modes (FMs) were introduced into twelve Pinnacle v9.8 treatment plans. One standard and one highly modulated plan on the IROC IMRT phantom and ten previous H&N patient treatment plans were used. FMs included physics components covered by basic QA near tolerance criteria levels (TG-142) such as beam energy, MLC positioning, and MLC modeling. Resultant DVHs were compared to those of failure-free plans and the severity of plan degradation was assessed considering PTV coverage and OAR and normal tissue tolerances and usedmore » for FMEA severity scoring. Six of these FMs were physically simulated and phantom irradiations performed. TLD and radiochromic film results are used for comparison to treatment planning studies. Results: Based on treatment planning studies, the largest clinical impact from the phantom cases was induced by 2 mm systematic MLC shift in one bank with the combination of a D95% target under dose near 16% and OAR overdose near 8%. Cord overdoses of 5%–11% occurred with gantry angle, collimator angle, couch angle, MLC leaf end modeling, and MLC transmission and leakage modeling FMs. PTV coverage and/or OAR sparing was compromised in all FMs introduced in phantom plans with the exception of CT number to electron density tables, MU linearity, and MLC tongue-and-groove modeling. Physical measurements did not entirely agree with treatment planning results. For example, symmetry errors resulted in the largest physically measured discrepancies of up to 3% in the PTVs while a maximum of 0.5% deviation was seen in the treatment planning studies. Patient treatment plan study results are under analysis. Conclusion: Even in the simplistic anatomy of the IROC phantom, some basic physics FMs, just outside of TG-142 tolerance criteria, appear to have the potential for large clinical implications.« less

The effect of MLC speed and acceleration on the plan delivery accuracy of VMAT

PubMed Central

Park, J M; Wu, H-G; Kim, J H; Carlson, J N K

2015-01-01

Objective: To determine a new metric utilizing multileaf collimator (MLC) speeds and accelerations to predict plan delivery accuracy of volumetric modulated arc therapy (VMAT). Methods: To verify VMAT delivery accuracy, gamma evaluations, analysis of mechanical parameter difference between plans and log files, and analysis of changes in dose–volumetric parameters between plans and plans reconstructed with log files were performed with 40 VMAT plans. The average proportion of leaf speeds ranging from l to h cm s−1 (Sl–h and l–h = 0–0.4, 0.4–0.8, 0.8–1.2, 1.2–1.6 and 1.6–2.0), mean and standard deviation of MLC speeds were calculated for each VMAT plan. The same was carried out for accelerations in centimetre per second squared (Al–h and l–h = 0–4, 4–8, 8–12, 12–16 and 16–20). The correlations of those indicators to plan delivery accuracy were analysed with Spearman's correlation coefficient (rs). Results: The S1.2–1.6 and mean acceleration of MLCs showed generally higher correlations to plan delivery accuracy than did others. The highest rs values were observed between S1.2–1.6 and global 1%/2 mm (rs = −0.698 with p < 0.001) as well as mean acceleration and global 1%/2 mm (rs = −0.650 with p < 0.001). As the proportion of MLC speeds and accelerations >0.4 and 4 cm s−2 increased, the plan delivery accuracy of VMAT decreased. Conclusion: The variations in MLC speeds and accelerations showed considerable correlations to VMAT delivery accuracy. Advances in knowledge: As the MLC speeds and accelerations increased, VMAT delivery accuracy reduced. PMID:25734490

A novel method for routine quality assurance of volumetric-modulated arc therapy.

PubMed

Wang, Qingxin; Dai, Jianrong; Zhang, Ke

2013-10-01

Volumetric-modulated arc therapy (VMAT) is delivered through synchronized variation of gantry angle, dose rate, and multileaf collimator (MLC) leaf positions. The delivery dynamic nature challenges the parameter setting accuracy of linac control system. The purpose of this study was to develop a novel method for routine quality assurance (QA) of VMAT linacs. ArcCheck is a detector array with diodes distributing in spiral pattern on cylindrical surface. Utilizing its features, a QA plan was designed to strictly test all varying parameters during VMAT delivery on an Elekta Synergy linac. In this plan, there are 24 control points. The gantry rotates clockwise from 181° to 179°. The dose rate, gantry speed, and MLC positions cover their ranges commonly used in clinic. The two borders of MLC-shaped field seat over two columns of diodes of ArcCheck when the gantry rotates to the angle specified by each control point. The ratio of dose rate between each of these diodes and the diode closest to the field center is a certain value and sensitive to the MLC positioning error of the leaf crossing the diode. Consequently, the positioning error can be determined by the ratio with the help of a relationship curve. The time when the gantry reaches the angle specified by each control point can be acquired from the virtual inclinometer that is a feature of ArcCheck. The gantry speed between two consecutive control points is then calculated. The aforementioned dose rate is calculated from an acm file that is generated during ArcCheck measurements. This file stores the data measured by each detector in 50 ms updates with each update in a separate row. A computer program was written in MATLAB language to process the data. The program output included MLC positioning errors and the dose rate at each control point as well as the gantry speed between control points. To evaluate this method, this plan was delivered for four consecutive weeks. The actual dose rate and gantry speed were compared with the QA plan specified. Additionally, leaf positioning errors were intentionally introduced to investigate the sensitivity of this method. The relationship curves were established for detecting MLC positioning errors during VMAT delivery. For four consecutive weeks measured, 98.4%, 94.9%, 89.2%, and 91.0% of the leaf positioning errors were within ± 0.5 mm, respectively. For the intentionally introduced leaf positioning systematic errors of -0.5 and +1 mm, the detected leaf positioning errors of 20 Y1 leaf were -0.48 ± 0.14 and 1.02 ± 0.26 mm, respectively. The actual gantry speed and dose rate closely followed the values specified in the VMAT QA plan. This method can assess the accuracy of MLC positions and the dose rate at each control point as well as the gantry speed between control points at the same time. It is efficient and suitable for routine quality assurance of VMAT.

Fluence-field modulated x-ray CT using multiple aperture devices

NASA Astrophysics Data System (ADS)

Stayman, J. Webster; Mathews, Aswin; Zbijewski, Wojciech; Gang, Grace; Siewerdsen, Jeffrey; Kawamoto, Satomi; Blevis, Ira; Levinson, Reuven

2016-03-01

We introduce a novel strategy for fluence field modulation (FFM) in x-ray CT using multiple aperture devices (MADs). MAD filters permit FFM by blocking or transmitting the x-ray beam on a fine (0.1-1 mm) scale. The filters have a number of potential advantages over other beam modulation strategies including the potential for a highly compact design, modest actuation speed and acceleration requirements, and spectrally neutral filtration due to their essentially binary action. In this work, we present the underlying MAD filtration concept including a design process to achieve a specific class of FFM patterns. A set of MAD filters is fabricated using a tungsten laser sintering process and integrated into an x-ray CT test bench. A characterization of the MAD filters is conducted and compared to traditional attenuating bowtie filters and the ability to flatten the fluence profile for a 32 cm acrylic phantom is demonstrated. MAD-filtered tomographic data was acquired on the CT test bench and reconstructed without artifacts associated with the MAD filter. These initial studies suggest that MAD-based FFM is appropriate for integration in clinical CT system to create patient-specific fluence field profile and reduce radiation exposures.

Optimizing fiducial visibility on periodically acquired megavoltage and kilovoltage image pairs during prostate volumetric modulated arc therapy

PubMed Central

Zhang, Pengpeng; Happersett, Laura; Ravindranath, Bosky; Zelefsky, Michael; Mageras, Gig; Hunt, Margie

2016-01-01

Purpose: Robust detection of implanted fiducials is essential for monitoring intrafractional motion during hypofractionated treatment. The authors developed a plan optimization strategy to ensure clear visibility of implanted fiducials and facilitate 3D localization during volumetric modulated arc therapy (VMAT). Methods: Periodic kilovoltage (kV) images were acquired at 20° gantry intervals and paired with simultaneously acquired 4.4° short arc megavoltage digital tomosynthesis (MV-DTS) to localize three fiducials during VMAT delivery for hypofractionated prostate cancer treatment. Beginning with the original optimized plan, control point segments where fiducials were consistently blocked by multileaf collimator (MLC) within each 4.4° MV-DTS interval were first identified. For each segment, MLC apertures were edited to expose the fiducial that led to the least increase in the cost function. Subsequently, MLC apertures of all control points not involved with fiducial visualization were reoptimized to compensate for plan quality losses and match the original dose–volume histogram. MV dose for each MV-DTS was also kept above 0.4 MU to ensure acceptable image quality. Different imaging (gantry) intervals and visibility margins around fiducials were also evaluated. Results: Fiducials were consistently blocked by the MLC for, on average, 36% of the imaging control points for five hypofractionated prostate VMAT plans but properly exposed after reoptimization. Reoptimization resulted in negligible dosimetric differences compared with original plans and outperformed simple aperture editing: on average, PTV D98 recovered from 87% to 94% of prescription, and PTV dose homogeneity improved from 9% to 7%. Without violating plan objectives and compromising delivery efficiency, the highest imaging frequency and largest margin that can be achieved are a 10° gantry interval, and 15 mm, respectively. Conclusions: VMAT plans can be made to accommodate MV-kV imaging of fiducials. Fiducial visualization rate and workflow efficiency are significantly improved with an automatic modification and reoptimization approach. PMID:27147314

Poster - Thur Eve - 10: Long term stability of VMAT quality assurance parameters using an EPID.

PubMed

Pekar, J; Diamond, K R

2012-07-01

The rapidly growing use of volumetric modulated arc therapy (VMAT) treatments in radiation therapy calls for a quantitative, automated, and reliable quality assurance (QA) procedure that can be used routinely in the clinical setting. In this work, we present a series VMAT QA procedures used to assess dynamic multi-leaf collimator (MLC) positional accuracy, variable dose-rate accuracy, and MLC leaf speed accuracy. The QA procedures were performed using amorphous silicon electronic portal imaging devices (EPID) to determine the long term stability of the measured parameters on two Varian linear accelerators. The measurements were repeated weekly on both linear accelerators for a period of three months and the EPID images were analyzed using custom Matlab software. The results of the picket fence tests indicate that MLC leaf positions can be identified to within 0.11 mm and 0.15 mm for static gantry delivery and VMAT delivery respectively. In addition, the dose-rate, gantry speed and MLC leaf speed tests both show very good stability over the measurement period. The measurements thus far, suggest that a number of the dosimetry tests may be suitable for quarterly QA for Varian iX and Trilogy linacs. However, additional measurements are required to confirm the frequency with which each test is required for safe and reliable VMAT delivery at our centre. © 2012 American Association of Physicists in Medicine.

Dependence of cross-bridge kinetics on myosin light chain isoforms in rabbit and rat skeletal muscle fibres.

PubMed

Andruchov, Oleg; Andruchova, Olena; Wang, Yishu; Galler, Stefan

2006-02-15

Cross-bridge kinetics underlying stretch-induced force transients was studied in fibres with different myosin light chain (MLC) isoforms from skeletal muscles of rabbit and rat. The force transients were induced by stepwise stretches (< 0.3% of fibre length) applied on maximally Ca2+-activated skinned fibres. Fast fibre types IIB, IID (or IIX) and IIA and the slow fibre type I containing the myosin heavy chain isoforms MHC-IIb, MHC-IId (or MHC-IIx), MHC-IIa and MHC-I, respectively, were investigated. The MLC isoform content varied within fibre types. Fast fibre types contained the fast regulatory MLC isoform MLC2f and different proportions of the fast alkali MLC isoforms MLC1f and MLC3f. Type I fibres contained the slow regulatory MLC isoform MLC2s and the slow alkali MLC isoform MLC1s. Slow MLC isoforms were also present in several type IIA fibres. The kinetics of force transients differed by a factor of about 30 between fibre types (order from fastest to slowest kinetics: IIB > IID > IIA > I). The kinetics of the force transients was not dependent on the relative content of MLC1f and MLC3f. Type IIA fibres containing fast and slow MLC isoforms were about 1.2 times slower than type IIA fibres containing only fast MLC isoforms. We conclude that while the cross-bridge kinetics is mainly determined by the MHC isoforms present, it is affected by fast and slow MLC isoforms but not by the relative content of MLC1f and MLC3f. Thus, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the cross-bridge kinetics.

Validation of Dosimetric Leaf Gap (DLG) prior to its implementation in Treatment Planning System (TPS): TrueBeam™ millennium 120 leaf MLC.

PubMed

Shende, Ravindra; Patel, Ganesh

2017-01-01

Objective of present study is to determine optimum value of DLG and its validation prior to being incorporated in TPS for Varian TrueBeam™ millennium 120 leaves MLC. Partial transmission through the rounded leaf ends of the Multi Leaf Collimator (MLC) causes a conflict between the edges of the light field and radiation field. Parameter account for this partial transmission is called Dosimetric Leaf Gap (DLG). The complex high precession technique, such as Intensity Modulated Radiation Therapy (IMRT), entails the modeling of optimum value of DLG inside Eclipse Treatment Planning System (TPS) for precise dose calculation. Distinct synchronized uniformed extension of sweeping dynamic MLC leaf gap fields created by Varian MLC shaper software were use to determine DLG. DLG measurements performed with both 0.13 cc semi-flex ionization chamber and 2D-Array I-Matrix were used to validate the DLG; similarly, values of DLG from TPS were estimated from predicted dose. Similar mathematical approaches were employed to determine DLG from delivered and TPS predicted dose. DLG determined from delivered dose measured with both ionization chamber (DLG Ion ) and I-Matrix (DLG I-Matrix ) compared with DLG estimate from TPS predicted dose (DLG TPS ). Measurements were carried out for all available 6MV, 10MV, 15MV, 6MVFFF and 10MVFFF beam energies. Maximum and minimum DLG deviation between measured and TPS calculated DLG was found to be 0.2 mm and 0.1 mm, respectively. Both of the measured DLGs (DLG Ion and DLG I-Matrix ) were found to be in a very good agreement with estimated DLG from TPS (DLG TPS ). Proposed method proved to be helpful in verifying and validating the DLG value prior to its clinical implementation in TPS.

Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments

PubMed Central

2016-01-01

This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5–30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ±2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ±15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ±3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI. PACS numbers: 87.55.km, 87.56.Fc PMID:26894347

Megalencephalic leukoencephalopathy with subcortical cysts: Characterization of disease variants.

PubMed

Hamilton, Eline M C; Tekturk, Pinar; Cialdella, Fia; van Rappard, Diane F; Wolf, Nicole I; Yalcinkaya, Cengiz; Çetinçelik, Ümran; Rajaee, Ahmad; Kariminejad, Ariana; Paprocka, Justyna; Yapici, Zuhal; Bošnjak, Vlatka Mejaški; van der Knaap, Marjo S

2018-04-17

To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features. We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review. We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B. Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Synchronized moving aperture radiation therapy (SMART): superimposing tumor motion on IMRT MLC leaf sequences under realistic delivery conditions

NASA Astrophysics Data System (ADS)

Xu, Jun; Papanikolaou, Nikos; Shi, Chengyu; Jiang, Steve B.

2009-08-01

Synchronized moving aperture radiation therapy (SMART) has been proposed to account for tumor motions during radiotherapy in prior work. The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumor motion induced by respiration. In this paper, a two-dimensional (2D) superimposing leaf sequencing method is presented for SMART. A leaf sequence optimization strategy was generated to assure the SMART delivery under realistic delivery conditions. The study of delivery performance using the Varian LINAC and the Millennium DMLC showed that clinical factors such as collimator angle, dose rate, initial phase and machine tolerance affect the delivery accuracy and efficiency. An in-house leaf sequencing software was developed to implement the 2D superimposing leaf sequencing method and optimize the motion-corrected leaf sequence under realistic clinical conditions. The analysis of dynamic log (Dynalog) files showed that optimization of the leaf sequence for various clinical factors can avoid beam hold-offs which break the synchronization of SMART and fail the SMART dose delivery. Through comparison between the simulated delivered fluence map and the planed fluence map, it was shown that the motion-corrected leaf sequence can greatly reduce the dose error.

Synchronized moving aperture radiation therapy (SMART): superimposing tumor motion on IMRT MLC leaf sequences under realistic delivery conditions.

PubMed

Xu, Jun; Papanikolaou, Nikos; Shi, Chengyu; Jiang, Steve B

2009-08-21

Synchronized moving aperture radiation therapy (SMART) has been proposed to account for tumor motions during radiotherapy in prior work. The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumor motion induced by respiration. In this paper, a two-dimensional (2D) superimposing leaf sequencing method is presented for SMART. A leaf sequence optimization strategy was generated to assure the SMART delivery under realistic delivery conditions. The study of delivery performance using the Varian LINAC and the Millennium DMLC showed that clinical factors such as collimator angle, dose rate, initial phase and machine tolerance affect the delivery accuracy and efficiency. An in-house leaf sequencing software was developed to implement the 2D superimposing leaf sequencing method and optimize the motion-corrected leaf sequence under realistic clinical conditions. The analysis of dynamic log (Dynalog) files showed that optimization of the leaf sequence for various clinical factors can avoid beam hold-offs which break the synchronization of SMART and fail the SMART dose delivery. Through comparison between the simulated delivered fluence map and the planed fluence map, it was shown that the motion-corrected leaf sequence can greatly reduce the dose error.

Characterization of a commercial multileaf collimator used for intensity modulated radiation therapy.

PubMed

Low, D A; Sohn, J W; Klein, E E; Markman, J; Mutic, S; Dempsey, J F

2001-05-01

The characteristics of a commercial multileaf collimator (MLC) to deliver static and dynamic multileaf collimation (SMLC and DMLC, respectively) were investigated to determine their influence on intensity modulated radiation therapy (IMRT) treatment planning and quality assurance. The influence of MLC leaf positioning accuracy on sequentially abutted SMLC fields was measured by creating abutting fields with selected gaps and overlaps. These data were also used to measure static leaf positioning precision. The characteristics of high leaf-velocity DMLC delivery were measured with constant velocity leaf sequences starting with an open field and closing a single leaf bank. A range of 1-72 monitor units (MU) was used providing a range of leaf velocities. The field abutment measurements yielded dose errors (as a percentage of the open field max dose) of 16.7+/-0.7% mm(-1) and 12.8+/-0.7% mm(-1) for 6 MV and 18 MV photon beams, respectively. The MLC leaf positioning precision was 0.080+/-0.018 mm (single standard deviation) highlighting the excellent delivery hardware tolerances for the tested beam delivery geometry. The high leaf-velocity DMLC measurements showed delivery artifacts when the leaf sequence and selected monitor units caused the linear accelerator to move the leaves at their maximum velocity while modulating the accelerator dose rate to deliver the desired leaf and MU sequence (termed leaf-velocity limited delivery). According to the vendor, a unique feature to their linear accelerator and MLC is that the dose rate is reduced to provide the correct cm MU(-1) leaf velocity when the delivery is leaf-velocity limited. However, it was found that the system delivered roughly 1 MU per pulse when the delivery was leaf-velocity limited causing dose profiles to exhibit discrete steps rather than a smooth dose gradient. The root mean square difference between the steps and desired linear gradient was less than 3% when more than 4 MU were used. The average dose per MU was greater and less than desired for closing and opening leaf patterns, respectively, when the delivery was leaf-velocity limited. The results indicated that the dose delivery artifacts should be minor for most clinical cases, but limit the assumption of dose linearity when significantly reducing the delivered dose for dosimeter characterization studies or QA measurements.

SU-E-J-174: Adaptive PET-Based Dose Painting with Tomotherapy

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

Darwish, N; Mackie, T; Thomadsen, B

2014-06-01

Purpose: PET imaging can be converted into dose prescription directly. Due to the variability of the intensity of PET the image, PET prescription maybe superior over uniform dose prescription. Furthermore, unlike the case in image reconstruction of not knowing the image solution in advance, the prescribed dose is known from a PET image a priori. Therefore, optimum beam orientations are derivable. Methods: We can assume the PET image to be the prescribed dose and invert it to determine the energy fluence. The same method used to reconstruct tissue images from projections could be used to solve the inverse problem ofmore » determining beam orientations and modulation patterns from a dose prescription [10]. Unlike standard tomographic reconstruction of images from measured projection profiles, the inversion of the prescribed dose results in photon fluence which may be negative and therefore unphysical. Two-dimensional modulated beams can be modelled in terms of the attenuated or exponential radon transform of the prescribed dose function (assumed to be the PET image in this case), an application of a Ram-Lak filter, and inversion by backprojection. Unlike the case in PET processing, however, the filtered beam obtained from the inversion represents a physical photon fluence. Therefore, a positivity constraint for the fluence (setting negative fluence to zero) must be applied (Brahme et al 1982, Bortfeld et al 1990) Results: Truncating the negative profiles from the PET data results in an approximation of the derivable energy fluence. Backprojection of the deliverable fluence is an approximation of the dose delivered. The deliverable dose is comparable to the original PET image and is similar to the PET image. Conclusion: It is possible to use the PET data or image as a direct indicator of deliverable fluence for cylindrical radiotherapy systems such as TomoTherapy.« less

An experimental comparison of conventional two-bank and novel four-bank dynamic MLC tracking.

PubMed

Davies, G A; Clowes, P; McQuaid, D; Evans, P M; Webb, S; Poludniowski, G

2013-03-07

The AccuLeaf mMLC featuring four multileaf-collimator (MLC) banks has been used for the first time for an experimental comparison of conventional two-bank with novel four-bank dynamic MLC tracking of a two-dimensional sinusoidal respiratory motion. This comparison was performed for a square aperture, and for three conformal treatment apertures from clinical radiotherapy lung cancer patients. The system latency of this prototype tracking system was evaluated and found to be 1.0 s and the frequency at which MLC positions could be updated, 1 Hz, and therefore accurate MLC tracking of irregular patient motion would be difficult with the system in its current form. The MLC leaf velocity required for two-bank-MLC and four-bank-MLC tracking was evaluated for the apertures studied and a substantial decrease was found in the maximum MLC velocity required when four-banks were used for tracking rather than two. A dosimetric comparison of the two techniques was also performed and minimal difference was found between two-bank-MLC and four-bank-MLC tracking. The use of four MLC banks for dynamic MLC tracking is shown to be potentially advantageous for increasing the delivery efficiency compared with two-bank-MLC tracking where difficulties are encountered if large leaf shifts are required to track motion perpendicular to the direction of leaf travel.

Multileaf collimator performance monitoring and improvement using semiautomated quality control testing and statistical process control.

PubMed

Létourneau, Daniel; Wang, An; Amin, Md Nurul; Pearce, Jim; McNiven, Andrea; Keller, Harald; Norrlinger, Bernhard; Jaffray, David A

2014-12-01

High-quality radiation therapy using highly conformal dose distributions and image-guided techniques requires optimum machine delivery performance. In this work, a monitoring system for multileaf collimator (MLC) performance, integrating semiautomated MLC quality control (QC) tests and statistical process control tools, was developed. The MLC performance monitoring system was used for almost a year on two commercially available MLC models. Control charts were used to establish MLC performance and assess test frequency required to achieve a given level of performance. MLC-related interlocks and servicing events were recorded during the monitoring period and were investigated as indicators of MLC performance variations. The QC test developed as part of the MLC performance monitoring system uses 2D megavoltage images (acquired using an electronic portal imaging device) of 23 fields to determine the location of the leaves with respect to the radiation isocenter. The precision of the MLC performance monitoring QC test and the MLC itself was assessed by detecting the MLC leaf positions on 127 megavoltage images of a static field. After initial calibration, the MLC performance monitoring QC test was performed 3-4 times/week over a period of 10-11 months to monitor positional accuracy of individual leaves for two different MLC models. Analysis of test results was performed using individuals control charts per leaf with control limits computed based on the measurements as well as two sets of specifications of ± 0.5 and ± 1 mm. Out-of-specification and out-of-control leaves were automatically flagged by the monitoring system and reviewed monthly by physicists. MLC-related interlocks reported by the linear accelerator and servicing events were recorded to help identify potential causes of nonrandom MLC leaf positioning variations. The precision of the MLC performance monitoring QC test and the MLC itself was within ± 0.22 mm for most MLC leaves and the majority of the apparent leaf motion was attributed to beam spot displacements between irradiations. The MLC QC test was performed 193 and 162 times over the monitoring period for the studied units and recalibration had to be repeated up to three times on one of these units. For both units, rate of MLC interlocks was moderately associated with MLC servicing events. The strongest association with the MLC performance was observed between the MLC servicing events and the total number of out-of-control leaves. The average elapsed time for which the number of out-of-specification or out-of-control leaves was within a given performance threshold was computed and used to assess adequacy of MLC test frequency. A MLC performance monitoring system has been developed and implemented to acquire high-quality QC data at high frequency. This is enabled by the relatively short acquisition time for the images and automatic image analysis. The monitoring system was also used to record and track the rate of MLC-related interlocks and servicing events. MLC performances for two commercially available MLC models have been assessed and the results support monthly test frequency for widely accepted ± 1 mm specifications. Higher QC test frequency is however required to maintain tighter specification and in-control behavior.

A comprehensive formulation for volumetric modulated arc therapy planning

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

Nguyen, Dan; Lyu, Qihui; Ruan, Dan

2016-07-15

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

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

Chen, Q; Read, P

Purpose: Multiple error pathways can lead to delivery errors during the treatment course that cannot be caught with pre-treatment QA. While in vivo solutions are being developed for linacs, no such solution exists for tomotherapy. The purpose of this study is to develop a near real-time system for tomotherapy that can monitor the delivery and dose accumulation process during the treatment-delivery, which enable the user to assess the impact of delivery variations and/or errors and to interrupt the treatment if necessary. Methods: A program running on a tomotherapy planning station fetches the raw DAS data during treatment. Exit detector datamore » is extracted as well as output, gantry angle, and other machine parameters. For each sample, the MLC open-close state is determined. The delivered plan is compared with the original plan via a Monte Carlo dose engine which transports fluence deviations from a pre-treatment Monte Carlo run. A report containing the difference in fluence, dose and DVH statistics is created in html format. This process is repeated until the treatment is completed. Results: Since we only need to compute the dose for the difference in fluence for a few projections each time, dose with 2% statistical uncertainty can be computed in less than 1 second on a 4-core cpu. However, the current bottleneck in this near real-time system is the repeated fetching and processing the growing DAS data file throughout the delivery. The frame rate drops from 10Hz at the beginning of treatment to 5Hz after 3 minutes and to 2Hz after 10 minutes. Conclusion: A during-treatment delivery monitor system has been built to monitor tomotherapy treatments. The system improves patient safety by allowing operators to assess the delivery variations and errors during treatment delivery and adopt appropriate actions.« less

Commissioning and quality assurance for VMAT delivery systems: An efficient time-resolved system using real-time EPID imaging.

PubMed

Zwan, Benjamin J; Barnes, Michael P; Hindmarsh, Jonathan; Lim, Seng B; Lovelock, Dale M; Fuangrod, Todsaporn; O'Connor, Daryl J; Keall, Paul J; Greer, Peter B

2017-08-01

An ideal commissioning and quality assurance (QA) program for Volumetric Modulated Arc Therapy (VMAT) delivery systems should assess the performance of each individual dynamic component as a function of gantry angle. Procedures within such a program should also be time-efficient, independent of the delivery system and be sensitive to all types of errors. The purpose of this work is to develop a system for automated time-resolved commissioning and QA of VMAT control systems which meets these criteria. The procedures developed within this work rely solely on images obtained, using an electronic portal imaging device (EPID) without the presence of a phantom. During the delivery of specially designed VMAT test plans, EPID frames were acquired at 9.5 Hz, using a frame grabber. The set of test plans was developed to individually assess the performance of the dose delivery and multileaf collimator (MLC) control systems under varying levels of delivery complexities. An in-house software tool was developed to automatically extract features from the EPID images and evaluate the following characteristics as a function of gantry angle: dose delivery accuracy, dose rate constancy, beam profile constancy, gantry speed constancy, dynamic MLC positioning accuracy, MLC speed and acceleration constancy, and synchronization between gantry angle, MLC positioning and dose rate. Machine log files were also acquired during each delivery and subsequently compared to information extracted from EPID image frames. The largest difference between measured and planned dose at any gantry angle was 0.8% which correlated with rapid changes in dose rate and gantry speed. For all other test plans, the dose delivered was within 0.25% of the planned dose for all gantry angles. Profile constancy was not found to vary with gantry angle for tests where gantry speed and dose rate were constant, however, for tests with varying dose rate and gantry speed, segments with lower dose rate and higher gantry speed exhibited less profile stability. MLC positional accuracy was not observed to be dependent on the degree of interdigitation. MLC speed was measured for each individual leaf and slower leaf speeds were shown to be compensated for by lower dose rates. The test procedures were found to be sensitive to 1 mm systematic MLC errors, 1 mm random MLC errors, 0.4 mm MLC gap errors and synchronization errors between the MLC, dose rate and gantry angle controls systems of 1°. In general, parameters measured by both EPID and log files agreed with the plan, however, a greater average departure from the plan was evidenced by the EPID measurements. QA test plans and analysis methods have been developed to assess the performance of each dynamic component of VMAT deliveries individually and as a function of gantry angle. This methodology relies solely on time-resolved EPID imaging without the presence of a phantom and has been shown to be sensitive to a range of delivery errors. The procedures developed in this work are both comprehensive and time-efficient and can be used for streamlined commissioning and QA of VMAT delivery systems. © 2017 American Association of Physicists in Medicine.

Multileaf collimator performance monitoring and improvement using semiautomated quality control testing and statistical process control

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

Létourneau, Daniel, E-mail: daniel.letourneau@rmp.uh.on.ca; McNiven, Andrea; Keller, Harald

2014-12-15

Purpose: High-quality radiation therapy using highly conformal dose distributions and image-guided techniques requires optimum machine delivery performance. In this work, a monitoring system for multileaf collimator (MLC) performance, integrating semiautomated MLC quality control (QC) tests and statistical process control tools, was developed. The MLC performance monitoring system was used for almost a year on two commercially available MLC models. Control charts were used to establish MLC performance and assess test frequency required to achieve a given level of performance. MLC-related interlocks and servicing events were recorded during the monitoring period and were investigated as indicators of MLC performance variations. Methods:more » The QC test developed as part of the MLC performance monitoring system uses 2D megavoltage images (acquired using an electronic portal imaging device) of 23 fields to determine the location of the leaves with respect to the radiation isocenter. The precision of the MLC performance monitoring QC test and the MLC itself was assessed by detecting the MLC leaf positions on 127 megavoltage images of a static field. After initial calibration, the MLC performance monitoring QC test was performed 3–4 times/week over a period of 10–11 months to monitor positional accuracy of individual leaves for two different MLC models. Analysis of test results was performed using individuals control charts per leaf with control limits computed based on the measurements as well as two sets of specifications of ±0.5 and ±1 mm. Out-of-specification and out-of-control leaves were automatically flagged by the monitoring system and reviewed monthly by physicists. MLC-related interlocks reported by the linear accelerator and servicing events were recorded to help identify potential causes of nonrandom MLC leaf positioning variations. Results: The precision of the MLC performance monitoring QC test and the MLC itself was within ±0.22 mm for most MLC leaves and the majority of the apparent leaf motion was attributed to beam spot displacements between irradiations. The MLC QC test was performed 193 and 162 times over the monitoring period for the studied units and recalibration had to be repeated up to three times on one of these units. For both units, rate of MLC interlocks was moderately associated with MLC servicing events. The strongest association with the MLC performance was observed between the MLC servicing events and the total number of out-of-control leaves. The average elapsed time for which the number of out-of-specification or out-of-control leaves was within a given performance threshold was computed and used to assess adequacy of MLC test frequency. Conclusions: A MLC performance monitoring system has been developed and implemented to acquire high-quality QC data at high frequency. This is enabled by the relatively short acquisition time for the images and automatic image analysis. The monitoring system was also used to record and track the rate of MLC-related interlocks and servicing events. MLC performances for two commercially available MLC models have been assessed and the results support monthly test frequency for widely accepted ±1 mm specifications. Higher QC test frequency is however required to maintain tighter specification and in-control behavior.« less

TomoTherapy MLC verification using exit detector data

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

Chen Quan; Westerly, David; Fang Zhenyu

2012-01-15

Purpose: Treatment delivery verification (DV) is important in the field of intensity modulated radiation therapy (IMRT). While IMRT and image guided radiation therapy (IGRT), allow us to create more conformal plans and enables the use of tighter margins, an erroneously executed plan can have detrimental effects on the treatment outcome. The purpose of this study is to develop a DV technique to verify TomoTherapy's multileaf collimator (MLC) using the onboard mega-voltage CT detectors. Methods: The proposed DV method uses temporal changes in the MVCT detector signal to predict actual leaf open times delivered on the treatment machine. Penumbra and scatteredmore » radiation effects may produce confounding results when determining leaf open times from the raw detector data. To reduce the impact of the effects, an iterative, Richardson-Lucy (R-L) deconvolution algorithm is applied. Optical sensors installed on each MLC leaf are used to verify the accuracy of the DV technique. The robustness of the DV technique is examined by introducing different attenuation materials in the beam. Additionally, the DV technique has been used to investigate several clinical plans which failed to pass delivery quality assurance (DQA) and was successful in identifying MLC timing discrepancies as the root cause. Results: The leaf open time extracted from the exit detector showed good agreement with the optical sensors under a variety of conditions. Detector-measured leaf open times agreed with optical sensor data to within 0.2 ms, and 99% of the results agreed within 8.5 ms. These results changed little when attenuation was added in the beam. For the clinical plans failing DQA, the dose calculated from reconstructed leaf open times played an instrumental role in discovering the root-cause of the problem. Throughout the retrospective study, it is found that the reconstructed dose always agrees with measured doses to within 1%. Conclusions: The exit detectors in the TomoTherapy treatment systems can provide valuable information about MLC behavior during delivery. A technique to estimate the TomoTherapy binary MLC leaf open time from exit detector signals is described. This technique is shown to be both robust and accurate for delivery verification.« less

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

Stathakis, S; Defoor, D; Linden, P

Purpose: To study the frequency of Multi-Leaf Collimator (MLC) leaf failures, investigate methods to predict them and reduce linac downtime. Methods: A Varian HD120 MLC was used in our study. The hyperterminal MLC errors logged from 06/2012 to 12/2014 were collected. Along with the hyperterminal errors, the MLC motor changes and all other MLC interventions by the linear accelerator engineer were recorded. The MLC dynalog files were also recorded on a daily basis for each treatment and during linac QA. The dynalog files were analyzed to calculate root mean square errors (RMS) and cumulative MLC travel distance per motor. Anmore » in-house MatLab code was used to analyze all dynalog files, record RMS errors and calculate the distance each MLC traveled per day. Results: A total of 269 interventions were recorded over a period of 18 months. Of these, 146 included MLC motor leaf change, 39 T-nut replacements, and 84 MLC cleaning sessions. Leaves close to the middle of each side required the most maintenance. In the A bank, leaves A27 to A40 recorded 73% of all interventions, while the same leaves in the B bank counted for 52% of the interventions. On average, leaves in the middle of the bank had their motors changed approximately every 1500m of travel. Finally, it was found that the number of RMS errors increased prior to an MLC motor change. Conclusion: An MLC dynalog file analysis software was developed that can be used to log daily MLC usage. Our eighteen-month data analysis showed that there is a correlation between the distance an MLC travels, the RMS and the life of the MLC motor. We plan to use this tool to predict MLC motor failures and with proper and timely intervention, reduce the downtime of the linac during clinical hours.« less

Forskolin induces myosin light chain dephosphorylation in bovine trabecular meshwork cells.

PubMed

Ramachandran, Charanya; Satpathy, Minati; Mehta, Dolly; Srinivas, Sangly P

2008-02-01

Enhanced contractility of the actin cytoskeleton in trabecular meshwork (TM) cells is implicated in increased resistance to aqueous humor outflow. In this study, we have investigated effects of forskolin, which is known to elevate cAMP and also enhance aqueous humor outflow, on myosin light chain (MLC) phosphorylation, a biochemical marker of actin contractility. Experiments were performed using cultured bovine TM cells. Phosphorylated MLC (pMLC), expressed as the % of untreated cells, was assessed by urea-glycerol gel electrophoresis and Western blotting. RhoA activity was determined by affinity precipitation of RhoA-GTP to RhoA binding domain of an effector of RhoA. Intracellular cAMP levels were measured by ELISA. Exposure to LPA (lysophosphatidic acid) led to increased MLC phosphorylation (LPA: pMLC=133%) and activation of RhoA. These responses of LPA were suppressed by co-treatment with forskolin (LPA+forskolin: pMLC=88%). Similarly, ET-1 and nocodazole-induced MLC phosphorylation (ET-1: pMLC=145%; nocodazole: pMLC=145%) as well as RhoA activation were suppressed by co-treatment with forskolin (ET-1+forskolin: pMLC=99%; nocodazole+forskolin: pMLC=107%). Exposure to forskolin alone led to MLC dephosphorylation (pMLC=68%). Forskolin alone led to a 4-fold increase in cAMP levels. This increase was not affected when co-treated with LPA or ET-1. Forskolin prevents MLC phosphorylation induced by LPA, ET-1, and nocodazole through inhibition of RhoA-Rho kinase axis. MLC dephosphorylation and consequent relaxation of actin cytoskeleton in TM cells presumably underlies the increased outflow facility reported in response to forskolin.

SU-G-BRB-02: An Open-Source Software Analysis Library for Linear Accelerator Quality Assurance

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

Kerns, J; Yaldo, D

Purpose: Routine linac quality assurance (QA) tests have become complex enough to require automation of most test analyses. A new data analysis software library was built that allows physicists to automate routine linear accelerator quality assurance tests. The package is open source, code tested, and benchmarked. Methods: Images and data were generated on a TrueBeam linac for the following routine QA tests: VMAT, starshot, CBCT, machine logs, Winston Lutz, and picket fence. The analysis library was built using the general programming language Python. Each test was analyzed with the library algorithms and compared to manual measurements taken at the timemore » of acquisition. Results: VMAT QA results agreed within 0.1% between the library and manual measurements. Machine logs (dynalogs & trajectory logs) were successfully parsed; mechanical axis positions were verified for accuracy and MLC fluence agreed well with EPID measurements. CBCT QA measurements were within 10 HU and 0.2mm where applicable. Winston Lutz isocenter size measurements were within 0.2mm of TrueBeam’s Machine Performance Check. Starshot analysis was within 0.2mm of the Winston Lutz results for the same conditions. Picket fence images with and without a known error showed that the library was capable of detecting MLC offsets within 0.02mm. Conclusion: A new routine QA software library has been benchmarked and is available for use by the community. The library is open-source and extensible for use in larger systems.« less

SU-E-T-424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases

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

Eldib, A; Al-Azhar University Cairo; Jin, L

2014-06-01

Purpose: Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC). Methods: We have used the MCBEAM code for treatment head simulation and formore » generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in-house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations. Results: The eMLC allows effective treatment of scalps with multi-lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup. Conclusion: MERT can improve treatment plan quality for patients with scalp cancers. Our in-house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.« less

Dosimetric performance of the new high-definition multileaf collimator for intracranial stereotactic radiosurgery.

PubMed

Dhabaan, Anees; Elder, Eric; Schreibmann, Eduard; Crocker, Ian; Curran, Walter J; Oyesiku, Nelson M; Shu, Hui-Kuo; Fox, Tim

2010-06-21

The objective was to evaluate the performance of a high-definition multileaf collimator (MLC) of 2.5 mm leaf width (MLC2.5) and compare to standard 5 mm leaf width MLC (MLC5) for the treatment of intracranial lesions using dynamic conformal arcs (DCA) technique with a dedicated radiosurgery linear accelerator. Simulated cases of spherical targets were created to study solely the effect of target volume size on the performance of the two MLC systems independent of target shape complexity. In addition, 43 patients previously treated for intracranial lesions in our institution were retrospectively planned using DCA technique with MLC2.5 and MLC5 systems. The gross tumor volume ranged from 0.07 to 40.57 cm3 with an average volume of 5.9 cm3. All treatment parameters were kept the same for both MLC-based plans. The plan evaluation was performed using figures of merits (FOM) for a rapid and objective assessment on the quality of the two treatment plans for MLC2.5 and MLC5. The prescription isodose surface was selected as the greatest isodose surface covering >or= 95% of the target volume and delivering 95% of the prescription dose to 99% of target volume. A Conformity Index (CI) and conformity distance index (CDI) were used to quantifying the dose conformity to a target volume. To assess normal tissue sparing, a normal tissue difference (NTD) was defined as the difference between the volume of normal tissue receiving a certain dose utilizing MLC5 and the volume receiving the same dose using MLC2.5. The CI and normal tissue sparing for the simulated spherical targets were better with the MLC2.5 as compared to MLC5. For the clinical patients, the CI and CDI results indicated that the MLC2.5 provides better treatment conformity than MLC5 even at large target volumes. The CI's range was 1.15 to 2.44 with a median of 1.59 for MLC2.5 compared to 1.60-2.85 with a median of 1.71 for MLC5. Improved normal tissue sparing was also observed for MLC2.5 over MLC5, with the NTD always positive, indicating improvement, and ranging from 0.1 to 8.3 for normal tissue receiving 50% (NTV50), 70% (NTV70) and 90% (NTV90) of the prescription dose. The MLC2.5 has a dosimetric advantage over the MLC5 in Linac-based radiosurgery using DCA method for intracranial lesions, both in treatment conformity and normal tissue sparing when target shape complexity increases.

The β1 subunit of the Na,K-ATPase pump interacts with megalencephalic leucoencephalopathy with subcortical cysts protein 1 (MLC1) in brain astrocytes: new insights into MLC pathogenesis

PubMed Central

Brignone, Maria S.; Lanciotti, Angela; Macioce, Pompeo; Macchia, Gianfranco; Gaetani, Matteo; Aloisi, Francesca; Petrucci, Tamara C.; Ambrosini, Elena

2011-01-01

Megalencephalic leucoencephalopathy with subcortical cysts (MLC) is a rare congenital leucodystrophy caused by mutations in MLC1, a membrane protein of unknown function. MLC1 expression in astrocyte end-feet contacting blood vessels and meninges, along with brain swelling, fluid cysts and myelin vacuolation observed in MLC patients, suggests a possible role for MLC1 in the regulation of fluid and ion homeostasis and cellular volume changes. To identify MLC1 direct interactors and dissect the molecular pathways in which MLC1 is involved, we used NH2-MLC1 domain as a bait to screen a human brain library in a yeast two-hybrid assay. We identified the β1 subunit of the Na,K-ATPase pump as one of the interacting clones and confirmed it by pull-downs, co-fractionation assays and immunofluorescence stainings in human and rat astrocytes in vitro and in brain tissue. By performing ouabain-affinity chromatography on astrocyte and brain extracts, we isolated MLC1 and the whole Na,K-ATPase enzyme in a multiprotein complex that included Kir4.1, syntrophin and dystrobrevin. Because Na,K-ATPase is involved in intracellular osmotic control and volume regulation, we investigated the effect of hypo-osmotic stress on MLC1/Na,K-ATPase relationship in astrocytes. We found that hypo-osmotic conditions increased MLC1 membrane expression and favoured MLC1/Na,K-ATPase-β1 association. Moreover, hypo-osmosis induced astrocyte swelling and the reversible formation of endosome-derived vacuoles, where the two proteins co-localized. These data suggest that through its interaction with Na,K-ATPase, MLC1 is involved in the control of intracellular osmotic conditions and volume regulation in astrocytes, opening new perspectives for understanding the pathological mechanisms of MLC disease. PMID:20926452

Evaluation of the Radiation Susceptibility of a 3D NAND Flash Memory

NASA Technical Reports Server (NTRS)

Chen, Dakai; Wilcox, Edward; Ladbury, Raymond; Seidleck, Christina; Kim, Hak; Phan, Anthony; LaBel, Kenneth

2017-01-01

We evaluated the heavy ion and proton-induced single-event effects (SEE) for a 3D NAND flash. The 3D NAND showed similar single-event upset (SEU) sensitivity to a planar NAND of similar density and performance in the multiple-cell level (MLC) storage mode. However, the single-level-cell (SLC) storage mode of the 3D NAND showed significantly reduced SEU susceptibility. Additionally, the 3D NAND showed less MBU susceptibility than the planar NAND, with reduced number of upset bits per byte and reduced cross sections overall. However, the 3D architecture exhibited angular sensitivities for both base and face angles, reflecting the anisotropic nature of the SEU vulnerability in space. Furthermore, the SEU cross section decreased with increasing fluence for both the 3D NAND and the latest generation planar NAND, indicating a variable upset rate for a space mission. These unique characteristics introduce complexity to traditional ground irradiation test procedures.

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

PubMed Central

Dubey, Mohit; Brouwers, Eelke; Hamilton, Eline M.C.; Stiedl, Oliver; Bugiani, Marianna; Koch, Henner; Kole, Maarten H.P.; Boschert, Ursula; Wykes, Robert C.; Mansvelder, Huibert D.; van der Knaap, Marjo S.

2018-01-01

Objective Loss of function of the astrocyte‐specific protein MLC1 leads to the childhood‐onset leukodystrophy “megalencephalic leukoencephalopathy with subcortical cysts” (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. Methods We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole‐cell patch‐clamp recordings and K+‐sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. Results An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice. Interpretation Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636–649 PMID:29466841

SU-E-T-627: Precision Modelling of the Leaf-Bank Rotation in Elekta’s Agility MLC: Is It Necessary?

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

Vujicic, M; Belec, J; Heath, E

Purpose: To demonstrate the method used to determine the leaf bank rotation angle (LBROT) as a parameter for modeling the Elekta Agility multi-leaf collimator (MLC) for Monte Carlo simulations and to evaluate the clinical impact of LBROT. Methods: A detailed model of an Elekta Infinity linac including an Agility MLC was built using the EGSnrc/BEAMnrc Monte Carlo code. The Agility 160-leaf MLC is modelled using the MLCE component module which allows for leaf bank rotation using the parameter LBROT. A precise value of LBROT is obtained by comparing measured and simulated profiles of a specific field, which has leaves arrangedmore » in a repeated pattern such that one leaf is opened and the adjacent one is closed. Profile measurements from an Agility linac are taken with gafchromic film, and an ion chamber is used to set the absolute dose. The measurements are compared to Monte Carlo (MC) simulations and the LBROT is adjusted until a match is found. The clinical impact of LBROT is evaluated by observing how an MC dose calculation changes with LBROT. A clinical Stereotactic Body Radiation Treatment (SBRT) plan is calculated using BEAMnrc/DOSXYZnrc simulations with different input values for LBROT. Results: Using the method outlined above, the LBROT is determined to be 9±1 mrad. Differences as high as 4% are observed in a clinical SBRT plan between the extreme case (LBROT not modeled) and the nominal case. Conclusion: In small-field radiation therapy treatment planning, it is important to properly account for LBROT as an input parameter for MC dose calculations with the Agility MLC. More work is ongoing to elucidate the observed differences by determining the contributions from transmission dose, change in field size, and source occlusion, which are all dependent on LBROT. This work was supported by OCAIRO (Ontario Consortium of Adaptive Interventions in Radiation Oncology), funded by the Ontario Research Fund.« less

SU-G-JeP1-12: Head-To-Head Performance Characterization of Two Multileaf Collimator Tracking Algorithms for Radiotherapy

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

Caillet, V; Colvill, E; Royal North Shore Hospital, St Leonards, Sydney

2016-06-15

Purpose: Multi-leaf collimator (MLC) tracking is being clinically pioneered to continuously compensate for thoracic and abdominal motion during radiotherapy. The purpose of this work is to characterize the performance of two MLC tracking algorithms for cancer radiotherapy, based on a direct optimization and a piecewise leaf fitting approach respectively. Methods: To test the algorithms, both physical and in silico experiments were performed. Previously published high and low modulation VMAT plans for lung and prostate cancer cases were used along with eight patient-measured organ-specific trajectories. For both MLC tracking algorithm, the plans were run with their corresponding patient trajectories. The physicalmore » experiments were performed on a Trilogy Varian linac and a programmable phantom (HexaMotion platform). For each MLC tracking algorithm, plan and patient trajectory, the tracking accuracy was quantified as the difference in aperture area between ideal and fitted MLC. To compare algorithms, the average cumulative tracking error area for each experiment was calculated. The two-sample Kolmogorov-Smirnov (KS) test was used to evaluate the cumulative tracking errors between algorithms. Results: Comparison of tracking errors for the physical and in silico experiments showed minor differences between the two algorithms. The KS D-statistics for the physical experiments were below 0.05 denoting no significant differences between the two distributions pattern and the average error area (direct optimization/piecewise leaf-fitting) were comparable (66.64 cm2/65.65 cm2). For the in silico experiments, the KS D-statistics were below 0.05 and the average errors area were also equivalent (49.38 cm2/48.98 cm2). Conclusion: The comparison between the two leaf fittings algorithms demonstrated no significant differences in tracking errors, neither in a clinically realistic environment nor in silico. The similarities in the two independent algorithms give confidence in the use of either algorithm for clinical implementation.« less

MO-FG-202-04: Gantry-Resolved Linac QA for VMAT: A Comprehensive and Efficient System Using An Electronic Portal Imaging Device

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

Zwan, B J; University of Newcastle, Newcastle, NSW; Barnes, M

2016-06-15

Purpose: To automate gantry-resolved linear accelerator (linac) quality assurance (QA) for volumetric modulated arc therapy (VMAT) using an electronic portal imaging device (EPID). Methods: A QA system for VMAT was developed that uses an EPID, frame-grabber assembly and in-house developed image processing software. The system relies solely on the analysis of EPID image frames acquired without the presence of a phantom. Images were acquired at 8.41 frames per second using a frame grabber and ancillary acquisition computer. Each image frame was tagged with a gantry angle from the linac’s on-board gantry angle encoder. Arc-dynamic QA plans were designed to assessmore » the performance of each individual linac component during VMAT. By analysing each image frame acquired during the QA deliveries the following eight machine performance characteristics were measured as a function of gantry angle: MLC positional accuracy, MLC speed constancy, MLC acceleration constancy, MLC-gantry synchronisation, beam profile constancy, dose rate constancy, gantry speed constancy, dose-gantry angle synchronisation and mechanical sag. All tests were performed on a Varian iX linear accelerator equipped with a 120 leaf Millennium MLC and an aS1000 EPID (Varian Medical Systems, Palo Alto, CA, USA). Results: Machine performance parameters were measured as a function of gantry angle using EPID imaging and compared to machine log files and the treatment plan. Data acquisition is currently underway at 3 centres, incorporating 7 treatment units, at 2 weekly measurement intervals. Conclusion: The proposed system can be applied for streamlined linac QA and commissioning for VMAT. The set of test plans developed can be used to assess the performance of each individual components of the treatment machine during VMAT deliveries as a function of gantry angle. The methodology does not require the setup of any additional phantom or measurement equipment and the analysis is fully automated to allow for regular routine testing.« less

The transcription factor Mlc promotes Vibrio cholerae biofilm formation through repression of phosphotransferase system components.

PubMed

Pickering, Bradley S; Lopilato, Jane E; Smith, Daniel R; Watnick, Paula I

2014-07-01

The phosphoenol phosphotransferase system (PTS) is a multicomponent signal transduction cascade that regulates diverse aspects of bacterial cellular physiology in response to the availability of high-energy sugars in the environment. Many PTS components are repressed at the transcriptional level when the substrates they transport are not available. In Escherichia coli, the transcription factor Mlc (for makes large colonies) represses transcription of the genes encoding enzyme I (EI), histidine protein (HPr), and the glucose-specific enzyme IIBC (EIIBC(Glc)) in defined media that lack PTS substrates. When glucose is present, the unphosphorylated form of EIIBC(Glc) sequesters Mlc to the cell membrane, preventing its interaction with DNA. Very little is known about Vibrio cholerae Mlc. We found that V. cholerae Mlc activates biofilm formation in LB broth but not in defined medium supplemented with either pyruvate or glucose. Therefore, we questioned whether V. cholerae Mlc functions differently than E. coli Mlc. Here we have shown that, like E. coli Mlc, V. cholerae Mlc represses transcription of PTS components in both defined medium and LB broth and that E. coli Mlc is able to rescue the biofilm defect of a V. cholerae Δmlc mutant. Furthermore, we provide evidence that Mlc indirectly activates transcription of the vps genes by repressing expression of EI. Because activation of the vps genes by Mlc occurs under only a subset of the conditions in which repression of PTS components is observed, we conclude that additional inputs present in LB broth are required for activation of vps gene transcription by Mlc. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

On the use of biomathematical models in patient-specific IMRT dose QA

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

Zhen Heming; Nelms, Benjamin E.; Tome, Wolfgang A.

2013-07-15

Purpose: To investigate the use of biomathematical models such as tumor control probability (TCP) and normal tissue complication probability (NTCP) as new quality assurance (QA) metrics.Methods: Five different types of error (MLC transmission, MLC penumbra, MLC tongue and groove, machine output, and MLC position) were intentionally induced to 40 clinical intensity modulated radiation therapy (IMRT) patient plans (20 H and N cases and 20 prostate cases) to simulate both treatment planning system errors and machine delivery errors in the IMRT QA process. The changes in TCP and NTCP for eight different anatomic structures (H and N: CTV, GTV, both parotids,more » spinal cord, larynx; prostate: CTV, rectal wall) were calculated as the new QA metrics to quantify the clinical impact on patients. The correlation between the change in TCP/NTCP and the change in selected DVH values was also evaluated. The relation between TCP/NTCP change and the characteristics of the TCP/NTCP curves is discussed.Results:{Delta}TCP and {Delta}NTCP were summarized for each type of induced error and each structure. The changes/degradations in TCP and NTCP caused by the errors vary widely depending on dose patterns unique to each plan, and are good indicators of each plan's 'robustness' to that type of error.Conclusions: In this in silico QA study the authors have demonstrated the possibility of using biomathematical models not only as patient-specific QA metrics but also as objective indicators that quantify, pretreatment, a plan's robustness with respect to possible error types.« less

The potential impact of multidimesional geriatric assessment in the social security system.

PubMed

Corbi, Graziamaria; Ambrosino, Immacolata; Massari, Marco; De Lucia, Onofrio; Simplicio, Sirio; Dragone, Michele; Paolisso, Giuseppe; Piccioni, Massimo; Ferrara, Nicola; Campobasso, Carlo Pietro

2018-01-12

To evaluate the efficacy of multidimensional geriatric assessment (MGA/CGA) in patients over 65 years old in predicting the release of the accompaniment allowance (AA) indemnity by a Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (MLC-INPS). In a longitudinal observational study, 200 Italian elder citizens requesting AA were first evaluated by MLC-NHS and later by MLC-INPS. Only MLC-INPS performed a MGA/CGA (including SPMSQ, Barthel Index, GDS-SF, and CIRS). This report was written according to the STROBE guidelines. The data analysis was performed on January 2016. The evaluation by the MLC-NHS and by the MLC-INPS was in agreement in 66% of cases. In the 28%, the AA benefit was recognized by the MLC-NHS, but not by the MLC-INPS. By the multivariate analysis, the best predictors of the AA release, by the MLC-NHS, were represented by gender and the Barthel Index score. The presence of carcinoma, the Barthel Index score, and the SPMQ score were the best predictors for the AA release by MLC-INPS. MGA/CGA could be useful in saving financial resources reducing the risk of incorrect indemnity release. It can improve the accuracy of the impairment assessment in social security system.

Dosimetric Comparison of Intensity-Modulated Stereotactic Radiotherapy With Other Stereotactic Techniques for Locally Recurrent Nasopharyngeal Carcinoma

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

Kung, Shiris Wai Sum; Wu, Vincent Wing Cheung; Kam, Michael Koon Ming, E-mail: kamkm@yahoo.co

2011-01-01

Purpose: Locally recurrent nasopharyngeal carcinoma (NPC) patients can be salvaged by reirradiation with a substantial degree of radiation-related complications. Stereotactic radiotherapy (SRT) is widely used in this regard because of its rapid dose falloff and high geometric precision. The aim of this study was to examine whether the newly developed intensity-modulated stereotactic radiotherapy (IMSRT) has any dosimetric advantages over three other stereotactic techniques, including circular arc (CARC), static conformal beam (SmMLC), and dynamic conformal arc (mARC), in treating locally recurrent NPC. Methods and Materials: Computed tomography images of 32 patients with locally recurrent NPC, previously treated with SRT, were retrievedmore » from the stereotactic planning system for contouring and computing treatment plans. Treatment planning of each patient was performed for the four treatment techniques: CARC, SmMLC, mARC, and IMSRT. The conformity index (CI) and homogeneity index (HI) of the planning target volume (PTV) and doses to the organs at risk (OARs) and normal tissue were compared. Results: All four techniques delivered adequate doses to the PTV. IMSRT, SmMLC, and mARC delivered reasonably conformal and homogenous dose to the PTV (CI <1.47, HI <0.53), but not for CARC (p < 0.05). IMSRT presented with the smallest CI (1.37) and HI (0.40). Among the four techniques, IMSRT spared the greatest number of OARs, namely brainstem, temporal lobes, optic chiasm, and optic nerve, and had the smallest normal tissue volume in the low-dose region. Conclusion: Based on the dosimetric comparison, IMSRT was optimal for locally recurrent NPC by delivering a conformal and homogenous dose to the PTV while sparing OARs.« less

Ultrafast treatment plan optimization for volumetric modulated arc therapy (VMAT)

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

Men Chunhua; Romeijn, H. Edwin; Jia Xun

2010-11-15

Purpose: To develop a novel aperture-based algorithm for volumetric modulated arc therapy (VMAT) treatment plan optimization with high quality and high efficiency. Methods: The VMAT optimization problem is formulated as a large-scale convex programming problem solved by a column generation approach. The authors consider a cost function consisting two terms, the first enforcing a desired dose distribution and the second guaranteeing a smooth dose rate variation between successive gantry angles. A gantry rotation is discretized into 180 beam angles and for each beam angle, only one MLC aperture is allowed. The apertures are generated one by one in a sequentialmore » way. At each iteration of the column generation method, a deliverable MLC aperture is generated for one of the unoccupied beam angles by solving a subproblem with the consideration of MLC mechanic constraints. A subsequent master problem is then solved to determine the dose rate at all currently generated apertures by minimizing the cost function. When all 180 beam angles are occupied, the optimization completes, yielding a set of deliverable apertures and associated dose rates that produce a high quality plan. Results: The algorithm was preliminarily tested on five prostate and five head-and-neck clinical cases, each with one full gantry rotation without any couch/collimator rotations. High quality VMAT plans have been generated for all ten cases with extremely high efficiency. It takes only 5-8 min on CPU (MATLAB code on an Intel Xeon 2.27 GHz CPU) and 18-31 s on GPU (CUDA code on an NVIDIA Tesla C1060 GPU card) to generate such plans. Conclusions: The authors have developed an aperture-based VMAT optimization algorithm which can generate clinically deliverable high quality treatment plans at very high efficiency.« less

Ultrafast treatment plan optimization for volumetric modulated arc therapy (VMAT).

PubMed

Men, Chunhua; Romeijn, H Edwin; Jia, Xun; Jiang, Steve B

2010-11-01

To develop a novel aperture-based algorithm for volumetric modulated are therapy (VMAT) treatment plan optimization with high quality and high efficiency. The VMAT optimization problem is formulated as a large-scale convex programming problem solved by a column generation approach. The authors consider a cost function consisting two terms, the first enforcing a desired dose distribution and the second guaranteeing a smooth dose rate variation between successive gantry angles. A gantry rotation is discretized into 180 beam angles and for each beam angle, only one MLC aperture is allowed. The apertures are generated one by one in a sequential way. At each iteration of the column generation method, a deliverable MLC aperture is generated for one of the unoccupied beam angles by solving a subproblem with the consideration of MLC mechanic constraints. A subsequent master problem is then solved to determine the dose rate at all currently generated apertures by minimizing the cost function. When all 180 beam angles are occupied, the optimization completes, yielding a set of deliverable apertures and associated dose rates that produce a high quality plan. The algorithm was preliminarily tested on five prostate and five head-and-neck clinical cases, each with one full gantry rotation without any couch/collimator rotations. High quality VMAT plans have been generated for all ten cases with extremely high efficiency. It takes only 5-8 min on CPU (MATLAB code on an Intel Xeon 2.27 GHz CPU) and 18-31 s on GPU (CUDA code on an NVIDIA Tesla C1060 GPU card) to generate such plans. The authors have developed an aperture-based VMAT optimization algorithm which can generate clinically deliverable high quality treatment plans at very high efficiency.

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

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

Nguyen, D; Lyu, Q; Ruan, D

2016-06-15

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

SU-E-T-35: A General Fill Factor Definition Serving to Characterise the MLC Misalignment Detection Capabilities of Two-Dimensional Detector Arrays

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

Stelljes, T.S.; Looe, H.K.; Poppe, B.

Purpose: To present a general definition of the fill factor realistically characterizing the “field coverage”, i.e. the MLC misalignment detection capabilities of a detector array. Methods: According to Gago-Arias et al.{sup 1} the fill factor of a 2D array is defined as the ratio of the area enclosed by the FWHM of the fluence response function KM(x) of a single detector and its cell area defined by the detector spacing. More generally - accounting also for the possible overlap between FWHM’s of neighboured detectors - the fill factor is here defined as that fraction of the sum of the detectormore » cell areas in which a defined MLC misalignment is detectable when the induced percentage signal changes exceed a detection threshold d. Ideally the generalized fill factor may reach 100 %. With user code EGS-chamber and a 2 MeV photon slit beam 0.25 mm wide, both types of the fill factor were calculated for an array with total cell area 100 cm{sup 2} for chamber widths 1–9 mm, using =1mm, d=5%. Results: For single chamber width 5 mm, fill factors were 0.49 (FWHM) and 0.61 (generalized). For chamber width 2 mm the FWHM fill factor was 0.13 whereas the generalized fill factor was 0.32. For chamber widths above 7 mm, the FWHM fill factor exceeds unity, and the general fill factor is exactly 1.00. Conclusions: An updated fill factor definition is introduced which, as a generalization of the FWHM-based definition, more closely estimates the performance of small array chambers and gives a realistic value in the case of overlapping sensitive areas of neighboured chambers. References:{sup 1}A. Gago-Arias, L. Brualla-Gonzalez, D.M. Gonzalez-Castano, F. Gomez, M.S. Garcia, V.L. Vega, J.M. Sueiro, J. Pardo-Montero, “Evaluation of chamber response function influence on IMRT verification using 2D commercial detector arrays,” Phys. Med. Biol. 57, 2005–2020 (2012)« less

TH-AB-202-02: Real-Time Verification and Error Detection for MLC Tracking Deliveries Using An Electronic Portal Imaging Device

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

J Zwan, B; Central Coast Cancer Centre, Gosford, NSW; Colvill, E

2016-06-15

Purpose: The added complexity of the real-time adaptive multi-leaf collimator (MLC) tracking increases the likelihood of undetected MLC delivery errors. In this work we develop and test a system for real-time delivery verification and error detection for MLC tracking radiotherapy using an electronic portal imaging device (EPID). Methods: The delivery verification system relies on acquisition and real-time analysis of transit EPID image frames acquired at 8.41 fps. In-house software was developed to extract the MLC positions from each image frame. Three comparison metrics were used to verify the MLC positions in real-time: (1) field size, (2) field location and, (3)more » field shape. The delivery verification system was tested for 8 VMAT MLC tracking deliveries (4 prostate and 4 lung) where real patient target motion was reproduced using a Hexamotion motion stage and a Calypso system. Sensitivity and detection delay was quantified for various types of MLC and system errors. Results: For both the prostate and lung test deliveries the MLC-defined field size was measured with an accuracy of 1.25 cm{sup 2} (1 SD). The field location was measured with an accuracy of 0.6 mm and 0.8 mm (1 SD) for lung and prostate respectively. Field location errors (i.e. tracking in wrong direction) with a magnitude of 3 mm were detected within 0.4 s of occurrence in the X direction and 0.8 s in the Y direction. Systematic MLC gap errors were detected as small as 3 mm. The method was not found to be sensitive to random MLC errors and individual MLC calibration errors up to 5 mm. Conclusion: EPID imaging may be used for independent real-time verification of MLC trajectories during MLC tracking deliveries. Thresholds have been determined for error detection and the system has been shown to be sensitive to a range of delivery errors.« less

Textural feature calculated from segmental fluences as a modulation index for VMAT.

PubMed

Park, So-Yeon; Park, Jong Min; Kim, Jung-In; Kim, Hyoungnyoun; Kim, Il Han; Ye, Sung-Joon

2015-12-01

Textural features calculated from various segmental fluences of volumetric modulated arc therapy (VMAT) plans were optimized to enhance its performance to predict plan delivery accuracy. Twenty prostate and twenty head and neck VMAT plans were selected retrospectively. Fluences were generated for each VMAT plan by summations of segments at sequential groups of control points. The numbers of summed segments were 5, 10, 20, 45, 90, 178 and 356. For each fluence, we investigated 6 textural features: angular second moment, inverse difference moment, contrast, variance, correlation and entropy (particular displacement distances, d = 1, 5 and 10). Spearman's rank correlation coefficients (rs) were calculated between each textural feature and several different measures of VMAT delivery accuracy. The values of rs of contrast (d = 10) with 10 segments to both global and local gamma passing rates with 2%/2 mm were 0.666 (p <0.001) and 0.573 (p <0.001), respectively. It showed rs values of -0.895 (p <0.001) and 0.727 (p <0.001) to multi-leaf collimator positional errors and gantry angle errors during delivery, respectively. The number of statistically significant rs values (p <0.05) to the changes in dose-volumetric parameters during delivery was 14 among a total of 35 tested parameters. Contrast (d = 10) with 10 segments showed higher correlations to the VMAT delivery accuracy than did the conventional modulation indices. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A novel technique for VMAT QA with EPID in cine mode on a Varian TrueBeam linac

NASA Astrophysics Data System (ADS)

Liu, Bo; Adamson, Justus; Rodrigues, Anna; Zhou, Fugen; Yin, Fang-fang; Wu, Qiuwen

2013-10-01

Volumetric modulated arc therapy (VMAT) is a relatively new treatment modality for dynamic photon radiation therapy. Pre-treatment quality assurance (QA) is necessary and many efforts have been made to apply electronic portal imaging device (EPID)-based IMRT QA methods to VMAT. It is important to verify the gantry rotation speed during delivery as this is a new variable that is also modulated in VMAT. In this paper, we present a new technique to perform VMAT QA using an EPID. The method utilizes EPID cine mode and was tested on Varian TrueBeam in research mode. The cine images were acquired during delivery and converted to dose matrices after profile correction and dose calibration. A sub-arc corresponding to each cine image was extracted from the original plan and its portal image prediction was calculated. Several analyses were performed including 3D γ analysis (2D images + gantry angle axis), 2D γ analysis, and other statistical analyses. The method was applied to 21 VMAT photon plans of 3 photon energies. The accuracy of the cine image information was investigated. Furthermore, this method's sensitivity to machine delivery errors was studied. The pass rate (92.8 ± 1.4%) for 3D γ analysis was comparable to those from Delta4 system (99.9 ± 0.1%) under similar criteria (3%, 3 mm, 5% threshold and 2° angle to agreement) at 6 MV. The recorded gantry angle and start/stop MUs were found to have sufficient accuracy for clinical QA. Machine delivery errors can be detected through combined analyses of 3D γ, gantry angle, and percentage dose difference. In summary, we have developed and validated a QA technique that can simultaneously verify the gantry angle and delivered MLC fluence for VMAT treatment.This technique is efficient and its accuracy is comparable to other QA methods.

Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking.

PubMed

Yoon, Jai-Woong; Sawant, Amit; Suh, Yelin; Cho, Byung-Chul; Suh, Tae-Suk; Keall, Paul

2011-07-01

In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a tgamma-test with a 3%/3 mm criterion. The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation. The delivery efficiency of moving average tracking was up to four times higher than that of real-time tracking and approached the efficiency of no compensation for all cases. The geometric accuracy and dosimetric accuracy of the moving average algorithm was between real-time tracking and no compensation, approximately half the percentage of dosimetric points failing the gamma-test compared with no compensation.

Fast leaf-fitting with generalized underdose/overdose constraints for real-time MLC tracking

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

Moore, Douglas, E-mail: douglas.moore@utsouthwestern.edu; Sawant, Amit; Ruan, Dan

2016-01-15

Purpose: Real-time multileaf collimator (MLC) tracking is a promising approach to the management of intrafractional tumor motion during thoracic and abdominal radiotherapy. MLC tracking is typically performed in two steps: transforming a planned MLC aperture in response to patient motion and refitting the leaves to the newly generated aperture. One of the challenges of this approach is the inability to faithfully reproduce the desired motion-adapted aperture. This work presents an optimization-based framework with which to solve this leaf-fitting problem in real-time. Methods: This optimization framework is designed to facilitate the determination of leaf positions in real-time while accounting for themore » trade-off between coverage of the PTV and avoidance of organs at risk (OARs). Derived within this framework, an algorithm is presented that can account for general linear transformations of the planned MLC aperture, particularly 3D translations and in-plane rotations. This algorithm, together with algorithms presented in Sawant et al. [“Management of three-dimensional intrafraction motion through real-time DMLC tracking,” Med. Phys. 35, 2050–2061 (2008)] and Ruan and Keall [Presented at the 2011 IEEE Power Engineering and Automation Conference (PEAM) (2011) (unpublished)], was applied to apertures derived from eight lung intensity modulated radiotherapy plans subjected to six-degree-of-freedom motion traces acquired from lung cancer patients using the kilovoltage intrafraction monitoring system developed at the University of Sydney. A quality-of-fit metric was defined, and each algorithm was evaluated in terms of quality-of-fit and computation time. Results: This algorithm is shown to perform leaf-fittings of apertures, each with 80 leaf pairs, in 0.226 ms on average as compared to 0.082 and 64.2 ms for the algorithms of Sawant et al., Ruan, and Keall, respectively. The algorithm shows approximately 12% improvement in quality-of-fit over the Sawant et al. approach, while performing comparably to Ruan and Keall. Conclusions: This work improves upon the quality of the Sawant et al. approach, but does so without sacrificing run-time performance. In addition, using this framework allows for complex leaf-fitting strategies that can be used to account for PTV/OAR trade-off during real-time MLC tracking.« less

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

Chengqiang, L; Yin, Y; Chen, L

Purpose: To investigate the impact of MLC position errors on simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with nasopharyngeal carcinoma. Methods: To compare the dosimetric differences between the simulated plans and the clinical plans, ten patients with locally advanced NPC treated with SIB-IMRT were enrolled in this study. All plans were calculated with an inverse planning system (Pinnacle3, Philips Medical System{sub )}. Random errors −2mm to 2mm{sub )},shift errors{sub (} 2mm,1mm and 0.5mm) and systematic extension/ contraction errors (±2mm, ±1mm and ±0.5mm) of the MLC leaf position were introduced respectively into the original plans to create the simulated plans.more » Dosimetry factors were compared between the original and the simulated plans. Results: The dosimetric impact of the random and system shift errors of MLC position was insignificant within 2mm, the maximum changes in D95% of PGTV,PTV1,PTV2 were-0.92±0.51%,1.00±0.24% and 0.62±0.17%, the maximum changes in the D0.1cc of spinal cord and brainstem were 1.90±2.80% and −1.78±1.42%, the maximum changes in the Dmean of parotids were1.36±1.23% and −2.25±2.04%.However,the impact of MLC extension or contraction errors was found significant. For 2mm leaf extension errors, the average changes in D95% of PGTV,PTV1,PTV2 were 4.31±0.67%,4.29±0.65% and 4.79±0.82%, the averaged value of the D0.1cc to spinal cord and brainstem were increased by 7.39±5.25% and 6.32±2.28%,the averaged value of the mean dose to left and right parotid were increased by 12.75±2.02%,13.39±2.17% respectively. Conclusion: The dosimetric effect was insignificant for random MLC leaf position errors up to 2mm. There was a high sensitivity to dose distribution for MLC extension or contraction errors.We should pay attention to the anatomic changes in target organs and anatomical structures during the course,individual radiotherapy was recommended to ensure adaptive doses.« less

SU-F-J-214: Dose Reduction by Spatially Optimized Image Quality Via Fluence Modulated Proton CT (FMpCT)

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

De Angelis, L; Landry, G; Dedes, G

Purpose: Proton CT (pCT) is a promising imaging modality for reducing range uncertainty in image-guided proton therapy. Range uncertainties partially originate from X-ray CT number conversion to stopping power ratio (SPR) and are limiting the exploitation of the full potential of proton therapy. In this study we explore the concept of spatially dependent fluence modulated proton CT (FMpCT), for achieving optimal image quality in a clinical region of interest (ROI), while reducing significantly the imaging dose to the patient. Methods: The study was based on simulated ideal pCT using pencil beam (PB) scanning. A set of 250 MeV protons PBsmore » was used to create 360 projections of a cylindrical water phantom and a head and neck cancer patient. The tomographic images were reconstructed using a filtered backprojection (FBP) as well as an iterative algorithm (ITR). Different fluence modulation levels were investigated and their impact on the image was quantified in terms of SPR accuracy as well as noise within and outside selected ROIs, as a function of imaging dose. The unmodulated image served as reference. Results: Both FBP reconstruction and ITR without total variation (TV) yielded image quality in the ROIs similar to the reference images, for modulation down to 0.1 of the full proton fluence. The average dose was reduced by 75% for the water phantom and by 40% for the patient. FMpCT does not improve the noise for ITR with TV and modulation 0.1. Conclusion: This is the first work proposing and investigating FMpCT for producing optimal image quality for treatment planning and image guidance, while simultaneously reducing imaging dose. Future work will address spatial resolution effects and the impact of FMpCT on the quality of proton treatment plans for a prototype pCT scanner capable of list mode data acquisition. Acknowledgement: DFG-MAP DFG - Munich-Centre for Advanced Photonics (MAP)« less

Modulations of anisotropic optical transmission on alumina-doped zinc oxide surface by femtosecond laser induced ripples

NASA Astrophysics Data System (ADS)

Lu, Yanhui; Jiang, Lan; Sun, Jingya; Cao, Qiang; Wang, Qingsong; Han, Weina; Lu, Yongfeng

2018-04-01

This study demonstrated that femtosecond-laser-induced ripples on an alumina-doped zinc oxide (AZO) film with space intervals of approximately 340 and 660 nm exhibit modulations of anisotropic optical transmission. At low laser fluence, ripples can not affect the original absorption peak of AZO film, but at higher laser fluence, the absorption peak of AZO film is disappeared due to the modulation by femtosecond laser induced ripples. Moreover, the relationship between the anisotropic optical transmission and the features of nanostructures is discussed. Ripples with a space interval of approximately 660 nm have a higher ability to block light than nanostructures with a space interval of approximately 340 nm. These observations indicate that anisotropic optical transmission has potential applications in the field of optoelectronics.

Software tool for portal dosimetry research.

PubMed

Vial, P; Hunt, P; Greer, P B; Oliver, L; Baldock, C

2008-09-01

This paper describes a software tool developed for research into the use of an electronic portal imaging device (EPID) to verify dose for intensity modulated radiation therapy (IMRT) beams. A portal dose image prediction (PDIP) model that predicts the EPID response to IMRT beams has been implemented into a commercially available treatment planning system (TPS). The software tool described in this work was developed to modify the TPS PDIP model by incorporating correction factors into the predicted EPID image to account for the difference in EPID response to open beam radiation and multileaf collimator (MLC) transmitted radiation. The processes performed by the software tool include; i) read the MLC file and the PDIP from the TPS, ii) calculate the fraction of beam-on time that each point in the IMRT beam is shielded by MLC leaves, iii) interpolate correction factors from look-up tables, iv) create a corrected PDIP image from the product of the original PDIP and the correction factors and write the corrected image to file, v) display, analyse, and export various image datasets. The software tool was developed using the Microsoft Visual Studio.NET framework with the C# compiler. The operation of the software tool was validated. This software provided useful tools for EPID dosimetry research, and it is being utilised and further developed in ongoing EPID dosimetry and IMRT dosimetry projects.

Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa Histone Deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

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

Compagnucci, Claudia; Barresi, Sabina; Petrini, Stefania

2015-04-03

Rho-kinase (ROCK) has been well documented to play a key role in RhoA-induced actin remodeling. ROCK activation results in myosin light chain (MLC) phosphorylation either by direct action on MLC kinase (MLCK) or by inhibition of MLC phosphatase (MLCP), modulating actin–myosin contraction. We found that inhibition of the ROCK pathway in induced pluripotent stem cells, leads to nuclear export of HDAC7 and transcriptional activation of the orphan nuclear receptor NR4A1 while in cells with constitutive ROCK hyperactivity due to loss of function of the RhoGTPase activating protein Oligophrenin-1 (OPHN1), the orphan nuclear receptor NR4A1 is downregulated. Our study identify amore » new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and Histone Deacetylase (HDAC7) at the nuclear level and provide new insights in the cellular functions of ROCK. - Highlights: • ROCK regulates nucleocytoplasmic shuttling of HDAC7 via phosphorylation of MYPT1. • Nuclear export of HDAC7 and upregulation of NR4A1 occurs with low ROCK activity. • High levels of ROCK activity due to OPHN1 loss of function downregulate NR4A1.« less

Micellar liquid chromatography

NASA Astrophysics Data System (ADS)

Basova, Elena M.; Ivanov, Vadim M.; Shpigun, Oleg A.

1999-12-01

Background and possibilities of practical applications of micellar liquid chromatography (MLC) are considered. Various retention models in MLC, the effects of the nature and concentration of surfactants and organic modifiers, pH, temperature and ionic strength on the MLC efficiency and selectivity are discussed. The advantages and limitations of MLC are demonstrated. The performance of MLC is critically evaluated in relationship to the reversed-phase HPLC and ion-pair chromatography. The potential of application of MLC for the analysis of pharmaceuticals including that in biological fluids and separation of inorganic anions, transition metal cations, metal chelates and heteropoly compounds is described. The bibliography includes 146 references.

Is mini-laparoscopic cholecystectomy any better than the gold standard?: A comparative study.

PubMed

Shaikh, Haris R; Abbas, Asad; Aleem, Salik; Lakhani, Miqdad R

2017-01-01

Mini-laparoscopic cholecystectomy (MLC) has widened the horizons of modern laparoscopic surgery. Standard four port laparoscopic cholecystectomy (SLC), which has long been established as the "Gold Standard" for gall bladder diseases, is under reconsideration following the advent of further minimally-invasive procedures including MLC. Our study aims to provide a comparison between MLC and SLC and assesses whether MLC has any added benefits. Patients with symptomatic gall bladder disease undergoing MLC or SLC during the 2.5-month period were included in the study. Thirty-two patients underwent MLC while SLC was performed on 40 patients by the same surgeon. Data was collected prospectively and analysed retrospectively using a predesigned questionnaire. In our study, both the groups had similar age, body mass index (BMI) and gender distribution. No cases of MLC required insertion of additional ports. The mean operative time for MLC was 38.2 min (33-61 min), which is longer than SLC; but it was not statistically significant. There was no significant difference in mean operative blood loss, postoperative pain, analgesia requirement and mobilization. Patients who underwent MLC were able to return to normal activity earlier than patients undergoing SLC (P < 0.01). Our experience suggests that MLC can safely be used as an alternative to SLC. Compared to SLC, it has the added benefit of an early return to work along with excellent cosmetic results. Further large scale trials are required to prove any additional benefit of MLC.

Is mini-laparoscopic cholecystectomy any better than the gold standard?: A comparative study

PubMed Central

Shaikh, Haris R.; Abbas, Asad; Aleem, Salik; Lakhani, Miqdad R.

2017-01-01

BACKGROUND: Mini-laparoscopic cholecystectomy (MLC) has widened the horizons of modern laparoscopic surgery. Standard four port laparoscopic cholecystectomy (SLC), which has long been established as the “Gold Standard” for gall bladder diseases, is under reconsideration following the advent of further minimally-invasive procedures including MLC. Our study aims to provide a comparison between MLC and SLC and assesses whether MLC has any added benefits. MATERIALS AND METHODS: Patients with symptomatic gall bladder disease undergoing MLC or SLC during the 2.5-month period were included in the study. Thirty-two patients underwent MLC while SLC was performed on 40 patients by the same surgeon. Data was collected prospectively and analysed retrospectively using a predesigned questionnaire. RESULTS: In our study, both the groups had similar age, body mass index (BMI) and gender distribution. No cases of MLC required insertion of additional ports. The mean operative time for MLC was 38.2 min (33-61 min), which is longer than SLC; but it was not statistically significant. There was no significant difference in mean operative blood loss, postoperative pain, analgesia requirement and mobilization. Patients who underwent MLC were able to return to normal activity earlier than patients undergoing SLC (P < 0.01). CONCLUSION: Our experience suggests that MLC can safely be used as an alternative to SLC. Compared to SLC, it has the added benefit of an early return to work along with excellent cosmetic results. Further large scale trials are required to prove any additional benefit of MLC. PMID:27251827

Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

PubMed

Jang, Si Young; Lalonde, Ron; Ozhasoglu, Cihat; Burton, Steven; Heron, Dwight; Huq, M Saiful

2016-09-08

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. © 2016 The Authors.

Complexity metric based on fraction of penumbra dose - initial study

NASA Astrophysics Data System (ADS)

Bäck, A.; Nordström, F.; Gustafsson, M.; Götstedt, J.; Karlsson Hauer, A.

2017-05-01

Volumetric modulated arc therapy improve radiotherapy outcome for many patients compared to conventional three dimensional conformal radiotherapy but require a more extensive, most often measurement based, quality assurance. Multi leaf collimator (MLC) aperture-based complexity metrics have been suggested to be used to distinguish complex treatment plans unsuitable for treatment without time consuming measurements. This study introduce a spatially resolved complexity score that correlate to the fraction of penumbra dose and will give information on the spatial distribution and the clinical relevance of the calculated complexity. The complexity metric is described and an initial study on the correlation between the complexity score and the difference between measured and calculated dose for 30 MLC openings is presented. The result of an analysis of the complexity scores were found to correlate to differences between measurements and calculations with a Pearson’s r-value of 0.97.

The Effects of Lactobacillus acidophilus on the Intestinal Smooth Muscle Contraction through PKC/MLCK/MLC Signaling Pathway in TBI Mouse Model

PubMed Central

Fang, Huan; Zhu, Lina; Gao, Ning; Zhu, Jingci

2015-01-01

Clinical studies have shown that probiotics influence gastrointestinal motility. However, the molecular mechanisms by which probiotic Lactobacillus modulates intestinal motility in traumatic brain injury (TBI) mouse model have not been explored. In the present study, we provided evidence showing that treatment of TBI mice with Lactobacillus acidophilus significantly improved the terminal ileum villus morphology, restored the impaired interstitial cells of Cajal (ICC) and the disrupted ICC networks after TBI, and prevented TBI-mediated inhibition of contractile activity in intestinal smooth muscle. Mechanistically, the decreased concentration of MLCK, phospho-MLC20 and phospho-MYPT1 and increased concentration of MLCP and PKC were observed after TBI, and these events mediated by TBI were efficiently prevented by Lactobacillus acidophilus application. These findings may provide a novel mechanistic basis for the application of Lactobacillus acidophilus in the treatment of TBI. PMID:26030918

The Effects of Lactobacillus acidophilus on the Intestinal Smooth Muscle Contraction through PKC/MLCK/MLC Signaling Pathway in TBI Mouse Model.

PubMed

Sun, Bo; Hu, Chen; Fang, Huan; Zhu, Lina; Gao, Ning; Zhu, Jingci

2015-01-01

Clinical studies have shown that probiotics influence gastrointestinal motility. However, the molecular mechanisms by which probiotic Lactobacillus modulates intestinal motility in traumatic brain injury (TBI) mouse model have not been explored. In the present study, we provided evidence showing that treatment of TBI mice with Lactobacillus acidophilus significantly improved the terminal ileum villus morphology, restored the impaired interstitial cells of Cajal (ICC) and the disrupted ICC networks after TBI, and prevented TBI-mediated inhibition of contractile activity in intestinal smooth muscle. Mechanistically, the decreased concentration of MLCK, phospho-MLC20 and phospho-MYPT1 and increased concentration of MLCP and PKC were observed after TBI, and these events mediated by TBI were efficiently prevented by Lactobacillus acidophilus application. These findings may provide a novel mechanistic basis for the application of Lactobacillus acidophilus in the treatment of TBI.

Role of RhoA and its effectors ROCK and mDia1 in the modulation of deformation-induced FAK, ERK, p38, and MLC motogenic signals in human Caco-2 intestinal epithelial cells

PubMed Central

Chaturvedi, Lakshmi S.; Marsh, Harold M.

2011-01-01

Repetitive deformation enhances intestinal epithelial migration across tissue fibronectin. We evaluated the contribution of RhoA and its effectors Rho-associated kinase (ROK/ROCK) and mammalian diaphanous formins (mDia1) to deformation-induced intestinal epithelial motility across fibronectin and the responsible focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), p38, and myosin light chain (MLC) signaling. We reduced RhoA, ROCK1, ROCK2, and mDia1 by smart-pool double-stranded short-interfering RNAs (siRNA) and pharmacologically inhibited RhoA, ROCK, and FAK in human Caco-2 intestinal epithelial monolayers on fibronectin-coated membranes subjected to 10% repetitive deformation at 10 cycles/min. Migration was measured by wound closure. Stimulation of migration by deformation was prevented by exoenzyme C3, Y27632, or selective RhoA, ROCK1, and ROCK2 or mDia1 siRNAs. RhoA, ROCK inhibition, or RhoA, ROCK1, ROCK2, mDia1, and FAK reduction by siRNA blocked deformation-induced nuclear ERK phosphorylation without preventing ERK phosphorylation in the cytoplasmic protein fraction. Furthermore, RhoA, ROCK inhibition or RhoA, ROCK1, ROCK2, and mDia1 reduction by siRNA also blocked strain-induced FAK-Tyr925, p38, and MLC phosphorylation. These results suggest that RhoA, ROCK, mDia1, FAK, ERK, p38, and MLC all mediate the stimulation of intestinal epithelial migration by repetitive deformation. This pathway may be an important target for interventions to promote mechanotransduced mucosal healing during inflammation. PMID:21849669

Determination of the optimal tolerance for MLC positioning in sliding window and VMAT techniques

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

Hernandez, V., E-mail: vhernandezmasgrau@gmail.com; Abella, R.; Calvo, J. F.

2015-04-15

Purpose: Several authors have recommended a 2 mm tolerance for multileaf collimator (MLC) positioning in sliding window treatments. In volumetric modulated arc therapy (VMAT) treatments, however, the optimal tolerance for MLC positioning remains unknown. In this paper, the authors present the results of a multicenter study to determine the optimal tolerance for both techniques. Methods: The procedure used is based on dynalog file analysis. The study was carried out using seven Varian linear accelerators from five different centers. Dynalogs were collected from over 100 000 clinical treatments and in-house software was used to compute the number of tolerance faults as amore » function of the user-defined tolerance. Thus, the optimal value for this tolerance, defined as the lowest achievable value, was investigated. Results: Dynalog files accurately predict the number of tolerance faults as a function of the tolerance value, especially for low fault incidences. All MLCs behaved similarly and the Millennium120 and the HD120 models yielded comparable results. In sliding window techniques, the number of beams with an incidence of hold-offs >1% rapidly decreases for a tolerance of 1.5 mm. In VMAT techniques, the number of tolerance faults sharply drops for tolerances around 2 mm. For a tolerance of 2.5 mm, less than 0.1% of the VMAT arcs presented tolerance faults. Conclusions: Dynalog analysis provides a feasible method for investigating the optimal tolerance for MLC positioning in dynamic fields. In sliding window treatments, the tolerance of 2 mm was found to be adequate, although it can be reduced to 1.5 mm. In VMAT treatments, the typically used 5 mm tolerance is excessively high. Instead, a tolerance of 2.5 mm is recommended.« less

SU-F-T-530: Characterization of a 60-Leaf Motorized MLC Designed for Cobalt-60 Units

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

Xu, L; Smith, L; Ciresianu, A

2016-06-15

Purpose: In a continuing effort to improve conformal radiation therapy with Cobalt-60 units, a 60-leaf MLC was designed, manufactured, and released to market. This work describes the physics measurements taken to characterize the clinical performance of this MLC. Methods: A 60 leaf MLC was custom designed with tungsten leaves of 4.5 cm height, single focused, achieving field size of 30×30 cm^2 when mounted on a 100cm SAD Cobalt-60 unit. Leakage and output factor measurements were performed using a single ion chamber in a solid water phantom. Penumbra and surface dose were measured using scanning chambers and diodes in a watermore » phantom. Radiation-light coincidence measurements were performed using radiographic films. Results: With MLC mounted, measured penumbras at all depths are smaller than with jaws only. Surface doses were not significantly affected by the presence of MLC, and remained below values recommended by regulatory bodies. Light-radiation coincidences were found to be better than 3 mm for all field sizes. Leakage through the MLC was found to be strongly dependent on field size, increasing from 1.0 % for a 10×10 cm field to 2.0% for a 30×30 cm field. Such results meet the requirements of IEC 60601-2-11. The MLC was found to have significant influence on the output factor, when field size defined by MLC is significantly smaller than field size defined by jaws. Such effect is also observed on linear accelerators, but it is more pronounced on Cobalt-60 units. A 10×10 “diamond” MLC shape inside a 14×14 cm jaw showed output factor that is 5.7% higher than 10×10 cm field defined by matching MLC and jaws. Conclusion: The MLC offers clinically acceptable performance in penumbra, surface dose, and light-radiation coincidence. Several units of this MLC have recently been installed and used clinically. Validation of Cobalt-60 based IMRT with this MLC is ongoing. The authors are employees of Best Theratrnics Ltd.« less

Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction

NASA Astrophysics Data System (ADS)

Hoegg-Beiler, Maja B.; Sirisi, Sònia; Orozco, Ian J.; Ferrer, Isidre; Hohensee, Svea; Auberson, Muriel; Gödde, Kathrin; Vilches, Clara; de Heredia, Miguel López; Nunes, Virginia; Estévez, Raúl; Jentsch, Thomas J.

2014-03-01

Defects in the astrocytic membrane protein MLC1, the adhesion molecule GlialCAM or the chloride channel ClC-2 underlie human leukoencephalopathies. Whereas GlialCAM binds ClC-2 and MLC1, and modifies ClC-2 currents in vitro, no functional connections between MLC1 and ClC-2 are known. Here we investigate this by generating loss-of-function Glialcam and Mlc1 mouse models manifesting myelin vacuolization. We find that ClC-2 is unnecessary for MLC1 and GlialCAM localization in brain, whereas GlialCAM is important for targeting MLC1 and ClC-2 to specialized glial domains in vivo and for modifying ClC-2’s biophysical properties specifically in oligodendrocytes (OLs), the cells chiefly affected by vacuolization. Unexpectedly, MLC1 is crucial for proper localization of GlialCAM and ClC-2, and for changing ClC-2 currents. Our data unmask an unforeseen functional relationship between MLC1 and ClC-2 in vivo, which is probably mediated by GlialCAM, and suggest that ClC-2 participates in the pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts.

Experimental pencil beam kernels derivation for 3D dose calculation in flattening filter free modulated fields

NASA Astrophysics Data System (ADS)

Diego Azcona, Juan; Barbés, Benigno; Wang, Lilie; Burguete, Javier

2016-01-01

This paper presents a method to obtain the pencil-beam kernels that characterize a megavoltage photon beam generated in a flattening filter free (FFF) linear accelerator (linac) by deconvolution from experimental measurements at different depths. The formalism is applied to perform independent dose calculations in modulated fields. In our previous work a formalism was developed for ideal flat fluences exiting the linac’s head. That framework could not deal with spatially varying energy fluences, so any deviation from the ideal flat fluence was treated as a perturbation. The present work addresses the necessity of implementing an exact analysis where any spatially varying fluence can be used such as those encountered in FFF beams. A major improvement introduced here is to handle the actual fluence in the deconvolution procedure. We studied the uncertainties associated to the kernel derivation with this method. Several Kodak EDR2 radiographic films were irradiated with a 10 MV FFF photon beam from two linacs from different vendors, at the depths of 5, 10, 15, and 20cm in polystyrene (RW3 water-equivalent phantom, PTW Freiburg, Germany). The irradiation field was a 50mm diameter circular field, collimated with a lead block. The 3D kernel for a FFF beam was obtained by deconvolution using the Hankel transform. A correction on the low dose part of the kernel was performed to reproduce accurately the experimental output factors. Error uncertainty in the kernel derivation procedure was estimated to be within 0.2%. Eighteen modulated fields used clinically in different treatment localizations were irradiated at four measurement depths (total of fifty-four film measurements). Comparison through the gamma-index to their corresponding calculated absolute dose distributions showed a number of passing points (3%, 3mm) mostly above 99%. This new procedure is more reliable and robust than the previous one. Its ability to perform accurate independent dose calculations was demonstrated.

Planning and delivery of four-dimensional radiation therapy with multileaf collimators

NASA Astrophysics Data System (ADS)

McMahon, Ryan L.

This study is an investigation of the application of multileaf collimators (MLCs) to the treatment of moving anatomy with external beam radiation therapy. First, a method for delivering intensity modulated radiation therapy (IMRT) to moving tumors is presented. This method uses an MLC control algorithm that calculates appropriate MLC leaf speeds in response to feedback from real-time imaging. The algorithm does not require a priori knowledge of a tumor's motion, and is based on the concept of self-correcting DMLC leaf trajectories . This gives the algorithm the distinct advantage of allowing for correction of DMLC delivery errors without interrupting delivery. The algorithm is first tested for the case of one-dimensional (1D) rigid tumor motion in the beam's eye view (BEV). For this type of motion, it is shown that the real-time tracking algorithm results in more accurate deliveries, with respect to delivered intensity, than those which ignore motion altogether. This is followed by an appropriate extension of the algorithm to two-dimensional (2D) rigid motion in the BEV. For this type of motion, it is shown that the 2D real-time tracking algorithm results in improved accuracy (in the delivered intensity) in comparison to deliveries which ignore tumor motion or only account for tumor motion which is aligned with MLC leaf travel. Finally, a method is presented for designing DMLC leaf trajectories which deliver a specified intensity over a moving tumor without overexposing critical structures which exhibit motion patterns that differ from that of the tumor. In addition to avoiding overexposure of critical organs, the method can, in the case shown, produce deliveries that are superior to anything achievable using stationary anatomy. In this regard, the method represents a systematic way to include anatomical motion as a degree of freedom in the optimization of IMRT while producing treatment plans that are deliverable with currently available technology. These results, combined with those related to the real-time MLC tracking algorithm, show that an MLC is a promising tool to investigate for the delivery of four-dimensional radiation therapy.

Multileaf collimator tracking integrated with a novel x-ray imaging system and external surrogate monitoring

NASA Astrophysics Data System (ADS)

Krauss, Andreas; Fast, Martin F.; Nill, Simeon; Oelfke, Uwe

2012-04-01

We have previously developed a tumour tracking system, which adapts the aperture of a Siemens 160 MLC to electromagnetically monitored target motion. In this study, we exploit the use of a novel linac-mounted kilovoltage x-ray imaging system for MLC tracking. The unique in-line geometry of the imaging system allows the detection of target motion perpendicular to the treatment beam (i.e. the directions usually featuring steep dose gradients). We utilized the imaging system either alone or in combination with an external surrogate monitoring system. We equipped a Siemens ARTISTE linac with two flat panel detectors, one directly underneath the linac head for motion monitoring and the other underneath the patient couch for geometric tracking accuracy assessments. A programmable phantom with an embedded metal marker reproduced three patient breathing traces. For MLC tracking based on x-ray imaging alone, marker position was detected at a frame rate of 7.1 Hz. For the combined external and internal motion monitoring system, a total of only 85 x-ray images were acquired prior to or in between the delivery of ten segments of an IMRT beam. External motion was monitored with a potentiometer. A correlation model between external and internal motion was established. The real-time component of the MLC tracking procedure then relied solely on the correlation model estimations of internal motion based on the external signal. Geometric tracking accuracies were 0.6 mm (1.1 mm) and 1.8 mm (1.6 mm) in directions perpendicular and parallel to the leaf travel direction for the x-ray-only (the combined external and internal) motion monitoring system in spite of a total system latency of ˜0.62 s (˜0.51 s). Dosimetric accuracy for a highly modulated IMRT beam-assessed through radiographic film dosimetry-improved substantially when tracking was applied, but depended strongly on the respective geometric tracking accuracy. In conclusion, we have for the first time integrated MLC tracking with x-ray imaging in the in-line geometry and demonstrated highly accurate respiratory motion tracking.

Inhibiting Myosin Light Chain Kinase Induces Apoptosis In Vitro and In Vivo

PubMed Central

Fazal, Fabeha; Gu, Lianzhi; Ihnatovych, Ivanna; Han, YooJeong; Hu, WenYang; Antic, Nenad; Carreira, Fernando; Blomquist, James F.; Hope, Thomas J.; Ucker, David S.; de Lanerolle, Primal

2005-01-01

Previous short-term studies have correlated an increase in the phosphorylation of the 20-kDa light chain of myosin II (MLC20) with blebbing in apoptotic cells. We have found that this increase in MLC20 phosphorylation is rapidly followed by MLC20 dephosphorylation when cells are stimulated with various apoptotic agents. MLC20 dephosphorylation is not a consequence of apoptosis because MLC20 dephosphorylation precedes caspase activation when cells are stimulated with a proapoptotic agent or when myosin light chain kinase (MLCK) is inhibited pharmacologically or by microinjecting an inhibitory antibody to MLCK. Moreover, blocking caspase activation increased cell survival when MLCK is inhibited or when cells are treated with tumor necrosis factor alpha. Depolymerizing actin filaments or detaching cells, processes that destabilize the cytoskeleton, or inhibiting myosin ATPase activity also resulted in MLC20 dephosphorylation and cell death. In vivo experiments showed that inhibiting MLCK increased the number of apoptotic cells and retarded the growth of mammary cancer cells in mice. Thus, MLC20 dephosphorylation occurs during physiological cell death and prolonged MLC20 dephosphorylation can trigger apoptosis. PMID:15988034

Myosin‑II heavy chain and formin mediate the targeting of myosin essential light chain to the division site before and during cytokinesis

PubMed Central

Feng, Zhonghui; Okada, Satoshi; Cai, Guoping; Zhou, Bing; Bi, Erfei

2015-01-01

MLC1 is a haploinsufficient gene encoding the essential light chain for Myo1, the sole myosin‑II heavy chain in the budding yeast Saccharomyces cerevisiae. Mlc1 defines an essential hub that coordinates actomyosin ring function, membrane trafficking, and septum formation during cytokinesis by binding to IQGAP, myosin‑II, and myosin‑V. However, the mechanism of how Mlc1 is targeted to the division site during the cell cycle remains unsolved. By constructing a GFP‑tagged MLC1 under its own promoter control and using quantitative live‑cell imaging coupled with yeast mutants, we found that septin ring and actin filaments mediate the targeting of Mlc1 to the division site before and during cytokinesis, respectively. Both mechanisms contribute to and are collectively required for the accumulation of Mlc1 at the division site during cytokinesis. We also found that Myo1 plays a major role in the septin‑dependent Mlc1 localization before cytokinesis, whereas the formin Bni1 plays a major role in the actin filament–dependent Mlc1 localization during cytokinesis. Such a two‑tiered mechanism for Mlc1 localization is presumably required for the ordered assembly and robustness of cytokinesis machinery and is likely conserved across species. PMID:25631819

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

Han, S; Ji, Y; Kim, K

Purpose: A diagnostics Multileaf Collimator (MLC) was designed for diagnostic radiography dose reduction. Monte Carlo simulation was used to evaluate efficiency of shielding material for producing leaves of Multileaf collimator. Material & Methods: The general radiography unit (Rex-650R, Listem, Korea) was modeling with Monte Carlo simulation (MCNPX, LANL, USA) and we used SRS-78 program to calculate the energy spectrum of tube voltage (80, 100, 120 kVp). The shielding materials was SKD 11 alloy tool steel that is composed of 1.6% carbon(C), 0.4% silicon (Si), 0.6% manganese (Mn), 5% chromium (Cr), 1% molybdenum (Mo), and vanadium (V). The density of itmore » was 7.89 g/m3. We simulated leafs diagnostic MLC using SKD 11 with general radiography unit. We calculated efficiency of diagnostic MLC using tally6 card of MCNPX depending on energy. Results: The diagnostic MLC consisted of 25 individual metal shielding leaves on both sides, with dimensions of 10 × 0.5 × 0.5 cm3. The leaves of MLC were controlled by motors positioned on both sides of the MLC. According to energy (tube voltage), the shielding efficiency of MLC in Monte Carlo simulation was 99% (80 kVp), 96% (100 kVp) and 93% (120 kVp). Conclusion: We certified efficiency of diagnostic MLC fabricated from SKD11 alloy tool steel. Based on the results, the diagnostic MLC was designed. We will make the diagnostic MLC for dose reduction of diagnostic radiography.« less

Embryonic essential myosin light chain regulates fetal lung development in rats.

PubMed

Santos, Marta; Moura, Rute S; Gonzaga, Sílvia; Nogueira-Silva, Cristina; Ohlmeier, Steffen; Correia-Pinto, Jorge

2007-09-01

Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.

Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle.

PubMed

Dimopoulos, George J; Semba, Shingo; Kitazawa, Kazuyo; Eto, Masumi; Kitazawa, Toshio

2007-01-05

Ca(2+) ion is a universal intracellular messenger that regulates numerous biological functions. In smooth muscle, Ca(2+) with calmodulin activates myosin light chain (MLC) kinase to initiate a rapid MLC phosphorylation and contraction. To test the hypothesis that regulation of MLC phosphatase is involved in the rapid development of MLC phosphorylation and contraction during Ca(2+) transient, we compared Ca(2+) signal, MLC phosphorylation, and 2 modes of inhibition of MLC phosphatase, phosphorylation of CPI-17 Thr38 and MYPT1 Thr853, during alpha(1) agonist-induced contraction with/without various inhibitors in intact rabbit femoral artery. Phenylephrine rapidly induced CPI-17 phosphorylation from a negligible amount to a peak value of 0.38+/-0.04 mol of Pi/mol within 7 seconds following stimulation, similar to the rapid time course of Ca(2+) rise and MLC phosphorylation. This rapid CPI-17 phosphorylation was dramatically inhibited by either blocking Ca(2+) release from the sarcoplasmic reticulum or by pretreatment with protein kinase C inhibitors, suggesting an involvement of Ca(2+)-dependent protein kinase C. This was followed by a slow Ca(2+)-independent and Rho-kinase/protein kinase C-dependent phosphorylation of CPI-17. In contrast, MYPT1 phosphorylation had only a slow component that increased from 0.29+/-0.09 at rest to the peak of 0.68+/-0.14 mol of Pi/mol at 1 minute, similar to the time course of contraction. Thus, there are 2 components of the Ca(2+) sensitization through inhibition of MLC phosphatase. Our results support the hypothesis that the initial rapid Ca(2+) rise induces a rapid inhibition of MLC phosphatase coincident with the Ca(2+)-induced MLC kinase activation to synergistically initiate a rapid MLC phosphorylation and contraction in arteries with abundant CPI-17 content.

Underestimation of Low-Dose Radiation in Treatment Planning of Intensity-Modulated Radiotherapy

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

Jang, Si Young; Liu, H. Helen; Mohan, Radhe

2008-08-01

Purpose: To investigate potential dose calculation errors in the low-dose regions and identify causes of such errors for intensity-modulated radiotherapy (IMRT). Methods and Materials: The IMRT treatment plans of 23 patients with lung cancer and mesothelioma were reviewed. Of these patients, 15 had severe pulmonary complications after radiotherapy. Two commercial treatment-planning systems (TPSs) and a Monte Carlo system were used to calculate and compare dose distributions and dose-volume parameters of the target volumes and critical structures. The effect of tissue heterogeneity, multileaf collimator (MLC) modeling, beam modeling, and other factors that could contribute to the differences in IMRT dose calculationsmore » were analyzed. Results: In the commercial TPS-generated IMRT plans, dose calculation errors primarily occurred in the low-dose regions of IMRT plans (<50% of the radiation dose prescribed for the tumor). Although errors in the dose-volume histograms of the normal lung were small (<5%) above 10 Gy, underestimation of dose <10 Gy was found to be up to 25% in patients with mesothelioma or large target volumes. These errors were found to be caused by inadequate modeling of MLC transmission and leaf scatter in commercial TPSs. The degree of low-dose errors depends on the target volumes and the degree of intensity modulation. Conclusions: Secondary radiation from MLCs contributes a significant portion of low dose in IMRT plans. Dose underestimation could occur in conventional IMRT dose calculations if such low-dose radiation is not properly accounted for.« less

Application of fluence field modulation to proton computed tomography for proton therapy imaging.

PubMed

Dedes, G; De Angelis, L; Rit, S; Hansen, D; Belka, C; Bashkirov, V; Johnson, R P; Coutrakon, G; Schubert, K E; Schulte, R W; Parodi, K; Landry, G

2017-07-12

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than  -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

MLC-based penumbra softener of EDW borders to reduce junction inhomogeneities.

PubMed

Szpala, Stanislaw; Kohli, Kirpal

2017-05-01

Junctions of fields are known to be susceptible to developing cold or hot spots in the presence of even small geometrical misalignments. Reduction of these dose inhomogeneities can be accomplished through decreasing the dose gradients in the penumbra, but currently it cannot be done for enhanced dynamic wedges (EDW). An MLC-based penumbra softener was developed in the developer mode of TrueBeam linacs to reduce dose gradients across the side border of EDWs. The movement of each leaf was individually synchronized with the movement of the dynamic Y jaw to soften the penumbra in the same manner along the entire field border, in spite of the presence of the dose gradient of the EDW. Junction homogeneity upon field misalignment for side-matched EDWs was examined with the MV imager. The fluence inhomogeneities were reduced from about 30% per mm of shift of the field borders for the conventional EDW to about 2% per mm for the softened-penumbra plan. The junction in a four-field monoisocentric breast plan delivered to the Rando phantom was assessed with film. The dose inhomogeneities across the junction in the superior-inferior direction were reduced from about 20% to 25% per mm for the conventional fields to about 5% per mm. The dose near the softened junction of the breast plan with no shifts did not deviate from the conventional plan by more than about 4%. The newly-developed softened-penumbra junction of EDW (and/or open) fields was shown to reduce sensitivity to misalignments without increasing complexity of the planning or delivery. This methodology needs to be adopted by the manufacturers for clinical use. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

A quantitative method to the analysis of MLC leaf position and speed based on EPID and EBT3 film for dynamic IMRT treatment with different types of MLC.

PubMed

Li, Yinghui; Chen, Lixin; Zhu, Jinhan; Wang, Bin; Liu, Xiaowei

2017-07-01

A quantitative method based on the electronic portal imaging system (EPID) and film was developed for MLC position and speed testing; this method was used for three MLC types (Millennium, MLCi, and Agility MLC). To determine the leaf position, a picket fence designed by the dynamic (DMLC) model was used. The full-width half-maximum (FWHM) values of each gap measured by EPID and EBT3 were converted to the gap width using the FWHM versus nominal gap width relationship. The algorithm developed for the picket fence analysis was able to quantify the gap width, the distance between gaps, and each individual leaf position. To determine the leaf speed, a 0.5 × 20 cm 2 MLC-defined sliding gap was applied across a 14 × 20 cm 2 symmetry field. The linacs ran at a fixed-dose rate. The use of different monitor units (MUs) for this test led to different leaf speeds. The effect of leaf transmission was considered in a speed accuracy analysis. The difference between the EPID and film results for the MLC position is less than 0.1 mm. For the three MLC types, twice the standard deviation (2 SD) is provided; 0.2, 0.4, and 0.4 mm for gap widths of three MLC types, and 0.1, 0.2, and 0.2 mm for distances between gaps. The individual leaf positions deviate from the preset positions within 0.1 mm. The variations in the speed profiles for the EPID and EBT3 results are consistent, but the EPID results are slightly better than the film results. Different speeds were measured for each MLC type. For all three MLC types, speed errors increase with increasing speed. The analysis speeds deviate from the preset speeds within approximately 0.01 cm s -1 . This quantitative analysis of MLC position and speed provides an intuitive evaluation for MLC quality assurance (QA). © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

SU-E-T-331: Dosimetric Impact of Multileaf Collimator Leaf Width On Stereotactic Radiosurgery (SRS) RapidArc Treatment Plans for Single and Multiple Brain Metastases

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

Hossain, S; Keeling, V; Ahmad, S

Purpose: To determine the effects of multileaf collimator (MLC) leaf width on normal-brain-tissue doses and dose conformity of SRS RapidArc treatment plans for brain tumors. Methods: Ten patients with 24 intracranial tumors (seven with 1–2 and three with 4–6 lesions) were planned using RapidArc for both Varian Millennium 120 MLC (5 mm leaf width) and high definition (HD) MLC (2.5 mm leaf width). Between 2 and 8 arcs were used with two full coplanar arcs and the rest non-coplanar half arcs. 6 MV beams were used and plans were optimized with a high priority to the Normal Tissue Objective (tomore » achieve dose conformity and sharp dose fall-off) and normal brain tissue. Calculation was done using AAA on a 1 mm grid size. The prescription dose ranged from 14–22 Gy. Plans were normalized such that 99% of the target received the prescription dose. Identical beam geometries, optimizations, calculations, and normalizations were used for both plans. Paddick Conformity Index (PCI), V4, V8 and V12 Gy for normal brain tissue and Integral Dose were used for analysis. Results: In all cases, HD MLC plans performed better in sparing normal brain tissue, achieving a higher PCI with a lower Integral Dose. The average PCI for all 24 targets was 0.75±0.23 and 0.70±0.23 (p ≤0.0015) for HD MLC and Millennium MLC plans, respectively. The average ratio of normal brain doses for Millennium MLC to HD MLC plans was 1.30±0.16, 1.27±0.15, and 1.31±0.18 for the V4, V8, and V12, respectively. The differences in normal brain dose for all criteria were statistically significant with p-value < 0.02. On average Millennium MLC plans had a 16% higher integral dose than HD MLC plans. Conclusion: Significantly better dose conformity with reduced volume of normal brain tissue and integral dose was achieved with HD MLC plans compared to Millennium MLC plans.« less

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

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

Ahmed, S; Kakakhel, MB; Ahmed, SBS

2015-06-15

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

SU-G-BRA-14: Dose in a Rigidly Moving Phantom with Jaw and MLC Compensation

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

Chao, E; Lucas, D

Purpose: To validate dose calculation for a rigidly moving object with jaw motion and MLC shifts to compensate for the motion in a TomoTherapy™ treatment delivery. Methods: An off-line version of the TomoTherapy dose calculator was extended to perform dose calculations for rigidly moving objects. A variety of motion traces were added to treatment delivery plans, along with corresponding jaw compensation and MLC shift compensation profiles. Jaw compensation profiles were calculated by shifting the jaws such that the center of the treatment beam moved by an amount equal to the motion in the longitudinal direction. Similarly, MLC compensation profiles weremore » calculated by shifting the MLC leaves by an amount that most closely matched the motion in the transverse direction. The same jaw and MLC compensation profiles were used during simulated treatment deliveries on a TomoTherapy system, and film measurements were obtained in a rigidly moving phantom. Results: The off-line TomoTherapy dose calculator accurately predicted dose profiles for a rigidly moving phantom along with jaw motion and MLC shifts to compensate for the motion. Calculations matched film measurements to within 2%/1 mm. Jaw and MLC compensation substantially reduced the discrepancy between the delivered dose distribution and the calculated dose with no motion. For axial motion, the compensated dose matched the no-motion dose within 2%/1mm. For transverse motion, the dose matched within 2%/3mm (approximately half the width of an MLC leaf). Conclusion: The off-line TomoTherapy dose calculator accurately computes dose delivered to a rigidly moving object, and accurately models the impact of moving the jaws and shifting the MLC leaf patterns to compensate for the motion. Jaw tracking and MLC leaf shifting can effectively compensate for the dosimetric impact of motion during a TomoTherapy treatment delivery.« less

SU-F-T-650: The Comparison of Robotic Partial Breast Stereotactic Irradiation Using MLC Vs. Iris Cone

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

Ding, C; Timmerman, R; Jiang, S

Purpose: To evaluate the dosimetric impact on treatment planning for partial breast stereotactic irradiation using Cyberknife with MLC versus Iris Cone. Methods: Ten patients whom underwent lumpectomy for DCIS or stage I invasive non-lobular epithelial breast cancer were included in this study. All patients were previously treated on the Cyberknife using Iris cone with the prescription dose of 37.5Gy in 5 fractions covering at least 95% of PTV on our phase I SBRT 5 fraction partial breast irradiation trial. Retrospectively, treatment planning was performed and compared using the new Cyberknife M6 MLC system for each patient. Using the same contoursmore » and critical organ constraints for both MLC and Iris cone plans, the dose on target and critical organs were analyzed accordingly. Results: Dose to critical organs such as ipsilateral lung, contralateral lung, heart, skin, ipsilateral breast, and rib were analyzed, as well as conformity index and high dose spillage of the target area. In 9 of 10 patients, the MLC plans had less total ipsilateral breast volume encompassing the 50% prescription isodose (mean:22.3±8.2% MLC vs. 31.6±8.0 Iris, p=0.00014) .The MLC plans mean estimated treatment delivery time was significantly less than the Iris plans (51±3.9min vs. 56.2±9min, p=0.03) Both MLC and Iris cone plans were able to meet all dose constraints and there was no statistical difference between those dose constraints. Conclusion: Both MLC and Iris Cone can deliver conformal dose to a partial breast target and satisfy the dose constraints of critical organs. The new Cyberknife with MLC can deliver a more conformal dose in the lower dose region and spare more ipsilateral breast tissue to the 50% prescription isodose. The treatment time for partial breast SBRT plans was also reduced using MLC. Project receives research support from Accuray Inc.« less

Comparison of MLC error sensitivity of various commercial devices for VMAT pre-treatment quality assurance.

PubMed

Saito, Masahide; Sano, Naoki; Shibata, Yuki; Kuriyama, Kengo; Komiyama, Takafumi; Marino, Kan; Aoki, Shinichi; Ashizawa, Kazunari; Yoshizawa, Kazuya; Onishi, Hiroshi

2018-05-01

The purpose of this study was to compare the MLC error sensitivity of various measurement devices for VMAT pre-treatment quality assurance (QA). This study used four QA devices (Scandidos Delta4, PTW 2D-array, iRT systems IQM, and PTW Farmer chamber). Nine retrospective VMAT plans were used and nine MLC error plans were generated for all nine original VMAT plans. The IQM and Farmer chamber were evaluated using the cumulative signal difference between the baseline and error-induced measurements. In addition, to investigate the sensitivity of the Delta4 device and the 2D-array, global gamma analysis (1%/1, 2%/2, and 3%/3 mm), dose difference (1%, 2%, and 3%) were used between the baseline and error-induced measurements. Some deviations of the MLC error sensitivity for the evaluation metrics and MLC error ranges were observed. For the two ionization devices, the sensitivity of the IQM was significantly better than that of the Farmer chamber (P < 0.01) while both devices had good linearly correlation between the cumulative signal difference and the magnitude of MLC errors. The pass rates decreased as the magnitude of the MLC error increased for both Delta4 and 2D-array. However, the small MLC error for small aperture sizes, such as for lung SBRT, could not be detected using the loosest gamma criteria (3%/3 mm). Our results indicate that DD could be more useful than gamma analysis for daily MLC QA, and that a large-area ionization chamber has a greater advantage for detecting systematic MLC error because of the large sensitive volume, while the other devices could not detect this error for some cases with a small range of MLC error. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

SU-E-T-479: IMRT Plan Recalculation in Patient Based On Dynalog Data and the Effect of a Single Failing MLC Motor

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

Morcos, M; Mitrou, E

2015-06-15

Purpose: Using Linac dynamic logs (Dynalogs) we evaluate the impact of a single failing MLC motor on the deliverability of an IMRT plan by assessing the recalculated dose volume histograms (DVHs) taking the delivered MLC positions and beam hold-offs into consideration. Methods: This is a retrospective study based on a deteriorating MLC motor (leaf 36B) which was observed to be failing via Dynalog analysis. To investigate further, Eclipse-importable MLC files were generated from Dynalogs to recalculate the actual delivered dose and to assess the clinical impact through DVHs. All deliveries were performed on a Varian 21EX linear accelerator equipped withmore » Millennium-120 MLC. The analysis of Dynalog files and subsequent conversion to Eclipse-importable MLC files were all performed by in-house programming in Python. Effects on plan DVH are presented in the following section on a particular brain-IMRT plan which was delivered with a failing MLC motor which was then replaced. Results: Global max dose increased by 13.5%, max dose to the brainstem PRV increased by 8.2%, max dose to the optic chiasm increased by 7.6%, max dose to optic nerve increased by 8.8% and the mean dose to the PTV increased by 7.9% when comparing the original plan to the fraction with the failing MLC motor. The reason the dose increased was due to the failure being on the B-bank which is the lagging side on a sliding window delivery, therefore any failures on this side will cause an over-irradiation as the B-bank leaves struggles to keep the window from growing. Conclusion: Our findings suggest that a single failing MLC motor may jeopardize the entire delivery. This may be due to the bad MLC motor drawing too much current causing all MLCs on the same bank to underperform. This hypothesis will be investigated in a future study.« less

SU-E-T-646: Quality Assurance of Truebeam Multi-Leaf Collimator Using a MLC QA Phantom

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

Zhang, J; Lu, J; Hong, D

2015-06-15

Purpose: To perform a routine quality assurance procedure for Truebeam multi-leaf collimator (MLC) using MLC QA phantom, verify the stability and reliability of MLC during the treatment. Methods: MLC QA phantom is a specialized phantom for MLC quality assurance (QA), and contains five radio-opaque spheres that are embedded in an “L” shape. The phantom was placed isocentrically on the Truebeam treatment couch for the tests. A quality assurance plan was setted up in the Eclipse v10.0, the fields that need to be delivered in order to acquire the necessary images, the MLC shapes can then be obtained by the images.more » The images acquired by the electronic portal imaging device (EPID), and imported into the PIPSpro software for the analysis. The tests were delivered twelve weeks (once a week) to verify consistency of the delivery, and the images are acquired in the same manner each time. Results: For the Leaf position test, the average position error was 0.23mm±0.02mm (range: 0.18mm∼0.25mm). The Leaf width was measured at the isocenter, the average error was 0.06mm±0.02mm (range: 0.02mm∼0.08mm) for the Leaf width test. Multi-Port test showed the dynamic leaf shift error, the average error was 0.28mm±0.03mm (range: 0.2mm∼0.35mm). For the leaf transmission test, the average inter-leaf leakage value was 1.0%±0.17% (range: 0.8%∼1.3%) and the average inter-bank leakage value was 32.6%±2.1% (range: 30.2%∼36.1%). Conclusion: By the test of 12 weeks, the MLC system of the Truebeam is running in a good condition and the MLC system can be steadily and reliably carried out during the treatment. The MLC QA phantom is a useful test tool for the MLC QA.« less

SU-E-T-501: Initial Orthovoltage Beam Profile Analysis of a Small Brass MLC

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

Loughery, B; Snyder, M

2015-06-15

Purpose To create brass leaves for an orthovoltage MLC and take initial beam profile measurements. Methods The low-energy MLC was designed in previous work. Brass was chosen for its self-lubrication and low cost. Stock brass rectangles (30cm × 1.0cm × 0.5cm) were ordered with pre-cut gear rack along the topmost long edges. Leaf designs were translated into G-code, then cut with a Tormach CNC-1100 mill. Intense bowing was observed in the beam direction, which required straightening via an in-house jig. Straightened leaves were placed into MLC assembly and mounted to a 320 kVp orthovoltage tube. EDR2 film was irradiated inmore » four situations: MLC open so one edge was isocentric, and MLC open more than isocentric, completely closed MLC, and an open field shot with the MLC removed. The first two scans tested penumbra for our rectangular edges due to unfocused design. The final two scans tested transmission and interleaf leakage. All four experiments were set to 120 kVp and 10 mA for two minutes. Results Transmission and interleaf leakage were found to be zero. Interleaf leakage is faintly visible on film, but undetected by our film scanner despite high spatial resolution. Penumbra at isocenter was found to be 0.72mm, which matched the penumbras of true field edges. Penumbra off-isocenter was 1.1mm. Mechanically, leaves are moving smoothly once straightened. Conclusion Beam profiles through our brass MLC are acceptable. Leaves attenuate and move as designed. Looking forward, we intend to animate our MLC to deliver more complicated treatment plans.« less

Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

PubMed Central

Al-Shboul, Othman A.; Al-Dwairi, Ahmed N.; Alqudah, Mohammad A.; Mustafa, Ayman G.

2018-01-01

Evidence of sex-related differences in gastrointestinal (GI) functions has been reported in the literature. In addition, various GI disorders have disproportionate prevalence between the sexes. An essential step in the initiation of smooth muscle contraction is the phosphorylation of the 20-kDa regulatory myosin light chain (MLC20) by the Ca2+/calmodulin-dependent myosin light chain kinase (MLCK). However, whether male stomach smooth muscle inherits different contractile signaling mechanisms for the regulation of MLC20 phosphorylation from that in females has not been established. The present study was designed to investigate sex-associated differences in the regulation of MLC20 phosphorylation and thus muscle contraction in gastric smooth muscle cells (GSMCs). Experiments were performed on GSMCs freshly isolated from male and female rats. Contraction of the GSMCs in response to acetylcholine (ACh), a muscarinic agonist, was measured via scanning micrometry in the presence or absence of the MLCK inhibitor, ML-7. Additionally, the protein levels of MLC20, MLCK and phosphorylated MLC20 were measured by ELISA. The protein levels of MLC20 and MLCK were indifferent between the sexes. ACh induced greater contraction (P<0.05) as well as greater MLC20 phosphorylation (P<0.05) in male GSMCs compared with female. Pretreatment of GSMCs with ML-7 significantly reduced the ACh-induced contraction (P<0.05) and MLC20 phosphorylation (P<0.05) in the male and female cells, and notably, abolished the contractile differences between the sexes. In conclusion, MLC20 phosphorylation and thus muscle contraction may be activated to a greater extent in male rat stomach compared with that in females. PMID:29599980

MO-FG-202-01: A Fast Yet Sensitive EPID-Based Real-Time Treatment Verification System

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

Ahmad, M; Nourzadeh, H; Neal, B

2016-06-15

Purpose: To create a real-time EPID-based treatment verification system which robustly detects treatment delivery and patient attenuation variations. Methods: Treatment plan DICOM files sent to the record-and-verify system are captured and utilized to predict EPID images for each planned control point using a modified GPU-based digitally reconstructed radiograph algorithm which accounts for the patient attenuation, source energy fluence, source size effects, and MLC attenuation. The DICOM and predicted images are utilized by our C++ treatment verification software which compares EPID acquired 1024×768 resolution frames acquired at ∼8.5hz from Varian Truebeam™ system. To maximize detection sensitivity, image comparisons determine (1) ifmore » radiation exists outside of the desired treatment field; (2) if radiation is lacking inside the treatment field; (3) if translations, rotations, and magnifications of the image are within tolerance. Acquisition was tested with known test fields and prior patient fields. Error detection was tested in real-time and utilizing images acquired during treatment with another system. Results: The computational time of the prediction algorithms, for a patient plan with 350 control points and 60×60×42cm^3 CT volume, is 2–3minutes on CPU and <27 seconds on GPU for 1024×768 images. The verification software requires a maximum of ∼9ms and ∼19ms for 512×384 and 1024×768 resolution images, respectively, to perform image analysis and dosimetric validations. Typical variations in geometric parameters between reference and the measured images are 0.32°for gantry rotation, 1.006 for scaling factor, and 0.67mm for translation. For excess out-of-field/missing in-field fluence, with masks extending 1mm (at isocenter) from the detected aperture edge, the average total in-field area missing EPID fluence was 1.5mm2 the out-of-field excess EPID fluence was 8mm^2, both below error tolerances. Conclusion: A real-time verification software, with EPID images prediction algorithm, was developed. The system is capable of performing verifications between frames acquisitions and identifying source(s) of any out-of-tolerance variations. This work was supported in part by Varian Medical Systems.« less

Catching errors with patient-specific pretreatment machine log file analysis.

PubMed

Rangaraj, Dharanipathy; Zhu, Mingyao; Yang, Deshan; Palaniswaamy, Geethpriya; Yaddanapudi, Sridhar; Wooten, Omar H; Brame, Scott; Mutic, Sasa

2013-01-01

A robust, efficient, and reliable quality assurance (QA) process is highly desired for modern external beam radiation therapy treatments. Here, we report the results of a semiautomatic, pretreatment, patient-specific QA process based on dynamic machine log file analysis clinically implemented for intensity modulated radiation therapy (IMRT) treatments delivered by high energy linear accelerators (Varian 2100/2300 EX, Trilogy, iX-D, Varian Medical Systems Inc, Palo Alto, CA). The multileaf collimator machine (MLC) log files are called Dynalog by Varian. Using an in-house developed computer program called "Dynalog QA," we automatically compare the beam delivery parameters in the log files that are generated during pretreatment point dose verification measurements, with the treatment plan to determine any discrepancies in IMRT deliveries. Fluence maps are constructed and compared between the delivered and planned beams. Since clinical introduction in June 2009, 912 machine log file analyses QA were performed by the end of 2010. Among these, 14 errors causing dosimetric deviation were detected and required further investigation and intervention. These errors were the result of human operating mistakes, flawed treatment planning, and data modification during plan file transfer. Minor errors were also reported in 174 other log file analyses, some of which stemmed from false positives and unreliable results; the origins of these are discussed herein. It has been demonstrated that the machine log file analysis is a robust, efficient, and reliable QA process capable of detecting errors originating from human mistakes, flawed planning, and data transfer problems. The possibility of detecting these errors is low using point and planar dosimetric measurements. Copyright © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

PubMed

Andruchov, Oleg; Galler, Stefan

2008-03-01

This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

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

Persson, Mats, E-mail: mats.persson@mi.physics.kth

Purpose: The highest photon fluence rate that a computed tomography (CT) detector must be able to measure is an important parameter. The authors calculate the maximum transmitted fluence rate in a commercial CT scanner as a function of patient size for standard head, chest, and abdomen protocols. Methods: The authors scanned an anthropomorphic phantom (Kyoto Kagaku PBU-60) with the reference CT protocols provided by AAPM on a GE LightSpeed VCT scanner and noted the tube current applied with the tube current modulation (TCM) system. By rescaling this tube current using published measurements on the tube current modulation of a GEmore » scanner [N. Keat, “CT scanner automatic exposure control systems,” MHRA Evaluation Report 05016, ImPACT, London, UK, 2005], the authors could estimate the tube current that these protocols would have resulted in for other patient sizes. An ECG gated chest protocol was also simulated. Using measured dose rate profiles along the bowtie filters, the authors simulated imaging of anonymized patient images with a range of sizes on a GE VCT scanner and calculated the maximum transmitted fluence rate. In addition, the 99th and the 95th percentiles of the transmitted fluence rate distribution behind the patient are calculated and the effect of omitting projection lines passing just below the skin line is investigated. Results: The highest transmitted fluence rates on the detector for the AAPM reference protocols with centered patients are found for head images and for intermediate-sized chest images, both with a maximum of 3.4 ⋅ 10{sup 8} mm{sup −2} s{sup −1}, at 949 mm distance from the source. Miscentering the head by 50 mm downward increases the maximum transmitted fluence rate to 5.7 ⋅ 10{sup 8} mm{sup −2} s{sup −1}. The ECG gated chest protocol gives fluence rates up to 2.3 ⋅ 10{sup 8} − 3.6 ⋅ 10{sup 8} mm{sup −2} s{sup −1} depending on miscentering. Conclusions: The fluence rate on a CT detector reaches 3 ⋅ 10{sup 8} − 6 ⋅ 10{sup 8} mm{sup −2} s{sup −1} in standard imaging protocols, with the highest rates occurring for ECG gated chest and miscentered head scans. These results will be useful to developers of CT detectors, in particular photon counting detectors.« less

Monte Carlo simulated corrections for beam commissioning measurements with circular and MLC shaped fields on the CyberKnife M6 System: a study including diode, microchamber, point scintillator, and synthetic microdiamond detectors.

PubMed

Francescon, P; Kilby, W; Noll, J M; Masi, L; Satariano, N; Russo, S

2017-02-07

Monte Carlo simulation was used to calculate correction factors for output factor (OF), percentage depth-dose (PDD), and off-axis ratio (OAR) measurements with the CyberKnife M6 System. These include the first such data for the InCise MLC. Simulated detectors include diodes, air-filled microchambers, a synthetic microdiamond detector, and point scintillator. Individual perturbation factors were also evaluated. OF corrections show similar trends to previous studies. With a 5 mm fixed collimator the diode correction to convert a measured OF to the corresponding point dose ratio varies between  -6.1% and  -3.5% for the diode models evaluated, while in a 7.6 mm  ×  7.7 mm MLC field these are  -4.5% to  -1.8%. The corresponding microchamber corrections are  +9.9% to  +10.7% and  +3.5% to  +4.0%. The microdiamond corrections have a maximum of  -1.4% for the 7.5 mm and 10 mm collimators. The scintillator corrections are  <1% in all beams. Measured OF showed uncorrected inter-detector differences  >15%, reducing to  <3% after correction. PDD corrections at d  >  d max were  <2% for all detectors except IBA Razor where a maximum 4% correction was observed at 300 mm depth. OAR corrections were smaller inside the field than outside. At the beam edge microchamber OAR corrections were up to 15%, mainly caused by density perturbations, which blurs the measured penumbra. With larger beams and depths, PTW and IBA diode corrections outside the beam were up to 20% while the Edge detector needed smaller corrections although these did vary with orientation. These effects are most noticeable for large field size and depth, where they are dominated by fluence and stopping power perturbations. The microdiamond OAR corrections were  <3% outside the beam. This paper provides OF corrections that can be used for commissioning new CyberKnife M6 Systems and retrospectively checking estimated corrections used previously. We recommend the PDD and OAR corrections are used to guide detector selection and inform the evaluation of results rather than to explicitly correct measurements.

Monte Carlo simulated corrections for beam commissioning measurements with circular and MLC shaped fields on the CyberKnife M6 System: a study including diode, microchamber, point scintillator, and synthetic microdiamond detectors

NASA Astrophysics Data System (ADS)

Francescon, P.; Kilby, W.; Noll, J. M.; Masi, L.; Satariano, N.; Russo, S.

2017-02-01

Monte Carlo simulation was used to calculate correction factors for output factor (OF), percentage depth-dose (PDD), and off-axis ratio (OAR) measurements with the CyberKnife M6 System. These include the first such data for the InCise MLC. Simulated detectors include diodes, air-filled microchambers, a synthetic microdiamond detector, and point scintillator. Individual perturbation factors were also evaluated. OF corrections show similar trends to previous studies. With a 5 mm fixed collimator the diode correction to convert a measured OF to the corresponding point dose ratio varies between  -6.1% and  -3.5% for the diode models evaluated, while in a 7.6 mm  ×  7.7 mm MLC field these are  -4.5% to  -1.8%. The corresponding microchamber corrections are  +9.9% to  +10.7% and  +3.5% to  +4.0%. The microdiamond corrections have a maximum of  -1.4% for the 7.5 mm and 10 mm collimators. The scintillator corrections are  <1% in all beams. Measured OF showed uncorrected inter-detector differences  >15%, reducing to  <3% after correction. PDD corrections at d  >  d max were  <2% for all detectors except IBA Razor where a maximum 4% correction was observed at 300 mm depth. OAR corrections were smaller inside the field than outside. At the beam edge microchamber OAR corrections were up to 15%, mainly caused by density perturbations, which blurs the measured penumbra. With larger beams and depths, PTW and IBA diode corrections outside the beam were up to 20% while the Edge detector needed smaller corrections although these did vary with orientation. These effects are most noticeable for large field size and depth, where they are dominated by fluence and stopping power perturbations. The microdiamond OAR corrections were  <3% outside the beam. This paper provides OF corrections that can be used for commissioning new CyberKnife M6 Systems and retrospectively checking estimated corrections used previously. We recommend the PDD and OAR corrections are used to guide detector selection and inform the evaluation of results rather than to explicitly correct measurements.

Combining MLC and SVM Classifiers for Learning Based Decision Making: Analysis and Evaluations

PubMed Central

Zhang, Yi; Ren, Jinchang; Jiang, Jianmin

2015-01-01

Maximum likelihood classifier (MLC) and support vector machines (SVM) are two commonly used approaches in machine learning. MLC is based on Bayesian theory in estimating parameters of a probabilistic model, whilst SVM is an optimization based nonparametric method in this context. Recently, it is found that SVM in some cases is equivalent to MLC in probabilistically modeling the learning process. In this paper, MLC and SVM are combined in learning and classification, which helps to yield probabilistic output for SVM and facilitate soft decision making. In total four groups of data are used for evaluations, covering sonar, vehicle, breast cancer, and DNA sequences. The data samples are characterized in terms of Gaussian/non-Gaussian distributed and balanced/unbalanced samples which are then further used for performance assessment in comparing the SVM and the combined SVM-MLC classifier. Interesting results are reported to indicate how the combined classifier may work under various conditions. PMID:26089862

Combining MLC and SVM Classifiers for Learning Based Decision Making: Analysis and Evaluations.

PubMed

Zhang, Yi; Ren, Jinchang; Jiang, Jianmin

2015-01-01

Maximum likelihood classifier (MLC) and support vector machines (SVM) are two commonly used approaches in machine learning. MLC is based on Bayesian theory in estimating parameters of a probabilistic model, whilst SVM is an optimization based nonparametric method in this context. Recently, it is found that SVM in some cases is equivalent to MLC in probabilistically modeling the learning process. In this paper, MLC and SVM are combined in learning and classification, which helps to yield probabilistic output for SVM and facilitate soft decision making. In total four groups of data are used for evaluations, covering sonar, vehicle, breast cancer, and DNA sequences. The data samples are characterized in terms of Gaussian/non-Gaussian distributed and balanced/unbalanced samples which are then further used for performance assessment in comparing the SVM and the combined SVM-MLC classifier. Interesting results are reported to indicate how the combined classifier may work under various conditions.

Comparison of anatomy-based, fluence-based and aperture-based treatment planning approaches for VMAT

NASA Astrophysics Data System (ADS)

Rao, Min; Cao, Daliang; Chen, Fan; Ye, Jinsong; Mehta, Vivek; Wong, Tony; Shepard, David

2010-11-01

Volumetric modulated arc therapy (VMAT) has the potential to reduce treatment times while producing comparable or improved dose distributions relative to fixed-field intensity-modulated radiation therapy. In order to take full advantage of the VMAT delivery technique, one must select a robust inverse planning tool. The purpose of this study was to evaluate the effectiveness and efficiency of VMAT planning techniques of three categories: anatomy-based, fluence-based and aperture-based inverse planning. We have compared these techniques in terms of the plan quality, planning efficiency and delivery efficiency. Fourteen patients were selected for this study including six head-and-neck (HN) cases, and two cases each of prostate, pancreas, lung and partial brain. For each case, three VMAT plans were created. The first VMAT plan was generated based on the anatomical geometry. In the Elekta ERGO++ treatment planning system (TPS), segments were generated based on the beam's eye view (BEV) of the target and the organs at risk. The segment shapes were then exported to Pinnacle3 TPS followed by segment weight optimization and final dose calculation. The second VMAT plan was generated by converting optimized fluence maps (calculated by the Pinnacle3 TPS) into deliverable arcs using an in-house arc sequencer. The third VMAT plan was generated using the Pinnacle3 SmartArc IMRT module which is an aperture-based optimization method. All VMAT plans were delivered using an Elekta Synergy linear accelerator and the plan comparisons were made in terms of plan quality and delivery efficiency. The results show that for cases of little or modest complexity such as prostate, pancreas, lung and brain, the anatomy-based approach provides similar target coverage and critical structure sparing, but less conformal dose distributions as compared to the other two approaches. For more complex HN cases, the anatomy-based approach is not able to provide clinically acceptable VMAT plans while highly conformal dose distributions were obtained using both aperture-based and fluence-based inverse planning techniques. The aperture-based approach provides improved dose conformity than the fluence-based technique in complex cases.

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO4 crystals

NASA Astrophysics Data System (ADS)

Adams, T.; Adzic, P.; Ahuja, S.; Anderson, D.; Andrews, M. B.; Antropov, I.; Antunovic, Z.; Arcidiacono, R.; Arenton, M. W.; Argirò, S.; Askew, A.; Attikis, A.; Auffray, E.; Baccaro, S.; Baffioni, S.; Bailleux, D.; Baillon, P.; Barney, D.; Barone, L.; Bartoloni, A.; Bartosik, N.; Becheva, E.; Bein, S.; Silva, C. Beirāo Da Cruz E.; Bell, K. W.; Benaglia, A.; Bendavid, J.; Berry, D.; Besancon, M.; Betev, B.; Bialas, W.; Bianchini, L.; Biino, C.; Bitioukov, S.; Bornheim, A.; Brianza, L.; Brinkerhoff, A.; Brown, R. M.; Brummitt, A.; Busson, P.; Candelise, V.; Carrillo Montoya, C. A.; Cartiglia, N.; Cavallari, F.; Chang, Y. W.; Chen, K. F.; Chevenier, G.; Chipaux, R.; Clement, E.; Cockerill, D. J. A.; Corpe, L.; Couderc, F.; Courbon, B.; Cox, B.; Cucciati, G.; Cussans, D.; D'imperio, G.; Da Silva Di Calafiori, D. R.; Dafinei, I.; Daguin, J.; Daskalakis, G.; Tinoco Mendes, A. D.; De Guio, F.; Degano, A.; Dejardin, M.; Del Re, D.; Della Ricca, G.; Denegri, D.; Depasse, P.; Dev, N.; Deyrail, D.; Di Marco, E.; Diamond, B.; Diemoz, M.; Dissertori, G.; Dittmar, M.; Djambazov, L.; Doan, T. H.; Dobrzynski, L.; Dolgopolov, A.; Donegà, M.; Dordevic, M.; Dröge, M.; Durkin, T.; Dutta, D.; El Mamouni, H.; Elliott-Peisert, A.; Elmalis, E.; Fabbro, B.; Fasanella, G.; Faure, J.; Fay, J.; Fedorov, A.; Ferri, F.; Francis, B.; Frank, N.; Franzoni, G.; Funk, W.; Ganjour, S.; Gascon, S.; Gastal, M.; Geerebaert, Y.; Gelli, S.; Gerosa, R.; Ghezzi, A.; Giakoumopoulou, V. A.; Givernaud, A.; Gninenko, S.; Godinovic, N.; Goeckner-Wald, N.; Golubev, N.; Govoni, P.; Gras, P.; Guilloux, F.; Haller, C.; Hamel de Monchenault, G.; Hansen, M.; Hansen, P.; Hardenbrook, J.; Heath, H. F.; Hill, J.; Hirosky, R.; Hobson, P. R.; Holme, O.; Honma, A.; Hou, W.-S.; Hsiung, Y.; Iiyama, Y.; Ille, B.; Ingram, Q.; Jain, S.; Jarry, P.; Jessop, C.; Jovanovic, D.; Kachanov, V.; Kalafut, S.; Kao, K. Y.; Kellams, N.; Kesisoglou, S.; Khatiwada, A.; Konoplyannikov, A.; Konstantinov, D.; Korzhik, M.; Kovac, M.; Kubota, Y.; Kucher, I.; Kumar, A.; Kumar, A.; Kuo, C.; Kyberd, P.; Kyriakis, A.; Latyshev, G.; Lecoq, P.; Ledovskoy, A.; Lei, Y. J.; Lelas, D.; Lethuillier, M.; Li, H.; Lin, W.; Liu, Y. F.; Locci, E.; Longo, E.; Loukas, D.; Lu, R.-S.; Lucchini, M. T.; Lustermann, W.; Mackay, C. K.; Magniette, F.; Malcles, J.; Malhotra, S.; Mandjavidze, I.; Maravin, Y.; Margaroli, F.; Marinelli, N.; Marini, A. C.; Martelli, A.; Marzocchi, B.; Massironi, A.; Matveev, V.; Mechinsky, V.; Meng, F.; Meridiani, P.; Micheli, F.; Milosevic, J.; Mousa, J.; Musella, P.; Nessi-Tedaldi, F.; Neu, C.; Newman, H.; Nicolaou, C.; Nourbakhsh, S.; Obertino, M. M.; Organtini, G.; Orimoto, T.; Paganini, P.; Paganis, E.; Paganoni, M.; Pandolfi, F.; Panov, V.; Paramatti, R.; Parracho, P.; Pastrone, N.; Paulini, M.; Pauss, F.; Pauwels, K.; Pellegrino, F.; Pena, C.; Perniè, L.; Peruzzi, M.; Petrakou, E.; Petyt, D.; Pigazzini, S.; Piroué, P.; Planer, M.; Plestina, R.; Polic, D.; Prosper, H.; Ptochos, F.; Puljak, I.; Quittnat, M.; Ragazzi, S.; Rahatlou, S.; Rander, J.; Ranjan, K.; Rasteiro Da Silva, J.; Razis, P. A.; Romanteau, T.; Rosowsky, A.; Rovelli, C.; Rusack, R.; Salerno, R.; Santanastasio, F.; Santra, A.; Schönenberger, M.; Seez, C.; Sharma, V.; Shepherd-Themistocleous, C.; Shiu, J. G.; Shivpuri, R. K.; Singovsky, A.; Sinthuprasith, T.; Sirois, Y.; Smiljkovic, N.; Soffi, L.; Sun, M.; Symonds, P.; Tabarelli de Fatis, T.; Tambe, N.; Tarasov, I.; Taroni, S.; Teixeira De Lima, R.; Thea, A.; Theofilatos, K.; Thiant, F.; Titov, M.; Torbet, M.; Trapani, P. P.; Tropea, P.; Tsai, J. f.; Tsirou, A.; Turkewitz, J.; Tyurin, N.; Tzeng, Y. M.; Uzunian, A.; Valls, N.; Varela, J.; Veeraraghavan, V.; Verdini, P. G.; Vichoudis, P.; Vlassov, E.; Wang, J.; Wang, T.; Weinberg, M.; Wolfe, E.; Wood, J.; Zabi, A.; Zahid, S.; Zelepoukine, S.; Zghiche, A.; Zhang, L.; Zhu, K.; Zhu, R.; Zuyeuski, R.

2016-04-01

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1× 1013 and 1.3× 1014 cm-2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb-1 and 3000 fb-1 respectively, corresponding to the end of the LHC and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. The experimental results obtained can be used to estimate the long term performance of the CMS ECAL.

SU-E-T-32: A Feasibility Study of Independent Dose Verification for IMAT

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

Kamima, T; Takahashi, R; Sato, Y

2015-06-15

Purpose: To assess the feasibility of the independent dose verification (Indp) for intensity modulated arc therapy (IMAT). Methods: An independent dose calculation software program (Simple MU Analysis, Triangle Products, JP) was used in this study, which can compute the radiological path length from the surface to the reference point for each control point using patient’s CT image dataset and the MLC aperture shape was simultaneously modeled in reference to the information of MLC from DICOM-RT plan. Dose calculation was performed using a modified Clarkson method considering MLC transmission and dosimetric leaf gap. In this study, a retrospective analysis was conductedmore » in which IMAT plans from 120 patients of the two sites (prostate / head and neck) from four institutes were retrospectively analyzed to compare the Indp to the TPS using patient CT images. In addition, an ion-chamber measurement was performed to verify the accuracy of the TPS and the Indp in water-equivalent phantom. Results: The agreements between the Indp and the TPS (mean±1SD) were −0.8±2.4% and −1.3±3.8% for the regions of prostate and head and neck, respectively. The measurement comparison showed similar results (−0.8±1.6% and 0.1±4.6% for prostate and head and neck). The variation was larger in the head and neck because the number of the segments was increased that the reference point was under the MLC and the modified Clarkson method cannot consider the smooth falloff of the leaf penumbra. Conclusion: The independent verification program would be practical and effective for secondary check for IMAT with the sufficient accuracy in the measurement and CT-based calculation. The accuracy would be improved if considering the falloff of the leaf penumbra.« less

SU-E-T-247: Multi-Leaf Collimator Model Adjustments Improve Small Field Dosimetry in VMAT Plans

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

Young, L; Yang, F

2014-06-01

Purpose: The Elekta beam modulator linac employs a 4-mm micro multileaf collimator (MLC) backed by a fixed jaw. Out-of-field dose discrepancies between treatment planning system (TPS) calculations and output water phantom measurements are caused by the 1-mm leaf gap required for all moving MLCs in a VMAT arc. In this study, MLC parameters are optimized to improve TPS out-of-field dose approximations. Methods: Static 2.4 cm square fields were created with a 1-mm leaf gap for MLCs that would normally park behind the jaw. Doses in the open field and leaf gap were measured with an A16 micro ion chamber andmore » EDR2 film for comparison with corresponding point doses in the Pinnacle TPS. The MLC offset table and tip radius were adjusted until TPS point doses agreed with photon measurements. Improvements to the beam models were tested using static arcs consisting of square fields ranging from 1.6 to 14.0 cm, with 45° collimator rotation, and 1-mm leaf gap to replicate VMAT conditions. Gamma values for the 3-mm distance, 3% dose difference criteria were evaluated using standard QA procedures with a cylindrical detector array. Results: The best agreement in point doses within the leaf gap and open field was achieved by offsetting the default rounded leaf end table by 0.1 cm and adjusting the leaf tip radius to 13 cm. Improvements in TPS models for 6 and 10 MV photon beams were more significant for smaller field sizes 3.6 cm or less where the initial gamma factors progressively increased as field size decreased, i.e. for a 1.6cm field size, the Gamma increased from 56.1% to 98.8%. Conclusion: The MLC optimization techniques developed will achieve greater dosimetric accuracy in small field VMAT treatment plans for fixed jaw linear accelerators. Accurate predictions of dose to organs at risk may reduce adverse effects of radiotherapy.« less

SU-E-T-604: Penumbra Characteristics of a New InCiseâ„¢ Multileaf Collimator of CyberKnife M6â„¢ System

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

Hwang, M; Jang, S; Ozhasoglu, C

2015-06-15

Purpose: The InCise™ Multileaf Collimator (MLC) of CyberKnife M6™ System has been released recently. The purpose of this study was to explore the dosimetric characteristics of the new MLC. In particular, the penumbra characteristics of MLC fields at varying locations are evaluated. Methods: EBT3-based film measurements were performed with varying MLC fields ranging from 7.5 mm to 27.5 mm. Seventeen regions of interests (ROIs) were identified for irradiation. These are regions located at the central area (denoted as reference field), at the left/right edge areas of reference open field, at an intermediate location between central and edge area. Single beammore » treatment plans were designed by using the MultiPlan and was delivered using the Blue Phantom. Gafchromic films were irradiated at 1.5 cm depth in the Blue Phantom and analyzed using the Film Pro software. Variation of maximum dose, penumbra of MLC-defined fields, and symmetry/flatness were calculated as a function of locations of MLC fields. Results: The InCise™ MLC System showed relatively consistent dose distribution and penumbra size with varying locations of MLC fields. The measured maximum dose varied within 5 % at different locations compared to that at the central location and agreed with the calculated data well within 2%. The measured penumbrae were in the range of 2.9 mm and 3.7 mm and were relatively consistent regardless of locations. However, dose profiles in the out-of-field and in-field regions varied with locations and field sizes. Strong variation was seen for all fields located at 55 mm away from the central field. The MLC leakage map showed that the leakage is dependent on position. Conclusion: The size of penumbra and normalized maximum dose for MLC-defined fields were consistent in different regions of MLC. However, dose profiles in the out-field region varied with locations and field sizes.« less

SU-E-T-293: Simplifying Assumption for Determining Sc and Sp

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

King, R; Cheung, A; Anderson, R

Purpose: Scp(mlc,jaw) is a two-dimensional function of collimator field size and effective field size. Conventionally, Scp(mlc,jaw) is treated as separable into components Sc(jaw) and Sp(mlc). Scp(mlc=jaw) is measured in phantom and Sc(jaw) is measured in air with Sp=Scp/Sc. Ideally, Sc and Sp would be able to predict measured values of Scp(mlc,jaw) for all combinations of mlc and jaw. However, ideal Sc and Sp functions do not exist and a measured two-dimensional Scp dataset cannot be decomposed into a unique pair of one-dimensional functions.If the output functions Sc(jaw) and Sp(mlc) were equal to each other and thus each equal to Scp(mlc=jaw){supmore » 0.5}, this condition would lead to a simpler measurement process by eliminating the need for in-air measurements. Without the distorting effect of the buildup-cap, small-field measurement would be limited only by the dimensions of the detector and would thus be improved by this simplification of the output functions. The goal of the present study is to evaluate an assumption that Sc=Sp. Methods: For a 6 MV x-ray beam, Sc and Sp were determined both by the conventional method and as Scp(mlc=jaw){sup 0.5}. Square field benchmark values of Scp(mlc,jaw) were then measured across the range from 2×2 to 29×29. Both Sc and Sp functions were then evaluated as to their ability to predict these measurements. Results: Both methods produced qualitatively similar results with <4% error for all cases and >3% error in 1 case. The conventional method produced 2 cases with >2% error, while the squareroot method produced only 1 such case. Conclusion: Though it would need to be validated for any specific beam to which it might be applied, under the conditions studied, the simplifying assumption that Sc = Sp is justified.« less

Substance P activates both contractile and inflammatory pathways in lymphatics through the neurokinin receptors NK1R and NK3R

PubMed Central

Chakraborty, Sanjukta; Nepiyushchikh, Zhanna; Davis, Michael J.; Zawieja, David C.; Muthuchamy, Mariappan

2010-01-01

Objective The aim of this study was to elucidate the molecular signaling mechanisms by which substance P (SP) modulates lymphatic muscle contraction and to determine whether SP stimulates both contractile as well as inflammatory pathways in the lymphatics. Methods A rat mesenteric lymphatic muscle cell culture model (RMLMCs) and known specific pharmacological inhibitors were utilized to delineate SP mediated signaling pathways in lymphatics. Results We detected expression of neurokinin receptor 1 (NK1R) and neurokinin receptor 3 (NK3R) in RMLMCs. SP stimulation increased phosphorylation of myosin light chain 20 (MLC20) as well as p38 mitogen associated protein kinase (p38-MAPK) and extracellular signal regulated kinase (ERK1/2) indicating activation of both a contractile and a pro-inflammatory MAPK pathway. Pharmacological inhibition of both NK1R and NK3R significantly affected the downstream SP signaling. We further examined whether there was any crosstalk between the two pathways upon SP stimulation. Inhibition of ERK1/2 decreased levels of p-MLC20 after SP activation, in a PKC dependent manner, indicating a potential crosstalk between these two pathways. Conclusions These data provide the first evidence that SP mediated crosstalk between pro-inflammatory and contractile signaling mechanisms exists in the lymphatic system and may be an important bridge between lymphatic function modulation and inflammation. PMID:21166923

The first clinical implementation of electromagnetic transponder-guided MLC tracking.

PubMed

Keall, Paul J; Colvill, Emma; O'Brien, Ricky; Ng, Jin Aun; Poulsen, Per Rugaard; Eade, Thomas; Kneebone, Andrew; Booth, Jeremy T

2014-02-01

We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy.

The first clinical implementation of electromagnetic transponder-guided MLC tracking

PubMed Central

Keall, Paul J.; Colvill, Emma; O’Brien, Ricky; Ng, Jin Aun; Poulsen, Per Rugaard; Eade, Thomas; Kneebone, Andrew; Booth, Jeremy T.

2014-01-01

Purpose: We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. Methods: An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. Results: The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. Conclusions: The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy. PMID:24506591

Effects of different fluences of low-level laser therapy in an experimental model of spinal cord injury in rats.

PubMed

Veronez, Suellen; Assis, Lívia; Del Campo, Paula; de Oliveira, Flávia; de Castro, Gláucia; Renno, Ana Claudia Muniz; Medalha, Carla Christina

2017-02-01

The aim of this study was to evaluate the in vivo response of different fluences of low-level laser therapy (LLLT) on the area of the injury, inflammatory markers, and functional recovery using an experimental model of traumatic spinal cord injury (SCI). Thirty two rats were randomly divided into four experimental groups: control group (CG), laser-treated group 500 J/cm 2 (L-500), laser-treated group 750 J/cm 2 (L-750), and laser-treated group 1000 J/cm 2 (L-1000). SCI was performed by an impactor equipment (between the ninth and tenth thoracic vertebrae), with a pressure of 150 kdyn. Afterwards, the injured region was irradiated daily for seven consecutive sessions, using an 808-nm laser, at the respective fluence of each experimental groups. Motor function and tactile sensitivity were performed on days 1 and 7 post-surgery. Animals were euthanized on the eighth day after injury, and the samples were retrieved for histological and immunohistochemistry analyses. Functional evaluation and tactile sensitivity were improved after LLLT, at the higher fluence. Additionally, LLLT, at 750 and 1000 J/cm 2 , reduces the lesion volume and modulates the inflammatory process with decrease of CD-68 protein expression. These results suggest that LLLT at higher doses was effective in promoting functional recovery and modulating inflammatory process in the spinal cord of rats after SCI.

Role of laser fluence in protein synthesis of cultured DRG neurons following low-level laser irradiation

NASA Astrophysics Data System (ADS)

Zheng, Liqin; Qiu, Caimin; Wang, Yuhua; Zeng, Yixiu; Yang, Hongqin; Zhang, Yanding; Xie, Shusen

2014-11-01

Low-level lasers have been used to relieve pain in clinical for many years. But the mechanism is not fully clear. In animal models, nitric oxide (NO) has been reported involving in the transmission and modulation of nociceptive signals. So the objective of this study was to establish whether low-level laser with different fluence could stimulate the production of nitric oxide synthese (NOS), which produces NO in cultured primary dorsal root ganglion neurons (DRG neurons). The primary DRG neurons were isolated from healthy Sprague Dawley rats (8-12 weeks of age) and spread on 35 mm culture dishes specially used for confocal microscopy. 24 hours after spreading, cells were irradiated with 658 nm laser for two consecutive days at the energy density of 20, 40, 60 and 80 mJ·cm-2 respectively. Control groups were not exposed to the laser, but were kept under the same conditions as the irradiated ones. The synthesis of NOS after laser irradiation was detected by immunofluorescence assay, and the changes of NOS were evaluated using confocal microscopy and Image J software. The results showed that all the laser fluence could promote the production of NOS in DRG neurons, especially the 60 mJ·cm-2 . These results demonstrated that low-level laser irradiation could modify protein synthesis in a dose- or fluence- dependent manner, and indicated that low-level laser irradiation might achieve the analgesic effect through modulation of NO production.

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

PubMed Central

Chen, Chuanli; Wang, Pei; Su, Qin; Wang, Shiliang; Wang, Fengjun

2012-01-01

Background Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. Conclusions/Significance The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury. PMID:22529961

Creation of an atlas of filter positions for fluence field modulated CT.

PubMed

Szczykutowicz, Timothy P; Hermus, James

2015-04-01

Fluence field modulated CT (FFMCT) and volume of interest (VOI) CT imaging applications require adjustment of the profile of the x-ray fluence incident on a patient as a function of view angle. Since current FFMCT prototypes can theoretically take on an infinite number of configurations, measuring a calibration data set for all possible positions would not be feasible. The present work details a methodology for calculating an atlas of configurations that will span all likely body regions, patient sizes, patient positioning, and imaging modes. The hypothesis is that there exists a finite number of unique modulator configurations that effectively span the infinite number of possible fluence profiles with minimal loss in performance. CT images of a head, shoulder, thorax, abdominal, wrist, and leg anatomical slices were dilated and contracted to model small, medium, and large sized patients. Additionally, the images were positioned from iso-center by three different amounts. The modulator configurations required to compensate for each image were computed assuming a FFMCT prototype, digital beam attenuator, (DBA), was set to equalize the detector exposure. Each atlas configuration should be different from the other atlas configurations. The degree of difference was quantified using the sum of the absolute differences in filter thickness between configurations. Using this metric, a set of unique wedge configurations for which no two configurations have a metric value smaller than some threshold can be constructed. Differences in the total number of incident photons between the unconstrained filters and the atlas were studied as a function of the number of atlas positions for each anatomical site and size/off-centering combination. By varying the threshold used in creating the atlas, it was found that roughly 322 atlas positions provided an incident number of photons within 20% of using 19,440 unique filters (the number of atlas entries ranged from 7213 to 1). Additionally, for VOI applications implemented with a single VOI region, the number of required filter configurations was expressed in a simple closed form solution. The methodology proposed in this work will enable DBA-FFMCT and DBA-VOI imaging in the clinic without the need for patient specific air-scans to be performed. In addition, the methodology proposed here is directly applicable to other modulator designs such as piecewise linear, TomoTherapy multi leaf collimators, 2D fluid arrays, and inverse geometry CT.

Error Characterization and Mitigation for 16Nm MLC NAND Flash Memory Under Total Ionizing Dose Effect

NASA Technical Reports Server (NTRS)

Li, Yue (Inventor); Bruck, Jehoshua (Inventor)

2018-01-01

A data device includes a memory having a plurality of memory cells configured to store data values in accordance with a predetermined rank modulation scheme that is optional and a memory controller that receives a current error count from an error decoder of the data device for one or more data operations of the flash memory device and selects an operating mode for data scrubbing in accordance with the received error count and a program cycles count.

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO 4 crystals

DOE PAGES

Adams, T.; Adzic, P.; Ahuja, S.; ...

2016-04-11

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO 4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO 4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1 × 10 13 and 1.3 × 10 14 cm –2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb –1 and 3000 fb –1 respectively, corresponding to the end of the LHCmore » and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. In conclusion, the experimental results obtained can be used to estimate the long term performance of the CMS ECAL.« less

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO 4 crystals

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

Adams, T.; Adzic, P.; Ahuja, S.

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO 4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO 4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1 × 10 13 and 1.3 × 10 14 cm –2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb –1 and 3000 fb –1 respectively, corresponding to the end of the LHCmore » and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. In conclusion, the experimental results obtained can be used to estimate the long term performance of the CMS ECAL.« less

Ten Novel Mutations in Chinese Patients with Megalencephalic Leukoencephalopathy with Subcortical Cysts and a Long-Term Follow-Up Research

PubMed Central

Cao, Binbin; Yan, Huifang; Guo, Mangmang; Xie, Han; Wu, Ye; Gu, Qiang; Xiao, Jiangxi; Shang, Jing; Yang, Yanling; Xiong, Hui; Niu, Zhengping; Wu, Xiru; Jiang, Yuwu; Wang, Jingmin

2016-01-01

Objective Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004) is a rare neurological deterioration disease. We aimed to clarify clinical and genetic features of Chinese MLC patients. Methods Clinical information and peripheral venous blood of 20 patients and their families were collected, Sanger-sequencing and Multiple Ligation-dependent Probe Amplification were performed to make genetic analysis. Splicing-site mutation was confirmed with RT-PCR. UPD was detected by haplotype analysis. Follow-up study was performed through telephone for 27 patients. Results Out of 20 patients, macrocephaly, classic MRI features, motor development delay and cognitive impairment were detected in 20(100%), 20(100%), 17(85%) and 4(20%) patients, respectively. 20(100%) were clinically diagnosed with MLC. 19(95%) were genetically diagnosed with 10 novel mutations in MLC1, MLC1 and GlialCAM mutations were identified in 15 and 4 patients, respectively. Deletion mutation from exon4 to exon9 and a homozygous point mutation due to maternal UPD of chromosome22 in MLC1 were found firstly. c.598-2A>C in MLC1 leads to the skip of exon8. c.772-1G>C in MLC1 accounting for 15.5%(9/58) alleles in Chinese patients might be a founder or a hot-spot mutation. Out of 27 patients in the follow-up study, head circumference was ranged from 56cm to 61cm in patients older than 5yeas old, with a median of 57cm. Motor development delay and cognitive impairment were detected in 22(81.5%) and 5(18.5%) patients, respectively. Motor and cognitive deterioration was found in 5 (18.5%) and 2 patients (7.4%), respectively. Improvements and MRI recovery were first found in Chinese patients. Rate of seizures (45.5%), transient motor retrogress (45.5%) and unconsciousness (13.6%) after head trauma was much higher than that after fever (18.2%, 9.1%, 0%, respectively). Significance It’s a clinical and genetic analysis and a follow-up study for largest sample of Chinese MLC patients, identifying 10 novel mutations, expanding mutation spectrums and discovering clinical features of Chinese MLC patients. PMID:27322623

Real-time tracking of respiratory-induced tumor motion by dose-rate regulation

NASA Astrophysics Data System (ADS)

Han-Oh, Yeonju Sarah

We have developed a novel real-time tumor-tracking technology, called Dose-Rate-Regulated Tracking (DRRT), to compensate for tumor motion caused by breathing. Unlike other previously proposed tumor-tracking methods, this new method uses a preprogrammed dynamic multileaf collimator (MLC) sequence in combination with real-time dose-rate control. This new scheme circumvents the technical challenge in MLC-based tumor tracking, that is to control the MLC motion in real time, based on real-time detected tumor motion. The preprogrammed MLC sequence describes the movement of the tumor, as a function of breathing phase, amplitude, or tidal volume. The irregularity of tumor motion during treatment is handled by real-time regulation of the dose rate, which effectively speeds up or slows down the delivery of radiation as needed. This method is based on the fact that all of the parameters in dynamic radiation delivery, including MLC motion, are enslaved to the cumulative dose, which, in turn, can be accelerated or decelerated by varying the dose rate. Because commercially available MLC systems do not allow the MLC delivery sequence to be modified in real time based on the patient's breathing signal, previously proposed tumor-tracking techniques using a MLC cannot be readily implemented in the clinic today. By using a preprogrammed MLC sequence to handle the required motion, the task for real-time control is greatly simplified. We have developed and tested the pre- programmed MLC sequence and the dose-rate regulation algorithm using lung-cancer patients breathing signals. It has been shown that DRRT can track the tumor with an accuracy of less than 2 mm for a latency of the DRRT system of less than 0.35 s. We also have evaluated the usefulness of guided breathing for DRRT. Since DRRT by its very nature can compensate for breathing-period changes, guided breathing was shown to be unnecessary for real-time tracking when using DRRT. Finally, DRRT uses the existing dose-rate control system that is provided for current linear accelerators. Therefore, DRRT can be achieved with minimal modification of existing technology, and this can shorten substantially the time necessary to establish DRRT in clinical practice.

A novel mechanism for the Ca(2+)-sensitizing effect of protein kinase C on vascular smooth muscle: inhibition of myosin light chain phosphatase

PubMed Central

1994-01-01

Mechanisms of Ca2+ sensitization of both myosin light chain (MLC) phosphorylation and force development by protein kinase C (PKC) were studied in permeabilized tonic smooth muscle obtained from the rabbit femoral artery. For comparison, the Ca2+ sensitizing effect of guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S) was examined, which had been previously shown to inhibit MLC phosphatase in phasic vascular smooth muscle. We now report that PKC activators (phorbol esters, short chain synthetic diacylglycerols and a diacylglycerol kinase inhibitor) and GTP gamma S significantly increase both MLC phosphorylation and force development at constant [Ca2+]. Major phosphorylation site occurring in the presence of phorbol-12,13- dibutyrate (PDBu) or GTP gamma S at constant [Ca2+] is the same serine residue (Ser-19) as that phosphorylated by MLC kinase in response to increased Ca2+ concentrations. In an ATP- and Ca(2+)-free solution containing 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4- diazepine (ML-9), to avoid the kinase activity, both PDBu and GTP gamma S significantly decreased the rate of MLC dephosphorylation to half its control value. However, PDBu inhibited the relaxation rate more than did GTP gamma S. In the presence of microcystin-LR to inhibit the phosphatase activity, neither PDBu nor GTP gamma S affected MLC phosphorylation and force development. These results indicate that PKC, like activation of GTP binding protein, increases Ca2+ sensitivity of both MLC phosphorylation and force production through inhibition of MLC phosphatase. PMID:7807049

SU-E-T-571: Newly Emerging Integrated Transmission Detector Systems Provide Online Quality Assurance of External Beam Radiation Therapy

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

Hoffman, D; Chung, E; Hess, C

2015-06-15

Purpose: Two newly emerging transmission detectors positioned upstream from the patient have been evaluated for online quality assurance of external beam radiotherapy. The prototype for the Integral Quality Monitor (IQM), developed by iRT Systems GmbH (Koblenz, Germany) is a large-area ion chamber mounted on the linac accessory tray to monitor photon fluence, energy, beam shape, and gantry position during treatment. The ion chamber utilizes a thickness gradient which records variable response dependent on beam position. The prototype of Delta4 Discover™, developed by ScandiDos (Uppsala, Sweden) is a linac accessory tray mounted 4040 diode array that measures photon fluence during patientmore » treatment. Both systems are employable for patient specific QA prior to treatment delivery. Methods: Our institution evaluated the reproducibility of measurements using various beam types, including VMAT treatment plans with both the IQM ion chamber and the Delta4 Discover diode array. Additionally, the IQM’s effect on photon fluence, dose response, simulated beam error detection, and the accuracy of the integrated barometer, thermometer, and inclinometer were characterized. The evaluated photon beam errors are based on the annual tolerances specified in AAPM TG-142. Results: Repeated VMAT treatments were measured with 0.16% reproducibility by the IQM and 0.55% reproducibility by the Delta4 Discover. The IQM attenuated 6, 10, and 15 MV photon beams by 5.43±0.02%, 4.60±0.02%, and 4.21±0.03% respectively. Photon beam profiles were affected <1.5% in the non-penumbra regions. The IQM’s ion chamber’s dose response was linear and the thermometer, barometer, and inclinometer agreed with other calibrated devices. The device detected variations in monitor units delivered (1%), field position (3mm), single MLC leaf positions (13mm), and photon energy. Conclusion: We have characterized two new transmissions detector systems designed to provide in-vivo like measurements upstream from the patient. Both systems demonstrate substantial utility for online treatment verification and QA of photon external beam radiotherapy.« less

SU-C-BRC-04: Efficient Dose Calculation Algorithm for FFF IMRT with a Simplified Bivariate Gaussian Source Model

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

Li, F; Park, J; Barraclough, B

2016-06-15

Purpose: To develop an efficient and accurate independent dose calculation algorithm with a simplified analytical source model for the quality assurance and safe delivery of Flattening Filter Free (FFF)-IMRT on an Elekta Versa HD. Methods: The source model consisted of a point source and a 2D bivariate Gaussian source, respectively modeling the primary photons and the combined effect of head scatter, monitor chamber backscatter and collimator exchange effect. The in-air fluence was firstly calculated by back-projecting the edges of beam defining devices onto the source plane and integrating the visible source distribution. The effect of the rounded MLC leaf end,more » tongue-and-groove and interleaf transmission was taken into account in the back-projection. The in-air fluence was then modified with a fourth degree polynomial modeling the cone-shaped dose distribution of FFF beams. Planar dose distribution was obtained by convolving the in-air fluence with a dose deposition kernel (DDK) consisting of the sum of three 2D Gaussian functions. The parameters of the source model and the DDK were commissioned using measured in-air output factors (Sc) and cross beam profiles, respectively. A novel method was used to eliminate the volume averaging effect of ion chambers in determining the DDK. Planar dose distributions of five head-and-neck FFF-IMRT plans were calculated and compared against measurements performed with a 2D diode array (MapCHECK™) to validate the accuracy of the algorithm. Results: The proposed source model predicted Sc for both 6MV and 10MV with an accuracy better than 0.1%. With a stringent gamma criterion (2%/2mm/local difference), the passing rate of the FFF-IMRT dose calculation was 97.2±2.6%. Conclusion: The removal of the flattening filter represents a simplification of the head structure which allows the use of a simpler source model for very accurate dose calculation. The proposed algorithm offers an effective way to ensure the safe delivery of FFF-IMRT.« less

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

Constantin, M; Sawkey, D; Johnsen, S

Purpose: To validate the physics parameters of a Monte Carlo model for patient plane leakage calculations on the 6MV Unique linac by comparing the simulations against IEC patient plane leakage measurements. The benchmarked model can further be used for shielding design optimization, to predict leakage in the proximity of intended treatment fields, reduce the system weight and cost, and improve components reliability. Methods: The treatment head geometry of the Unique linac was simulated in Geant4 (v9.4.p02 with “Opt3” standard electromagnetic physics list) based on CAD drawings of all collimation and shielding components projected from the target to the area withinmore » 2m from isocenter. A 4×4m2 scorer was inserted 1m from the target in the patient plane and multiple phase space files were recorded by performing a 40-node computing cluster simulation on the EC2 cloud. The photon energy fluence was calculated relative to the value at isocenter for a 10×10cm2 field using 10×10mm2 bins. Tungsten blocks were parked accordingly to represent MLC120. The secondary particle contamination to patient plane was eliminated by “killing” those particles prior to the primary collimator entrance using a “kill-plane”, which represented the upper head shielding components not being modeled. Both IEC patient-plane leakage and X/Y-jaws transmission were simulated. Results: The contribution of photons to energy fluence was 0.064% on average, in excellent agreement with the experimental data available at 0.5, 1.0, and 1.5m from isocenter, characterized by an average leakage of 0.045% and a maximum leakage of 0.085%. X- and Y-jaws transmissions of 0.43% and 0.44% were found in good agreement with measurements of 0.48% and 0.43%, respectively. Conclusion: A Geant4 model based on energy fluence calculations for the 6MV Unique linac was created and validated using IEC patient plane leakage measurements. The “kill-plane” has effectively eliminated electron contamination to patient plane in these simulations.« less

The Mathematics and Computer Science Learning Center (MLC).

ERIC Educational Resources Information Center

Abraham, Solomon T.

The Mathematics and Computer Science Learning Center (MLC) was established in the Department of Mathematics at North Carolina Central University during the fall semester of the 1982-83 academic year. The initial operations of the MLC were supported by grants to the University from the Burroughs-Wellcome Company and the Kenan Charitable Trust Fund.…

76 FR 4375 - In the Matter of Certain MLC Flash Memory Devices and Products Containing Same; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-683] In the Matter of Certain MLC Flash Memory Devices and Products Containing Same; Notice of Commission Determination Not To Review an Initial... the United States after importation of certain MLC flash memory devices and products containing same...

Carbachol-induced rabbit bladder smooth muscle contraction: roles of protein kinase C and Rho kinase.

PubMed

Wang, Tanchun; Kendig, Derek M; Smolock, Elaine M; Moreland, Robert S

2009-12-01

Smooth muscle contraction is regulated by phosphorylation of the myosin light chain (MLC) catalyzed by MLC kinase and dephosphorylation catalyzed by MLC phosphatase. Agonist stimulation of smooth muscle results in the inhibition of MLC phosphatase activity and a net increase in MLC phosphorylation and therefore force. The two pathways believed to be primarily important for inhibition of MLC phosphatase activity are protein kinase C (PKC)-catalyzed CPI-17 phosphorylation and Rho kinase (ROCK)-catalyzed myosin phosphatase-targeting subunit (MYPT1) phosphorylation. The goal of this study was to determine the roles of PKC and ROCK and their downstream effectors in regulating MLC phosphorylation levels and force during the phasic and sustained phases of carbachol-stimulated contraction in intact bladder smooth muscle. These studies were performed in the presence and absence of the PKC inhibitor bisindolylmaleimide-1 (Bis) or the ROCK inhibitor H-1152. Phosphorylation levels of Thr(38)-CPI-17 and Thr(696)/Thr(850)-MYPT1 were measured at different times during carbachol stimulation using site-specific antibodies. Thr(38)-CPI-17 phosphorylation increased concurrently with carbachol-stimulated force generation. This increase was reduced by inhibition of PKC during the entire contraction but was only reduced by ROCK inhibition during the sustained phase of contraction. MYPT1 showed high basal phosphorylation levels at both sites; however, only Thr(850) phosphorylation increased with carbachol stimulation; the increase was abolished by the inhibition of either ROCK or PKC. Our results suggest that during agonist stimulation, PKC regulates MLC phosphatase activity through phosphorylation of CPI-17. In contrast, ROCK phosphorylates both Thr(850)-MYPT1 and CPI-17, possibly through cross talk with a PKC pathway, but is only significant during the sustained phase of contraction. Last, our results demonstrate that there is a constitutively activate pool of ROCK that phosphorylates MYPT1 in the basal state, which may account for the high resting levels of MLC phosphorylation measured in rabbit bladder smooth muscle.

On the suitability of Elekta’s Agility 160 MLC for tracked radiation delivery: closed-loop machine performance

NASA Astrophysics Data System (ADS)

Glitzner, M.; Crijns, S. P. M.; de Senneville, B. Denis; Lagendijk, J. J. W.; Raaymakers, B. W.

2015-03-01

For motion adaptive radiotherapy, dynamic multileaf collimator tracking can be employed to reduce treatment margins by steering the beam according to the organ motion. The Elekta Agility 160 MLC has hitherto not been evaluated for its tracking suitability. Both dosimetric performance and latency are key figures and need to be assessed generically, independent of the used motion sensor. In this paper, we propose the use of harmonic functions directly fed to the MLC to determine its latency during continuous motion. Furthermore, a control variable is extracted from a camera system and fed to the MLC. Using this setup, film dosimetry and subsequent γ statistics are performed, evaluating the response when tracking (MRI)-based physiologic motion in a closed-loop. The delay attributed to the MLC itself was shown to be a minor contributor to the overall feedback chain as compared to the impact of imaging components such as MRI sequences. Delay showed a linear phase behaviour of the MLC employed in continuously dynamic applications, which enables a general MLC-characterization. Using the exemplary feedback chain, dosimetry showed a vast increase in pass rate employing γ statistics. In this early stage, the tracking performance of the Agility using the test bench yielded promising results, making the technique eligible for translation to tracking using clinical imaging modalities.

The Rho-GTPase effector ROCK regulates meiotic maturation of the bovine oocyte via myosin light chain phosphorylation and cofilin phosphorylation.

PubMed

Lee, So-Rim; Xu, Yong-Nan; Jo, Yu-Jin; Namgoong, Suk; Kim, Nam-Hyung

2015-11-01

Oocyte meiosis involves a unique asymmetric division involving spindle movement from the central cytoplasm to the cortex, followed by polar body extrusion. ROCK is a Rho-GTPase effector involved in various cellular functions in somatic cells as well as oocyte meiosis. ROCK was previously shown to promote actin organization by phosphorylating several downstream targets, including LIM domain kinase (LIMK), phosphorylated cofilin (p-cofilin), and myosin light chain (MLC). In this study, we investigated the roles of ROCK and MLC during bovine oocyte meiosis. We found that ROCK was localized around the nucleus at the oocyte's germinal-vesicle (GV) stage, but spreads to the rest of the cytoplasm in later developmental stages. On the other hand, phosphorylated MLC (p-MLC) localized at the cortex, and its abundance decreased by the metaphase-II stage. Disrupting ROCK activity, via RNAi or the chemical inhibitor Y-27632, blocked both cell cycle progression and polar body extrusion. ROCK inhibition also resulted in decreased cortical actin, p-cofilin, and p-MLC levels. Similar to the phenotype associated with inhibition of ROCK activity, inhibition of MLC kinase by the chemical inhibitor ML-7 caused defects in polar body extrusion. Collectively, our results suggest that the ROCK/MLC/actomyosin as well as ROCK/LIMK/cofilin pathways regulate meiotic spindle migration and cytokinesis during bovine oocyte maturation. © 2015 Wiley Periodicals, Inc.

SU-E-T-593: Outcomes and Toxicities From a Clinical Trial of APBI Using MERT+IMRT with the Same XMLC

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

Jimenez-Ortega, E.; Ureba, A.; Barbeiro, A.R.

2015-06-15

Purpose: We present the results from a clinical trial of accelerated partial breast irradiation (APBI), using mixed modulated photon and electron beams (MERT+IMRT) with the same photon multileaf collimator (xMLC). Methods: Seven patients were enrolled in the first year of the APBI clinical trial. Patients were selected following the conditions included in the NSABP B-39/RTOG 0413 protocol. The targets and clinically relevant normal structures were contoured on the CT images following this protocol for APBI-EBRT. All treatments were delivered using combined modulated electron and photon beams by means of the same xMLC installed in a SIEMENS Primus linac, with amore » reduced SSD equal to 60 cm for electron beams. The plans were performed with a treatment planning system based on full Monte Carlo simulations, called CARMEN, developed by our group. Simultaneously, an alternative IMRT plan was calculated with the commercial TPS PINNACLE v8.0m (Philips), and both plans were compared. An ad-hoc breast phantom with semi-spherical geometry called NAOMI was designed for a specific QA protocol. Patients received a total dose of 38.5 Gy, delivered in 10 fractions over 5 consecutive days, with a twice-a-day hypofractionated schema.Follow-up visits during 2.5 years on average were repeated at 1 month post-treatment, every 3 months for the first year, and every 6 months for the second year. Toxicity was scored according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0). Results: This APBI technique achieved high loco-regional control rates and showed low acute toxicity (grade 1 of CTCAE) and no toxicities from first month onwards. Photographic assessment of cosmesis showed skin excellent results. Conclusion: The clinical results achieved with MERT+IMRT by using the same xMLC are comparable or even better than those obtained with other APBI techniques, thanks to a software solution without any additional equipment or specific device.« less

High-Fluence Light-Emitting Diode-Generated Red Light Modulates the Transforming Growth Factor-Beta Pathway in Human Skin Fibroblasts.

PubMed

Mamalis, Andrew; Jagdeo, Jared

2018-05-24

Skin fibrosis is a significant medical problem with limited available treatment modalities. The key cellular characteristics include increased fibroblast proliferation, collagen production, and transforming growth factor-beta (TGF-B)/SMAD pathway signaling. The authors have previously shown that high-fluence light-emitting diode red light (HF-LED-RL) decreases cellular proliferation and collagen production. Herein, the authors investigate the ability of HF-LED-RL to modulate the TGF-B/SMAD pathway. Normal human dermal fibroblasts were cultured and irradiated with a commercially available hand-held LED array. After irradiation, cell lysates were collected and levels of pSMAD2, TGF-Beta 1, and TGF-Beta I receptor were measured using Western blot. High-fluence light-emitting diode red light decreased TGF-Beta 1 ligand (TGF-B1) levels after irradiation. 320 J/cm HF-LED-RL resulted in 59% TGF-B1 and 640 J/cm HF-LED-RL resulted in 54% TGF-B1, relative to controls. 640 J/cm HF-LED-RL resulted in 62% pSMAD2 0 hours after irradiation, 65% pSMAD2 2 hours after irradiation, and 95% 4 hours after irradiation, compared with matched controls. High-fluence light-emitting diode red light resulted in no significant difference in transforming growth factor-beta receptor I levels compared with matched controls. Skin fibrosis is a significant medical problem with limited available treatment modalities. Light-emitting diode-generated red light is a safe, economic, and noninvasive modality that has a body of in vitro evidence supporting the reduction of key cellular characteristics associated with skin fibrosis.

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age.

PubMed

Gannon, Joan; Doran, Philip; Kirwan, Anne; Ohlendieck, Kay

2009-11-01

The age-dependent decline in skeletal muscle mass and function is believed to be due to a multi-factorial pathology and represents a major factor that blocks healthy aging by increasing physical disability, frailty and loss of independence in the elderly. This study has focused on the comparative proteomic analysis of contractile elements and revealed that the most striking age-related changes seem to occur in the protein family representing myosin light chains (MLCs). Comparative screening of total muscle extracts suggests a fast-to-slow transition in the aged MLC population. The mass spectrometric analysis of the myofibril-enriched fraction identified the MLC2 isoform of the slow-type MLC as the contractile protein with the most drastically changed expression during aging. Immunoblotting confirmed an increased abundance of slow MLC2, concomitant with a switch in fast versus slow myosin heavy chains. Staining of two-dimensional gels of crude extracts with the phospho-specific fluorescent dye ProQ-Diamond identified the increased MLC2 spot as a muscle protein with a drastically enhanced phosphorylation level in aged fibres. Comparative immunofluorescence microscopy, using antibodies to fast and slow myosin isoforms, confirmed a fast-to-slow transformation process during muscle aging. Interestingly, the dramatic increase in slow MLC2 expression was restricted to individual senescent fibres. These findings agree with the idea that aged skeletal muscles undergo a shift to more aerobic-oxidative metabolism in a slower-twitching fibre population and suggest the slow MLC2 isoform as a potential biomarker for fibre type shifting in sarcopenia of old age.

SU-F-T-313: Clinical Results of a New Customer Acceptance Test for Elekta VMAT

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

Rusk, B; Fontenot, J

Purpose: To report the results of a customer acceptance test (CAT) for VMAT treatments for two matched Elekta linear accelerators. Methods: The CAT tests were performed on two clinically matched Elekta linear accelerators equipped with a 160-leaf MLC. Functional tests included performance checks of the control system during dynamic movements of the diaphragms, MLC, and gantry. Dosimetric tests included MLC picket fence tests at static and variable dose rates and a diaphragm alignment test, all performed using the on-board EPID. Additionally, beam symmetry during arc delivery was measured at the four cardinal angles for high and low dose rate modesmore » using a 2D detector array. Results of the dosimetric tests were analyzed using the VMAT CAT analysis tool. Results: Linear accelerator 1 (LN1) met all stated CAT tolerances. Linear accelerator 2 (LN2) passed the geometric, beam symmetry, and MLC position error tests but failed the relative dose average test for the diaphragm abutment and all three picket fence fields. Though peak doses in the abutment regions were consistent, the average dose was below the stated tolerance corresponding to a leaf junction that was too narrow. Despite this, no significant differences in patient specific VMAT quality assurance measured were observed between the accelerators and both passed monthly MLC quality assurance performed with the Hancock test. Conclusion: Results from the CAT showed LN2 with relative dose averages in the abutment regions of the diaphragm and MLC tests outside the tolerances resulting from differences in leaf gap distances. Tolerances of the dose average tests from the CAT may be small enough to detect MLC errors which do not significantly affect patient QA or the routine MLC tests.« less

SU-F-T-266: Dynalogs Based Evaluation of Different Dose Rate IMRT Using DVH and Gamma Index

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

Ahmed, S; Ahmed, S; Ahmed, F

2016-06-15

Purpose: This work investigates the impact of low and high dose rate on IMRT through Dynalogs by evaluating Gamma Index and Dose Volume Histogram. Methods: The Eclipse™ treatment planning software was used to generate plans on prostate and head and neck sites. A range of dose rates 300 MU/min and 600 MU/min were applied to each plan in order to investigate their effect on the beam ON time, efficiency and accuracy. Each plan had distinct monitor units per fraction, delivery time, mean dose rate and leaf speed. The DVH data was used in the assessment of the conformity and planmore » quality.The treatments were delivered on Varian™ Clinac 2100C accelerator equipped with 120 leaf millennium MLC. Dynalogs of each plan were analyzed by MATLAB™ program. Fluence measurements were performed using the Sun Nuclear™ 2D diode array and results were assessed, based on Gamma analysis of dose fluence maps, beam delivery statistics and Dynalogs data. Results: Minor differences found by adjusted R-squared analysis of DVH’s for all the plans with different dose rates. It has been also found that more and larger fields have greater time reduction at high dose rate and there was a sharp decrease in number of control points observed in dynalog files by switching dose rate from 300 MU/min to 600 MU/min. Gamma Analysis of all plans passes the confidence limit of ≥95% with greater number of passing points in 300 MU/min dose rate plans. Conclusion: The dynalog files are compatible tool for software based IMRT QA. It can work perfectly parallel to measurement based QA setup and stand-by procedure for pre and post delivery of treatment plan.« less

Engineering of electronic properties of single layer graphene by swift heavy ion irradiation

NASA Astrophysics Data System (ADS)

Kumar, Sunil; Kumar, Ashish; Tripathi, Ambuj; Tyagi, Chetna; Avasthi, D. K.

2018-04-01

In this work, swift heavy ion irradiation induced effects on the electrical properties of single layer graphene are reported. The modulation in minimum conductivity point in graphene with in-situ electrical measurement during ion irradiation was studied. It is found that the resistance of graphene layer decreases at lower fluences up to 3 × 1011 ions/cm2, which is accompanied by the five-fold increase in electron and hole mobilities. The ion irradiation induced increase in electron and hole mobilities at lower fluence up to 1 × 1011 ions/cm2 is verified by separate Hall measurements on another irradiated graphene sample at the selected fluence. In contrast to the adverse effects of irradiation on the electrical properties of materials, we have found improvement in electrical mobility after irradiation. The increment in mobility is explained by considering the defect annealing in graphene after irradiation at a lower fluence regime. The modification in carrier density after irradiation is also observed. Based on findings of the present work, we suggest ion beam irradiation as a useful tool for tuning of the electrical properties of graphene.

Can cost make a difference dosimetrically? Volumetric modulated arc therapy study for multileaf collimators of various widths for head and neck and prostate cancers

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

Ho, Jong-Han, E-mail: jonghanho@gmail.com; Hagler, Shane; Lujano, Carrie

Cancer is a global health issue that disproportionately kills based on stage of disease, cellular pathology, and genetics, to name a few. Another variable to consider in this ongoing fight is treatment machine complexity that leads to elevated development and purchasing cost, leading to a reduced use. Reducing the complexity (in hopes of lowering costs) would benefit underdeveloped, low- and middle-income countries by introducing newer treatment technology, as their currently accepted standards do not meet standards of more advanced, developed countries. In this study, unilateral head and neck (H&N), and prostate cases using volumetric modulated arc therapy (VMAT) were testedmore » with multiple segment widths of 5, 10, 15, and 20 mm to create treatable plans. Pinnacle 9.10v was used for planning purposes. A total of 12 cases were planned with varying multileaf collimator (MLC) widths. Treatment plans were evaluated retrospectively. Results show that altering the MLC widths from 5 through 20 mm produces both comparable and treatable plans up to 99% and 98% target coverage for H&N and prostate, respectively, albeit clinically significant hot spots were shown to increase with increasing segment width. Furthermore, the results show that increasing widths can produce comparable treatment plans as measured against our current Food and Drug Administration (FDA)–approved treatment devices—leading to an increase in treatment efficacy in economically underdeveloped countries.« less

Linking log files with dosimetric accuracy--A multi-institutional study on quality assurance of volumetric modulated arc therapy.

PubMed

Pasler, Marlies; Kaas, Jochem; Perik, Thijs; Geuze, Job; Dreindl, Ralf; Künzler, Thomas; Wittkamper, Frits; Georg, Dietmar

2015-12-01

To systematically evaluate machine specific quality assurance (QA) for volumetric modulated arc therapy (VMAT) based on log files by applying a dynamic benchmark plan. A VMAT benchmark plan was created and tested on 18 Elekta linacs (13 MLCi or MLCi2, 5 Agility) at 4 different institutions. Linac log files were analyzed and a delivery robustness index was introduced. For dosimetric measurements an ionization chamber array was used. Relative dose deviations were assessed by mean gamma for each control point and compared to the log file evaluation. Fourteen linacs delivered the VMAT benchmark plan, while 4 linacs failed by consistently terminating the delivery. The mean leaf error (±1SD) was 0.3±0.2 mm for all linacs. Large MLC maximum errors up to 6.5 mm were observed at reversal positions. Delivery robustness index accounting for MLC position correction (0.8-1.0) correlated with delivery time (80-128 s) and depended on dose rate performance. Dosimetric evaluation indicated in general accurate plan reproducibility with γ(mean)(±1 SD)=0.4±0.2 for 1 mm/1%. However single control point analysis revealed larger deviations and attributed well to log file analysis. The designed benchmark plan helped identify linac related malfunctions in dynamic mode for VMAT. Log files serve as an important additional QA measure to understand and visualize dynamic linac parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mainland Chinese Students at an Elite Hong Kong University: Habitus-Field Disjuncture in a Transborder Context

ERIC Educational Resources Information Center

Xu, Cora Lingling

2017-01-01

Drawing on in-depth interview data from 31 mainland Chinese (MLC) students in a Hong Kong university, this article conceptualises MLC and Hong Kong higher education as two dissonant but interrelated subfields of the Chinese higher education field. The article argues that these MLC students' habitus, one that possesses rich economic, social and…

SU-E-J-67: Evaluation of Adaptive MLC Morphing for Online Correction of Prostate Cancer Radiotherapy

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

Sandhu, R; Qin, A; Yan, D

Purpose: Online adaptive MLC morphing is desirable over translational couch shifts to accommodate target position as well as anatomic changes. A reliable method of adaptive MLC segment to target during prostate cancer IMRT treatment is proposed and evaluated by comparison with daily online-image guidance (IGRT) correction and online-IMRT planning. Methods: The MLC adaptive algorithm involves following steps; move the MLC segments according to target translational shifts, and then morph the segment shape to maintain the spatial relationship between the planning-target contour and MLC segment. Efficacy of this method was evaluated retrospectively using daily-CBCT images on seven prostate patients treated withmore » seven-beam IMRT treatment to deliver 64Gy in 20 fractions. Daily modification was simulated with three approaches; daily-IGRT correction based on implanted radio-markers, adaptive MLC morphing, and online-IMRT planning, with no-residual variation. The selected dosimetric endpoints and nEUD (normalized equivalent uniform dose to online-IMRT planning) of each organ of interest were determined for evaluation and comparison. Results: For target(prostate), bladder and rectal-wall, the mean±sd of nEUD were 97.6%+3.2%, 103.9%±4.9% and 97.4%±1.1% for daily-IGRT correction; and 100.2%+0.2%, 108.9%±5.1% and 99.8%±1.2% for adaptive MLC morphing, respectively. For daily-IGRT correction, adaptive MLC morphing and online-IMRT planning, target D99 was <95% of the prescription dose in 30%, 0% and 0% of 140 fractions, respectively. For the rectal-wall, D5 exceeded 105% of the planned-D5 in 2.8%, 11.4% and 0% of 140 fractions, respectively. For the bladder, Dmax exceeded 105% of the planned-D5 in 2.8%, 5.6% and 0% of 140 fractions, respectively. D30 of bladder and rectal-wall were well within the planned-D30 for all three approaches. Conclusion: The proposed method of adaptive MLC morphing can be beneficial for the prostate patient population with large deformation and rotation. It is superior to the daily-IGRT correction, and comparable to the online-IMRT planning for dose to the target and rectal-wall.« less

The first patient treatment of electromagnetic-guided real time adaptive radiotherapy using MLC tracking for lung SABR.

PubMed

Booth, Jeremy T; Caillet, Vincent; Hardcastle, Nicholas; O'Brien, Ricky; Szymura, Kathryn; Crasta, Charlene; Harris, Benjamin; Haddad, Carol; Eade, Thomas; Keall, Paul J

2016-10-01

Real time adaptive radiotherapy that enables smaller irradiated volumes may reduce pulmonary toxicity. We report on the first patient treatment of electromagnetic-guided real time adaptive radiotherapy delivered with MLC tracking for lung stereotactic ablative body radiotherapy. A clinical trial was developed to investigate the safety and feasibility of MLC tracking in lung. The first patient was an 80-year old man with a single left lower lobe lung metastasis to be treated with SABR to 48Gy in 4 fractions. In-house software was integrated with a standard linear accelerator to adapt the treatment beam shape and position based on electromagnetic transponders implanted in the lung. MLC tracking plans were compared against standard ITV-based treatment planning. MLC tracking plan delivery was reconstructed in the patient to confirm safe delivery. Real time adaptive radiotherapy delivered with MLC tracking compared to standard ITV-based planning reduced the PTV by 41% (18.7-11cm 3 ) and the mean lung dose by 30% (202-140cGy), V20 by 35% (2.6-1.5%) and V5 by 9% (8.9-8%). An emerging technology, MLC tracking, has been translated into the clinic and used to treat lung SABR patients for the first time. This milestone represents an important first step for clinical real-time adaptive radiotherapy that could reduce pulmonary toxicity in lung radiotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning.

PubMed

Liu, Shi; Wu, Yu; Wooten, H Omar; Green, Olga; Archer, Brent; Li, Harold; Yang, Deshan

2016-03-08

A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image-guided radiation therapy (MR-IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam-on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam-on time can be calculated using both the planned beam-on time and the decay-corrected dose rate. To predict the remain-ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of the proposed prediction algorithm is sufficient to support patient treatment appointment scheduling. This developed software tool is currently applied in use on a daily basis in our clinic, and could also be used as an important indicator for treatment plan complexity.

Treatment plan comparison between helical tomotherapy and MLC-based IMRT using radiobiological measures

NASA Astrophysics Data System (ADS)

Mavroidis, Panayiotis; Costa Ferreira, Brigida; Shi, Chengyu; Lind, Bengt K.; Papanikolaou, Nikos

2007-07-01

The rapid implementation of advanced treatment planning and delivery technologies for radiation therapy has brought new challenges in evaluating the most effective treatment modality. Intensity-modulated radiotherapy (IMRT) using multi-leaf collimators (MLC) and helical tomotherapy (HT) are becoming popular modes of treatment delivery and their application and effectiveness continues to be investigated. Presently, there are several treatment planning systems (TPS) that can generate and optimize IMRT plans based on user-defined objective functions for the internal target volume (ITV) and organs at risk (OAR). However, the radiobiological parameters of the different tumours and normal tissues are typically not taken into account during dose prescription and optimization of a treatment plan or during plan evaluation. The suitability of a treatment plan is typically decided based on dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean and standard deviation of the dose distribution. For a more comprehensive treatment plan evaluation, the biologically effective uniform dose ({\\bar{\\bar{D}}}) is applied together with the complication-free tumour control probability (P+). Its utilization is demonstrated using three clinical cases that were planned with two different forms of IMRT. In this study, three different cancer types at different anatomical sites were investigated: head and neck, lung and prostate cancers. For each cancer type, a linac MLC-based step-and-shoot IMRT plan and a HT plan were developed. The MLC-based IMRT treatment plans were developed on the Philips treatment-planning platform, using the Pinnacle 7.6 software release. For the tomotherapy HiArt plans, the dedicated tomotherapy treatment planning station was used, running version 2.1.2. By using {\\bar{\\bar{D}}} as the common prescription point of the treatment plans and plotting the tissue response probabilities versus {\\bar{\\bar{D}}} for a range of prescription doses, a number of plan trials can be compared based on radiobiological measures. The applied plan evaluation method shows that in the head and neck cancer case the HT treatment gives better results than MLC-based IMRT in terms of expected clinical outcome (P+ of 62.2% and 46.0%, {\\bar{\\bar{D}}} to the ITV of 72.3 Gy and 70.7 Gy, respectively). In the lung cancer and prostate cancer cases, the MLC-based IMRT plans are better over the clinically useful dose prescription range. For the lung cancer case, the HT and MLC-based IMRT plans give a P+ of 66.9% and 72.9%, {\\bar{\\bar{D}}} to the ITV of 64.0 Gy and 66.9 Gy, respectively. Similarly, for the prostate cancer case, the two radiation modalities give a P+ of 68.7% and 72.2%, {\\bar{\\bar{D}}} to the ITV of 86.0 Gy and 85.9 Gy, respectively. If a higher risk of complications (higher than 5%) could be allowed, the complication-free tumour control could increase by over 40%, 2% and 30% compared to the initial dose prescription for the three cancer cases, respectively. Both MLC-based IMRT and HT can encompass the often-large ITV required while they minimize the volume of the organs at risk receiving high doses. Radiobiological evaluation of treatment plans may provide an improved correlation of the delivered treatment with the clinical outcome by taking into account the dose-response characteristics of the irradiated targets and normal tissues. There may exist clinical cases, which may look dosimetrically similar but in radiobiological terms may be quite different. In such situations, traditional dose-based evaluation tools can be complemented by the use of P_ +{-}{\\bar{\\bar{D}}} diagrams to effectively evaluate and compare treatment plans.

Creation of an atlas of filter positions for fluence field modulated CT

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

Szczykutowicz, Timothy P., E-mail: TSzczykutowicz@uwhealth.org; Hermus, James

2015-04-15

Purpose: Fluence field modulated CT (FFMCT) and volume of interest (VOI) CT imaging applications require adjustment of the profile of the x-ray fluence incident on a patient as a function of view angle. Since current FFMCT prototypes can theoretically take on an infinite number of configurations, measuring a calibration data set for all possible positions would not be feasible. The present work details a methodology for calculating an atlas of configurations that will span all likely body regions, patient sizes, patient positioning, and imaging modes. The hypothesis is that there exists a finite number of unique modulator configurations that effectivelymore » span the infinite number of possible fluence profiles with minimal loss in performance. Methods: CT images of a head, shoulder, thorax, abdominal, wrist, and leg anatomical slices were dilated and contracted to model small, medium, and large sized patients. Additionally, the images were positioned from iso-center by three different amounts. The modulator configurations required to compensate for each image were computed assuming a FFMCT prototype, digital beam attenuator, (DBA), was set to equalize the detector exposure. Each atlas configuration should be different from the other atlas configurations. The degree of difference was quantified using the sum of the absolute differences in filter thickness between configurations. Using this metric, a set of unique wedge configurations for which no two configurations have a metric value smaller than some threshold can be constructed. Differences in the total number of incident photons between the unconstrained filters and the atlas were studied as a function of the number of atlas positions for each anatomical site and size/off-centering combination. Results: By varying the threshold used in creating the atlas, it was found that roughly 322 atlas positions provided an incident number of photons within 20% of using 19 440 unique filters (the number of atlas entries ranged from 7213 to 1). Additionally, for VOI applications implemented with a single VOI region, the number of required filter configurations was expressed in a simple closed form solution. Conclusions: The methodology proposed in this work will enable DBA-FFMCT and DBA-VOI imaging in the clinic without the need for patient specific air-scans to be performed. In addition, the methodology proposed here is directly applicable to other modulator designs such as piecewise linear, TomoTherapy multi leaf collimators, 2D fluid arrays, and inverse geometry CT.« less

The national cholesterol education program diet vs a diet lower in carbohydrates and higher in protein and monounsaturated fat: a randomized trial.

PubMed

Aude, Y Wady; Agatston, Arthur S; Lopez-Jimenez, Francisco; Lieberman, Eric H; Marie Almon; Hansen, Melinda; Rojas, Gerardo; Lamas, Gervasio A; Hennekens, Charles H

2004-10-25

In the United States, obesity is a major clinical and public health problem causing diabetes, dyslipidemia, and hypertension, as well as increasing cardiovascular and total mortality. Dietary restrictions of calories and saturated fat are beneficial. However, it remains unclear whether replacement of saturated fat with carbohydrates (as in the US National Cholesterol Education Program [NCEP] diet) or protein and monounsaturated fat (as in our isocaloric modified low-carbohydrate [MLC] diet, which is lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates) is optimal. We randomized 60 participants (29 women and 31 men) to the NCEP or the MLC diet and evaluated them every 2 weeks for 12 weeks. They were aged 28 to 71 years (mean age, 44 years in the NCEP and 46 years in the MLC group). A total of 36% of participants from the NCEP group and 35% from the MLC group had a body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than 27. The primary end point was weight loss, and secondary end points were blood lipid levels and waist-to-hip ratio. Weight loss was significantly greater in the MLC (13.6 lb) than in the NCEP group (7.5 lb), a difference of 6.1 lb (P = .02). There were no significant differences between the groups for total, low density, and high-density lipoprotein cholesterol, triglycerides, or the proportion of small, dense low-density lipoprotein particles. There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group. Waist-to-hip ratio was not significantly reduced between the groups (P = .27), but it significantly decreased within the MLC group (P = .009). Compared with the NCEP diet, the MLC diet, which is lower in total carbohydrates but higher in complex carbohydrates, protein, and monounsaturated fat, caused significantly greater weight loss over 12 weeks. There were no significant differences between the groups in blood lipid levels, but favorable changes were observed within the MLC diet group.

TH-E-BRE-05: Analysis of Dosimetric Characteristics in Two Leaf Motion Calculator Algorithms for Sliding Window IMRT

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

Wu, L; Huang, B; Rowedder, B

Purpose: The Smart leaf motion calculator (SLMC) in Eclipse treatment planning system is an advanced fluence delivery modeling algorithm as it takes into account fine MLC features including inter-leaf leakage, rounded leaf tips, non-uniform leaf thickness, and the spindle cavity etc. In this study, SLMC and traditional Varian LMC (VLMC) algorithms were investigated, for the first time, in dosimetric characteristics and delivery accuracy of sliding window (SW) IMRT. Methods: The SW IMRT plans of 51 cancer cases were included to evaluate dosimetric characteristics and dose delivery accuracy from leaf motion calculated by SLMC and VLMC, respectively. All plans were deliveredmore » using a Varian TrueBeam Linac. The DVH and MUs of the plans were analyzed. Three patient specific QA tools - independent dose calculation software IMSure, Delta4 phantom, and EPID portal dosimetry were also used to measure the delivered dose distribution. Results: Significant differences in the MUs were observed between the two LMCs (p≤0.001).Gamma analysis shows an excellent agreement between the planned dose distribution calculated by both LMC algorithms and delivered dose distribution measured by three QA tools in all plans at 3%/3 mm, leading to a mean pass rate exceeding 97%. The mean fraction of pixels with gamma < 1 of SLMC is slightly lower than that of VLMC in the IMSure and Delta4 results, but higher in portal dosimetry (the highest spatial resolution), especially in complex cases such as nasopharynx. Conclusion: The study suggests that the two LMCs generates the similar target coverage and sparing patterns of critical structures. However, SLMC is modestly more accurate than VLMC in modeling advanced MLC features, which may lead to a more accurate dose delivery in SW IMRT. Current clinical QA tools might not be specific enough to differentiate the dosimetric discrepancies at the millimeter level calculated by these two LMC algorithms. NIH/NIGMS grant U54 GM104944, Lincy Endowed Assistant Professorship.« less

SU-E-T-624: Portal Dosimetry Commissioning of Multiple (6) Varian TrueBeam Linacs Equipped with PortalVision DMI MV Imager

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

Weldon, M; DiCostanzo, D; Grzetic, S

2015-06-15

Purpose: To show that a single model for Portal Domisetry (PD) can be established for beam-matched TrueBeam™ linacs that are equipped with the DMI imager (43×43cm effective area). Methods: Our department acquired 6 new TrueBeam™s, 4 “Slim” and 2 “Edge” models. The Slims were equipped with 6 and 10MV photons, and the Edges with 6MV. MLCs differed between the Slims and Edges (Millennium 120 vs HD-MLC respectively). PD model was created from data acquired using a single linac (Slim). This includes maximum field size profile, as well as output factors and acquired measured fluence using the DMI imager. All identicalmore » linacs were beam-matched, profiles were within 1% at maximum field size at a variety of depths. The profile correction file was generated from 40×40 profile acquired at 5cm depth, 95cm SSD, and was adjusted for deviation at the field edges and corners. The PD model and profile correction was applied to all six TrueBeam™s and imagers. A variety of jaw only and sliding window (SW) MLC test fields, as well as TG-119 and clinical SW and VMAT plans were run on each linac to validate the model. Results: For 6X and 10X, field by field comparison using 3mm/3% absolute gamma criteria passed 90% or better for all cases. This was also true for composite comparisons of TG-199 and clinical plans, matching our current department criteria. Conclusion: Using a single model per photon energy for PD for the TrueBeam™ equipped with a DMI imager can produce clinically acceptable results across multiple identical and matched linacs. It is also possible to use the same PD model despite different MLCs. This can save time during commissioning and software updates.« less

Thrombin-induced activation of RhoA in platelet shape change.

PubMed

Bodie, S L; Ford, I; Greaves, M; Nixon, G F

2001-09-14

Thrombin-induced activation of RhoA and its involvement in the regulation of myosin II light chain(20) phosphorylation (MLC-P) in alpha-toxin permeabilized platelets was investigated. Permeabilized platelets, expressing normal levels of P-selectin, displayed a Ca(2+)-dependent increase in shape change and MLC-P. Thrombin activated RhoA as measured by a rhotekin-binding assay within 30 s of stimulation under conditions of constant [Ca(2+)](i). Under the same conditions and timecourse, thrombin or GTPgammaS induced an increase in MLC-P and platelet shape change which was not dependent on an increase in [Ca(2+)](i). The thrombin- and GTPgammaS-induced MLC-P in constant [Ca(2+)](i) was inhibited by the addition of Y27632, a Rho-kinase inhibitor. This study directly demonstrates that thrombin can activate RhoA in platelets in a timecourse compatible with a role in increasing MLC-P and shape change (not involving an increase in [Ca(2+)](i)). This is also Rho-kinase-dependent. Copyright 2001 Academic Press.

Poster - 53: Improving inter-linac DMLC IMRT dose precision by fine tuning of MLC leaf calibration

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

Nakonechny, Keith; Tran, Muoi; Sasaki, David

Purpose: To develop a method to improve the inter-linac precision of DMLC IMRT dosimetry. Methods: The distance between opposing MLC leaf banks (“gap size”) can be finely tuned on Varian linacs. The dosimetric effect due to small deviations from the nominal gap size (“gap error”) was studied by introducing known errors for several DMLC sliding gap sizes, and for clinical plans based on the TG119 test cases. The plans were delivered on a single Varian linac and the relationship between gap error and the corresponding change in dose was measured. The plans were also delivered on eight Varian 2100 seriesmore » linacs (at two institutions) in order to quantify the inter-linac variation in dose before and after fine tuning the MLC calibration. Results: The measured dose differences for each field agreed well with the predictions of LoSasso et al. Using the default MLC calibration, the variation in the physical MLC gap size was determined to be less than 0.4 mm between all linacs studied. The dose difference between the linacs with the largest and smallest physical gap was up to 5.4% (spinal cord region of the head and neck TG119 test case). This difference was reduced to 2.5% after fine tuning the MLC gap calibration. Conclusions: The inter-linac dose precision for DMLC IMRT on Varian linacs can be improved using a simple modification of the MLC calibration procedure that involves fine adjustment of the nominal gap size.« less

A post-transcriptional compensatory pathway in heterozygous ventricular myosin light chain 2-deficient mice results in lack of gene dosage effect during normal cardiac growth or hypertrophy.

PubMed

Minamisawa, S; Gu, Y; Ross, J; Chien, K R; Chen, J

1999-04-09

Our previous study of homozygous mutants of the ventricular specific isoform of myosin light chain 2 (mlc-2v) demonstrated that mlc-2v plays an essential role in murine heart development (Chen, J., Kubalak, S. W., Minamisawa, S., Price, R. L., Becker, K. D., Hickey, R., Ross, J., Jr., and Chien, K. R. (1998) J. Biol. Chem. 273, 1252-1256). As gene dosage of some myofibrillar proteins can affect muscle function, we have analyzed heterozygous mutants in depth. Ventricles of heterozygous mutants displayed a 50% reduction in mlc-2v mRNA, yet expressed normal levels of protein both under basal conditions and following induction of cardiac hypertrophy by aortic constriction. Heterozygous mutants exhibited cardiac function comparable to that of wild-type littermate controls both prior to and following aortic constriction. There were no significant differences in contractility and responses to calcium between wild-type and heterozygous unloaded cardiomyocytes. We conclude that heterozygous mutants show neither a molecular nor a physiological cardiac phenotype either at base line or following hypertrophic stimuli. These results suggest that post-transcriptional compensatory mechanisms play a major role in maintaining the level of MLC-2v protein in murine hearts. In addition, as our mlc-2v knockout mutants were created by a knock-in of Cre recombinase into the endogenous mlc-2v locus, this study demonstrates that heterozygous mlc-2v cre knock-in mice are appropriate for ventricular specific gene targeting.

SU-E-T-195: Gantry Angle Dependency of MLC Leaf Position Error

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

Ju, S; Hong, C; Kim, M

Purpose: The aim of this study was to investigate the gantry angle dependency of the multileaf collimator (MLC) leaf position error. Methods: An automatic MLC quality assurance system (AutoMLCQA) was developed to evaluate the gantry angle dependency of the MLC leaf position error using an electronic portal imaging device (EPID). To eliminate the EPID position error due to gantry rotation, we designed a reference maker (RM) that could be inserted into the wedge mount. After setting up the EPID, a reference image was taken of the RM using an open field. Next, an EPID-based picket-fence test (PFT) was performed withoutmore » the RM. These procedures were repeated at every 45° intervals of the gantry angle. A total of eight reference images and PFT image sets were analyzed using in-house software. The average MLC leaf position error was calculated at five pickets (-10, -5, 0, 5, and 10 cm) in accordance with general PFT guidelines using in-house software. This test was carried out for four linear accelerators. Results: The average MLC leaf position errors were within the set criterion of <1 mm (actual errors ranged from -0.7 to 0.8 mm) for all gantry angles, but significant gantry angle dependency was observed in all machines. The error was smaller at a gantry angle of 0° but increased toward the positive direction with gantry angle increments in the clockwise direction. The error reached a maximum value at a gantry angle of 90° and then gradually decreased until 180°. In the counter-clockwise rotation of the gantry, the same pattern of error was observed but the error increased in the negative direction. Conclusion: The AutoMLCQA system was useful to evaluate the MLC leaf position error for various gantry angles without the EPID position error. The Gantry angle dependency should be considered during MLC leaf position error analysis.« less

Investigation of the feasibility of a simple method for verifying the motion of a binary multileaf collimator synchronized with the rotation of the gantry for helical tomotherapy

PubMed Central

Uematsu, Masahiro; Ito, Makiko; Hama, Yukihiro; Inomata, Takayuki; Fujii, Masahiro; Nishio, Teiji; Nakamura, Naoki; Nakagawa, Keiichi

2012-01-01

In this paper, we suggest a new method for verifying the motion of a binary multileaf collimator (MLC) in helical tomotherapy. For this we used a combination of a cylindrical scintillator and a general‐purpose camcorder. The camcorder records the light from the scintillator following photon irradiation, which we use to track the motion of the binary MLC. The purpose of this study is to demonstrate the feasibility of this method as a binary MLC quality assurance (QA) tool. First, the verification was performed using a simple binary MLC pattern with a constant leaf open time; secondly, verification using the binary MLC pattern used in a clinical setting was also performed. Sinograms of simple binary MLC patterns, in which leaves that were open were detected as “open” from the measured light, define the sensitivity which, in this case, was 1.000. On the other hand, the specificity, which gives the fraction of closed leaves detected as “closed”, was 0.919. The leaf open error identified by our method was −1.3±7.5%. The 68.6% of observed leaves were performed within ± 3% relative error. The leaf open error was expressed by the relative errors calculated on the sinogram. In the clinical binary MLC pattern, the sensitivity and specificity were 0.994 and 0.997, respectively. The measurement could be performed with −3.4±8.0% leaf open error. The 77.5% of observed leaves were performed within ± 3% relative error. With this method, we can easily verify the motion of the binary MLC, and the measurement unit developed was found to be an effective QA tool. PACS numbers: 87.56.Fc, 87.56.nk PMID:22231222

SU-E-T-144: Effective Analysis of VMAT QA Generated Trajectory Log Files for Medical Accelerator Predictive Maintenance

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

Able, CM; Baydush, AH; Nguyen, C

Purpose: To determine the effectiveness of SPC analysis for a model predictive maintenance process that uses accelerator generated parameter and performance data contained in trajectory log files. Methods: Each trajectory file is decoded and a total of 131 axes positions are recorded (collimator jaw position, gantry angle, each MLC, etc.). This raw data is processed and either axis positions are extracted at critical points during the delivery or positional change over time is used to determine axis velocity. The focus of our analysis is the accuracy, reproducibility and fidelity of each axis. A reference positional trace of the gantry andmore » each MLC is used as a motion baseline for cross correlation (CC) analysis. A total of 494 parameters (482 MLC related) were analyzed using Individual and Moving Range (I/MR) charts. The chart limits were calculated using a hybrid technique that included the use of the standard 3σ limits and parameter/system specifications. Synthetic errors/changes were introduced to determine the initial effectiveness of I/MR charts in detecting relevant changes in operating parameters. The magnitude of the synthetic errors/changes was based on: TG-142 and published analysis of VMAT delivery accuracy. Results: All errors introduced were detected. Synthetic positional errors of 2mm for collimator jaw and MLC carriage exceeded the chart limits. Gantry speed and each MLC speed are analyzed at two different points in the delivery. Simulated Gantry speed error (0.2 deg/sec) and MLC speed error (0.1 cm/sec) exceeded the speed chart limits. Gantry position error of 0.2 deg was detected by the CC maximum value charts. The MLC position error of 0.1 cm was detected by the CC maximum value location charts for every MLC. Conclusion: SPC I/MR evaluation of trajectory log file parameters may be effective in providing an early warning of performance degradation or component failure for medical accelerator systems.« less

SU-F-T-372: Surface and Peripheral Dose in Compensator-Based FFF Beam IMRT

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

Zhang, D; Feygelman, V; Moros, E

2016-06-15

Purpose: Flattening filter free (FFF) beams produce higher dose rates. Combined with compensator IMRT techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or compensator-based IMRT. This ‘snap shot’ IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, surface doses in FFF beam treatment are usually higher than those from flattened beams. Because of less scattering due to no flattening filter, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introducemore » beam hardening effects and scattering such that the surface dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? Methods: This study applied Monte Carlo techniques to investigate the surface and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides various thicknesses of copper slabs to simulate various thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC defined FFF and flattened beams with various openings. After normalized to Dmax, the surface and peripheral dose was compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. Results: The surface dose at the central 0.5mm depth was close between the compensator and 6FFF MLC dose distributions, and about 8% (of Dmax) higher than the flattened 6MV MLC dose. At 8cm off axis at dmax, the peripheral dose between the 6FFF and flattened 6MV MLC demonstrated similar doses, while the compensator dose was about 1% higher. Conclusion: Compensator does not reduce the surface doses but slightly increases the peripheral doses due to scatter inside compensator.« less

SU-E-T-122: Dosimetric Comparison Between Cone, HDMLC and MicroMLC for the Treatment of Trigeminal Neuralgia

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

Vacca, N; Caussa, L; Filipuzzi, M

2014-06-01

Purpose: The purpose of this work was to evaluate the dosimetric characteristics of three collimation systems, 5mm circular cone (Brainlab) and square fields of 5mm with HDMLC (Varian) and microMLC Moduleaf, Siemens) for trigeminal neuralgia treatment. Methods: A TPS Iplan v4.5 BrainLAB was used to do treatment plans for each collimations system in a square solid water phantom with isocenter at 5cm depth. Single field and treatment plan including 11 arcs with fix field and 100° gantry range was made for each collimation systems. EBT3 films were positioned at isocenter in a coronal plane to measured dose distribution for allmore » geometries. Films were digitized with a Vidar DosimetryPro Red scanner with a resolution of 89dpi and RIT113v6.1 software was used for analysis. Penumbra region (80%–20%), FWHM and dose percentage at 5mm and 10mm from CAX were determined. All profiles were normalized at CAX. Results: For single beam the penumbra (FWHM) was 1.5mm (5.3mm) for the cone, 1.9mm (5.5mm) for HDMLC and 1.8mm (5.4mm) for the microMLC. Dose percentage at 5mm was 6.9% for cone, 12.5% for HDMLC and 8.7% for the microMLC. For treatment plan the penumbra (FWHM) was 2.58mm (5.47mm) for the cone, 2.8mm (5.84mm) for HDMLC and 2.58mm (6.09mm) for the microMLC. Dose perecentage at 5mm was 13.1% for cone, 16.1% for HDMLC, 15.2% for the microMLC. Conclusion: The cone has a dose falloff larger than the microMLC and HDMLC, by its reduced penumbra, this translates into better protection of surrounding healthy tissue, however, the microMLC and HDMLC have similar accuracy to cone.« less

SU-F-T-230: A Simple Method to Assess Accuracy of Dynamic Wave Arc Irradiation Using An Electronic Portal Imaging Device and Log Files

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

Hirashima, H; Miyabe, Y; Yokota, K

2016-06-15

Purpose: The Dynamic Wave Arc (DWA) technique, where the multi-leaf collimator (MLC) and gantry/ring move simultaneously in a predefined non-coplanar trajectory, has been developed on the Vero4DRT. The aim of this study is to develop a simple method for quality assurance of DWA delivery using an electronic portal imaging device (EPID) measurements and log files analysis. Methods: The Vero4DRT has an EPID on the beam axis, the resolution of which is 0.18 mm/pixel at the isocenter plane. EPID images were acquired automatically. To verify the detection accuracy of the MLC position by EPID images, the MLC position with intentional errorsmore » was assessed. Tests were designed considering three factors: (1) accuracy of the MLC position (2) dose output consistency with variable dose rate (160–400 MU/min), gantry speed (2.4–6°/s), ring speed (0.5–2.5°/s), and (3) MLC speed (1.6–4.2 cm/s). All the patterns were delivered to the EPID and compared with those obtained with a stationary radiation beam with a 0° gantry angle. The irradiation log, including the MLC position and gantry/ring angle, were recorded simultaneously. To perform independent checks of the machine accuracy, the MLC position and gantry/ring angle position were assessed using log files. Results: 0.1 mm intentional error can be detected by the EPID, which is smaller than the EPID pixel size. The dose outputs with different conditions of the dose rate and gantry/ring speed and MLC speed showed good agreement, with a root mean square (RMS) error of 0.76%. The RMS error between the detected and recorded data were 0.1 mm for the MLC position, 0.12° for the gantry angle, and 0.07° for the ring angle. Conclusion: The MLC position and dose outputs in variable conditions during DWA irradiation can be easily detected using EPID measurements and log file analysis. The proposed method is useful for routine verification. This research is (partially) supported by the Practical Research for Innovative Cancer Control (15Ack0106151h0001) from Japan Agency for Medical Research and development, AMED. Authors Takashi Mizowaki and Masahiro Hiraoka have consultancy agreement with Mitsubishi Heavy Industries, Ltd., Japan.« less

Task-Driven Optimization of Fluence Field and Regularization for Model-Based Iterative Reconstruction in Computed Tomography.

PubMed

Gang, Grace J; Siewerdsen, Jeffrey H; Stayman, J Webster

2017-12-01

This paper presents a joint optimization of dynamic fluence field modulation (FFM) and regularization in quadratic penalized-likelihood reconstruction that maximizes a task-based imaging performance metric. We adopted a task-driven imaging framework for prospective designs of the imaging parameters. A maxi-min objective function was adopted to maximize the minimum detectability index ( ) throughout the image. The optimization algorithm alternates between FFM (represented by low-dimensional basis functions) and local regularization (including the regularization strength and directional penalty weights). The task-driven approach was compared with three FFM strategies commonly proposed for FBP reconstruction (as well as a task-driven TCM strategy) for a discrimination task in an abdomen phantom. The task-driven FFM assigned more fluence to less attenuating anteroposterior views and yielded approximately constant fluence behind the object. The optimal regularization was almost uniform throughout image. Furthermore, the task-driven FFM strategy redistribute fluence across detector elements in order to prescribe more fluence to the more attenuating central region of the phantom. Compared with all strategies, the task-driven FFM strategy not only improved minimum by at least 17.8%, but yielded higher over a large area inside the object. The optimal FFM was highly dependent on the amount of regularization, indicating the importance of a joint optimization. Sample reconstructions of simulated data generally support the performance estimates based on computed . The improvements in detectability show the potential of the task-driven imaging framework to improve imaging performance at a fixed dose, or, equivalently, to provide a similar level of performance at reduced dose.

A role for long chain myosin light chain kinase (MLCK-210) in microvascular hyperpermeability during severe burns.

PubMed

Reynoso, Rashell; Perrin, Rachel M; Breslin, Jerome W; Daines, Dayle A; Watson, Katherine D; Watterson, D Martin; Wu, Mack H; Yuan, Sarah

2007-11-01

Microvascular leakage has been implicated in the pathogenesis of multiple organ dysfunction during trauma. Previous studies suggest the involvement of myosin light chain (MLC) phosphorylation-triggered endothelial contraction in the development of microvascular hyperpermeability. Myosin light chain kinase (MLCK) plays a key role in the control of MLC-phosphorylation status; thus, it is thought to modulate barrier function through its regulation of intracellular contractile machinery. The aim of this study was to further investigate the endothelial mechanism of MLC-dependent barrier injury in burns, focusing on the long isoform of MLCK (MLCK-210) that has recently been identified as the predominant isoform expressed in vascular endothelial cells. An MLCK-210 knockout mouse model was subjected to third-degree scald burn covering 25% total body surface area. The mesenteric microcirculation was observed using intravital microscopy, and the microvascular permeability was assessed by measuring the transvenular flux of fluorescein isothiocyanate-albumin. In a separate experiment, in vivo mesenteric hydraulic conductivity (Lp) was measured using the modified Landis technique. The injury caused a profound microvascular leakage, as indicated by a 2-fold increase in albumin flux and 4-fold increase in Lp at the early stages, which was associated with a high mortality within the 24-h period. Compared with wild-type control, the MLCK-210-deficient mice displayed a significantly improved survival with a greatly attenuated microvascular hyperpermeability response to albumin and fluid. These results provide direct evidence for a role of MLCK-210 in mediating burn-induced microvascular barrier injury and validate MLCK-210 as a potential therapeutic target in the treatment of burn edema.

Design considerations for a computer controlled multileaf collimator for the Harper Hospital fast neutron therapy facility.

PubMed

Maughan, Richard L; Yudelev, Mark; Aref, Amr; Chuba, Paul J; Forman, Jeffrey; Blosser, Emanuel J; Horste, Timothy

2002-04-01

The d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron is collimated using a unique multirod collimator (MRC). A computer controlled multileaf collimator (MLC) is being designed to improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. For the current study the use of focused or unfocused collimator leaves has been studied. Since the engineering effort associated with the leaf design and materials choice impacts significantly on cost, it was desirable to determine the clinical impact of using unfocused leaves in the MLC design. The MRC is a useful tool for studying the effects of using focused versus unfocused beams on beam penumbra. The effects of the penumbra for the different leaf designs on tumor and normal tissue DVHs in two selected sites (prostate and head and neck) was investigated. The increase in the penumbra resulting from using unfocused beams was small (approximately 1.5 mm for a 5 x 5 cm2 field and approximately 7.6 mm for a 25 x 25 cm2 field at 10 cm depth) compared to the contribution of phantom scatter to the penumbra width (5.4 and 20 mm for the small and large fields at 10 cm depth, respectively). Comparison of DVHs for tumor and critical normal tissue in a prostate and head and neck case showed that the dosimetric disadvantages of using an unfocused rather than focused beam were minimal and only significant at shallow depths. For the rare cases, where optimum penumbra conditions are required, a MLC incorporating tapered leaves and, thus, providing focused collimation in one plane is necessary.

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy*

PubMed Central

Woodall, Benjamin P.; Woodall, Meryl C.; Luongo, Timothy S.; Grisanti, Laurel A.; Tilley, Douglas G.; Elrod, John W.; Koch, Walter J.

2016-01-01

GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2fl/fl) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. PMID:27566547

Error detection capability of a novel transmission detector: a validation study for online VMAT monitoring.

PubMed

Pasler, Marlies; Michel, Kilian; Marrazzo, Livia; Obenland, Michael; Pallotta, Stefania; Björnsgard, Mari; Lutterbach, Johannes

2017-09-01

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min -1 . Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean : R 2   =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.

PubMed

Ringvold, H C; Khalil, R A

2017-01-01

Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca 2+ -dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca 2+ -dependent α, β, and γ, novel Ca 2+ -independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs. Activated PKC phosphorylates different substrates including ion channels, pumps, and nuclear proteins. PKC also phosphorylates CPI-17 leading to inhibition of MLC phosphatase, increased MLC phosphorylation, and enhanced VSM contraction. PKC could also initiate a cascade of protein kinases leading to phosphorylation of the actin-binding proteins calponin and caldesmon, increased actin-myosin interaction, and VSM contraction. Increased PKC activity has been associated with vascular disorders including ischemia-reperfusion injury, coronary artery disease, hypertension, and diabetic vasculopathy. PKC inhibitors could test the role of PKC in different systems and could reduce PKC hyperactivity in vascular disorders. First-generation PKC inhibitors such as staurosporine and chelerythrine are not very specific. Isoform-specific PKC inhibitors such as ruboxistaurin have been tested in clinical trials. Target delivery of PKC pseudosubstrate inhibitory peptides and PKC siRNA may be useful in localized vascular disease. Further studies of PKC and its role in VSM should help design isoform-specific PKC modulators that are experimentally potent and clinically safe to target PKC in vascular disease. © 2017 Elsevier Inc. All rights reserved.

Comparison of the helical tomotherapy against the multileaf collimator-based intensity-modulated radiotherapy and 3D conformal radiation modalities in lung cancer radiotherapy

PubMed Central

Mavroidis, P; Shi, C; Plataniotis, G A; Delichas, M G; Costa Ferreira, B; Rodriguez, S; Lind, B K; Papanikolaou, N

2011-01-01

Objectives The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy. Methods Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P+) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures. Results The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P+ of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average ΔP+ of 27.0% for a Δ effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average ΔP+ of 23.8% for a Δ effective uniform dose of 11.6 Gy. Conclusion A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose–response relations of the irradiated tumours and normal tissues. The use of P – effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans. PMID:20858664

Error detection capability of a novel transmission detector: a validation study for online VMAT monitoring

NASA Astrophysics Data System (ADS)

Pasler, Marlies; Michel, Kilian; Marrazzo, Livia; Obenland, Michael; Pallotta, Stefania; Björnsgard, Mari; Lutterbach, Johannes

2017-09-01

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min-1. Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean: R 2  =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

TM 4: Beam through the Main Linac Cryomodule

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

Bartnik, A.

2017-06-14

On May 15th 2017, the CBETA project reached the major funding milestone, “Beam through the MLC.” For this test, the team had to successfully accelerate the electron beam to 6 MeV in the Injector Cryomodule (ICM), and then to a final energy of 12 MeV in the Main Linac Cryomodule (MLC). The MLC contains six superconducting accelerating cavities; for this initial test only a single cavity was powered.

Optimization in Radiation Therapy: Applications in Brachytherapy and Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

McGeachy, Philip David

Over 50% of cancer patients require radiation therapy (RT). RT is an optimization problem requiring maximization of the radiation damage to the tumor while minimizing the harm to the healthy tissues. This dissertation focuses on two main RT optimization problems: 1) brachytherapy and 2) intensity modulated radiation therapy (IMRT). The brachytherapy research involved solving a non-convex optimization problem by creating an open-source genetic algorithm optimizer to determine the optimal radioactive seed distribution for a given set of patient volumes and constraints, both dosimetric- and implant-based. The optimizer was tested for a set of 45 prostate brachytherapy patients. While all solutions met the clinical standards, they also benchmarked favorably with those generated by a standard commercial solver. Compared to its compatriot, the salient features of the generated solutions were: slightly reduced prostate coverage, lower dose to the urethra and rectum, and a smaller number of needles required for an implant. Historically, IMRT requires modulation of fluence while keeping the photon beam energy fixed. The IMRT-related investigation in this thesis aimed at broadening the solution space by varying photon energy. The problem therefore involved simultaneous optimization of photon beamlet energy and fluence, denoted by XMRT. Formulating the problem as convex, linear programming was applied to obtain solutions for optimal energy-dependent fluences, while achieving all clinical objectives and constraints imposed. Dosimetric advantages of XMRT over single-energy IMRT in the improved sparing of organs at risk (OARs) was demonstrated in simplified phantom studies. The XMRT algorithm was improved to include clinical dose-volume constraints and clinical studies for prostate and head and neck cancer patients were investigated. Compared to IMRT, XMRT provided improved dosimetric benefit in the prostate case, particularly within intermediate- to low-dose regions (≤ 40 Gy) for OARs. For head and neck cases, XMRT solutions showed no significant disadvantage or advantage over IMRT. The deliverability concerns for the fluence maps generated from XMRT were addressed by incorporating smoothing constraints during the optimization and through successful generation of treatment machine files. Further research is needed to explore the full potential of the XMRT approach to RT.

Triggering of spin-flipping-modulated exchange bias in FeCo nanoparticles by electronic excitation

PubMed Central

Sarker, Debalaya; Bhattacharya, Saswata; Srivastava, Pankaj; Ghosh, Santanu

2016-01-01

The exchange coupling between ferromagnetic (FM)-antiferromagnetic (AF) interfaces is a key element of modern spintronic devices. We here introduce a new way of triggering exchange bias (EB) in swift heavy ion (SHI) irradiated FeCo-SiO2 films, which is a manifestation of spin-flipping at high irradiation fluence. The elongation of FeCo nanoparticles (NPs) in SiO2 matrix gives rise to perpendicular magnetic anisotropy at intermediate fluence. However, a clear shift in hysteresis loop is evident at the highest fluence. This reveals the existence of an AF exchange pinning domain in the NPs, which is identified not to be oxide shell from XANES analysis. Thermal spike calculations along with first-principles based simulations under the framework of density functional theory (DFT) demonstrate that spin flipping of 3d valence electrons is responsible for formation of these AF domains inside the FM NPs. EXAFS experiments at Fe and Co K-edges further unravel that spin-flipping in highest fluence irradiated film results in reduced bond lengths. The results highlight the possibility of miniaturization of magnetic storage devices by using irradiated NPs instead of conventionally used FM-AF multilayers. PMID:27991552

SU-G-BRB-10: New Generation of High Frame-Rate and High Spatial-Resolution EPID QA System for Full-Body MLC-Based Robotic Radiosurgery

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

Han, B; Xing, L; Wang, L

Purpose: To systematically investigate an ultra-high spatial-resolution amorphous silicon flat-panel electronic portal imaging device (EPID) for MLC-based full-body robotic radiosurgery geometric and dosimetric quality assurance (QA). Methods: The high frame-rate and ultra-high spatial resolution EPID is an outstanding detector for measuring profiles, MLC-shaped radiosurgery field aperture verification, and small field dosimetry. A Monte Carlo based technique with a robotic linac specific response and calibration is developed to convert a raw EPID-measured image of a radiosurgery field into water-based dose distribution. The technique is applied to measure output factors and profiles for 6MV MLC-defined radiosurgery fields with various sizes ranging frommore » 7.6mm×7.7mm to 100mm×100.1mm and the results are compared with the radiosurgery diode scan measurements in water tank. The EPID measured field sizes and the penumbra regions are analyzed to evaluate the MLC positioning accuracy. Results: For all MLC fields, the EPID measured output factors of MLC-shaped fields are in good agreement with the diode measurements. The mean output difference between the EPID and diode measurement is 0.05±0.87%. The max difference is −1.33% for 7.6mm×7.7mm field. The MLC field size derived from the EPID measurements are in good agreement comparing to the diode scan result. For crossline field sizes, the mean difference is −0.17mm±0.14mm with a maximum of −0.35mm for the 30.8mm×30.8mm field. For inline field sizes, the mean difference is +0.08mm±0.18mm with a maximum of +0.45mm for the 100mm×100.1mm field. The high resolution EPID is able to measure the whole radiation field, without the need to align the detector center perfectly at field center as diode or ion chamber measurement. The setup time is greatly reduced so that the whole process is possible for machine and patient-specific QA. Conclusion: The high spatial-resolution EPID is proved to be an accurate and efficient tool for QA of MLC-equipped robotic radiosurgery system.« less

A study to establish reasonable action limits for patient-specific quality assurance in intensity-modulated radiation therapy.

PubMed

Both, Stefan; Alecu, Ionut M; Stan, Andrada R; Alecu, Marius; Ciura, Andrei; Hansen, Jeremy M; Alecu, Rodica

2007-03-07

An effective patient quality assurance (QA) program for intensity-modulated radiation therapy (IMRT) requires accurate and realistic plan acceptance criteria--that is, action limits. Based on dose measurements performed with a commercially available two-dimensional (2D) diode array, we analyzed 747 fluence maps resulting from a routine patient QA program for IMRT plans. The fluence maps were calculated by three different commercially available (ADAC, CMS, Eclipse) treatment planning systems (TPSs) and were delivered using 6-MV X-ray beams produced by linear accelerators. To establish reasonably achievable and clinically acceptable limits for the dose deviations, the agreement between the measured and calculated fluence maps was evaluated in terms of percent dose error (PDE) for a few points and percent of passing points (PPP) for the isodose distribution. The analysis was conducted for each TPS used in the study (365 ADAC, 162 CMS,220 Eclipse), for multiple treatment sites (prostate, pelvis, head and neck, spine, rectum, anus, lung, brain), at the normalization point for 3% percentage difference (%Diff) and 3-mm distance to agreement (DTA) criteria. We investigated the treatment-site dependency of PPP and PDE. The results show that, at 3% and 3-mm criteria, a 95% PPP and 3% PDE can be achieved for prostate treatments and a 90% PPP and 5% PDE are attainable for any treatment site.

Ultrafast modulation of the plasma frequency of vertically aligned indium tin oxide rods.

PubMed

Tice, Daniel B; Li, Shi-Qiang; Tagliazucchi, Mario; Buchholz, D Bruce; Weiss, Emily A; Chang, Robert P H

2014-03-12

Light-matter interaction at the nanoscale is of particular interest for future photonic integrated circuits and devices with applications ranging from communication to sensing and imaging. In this Letter a combination of transient absorption (TA) and the use of third harmonic generation as a probe (THG-probe) has been adopted to investigate the response of the localized surface plasmon resonances (LSPRs) of vertically aligned indium tin oxide rods (ITORs) upon ultraviolet light (UV) excitation. TA experiments, which are sensitive to the extinction of the LSPR, show a fluence-dependent increase in the frequency and intensity of the LSPR. The THG-probe experiments show a fluence-dependent decrease of the LSPR-enhanced local electric field intensity within the rod, consistent with a shift of the LSPR to higher frequency. The kinetics from both TA and THG-probe experiments are found to be independent of the fluence of the pump. These results indicate that UV excitation modulates the plasma frequency of ITO on the ultrafast time scale by the injection of electrons into, and their subsequent decay from, the conduction band of the rods. Increases to the electron concentration in the conduction band of ∼13% were achieved in these experiments. Computer simulation and modeling have been used throughout the investigation to guide the design of the experiments and to map the electric field distribution around the rods for interpreting far-field measurement results.

Phototropin 1 and dim-blue light modulate the red light de-etiolation response.

PubMed

Wang, Yihai; M Folta, Kevin

2014-01-01

Light signals regulate seedling morphological changes during de-etiolation through the coordinated actions of multiple light-sensing pathways. Previously we have shown that red-light-induced hypocotyl growth inhibition can be reversed by addition of dim blue light through the action of phototropin 1 (phot1). Here we further examine the fluence-rate relationships of this blue light effect in short-term (hours) and long-term (days) hypocotyl growth assays. The red stem-growth inhibition and blue promotion is a low-fluence rate response, and blue light delays or attenuates both the red light and far-red light responses. These de-etiolation responses include blue light reversal of red or far-red induced apical hook opening. This response also requires phot1. Cryptochromes (cry1 and cry2) are activated by higher blue light fluence-rates and override phot1's influence on hypocotyl growth promotion. Exogenous application of auxin transport inhibitor naphthylphthalamic acid abolished the blue light stem growth promotion in both hypocotyl growth and hook opening. Results from the genetic tests of this blue light effect in auxin transporter mutants, as well as phytochrome kinase substrate mutants indicated that aux1 may play a role in blue light reversal of red light response. Together, the phot1-mediated adjustment of phytochrome-regulated photomorphogenic events is most robust in dim blue light conditions and is likely modulated by auxin transport through its transporters.

Intensity-modulated radiation therapy (IMRT) with different combinations of treatment-planning systems and linacs: issues and how to detect them.

PubMed

Dobler, Barbara; Lorenz, Friedlieb; Wertz, Hansjörg; Polednik, Martin; Wolff, Dirk; Steil, Volker; Lohr, Frank; Wenz, Frederik

2006-08-01

To compare different combinations of intensity-modulated radiation therapy (IMRT) system components with regard to quality assurance (QA), especially robustness against malfunctions and dosimetry. Three different treatment-planning systems (TPS), two types of linacs and three multileaf collimator (MLC) types were compared: commissioning procedures were performed for the combination of the TPS Corvus 5.0 (Nomos) and KonRad v2.1.3 (Siemens OCS) with the linacs KD2 (Siemens) and Synergy (Elekta). For PrecisePLAN 2.03 (Elekta) measurements were performed for Elekta Synergy only. As record and verify (R&V) system Multi-Access v7 (IMPAC) was used. The use of the serial tomotherapy system Peacock (Nomos) was investigated in combination with the Siemens KD2 linac. In the comparison of calculated to measured dose, problems were encountered for the combination of KonRad and Elekta MLC as well as for the Peacock system. Multi-Access failed to assign the collimator angle correctly for plans with multiple collimator angles per beam. Communication problems of Multi-Access with both linacs were observed, resulting in incorrect recording of the treatment. All reported issues were addressed by the manufacturers. For the commissioning of IMRT systems, the whole chain from the TPS to the linac has to be investigated. Components that passed the commissioning in another clinical environment can have severe malfunctions when used in a new environment. Therefore, not only single components but the whole chain from planning to delivery has to be evaluated in commissioning and checked regularly for QA.

Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes

PubMed Central

Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B. Cicero; Zarzoso, Manuel; Ramirez, Rafael J.; Sener, Michelle F.; Mundada, Lakshmi V.; Klos, Matthew; Devaney, Eric J.; Vikstrom, Karen L.; Herron, Todd J.; Jalife, José

2014-01-01

Applications of human induced pluripotent stemcell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricularmyocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. PMID:24095945

Patient views through the keyhole: new perspectives on single-incision vs. multiport laparoscopic cholecystectomy

PubMed Central

Hey, Jennifer; Roberts, Keith John; Morris-Stiff, Gareth J; Toogood, Giles J

2012-01-01

Objectives Single-incision laparoscopic cholecystectomy (SILC) may be associated with less pain, shorter hospital stay and better cosmetic results than multiport laparoscopic cholecystectomy (MLC). Advocates suggest that patients prefer SILC, although research directly addressing the question of patient preferences is limited. This study aimed to assess patient preferences using currently available evidence. Methods Patients awaiting elective cholecystectomy were shown a series of postoperative images taken after SILC or MLC and asked which procedure this led them to prefer. This was repeated after patients had completed a questionnaire constructed using published objective data comparing patient-reported outcomes of SILC and MLC. Results The study was completed by 113 consecutive patients. After their initial viewing of the images, 16% of subjects preferred MLC. Younger age, lower body mass index and female sex were associated with choosing SILC. After completing the questionnaire, 88% of patients preferred MLC (P < 0.001). Patients ranked the level of risk for complications and postoperative pain above cosmetic results in determining their choice of procedure. Conclusions Patients' initial preference when presented with cosmetic appearance was for SILC. When contemporary outcome data were included, the majority chose MLC. This underlines the need to fully inform patients during the consent process and indicates that patient views of SILC may differ from the views of those introducing the technology. PMID:22404262

Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

PubMed

Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B Cicero; Zarzoso, Manuel; Ramirez, Rafael J; Sener, Michelle F; Mundada, Lakshmi V; Klos, Matthew; Devaney, Eric J; Vikstrom, Karen L; Herron, Todd J; Jalife, José

2013-11-01

Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. © 2013.

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

SU-F-T-463: Light-Field Based Dynalog Verification

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

Atwal, P; Ramaseshan, R

2016-06-15

Purpose: To independently verify leaf positions in so-called dynalog files for a Varian iX linac with a Millennium 120 MLC. This verification provides a measure of confidence that the files can be used directly as part of a more extensive intensity modulated radiation therapy / volumetric modulated arc therapy QA program. Methods: Initial testing used white paper placed at the collimator plane and a standard hand-held digital camera to image the light and shadow of a static MLC field through the paper. Known markings on the paper allow for image calibration. Noise reduction was attempted with removal of ‘inherent noise’more » from an open-field light image through the paper, but the method was found to be inconsequential. This is likely because the environment could not be controlled to the precision required for the sort of reproducible characterization of the quantum noise needed in order to meaningfully characterize and account for it. A multi-scale iterative edge detection algorithm was used for localizing the leaf ends. These were compared with the planned locations from the treatment console. Results: With a very basic setup, the image of the central bank A leaves 15–45, which are arguably the most important for beam modulation, differed from the planned location by [0.38±0.28] mm. Similarly, for bank B leaves 15–45 had a difference of [0.42±0.28] mm Conclusion: It should be possible to determine leaf position accurately with not much more than a modern hand-held camera and some software. This means we can have a periodic and independent verification of the dynalog file information. This is indicated by the precision already achieved using a basic setup and analysis methodology. Currently, work is being done to reduce imaging and setup errors, which will bring the leaf position error down further, and allow meaningful analysis over the full range of leaves.« less

Dynamic-MLC leaf control utilizing on-flight intensity calculations: a robust method for real-time IMRT delivery over moving rigid targets.

PubMed

McMahon, Ryan; Papiez, Lech; Rangaraj, Dharanipathy

2007-08-01

An algorithm is presented that allows for the control of multileaf collimation (MLC) leaves based entirely on real-time calculations of the intensity delivered over the target. The algorithm is capable of efficiently correcting generalized delivery errors without requiring the interruption of delivery (self-correcting trajectories), where a generalized delivery error represents anything that causes a discrepancy between the delivered and intended intensity profiles. The intensity actually delivered over the target is continually compared to its intended value. For each pair of leaves, these comparisons are used to guide the control of the following leaf and keep this discrepancy below a user-specified value. To demonstrate the basic principles of the algorithm, results of corrected delivery are shown for a leading leaf positional error during dynamic-MLC (DMLC) IMRT delivery over a rigid moving target. It is then shown that, with slight modifications, the algorithm can be used to track moving targets in real time. The primary results of this article indicate that the algorithm is capable of accurately delivering DMLC IMRT over a rigid moving target whose motion is (1) completely unknown prior to delivery and (2) not faster than the maximum MLC leaf velocity over extended periods of time. These capabilities are demonstrated for clinically derived intensity profiles and actual tumor motion data, including situations when the target moves in some instances faster than the maximum admissible MLC leaf velocity. The results show that using the algorithm while calculating the delivered intensity every 50 ms will provide a good level of accuracy when delivering IMRT over a rigid moving target translating along the direction of MLC leaf travel. When the maximum velocities of the MLC leaves and target were 4 and 4.2 cm/s, respectively, the resulting error in the two intensity profiles used was 0.1 +/- 3.1% and -0.5 +/- 2.8% relative to the maximum of the intensity profiles. For the same target motion, the error was shown to increase rapidly as (1) the maximum MLC leaf velocity was reduced below 75% of the maximum target velocity and (2) the system response time was increased.

SU-F-T-629: Effect of Multi-Leaf Collimator (MLC) Width On Plan Quality of Single-Isocenter VMAT Intracranial Stereotactic Radiosurgery for Multiple Metastases

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

Kraus, J; Thomas, E; Wu, X

2016-06-15

Purpose: Single-isocenter VMAT has been shown able to create high quality plans for complex intracranial multiple metastasis SRS cases. Linacs capable of the technique are typically outfitted with an MLC that consists of a combination of 5 mm and 10 mm leaves (standard) or 2.5 mm and 5 mm leaves (high-definition). In this study, we test the hypothesis that thinner collimator leaves are associated with improved plan quality. Methods: Ten multiple metastasis cases were identified and planned for VMAT SRS using a 10 MV flattening filter free beam. Plans were created for a standard (std) and a high-definition (HD) MLC.more » Published values for leaf transmission factor and dosimetric leaf gap were utilized. All other parameters were invariant. Conformity (plan and individual target), moderate isodose spill (V50%), and low isodose spill (mean brain dose) were selected for analysis. Results: Compared to standard MLC, HD-MLC improved overall plan conformity (median: Paddick CI-HD = 0.83, Paddick CI-std = 0.79; p = 0.004 and median: RTOG CI-HD =1.18, RTOG CI-std =1.24; p = 0.01 ), improved individual lesion conformity (median: Paddick CI-HD,i =0.77, Paddick CI-std,i =0.72; p < 0.001 and median: RTOG CI-HD,i = 1.28, RTOG CI-std,i =1.35; p < 0.001), improved moderate isodose spill (median: V50%-HD = 37.0 cc, V50%-std = 45.7 cc; p = 0.002), and improved low dose spill (median: dmean-HD = 2.90 Gy, dmean-std = 3.19 Gy; p = 0.002). Conclusion: For the single-isocenter VMAT SRS of multiple metastasis plans examined, use of HD-MLC modestly improved conformity, moderate isodose, and low isodose spill compared to standard MLC. However, in all cases we were able to generate clinically acceptable plans with the standard MLC. More work is need to further quantify the difference in cases with higher numbers of small targets and to better understand any potential clinical significance. This research was supported in part by Varian Medical Systems.« less

SU-D-201-04: Evaluation of Elekta Agility MLC Performance Using Statistical Process Control

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

Meyers, SM; Balderson, MJ; Letourneau, D

2016-06-15

Purpose: to evaluate the performance and stability of the Elekta Agility MLC model using an automated quality control (QC) test in combination with statistical process control tools. Methods: Leaf positions were collected daily for 11 Elekta units over 5–19 months using the automated QC test, which analyzes 23 MV images to determine the location of MLC leaves relative to the radiation isocenter. The leaf positions are measured at 5 nominal positions, and images are acquired at collimator 0° and 180° to capture all MLC leaves in the field-of-view. Leaf positioning accuracy was assessed using individual and moving range control charts.more » Control limits were recomputed following MLC recalibration (occurred 1–2 times for 4 units). Specification levels of ±0.5, ±1 and ±1.5mm were tested. The mean and range of duration between out-of-control and out-of-specification events were determined. Results: Leaf position varied little over time, as confirmed by very tight individual control limits (mean ±0.19mm, range 0.09–0.44). Mean leaf position error was −0.03mm (range −0.89–0.83). Due to sporadic out-of-control events, the mean in-control duration was 3.3 days (range 1–23). Data stayed within ±1mm specification for 205 days on average (range 3–372) and within ±1.5mm for the entire date range. Measurements stayed within ±0.5mm for 1 day on average (range 0–17); however, our MLC leaves were not calibrated to this level of accuracy. Conclusion: The Elekta Agility MLC model was found to perform with high stability, as evidenced by the tight control limits. The in-specification durations support the current recommendation of monthly MLC QC tests with a ±1mm tolerance. Future work is on-going to determine if Agility performance can be optimized further using high-frequency QC test results to drive recalibration frequency. Factors that can affect leaf positioning accuracy, including beam spot motion, leaf gain calibration, drifting leaves, and image artifacts, are under investigation.« less

SU-G-JeP2-03: Automatic Quantification of MLC Positional Accuracy in An MRI Guided Radiotherapy System

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

Li, X; Studenski, M; Yang, F

Purpose: MRI-guided-radiotherapy (MRIGRT) systems lack many features of traditional Linac based RT systems and specialized tests need to be developed to evaluate MLC performance. This work describes automatic tools for the analysis of positional accuracy of an MLC equipped MRIGRT system. Methods: This MLC analysis tool was developed for the MRIdian™ RT system which has three Co-60 equipped treatment heads each with a double focused MLC containing 30 leaf pairs, leaf thickness is 1.05cm defined at isocenter (SAD 105 cm). For MLC positional analysis a picket fence test was performed using a 25.4cm × 25.4cm Gafchromic™ RTQA2 film placed betweenmore » 5cm solidwater and a 30cm × 30cm × 1cm jigwire phantom with seven embedded parallel metal strips 4cm apart. A plan was generated to deliver 2Gy per field and seven 23.1cm × 2cm fields centered over each wire in the phantom. For each leaf pair the center of the radiation profile was determined by fitting the horizontal profile with a Gaussian model and determining the center of the FWHM. This was compared with the metal strip location to determine any deviation. The following metrics were used to evaluate the deviations per gantry angle including maximum, minimum, mean, Kurtosis, and skewness. Results: The identified maximum/mean leaf deviations are, 1.32/0.55 mm for gantry 0°, 1.59/0.76 mm for gantry 90°, and 1.19/0.39 mm for gantry 270°. The percentage of leaf deviation less than 1mm are 90.0% at 0°, 74.6% at 90°, and 97.0% at 270°. Kurtosis/skewness of the leaf deviation are 2.41/0.14 at 0°, 2.53/0.23 at 90°, 3.33/0.83 at 270°, respectively. Conclusion: This work presents an automatic tool for evaluation of the MLC position accuracy of the MRIdian™ radiotherapy system which can be used to benchmark the performance of the MLC system for each treatment head and track the results longitudinally.« less

Characteristics and performance of the first commercial multileaf collimator for a robotic radiosurgery system

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

Fürweger, Christoph, E-mail: christoph.fuerweger@cyber-knife.net; Prins, Paulette; Coskan, Harun

Purpose: The “InCise™ multileaf-collimator (MLC)” is the first commercial MLC to be mounted on a robotic SRS/SBRT platform (CyberKnife). The authors assessed characteristics and performance of this novel device in a preclinical five months test period. Methods: Commissioning beam data were acquired with unshielded diodes. EBT3 radiochromic films were employed for measurement of transmission, leaf/bank position accuracy (garden fence) before and after exercising the MLC, for end-to-end testing and further characterization of the beam. The robot workspace with MLC was assessed analytically by transformation to an Euler geometry (“plane,” “gantry,” and “collimator” angles) and by measuring pointing accuracy at eachmore » node. Stability over time was evaluated in picket fence and adapted Winston–Lutz tests (AQA). Results: Beam penumbrae (80%–20%, with 100% = 2 × dose at inflection point for field sizes ≥ 50 × 50 mm{sup 2}) were 2.2–3.7 mm for square fields in reference condition (source-axis-distance 800 mm, depth 15 mm) and depended on field size and off-axis position. Transmission and leakage did not exceed 0.5%. Accessible clinical workspace with MLC covered non-coplanar gantry angles of [−113°; +112°] and collimator angles of [−100°; +107°], with an average robot pointing accuracy of 0.12 ± 0.09 mm. For vertical beams, garden fence tests exhibited an average leaf positioning error of ≤0.2 mm, which increased by 0.25 and 0.30 mm (banks X1 and X2) with leaves traveling parallel to gravity. After execution of a leaf motion stress routine, garden fence tests showed slightly increased jaggedness and allowed to identify one malfunctioning leaf motor. Total system accuracy with MLC was 0.38 ± 0.05 mm in nine end-to-end tests. Picket fence and AQA tests displayed stable results over the test period. Conclusions: The InCise™ MLC for CyberKnife showed high accuracy and adequate characteristics for SRS/SBRT applications. MLC performance after exercise demands specific quality assurance measures.« less

Characteristics and performance of the first commercial multileaf collimator for a robotic radiosurgery system.

PubMed

Fürweger, Christoph; Prins, Paulette; Coskan, Harun; Heijmen, Ben J M

2016-05-01

The "InCise™ multileaf-collimator (MLC)" is the first commercial MLC to be mounted on a robotic SRS/SBRT platform (CyberKnife). The authors assessed characteristics and performance of this novel device in a preclinical five months test period. Commissioning beam data were acquired with unshielded diodes. EBT3 radiochromic films were employed for measurement of transmission, leaf/bank position accuracy (garden fence) before and after exercising the MLC, for end-to-end testing and further characterization of the beam. The robot workspace with MLC was assessed analytically by transformation to an Euler geometry ("plane," "gantry," and "collimator" angles) and by measuring pointing accuracy at each node. Stability over time was evaluated in picket fence and adapted Winston-Lutz tests (AQA). Beam penumbrae (80%-20%, with 100% = 2 × dose at inflection point for field sizes ≥ 50 × 50 mm(2)) were 2.2-3.7 mm for square fields in reference condition (source-axis-distance 800 mm, depth 15 mm) and depended on field size and off-axis position. Transmission and leakage did not exceed 0.5%. Accessible clinical workspace with MLC covered non-coplanar gantry angles of [-113°; +112°] and collimator angles of [-100°; +107°], with an average robot pointing accuracy of 0.12 ± 0.09 mm. For vertical beams, garden fence tests exhibited an average leaf positioning error of ≤0.2 mm, which increased by 0.25 and 0.30 mm (banks X1 and X2) with leaves traveling parallel to gravity. After execution of a leaf motion stress routine, garden fence tests showed slightly increased jaggedness and allowed to identify one malfunctioning leaf motor. Total system accuracy with MLC was 0.38 ± 0.05 mm in nine end-to-end tests. Picket fence and AQA tests displayed stable results over the test period. The InCise™ MLC for CyberKnife showed high accuracy and adequate characteristics for SRS/SBRT applications. MLC performance after exercise demands specific quality assurance measures.

Fluence compensated photoacoustic tomography in small animals (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hussain, Altaf; Pool, Martin; Daoudi, Khalid; de Vries, Liesbeth G.; Steenbergen, Wiendelt

2017-03-01

Light fluence inside turbid media can be experimentally mapped by measuring ultrasonically modulated light (Acousto-optics). To demonstrate the feasibility of fluence corrected Photoacoustic (PA) imaging, we have realized a tri-modality (i.e. photoacoustic, acousto-optic and ultrasound) tomographic small animal imaging system. Wherein PA imaging provides high resolution map of absorbed optical energy density, Acousto-optics yields the fluence distribution map in the corresponding PA imaging plane and Ultrasound provides morphological information. Further, normalization of the PA image with the acousto-optically measured fluence map results in an image that directly represents the optical absorption. Human epidermal growth factor receptor 2 (HER2) is commonly found overexpressed in human cancers, among which breast cancers, resulting in a more aggressive tumor phenotype. Identification of HER2-expression is clinically relevant, because cancers overexpressing this marker are amenable to HER2-directed therapies, among which antibodies trastuzumab and pertuzumab. Here, we investigate the feasibility and advantage of acousto-optically assisted fluence compensated PA imaging over PA imaging alone in visualizing and quantifying HER2 expression. For this experiment, nude mice were xenografted with human breast cancer cell lines SKBR3 and BT474 (both HER2 overexpressing), as well as HER2-negative MDA-MB-231. To visualize HER2 expression in these mice, HER2 monoclonal antibody pertuzumab (Perjeta®, Roche), was conjugated to near-infrared dye IRDye 800CW (800CW, LICOR Biosciences) at a ratio of 1∶2 antibody to 800CW. When xenograft tumors measured ≥ 100 mm3, mice received 100 µg 800CW-pertuzumab intravenously. Three days post injection, mice were scanned for fluorescence signal with an IVIS scanner. After fluorescence scans, mice were euthanized and imaged in our PA tomographic imaging system.

LONG-TERM EVOLUTION OF THE MAIN-ON STATES IN HERCULES X-1

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

Šimon, Vojtech, E-mail: simon@asu.cas.cz

2015-07-15

Rossi X-ray Timing Explorer All-sky Monitor (RXTE ASM) observations and American Association of Variable Star Observers (AAVSO) optical data were used for a time-series analysis of the long-term activity of Her X-1. The problem of measuring the long-term evolution of the X-ray intensity in the light curve which consists only of separated intense spikes was addressed. For this purpose, the fluence of each Main-On state was determined. The fluences vary generally (not only in the transitions into/from anomalous low states (ALSs)) by tens of percent on timescales of at least several epochs of the cycle length of the superorbital cyclemore » (but without any stable cycle) while irradiation of the donor producing the optical modulation remains considerably more stable. ALS1 and ALS2 are extensions of the tail in the statistical distribution of these fluences. In this interpretation, the variations of the fluences are caused by the changes of the structure of the inner disk region, which produces variable obscuration of the beams (emitting in the ASM band) at the neutron star. A small change of obscuration of these beams by the inner disk region suffices to change the fluences largely. However, the irradiation of the donor is changed significantly less because this inner disk region (which emits beyond the ASM band and acts as the occulting region of the beams) also irradiates the donor.« less

Pitfalls of tungsten multileaf collimator in proton beam therapy.

PubMed

Moskvin, Vadim; Cheng, Chee-Wai; Das, Indra J

2011-12-01

Particle beam therapy is associated with significant startup and operational cost. Multileaf collimator (MLC) provides an attractive option to improve the efficiency and reduce the treatment cost. A direct transfer of the MLC technology from external beam radiation therapy is intuitively straightforward to proton therapy. However, activation, neutron production, and the associated secondary cancer risk in proton beam should be an important consideration which is evaluated. Monte Carlo simulation with FLUKA particle transport code was applied in this study for a number of treatment models. The authors have performed a detailed study of the neutron generation, ambient dose equivalent [H∗(10)], and activation of a typical tungsten MLC and compared with those obtained from a brass aperture used in a typical proton therapy system. Brass aperture and tungsten MLC were modeled by absorber blocks in this study, representing worst-case scenario of a fully closed collimator. With a tungsten MLC, the secondary neutron dose to the patient is at least 1.5 times higher than that from a brass aperture. The H∗(10) from a tungsten MLC at 10 cm downstream is about 22.3 mSv/Gy delivered to water phantom by noncollimated 200 MeV beam of 20 cm diameter compared to 14 mSv/Gy for the brass aperture. For a 30-fraction treatment course, the activity per unit volume in brass aperture reaches 5.3 × 10⁴ Bq cm(-3) at the end of the last treatment. The activity in brass decreases by a factor of 380 after 24 h, additional 6.2 times after 40 days of cooling, and is reduced to background level after 1 yr. Initial activity in tungsten after 30 days of treating 30 patients per day is about 3.4 times higher than in brass that decreases only by a factor of 2 after 40 days and accumulates to 1.2 × 10⁶ Bq cm(-3) after a full year of operation. The daily utilization of the MLC leads to buildup of activity with time. The overall activity continues to increase due to (179)Ta with a half-life of 1.82 yr and thus require prolonged storage for activity cooling. The H∗(10) near the patient side of the tungsten block is about 100 μSv/h and is 27 times higher at the upstream side of the block. This would lead to an accumulated dose for therapists in a year that may exceed occupational maximum permissible dose (50 mSv/yr). The value of H∗(10) at the upstream surface of the tungsten block is about 220 times higher than that of the brass. MLC is an efficient way for beam shaping and overall cost reduction device in proton therapy. However, based on this study, tungsten seems to be not an optimal material for MLC in proton beam therapy. Usage of tungsten MLC in clinic may create unnecessary risks associated with the secondary neutrons and induced radioactivity for patients and staff depending on the patient load. A careful selection of material for manufacturing of an optimal MLC for proton therapy is thus desired.

Second Positive Phototropism Results from Coordinated Co-Action of the Phototropins and Cryptochromes1

PubMed Central

Whippo, Craig W.; Hangarter, Roger P.

2003-01-01

Phototropism and hypocotyl growth inhibition are modulated by the coaction of different blue-light photoreceptors and their signaling pathways. How seedlings integrate the activities of the different blue-light photoreceptors to coordinate these hypocotyl growth responses is still unclear. We have used time-lapse imaging and a nontraditional mathematical approach to conduct a detailed examination of phototropism in wild-type Arabidopsis and various blue-light photoreceptor mutants. Our results indicate that high fluence rates of blue light (100 μmol m–2 s–1) attenuate phototropism through the coaction of the phototropin and cryptochrome blue-light photoreceptors. In contrast, we also demonstrate that phototropins and cryptochromes function together to enhance phototropism under low fluence rates (<1.0 μmol m–2 s–1) of blue light. Based on our results, we hypothesize that phototropins and cryptochromes regulate phototropism by coordinating the balance between stimulation and inhibition of growth of the hypocotyl depending on the fluence rate of blue light. PMID:12857830

Second positive phototropism results from coordinated co-action of the phototropins and cryptochromes.

PubMed

Whippo, Craig W; Hangarter, Roger P

2003-07-01

Phototropism and hypocotyl growth inhibition are modulated by the coaction of different blue-light photoreceptors and their signaling pathways. How seedlings integrate the activities of the different blue-light photoreceptors to coordinate these hypocotyl growth responses is still unclear. We have used time-lapse imaging and a nontraditional mathematical approach to conduct a detailed examination of phototropism in wild-type Arabidopsis and various blue-light photoreceptor mutants. Our results indicate that high fluence rates of blue light (100 micro mol m(-)(2) s(-)(1)) attenuate phototropism through the coaction of the phototropin and cryptochrome blue-light photoreceptors. In contrast, we also demonstrate that phototropins and cryptochromes function together to enhance phototropism under low fluence rates (<1.0 micro mol m(-)(2) s(-)(1)) of blue light. Based on our results, we hypothesize that phototropins and cryptochromes regulate phototropism by coordinating the balance between stimulation and inhibition of growth of the hypocotyl depending on the fluence rate of blue light.

Dosimetric verification of radiation therapy including intensity modulated treatments, using an amorphous-silicon electronic portal imaging device

NASA Astrophysics Data System (ADS)

Chytyk-Praznik, Krista Joy

Radiation therapy is continuously increasing in complexity due to technological innovation in delivery techniques, necessitating thorough dosimetric verification. Comparing accurately predicted portal dose images to measured images obtained during patient treatment can determine if a particular treatment was delivered correctly. The goal of this thesis was to create a method to predict portal dose images that was versatile and accurate enough to use in a clinical setting. All measured images in this work were obtained with an amorphous silicon electronic portal imaging device (a-Si EPID), but the technique is applicable to any planar imager. A detailed, physics-motivated fluence model was developed to characterize fluence exiting the linear accelerator head. The model was further refined using results from Monte Carlo simulations and schematics of the linear accelerator. The fluence incident on the EPID was converted to a portal dose image through a superposition of Monte Carlo-generated, monoenergetic dose kernels specific to the a-Si EPID. Predictions of clinical IMRT fields with no patient present agreed with measured portal dose images within 3% and 3 mm. The dose kernels were applied ignoring the geometrically divergent nature of incident fluence on the EPID. A computational investigation into this parallel dose kernel assumption determined its validity under clinically relevant situations. Introducing a patient or phantom into the beam required the portal image prediction algorithm to account for patient scatter and attenuation. Primary fluence was calculated by attenuating raylines cast through the patient CT dataset, while scatter fluence was determined through the superposition of pre-calculated scatter fluence kernels. Total dose in the EPID was calculated by convolving the total predicted incident fluence with the EPID-specific dose kernels. The algorithm was tested on water slabs with square fields, agreeing with measurement within 3% and 3 mm. The method was then applied to five prostate and six head-and-neck IMRT treatment courses (˜1900 clinical images). Deviations between the predicted and measured images were quantified. The portal dose image prediction model developed in this thesis work has been shown to be accurate, and it was demonstrated to be able to verify patients' delivered radiation treatments.

Evaluation of Video Image Analysis (VIA) technology to predict meat yield of sheep carcasses on-line under UK abattoir conditions.

PubMed

Rius-Vilarrasa, E; Bünger, L; Maltin, C; Matthews, K R; Roehe, R

2009-05-01

The Meat and Livestock Commission's (MLC) EUROP classification based scheme and Video Image Analysis (VIA) system were compared in their ability to predict weights of primal carcass joints. A total of 443 commercial lamb carcasses under 12 months of age and mixed gender were selected by their cold carcass weight (CCW), conformation and fat scores. Lamb carcasses were classified for conformation and fatness, scanned by the VIA system and dissected into primal joints of leg, chump, loin, breast and shoulder. After adjustment for CCW, the estimation of primal joints using MLC EUROP scores showed high coefficients of determination (R(2)) in the range of 0.82-0.99. The use of VIA always resulted in equal or higher R(2). The precision measured as root mean square error (RMSE) was 27% (leg), 13% (chump), 1% (loin), 11% (breast), 5% (shoulders) and 13% (total primals) higher using VIA than MLC carcass information. Adjustment for slaughter day and gender effects indicated that estimations of primal joints using MLC EUROP scores were more sensitive to these factors than using VIA. This was consistent with an increase in stability of the prediction model of 28%, 11%, 2%, 12%, 6% and 14% for leg, chump, loin, breast and shoulder and total primals, respectively, using VIA compared to MLC EUROP scores. Consequently, VIA was capable of improving the prediction of primal meat yields compared to the current MLC EUROP carcass classification scheme used in the UK abattoirs.

Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning

PubMed Central

Liu, Shi; Wu, Yu; Wooten, H. Omar; Green, Olga; Archer, Brent; Li, Harold

2016-01-01

A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image‐guided radiation therapy (MR‐IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam‐on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam‐on time can be calculated using both the planned beam‐on time and the decay‐corrected dose rate. To predict the remain‐ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22 min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of the proposed prediction algorithm is sufficient to support patient treatment appointment scheduling. This developed software tool is currently applied in use on a daily basis in our clinic, and could also be used as an important indicator for treatment plan complexity. PACS number(s): 87.55.N PMID:27074472

Comparison of secondary neutron dose in proton therapy resulting from the use of a tungsten alloy MLC or a brass collimator system.

PubMed

Diffenderfer, Eric S; Ainsley, Christopher G; Kirk, Maura L; McDonough, James E; Maughan, Richard L

2011-11-01

To apply the dual ionization chamber method for mixed radiation fields to an accurate comparison of the secondary neutron dose arising from the use of a tungsten alloy multileaf collimator (MLC) as opposed to a brass collimator system for defining the shape of a therapeutic proton field. Hydrogenous and nonhydrogenous ionization chambers were constructed with large volumes to enable measurements of absorbed doses below 10(-4) Gy in mixed radiation fields using the dual ionization chamber method for mixed-field dosimetry. Neutron dose measurements were made with a nominal 230 MeV proton beam incident on a closed tungsten alloy MLC and a solid brass block. The chambers were cross-calibrated against a (60)Co-calibrated Farmer chamber in water using a 6 MV x-ray beam and Monte Carlo simulations were performed to account for variations in ionization chamber response due to differences in secondary neutron energy spectra. The neutron and combined proton plus γ-ray absorbed doses are shown to be nearly equivalent downstream from either a closed tungsten alloy MLC or a solid brass block. At 10 cm downstream from the distal edge of the collimating material the neutron dose from the closed MLC was (5.3 ± 0.4) × 10(- 5) Gy/Gy. The neutron dose with brass was (6.4 ± 0.7) × 10(- 5) Gy/Gy. Further from the secondary neutron source, at 50 cm, the neutron doses remain close for both the MLC and brass block at (6.9 ± 0.6) × 10(- 6) Gy/Gy and (6.3 ± 0.7) × 10(- 6) Gy/Gy, respectively. The dual ionization chamber method is suitable for measuring secondary neutron doses resulting from proton irradiation. The results of measurements downstream from a closed tungsten alloy MLC and a brass block indicate that, even in an overly pessimistic worst-case scenario, secondary neutron production in a tungsten alloy MLC leads to absorbed doses that are nearly equivalent to those seen from brass collimators. Therefore, the choice of tungsten alloy in constructing the leaves of a proton MLC is appropriate, and does not lead to a substantial increase in the secondary neutron dose to the patient compared to that generated in a brass collimator.

Thrombin-induced phosphorylation of the regulatory light chain of myosin II in cultured bovine corneal endothelial cells.

PubMed

Satpathy, M; Gallagher, P; Lizotte-Waniewski, M; Srinivas, S P

2004-10-01

Phosphorylation of the regulatory light chain of myosin II (referred to as myosin light chain or MLC) leads to a loss of barrier integrity in cellular monolayers by an increase in the contractility of the cortical actin cytoskeleton. This effect has been examined in corneal endothelial (CE) cells. Experiments were performed using cultured bovine CE cells (BCEC). MLC phosphorylation was induced by a thrombin-mediated activation of the proteinase-activated receptor-1 (PAR-1). Expression of MLC kinase (MLCK), a Ca2+/calmodulin-dependent protein kinase that phosphorylates MLC at its Ser-19 and Thr-18 residues, was determined by RT-PCR and Western blotting. Expression of PAR-1, RhoA, and Rho kinase-1 (effector of RhoA) was ascertained by RT-PCR. MLC phosphorylation was assessed by urea-glycerol gel electrophoresis followed by immunoblotting. The effects of Rho kinase-1 and PKC were characterized by using their selective inhibitors, Y-27632 and chelerythrine, respectively. Reorganization of the cytoskeleton was evaluated by the phalloidin staining of actin. [Ca2+]i was measured using Fura-2. The barrier integrity was assayed as permeability of BCEC monolayers to horseradish peroxidase (HRP; 44 kDa). RT-PCR showed expression of MLCK, PAR-1, Rho kinase-1, and RhoA. Western blotting indicated expression of the non-muscle and smooth muscle isoforms of MLCK. Exposure to thrombin induced an increase in [Ca2+]i with the peak unaffected by an absence of extracellular Ca2+. Pre-exposure to thrombin (2 U ml(-1); 2 min) led to mono- and di-phosphorylation of MLC. Under both basal conditions and in the presence of thrombin, MLC phosphorylation was prevented by chelerythrine (10 microm) and Y-27632 (<25 microm). Thrombin led to inter-endothelial gaps secondary to the disruption of the cortical actin cytoskeleton, which under resting conditions was organized as a perijunctional actomyosin ring (PAMR). These responses were blocked by pre-treatment with Y-27632. Thrombin also increased permeability to HRP, which was abolished by pre-treatment with Y-27632. Thrombin induces MLC phosphorylation in BCEC. The consequent increase in the contractility of the actin cytoskeleton produces a centripetal force resulting in inter-endothelial gaps and a breakdown of barrier integrity. These responses are PKC- and Rho kinase-dependent. [Ca2+]i increase, as well as sensitivity of the thrombin response to PKC and Rho kinase inhibitors, are consistent with the expression of PAR-1 receptors in BCEC. Thrombin-induced hyperpermeability is a model to investigate barrier dysfunction induced by MLC phosphorylation.

SU-F-T-315: Comparative Studies of Planar Dose with Different Spatial Resolution for Head and Neck IMRT QA

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

Hwang, T; Koo, T

Purpose: To quantitatively investigate the planar dose difference and the γ value between the reference fluence map with the 1 mm detector-to-detector distance and the other fluence maps with less spatial resolution for head and neck intensity modulated radiation (IMRT) therapy. Methods: For ten head and neck cancer patients, the IMRT quality assurance (QA) beams were generated using by the commercial radiation treatment planning system, Pinnacle3 (ver. 8.0.d Philips Medical System, Madison, WI). For each beam, ten fluence maps (detector-to-detector distance: 1 mm to 10 mm by 1 mm) were generated. The fluence maps with larger than 1 mm detector-todetectormore » distance were interpolated using MATLAB (R2014a, the Math Works,Natick, MA) by four different interpolation Methods: for the bilinear, the cubic spline, the bicubic, and the nearest neighbor interpolation, respectively. These interpolated fluence maps were compared with the reference one using the γ value (criteria: 3%, 3 mm) and the relative dose difference. Results: As the detector-to-detector distance increases, the dose difference between the two maps increases. For the fluence map with the same resolution, the cubic spline interpolation and the bicubic interpolation are almost equally best interpolation methods while the nearest neighbor interpolation is the worst.For example, for 5 mm distance fluence maps, γ≤1 are 98.12±2.28%, 99.48±0.66%, 99.45±0.65% and 82.23±0.48% for the bilinear, the cubic spline, the bicubic, and the nearest neighbor interpolation, respectively. For 7 mm distance fluence maps, γ≤1 are 90.87±5.91%, 90.22±6.95%, 91.79±5.97% and 71.93±4.92 for the bilinear, the cubic spline, the bicubic, and the nearest neighbor interpolation, respectively. Conclusion: We recommend that the 2-dimensional detector array with high spatial resolution should be used as an IMRT QA tool and that the measured fluence maps should be interpolated using by the cubic spline interpolation or the bicubic interpolation for head and neck IMRT delivery. This work was supported by Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)« less

Bridge Crossing Simulator

DTIC Science & Technology

2014-10-07

is counted as. Per the TDTC, a test bridge with longitudinal and/or lateral symmetry under non- eccentric loading can be considered as 1, 2, or 4...Level Run036 3 MLC70T (tracked) BA Run046 6 AB Run055 9 AB Run060 9 BA Run064 12 BA Run071 15 AB Run155 3 MLC96W ( wheeled ) AB...Run331 9 AB Run359 15 AB Run430 12 MLC96W ( wheeled ) BA Run434 12 AB Run447 3 BA Bank Condition: Side Slope, Even Strain Channels High

A temporal forecast of radiation environments for future space exploration missions.

PubMed

Kim, Myung-Hee Y; Cucinotta, Francis A; Wilson, John W

2007-06-01

The understanding of future space radiation environments is an important goal for space mission operations, design, and risk assessment. We have developed a solar cycle statistical model in which sunspot number is coupled to space-related quantities, such as the galactic cosmic radiation (GCR) deceleration potential (phi) and the mean occurrence frequency of solar particle events (SPEs). Future GCR fluxes were derived from a predictive model, in which the temporal dependence represented by phi was derived from GCR flux and ground-based Climax neutron monitor rate measurements over the last four decades. These results showed that the point dose equivalent inside a typical spacecraft in interplanetary space was influenced by solar modulation by up to a factor of three. It also has been shown that a strong relationship exists between large SPE occurrences and phi. For future space exploration missions, cumulative probabilities of SPEs at various integral fluence levels during short-period missions were defined using a database of proton fluences of past SPEs. Analytic energy spectra of SPEs at different ranks of the integral fluences for energies greater than 30 MeV were constructed over broad energy ranges extending out to GeV for the analysis of representative exposure levels at those fluences. Results will guide the design of protection systems for astronauts during future space exploration missions.

Effect of high fluence neutron irradiation on transport properties of thermoelectrics

NASA Astrophysics Data System (ADS)

Wang, H.; Leonard, K. J.

2017-07-01

Thermoelectric materials were subjected to high fluence neutron irradiation in order to understand the effect of radiation damage on transport properties. This study is relevant to the NASA Radioisotope Thermoelectric Generator (RTG) program in which thermoelectric elements are exposed to radiation over a long period of time in space missions. Selected n-type and p-type bismuth telluride materials were irradiated at the High Flux Isotope Reactor with a neutron fluence of 1.3 × 1018 n/cm2 (E > 0.1 MeV). The increase in the Seebeck coefficient in the n-type material was partially off-set by an increase in electrical resistivity, making the power factor higher at lower temperatures. For the p-type materials, although the Seebeck coefficient was not affected by irradiation, electrical resistivity decreased slightly. The figure of merit, zT, showed a clear drop in the 300-400 K range for the p-type material and an increase for the n-type material. Considering that the p-type and n-type materials are connected in series in a module, the overall irradiation damages at the device level were limited. These results, at neutron fluences exceeding a typical space mission, are significant to ensure that the radiation damage to thermoelectrics does not affect the performance of RTGs.

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 02: Feasibility of using multileaf collimation for stereotactic radiosurgery of arteriovenous malformation

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

Lee, Young; Ruschin, Mark

SRS using linac and cones offers steep dose fall-off but a tradeoff exists between conformality and treatment time, which depends on the number of isocentres. Purpose of this study is to quantify planning metrics between cones- and MLC-based SRS for arteriovenous malformation(AVM). Seven AVM cases treated with cones were re-planned with MLC on Pinnacle treatment planning system. Planning target volume(PTV) was created with 1mm uniform margin to the AVM to account for MLC positional variation. Clinically-planned prescription dose(15–25Gy) was used. Four plans were generated per case:non-coplanar VMAT(ncV), single-arc VMAT(saV), non-coplanar IMRT(ncI), non-coplanar conformal(ncC). Plans were compared for conformity(CI), heterogeneity(HI) andmore » gradient(GI) indices and brain doses. Estimated treatment times and monitor units(MU) were compared. Cone-based plans required 2–6 isocentres. Though CI-RTOG was similar for plans(median=0.98), CI-Paddick was most favourable for ncV(median=0.86) and worst for cones(0.54). HI for MLC plans(median=1.19–1.27) were lower than cone-based plans(1.43). GI was similar for all plans. For 2/7 ncC had brainstem maximum dose>16.7Gy and therefore were clinically unacceptable. Brain V12Gy,V10Gy,V2Gy were lowest in the cones plan. ncV brain V12Gy,V10Gy,V2Gy were lowest of all MLC-based plans studied. Treatment MUs were similar for MLC-based plans and up to 70% lower than clinically delivered plans. ncV showed best conformality in this study. Of the MLC-based plans, ncV also showed lowest normal tissue dose with reasonable treatment time.« less

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations.

PubMed

Davidson, Scott E; Cui, Jing; Kry, Stephen; Deasy, Joseph O; Ibbott, Geoffrey S; Vicic, Milos; White, R Allen; Followill, David S

2016-08-01

A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who uses these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today's modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.

A study to establish reasonable action limits for patient‐specific quality assurance in intensity‐modulated radiation therapy

PubMed Central

Alecu, Ionut M.; Stan, Andrada R.; Alecu, Marius; Ciura, Andrei; Hansen, Jeremy M.; Alecu, Rodica

2007-01-01

An effective patient quality assurance (QA) program for intensity‐modulated radiation therapy (IMRT) requires accurate and realistic plan acceptance criteria—that is, action limits. Based on dose measurements performed with a commercially available two‐dimensional (2D) diode array, we analyzed 747 fluence maps resulting from a routine patient QA program for IMRT plans. The fluence maps were calculated by three different commercially available (ADAC, CMS, Eclipse) treatment planning systems (TPSs) and were delivered using 6‐MV X‐ray beams produced by linear accelerators. To establish reasonably achievable and clinically acceptable limits for the dose deviations, the agreement between the measured and calculated fluence maps was evaluated in terms of percent dose error (PDE) for a few points and percent of passing points (PPP) for the isodose distribution. The analysis was conducted for each TPS used in the study (365 ADAC, 162 CMS, 220 Eclipse), for multiple treatment sites (prostate, pelvis, head and neck, spine, rectum, anus, lung, brain), at the normalization point for 3% percentage difference (%Diff) and 3‐mm distance to agreement (DTA) criteria. We investigated the treatment‐site dependency of PPP and PDE. The results show that, at 3% and 3‐mm criteria, a 95% PPP and 3% PDE can be achieved for prostate treatments and a 90% PPP and 5% PDE are attainable for any treatment site. PACS Numbers: 87.53Dq, 87.53Tf, 87.53Xd, 87.56Fc PMID:17592459

Phototropin 1 and dim-blue light modulate the red light de-etiolation response

PubMed Central

Wang, Yihai; M Folta, Kevin

2014-01-01

Light signals regulate seedling morphological changes during de-etiolation through the coordinated actions of multiple light-sensing pathways. Previously we have shown that red-light-induced hypocotyl growth inhibition can be reversed by addition of dim blue light through the action of phototropin 1 (phot1). Here we further examine the fluence-rate relationships of this blue light effect in short-term (hours) and long-term (days) hypocotyl growth assays. The red stem-growth inhibition and blue promotion is a low-fluence rate response, and blue light delays or attenuates both the red light and far-red light responses. These de-etiolation responses include blue light reversal of red or far-red induced apical hook opening. This response also requires phot1. Cryptochromes (cry1 and cry2) are activated by higher blue light fluence-rates and override phot1's influence on hypocotyl growth promotion. Exogenous application of auxin transport inhibitor naphthylphthalamic acid abolished the blue light stem growth promotion in both hypocotyl growth and hook opening. Results from the genetic tests of this blue light effect in auxin transporter mutants, as well as phytochrome kinase substrate mutants indicated that aux1 may play a role in blue light reversal of red light response. Together, the phot1-mediated adjustment of phytochrome-regulated photomorphogenic events is most robust in dim blue light conditions and is likely modulated by auxin transport through its transporters. PMID:25482790

Multiple Leader Candidate and Competitive Position Allocation for Robust Formation against Member Robot Faults

PubMed Central

Kwon, Ji-Wook; Kim, Jin Hyo; Seo, Jiwon

2015-01-01

This paper proposes a Multiple Leader Candidate (MLC) structure and a Competitive Position Allocation (CPA) algorithm which can be applicable for various applications including environmental sensing. Unlike previous formation structures such as virtual-leader and actual-leader structures with position allocation including a rigid allocation and an optimization based allocation, the formation employing the proposed MLC structure and CPA algorithm is robust against the fault (or disappearance) of the member robots and reduces the entire cost. In the MLC structure, a leader of the entire system is chosen among leader candidate robots. The CPA algorithm is the decentralized position allocation algorithm that assigns the robots to the vertex of the formation via the competition of the adjacent robots. The numerical simulations and experimental results are included to show the feasibility and the performance of the multiple robot system employing the proposed MLC structure and the CPA algorithm. PMID:25954956

Impact of the MLC on the MRI field distortion of a prototype MRI-linac

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

Kolling, Stefan; Keall, Paul; Oborn, Brad

2013-12-15

Purpose: To cope with intrafraction tumor motion, integrated MRI-linac systems for real-time image guidance are currently under development. The multileaf collimator (MLC) is a key component in every state-of-the-art radiotherapy treatment system, allowing for accurate field shaping and tumor tracking. This work quantifies the magnetic impact of a widely used MLC on the MRI field homogeneity for such a modality.Methods: The finite element method was employed to model a MRI-linac assembly comprised of a 1.0 T split-bore MRI magnet and the key ferromagnetic components of a Varian Millennium 120 MLC, namely, the leaves and motors. Full 3D magnetic field maps ofmore » the system were generated. From these field maps, the peak-to-peak distortion within the MRI imaging volume was evaluated over a 30 cm diameter sphere volume (DSV) around the isocenter and compared to a maximum preshim inhomogeneity of 300 μT. Five parametric studies were performed: (1) The source-to-isocenter distance (SID) was varied from 100 to 200 cm, to span the range of a compact system to that with lower magnetic coupling. (2) The MLC model was changed from leaves only to leaves with motors, to determine the contribution to the total distortion caused by MLC leaves and motors separately. (3) The system was configured in the inline or perpendicular orientation, i.e., the linac treatment beam was oriented parallel or perpendicular to the magnetic field direction. (4) The treatment field size was varied from 0 × 0 to 20×20 cm{sup 2}, to span the range of clinical treatment fields. (5) The coil currents were scaled linearly to produce magnetic field strengths B{sub 0} of 0.5, 1.0, and 1.5 T, to estimate how the MLC impact changes with B{sub 0}.Results: (1) The MLC-induced MRI field distortion fell continuously with increasing SID. (2) MLC leaves and motors were found to contribute to the distortion in approximately equal measure. (3) Due to faster falloff of the fringe field, the field distortion was generally smaller in the perpendicular beam orientation. The peak-to-peak DSV distortion was below 300 μT at SID≥130 cm (perpendicular) and SID≥140 cm (inline) for the 1.0 T design. (4) The simulation of different treatment fields was identified to cause dynamic changes in the field distribution. However, the estimated residual distortion was below 1.2 mm geometric distortion at SID≥120 cm (perpendicular) and SID≥130 cm (inline) for a 10 mT/m frequency-encoding gradient. (5) Due to magnetic saturation of the MLC materials, the field distortion remained constant at B{sub 0}>1.0 T.Conclusions: This work shows that the MRI field distortions caused by the MLC cannot be ignored and must be thoroughly investigated for any MRI-linac system. The numeric distortion values obtained for our 1.0 T magnet may vary for other magnet designs with substantially different fringe fields, however the concept of modest increases in the SID to reduce the distortion to a shimmable level is generally applicable.« less

Management of three-dimensional intrafraction motion through real-time DMLC tracking.

PubMed

Sawant, Amit; Venkat, Raghu; Srivastava, Vikram; Carlson, David; Povzner, Sergey; Cattell, Herb; Keall, Paul

2008-05-01

Tumor tracking using a dynamic multileaf collimator (DMLC) represents a promising approach for intrafraction motion management in thoracic and abdominal cancer radiotherapy. In this work, we develop, empirically demonstrate, and characterize a novel 3D tracking algorithm for real-time, conformal, intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based radiation delivery to targets moving in three dimensions. The algorithm obtains real-time information of target location from an independent position monitoring system and dynamically calculates MLC leaf positions to account for changes in target position. Initial studies were performed to evaluate the geometric accuracy of DMLC tracking of 3D target motion. In addition, dosimetric studies were performed on a clinical linac to evaluate the impact of real-time DMLC tracking for conformal, step-and-shoot (S-IMRT), dynamic (D-IMRT), and VMAT deliveries to a moving target. The efficiency of conformal and IMRT delivery in the presence of tracking was determined. Results show that submillimeter geometric accuracy in all three dimensions is achievable with DMLC tracking. Significant dosimetric improvements were observed in the presence of tracking for conformal and IMRT deliveries to moving targets. A gamma index evaluation with a 3%-3 mm criterion showed that deliveries without DMLC tracking exhibit between 1.7 (S-IMRT) and 4.8 (D-IMRT) times more dose points that fail the evaluation compared to corresponding deliveries with tracking. The efficiency of IMRT delivery, as measured in the lab, was observed to be significantly lower in case of tracking target motion perpendicular to MLC leaf travel compared to motion parallel to leaf travel. Nevertheless, these early results indicate that accurate, real-time DMLC tracking of 3D tumor motion is feasible and can potentially result in significant geometric and dosimetric advantages leading to more effective management of intrafraction motion.

Increasing O-GlcNAcylation level on organ culture of soleus modulates the calcium activation parameters of muscle fibers.

PubMed

Cieniewski-Bernard, Caroline; Montel, Valerie; Berthoin, Serge; Bastide, Bruno

2012-01-01

O-N-acetylglucosaminylation is a reversible post-translational modification which presents a dynamic and highly regulated interplay with phosphorylation. New insights suggest that O-GlcNAcylation might be involved in striated muscle physiology, in particular in contractile properties such as the calcium activation parameters. By the inhibition of O-GlcNAcase, we investigated the effect of the increase of soleus O-GlcNAcylation level on the contractile properties by establishing T/pCa relationships. We increased the O-GlcNAcylation level on soleus biopsies performing an organ culture of soleus treated or not with PUGNAc or Thiamet-G, two O-GlcNAcase inhibitors. The enhancement of O-GlcNAcylation pattern was associated with an increase of calcium affinity on slow soleus skinned fibers. Analysis of the glycoproteins pattern showed that this effect is solely due to O-GlcNAcylation of proteins extracted from skinned biopsies. We also characterized the O-GlcNAcylated contractile proteins using a proteomic approach, and identified among others troponin T and I as being O-GlcNAc modified. We quantified the variation of O-GlcNAc level on all these identified proteins, and showed that several regulatory contractile proteins, predominantly fast isoforms, presented a drastic increase in their O-GlcNAc level. Since the only slow isoform of contractile protein presenting an increase of O-GlcNAc level was MLC2, the effect of enhanced O-GlcNAcylation pattern on calcium activation parameters could involve the O-GlcNAcylation of sMLC2, without excluding that an unidentified O-GlcNAc proteins, such as TnC, could be potentially involved in this mechanism. All these data strongly linked O-GlcNAcylation to the modulation of contractile activity of skeletal muscle.

Incorrect dosimetric leaf separation in IMRT and VMAT treatment planning: Clinical impact and correlation with pretreatment quality assurance.

PubMed

Sjölin, Maria; Edmund, Jens Morgenthaler

2016-07-01

Dynamic treatment planning algorithms use a dosimetric leaf separation (DLS) parameter to model the multi-leaf collimator (MLC) characteristics. Here, we quantify the dosimetric impact of an incorrect DLS parameter and investigate whether common pretreatment quality assurance (QA) methods can detect this effect. 16 treatment plans with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique for multiple treatment sites were calculated with a correct and incorrect setting of the DLS, corresponding to a MLC gap difference of 0.5mm. Pretreatment verification QA was performed with a bi-planar diode array phantom and the electronic portal imaging device (EPID). Measurements were compared to the correct and incorrect planned doses using gamma evaluation with both global (G) and local (L) normalization. Correlation, specificity and sensitivity between the dose volume histogram (DVH) points for the planning target volume (PTV) and the gamma passing rates were calculated. The change in PTV and organs at risk DVH parameters were 0.4-4.1%. Good correlation (>0.83) between the PTVmean dose deviation and measured gamma passing rates was observed. Optimal gamma settings with 3%L/3mm (per beam and composite plan) and 3%G/2mm (composite plan) for the diode array phantom and 2%G/2mm (composite plan) for the EPID system were found. Global normalization and per beam ROC analysis of the diode array phantom showed an area under the curve <0.6. A DLS error can worsen pretreatment QA using gamma analysis with reasonable credibility for the composite plan. A low detectability was demonstrated for a 3%G/3mm per beam gamma setting. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Genetics Home Reference: megalencephalic leukoencephalopathy with subcortical cysts

MedlinePlus

... is unable to correctly transport GlialCAM and MLC1 proteins to cell junctions. It is unknown how a lack of functional MLC1 or GlialCAM protein at cell junctions in the brain impairs brain development and ...

Quantitative measurement of MLC leaf displacements using an electronic portal image device

NASA Astrophysics Data System (ADS)

Yang, Yong; Xing, Lei

2004-04-01

The success of an IMRT treatment relies on the positioning accuracy of the MLC (multileaf collimator) leaves for both step-and-shoot and dynamic deliveries. In practice, however, there exists no effective and quantitative means for routine MLC QA and this has become one of the bottleneck problems in IMRT implementation. In this work we present an electronic portal image device (EPID) based method for fast and accurate measurement of MLC leaf positions at arbitrary locations within the 40 cm × 40 cm radiation field. The new technique utilizes the fact that the integral signal in a small region of interest (ROI) is a sensitive and reliable indicator of the leaf displacement. In this approach, the integral signal at a ROI was expressed as a weighted sum of the contributions from the displacements of the leaf above the point and the adjacent leaves. The weighting factors or linear coefficients of the system equations were determined by fitting the integral signal data for a group of pre-designed MLC leaf sequences to the known leaf displacements that were intentionally introduced during the creation of the leaf sequences. Once the calibration is done, the system can be used for routine MLC leaf positioning QA to detect possible leaf errors. A series of tests was carried out to examine the functionality and accuracy of the technique. Our results show that the proposed technique is potentially superior to the conventional edge-detecting approach in two aspects: (i) it deals with the problem in a systematic approach and allows us to take into account the influence of the adjacent MLC leaves effectively; and (ii) it may improve the signal-to-noise ratio and is thus capable of quantitatively measuring extremely small leaf positional displacements. Our results indicate that the technique can detect a leaf positional error as small as 0.1 mm at an arbitrary point within the field in the absence of EPID set-up error and 0.3 mm when the uncertainty is considered. Given its simplicity, efficiency and accuracy, we believe that the technique is ideally suitable for routine MLC leaf positioning QA. This work was presented at the 45th Annual Meeting of American Society of Therapeutic Radiology and Oncology (ASTRO), Salt Lake City, UT, 2003. A US Patent is pending (application no. 10/197,232).

SU-F-T-481: Physics Evaluation of a Newly Released InCise™ Multileaf Collimator for CyberKnife M6™ System

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

Wang, L; Chin, E; Lo, A

2016-06-15

Purpose: This work reports the results of the physics evaluation of a newly released InCise™2 Multileaf Collimator (MLC) installed in our institution. Methods: Beam property data was measured with unshielded diode and EBT2 films. The measurements included MLC leaf transmission, beam profiles, output factors and tissue-phantom ratios. MLC performance was evaluated for one month after commissioning. Weekly Garden Fence tests were performed for leaf / bank positioning in standard (A/P) and clinically relevant non-standard positions, before and after MLC driving exercises of 10+ minutes. Daily Picket Fence test and AQA test, End-to-End tests and dosimetric quality assurance were performed tomore » evaluate the overall system performance. Results: All measurements including beam energy, flatness and symmetry, were within manufacture specifications. Leaf transmission was 0.4% <0.5% specification. The values of output factors ranged from 0.825 (7.6 mm × 7.5 mm) to 1.026 (115.0 mm × 100.1 mm). Average beam penumbra at 10 cm depth ranged from 2.7mm/2.7mm(7.6 mm × 7.5 mm) to 6.0 mm/6.2mm(84.6 mm × 84.7 mm). Slight penumbra difference (<10% from average penumbra for fields >20 mm) was observed in the direction perpendicular to leaf motion due to the tilting of the leaf housing. Mean leaf position offsets was −0.08±0.07mm and −0.13 ± 0.08 for X1 and X2 leaf banks in 13 Garden Fence tests. No significant difference on average leaf positioning offsets was observed between different leaf orientations and before/after MLC driving exercises. Six End-to-End tests showed 0.43±0.23mm overall targeting accuracy. Picket-Fence and AQA showed stable performance of MLC during the test period. Dosimetric point dose measurements for test cases agreed with calculation within 3%. All film measurements on relative dose had Gamma (2%, 2mm) passing rate of >95%. Conclusion: The Incise™2 MLC for CyberKnife M6™ was proven to be accurate and reliable, and it is currently in clinical use. Stanford was one of the physics evaluation sites for the newly released InCise 2 MLC for Accuray Inc.« less

TU-H-BRC-05: Stereotactic Radiosurgery Optimized with Orthovoltage Beams

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

Fagerstrom, J; Culberson, W; Bender, E

2016-06-15

Purpose: To achieve improved stereotactic radiosurgery (SRS) dose distributions using orthovoltage energy fluence modulation with inverse planning optimization techniques. Methods: A pencil beam model was used to calculate dose distributions from the institution’s orthovoltage unit at 250 kVp. Kernels for the model were derived using Monte Carlo methods as well as measurements with radiochromic film. The orthovoltage photon spectra, modulated by varying thicknesses of attenuating material, were approximated using open-source software. A genetic algorithm search heuristic routine was used to optimize added tungsten filtration thicknesses to approach rectangular function dose distributions at depth. Optimizations were performed for depths of 2.5,more » 5.0, and 7.5 cm, with cone sizes of 8, 10, and 12 mm. Results: Circularly-symmetric tungsten filters were designed based on the results of the optimization, to modulate the orthovoltage beam across the aperture of an SRS cone collimator. For each depth and cone size combination examined, the beam flatness and 80–20% and 90–10% penumbrae were calculated for both standard, open cone-collimated beams as well as for the optimized, filtered beams. For all configurations tested, the modulated beams were able to achieve improved penumbra widths and flatness statistics at depth, with flatness improving between 33 and 52%, and penumbrae improving between 18 and 25% for the modulated beams compared to the unmodulated beams. Conclusion: A methodology has been described that may be used to optimize the spatial distribution of added filtration material in an orthovoltage SRS beam to result in dose distributions at depth with improved flatness and penumbrae compared to standard open cones. This work provides the mathematical foundation for a novel, orthovoltage energy fluence-modulated SRS system.« less

Feasibility of using the linac real-time log data for VMAT treatment verification

NASA Astrophysics Data System (ADS)

Midi, N. S.; Zin, Hafiz M.

2017-05-01

This study investigates the feasibility of using the real-time log data from a linac to verify Volumetric Modulated Arc Therapy (VMAT) treatment. The treatment log data for an Elekta Synergy linac can be recorded at a sampling rate of 4 Hz using the service graphing tool on the linac control computer. A treatment plan that simulates a VMAT treatment was delivered from the linac and all the dynamic treatment parameters including monitor unit (MU), Multileaf Collimator (MLC) position, jaw position, gantry angle and collimator angle were recorded in real-time using the service graphing tool. The recorded raw data were extracted and analysed using algorithms written in Matlab (MathWorks, Natick, MA). The actual treatment parameters logged using the service graphing tool was compared to the prescription and the deviations were analysed. The MLC position errors travelling at the speed range from -3.25 to 5.92 cm/s were between -1.7 mm to 2.5 mm, well within the 3.5 mm tolerance value (AAPM TG-142). The discrepancies of other delivery parameters were also within the tolerance. The real-time linac parameters logged using the service graphing tool can be used as a supplementary data for patient specific VMAT pre-treatment quality assurance.

Improving cardiovascular health of underserved populations in the community with Life's Simple 7.

PubMed

Murphy, Marcia Pencak; Coke, Lola; Staffileno, Beth A; Robinson, Janis D; Tillotson, Robin

2015-11-01

The purpose of this nurse practitioner (NP) led initiative was to improve the cardiovascular health of two underserved populations in the community using the American Heart Association (AHA) Life's Simple 7 and My Life Check (MLC) tools. Two inner city community sites were targeted: (a) a senior center servicing African American (AA) older adults, and (b) a residential facility servicing homeless women. Preprogram health data (blood pressure, cholesterol, blood glucose levels, body mass index, and health behaviors) were collected to calculate MLC scores. Postprogram health data were obtained on participants with the lowest MLC scores who completed the program. Eight older adults completed the program with a 37.1% increase in average MLC score (6.2 vs. 8.5). Ten women completed the program with a 9.3% decrease in average MLC score (4.3 vs. 3.9). Favorable benefits were observed in the AA older adults. In contrast, similar benefits were not observed in the women, which may be because of a constellation of social, environmental, biological, and mental health factors. NPs are prepared to target community-based settings to address the health of underserved populations. Engaging key stakeholders in the planning and implementation is essential for success. ©2015 American Association of Nurse Practitioners.

The effect of iron on metronidazole activity against Trichomonas vaginalis in vitro.

PubMed

Elwakil, Hala Salah; Tawfik, Rania Ayman; Alam-Eldin, Yosra Hussein; Nassar, Doaa Ashraf

2017-11-01

Metronidazole is administered in an inactive form then activated to its cytotoxic form within the hydrogenosome of trichomonads. Two hydrogenosomal proteins, pyruvate ferredoxin oxidoreductase (PFOR) and ferredoxin, play a critical role in the reductive activation of metronidazole. The expression of these proteins and other hydrogenosomal proteins are likewise positively regulated by iron. In the present study, the effect of iron on minimal lethal concentration (MLC) of metronidazole on in vitro cultured Trichomonas vaginalis(T. vaginalis) isolates was investigated. Interestingly, Addition of Ferrous ammonium sulphate (FAS) to T. vaginalis culture led to decrease in the MLC of metronidazole. On using aerobic assay, MLC of metronidazole on untreated T. vaginalis of both isolates was 12.5 μg/ml that decreased to 0.38 μg/ml on FAS treated trichomonads. Also anaerobic assay revealed that MLC on untreated parasites was 3.12 μg/ml that decreased to 0.097 μg/ml and 0.19 μg/ml for isolate 1 and isolate 2 respectively after iron addition. It was concluded that, addition of iron to in vitro cultured T. vaginalis decreases metronidazole MLC that was detected by both aerobic and anaerobic assays. Copyright © 2017 Elsevier Inc. All rights reserved.

IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures.

PubMed

Vercelli, D; Jabara, H H; Lauener, R P; Geha, R S

1990-01-15

The T cell-derived lymphokine IL-4 is essential for the induction of IgE synthesis by human lymphocytes. The IgE-inducing effect of IL-4 is antagonized by IFN-gamma. The secretion of IFN-gamma is vigorously triggered in MLC. Thus, IL-4-stimulated MLC represent a suitable model to characterize the functional antagonism between IL-4 and IFN-gamma. In this report, we show that rIL-4 consistently induced IgE synthesis when added to human primary MLC. IL-4-dependent IgE production required cognate T/B cell recognition, because it was inhibited by antibodies to CD3 and MHC class II (HlA-DR) Ag. A neutralizing anti-IFN-gamma mAb dramatically enhanced IL-4-dependent IgE synthesis by MLC, indicating that endogenous IFN-gamma is a major inhibitor of IgE production. More importantly, addition of rIL-4 markedly inhibited the release of IFN-gamma in supernatants of MLC and Con A-activated PBMC. The decrease in IFN-gamma protein was accompanied by a decreased expression of IFN-gamma mRNA transcripts. The downregulation of IFN-gamma by IL-4 is likely to play an important role in the IL-4-dependent induction of IgE synthesis.

An increase or a decrease in myosin II phosphorylation inhibits macrophage motility

PubMed Central

1991-01-01

Myosin II purified from mammalian non-muscle cells is phosphorylated on the 20-kD light chain subunit (MLC20) by the Ca2+/calmodulin-dependent enzyme myosin light chain kinase (MLCK). The importance of MLC20 phosphorylation in regulating cell motility was investigated by introducing either antibodies to MLCK (MK-Ab) or a Ca2+/calmodulin- independent, constitutively active form of MLCK (MK-) into macrophages. The effects of these proteins on cell motility were then determined using a quantitative chemotaxis assay. Chemotaxis is significantly diminished in macrophages containing MK-Ab compared to macrophages containing control antibodies. Moreover, there is an inverse relationship between the number of cells that migrate and the amount of MK-Ab introduced into cells. Interestingly, there is also an inverse relationship between the number of cells that migrate and the amount of MK- introduced into cells. Other experiments demonstrated that MK-Ab decreased intracellular MLC20 phosphorylation while MK- increased MLC20 phosphorylation. MK- also increased the amount of myosin associated with the cytoskeleton. These data demonstrate that the regulation of MLCK is an important aspect of cell motility and suggest that MLC20 phosphorylation must be maintained within narrow limits during translational motility by mammalian cells. PMID:2071674

Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.).

PubMed

Georgiou, Stella; Alami-Durante, Hélène; Power, Deborah M; Sarropoulou, Elena; Mamuris, Zissis; Moutou, Katerina A

2016-02-01

Hyperplasia and hypertrophy are the two mechanisms by which muscle develops and grows. We study these two mechanisms, during the early development of white muscle in Sparus aurata, by means of histology and the expression of structural and regulatory genes. A clear stage of stratified hyperplasia was identified early in the development of gilthead sea bream but ceased by 35 dph when hypertrophy took over. Mosaic recruitment of new white fibers began as soon as 60 dph. The genes mlc2a and mlc2b were expressed at various levels during the main phases of hyperplasia and hypertrophy. The genes myog and mlc2a were significantly up-regulated during the intensive stratified formation of new fibers and their expression was significantly correlated. Expression of mstn1 and igf1 increased at 35 dph, appeared to regulate the hyperplasia-to-hypertrophy transition, and may have stimulated the expression of mlc2a, mlc2b and col1a1 at the onset of mosaic hyperplasia. The up-regulation of mstn1 at transitional phases in muscle development indicates a dual regulatory role of myostatin in fish larval muscle growth.

SU-C-BRB-04: Characteristics and Performance Evaluation of the First Commercial MLC for a Robotic Delivery System

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

Fuerweger, C; European Cyberknife Center Munich, Munich, DE; Prins, P

Purpose: To assess characteristics and performance of the “Incise™” MLC (41 leaf pairs, 2.5mm width, FFF linac) mounted on the robotic SRS/SBRT platform “CyberKnife M6™” in a pre-clinical 5 months (11/2014–03/2015) test period. Methods: Beam properties were measured with unshielded diodes and EBT3 film. The CyberKnife workspace for MLC was analyzed by transforming robot node coordinates (cranial / body paths) into Euler geometry. Bayouth tests for leaf / bank position accuracy were performed in standard (A/P) and clinically relevant non-standard positions, before and after exercising the MLC for 10+ minutes. Total system and delivery accuracy were assessed in End-to-End testsmore » and dosimetric verification of exemplary plans. Stability over time was evaluated in Picket-Fence-and adapted Winston-Lutz-tests (AQA) for different collimator angles. Results: Penumbrae (80–20%, with 100%=2*dose at inflection point; SAD 80cm; 10cm depth) parallel / perpendicular to leaf motion were 2.87/2.64mm for the smallest (0×76×0.75cm{sup 2}) and 5.34/4.94mm for the largest (9.76×9.75cm{sup 2}) square field. MLC circular field penumbrae exceeded fixed cones by 10–20% (e.g. 60mm: 4.0 vs. 3.6mm; 20mm: 3.6 vs. 2.9mm). Interleaf leakage was <0.5%. Clinically accessible workspace with MLC covered (non-coplanar) gantry angles of [-113°;+112°] (cranial) and [-108°;+102°] (body), and collimator angles of [-100°;+107°] (cranial) and [-91°;+100°] (body). Average leaf position offsets were ≤0.2mm in 14 standard A/P Bayouth tests and ≤0.6mm in 8 non-standard direction tests. Pre-test MLC exercise increased jaggedness (range ±0.3mm vs. ±0.5mm) and allowed to identify one malfunctioning leaf motor. Total system accuracy with MLC was 0.39±0.06mm in 6 End-to-End tests. Picket-Fence and AQA showed no adverse trends during the test period. Conclusion: The Incise™ MLC for CyberKnife M6™ displayed high accuracy and mechanical stability over the test period. The specific CyberKnife geometry and performance after exercise demand dedicated QA measures. This work is in part funded by a research grant from Accuray Inc, Sunnyvale, USA. Erasmus MC Cancer Institute also has research collaborations with Elekta AB, Stockholm, Sweden. C Fuerweger has previously received speaker honoraria from Accuray Inc, Sunnyvale, USA.« less

Automating linear accelerator quality assurance.

PubMed

Eckhause, Tobias; Al-Hallaq, Hania; Ritter, Timothy; DeMarco, John; Farrey, Karl; Pawlicki, Todd; Kim, Gwe-Ya; Popple, Richard; Sharma, Vijeshwar; Perez, Mario; Park, SungYong; Booth, Jeremy T; Thorwarth, Ryan; Moran, Jean M

2015-10-01

The purpose of this study was 2-fold. One purpose was to develop an automated, streamlined quality assurance (QA) program for use by multiple centers. The second purpose was to evaluate machine performance over time for multiple centers using linear accelerator (Linac) log files and electronic portal images. The authors sought to evaluate variations in Linac performance to establish as a reference for other centers. The authors developed analytical software tools for a QA program using both log files and electronic portal imaging device (EPID) measurements. The first tool is a general analysis tool which can read and visually represent data in the log file. This tool, which can be used to automatically analyze patient treatment or QA log files, examines the files for Linac deviations which exceed thresholds. The second set of tools consists of a test suite of QA fields, a standard phantom, and software to collect information from the log files on deviations from the expected values. The test suite was designed to focus on the mechanical tests of the Linac to include jaw, MLC, and collimator positions during static, IMRT, and volumetric modulated arc therapy delivery. A consortium of eight institutions delivered the test suite at monthly or weekly intervals on each Linac using a standard phantom. The behavior of various components was analyzed for eight TrueBeam Linacs. For the EPID and trajectory log file analysis, all observed deviations which exceeded established thresholds for Linac behavior resulted in a beam hold off. In the absence of an interlock-triggering event, the maximum observed log file deviations between the expected and actual component positions (such as MLC leaves) varied from less than 1% to 26% of published tolerance thresholds. The maximum and standard deviations of the variations due to gantry sag, collimator angle, jaw position, and MLC positions are presented. Gantry sag among Linacs was 0.336 ± 0.072 mm. The standard deviation in MLC position, as determined by EPID measurements, across the consortium was 0.33 mm for IMRT fields. With respect to the log files, the deviations between expected and actual positions for parameters were small (<0.12 mm) for all Linacs. Considering both log files and EPID measurements, all parameters were well within published tolerance values. Variations in collimator angle, MLC position, and gantry sag were also evaluated for all Linacs. The performance of the TrueBeam Linac model was shown to be consistent based on automated analysis of trajectory log files and EPID images acquired during delivery of a standardized test suite. The results can be compared directly to tolerance thresholds. In addition, sharing of results from standard tests across institutions can facilitate the identification of QA process and Linac changes. These reference values are presented along with the standard deviation for common tests so that the test suite can be used by other centers to evaluate their Linac performance against those in this consortium.

SU-E-T-88: Comprehensive Automated Daily QA for Hypo- Fractionated Treatments

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

McGuinness, C; Morin, O

2014-06-01

Purpose: The trend towards more SBRT treatments with fewer high dose fractions places increased importance on daily QA. Patient plan specific QA with 3%/3mm gamma analysis and daily output constancy checks may not be enough to guarantee the level of accuracy required for SBRT treatments. But increasing the already extensive amount of QA procedures that are required is a daunting proposition. We performed a feasibility study for more comprehensive automated daily QA that could improve the diagnostic capabilities of QA without increasing workload. Methods: We performed the study on a Siemens Artiste linear accelerator using the integrated flat panel EPID.more » We included square fields, a picket fence, overlap and representative IMRT fields to measure output, flatness, symmetry, beam center, and percent difference from the standard. We also imposed a set of machine errors: MLC leaf position, machine output, and beam steering to compare with the standard. Results: Daily output was consistent within +/− 1%. Change in steering current by 1.4% and 2.4% resulted in a 3.2% and 6.3% change in flatness. 1 and 2mm MLC leaf offset errors were visibly obvious in difference plots, but passed a 3%/3mm gamma analysis. A simple test of transmission in a picket fence can catch a leaf offset error of a single leaf by 1mm. The entire morning QA sequence is performed in less than 30 minutes and images are automatically analyzed. Conclusion: Automated QA procedures could be used to provide more comprehensive information about the machine with less time and human involvement. We have also shown that other simple tests are better able to catch MLC leaf position errors than a 3%/3mm gamma analysis commonly used for IMRT and modulated arc treatments. Finally, this information could be used to watch trends of the machine and predict problems before they lead to costly machine downtime.« less

SU-F-T-549: Validation of a Method for in Vivo 3D Dose Reconstruction for SBRT Using a New Transmission Detector

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

Nakaguchi, Y; Shimohigashi, Y; Onizuka, R

Purpose: Recently, there has been increased clinical use of stereotactic body radiation therapy (SBRT). SBRT treatments will strongly benefit from in vivo patient dose verification, as any errors in delivery can be more detrimental to the radiobiology of the patient as compared to conventional therapy. In vivo dose measurements, a commercially available quality assurance platform which is able to correlate the delivered dose to the patient’s anatomy and take into account tissue inhomogeneity, is the COMPASS system (IBA Dosimetry, Germany) using a new transmission detector (Dolphin, IBA Dosimetry). In this work, we evaluate a method for in vivo 3D dosemore » reconstruction for SBRT using a new transmission detector, which was developed for in vivo dose verification for intensity-modulated radiation therapy (IMRT). Methods: We evaluated the accuracy of measurement for SBRT using simple small fields (2×2−10×10 cm2), a multileaf collimator (MLC) test pattern, and clinical cases. The dose distributions from the COMPASS were compared with those of EDR2 films (Kodak, USA) and the Monte Carlo simulations (MC). For clinical cases, we compared MC using dose-volume-histograms (DVHs) and dose profiles. Results: The dose profiles from the COMPASS for small fields and the complicated MLC test pattern agreed with those of EDR2 films, and MC within 3%. This showed the COMPASS with Dolphin system showed good spatial resolution and can measure small fields which are required for SBRT. Those results also suggest that COMPASS with Dolphin is able to detect MLC leaf position errors for SBRT. In clinical cases, the COMPASS with Dolphin agreed well with MC. The Dolphin detector, which consists of ionization chambers, provided stable measurement. Conclusion: COMPASS with Dolphin detector showed a useful in vivo 3D dose reconstruction for SBRT. The accuracy of the results indicates that this approach is suitable for clinical implementation.« less

SU-E-T-545: A MLC-Equipped Robotic Radiosurgery-Radiotherapy Combined System in Treating Hepatic Lesions: Delivery Efficiency as Compared to a Standard Linac for Treating Hepatic Lesions

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

Jin, L; Price, R; Wang, L

Purpose: The CyberKnife (CK) M6 Series introduced a mulitleaf collimator (MLC) beam for extending its capability to the conventional radiotherapy. This work is to investigate delivery efficiency of this system as compared to a standard Varian linac when treating hepatic lesions. Methods: Nine previously treated patients were divided into three groups with three patients in each. Group one: fractionated radiotherapy; Group two: SBRT-like treatments and Group three: fractionated radiotherapy targeting two PTVs. The clinically used plans were generated with the Eclipse treatment planning system (TPS). We re-planned these cases using a Mulitplan (MP) TPS for the CK M6 and normalizedmore » to the same PTV dose coverage. CK factors (CF) (defined as modulation scaling factor in this work), number of nodes (NN), number of MLC segments (NS) and beam delivery time (BT) with an estimated image interval of 60 seconds, were used for evaluation of delivery efficiency. Results: Generated plans from the MP and Eclipse TPS demonstrated the similar quality in terms of PTV confomality index, minimum and maximum PTV doses, and doses received by critical structures. Group one: CF ranged from 8.1 to 8.7, NN from 30 to 40, NS from 120 to 155 and BT from 20 to 23 minutes; group two: CF from 4.7 to 8.5, NN from 15 to 19, NS from 82 to 141 and BT from 18 to 24 minutes; and group three: CF from 7.9 to 10, NN from 47 to 49, NS from 110 to 113 and BT from 20 to 22 minutes. Conclusions: Delivery time is longer for the CK M6 than for the Varian linac (7.8 to 13.7 minutes). Further investigation will be necessary to determine if a PTV reduction from the tracking feature will shorten the delivery time without decreasing plan quality.« less

Real-time tracking of tumor motions and deformations along the leaf travel direction with the aid of a synchronized dynamic MLC leaf sequencer.

PubMed

Tacke, Martin; Nill, Simeon; Oelfke, Uwe

2007-11-21

Advanced radiotherapeutical techniques like intensity-modulated radiation therapy (IMRT) are based on an accurate knowledge of the location of the radiation target. An accurate dose delivery, therefore, requires a method to account for the inter- and intrafractional target motion and the target deformation occurring during the course of treatment. A method to compensate in real time for changes in the position and shape of the target is the use of a dynamic multileaf collimator (MLC) technique which can be devised to automatically arrange the treatment field according to real-time image information. So far, various approaches proposed for leaf sequencers have had to rely on a priori known target motion data and have aimed to optimize the overall treatment time. Since for a real-time dose delivery the target motion is not known a priori, the velocity range of the leading leaves is restricted by a safety margin to c x v(max) while the following leaves can travel with an additional maximum speed to compensate for the respective target movements. Another aspect to be considered is the tongue and groove effect. A uniform radiation field can only be achieved if the leaf movements are synchronized. The method presented in this note is the first to combine a synchronizing sequencer and real-time tracking with a dynamic MLC. The newly developed algorithm is capable of online optimizing the leaf velocities by minimizing the overall treatment time while at the same time it synchronizes the leaf trajectories in order to avoid the tongue and groove effect. The simultaneous synchronization is performed with the help of an online-calculated mid-time leaf trajectory which is common for all leaf pairs and which takes into account the real-time target motion and deformation information.

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

PubMed

Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

2016-10-14

GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2 fl/fl ) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2 fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist, was significantly enhanced in MLC-Cre:GRK2 fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Detector system dose verification comparisons for arc therapy: couch vs. gantry mount

PubMed Central

Manikandan, Arjunan; Nandy, Maitreyee; Sureka, Chandra Sekaran; Gossman, Michael S.; Sujatha, Nadendla; Rajendran, Vivek Thirupathur

2014-01-01

The aim of this study was to assess the performance of a gantry‐mounted detector system and a couch set detector system using a systematic multileaf collimator positional error manually introduced for volumetric‐modulated arc therapy. Four head and neck and esophagus VMAT plans were evaluated by measurement using an electronic portal imaging device and an ion chamber array. Each plan was copied and duplicated with a 1 mm systematic MLC positional error in the left leaf bank. Direct comparison of measurements for plans with and without the error permitted observational characteristics for quality assurance performance between detectors. A total of 48 different plans were evaluated for this testing. The mean percentage planar dose differences required to satisfy a 95% match between plans with and without the MLCPE were 5.2% ± 0.5% for the chamber array with gantry motion, 8.12% ± 1.04% for the chamber array with a static gantry at 0°, and 10.9% ± 1.4% for the EPID with gantry motion. It was observed that the EPID was less accurate due to overresponse of the MLCPE in the left leaf bank. The EPID always images bank‐A on the ipsilateral side of the detector, whereas for a chamber array or for a patient, that bank changes as it crosses the ‐90° or +90° position. A couch set detector system can reproduce the TPS calculated values most consistently. We recommend it as the most reliable patient specific QA system for MLC position error testing. This research is highlighted by the finding of up to 12.7% dose variation for H/N and esophagus cases for VMAT delivery, where the mere source of error was the stated clinically acceptability of 1 mm MLC position deviation of TG‐142. PACS numbers: 87.56.‐v, 87.55.‐x, 07.57.KP, 29.40.‐n, 85.25.Pb PMID:24892330

Myosin light chain phosphorylation is critical for adaptation to cardiac stress.

PubMed

Warren, Sonisha A; Briggs, Laura E; Zeng, Huadong; Chuang, Joyce; Chang, Eileen I; Terada, Ryota; Li, Moyi; Swanson, Maurice S; Lecker, Stewart H; Willis, Monte S; Spinale, Francis G; Maupin-Furlowe, Julie; McMullen, Julie R; Moss, Richard L; Kasahara, Hideko

2012-11-27

Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress. We previously identified an enzyme that predominantly phosphorylates MLC2v in cardiomyocytes, cardiac myosin light-chain kinase (cMLCK), yet the role(s) played by cMLCK in regulating cardiac function in health and disease remain to be determined. We found that pressure overload induced by transaortic constriction in wild-type mice reduced phosphorylated MLC2v levels by ≈40% and cMLCK levels by ≈85%. To examine how a reduction in cMLCK and the corresponding reduction in phosphorylated MLC2v affect function, we generated Mylk3 gene-targeted mice and transgenic mice overexpressing cMLCK specifically in cardiomyocytes. Pressure overload led to severe heart failure in cMLCK knockout mice but not in mice with cMLCK overexpression in which cMLCK protein synthesis exceeded degradation. The reduction in cMLCK protein during pressure overload was attenuated by inhibition of ubiquitin-proteasome protein degradation systems. Our results suggest the novel idea that accelerated cMLCK protein turnover by the ubiquitin-proteasome system underlies the transition from compensated hypertrophy to decompensated heart failure as a result of reduced phosphorylation of MLC2v.

Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction.

PubMed

Ait-Belgnaoui, A; Han, W; Lamine, F; Eutamene, H; Fioramonti, J; Bueno, L; Theodorou, V

2006-08-01

Stress induced increase in colonic paracellular permeability results from epithelial cell cytoskeleton contraction and is responsible for stress induced hypersensitivity to colorectal distension (CRD). The probiotic Lactobacillus farciminis releases spontaneously nitric oxide (NO) in the colonic lumen in vivo and exerts anti-inflammatory effects. This study aimed: (i) to evaluate the effects of L farciminis on stress induced hypersensitivity to CRD and increase in colonic paracellular permeability; and (ii) to ascertain whether these effects are NO mediated and related to changes in colonocyte myosin light chain phosphorylation (p-MLC). Female Wistar rats received either 10(11) CFU/day of L farciminis or saline orally over 15 days before partial restraint stress (PRS) or sham-PRS application. Visceral sensitivity to CRD and colonic paracellular permeability was assessed after PRS or sham-PRS. Haemoglobin was used as an NO scavenger. Western blotting for MLC kinase, MLC, and p-MLC were performed in colonic mucosa from L farciminis treated and control rats after PRS or sham-PRS. PRS significantly increased the number of spike bursts for CRD pressures of 30-60 mm Hg as well as colonic paracellular permeability. L farciminis treatment prevented both effects, while haemoglobin reversed the protective effects of L farciminis. p-MLC expression increased significantly from 15 to 45 minutes after PRS, and L farciminis treatment prevented this increase. L farciminis treatment prevents stress induced hypersensitivity, increase in colonic paracellular permeability, and colonocyte MLC phosphorylation. This antinociceptive effect occurs via inhibition of contraction of colonic epithelial cell cytoskeleton and the subsequent tight junction opening, and may also involve direct or indirect effects of NO produced by this probiotic.

Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction

PubMed Central

Ait‐Belgnaoui, A; Han, W; Lamine, F; Eutamene, H; Fioramonti, J; Bueno, L; Theodorou, V

2006-01-01

Background Stress induced increase in colonic paracellular permeability results from epithelial cell cytoskeleton contraction and is responsible for stress induced hypersensitivity to colorectal distension (CRD). The probiotic Lactobacillus farciminis releases spontaneously nitric oxide (NO) in the colonic lumen in vivo and exerts anti‐inflammatory effects. This study aimed: (i) to evaluate the effects of L farciminis on stress induced hypersensitivity to CRD and increase in colonic paracellular permeability; and (ii) to ascertain whether these effects are NO mediated and related to changes in colonocyte myosin light chain phosphorylation (p‐MLC). Methods Female Wistar rats received either 1011 CFU/day of L farciminis or saline orally over 15 days before partial restraint stress (PRS) or sham‐PRS application. Visceral sensitivity to CRD and colonic paracellular permeability was assessed after PRS or sham‐PRS. Haemoglobin was used as an NO scavenger. Western blotting for MLC kinase, MLC, and p‐MLC were performed in colonic mucosa from L farciminis treated and control rats after PRS or sham‐PRS. Results PRS significantly increased the number of spike bursts for CRD pressures of 30–60 mm Hg as well as colonic paracellular permeability. L farciminis treatment prevented both effects, while haemoglobin reversed the protective effects of L farciminis. p‐MLC expression increased significantly from 15 to 45 minutes after PRS, and L farciminis treatment prevented this increase. Conclusion L farciminis treatment prevents stress induced hypersensitivity, increase in colonic paracellular permeability, and colonocyte MLC phosphorylation. This antinociceptive effect occurs via inhibition of contraction of colonic epithelial cell cytoskeleton and the subsequent tight junction opening, and may also involve direct or indirect effects of NO produced by this probiotic. PMID:16507583

Testing the Role of Meander Cutoff in Promoting Gene Flow across a Riverine Barrier in Ground Skinks (Scincella lateralis)

PubMed Central

Jackson, Nathan D.; Austin, Christopher C.

2013-01-01

Despite considerable attention, the long-term impact of rivers on species diversification remains uncertain. Meander loop cutoff (MLC) is one river phenomenon that may compromise a river’s diversifying effects by passively transferring organisms from one side of the river to the other. However, the ability of MLC to promote gene flow across rivers has not been demonstrated empirically. Here, we test several predictions of MLC-mediated gene flow in populations of North American ground skinks (Scincella lateralis) separated by a well-established riverine barrier, the Mississippi River: 1) individuals collected from within meander cutoffs should be more closely related to individuals across the river than on the same side, 2) individuals within meander cutoffs should contain more immigrants than individuals away from meander cutoffs, 3) immigration rates estimated across the river should be highest in the direction of the cutoff event, and 4) the distribution of alleles native to one side of the river should be better predicted by the historical rather than current path of the river. To test these predictions we sampled 13 microsatellite loci and mitochondrial DNA from ground skinks collected near three ancient meander loops. These predictions were generally supported by genetic data, although support was stronger for mtDNA than for microsatellite data. Partial support for genetic divergence of samples within ancient meander loops also provides evidence for the MLC hypothesis. Although a role for MLC-mediated gene flow was supported here for ground skinks, the transient nature of river channels and morphologies may limit the long-term importance of MLC in stemming population divergence across major rivers. PMID:23658778

A plasmid collection for PCR-based gene targeting in the filamentous ascomycete Ashbya gossypii.

PubMed

Kaufmann, Andreas

2009-08-01

PCR-based gene targeting with heterologous markers is an efficient method to delete genes, generate gene fusions, and modulate gene expression. For the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, several plasmid collections are available covering a wide range of tags and markers. For several reasons, many of these cassettes cannot be used in the filamentous ascomycete Ashbya gossypii. This article describes the construction of 93 heterologous modules for C- and N-terminal tagging and promoter replacements in A. gossypii. The performance of 12 different fluorescent tags was evaluated by monitoring their brightness, detectability, and photostability when fused to the myosin light-chain protein Mlc2. Furthermore, the thiamine-repressible S. cerevisiae THI13 promoter was established to regulate gene expression in A. gossypii. This collection will help accelerate analysis of gene function in A. gossypii and in other ascomycetes where S. cerevisiae promoter elements are functional.

Fluence-dependent singlet exciton dynamics in length-sorted chirality-enriched single-walled carbon nanotubes.

PubMed

Park, Jaehong; Deria, Pravas; Olivier, Jean-Hubert; Therien, Michael J

2014-02-12

We utilize individualized, length-sorted (6,5)-chirality enriched single-walled carbon nanotubes (SWNTs) having dimensions of 200 and 800 nm, femtosecond transient absorption spectroscopy, and variable excitation fluences that modulate the exciton density per nanotube unit length, to interrogate nanotube exciton/biexciton dynamics. For pump fluences below 30 μJ/cm(2), transient absorption (TA) spectra of (6,5) SWNTs reveal the instantaneous emergence of the exciton to biexciton transition (E11 → E11,BX) at 1100 nm; in contrast, under excitation fluences exceeding 100 μJ/cm(2), this TA signal manifests a rise time (τ rise ∼ 250 fs), indicating that E11 state repopulation is required to produce this signal. Femtosecond transient absorption spectroscopic data acquired over the 900-1400 nm spectral region of the near-infrared (NIR) region for (6,5) SWNTs, as a function of nanotube length and exciton density, reveal that over time delays that exceed 200 fs exciton-exciton interactions do not occur over spatial domains larger than 200 nm. Furthermore, the excitation fluence dependence of the E11 → E11,BX transient absorption signal demonstrates that relaxation of the E11 biexciton state (E11,BX) gives rise to a substantial E11 state population, as increasing delay times result in a concomitant increase of E11 → E11,BX transition oscillator strength. Numerical simulations based on a three-state model are consistent with a mechanism whereby biexcitons are generated at high excitation fluences via sequential SWNT ground- and E11-state excitation that occurs within the 980 nm excitation pulse duration. These studies that investigate fluence-dependent TA spectral evolution show that SWNT ground → E11 and E11 → E11,BX excitations are coresonant and provide evidence that E11,BX → E11 relaxation constitutes a significant decay channel for the SWNT biexciton state over delay times that exceed 200 fs, a finding that runs counter to assumptions made in previous analyses of SWNT biexciton dynamical data where exciton-exciton annihilation has been assumed to play a dominant role.

Swift heavy ion-induced radiation damage in isotropic graphite studied by micro-indentation and in-situ electrical resistivity

NASA Astrophysics Data System (ADS)

Hubert, Christian; Voss, Kay Obbe; Bender, Markus; Kupka, Katharina; Romanenko, Anton; Severin, Daniel; Trautmann, Christina; Tomut, Marilena

2015-12-01

Due to its excellent thermo-physical properties and radiation hardness, isotropic graphite is presently the most promising material candidate for new high-power ion accelerators which will provide highest beam intensities and energies. Under these extreme conditions, specific accelerator components including production targets and beam protection modules are facing the risk of degradation due to radiation damage. Ion-beam induced damage effects were tested by irradiating polycrystalline, isotropic graphite samples at the UNILAC (GSI, Darmstadt) with 4.8 MeV per nucleon 132Xe, 150Sm, 197Au, and 238U ions applying fluences between 1 × 1011 and 1 × 1014 ions/cm2. The overall damage accumulation and its dependence on energy loss of the ions were studied by in situ 4-point resistivity measurements. With increasing fluence, the electric resistivity increases due to disordering of the graphitic structure. Irradiated samples were also analyzed off-line by means of micro-indentation in order to characterize mesoscale effects such as beam-induced hardening and stress fields within the specimen. With increasing fluence and energy loss, hardening becomes more pronounced.

Frequency domain photothermoacoustic signal amplitude dependence on the optical properties of water: turbid polyvinyl chloride-plastisol system.

PubMed

Spirou, Gloria M; Mandelis, Andreas; Vitkin, I Alex; Whelan, William M

2008-05-10

Photoacoustic (more precisely, photothermoacoustic) signals generated by the absorption of photons can be related to the incident laser fluence rate. The dependence of frequency domain photoacoustic (FD-PA) signals on the optical absorption coefficient (micro(a)) and the effective attenuation coefficient (micro(eff)) of a turbid medium [polyvinyl chloride-plastisol (PVCP)] with tissuelike optical properties was measured, and empirical relationships between these optical properties and the photoacoustic (PA) signal amplitude and the laser fluence rate were derived for the water (PVCP system with and without optical scatterers). The measured relationships between these sample optical properties and the PA signal amplitude were found to be linear, consistent with FD-PA theory: micro(a)=a(A/Phi)-b and micro(eff)=c(A/Phi)+d, where Phi is the laser fluence, A is the FD-PA amplitude, and a, ...,d are empirical coefficients determined from the experiment using linear frequency-swept modulation and a lock-in heterodyne detection technique. This quantitative technique can easily be used to measure the optical properties of general turbid media using FD-PAs.

SU-F-T-288: Impact of Trajectory Log Files for Clarkson-Based Independent Dose Verification of IMRT and VMAT

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

Takahashi, R; Kamima, T; Tachibana, H

2016-06-15

Purpose: To investigate the effect of the trajectory files from linear accelerator for Clarkson-based independent dose verification in IMRT and VMAT plans. Methods: A CT-based independent dose verification software (Simple MU Analysis: SMU, Triangle Products, Japan) with a Clarksonbased algorithm was modified to calculate dose using the trajectory log files. Eclipse with the three techniques of step and shoot (SS), sliding window (SW) and Rapid Arc (RA) was used as treatment planning system (TPS). In this study, clinically approved IMRT and VMAT plans for prostate and head and neck (HN) at two institutions were retrospectively analyzed to assess the dosemore » deviation between DICOM-RT plan (PL) and trajectory log file (TJ). An additional analysis was performed to evaluate MLC error detection capability of SMU when the trajectory log files was modified by adding systematic errors (0.2, 0.5, 1.0 mm) and random errors (5, 10, 30 mm) to actual MLC position. Results: The dose deviations for prostate and HN in the two sites were 0.0% and 0.0% in SS, 0.1±0.0%, 0.1±0.1% in SW and 0.6±0.5%, 0.7±0.9% in RA, respectively. The MLC error detection capability shows the plans for HN IMRT were the most sensitive and 0.2 mm of systematic error affected 0.7% dose deviation on average. Effect of the MLC random error did not affect dose error. Conclusion: The use of trajectory log files including actual information of MLC location, gantry angle, etc should be more effective for an independent verification. The tolerance level for the secondary check using the trajectory file may be similar to that of the verification using DICOM-RT plan file. From the view of the resolution of MLC positional error detection, the secondary check could detect the MLC position error corresponding to the treatment sites and techniques. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

Identification of T. gondii Myosin Light Chain-1 as a Direct Target of TachypleginA-2, a Small-Molecule Inhibitor of Parasite Motility and Invasion

PubMed Central

Leung, Jacqueline M.; Tran, Fanny; Pathak, Ravindra B.; Poupart, Séverine; Heaslip, Aoife T.; Ballif, Bryan A.; Westwood, Nicholas J.; Ward, Gary E.

2014-01-01

Motility of the protozoan parasite Toxoplasma gondii plays an important role in the parasite’s life cycle and virulence within animal and human hosts. Motility is driven by a myosin motor complex that is highly conserved across the Phylum Apicomplexa. Two key components of this complex are the class XIV unconventional myosin, TgMyoA, and its associated light chain, TgMLC1. We previously showed that treatment of parasites with a small-molecule inhibitor of T. gondii invasion and motility, tachypleginA, induces an electrophoretic mobility shift of TgMLC1 that is associated with decreased myosin motor activity. However, the direct target(s) of tachypleginA and the molecular basis of the compound-induced TgMLC1 modification were unknown. We show here by “click” chemistry labelling that TgMLC1 is a direct and covalent target of an alkyne-derivatized analogue of tachypleginA. We also show that this analogue can covalently bind to model thiol substrates. The electrophoretic mobility shift induced by another structural analogue, tachypleginA-2, was associated with the formation of a 225.118 Da adduct on S57 and/or C58, and treatment with deuterated tachypleginA-2 confirmed that the adduct was derived from the compound itself. Recombinant TgMLC1 containing a C58S mutation (but not S57A) was refractory to click labelling and no longer exhibited a mobility shift in response to compound treatment, identifying C58 as the site of compound binding on TgMLC1. Finally, a knock-in parasite line expressing the C58S mutation showed decreased sensitivity to compound treatment in a quantitative 3D motility assay. These data strongly support a model in which tachypleginA and its analogues inhibit the motility of T. gondii by binding directly and covalently to C58 of TgMLC1, thereby causing a decrease in the activity of the parasite’s myosin motor. PMID:24892871

SU-G-BRB-03: Assessing the Sensitivity and False Positive Rate of the Integrated Quality Monitor (IQM) Large Area Ion Chamber to MLC Positioning Errors

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

Boehnke, E McKenzie; DeMarco, J; Steers, J

2016-06-15

Purpose: To examine both the IQM’s sensitivity and false positive rate to varying MLC errors. By balancing these two characteristics, an optimal tolerance value can be derived. Methods: An un-modified SBRT Liver IMRT plan containing 7 fields was randomly selected as a representative clinical case. The active MLC positions for all fields were perturbed randomly from a square distribution of varying width (±1mm to ±5mm). These unmodified and modified plans were measured multiple times each by the IQM (a large area ion chamber mounted to a TrueBeam linac head). Measurements were analyzed relative to the initial, unmodified measurement. IQM readingsmore » are analyzed as a function of control points. In order to examine sensitivity to errors along a field’s delivery, each measured field was divided into 5 groups of control points, and the maximum error in each group was recorded. Since the plans have known errors, we compared how well the IQM is able to differentiate between unmodified and error plans. ROC curves and logistic regression were used to analyze this, independent of thresholds. Results: A likelihood-ratio Chi-square test showed that the IQM could significantly predict whether a plan had MLC errors, with the exception of the beginning and ending control points. Upon further examination, we determined there was ramp-up occurring at the beginning of delivery. Once the linac AFC was tuned, the subsequent measurements (relative to a new baseline) showed significant (p <0.005) abilities to predict MLC errors. Using the area under the curve, we show the IQM’s ability to detect errors increases with increasing MLC error (Spearman’s Rho=0.8056, p<0.0001). The optimal IQM count thresholds from the ROC curves are ±3%, ±2%, and ±7% for the beginning, middle 3, and end segments, respectively. Conclusion: The IQM has proven to be able to detect not only MLC errors, but also differences in beam tuning (ramp-up). Partially supported by the Susan Scott Foundation.« less

SU-D-201-01: A Multi-Institutional Study Quantifying the Impact of Simulated Linear Accelerator VMAT Errors for Nasopharynx

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

Pogson, E; Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW; Ingham Institute for Applied Medical Research, Sydney, NSW

Purpose: To quantify the impact of differing magnitudes of simulated linear accelerator errors on the dose to the target volume and organs at risk for nasopharynx VMAT. Methods: Ten nasopharynx cancer patients were retrospectively replanned twice with one full arc VMAT by two institutions. Treatment uncertainties (gantry angle and collimator in degrees, MLC field size and MLC shifts in mm) were introduced into these plans at increments of 5,2,1,−1,−2 and −5. This was completed using an in-house Python script within Pinnacle3 and analysed using 3DVH and MatLab. The mean and maximum dose were calculated for the Planning Target Volume (PTV1),more » parotids, brainstem, and spinal cord and then compared to the original baseline plan. The D1cc was also calculated for the spinal cord and brainstem. Patient average results were compared across institutions. Results: Introduced gantry angle errors had the smallest effect of dose, no tolerances were exceeded for one institution, and the second institutions VMAT plans were only exceeded for gantry angle of ±5° affecting different sided parotids by 14–18%. PTV1, brainstem and spinal cord tolerances were exceeded for collimator angles of ±5 degrees, MLC shifts and MLC field sizes of ±1 and beyond, at the first institution. At the second institution, sensitivity to errors was marginally higher for some errors including the collimator error producing doses exceeding tolerances above ±2 degrees, and marginally lower with tolerances exceeded above MLC shifts of ±2. The largest differences occur with MLC field sizes, with both institutions reporting exceeded tolerances, for all introduced errors (±1 and beyond). Conclusion: The plan robustness for VMAT nasopharynx plans has been demonstrated. Gantry errors have the least impact on patient doses, however MLC field sizes exceed tolerances even with relatively low introduced errors and also produce the largest errors. This was consistent across both departments. The authors acknowledge funding support from the NSW Cancer Council.« less

Brushed permanent magnet DC MLC motor operation in an external magnetic field.

PubMed

Yun, J; St Aubin, J; Rathee, S; Fallone, B G

2010-05-01

Linac-MR systems for real-time image-guided radiotherapy will utilize the multileaf collimators (MLCs) to perform conformal radiotherapy and tumor tracking. The MLCs would be exposed to the external fringe magnetic fields of the linac-MR hybrid systems. Therefore, an experimental investigation of the effect of an external magnetic field on the brushed permanent magnet DC motors used in some MLC systems was performed. The changes in motor speed and current were measured for varying external magnetic field strengths up to 2000 G generated by an EEV electromagnet. These changes in motor characteristics were measured for three orientations of the motor in the external magnetic field, mimicking changes in motor orientations due to installation and/or collimator rotations. In addition, the functionality of the associated magnetic motor encoder was tested. The tested motors are used with the Varian 120 leaf Millennium MLC (Maxon Motor half leaf and full leaf motors) and the Varian 52 leaf MKII MLC (MicroMo Electronics leaf motor) including a carriage motor (MicroMo Electronics). In most cases, the magnetic encoder of the motors failed prior to any damage to the gearbox or the permanent magnet motor itself. This sets an upper limit of the external magnetic field strength on the motor function. The measured limits of the external magnetic fields were found to vary by the motor type. The leaf motor used with a Varian 52 leaf MKII MLC system tolerated up to 450 +/- 10 G. The carriage motor tolerated up to 2000 +/- 10 G field. The motors used with the Varian 120 leaf Millennium MLC system were found to tolerate a maximum of 600 +/- 10 G. The current Varian MLC system motors can be used for real-time image-guided radiotherapy coupled to a linac-MR system, provided the fringe magnetic fields at their locations are below the determined tolerance levels. With the fringe magnetic fields of linac-MR systems expected to be larger than the tolerance levels determined, some form of magnetic shielding would be required.

SU-G-TeP4-03: A Multileaf Collimator Calibration and Quality Assurance Technique Using An Electronic Portal Imaging Device

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

Lebron, S; Yan, G; Li, J

2016-06-15

Purpose: To develop an accurate and quick multileaf collimator (MLC) calibration and quality assurance technique using an electronic portal imaging device (EPID) Methods: The MLC models used include the MLCi and Agility (Elekta Ltd). This technique consists of two 22(L)x10(W) cm{sup 2} fields with 0{sup 0} and 180{sup 0} collimator angles centered to an offset EPID. The MLC opening is estimated by calculating the profile at the image’s center in the image’s horizontal direction. Scans in the image’s vertical direction were calculated every 20 pixels in the inner 70% of estimated MLC opening. The profiles’ edges were fitted with linearmore » equations to determine the image’s rotation angle. Then, crossline profiles were scanned at the center of each leaf taking into account the leaf’s width at isocenter and the rotation angle. The profiles’ edges determine the location of the leaves’ edges and these were subtracted from the reference leaf’s position in order to determine the relative leaf offsets. The edge location of all profiles was determined by using the parameterized gradient of the penumbra region. The technique was tested against an established diode array-based method, and for different MLC systems, patterns, gantry angles, days, energies, beam modalities and MLC openings. Results: The differences between the proposed and established methods were 0.26±0.19mm. The leaf offsets’ deviation was <0.3mm (5 months period). For pattern fields, the differences between predetermined and calculated offsets were 0.18±0.18mm. The leaf offset deviation of measurements with different energies and MLC openings were <0.1mm and <0.3mm, respectively. The differences between offsets of FF and FFF beams were 0.01±0.02mm (<0.07mm). The differences between the offsets at different gantry angles were 0.08±0.15mm. Conclusion: The proposed method proved to be accurate and efficient in calculating the relative leaf offsets. Parameterized field edge is essential to obtain accurate result by eliminating the noise from EPID.« less

Low-level infrared laser modulates muscle repair and chromosome stabilization genes in myoblasts.

PubMed

da Silva Neto Trajano, Larissa Alexsandra; Stumbo, Ana Carolina; da Silva, Camila Luna; Mencalha, Andre Luiz; Fonseca, Adenilson S

2016-08-01

Infrared laser therapy is used for skeletal muscle repair based on its biostimulative effect on satellite cells. However, shortening of telomere length limits regenerative potential in satellite cells, which occurs after each cell division cycle. Also, laser therapy could be more effective on non-physiologic tissues. This study evaluated low-level infrared laser exposure effects on mRNA expression from muscle injury repair and telomere stabilization genes in myoblasts in normal and stressful conditions. Laser fluences were those used in clinical protocols. C2C12 myoblast cultures were exposed to low-level infrared laser (10, 35, and 70 J/cm(2)) in standard or normal (10 %) and reduced (2 %) fetal bovine serum concentrations; total RNA was extracted for mRNA expression evaluation from muscle injury repair (MyoD and Pax7) and chromosome stabilization (TRF1 and TRF2) genes by real time quantitative polymerization chain reaction. Data show that low-level infrared laser increases the expression of MyoD and Pax7 in 10 J/cm(2) fluence, TRF1 expression in all fluences, and TRF2 expression in 70 J/cm(2) fluence in both 10 and 2 % fetal bovine serum. Low-level infrared laser increases mRNA expression from genes related to muscle repair and telomere stabilization in myoblasts in standard or normal and stressful conditions.

Effect of high fluence neutron irradiation on transport properties of thermoelectrics

DOE PAGES

Wang, H.; Leonard, K. J.

2017-07-25

Thermoelectric materials were subjected to high fluence neutron irradiation in order to understand the effect of radiation damage on transport properties. This paper is relevant to the NASA Radioisotope Thermoelectric Generator (RTG) program in which thermoelectric elements are exposed to radiation over a long period of time in space missions. Selected n-type and p-type bismuth telluride materials were irradiated at the High Flux Isotope Reactor with a neutron fluence of 1.3 × 10 18 n/cm 2 (E > 0.1 MeV). The increase in the Seebeck coefficient in the n-type material was partially off-set by an increase in electrical resistivity, makingmore » the power factor higher at lower temperatures. For the p-type materials, although the Seebeck coefficient was not affected by irradiation, electrical resistivity decreased slightly. The figure of merit, zT, showed a clear drop in the 300–400 K range for the p-type material and an increase for the n-type material. Considering that the p-type and n-type materials are connected in series in a module, the overall irradiation damages at the device level were limited. Finally, these results, at neutron fluences exceeding a typical space mission, are significant to ensure that the radiation damage to thermoelectrics does not affect the performance of RTGs.« less

Effect of high fluence neutron irradiation on transport properties of thermoelectrics

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

Wang, H.; Leonard, K. J.

Thermoelectric materials were subjected to high fluence neutron irradiation in order to understand the effect of radiation damage on transport properties. This paper is relevant to the NASA Radioisotope Thermoelectric Generator (RTG) program in which thermoelectric elements are exposed to radiation over a long period of time in space missions. Selected n-type and p-type bismuth telluride materials were irradiated at the High Flux Isotope Reactor with a neutron fluence of 1.3 × 10 18 n/cm 2 (E > 0.1 MeV). The increase in the Seebeck coefficient in the n-type material was partially off-set by an increase in electrical resistivity, makingmore » the power factor higher at lower temperatures. For the p-type materials, although the Seebeck coefficient was not affected by irradiation, electrical resistivity decreased slightly. The figure of merit, zT, showed a clear drop in the 300–400 K range for the p-type material and an increase for the n-type material. Considering that the p-type and n-type materials are connected in series in a module, the overall irradiation damages at the device level were limited. Finally, these results, at neutron fluences exceeding a typical space mission, are significant to ensure that the radiation damage to thermoelectrics does not affect the performance of RTGs.« less

Joint Optimization of Fluence Field Modulation and Regularization in Task-Driven Computed Tomography.

PubMed

Gang, G J; Siewerdsen, J H; Stayman, J W

2017-02-11

This work presents a task-driven joint optimization of fluence field modulation (FFM) and regularization in quadratic penalized-likelihood (PL) reconstruction. Conventional FFM strategies proposed for filtered-backprojection (FBP) are evaluated in the context of PL reconstruction for comparison. We present a task-driven framework that leverages prior knowledge of the patient anatomy and imaging task to identify FFM and regularization. We adopted a maxi-min objective that ensures a minimum level of detectability index ( d' ) across sample locations in the image volume. The FFM designs were parameterized by 2D Gaussian basis functions to reduce dimensionality of the optimization and basis function coefficients were estimated using the covariance matrix adaptation evolutionary strategy (CMA-ES) algorithm. The FFM was jointly optimized with both space-invariant and spatially-varying regularization strength ( β ) - the former via an exhaustive search through discrete values and the latter using an alternating optimization where β was exhaustively optimized locally and interpolated to form a spatially-varying map. The optimal FFM inverts as β increases, demonstrating the importance of a joint optimization. For the task and object investigated, the optimal FFM assigns more fluence through less attenuating views, counter to conventional FFM schemes proposed for FBP. The maxi-min objective homogenizes detectability throughout the image and achieves a higher minimum detectability than conventional FFM strategies. The task-driven FFM designs found in this work are counter to conventional patterns for FBP and yield better performance in terms of the maxi-min objective, suggesting opportunities for improved image quality and/or dose reduction when model-based reconstructions are applied in conjunction with FFM.

Potential of discrete Gaussian edge feathering method for improving abutment dosimetry in eMLC-delivered segmented-field electron conformal therapy

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

Eley, John G.; Hogstrom, Kenneth R.; Matthews, Kenneth L.

2011-12-15

Purpose: The purpose of this work was to investigate the potential of discrete Gaussian edge feathering of the higher energy electron fields for improving abutment dosimetry in the planning volume when using an electron multileaf collimator (eMLC) to deliver segmented-field electron conformal therapy (ECT). Methods: A discrete (five-step) Gaussian edge spread function was used to match dose penumbras of differing beam energies (6-20 MeV) at a specified depth in a water phantom. Software was developed to define the leaf eMLC positions of an eMLC that most closely fit each electron field shape. The effect of 1D edge feathering of themore » higher energy field on dose homogeneity was computed and measured for segmented-field ECT treatment plans for three 2D PTVs in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of the x-axis (parallel to leaf motion) and remained constant along the y-axis (perpendicular to leaf motion). Additionally, the effect of 2D edge feathering was computed and measured for one radially symmetric, 3D PTV in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of both axes. For the 3D PTV, the feathering scheme was evaluated for 0.1-1.0-cm leaf widths. Dose calculations were performed using the pencil beam dose algorithm in the Pinnacle{sup 3} treatment planning system. Dose verification measurements were made using a prototype eMLC (1-cm leaf width). Results: 1D discrete Gaussian edge feathering reduced the standard deviation of dose in the 2D PTVs by 34, 34, and 39%. In the 3D PTV, the broad leaf width (1 cm) of the eMLC hindered the 2D application of the feathering solution to the 3D PTV, and the standard deviation of dose increased by 10%. However, 2D discrete Gaussian edge feathering with simulated eMLC leaf widths of 0.1-0.5 cm reduced the standard deviation of dose in the 3D PTV by 33-28%, respectively. Conclusions: A five-step discrete Gaussian edge spread function applied in 2D improves the abutment dosimetry but requires an eMLC leaf resolution better than 1 cm.« less

Matching extended-SSD electron beams to multileaf collimated photon beams in the treatment of head and neck cancer.

PubMed

Steel, Jared; Stewart, Allan; Satory, Philip

2009-09-01

Matching the penumbra of a 6 MeV electron beam to the penumbra of a 6 MV photon beam is a dose optimization challenge, especially when the electron beam is applied from an extended source-to-surface distance (SSD), as in the case of some head and neck treatments. Traditionally low melting point alloy blocks have been used to define the photon beam shielding over the spinal cord region. However, these are inherently time consuming to construct and employ in the clinical situation. Multileaf collimators (MLCs) provide a fast and reproducible shielding option but generate geometrically nonconformal approximations to the desired beam edge definition. The effects of substituting Cerrobend for the MLC shielding mode in the context of beam matching with extended-SSD electron beams are the subject of this investigation. Relative dose beam data from a Varian EX 2100 linear accelerator were acquired in a water tank under the 6 MeV electron beam at both standard and extended-SSD and under the 6 MV photon beam defined by Cerrobend and a number of MLC stepping regimes. The effect of increasing the electron beam SSD on the beam penumbra was assessed. MLC stepping was also assessed in terms of the effects on both the mean photon beam penumbra and the intraleaf dose-profile nonuniformity relative to the MLC midleaf. Computational techniques were used to combine the beam data so as to simulate composite relative dosimetry in the water tank, allowing fine control of beam abutment gap variation. Idealized volumetric dosimetry was generated based on the percentage depth-dose data for the beam modes and the abutment geometries involved. Comparison was made between each composite dosimetry dataset and the relevant ideal dosimetry dataset by way of subtraction. Weighted dose-difference volume histograms (DDVHs) were produced, and these, in turn, summed to provide an overall dosimetry score for each abutment and shielding type/angle combination. Increasing the electron beam SSD increased the penumbra width (defined as the lateral distance of the 80% and 20% isodose contours) by 8-10 mm at the depths of 10-20 mm. Mean photon beam penumbra width increased with increased MLC stepping, and the mean MLC penumbra was approximately 1.5 times greater than that across the corresponding Cerrobend shielding. Intraleaf dose discrepancy in the direction orthogonal to the beam edge also increased with MLC stepping. The weighted DDVH comparison techniques allowed the composite dosimetry resulting from the interplay of the abovementioned variables to be ranked. The MLC dosimetry ranked as good or better than that resulting from beam matching with Cerrobend for all except large field overlaps (-2.5 mm gap). The results for the linear-weighted DDVH comparison suggest that optimal MLC abutment dosimetry results from an optical surface gap of around 1 +/- 0.5 mm. Furthermore, this appears reasonably lenient to abutment gap variation, such as that arising from uncertainty in beam markup or other setup errors.

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

Riis, Hans L.; Zimmermann, Sune J.; Hjelm-Hansen, Mogens

Purpose: The delivery of high quality stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) treatments to the patient requires knowledge of the position of the isocenter to submillimeter accuracy. To meet the requirements the deviation between the radiation and mechanical isocenters must be less than 1 mm. The use of add-on micromultileaf collimators ({mu}MLCs) in SRS and SRT is an additional challenge to the anticipated high-level geometric and dosimetric accuracy of the treatment. The aim of this work was to quantify the gantry excursions during rotation with and without an add-on {mu}MLC attached to the gantry head. In addition, the shiftmore » in the position of the isocenter and its correlation to the kV beam center of the cone-beam CT system was included in the study. Methods: The quantification of the gantry rotational performance was done using a pointer supported by an in-house made rigid holder attached to the gantry head of the accelerator. The pointer positions were measured using a digital theodolite. To quantify the effect of an {mu}MLC of 50 kg, the measurements were repeated with the {mu}MLC attached to the gantry head. The displacement of the isocenter due to an add-on {mu}MLC of 50 kg was also investigated. In case of the pointer measurement the {mu}MLC was simulated by weights attached to the gantry head. A method of least squares was applied to determine the position and displacement of the mechanical isocenter. Additionally, the displacement of the radiation isocenter was measured using a ball-bearing phantom and the electronic portal image device system. These measurements were based on 8 MV photon beams irradiated onto the ball from the four cardinal angles and two opposed collimator angles. The measurements and analysis of the data were carried out automatically using software delivered by the manufacturer. Results: The displacement of the mechanical isocenter caused by a 50 kg heavy {mu}MLC was found to be (-0.01 {+-} 0.05, -0.10 {+-} 0.03, -0.26 {+-} 0.05) mm in lateral, longitudinal, and vertical direction, respectively. Similarly, the displacement of the radiation isocenter was found to be (0.00 {+-} 0.03, -0.08 {+-} 0.06, -0.32 {+-} 0.02) mm. Good agreement was found between the displacement of the two isocenters. A displacement of the kV cone-beam CT beam center due to the attached weight of 50 kg could not be detected. Conclusions: General characteristics of the gantry arm excursions and displacements caused by an add-on {mu}MLC have been reported. A 50 kg heavy add-on {mu}MLC results in a isocenter displacement downward of 0.26-0.32 mm. The authors recommend that the beam center of the kV cone-beam CT image system should be matched to the isocenter related to the weight of the {mu}MLC. Consequently, the imperfections in isocenter localizations are transferred to the conventional radiotherapy where the clinical consequences of uncertainties in the submillimeter regime are negligible.« less

Ionization chamber-based reference dosimetry of intensity modulated radiation beams.

PubMed

Bouchard, Hugo; Seuntjens, Jan

2004-09-01

The present paper addresses reference dose measurements using thimble ionization chambers for quality assurance in IMRT fields. In these radiation fields, detector fluence perturbation effects invalidate the application of open-field dosimetry protocol data for the derivation of absorbed dose to water from ionization chamber measurements. We define a correction factor C(Q)IMRT to correct the absorbed dose to water calibration coefficient N(D, w)Q for fluence perturbation effects in individual segments of an IMRT delivery and developed a calculation method to evaluate the factor. The method consists of precalculating, using accurate Monte Carlo techniques, ionization chamber, type-dependent cavity air dose, and in-phantom dose to water at the reference point for zero-width pencil beams as a function of position of the pencil beams impinging on the phantom surface. These precalculated kernels are convolved with the IMRT fluence distribution to arrive at the dose-to-water-dose-to-cavity air ratio [D(a)w (IMRT)] for IMRT fields and with a 10x10 cm2 open-field fluence to arrive at the same ratio D(a)w (Q) for the 10x10 cm2 reference field. The correction factor C(Q)IMRT is then calculated as the ratio of D(a)w (IMRT) and D(a)w (Q). The calculation method was experimentally validated and the magnitude of chamber correction factors in reference dose measurements in single static and dynamic IMRT fields was studied. The results show that, for thimble-type ionization chambers the correction factor in a single, realistic dynamic IMRT field can be of the order of 10% or more. We therefore propose that for accurate reference dosimetry of complete n-beam IMRT deliveries, ionization chamber fluence perturbation correction factors must explicitly be taken into account.

Fluence correction factor for graphite calorimetry in a clinical high-energy carbon-ion beam.

PubMed

Lourenço, A; Thomas, R; Homer, M; Bouchard, H; Rossomme, S; Renaud, J; Kanai, T; Royle, G; Palmans, H

2017-04-07

The aim of this work is to develop and adapt a formalism to determine absorbed dose to water from graphite calorimetry measurements in carbon-ion beams. Fluence correction factors, [Formula: see text], needed when using a graphite calorimeter to derive dose to water, were determined in a clinical high-energy carbon-ion beam. Measurements were performed in a 290 MeV/n carbon-ion beam with a field size of 11  ×  11 cm 2 , without modulation. In order to sample the beam, a plane-parallel Roos ionization chamber was chosen for its small collecting volume in comparison with the field size. Experimental information on fluence corrections was obtained from depth-dose measurements in water. This procedure was repeated with graphite plates in front of the water phantom. Fluence corrections were also obtained with Monte Carlo simulations through the implementation of three methods based on (i) the fluence distributions differential in energy, (ii) a ratio of calculated doses in water and graphite at equivalent depths and (iii) simulations of the experimental setup. The [Formula: see text] term increased in depth from 1.00 at the entrance toward 1.02 at a depth near the Bragg peak, and the average difference between experimental and numerical simulations was about 0.13%. Compared to proton beams, there was no reduction of the [Formula: see text] due to alpha particles because the secondary particle spectrum is dominated by projectile fragmentation. By developing a practical dose conversion technique, this work contributes to improving the determination of absolute dose to water from graphite calorimetry in carbon-ion beams.

Minimal-Level Cataloging: A Look at the Issues--A Symposium.

ERIC Educational Resources Information Center

Horny, Karen L.; And Others

1986-01-01

Six articles on pros and cons of minimal-level cataloging (MLC) highlight patron access and browsability, time and cost savings, network and bibliographic utility cooperation, standards, alternatives to MLC, levels of records, online catalogs, experimental cataloging program at University of Michigan, and experiences at Kent State University…

Intensity modulated neutron radiotherapy optimization by photon proxy

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

Snyder, Michael; Hammoud, Ahmad; Bossenberger, Todd

2012-08-15

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

TU-CD-304-01: FEATURED PRESENTATION and BEST IN PHYSICS (THERAPY): Trajectory Modulated Arc Therapy: Development of Novel Arc Delivery Techniques Integrating Dynamic Table Motion for Extended Volume Treatments

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

Chin, E; Hoppe, R; Million, L

2015-06-15

Purpose: Integration of coordinated robotic table motion with inversely-planned arc delivery has the potential to resolve table-top delivery limitations of large-field treatments such as Total Body Irradiation (TBI), Total Lymphoid Irradiation (TLI), and Cranial-Spinal Irradiation (CSI). We formulate the foundation for Trajectory Modulated Arc Therapy (TMAT), and using Varian Developer Mode capabilities, experimentally investigate its practical implementation for such techniques. Methods: A MATLAB algorithm was developed for inverse planning optimization of the table motion, MLC positions, and gantry motion under extended-SSD geometry. To maximize the effective field size, delivery trajectories for TMAT TBI were formed with the table rotated atmore » 270° IEC and dropped vertically to 152.5cm SSD. Preliminary testing of algorithm parameters was done through retrospective planning analysis. Robotic delivery was programmed using custom XML scripting on the TrueBeam Developer Mode platform. Final dose was calculated using the Eclipse AAA algorithm. Initial verification of delivery accuracy was measured using OSLDs on a solid water phantom of varying thickness. Results: A comparison of DVH curves demonstrated that dynamic couch motion irradiation was sufficiently approximated by static control points spaced in intervals of less than 2cm. Optimized MLC motion decreased the average lung dose to 68.5% of the prescription dose. The programmed irradiation integrating coordinated table motion was deliverable on a TrueBeam STx linac in 6.7 min. With the couch translating under an open 10cmx20cm field angled at 10°, OSLD measurements along the midline of a solid water phantom at depths of 3, 5, and 9cm were within 3% of the TPS AAA algorithm with an average deviation of 1.2%. Conclusion: A treatment planning and delivery system for Trajectory Modulated Arc Therapy of extended volumes has been established and experimentally demonstrated for TBI. Extension to other treatment techniques such as TLI and CSI is readily achievable through the developed platform. Grant Funding by Varian Medical Systems.« less

TH-EF-BRB-10: Dosimetric Validation of a Trajectory Based Cranial SRS Treatment Technique On a Varian TrueBeam Linac

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

Wilson, B; Vancouver Cancer Centre, Vancouver, BC; Gete, E

2016-06-15

Purpose: This work investigates the dosimetric accuracy of a trajectory based delivery technique in which an optimized radiation beam is delivered along a Couch-Gantry trajectory that is formed by simultaneous rotation of the linac gantry and the treatment couch. Methods: Nine trajectory based cranial SRS treatment plans were created using in-house optimization software. The plans were calculated for delivery on the TrueBeam STx linac with 6MV photon beam. Dose optimization was performed along a user-defined trajectory using MLC modulation, dose rate modulation and jaw tracking. The pre-defined trajectory chosen for this study is formed by a couch rotation through itsmore » full range of 180 degrees while the gantry makes four partial arc sweeps which are 170 degrees each. For final dose calculation, the trajectory based plans were exported to the Varian Eclipse Treatment Planning System. The plans were calculated on a homogeneous cube phantom measuring 18.2×18.2×18.2 cm3 with the analytical anisotropic algorithm (AAA) using a 1mm3 calculation voxel. The plans were delivered on the TrueBeam linac via the developer’s mode. Point dose measurements were performed on 9 patients with the IBA CC01 mini-chamber with a sensitive volume of 0.01 cc. Gafchromic film measurements along the sagittal and coronal planes were performed on three of the 9 treatment plans. Point dose values were compared with ion chamber measurements. Gamma analysis comparing film measurement and AAA calculations was performed using FilmQA Pro. Results: The AAA calculations and measurements were in good agreement. The point dose difference between AAA and ion chamber measurements were within 2.2%. Gamma analysis test pass rates (2%, 2mm passing criteria) for the Gafchromic film measurements were >95%. Conclusion: We have successfully tested TrueBeam’s ability to deliver accurate trajectory based treatments involving simultaneous gantry and couch rotation with MLC and dose rate modulation along the trajectory.« less

TH-AB-BRB-01: Trajectory Modulated Arc Therapy: Application to Partial Breast Irradiation

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

Hristov, D.

2016-06-15

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapymore » involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.« less

Ultrahigh precision nonlinear reflectivity measurement system for saturable absorber mirrors with self-referenced fluence characterization.

PubMed

Orsila, Lasse; Härkönen, Antti; Hyyti, Janne; Guina, Mircea; Steinmeyer, Günter

2014-08-01

Measurement of nonlinear optical reflectivity of saturable absorber devices is discussed. A setup is described that enables absolute accuracy of reflectivity measurements better than 0.3%. A repeatability within 0.02% is shown for saturable absorbers with few-percent modulation depth. The setup incorporates an in situ knife-edge characterization of beam diameters, making absolute reflectivity estimations and determination of saturation fluences significantly more reliable. Additionally, several measures are discussed to substantially improve the reliability of the reflectivity measurements. At its core, the scheme exploits the limits of state-of-the-art digital lock-in technology but also greatly benefits from a fiber-based master-oscillator power-amplifier source, the use of an integrating sphere, and simultaneous comparison with a linear reflectivity standard.

Characterisation of novel thin n-in-p planar pixel modules for the ATLAS Inner Tracker upgrade

NASA Astrophysics Data System (ADS)

Beyer, J.-C.; La Rosa, A.; Macchiolo, A.; Nisius, R.; Savic, N.; Taibah, R.

2018-01-01

In view of the high luminosity phase of the LHC (HL-LHC) to start operation around 2026, a major upgrade of the tracker system for the ATLAS experiment is in preparation. The expected neutron equivalent fluence of up to 2.4×1016 1 MeV neq./cm2 at the innermost layer of the pixel detector poses the most severe challenge. Thanks to their low material budget and high charge collection efficiency after irradiation, modules made of thin planar pixel sensors are promising candidates to instrument these layers. To optimise the sensor layout for the decreased pixel cell size of 50×50 μm2, TCAD device simulations are being performed to investigate the charge collection efficiency before and after irradiation. In addition, sensors of 100-150 μm thickness, interconnected to FE-I4 read-out chips featuring the previous generation pixel cell size of 50×250 μm2, are characterised with testbeams at the CERN-SPS and DESY facilities. The performance of sensors with various designs, irradiated up to a fluence of 1×1016 neq./cm2, is compared in terms of charge collection and hit efficiency. A replacement of the two innermost pixel layers is foreseen during the lifetime of HL-LHC . The replacement will require several months of intervention, during which the remaining detector modules cannot be cooled. They are kept at room temperature, thus inducing an annealing. The performance of irradiated modules will be investigated with testbeam campaigns and the method of accelerated annealing at higher temperatures.

Experimental verification of a Monte Carlo-based MLC simulation model for IMRT dose calculations in heterogeneous media

NASA Astrophysics Data System (ADS)

Tyagi, N.; Curran, B. H.; Roberson, P. L.; Moran, J. M.; Acosta, E.; Fraass, B. A.

2008-02-01

IMRT often requires delivering small fields which may suffer from electronic disequilibrium effects. The presence of heterogeneities, particularly low-density tissues in patients, complicates such situations. In this study, we report on verification of the DPM MC code for IMRT treatment planning in heterogeneous media, using a previously developed model of the Varian 120-leaf MLC. The purpose of this study is twofold: (a) design a comprehensive list of experiments in heterogeneous media for verification of any dose calculation algorithm and (b) verify our MLC model in these heterogeneous type geometries that mimic an actual patient geometry for IMRT treatment. The measurements have been done using an IMRT head and neck phantom (CIRS phantom) and slab phantom geometries. Verification of the MLC model has been carried out using point doses measured with an A14 slim line (SL) ion chamber inside a tissue-equivalent and a bone-equivalent material using the CIRS phantom. Planar doses using lung and bone equivalent slabs have been measured and compared using EDR films (Kodak, Rochester, NY).

Coordinate changes of myosin light and heavy chain isoforms during forced fiber type transitions in rabbit muscle.

PubMed

Leeuw, T; Pette, D

1996-01-01

Skeletal muscle fibers are versatile entities, capable of changing their phenotype in response to altered functional demands. In the present study, fast-to-slow fiber type transitions were induced in rabbit tibialis anterior (fA) muscles by chronic low-frequency stimulation (CLFS). The time course of changes in relative protein concentrations of fast and slow myosin light chain (MLC) isoforms and changes in their relative synthesis rates by in vivo labeling with [35S]methionine were followed during stimulation periods of up to 60 days. Generally, relative synthesis rates and protein concentrations changed in parallel; i.e., fast isoforms decreased and slow isoforms increased. MLC3f, however, which turns over at a higher rate than the other light chains, exhibited a conspicuous discrepancy between a markedly reduced relative synthesis but only a moderate decrease in protein amount during the initial 2 weeks of CLFS. Apparently, MLC3f is regulated independent of MLC1f, with protein degradation playing an important role in its regulation. The exchange of fast MLC isoforms with their slow counterparts seemed to correspond to the ultimate fast-to-slow (MHCIIa-->MHCI) transition at the MHC level. However, due to an earlier onset of the fast-to-slow transition of the regulatory light chain and the delayed fast-to-slow exchange of the alkali light chains, a spectrum of hybrid isomyosins composed of fast and slow light and heavy chains must have existed transiently in transforming fibers. Such hybrid isomyosins appeared to be restricted to MHCIIa- and MHCI-based combinations. In conclusion, fiber type specific programs that normally coordinate the expression of myofibrillar protein isoforms seem to be maintained during fiber type transitions. Possible differences in post-transcriptional regulation may result in the transient accumulation of atypical combinations of fast and slow MLC and MHC isoforms, giving rise to the appearance of hybrid fibers under the conditions of forced fiber type conversion.

Ultrasound-Guided Delivery of siRNA and a Chemotherapeutic Drug by Using Microbubble Complexes: In Vitro and In Vivo Evaluations in a Prostate Cancer Model.

PubMed

Bae, Yun Jung; Yoon, Young Il; Yoon, Tae-Jong; Lee, Hak Jong

2016-01-01

To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo. Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo. Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 ± 2.9%), which was further potentiated by application of ultrasound (55.0 ± 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 ± 4.90% to 36.7 ± 1.34%, p = 0.027). Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin-targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo.

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

Tien, C; Brewer, M; Studenski, M

Purpose: Dynamic-jaw tracking maximizes the area blocked by both jaw and MLC in RapidArc. We developed a method to quantify jaw tracking. Methods: An Eclipse Scripting API (ESAPI) was used to export beam parameters for each arc’s control points. The specific beam parameters extracted were: gantry angle, control point number, meterset, x-jaw positions, y-jaw positions, MLC bank-number, MLC leaf-number, and MLC leaf-position. Each arc contained 178 control points with 120 MLC positions. MATLAB routines were written to process these parameters in order to calculate both the beam aperture (unblocked) size for each control point. An average aperture size was weightedmore » by meterset. Jaw factor was defined as the ratio between dynamic-jaw to static-jaw aperture size. Jaw factor was determined for forty retrospectively replanned patients treated with static-jaw delivery sites including lung, brain, prostate, H&N, rectum, and bladder. Results: Most patients had multiple arcs and reduced-field boosts, resulting in 151 fields. Of these, the lowest (0.4722) and highest (0.9622) jaw factor was observed in prostate and rectal cases, respectively. The median jaw factor was 0.7917 meaning there is the potential unincreased blocking by 20%. Clinically, the dynamic-jaw tracking represents an area surrounding the target which would receive MLC-only leakage transmission of 1.68% versus 0.1% with jaws. Jaw-tracking was more pronounced at areas farther from the target. In prostate patients, the rectum and bladder had 5.5% and 6.3% lower mean dose, respectively; the structures closer to the prostate such as the rectum and bladder both had 1.4% lower mean dose. Conclusion: A custom ESAPI script was coupled with a MATLAB routine in order to extract beam parameters from static-jaw plans and their replanned dynamic-jaw deliveries. The effects were quantified using jaw factor which is the ratio between the meterset weighted aperture size for dynamic-jaw fields versus static-jaw fields.« less

SU-E-T-392: Evaluation of Ion Chamber/film and Log File Based QA to Detect Delivery Errors

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

Nelson, C; Mason, B; Kirsner, S

2015-06-15

Purpose: Ion chamber and film (ICAF) is a method used to verify patient dose prior to treatment. More recently, log file based QA has been shown as an alternative for measurement based QA. In this study, we delivered VMAT plans with and without errors to determine if ICAF and/or log file based QA was able to detect the errors. Methods: Using two VMAT patients, the original treatment plan plus 7 additional plans with delivery errors introduced were generated and delivered. The erroneous plans had gantry, collimator, MLC, gantry and collimator, collimator and MLC, MLC and gantry, and gantry, collimator, andmore » MLC errors. The gantry and collimator errors were off by 4{sup 0} for one of the two arcs. The MLC error introduced was one in which the opening aperture didn’t move throughout the delivery of the field. For each delivery, an ICAF measurement was made as well as a dose comparison based upon log files. Passing criteria to evaluate the plans were ion chamber less and 5% and film 90% of pixels pass the 3mm/3% gamma analysis(GA). For log file analysis 90% of voxels pass the 3mm/3% 3D GA and beam parameters match what was in the plan. Results: Two original plans were delivered and passed both ICAF and log file base QA. Both ICAF and log file QA met the dosimetry criteria on 4 of the 12 erroneous cases analyzed (2 cases were not analyzed). For the log file analysis, all 12 erroneous plans alerted a mismatch in delivery versus what was planned. The 8 plans that didn’t meet criteria all had MLC errors. Conclusion: Our study demonstrates that log file based pre-treatment QA was able to detect small errors that may not be detected using an ICAF and both methods of were able to detect larger delivery errors.« less

SU-E-T-312: Dosimetric Consideration for the Agility MLC When Planning Rotational SRT/SBRT Treatments

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

Kong, X; Harris, J; Spitznagel, D

2015-06-15

Purpose: To analyze the radiation transmission of the Agility MLC and make recommendation based on the MLC dosimetric characteristics for SRT, SBRT and VMAT planning Method and Materials: Agility MLC is the newest model from Elekta and has no back up diaphragm behind leaves for this generation. Leaves are single focused with rounded end; composed of leafs each 0.5cm wide, 9cm thick, constructed from tungsten alloy and provide low transmission <0.5%. Total radiation transmission from leaves and diaphragm is <0.13%. A 360degree arc was generated using iCom tools; leaves were programmed closed while keeping the diaphragm fully open to maximizemore » the MLC transmission effect. Gafchromic EBT films were sandwiched between 4cm of solid water and situated at midplane to take dose measurement. 5000MU was delivered using 6MV VersaHD, various collimator angles, and a 5cm central axis offset was tested also. Films were scanned with Epson 10000XL scanner and analyzed using DoseLab Pro. Results: Due to the rounded leaf end and nature of rotation therapy, dose accumulation through the leaf gap is significant. By offsetting the leaf gap from central axis, this accumulation can be greatly reduced. There are dark bands showing accumulation of interleaf transmission which is improved by increasing collimator angle from 0 to 45dgree. However for 45 degree, in most cases, there are larger volumes sweeping under MLC alone, which needs considered planning. Conclusions: While inter-leaf leakage is minimized by using collimator angles greater than 0 degrees, the location of the leaf gap must also be managed. The leaf gap position becomes critically important when the treatment area is off axis such is the case when more than one PTV is being treated. With VMAT for SRT, SBRT becoming a more popular planning technique, special attention needs to be paid when initially setting up the field geometry.« less

SU-E-T-610: Comparison of Treatment Times Between the MLCi and Agility Multileaf Collimators

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

Ramsey, C; Bowling, J

2014-06-01

Purpose: The Agility is a new 160-leaf MLC developed by Elekta for use in their Infinity and Versa HD linacs. As compared to the MLCi, the Agility increased the maximum leaf speed from 2 cm/s to 3.5 cm/s, and the maximum primary collimator speed from 1.5 cm/s to 9.0 cm/s. The purpose of this study was to determine if the Agility MLC resulted in improved plan quality and/or shorter treatment times. Methods: An Elekta Infinity that was originally equipped with a 80 leaf MLCi was upgraded to an 160 leaf Agility. Treatment plan quality was evaluated using the Pinnacle planningmore » system with SmartArc. Optimization was performed once for the MLCi and once for the Agility beam models using the same optimization parameters and the same number of iterations. Patient treatment times were measured for all IMRT, VMAT, and SBRT patients treated on the Infinity with the MLCi and Agility MLCs. Treatment times were extracted from the EMR and measured from when the patient first walked into the treatment room until exiting the treatment room. Results: 11,380 delivery times were measured for patients treated with the MLCi, and 1,827 measurements have been made for the Agility MLC. The average treatment times were 19.1 minutes for the MLCi and 20.8 minutes for the Agility. Using a t-test analysis, there was no difference between the two groups (t = 0.22). The dose differences between patients planned with the MLCi and the Agility MLC were minimal. For example, the dose difference for the PTV, GTV, and cord for a head and neck patient planned using Pinnacle were effectively equivalent. However, the dose to the parotid glands was slightly worse with the Agility MLC. Conclusion: There was no statistical difference in treatment time, or any significant dosimetric difference between the Agility MLC and the MLCi.« less

Verification of dosimetric accuracy on the TrueBeam STx: rounded leaf effect of the high definition MLC.

PubMed

Kielar, Kayla N; Mok, Ed; Hsu, Annie; Wang, Lei; Luxton, Gary

2012-10-01

The dosimetric leaf gap (DLG) in the Varian Eclipse treatment planning system is determined during commissioning and is used to model the effect of the rounded leaf-end of the multileaf collimator (MLC). This parameter attempts to model the physical difference between the radiation and light field and account for inherent leakage between leaf tips. With the increased use of single fraction high dose treatments requiring larger monitor units comes an enhanced concern in the accuracy of leakage calculations, as it accounts for much of the patient dose. This study serves to verify the dosimetric accuracy of the algorithm used to model the rounded leaf effect for the TrueBeam STx, and describes a methodology for determining best-practice parameter values, given the novel capabilities of the linear accelerator such as flattening filter free (FFF) treatments and a high definition MLC (HDMLC). During commissioning, the nominal MLC position was verified and the DLG parameter was determined using MLC-defined field sizes and moving gap tests, as is common in clinical testing. Treatment plans were created, and the DLG was optimized to achieve less than 1% difference between measured and calculated dose. The DLG value found was tested on treatment plans for all energies (6 MV, 10 MV, 15 MV, 6 MV FFF, 10 MV FFF) and modalities (3D conventional, IMRT, conformal arc, VMAT) available on the TrueBeam STx. The DLG parameter found during the initial MLC testing did not match the leaf gap modeling parameter that provided the most accurate dose delivery in clinical treatment plans. Using the physical leaf gap size as the DLG for the HDMLC can lead to 5% differences in measured and calculated doses. Separate optimization of the DLG parameter using end-to-end tests must be performed to ensure dosimetric accuracy in the modeling of the rounded leaf ends for the Eclipse treatment planning system. The difference in leaf gap modeling versus physical leaf gap dimensions is more pronounced in the more recent versions of Eclipse for both the HDMLC and the Millennium MLC. Once properly commissioned and tested using a methodology based on treatment plan verification, Eclipse is able to accurately model radiation dose delivered for SBRT treatments using the TrueBeam STx.

SU-E-T-347: Effect of MLC Leaf Position Inaccuracy On Dose Distribution for Spinal SBRT with Different Energies and Dose Rates

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

You, T; Dang, J; Dai, C

2015-06-15

Purpose: To evaluate dosimetric impact of spinal SBRT when MLC leaf positions deviate from planning positions for different energies and doserates. Methods and Materials: 18 localized spinal metastases patients were selected for SBRT using IMRT planning with 9 posterior beams delivered at gantry angles ranging between 100°–260°. A modern linear accelerator(Varian Turebeam STX with HDMLC 2.5 mm thick leaf at isocenter) IMRT plans were generated using both 6X and 6X-FFF(Flattening filter free) beams with a nominal prescription dose of 6 Gy/fraction to PTV. Doserates ranging from 200–600 MU/min for 6X and 400–1400 MU/min for 6X-FFF, with 200 increments were examined.more » A fixed amount(0.3, 0.5, 1, and 2 mm) of MLC-leaf position deviation was simulated to each plan under following conditions: 1)only along X1 collimator; 2)with increments at both X1 and X2 collimator directions;3)with reductions at both X1 and X2 collimator directions. Dose was recalculated for each modified plans. Both original and modified plans were delivered using Turebeam STX machine and measured using both portal dosimetry and a 3D dosimeter(Delta4 of ScandiDos). Each field’s Result were compared using following three parameters: the 95% iso-dose level Conformal Index(95%CI), the spinal cord maximum dose(SCDmax), and the planned target volume(PTV) mean dose. Results: Dosimetric impacts on the 95%CI, SCDmax and the PTV mean dose are: 1)negligible if MLC-leaf position deviation only along a single collimator direction ≥1.0 mm,2)substantial if MLC-leaf position increment along both collimator directions ≥0.3 mm(95% CI decreases while SCDmax and PTV mean-dose increase), 3)substantial if MLC-leaf position reduction along both collimator directions ≥0.3 mm(95% CI first increases and then decreases while SCDmax and PTV mean-dose decrease). Different energies and doserates demonstrated comparable dosimetric impacts. Conclusion: Substantial dose deviations could happen for spinal SBRT using IMRT plan with HD-MLC if leaf position deviation ≥0.3 mm. The effects of different energy and doserate are negligible.« less

Monte Carlo-based QA for IMRT of head and neck cancers

NASA Astrophysics Data System (ADS)

Tang, F.; Sham, J.; Ma, C.-M.; Li, J.-S.

2007-06-01

It is well-known that the presence of large air cavity in a dense medium (or patient) introduces significant electronic disequilibrium when irradiated with megavoltage X-ray field. This condition may worsen by the possible use of tiny beamlets in intensity-modulated radiation therapy (IMRT). Commercial treatment planning systems (TPSs), in particular those based on the pencil-beam method, do not provide accurate dose computation for the lungs and other cavity-laden body sites such as the head and neck. In this paper we present the use of Monte Carlo (MC) technique for dose re-calculation of IMRT of head and neck cancers. In our clinic, a turn-key software system is set up for MC calculation and comparison with TPS-calculated treatment plans as part of the quality assurance (QA) programme for IMRT delivery. A set of 10 off-the-self PCs is employed as the MC calculation engine with treatment plan parameters imported from the TPS via a graphical user interface (GUI) which also provides a platform for launching remote MC simulation and subsequent dose comparison with the TPS. The TPS-segmented intensity maps are used as input for the simulation hence skipping the time-consuming simulation of the multi-leaf collimator (MLC). The primary objective of this approach is to assess the accuracy of the TPS calculations in the presence of air cavities in the head and neck whereas the accuracy of leaf segmentation is verified by fluence measurement using a fluoroscopic camera-based imaging device. This measurement can also validate the correct transfer of intensity maps to the record and verify system. Comparisons between TPS and MC calculations of 6 MV IMRT for typical head and neck treatments review regional consistency in dose distribution except at and around the sinuses where our pencil-beam-based TPS sometimes over-predicts the dose by up to 10%, depending on the size of the cavities. In addition, dose re-buildup of up to 4% is observed at the posterior nasopharyngeal mucosa for some treatments with heavily-weighted anterior fields.

High-efficiency volume holograms recording on acrylamide and N,N‧methylene-bis-acrylamide photopolymer with pulsed laser

NASA Astrophysics Data System (ADS)

Gallego, S.; Ortuño, M.; García, C.; Neipp, C.; Beléndez, A.; Pascual, I.

2005-11-01

In order to achieve a better understanding of the mechanisms of hologram formation and higher diffraction efficiencies in volume gratings stored in acrylamide based photopolymers, a crosslinker (N,N'methylene-bis-acrylamide) has been incorporated in the photopolymer to record holograms by pulsed laser exposure. The presence of this component increases the polymerization rate and refractive index modulation. The recording was performed using a holographic copying process. The original was a grating of 1000?lines/mm processed using silver halide sensitized gelatin. First, the effect of the pulse fluence was investigated. When the pulse fluence was optimized, the results obtained using the new composition of material were compared with those using the composition without a crosslinker. Using a pulsed laser at 532?nm the photopolymer without crosslinker presented diffraction efficiencies slightly less than 60%. On the other hand, when the crosslinker was introduced in the photopolymer composition, the diffraction efficiencies achieved were higher than 85%. The non-linearity of the material's response was also studied comparing the energetic sensitivity, diffraction efficiencies and index modulation of gratings recorded with pulsed and continuous laser exposure. This study was performed fitting the angular scan of each grating using Kogelnik's theory.

A fast optimization approach for treatment planning of volumetric modulated arc therapy.

PubMed

Yan, Hui; Dai, Jian-Rong; Li, Ye-Xiong

2018-05-30

Volumetric modulated arc therapy (VMAT) is widely used in clinical practice. It not only significantly reduces treatment time, but also produces high-quality treatment plans. Current optimization approaches heavily rely on stochastic algorithms which are time-consuming and less repeatable. In this study, a novel approach is proposed to provide a high-efficient optimization algorithm for VMAT treatment planning. A progressive sampling strategy is employed for beam arrangement of VMAT planning. The initial beams with equal-space are added to the plan in a coarse sampling resolution. Fluence-map optimization and leaf-sequencing are performed for these beams. Then, the coefficients of fluence-maps optimization algorithm are adjusted according to the known fluence maps of these beams. In the next round the sampling resolution is doubled and more beams are added. This process continues until the total number of beams arrived. The performance of VMAT optimization algorithm was evaluated using three clinical cases and compared to those of a commercial planning system. The dosimetric quality of VMAT plans is equal to or better than the corresponding IMRT plans for three clinical cases. The maximum dose to critical organs is reduced considerably for VMAT plans comparing to those of IMRT plans, especially in the head and neck case. The total number of segments and monitor units are reduced for VMAT plans. For three clinical cases, VMAT optimization takes < 5 min accomplished using proposed approach and is 3-4 times less than that of the commercial system. The proposed VMAT optimization algorithm is able to produce high-quality VMAT plans efficiently and consistently. It presents a new way to accelerate current optimization process of VMAT planning.

Joint Optimization of Fluence Field Modulation and Regularization in Task-Driven Computed Tomography

PubMed Central

Gang, G. J.; Siewerdsen, J. H.; Stayman, J. W.

2017-01-01

Purpose This work presents a task-driven joint optimization of fluence field modulation (FFM) and regularization in quadratic penalized-likelihood (PL) reconstruction. Conventional FFM strategies proposed for filtered-backprojection (FBP) are evaluated in the context of PL reconstruction for comparison. Methods We present a task-driven framework that leverages prior knowledge of the patient anatomy and imaging task to identify FFM and regularization. We adopted a maxi-min objective that ensures a minimum level of detectability index (d′) across sample locations in the image volume. The FFM designs were parameterized by 2D Gaussian basis functions to reduce dimensionality of the optimization and basis function coefficients were estimated using the covariance matrix adaptation evolutionary strategy (CMA-ES) algorithm. The FFM was jointly optimized with both space-invariant and spatially-varying regularization strength (β) - the former via an exhaustive search through discrete values and the latter using an alternating optimization where β was exhaustively optimized locally and interpolated to form a spatially-varying map. Results The optimal FFM inverts as β increases, demonstrating the importance of a joint optimization. For the task and object investigated, the optimal FFM assigns more fluence through less attenuating views, counter to conventional FFM schemes proposed for FBP. The maxi-min objective homogenizes detectability throughout the image and achieves a higher minimum detectability than conventional FFM strategies. Conclusions The task-driven FFM designs found in this work are counter to conventional patterns for FBP and yield better performance in terms of the maxi-min objective, suggesting opportunities for improved image quality and/or dose reduction when model-based reconstructions are applied in conjunction with FFM. PMID:28626290

Joint optimization of fluence field modulation and regularization in task-driven computed tomography

NASA Astrophysics Data System (ADS)

Gang, G. J.; Siewerdsen, J. H.; Stayman, J. W.

2017-03-01

Purpose: This work presents a task-driven joint optimization of fluence field modulation (FFM) and regularization in quadratic penalized-likelihood (PL) reconstruction. Conventional FFM strategies proposed for filtered-backprojection (FBP) are evaluated in the context of PL reconstruction for comparison. Methods: We present a task-driven framework that leverages prior knowledge of the patient anatomy and imaging task to identify FFM and regularization. We adopted a maxi-min objective that ensures a minimum level of detectability index (d') across sample locations in the image volume. The FFM designs were parameterized by 2D Gaussian basis functions to reduce dimensionality of the optimization and basis function coefficients were estimated using the covariance matrix adaptation evolutionary strategy (CMA-ES) algorithm. The FFM was jointly optimized with both space-invariant and spatially-varying regularization strength (β) - the former via an exhaustive search through discrete values and the latter using an alternating optimization where β was exhaustively optimized locally and interpolated to form a spatially-varying map. Results: The optimal FFM inverts as β increases, demonstrating the importance of a joint optimization. For the task and object investigated, the optimal FFM assigns more fluence through less attenuating views, counter to conventional FFM schemes proposed for FBP. The maxi-min objective homogenizes detectability throughout the image and achieves a higher minimum detectability than conventional FFM strategies. Conclusions: The task-driven FFM designs found in this work are counter to conventional patterns for FBP and yield better performance in terms of the maxi-min objective, suggesting opportunities for improved image quality and/or dose reduction when model-based reconstructions are applied in conjunction with FFM.

Direct measurements of multi-photon induced nonlinear lattice dynamics in semiconductors via time-resolved x-ray scattering.

PubMed

Williams, G Jackson; Lee, Sooheyong; Walko, Donald A; Watson, Michael A; Jo, Wonhuyk; Lee, Dong Ryeol; Landahl, Eric C

2016-12-22

Nonlinear optical phenomena in semiconductors present several fundamental problems in modern optics that are of great importance for the development of optoelectronic devices. In particular, the details of photo-induced lattice dynamics at early time-scales prior to carrier recombination remain poorly understood. We demonstrate the first integrated measurements of both optical and structural, material-dependent quantities while also inferring the bulk impulsive strain profile by using high spatial-resolution time-resolved x-ray scattering (TRXS) on bulk crystalline gallium arsenide. Our findings reveal distinctive laser-fluence dependent crystal lattice responses, which are not described by previous TRXS experiments or models. The initial linear expansion of the crystal upon laser excitation stagnates at a laser fluence corresponding to the saturation of the free carrier density before resuming expansion in a third regime at higher fluences where two-photon absorption becomes dominant. Our interpretations of the lattice dynamics as nonlinear optical effects are confirmed by numerical simulations and by additional measurements in an n-type semiconductor that allows higher-order nonlinear optical processes to be directly observed as modulations of x-ray diffraction lineshapes.

Spectroscopic ellipsometry study of N+ ion-implanted ethylene-norbornene films

NASA Astrophysics Data System (ADS)

Šiljegović, M.; Kačarević-Popović, Z. M.; Stchakovsky, M.; Radosavljević, A. N.; Korica, S.; Novaković, M.; Popović, M.

2014-05-01

The optical properties of 150 keV N+ implanted ethylene-norbornene (TOPAS 6017S-04) copolymer were investigated using phase modulated spectroscopic ellipsometry (PMSE) and ultraviolet-visible (UV-Vis) spectroscopy in the ranges of 0.6-6.5 eV and of 1.5-6.2 eV, respectively. The single-effective-oscillator model was used to fit the calculated data to the experimental ellipsometric spectra. The results show that the oscillator and dispersion energies decrease with increasing ion fluence up to 1015 cm-2, and then these parameters increase with further fluence increasing. Analysis of the UV-Vis absorption spectra revealed the presence of indirect electronic transitions with the band gap energy in the range of 1.3 to 2.8 eV. It was found that both the band gap energy and the energy width of the distribution of localized band tail states decrease, while the values of Tauc coefficient increase with increasing the ion fluence. From the ellipsometric data we found that the real part of the dielectric function increased about 7% after irradiation with 1015 cm-2, and decreased about 10% in samples modified with 1016 cm-2.

Direct measurements of multi-photon induced nonlinear lattice dynamics in semiconductors via time-resolved x-ray scattering

DOE PAGES

Williams, G. Jackson; Lee, Sooheyong; Walko, Donald A.; ...

2016-12-22

Nonlinear optical phenomena in semiconductors present several fundamental problems in modern optics that are of great importance for the development of optoelectronic devices. In particular, the details of photo-induced lattice dynamics at early time-scales prior to carrier recombination remain poorly understood. We demonstrate the first integrated measurements of both optical and structural, material-dependent quantities while also inferring the bulk impulsive strain profile by using high spatial-resolution time-resolved x-ray scattering (TRXS) on bulk crystalline gallium arsenide. Our findings reveal distinctive laser-fluence dependent crystal lattice responses, which are not described by previous TRXS experiments or models. The initial linear expansion of themore » crystal upon laser excitation stagnates at a laser fluence corresponding to the saturation of the free carrier density before resuming expansion in a third regime at higher fluences where two-photon absorption becomes dominant. Our interpretations of the lattice dynamics as nonlinear optical effects are confirmed by numerical simulations and by additional measurements in an n-type semiconductor that allows higher-order nonlinear optical processes to be directly observed as modulations of x-ray diffraction lineshapes.« less

Direct measurements of multi-photon induced nonlinear lattice dynamics in semiconductors via time-resolved x-ray scattering

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

Williams, G. Jackson; Lee, Sooheyong; Walko, Donald A.

Nonlinear optical phenomena in semiconductors present several fundamental problems in modern optics that are of great importance for the development of optoelectronic devices. In particular, the details of photo-induced lattice dynamics at early time-scales prior to carrier recombination remain poorly understood. We demonstrate the first integrated measurements of both optical and structural, material-dependent quantities while also inferring the bulk impulsive strain profile by using high spatial-resolution time-resolved x-ray scattering (TRXS) on bulk crystalline gallium arsenide. Our findings reveal distinctive laser-fluence dependent crystal lattice responses, which are not described by previous TRXS experiments or models. The initial linear expansion of themore » crystal upon laser excitation stagnates at a laser fluence corresponding to the saturation of the free carrier density before resuming expansion in a third regime at higher fluences where two-photon absorption becomes dominant. Our interpretations of the lattice dynamics as nonlinear optical effects are confirmed by numerical simulations and by additional measurements in an n-type semiconductor that allows higher-order nonlinear optical processes to be directly observed as modulations of x-ray diffraction lineshapes.« less

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations

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

Davidson, Scott E., E-mail: sedavids@utmb.edu

Purpose: A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who usesmore » these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today’s modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. Methods: The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Results: Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. Conclusions: A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.« less

Purification, Characterization and Analysis of the Allergenic Properties of Myosin Light Chain in Procambarus clarkia.

USDA-ARS?s Scientific Manuscript database

Myosin light chain (MLC) plays a vital role in cell and muscle functions and has been identified as an allergen in close species. In this study, MLC with the molecular mass of 18kDa was purified from crayfish (Procambarus clarkii) muscle fibrils. Its physicochemical characterization showed that the...

Patterning of OPV modules by ultra-fast laser

NASA Astrophysics Data System (ADS)

Kubiš, Peter; Lucera, Luca; Guo, Fei; Spyropolous, George; Voigt, Monika M.; Brabec, Christoph J.

2014-10-01

A novel production process combining slot-die coating, transparent flexible IMI (ITO-Metal-ITO) electrodes and ultra-fast laser ablation can be used for the realization of P3HT:PCBM based thin film flexible OPV modules. The fast and precise laser ablation allows an overall efficiency over 3 % and a device geometric fill factor (GFF) over 95 %. Three functional layers can be ablated using the same wavelength only with varying the laser fluence and overlap. Different OPV device architectures with multilayers utilizing various materials are challenging for ablation but can be structured by using a systematical approach.

Isolation and characterization of ventricular-like cells derived from NKX2-5eGFP/w and MLC2vmCherry/w double knock-in human pluripotent stem cells.

PubMed

Yamauchi, Kaori; Li, Junjun; Morikawa, Kumi; Liu, Li; Shirayoshi, Yasuaki; Nakatsuji, Norio; Elliott, David A; Hisatome, Ichiro; Suemori, Hirofumi

2018-01-01

Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) are a promising source for cell transplantation into the damaged heart, which has limited regenerative ability. Many methods have been developed to obtain large amounts of functional CMs from hPSCs for therapeutic applications. However, during the differentiation process, a mixed population of various cardiac cells, including ventricular, atrial, and pacemaker cells, is generated, which hampers the proper functional analysis and evaluation of cell properties. Here, we established NKX2-5 eGFP/w and MLC2v mCherry/w hPSC double knock-ins that allow for labeling, tracing, purification, and analysis of the development of ventricular cells from early to late stages. As with the endogenous transcriptional activities of these genes, MLC2v-mCherry expression following NKX2-5-eGFP expression was observed under previously established culture conditions, which mimic the in vivo cardiac developmental process. Patch-clamp and microelectrode array electrophysiological analyses showed that the NKX2-5 and MLC2v double-positive cells possess ventricular-like properties. The results demonstrate that the NKX2-5 eGFP/w and MLC2v mCherry/w hPSCs provide a powerful model system to capture region-specific cardiac differentiation from early to late stages. Our study would facilitate subtype-specific cardiac development and functional analysis using the hPSC-derived sources. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-F-P-36: Automation of Linear Accelerator Star Shot Measurement with Advanced XML Scripting and Electronic Portal Imaging Device

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

Nguyen, N; Knutson, N; Schmidt, M

Purpose: To verify a method used to automatically acquire jaw, MLC, collimator and couch star shots for a Varian TrueBeam linear accelerator utilizing Developer Mode and an Electronic Portal Imaging Device (EPID). Methods: An XML script was written to automate motion of the jaws, MLC, collimator and couch in TrueBeam Developer Mode (TBDM) to acquire star shot measurements. The XML script also dictates MV imaging parameters to facilitate automatic acquisition and recording of integrated EPID images. Since couch star shot measurements cannot be acquired using a combination of EPID and jaw/MLC collimation alone due to a fixed imager geometry, amore » method utilizing a 5mm wide steel ruler placed on the table and centered within a 15×15cm2 open field to produce a surrogate of the narrow field aperture was investigated. Four individual star shot measurements (X jaw, Y jaw, MLC and couch) were obtained using our proposed as well as traditional film-based method. Integrated EPID images and scanned measurement films were analyzed and compared. Results: Star shot (X jaw, Y jaw, MLC and couch) measurements were obtained in a single 5 minute delivery using the TBDM XML script method compared to 60 minutes for equivalent traditional film measurements. Analysis of the images and films demonstrated comparable isocentricity results, agreeing within 0.3mm of each other. Conclusion: The presented automatic approach of acquiring star shot measurements using TBDM and EPID has proven to be more efficient than the traditional film approach with equivalent results.« less

Real-time auto-adaptive margin generation for MLC-tracked radiotherapy

NASA Astrophysics Data System (ADS)

Glitzner, M.; Fast, M. F.; de Senneville, B. Denis; Nill, S.; Oelfke, U.; Lagendijk, J. J. W.; Raaymakers, B. W.; Crijns, S. P. M.

2017-01-01

In radiotherapy, abdominal and thoracic sites are candidates for performing motion tracking. With real-time control it is possible to adjust the multileaf collimator (MLC) position to the target position. However, positions are not perfectly matched and position errors arise from system delays and complicated response of the electromechanic MLC system. Although, it is possible to compensate parts of these errors by using predictors, residual errors remain and need to be compensated to retain target coverage. This work presents a method to statistically describe tracking errors and to automatically derive a patient-specific, per-segment margin to compensate the arising underdosage on-line, i.e. during plan delivery. The statistics of the geometric error between intended and actual machine position are derived using kernel density estimators. Subsequently a margin is calculated on-line according to a selected coverage parameter, which determines the amount of accepted underdosage. The margin is then applied onto the actual segment to accommodate the positioning errors in the enlarged segment. The proof-of-concept was tested in an on-line tracking experiment and showed the ability to recover underdosages for two test cases, increasing {{V}90 %} in the underdosed area about 47 % and 41 % , respectively. The used dose model was able to predict the loss of dose due to tracking errors and could be used to infer the necessary margins. The implementation had a running time of 23 ms which is compatible with real-time requirements of MLC tracking systems. The auto-adaptivity to machine and patient characteristics makes the technique a generic yet intuitive candidate to avoid underdosages due to MLC tracking errors.

MO-H-19A-02: Investigation of Modulated Electron Arc (MeArc) Therapy for the Treatment of Scalp Tumors

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

Eldib, A; Al-Azhar University, Cairo; Jin, L

2014-06-15

Purpose: Electron arc therapy has long been proposed as the most suitable technique for the treatment of superficial tumors that follow circularly curved surfaces. However it was challenged by unsuitability of the conventional applicators and the lack of adequate 3-D dose calculation tools for arc electron beams in the treatment planning systems (TPS). Now with the availability of an electron specific multi-leaf collimator (eMLC) and an in-house Monte Carlo (MC) based TPS, we were motivated to investigate more advanced modulated electron arc (MeARC) therapy and its beneficial outcome. Methods: We initiated the study by a film measurement conducted in amore » head and neck phantom, where we delivered electron arcs in a step and shoot manner using the light field as a guide to avoid fields abutments. This step was done to insure enough clearance for the arcs with eMLC. MCBEAM and MCPLAN MC codes were used for the treatment head simulation and phantom dose calculation, respectively. Treatment plans were generated for targets drawn in real patient CTs and head and neck phantom. We utilized beams eye view available from a commercial planning system to create beamlets having same isocenter and adjoined at the scalp surface. Then dose-deposition coefficients from those beamlets were calculated for all electron energies using MCPLAN. An in-house optimization code was then used to find the optimum weights needed from individual beamlets. Results: MeARC showed a nicely tailored dose distribution around the circular curved target on the scalp. Some hot spots were noticed and could be attributed to fields abutment problem owing to the bulging nature of electron profiles. Brain dose was shown to be at lower levels compared to photon treatment. Conclusion: MeARC was shown to be a promising modality for treating scalp cases and could be beneficial to all superficial tumors with a circular curvature.« less

TH-AB-BRB-04: Quality Assurance for Advanced Digital Linac Implementations

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

Yu, V.

2016-06-15

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapymore » involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.« less

TH-AB-BRB-00: Research Opportunities with Digital Linear Accelerators

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

NONE

2016-06-15

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapymore » involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.« less

Impact of Multileaf Collimator Configuration Parameters on the Dosimetric Accuracy of 6-MV Intensity-Modulated Radiation Therapy Treatment Plans.

PubMed

Petersen, Nick; Perrin, David; Newhauser, Wayne; Zhang, Rui

2017-01-01

The purpose of this study was to evaluate the impact of selected configuration parameters that govern multileaf collimator (MLC) transmission and rounded leaf offset in a commercial treatment planning system (TPS) (Pinnacle 3 , Philips Medical Systems, Andover, MA, USA) on the accuracy of intensity-modulated radiation therapy (IMRT) dose calculation. The MLC leaf transmission factor was modified based on measurements made with ionization chambers. The table of parameters containing rounded-leaf-end offset values was modified by measuring the radiation field edge as a function of leaf bank position with an ionization chamber in a scanning water-tank dosimetry system and comparing the locations to those predicted by the TPS. The modified parameter values were validated by performing IMRT quality assurance (QA) measurements on 19 gantry-static IMRT plans. Planar dose measurements were performed with radiographic film and a diode array (MapCHECK2) and compared to TPS calculated dose distributions using default and modified configuration parameters. Based on measurements, the leaf transmission factor was changed from a default value of 0.001 to 0.005. Surprisingly, this modification resulted in a small but statistically significant worsening of IMRT QA gamma-index passing rate, which revealed that the overall dosimetric accuracy of the TPS depends on multiple configuration parameters in a manner that is coupled and not intuitive because of the commissioning protocol used in our clinic. The rounded leaf offset table had little room for improvement, with the average difference between the default and modified offset values being -0.2 ± 0.7 mm. While our results depend on the current clinical protocols, treatment unit and TPS used, the methodology used in this study is generally applicable. Different clinics could potentially obtain different results and improve their dosimetric accuracy using our approach.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PubMed

Moustakis, Christos; Chan, Mark K H; Kim, Jinkoo; Nilsson, Joakim; Bergman, Alanah; Bichay, Tewfik J; Palazon Cano, Isabel; Cilla, Savino; Deodato, Francesco; Doro, Raffaela; Dunst, Jürgen; Eich, Hans Theodor; Fau, Pierre; Fong, Ming; Haverkamp, Uwe; Heinze, Simon; Hildebrandt, Guido; Imhoff, Detlef; de Klerck, Erik; Köhn, Janett; Lambrecht, Ulrike; Loutfi-Krauss, Britta; Ebrahimi, Fatemeh; Masi, Laura; Mayville, Alan H; Mestrovic, Ante; Milder, Maaike; Morganti, Alessio G; Rades, Dirk; Ramm, Ulla; Rödel, Claus; Siebert, Frank-Andre; den Toom, Wilhelm; Wang, Lei; Wurster, Stefan; Schweikard, Achim; Soltys, Scott G; Ryu, Samuel; Blanck, Oliver

2018-05-25

To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Divergent modulation of Rho‐kinase and Ca2+ influx pathways by Src family kinases and focal adhesion kinase in airway smooth muscle

PubMed Central

Shaifta, Yasin; Irechukwu, Nneka; Prieto‐Lloret, Jesus; MacKay, Charles E; Marchon, Keisha A; Ward, Jeremy P T

2015-01-01

Background and Purpose The importance of tyrosine kinases in airway smooth muscle (ASM) contraction is not fully understood. The aim of this study was to investigate the role of Src‐family kinases (SrcFK) and focal adhesion kinase (FAK) in GPCR‐mediated ASM contraction and associated signalling events. Experimental Approach Contraction was recorded in intact or α‐toxin permeabilized rat bronchioles. Phosphorylation of SrcFK, FAK, myosin light‐chain‐20 (MLC20) and myosin phosphatase targeting subunit‐1 (MYPT‐1) was evaluated in cultured human ASM cells (hASMC). [Ca2+]i was evaluated in Fura‐2 loaded hASMC. Responses to carbachol (CCh) and bradykinin (BK) and the contribution of SrcFK and FAK to these responses were determined. Key Results Contractile responses in intact bronchioles were inhibited by antagonists of SrcFK, FAK and Rho‐kinase, while after α‐toxin permeabilization, they were sensitive to inhibition of SrcFK and Rho‐kinase, but not FAK. CCh and BK increased phosphorylation of MYPT‐1 and MLC20 and auto‐phosphorylation of SrcFK and FAK. MYPT‐1 phosphorylation was sensitive to inhibition of Rho‐kinase and SrcFK, but not FAK. Contraction induced by SR Ca2+ depletion and equivalent [Ca2+]i responses in hASMC were sensitive to inhibition of both SrcFK and FAK, while depolarization‐induced contraction was sensitive to FAK inhibition only. SrcFK auto‐phosphorylation was partially FAK‐dependent, while FAK auto‐phosphorylation was SrcFK‐independent. Conclusions and Implications SrcFK mediates Ca2+‐sensitization in ASM, while SrcFK and FAK together and individually influence multiple Ca2+ influx pathways. Tyrosine phosphorylation is therefore a key upstream signalling event in ASM contraction and may be a viable target for modulating ASM tone in respiratory disease. PMID:26294392

HRR Upgrade to mass loss calorimeter and modified Schlyter test for FR Wood

Treesearch

Mark A. Dietenberger; Charles R. Boardman

2013-01-01

Enhanced Heat Release Rate (HRR) methodology has been extended to the Mass Loss Calorimeter (MLC) and the Modified Schlyter flame spread test to evaluate fire retardant effectiveness used on wood based materials. Modifications to MLC include installation of thermopile on the chimney walls to correct systematic errors to the sensible HRR calculations to account for...

Tomotherapy as a tool in image-guided radiation therapy (IGRT): theoretical and technological aspects

PubMed Central

Yartsev, S; Kron, T; Van Dyk, J

2007-01-01

Helical tomotherapy (HT) is a novel treatment approach that combines Intensity-Modulate Radiation Therapy (IMRT) delivery with in-built image guidance using megavoltage (MV) CT scanning. The technique utilises a 6 MV linear accelerator mounted on a CT type ring gantry. The beam is collimated to a fan beam, which is intensity modulated using a binary multileaf collimator (MLC). As the patient advances slowly through the ring gantry, the linac rotates around the patient with a leaf-opening pattern optimised to deliver a highly conformal dose distribution to the target in the helical beam trajectory. The unit also allows the acquisition of MVCT images using the same radiation source detuned to reduce its effective energy to 3.5 MV, making the dose required for imaging less than 3 cGy. This paper discusses the major features of HT and describes the advantages and disadvantages of this approach in the context of the commercial Hi-ART system. PMID:21614257

Fundamental radiological and geometric performance of two types of proton beam modulated discrete scanning systems.

PubMed

Farr, J B; Dessy, F; De Wilde, O; Bietzer, O; Schönenberg, D

2013-07-01

The purpose of this investigation was to compare and contrast the measured fundamental properties of two new types of modulated proton scanning systems. This provides a basis for clinical expectations based on the scanned beam quality and a benchmark for computational models. Because the relatively small beam and fast scanning gave challenges to the characterization, a secondary purpose was to develop and apply new approaches where necessary to do so. The following performances of the proton scanning systems were investigated: beamlet alignment, static in-air beamlet size and shape, scanned in-air penumbra, scanned fluence map accuracy, geometric alignment of scanning system to isocenter, maximum field size, lateral and longitudinal field uniformity of a 1 l cubic uniform field, output stability over time, gantry angle invariance, monitoring system linearity, and reproducibility. A range of detectors was used: film, ionization chambers, lateral multielement and longitudinal multilayer ionization chambers, and a scintillation screen combined with a digital video camera. Characterization of the scanned fluence maps was performed with a software analysis tool. The resulting measurements and analysis indicated that the two types of delivery systems performed within specification for those aspects investigated. The significant differences were observed between the two types of scanning systems where one type exhibits a smaller spot size and associated penumbra than the other. The differential is minimum at maximum energy and increases inversely with decreasing energy. Additionally, the large spot system showed an increase in dose precision to a static target with layer rescanning whereas the small spot system did not. The measured results from the two types of modulated scanning types of system were consistent with their designs under the conditions tested. The most significant difference between the types of system was their proton spot size and associated resolution, factors of magnetic optics, and vacuum length. The need and benefit of mutielement detectors and high-resolution sensors was also shown. The use of a fluence map analytical software tool was particularly effective in characterizing the dynamic proton energy-layer scanning.

SU-E-T-644: Evaluation of Angular Dependence Correction for 2D Array Detector Using for Quality Assurance of Volumetric Modulated Arc Therapy

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

Karthikeyan, N; Ganesh, K M; Vikraman, S

2014-06-15

Purpose: To evaluate the angular dependence correction for Matrix Evolution 2D array detector in quality assurance of volumetric modulated arc therapy(VMAT). Methods: Total ten patients comprising of different sites were planned for VMAT and taken for the study. Each plan was exposed on Matrix Evolution 2D array detector with Omnipro IMRT software based on the following three different methods using 6MV photon beams from Elekta Synergy linear accelerator. First method, VMAT plan was delivered on Matrix Evolution detector as it gantry mounted with dedicated holder with build-up of 2.3cm. Second, the VMAT plan was delivered with the static gantry anglemore » on to the table mounted setup. Third, the VMAT plan was delivered with actual gantry angle on Matrix Evolution detector fixed in Multicube phantom with gantry angle sensor and angular dependence correction were applied to quantify the plan quality. For all these methods, the corresponding QA plans were generated in TPS and the dose verification was done for both point and 2D fluence analysis with pass criteria of 3% dose difference and 3mm distance to agreement. Results: The measured point dose variation for the first method was observed as 1.58±0.6% of mean and SD with TPS calculated. For second and third method, the mean and standard deviation(SD) was observed as 1.67±0.7% and 1.85±0.8% respectively. The 2D fluence analysis of measured and TPS calculated has the mean and SD of 97.9±1.1%, 97.88±1.2% and 97.55±1.3% for first, second and third methods respectively. The calculated two-tailed Pvalue for point dose and 2D fluence analysis shows the insignificance with values of 0.9316 and 0.9015 respectively, among the different methods of QA. Conclusion: The qualitative evaluation of angular dependence correction for Matrix Evolution 2D array detector shows its competency in accuracy of quality assurance measurement of composite dose distribution of volumetric modulated arc therapy.« less

Dose calculation of dynamic trajectory radiotherapy using Monte Carlo.

PubMed

Manser, P; Frauchiger, D; Frei, D; Volken, W; Terribilini, D; Fix, M K

2018-04-06

Using volumetric modulated arc therapy (VMAT) delivery technique gantry position, multi-leaf collimator (MLC) as well as dose rate change dynamically during the application. However, additional components can be dynamically altered throughout the dose delivery such as the collimator or the couch. Thus, the degrees of freedom increase allowing almost arbitrary dynamic trajectories for the beam. While the dose delivery of such dynamic trajectories for linear accelerators is technically possible, there is currently no dose calculation and validation tool available. Thus, the aim of this work is to develop a dose calculation and verification tool for dynamic trajectories using Monte Carlo (MC) methods. The dose calculation for dynamic trajectories is implemented in the previously developed Swiss Monte Carlo Plan (SMCP). SMCP interfaces the treatment planning system Eclipse with a MC dose calculation algorithm and is already able to handle dynamic MLC and gantry rotations. Hence, the additional dynamic components, namely the collimator and the couch, are described similarly to the dynamic MLC by defining data pairs of positions of the dynamic component and the corresponding MU-fractions. For validation purposes, measurements are performed with the Delta4 phantom and film measurements using the developer mode on a TrueBeam linear accelerator. These measured dose distributions are then compared with the corresponding calculations using SMCP. First, simple academic cases applying one-dimensional movements are investigated and second, more complex dynamic trajectories with several simultaneously moving components are compared considering academic cases as well as a clinically motivated prostate case. The dose calculation for dynamic trajectories is successfully implemented into SMCP. The comparisons between the measured and calculated dose distributions for the simple as well as for the more complex situations show an agreement which is generally within 3% of the maximum dose or 3mm. The required computation time for the dose calculation remains the same when the additional dynamic moving components are included. The results obtained for the dose comparisons for simple and complex situations suggest that the extended SMCP is an accurate dose calculation and efficient verification tool for dynamic trajectory radiotherapy. This work was supported by Varian Medical Systems. Copyright © 2018. Published by Elsevier GmbH.

SU-F-T-364: Monte Carlo-Dose Verification of Volumetric Modulated Arc Therapy Plans Using AAPM TG-119 Test Patterns

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

Onizuka, R; Araki, F; Ohno, T

2016-06-15

Purpose: To investigate the Monte Carlo (MC)-based dose verification for VMAT plans by a treatment planning system (TPS). Methods: The AAPM TG-119 test structure set was used for VMAT plans by the Pinnacle3 (convolution/superposition), using a Synergy radiation head of a 6 MV beam with the Agility MLC. The Synergy was simulated with the EGSnrc/BEAMnrc code, and VMAT dose distributions were calculated with the EGSnrc/DOSXYZnrc code by the same irradiation conditions as TPS. VMAT dose distributions of TPS and MC were compared with those of EBT3 film, by 2-D gamma analysis of ±3%/3 mm criteria with a threshold of 30%more » of prescribed doses. VMAT dose distributions between TPS and MC were also compared by DVHs and 3-D gamma analysis of ±3%/3 mm criteria with a threshold of 10%, and 3-D passing rates for PTVs and OARs were analyzed. Results: TPS dose distributions differed from those of film, especially for Head & neck. The dose difference between TPS and film results from calculation accuracy for complex motion of MLCs like tongue and groove effect. In contrast, MC dose distributions were in good agreement with those of film. This is because MC can model fully the MLC configuration and accurately reproduce the MLC motion between control points in VMAT plans. D95 of PTV for Prostate, Head & neck, C-shaped, and Multi Target was 97.2%, 98.1%, 101.6%, and 99.7% for TPS and 95.7%, 96.0%, 100.6%, and 99.1% for MC, respectively. Similarly, 3-D gamma passing rates of each PTV for TPS vs. MC were 100%, 89.5%, 99.7%, and 100%, respectively. 3-D passing rates of TPS reduced for complex VMAT fields like Head & neck because MLCs are not modeled completely for TPS. Conclusion: MC-calculated VMAT dose distributions is useful for the 3-D dose verification of VMAT plans by TPS.« less

Quantifying the performance of in vivo portal dosimetry in detecting four types of treatment parameter variations

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

Bojechko, C.; Ford, E. C., E-mail: eford@uw.edu

Purpose: To quantify the ability of electronic portal imaging device (EPID) dosimetry used during treatment (in vivo) in detecting variations that can occur in the course of patient treatment. Methods: Images of transmitted radiation from in vivo EPID measurements were converted to a 2D planar dose at isocenter and compared to the treatment planning dose using a prototype software system. Using the treatment planning system (TPS), four different types of variability were modeled: overall dose scaling, shifting the positions of the multileaf collimator (MLC) leaves, shifting of the patient position, and changes in the patient body contour. The gamma passmore » rate was calculated for the modified and unmodified plans and used to construct a receiver operator characteristic (ROC) curve to assess the detectability of the different parameter variations. The detectability is given by the area under the ROC curve (AUC). The TPS was also used to calculate the impact of the variations on the target dose–volume histogram. Results: Nine intensity modulation radiation therapy plans were measured for four different anatomical sites consisting of 70 separate fields. Results show that in vivo EPID dosimetry was most sensitive to variations in the machine output, AUC = 0.70 − 0.94, changes in patient body habitus, AUC = 0.67 − 0.88, and systematic shifts in the MLC bank positions, AUC = 0.59 − 0.82. These deviations are expected to have a relatively small clinical impact [planning target volume (PTV) D{sub 99} change <7%]. Larger variations have even higher detectability. Displacements in the patient’s position and random variations in MLC leaf positions were not readily detectable, AUC < 0.64. The D{sub 99} of the PTV changed by up to 57% for the patient position shifts considered here. Conclusions: In vivo EPID dosimetry is able to detect relatively small variations in overall dose, systematic shifts of the MLC’s, and changes in the patient habitus. Shifts in the patient’s position which can introduce large changes in the target dose coverage were not readily detected.« less

Use of plan quality degradation to evaluate tradeoffs in delivery efficiency and clinical plan metrics arising from IMRT optimizer and sequencer compromises

PubMed Central

Wilkie, Joel R.; Matuszak, Martha M.; Feng, Mary; Moran, Jean M.; Fraass, Benedick A.

2013-01-01

Purpose: Plan degradation resulting from compromises made to enhance delivery efficiency is an important consideration for intensity modulated radiation therapy (IMRT) treatment plans. IMRT optimization and/or multileaf collimator (MLC) sequencing schemes can be modified to generate more efficient treatment delivery, but the effect those modifications have on plan quality is often difficult to quantify. In this work, the authors present a method for quantitative assessment of overall plan quality degradation due to tradeoffs between delivery efficiency and treatment plan quality, illustrated using comparisons between plans developed allowing different numbers of intensity levels in IMRT optimization and/or MLC sequencing for static segmental MLC IMRT plans. Methods: A plan quality degradation method to evaluate delivery efficiency and plan quality tradeoffs was developed and used to assess planning for 14 prostate and 12 head and neck patients treated with static IMRT. Plan quality was evaluated using a physician's predetermined “quality degradation” factors for relevant clinical plan metrics associated with the plan optimization strategy. Delivery efficiency and plan quality were assessed for a range of optimization and sequencing limitations. The “optimal” (baseline) plan for each case was derived using a clinical cost function with an unlimited number of intensity levels. These plans were sequenced with a clinical MLC leaf sequencer which uses >100 segments, assuring delivered intensities to be within 1% of the optimized intensity pattern. Each patient's optimal plan was also sequenced limiting the number of intensity levels (20, 10, and 5), and then separately optimized with these same numbers of intensity levels. Delivery time was measured for all plans, and direct evaluation of the tradeoffs between delivery time and plan degradation was performed. Results: When considering tradeoffs, the optimal number of intensity levels depends on the treatment site and on the stage in the process at which the levels are limited. The cost of improved delivery efficiency, in terms of plan quality degradation, increased as the number of intensity levels in the sequencer or optimizer decreased. The degradation was more substantial for the head and neck cases relative to the prostate cases, particularly when fewer than 20 intensity levels were used. Plan quality degradation was less severe when the number of intensity levels was limited in the optimizer rather than the sequencer. Conclusions: Analysis of plan quality degradation allows for a quantitative assessment of the compromises in clinical plan quality as delivery efficiency is improved, in order to determine the optimal delivery settings. The technique is based on physician-determined quality degradation factors and can be extended to other clinical situations where investigation of various tradeoffs is warranted. PMID:23822412

Molecular prenatal diagnosis of megalencephalic leukoencephalopathy with subcortical cysts in a child from southwest of Iran.

PubMed

Shariati, Gholamreza; Hamid, Mohammad; Saberi, Alihossein; Andashti, Behnaz; Galehdari, Hamid

2015-02-01

Megalencephalic leukoencephalopathy (MLC) is a rare neurological disorder with an autosomal recessive pattern. Clinical diagnosis was based on macrocephaly, recurrent seizure, and magnetic resonance imaging (MRI). Here we report first finding of a novel homozygous single base deletion in the MLC1 gene in an affected Iranian child causing a premature stop codon (p.L150fs.160X).

Development of a Multileaf Collimator for Proton Radiotherapy

DTIC Science & Technology

2007-06-01

for proton radiotherapy, and the first year of the project to develop image guided treatment protocols for proton therapy . This research...multileaf collimator (MLC) for proton therapy and investigates the issues that must be resolved to use an MLC in proton therapy . The second technology...the contract included three development agreements directly related to the work supported by this grant to develop technology for proton therapy .

MLC Libraries--A School Library's Journey with Students, Staff and Web 2.0 Technologies: Blogs, Wikis and E-Books--Where Are We Going Next?

ERIC Educational Resources Information Center

Viner, Jane; Lucas, Amanda; Ricchini, Tracey; Ri, Regina

2010-01-01

This workshop paper explores the Web 2.0 journey of the MLC Libraries' teacher-librarians, librarian, library and audio visual technicians. Our journey was initially inspired by Will Richardson and supported by the School Library Association of Victoria (SLAV) Web 2.0 professional development program. The 12 week technological skills program…

Long-term outcomes after hepatic resection combined with radiofrequency ablation for initially unresectable multiple and bilobar liver malignancies.

PubMed

Qiu, Jianguo; Chen, Shuting; Wu, Hong

2014-05-01

Hepatic resection (HRE) combined with radiofrequency ablation (RFA) offers a surgical option to a group of patients with multiple and bilobar liver malignancies who are traditionally unresectable for inadequate functional hepatic reserve. The aims of the present study were to assess the perioperative outcomes, recurrence, and long-term survival rates for patients treated with HRE plus RFA in the management of primary hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC). Data from all consecutive patients with primary and secondary hepatic malignancies who were treated with HRE combined with RFA between 2007 and 2013 were prospectively collected and retrospectively reviewed. A total of 112 patients, with 368 hepatic tumors underwent HRE combined with ultrasound-guided RFA, were included in the present study. There were 40 cases of HCC with 117 tumors and 72 cases of MLC with 251 metastases. Most cases of liver metastases originated from the gastrointestinal tract (44, 61.1%). Other uncommon lesions included breast cancer (5, 6.9%), pancreatic cancer (3, 4.2%), lung cancer (4, 5.6%), cholangiocarcinoma (4, 5.6%), and so on. The ablation success rates were 93.3% for HCC and 96.7% for MLC. The 1-, 2-, 3-, 4-, and 5-y overall recurrence rates were 52.5%, 59.5%, 72.3%, 75%, and 80% for the HCC group and 44.4%, 52.7%, 56.1%, 69.4%, and 77.8% for the MLC group, respectively. The 1-, 2-, 3-, 4-, and 5-y overall survival rates for the HCC patients were 67.5%, 50%, 32.5%, 22.5%, and 12.5% and for the MLC patients were 66.5%, 55.5%, 50%, 30.5%, and 19.4%, respectively. The corresponding recurrence-free survival rates for the HCC patients were 52.5%, 35%, 22.5%, 15%, and 10% and for the MLC patients were 58.3%, 41.6%, 23.6%, 16.9%, and 12.5%, respectively. HRE combined with RFA provides an effective treatment approach for patients with primary and secondary liver malignancies who are initially unsuitable for radical resection, with high local tumor control rates and promising survival data. Copyright © 2014 Elsevier Inc. All rights reserved.

An MLC-based linac QA procedure for the characterization of radiation isocenter and room lasers' position.

PubMed

Rosca, Florin; Lorenz, Friedlieb; Hacker, Fred L; Chin, Lee M; Ramakrishna, Naren; Zygmanski, Piotr

2006-06-01

We have designed and implemented a new stereotactic linac QA test with stereotactic precision. The test is used to characterize gantry sag, couch wobble, cone placement, MLC offsets, and room lasers' positions relative to the radiation isocenter. Two MLC star patterns, a cone pattern, and the laser line patterns are recorded on the same imaging medium. Phosphor plates are used as imaging medium due to their sensitivity to red light. The red light of room lasers erases some of the irradiation information stored on the phosphor plates enabling accurate and direct measurements for the position of room lasers and radiation isocenter. Using film instead of the phosphor plate as imaging medium is possible, however, it is less practical. The QA method consists of irradiating four phosphor plates that record the gantry sag between the 0 degrees and 180 degrees gantry angles, the position and stability of couch rotational axis, the sag between the 90 degrees and 270 degrees gantry angles, the accuracy of cone placement on the collimator, the MLC offsets from the collimator rotational axis, and the position of laser lines relative to the radiation isocenter. The estimated accuracy of the method is +/- 0.2 mm. The observed reproducibility of the method is about +/- 0.1 mm. The total irradiation/ illumination time is about 10 min per image. Data analysis, including the phosphor plate scanning, takes less than 5 min for each image. The method characterizes the radiation isocenter geometry with the high accuracy required for the stereotactic radiosurgery. In this respect, it is similar to the standard ball test for stereotactic machines. However, due to the usage of the MLC instead of the cross-hair/ball, it does not depend on the cross-hair/ball placement errors with respect to the lasers and it provides more information on the mechanical integrity of the linac/couch/laser system. Alternatively, it can be used as a highly accurate QA procedure for the nonstereotactic machines. Noteworthy is its ability to characterize the MLC position accuracy, which is an important factor in IMRT delivery.

Monte Carlo modeling of HD120 multileaf collimator on Varian TrueBeam linear accelerator for verification of 6X and 6X FFF VMAT SABR treatment plans

PubMed Central

Gete, Ermias; Duzenli, Cheryl; Teke, Tony

2014-01-01

A Monte Carlo (MC) validation of the vendor‐supplied Varian TrueBeam 6 MV flattened (6X) phase‐space file and the first implementation of the Siebers‐Keall MC MLC model as applied to the HD120 MLC (for 6X flat and 6X flattening filterfree (6X FFF) beams) are described. The MC model is validated in the context of VMAT patient‐specific quality assurance. The Monte Carlo commissioning process involves: 1) validating the calculated open‐field percentage depth doses (PDDs), profiles, and output factors (OF), 2) adapting the Siebers‐Keall MLC model to match the new HD120‐MLC geometry and material composition, 3) determining the absolute dose conversion factor for the MC calculation, and 4) validating this entire linac/MLC in the context of dose calculation verification for clinical VMAT plans. MC PDDs for the 6X beams agree with the measured data to within 2.0% for field sizes ranging from 2 × 2 to 40 × 40 cm2. Measured and MC profiles show agreement in the 50% field width and the 80%‐20% penumbra region to within 1.3 mm for all square field sizes. MC OFs for the 2 to 40 cm2 square fields agree with measurement to within 1.6%. Verification of VMAT SABR lung, liver, and vertebra plans demonstrate that measured and MC ion chamber doses agree within 0.6% for the 6X beam and within 2.0% for the 6X FFF beam. A 3D gamma factor analysis demonstrates that for the 6X beam, > 99% of voxels meet the pass criteria (3%/3 mm). For the 6X FFF beam, > 94% of voxels meet this criteria. The TrueBeam accelerator delivering 6X and 6X FFF beams with the HD120 MLC can be modeled in Monte Carlo to provide an independent 3D dose calculation for clinical VMAT plans. This quality assurance tool has been used clinically to verify over 140 6X and 16 6X FFF TrueBeam treatment plans. PACS number: 87.55.K‐ PMID:24892341

Dynamic tumor tracking using the Elekta Agility MLC

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

Fast, Martin F., E-mail: martin.fast@icr.ac.uk; Nill, Simeon, E-mail: simeon.nill@icr.ac.uk; Bedford, James L.

2014-11-01

Purpose: To evaluate the performance of the Elekta Agility multileaf collimator (MLC) for dynamic real-time tumor tracking. Methods: The authors have developed a new control software which interfaces to the Agility MLC to dynamically program the movement of individual leaves, the dynamic leaf guides (DLGs), and the Y collimators (“jaws”) based on the actual target trajectory. A motion platform was used to perform dynamic tracking experiments with sinusoidal trajectories. The actual target positions reported by the motion platform at 20, 30, or 40 Hz were used as shift vectors for the MLC in beams-eye-view. The system latency of the MLCmore » (i.e., the average latency comprising target device reporting latencies and MLC adjustment latency) and the geometric tracking accuracy were extracted from a sequence of MV portal images acquired during irradiation for the following treatment scenarios: leaf-only motion, jaw + leaf motion, and DLG + leaf motion. Results: The portal imager measurements indicated a clear dependence of the system latency on the target position reporting frequency. Deducting the effect of the target frequency, the leaf adjustment latency was measured to be 38 ± 3 ms for a maximum target speed v of 13 mm/s. The jaw + leaf adjustment latency was 53 ± 3 at a similar speed. The system latency at a target position frequency of 30 Hz was in the range of 56–61 ms for the leaves (v ≤ 31 mm/s), 71–78 ms for the jaw + leaf motion (v ≤ 25 mm/s), and 58–72 ms for the DLG + leaf motion (v ≤ 59 mm/s). The tracking accuracy showed a similar dependency on the target position frequency and the maximum target speed. For the leaves, the root-mean-squared error (RMSE) was between 0.6–1.5 mm depending on the maximum target speed. For the jaw + leaf (DLG + leaf) motion, the RMSE was between 0.7–1.5 mm (1.9–3.4 mm). Conclusions: The authors have measured the latency and geometric accuracy of the Agility MLC, facilitating its future use for clinical tracking applications.« less

Neutron production from flattening filter free high energy medical linac: A Monte Carlo study

NASA Astrophysics Data System (ADS)

Najem, M. A.; Abolaban, F. A.; Podolyák, Z.; Spyrou, N. M.

2015-11-01

One of the problems arising from using a conventional linac at high energy (>8 MV) is the production of neutrons. One way to reduce neutron production is to remove the flattening filter (FF). The main purpose of this work was to study the effect of FF removal on neutron fluence and neutron dose equivalent inside the treatment room at different photon beam energies. Several simulations based on Monte Carlo techniques were carried out in order to calculate the neutron fluence at different locations in the treatment room from different linac energies with and without a FF. In addition, a step-and-shoot intensity modulated radiotherapy (SnS IMRT) for prostate cancer was modelled using the 15 MV photon beam with and without a FF on a water phantom to calculate the neutron dose received in a full treatment. The results obtained show a significant drop-off in neutrons fluence and dose equivalent when the FF was removed. For example, the neutron fluence was decreased by 54%, 76% and 75% for 10, 15 and 18 MV, respectively. This can decrease the neutron dose to the patient as well as reduce the shielding cost of the treatment room. The neutron dose equivalent of the SnS IMRT for prostate cancer was reduced significantly by 71.3% when the FF was removed. It can be concluded that the flattening filter removal from the head of the linac could reduce the risk of causing secondary cancers and the shielding cost of radiotherapy treatment rooms.

A flexible Monte Carlo tool for patient or phantom specific calculations: comparison with preliminary validation measurements

NASA Astrophysics Data System (ADS)

Davidson, S.; Cui, J.; Followill, D.; Ibbott, G.; Deasy, J.

2008-02-01

The Dose Planning Method (DPM) is one of several 'fast' Monte Carlo (MC) computer codes designed to produce an accurate dose calculation for advanced clinical applications. We have developed a flexible machine modeling process and validation tests for open-field and IMRT calculations. To complement the DPM code, a practical and versatile source model has been developed, whose parameters are derived from a standard set of planning system commissioning measurements. The primary photon spectrum and the spectrum resulting from the flattening filter are modeled by a Fatigue function, cut-off by a multiplying Fermi function, which effectively regularizes the difficult energy spectrum determination process. Commonly-used functions are applied to represent the off-axis softening, increasing primary fluence with increasing angle ('the horn effect'), and electron contamination. The patient dependent aspect of the MC dose calculation utilizes the multi-leaf collimator (MLC) leaf sequence file exported from the treatment planning system DICOM output, coupled with the source model, to derive the particle transport. This model has been commissioned for Varian 2100C 6 MV and 18 MV photon beams using percent depth dose, dose profiles, and output factors. A 3-D conformal plan and an IMRT plan delivered to an anthropomorphic thorax phantom were used to benchmark the model. The calculated results were compared to Pinnacle v7.6c results and measurements made using radiochromic film and thermoluminescent detectors (TLD).

SU-E-T-250: New IMRT Sequencing Strategy: Towards Intra-Fraction Plan Adaptation for the MR-Linac

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

Kontaxis, C; Bol, G; Lagendijk, J

2014-06-01

Purpose: To develop a new sequencer for IMRT planning that during treatment makes the inclusion of external factors possible and by doing so accounts for intra-fraction anatomy changes. Given a real-time imaging modality that will provide the updated patient anatomy during delivery, this sequencer is able to take these changes into account during the calculation of subsequent segments. Methods: Pencil beams are generated for each beam angle of the treatment and a fluence optimization is performed. The pencil beams, together with the patient anatomy and the above optimal fluence form the input of our algorithm. During each iteration the followingmore » steps are performed: A fluence optimization is done and each beam's fluence is then split to discrete intensity levels. Deliverable segments are calculated for each one of these. Each segment's area multiplied by its intensity describes its efficiency. The most efficient segment among all beams is then chosen to deliver a part of the calculated fluence and the dose that will be delivered by this segment is calculated. This delivered dose is then subtracted from the remaining dose. This loop is repeated until 90% of the dose has been delivered and a final segment weight optimization is performed to reach full convergence. Results: This algorithm was tested in several prostate cases yielding results that meet all clinical constraints. Quality assurance was performed on Delta4 and film phantoms for one of these prostate cases and received clinical acceptance after passing both gamma analyses with the 3%/3mm criteria. Conclusion: A new sequencing algorithm was developed to facilitate the needs of intensity modulated treatment. The first results on static anatomy confirm that it can calculate clinical plans equivalent to those of the commercially available planning systems. We are now working towards 100% dose convergence which will allow us to handle anatomy deformations. This work is financially supported by Elekta AB, Stockholm, Sweden.« less

Light quality modulates metabolic synchronization over the diel phases of crassulacean acid metabolism

PubMed Central

Ceusters, Johan; Borland, Anne M.; Taybi, Tahar; Frans, Mario; Godts, Christof; De Proft, Maurice P.

2014-01-01

Temporal compartmentation of carboxylation processes is a defining feature of crassulacean acid metabolism and involves circadian control of key metabolic and transport steps that regulate the supply and demand for carbon over a 24h cycle. Recent insights on the molecular workings of the circadian clock and its connection with environmental inputs raise new questions on the importance of light quality and, by analogy, certain photoreceptors for synchronizing the metabolic components of CAM. The present work tested the hypothesis that optimal coupling of stomatal conductance, net CO2 uptake, and the reciprocal turnover of carbohydrates and organic acids over the diel CAM cycle requires both blue and red light input signals. Contrasting monochromatic wavelengths of blue, green, and red light (i.e. 475, 530, 630nm) with low fluence rates (10 μmol m–2 s–1) were administered for 16 hours each diel cycle for a total treatment time of 48 hours to the obligate CAM bromeliad, Aechmea ‘Maya’. Of the light treatments imposed, low-fluence blue light was a key determinant in regulating stomatal responses, organic acid mobilization from the vacuole, and daytime decarboxylation. However, the reciprocal relationship between starch and organic acid turnover that is typical for CAM was uncoupled under low-fluence blue light. Under low-fluence red or green light, the diel turnover of storage carbohydrates was orchestrated in line with the requirements of CAM, but a consistent delay in acid consumption at dawn compared with plants under white or low-fluence blue light was noted. Consistent with the acknowledged influences of both red and blue light as input signals for the circadian clock, the data stress the importance of both red and blue-light signalling pathways for synchronizing the metabolic and physiological components of CAM over the day/night cycle. PMID:24803500

TH-A-9A-02: BEST IN PHYSICS (THERAPY) - 4D IMRT Planning Using Highly- Parallelizable Particle Swarm Optimization

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

Modiri, A; Gu, X; Sawant, A

2014-06-15

Purpose: We present a particle swarm optimization (PSO)-based 4D IMRT planning technique designed for dynamic MLC tracking delivery to lung tumors. The key idea is to utilize the temporal dimension as an additional degree of freedom rather than a constraint in order to achieve improved sparing of organs at risk (OARs). Methods: The target and normal structures were manually contoured on each of the ten phases of a 4DCT scan acquired from a lung SBRT patient who exhibited 1.5cm tumor motion despite the use of abdominal compression. Corresponding ten IMRT plans were generated using the Eclipse treatment planning system. Thesemore » plans served as initial guess solutions for the PSO algorithm. Fluence weights were optimized over the entire solution space i.e., 10 phases × 12 beams × 166 control points. The size of the solution space motivated our choice of PSO, which is a highly parallelizable stochastic global optimization technique that is well-suited for such large problems. A summed fluence map was created using an in-house B-spline deformable image registration. Each plan was compared with a corresponding, internal target volume (ITV)-based IMRT plan. Results: The PSO 4D IMRT plan yielded comparable PTV coverage and significantly higher dose—sparing for parallel and serial OARs compared to the ITV-based plan. The dose-sparing achieved via PSO-4DIMRT was: lung Dmean = 28%; lung V20 = 90%; spinal cord Dmax = 23%; esophagus Dmax = 31%; heart Dmax = 51%; heart Dmean = 64%. Conclusion: Truly 4D IMRT that uses the temporal dimension as an additional degree of freedom can achieve significant dose sparing of serial and parallel OARs. Given the large solution space, PSO represents an attractive, parallelizable tool to achieve globally optimal solutions for such problems. This work was supported through funding from the National Institutes of Health and Varian Medical Systems. Amit Sawant has research funding from Varian Medical Systems, VisionRT Ltd. and Elekta.« less

A virtual source model for Monte Carlo simulation of helical tomotherapy.

PubMed

Yuan, Jiankui; Rong, Yi; Chen, Quan

2015-01-08

The purpose of this study was to present a Monte Carlo (MC) simulation method based on a virtual source, jaw, and MLC model to calculate dose in patient for helical tomotherapy without the need of calculating phase-space files (PSFs). Current studies on the tomotherapy MC simulation adopt a full MC model, which includes extensive modeling of radiation source, primary and secondary jaws, and multileaf collimator (MLC). In the full MC model, PSFs need to be created at different scoring planes to facilitate the patient dose calculations. In the present work, the virtual source model (VSM) we established was based on the gold standard beam data of a tomotherapy unit, which can be exported from the treatment planning station (TPS). The TPS-generated sinograms were extracted from the archived patient XML (eXtensible Markup Language) files. The fluence map for the MC sampling was created by incorporating the percentage leaf open time (LOT) with leaf filter, jaw penumbra, and leaf latency contained from sinogram files. The VSM was validated for various geometry setups and clinical situations involving heterogeneous media and delivery quality assurance (DQA) cases. An agreement of < 1% was obtained between the measured and simulated results for percent depth doses (PDDs) and open beam profiles for all three jaw settings in the VSM commissioning. The accuracy of the VSM leaf filter model was verified in comparing the measured and simulated results for a Picket Fence pattern. An agreement of < 2% was achieved between the presented VSM and a published full MC model for heterogeneous phantoms. For complex clinical head and neck (HN) cases, the VSM-based MC simulation of DQA plans agreed with the film measurement with 98% of planar dose pixels passing on the 2%/2 mm gamma criteria. For patient treatment plans, results showed comparable dose-volume histograms (DVHs) for planning target volumes (PTVs) and organs at risk (OARs). Deviations observed in this study were consistent with literature. The VSM-based MC simulation approach can be feasibly built from the gold standard beam model of a tomotherapy unit. The accuracy of the VSM was validated against measurements in homogeneous media, as well as published full MC model in heterogeneous media.

A virtual source model for Monte Carlo simulation of helical tomotherapy

PubMed Central

Yuan, Jiankui; Rong, Yi

2015-01-01

The purpose of this study was to present a Monte Carlo (MC) simulation method based on a virtual source, jaw, and MLC model to calculate dose in patient for helical tomotherapy without the need of calculating phase‐space files (PSFs). Current studies on the tomotherapy MC simulation adopt a full MC model, which includes extensive modeling of radiation source, primary and secondary jaws, and multileaf collimator (MLC). In the full MC model, PSFs need to be created at different scoring planes to facilitate the patient dose calculations. In the present work, the virtual source model (VSM) we established was based on the gold standard beam data of a tomotherapy unit, which can be exported from the treatment planning station (TPS). The TPS‐generated sinograms were extracted from the archived patient XML (eXtensible Markup Language) files. The fluence map for the MC sampling was created by incorporating the percentage leaf open time (LOT) with leaf filter, jaw penumbra, and leaf latency contained from sinogram files. The VSM was validated for various geometry setups and clinical situations involving heterogeneous media and delivery quality assurance (DQA) cases. An agreement of <1% was obtained between the measured and simulated results for percent depth doses (PDDs) and open beam profiles for all three jaw settings in the VSM commissioning. The accuracy of the VSM leaf filter model was verified in comparing the measured and simulated results for a Picket Fence pattern. An agreement of <2% was achieved between the presented VSM and a published full MC model for heterogeneous phantoms. For complex clinical head and neck (HN) cases, the VSM‐based MC simulation of DQA plans agreed with the film measurement with 98% of planar dose pixels passing on the 2%/2 mm gamma criteria. For patient treatment plans, results showed comparable dose‐volume histograms (DVHs) for planning target volumes (PTVs) and organs at risk (OARs). Deviations observed in this study were consistent with literature. The VSM‐based MC simulation approach can be feasibly built from the gold standard beam model of a tomotherapy unit. The accuracy of the VSM was validated against measurements in homogeneous media, as well as published full MC model in heterogeneous media. PACS numbers: 87.53.‐j, 87.55.K‐ PMID:25679157

A new application of micellar liquid chromatography in the determination of free ampicillin concentration in the drug-human serum albumin standard solution in comparison with the adsorption method.

PubMed

Stępnik, Katarzyna E; Malinowska, Irena; Maciejewska, Małgorzata

2016-06-01

The determination of free drug concentration is a very important issue in the field of pharmacology because only the unbound drug fraction can achieve a pharmacological effect. Due to the ability to solubilize many different compounds in micellar aggregates, micellar liquid chromatography (MLC) can be used for direct determination of free drug concentration. Proteins are not retained on the stationary phase probably due to the formation of protein - surfactant complexes which are excluded from the pores of stationary phase. The micellar method is simple and fast. It does not require any pre-preparation of the tested samples for analysis. The main aim of this paper is to demonstrate a completely new applicability of the analytical use of MLC concerning the determination of free drug concentration in the standard solution of human serum albumin. The well-known adsorption method using RP-HPLC and the spectrophotometric technique was applied as the reference method. The results show that the free drug concentration value obtained in the MLC system (based on the RP-8 stationary phase and CTAB) is similar to that obtained by the adsorption method: both RP-HPLC (95.83μgmL(-1), 79.86% of free form) and spectrophotometry (95.71μgmL(-1), 79.76%). In the MLC the free drug concentration was 93.98μgmL(-1) (78.3%). This indicates that the obtained results are within the analytical range of % of free ampicillin fraction and the MLC with direct sample injection can be treated like a promising method for the determination of free drug concentration. Copyright © 2016 Elsevier B.V. All rights reserved.

TU-FG-201-04: Computer Vision in Autonomous Quality Assurance of Linear Accelerators

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

Yu, H; Jenkins, C; Yu, S

Purpose: Routine quality assurance (QA) of linear accelerators represents a critical and costly element of a radiation oncology center. Recently, a system was developed to autonomously perform routine quality assurance on linear accelerators. The purpose of this work is to extend this system and contribute computer vision techniques for obtaining quantitative measurements for a monthly multi-leaf collimator (MLC) QA test specified by TG-142, namely leaf position accuracy, and demonstrate extensibility for additional routines. Methods: Grayscale images of a picket fence delivery on a radioluminescent phosphor coated phantom are captured using a CMOS camera. Collected images are processed to correct formore » camera distortions, rotation and alignment, reduce noise, and enhance contrast. The location of each MLC leaf is determined through logistic fitting and a priori modeling based on knowledge of the delivered beams. Using the data collected and the criteria from TG-142, a decision is made on whether or not the leaf position accuracy of the MLC passes or fails. Results: The locations of all MLC leaf edges are found for three different picket fence images in a picket fence routine to 0.1mm/1pixel precision. The program to correct for image alignment and determination of leaf positions requires a runtime of 21– 25 seconds for a single picket, and 44 – 46 seconds for a group of three pickets on a standard workstation CPU, 2.2 GHz Intel Core i7. Conclusion: MLC leaf edges were successfully found using techniques in computer vision. With the addition of computer vision techniques to the previously described autonomous QA system, the system is able to quickly perform complete QA routines with minimal human contribution.« less

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

Li, X; Yang, F

Purpose: Knowing MLC leaf positioning error over the course of treatment would be valuable for treatment planning, QA design, and patient safety. The objective of the current study was to quantify the MLC positioning accuracy for VMAT delivery of head and neck treatment plans. Methods: A total of 837 MLC log files were collected from 14 head and neck cancer patients undergoing full arc VMAT treatment on one Varian Trilogy machine. The actual and planned leaf gaps were extracted from the retrieved MLC log files. For a given patient, the leaf gap error percentage (LGEP), defined as the ratio ofmore » the actual leaf gap over the planned, was evaluated for each leaf pair at all the gantry angles recorded over the course of the treatment. Statistics describing the distribution of the largest LGEP (LLGEP) of the 60 leaf pairs including the maximum, minimum, mean, Kurtosis, and skewness were evaluated. Results: For the 14 studied patients, their PTV located at tonsil, base of tongue, larynx, supraglottis, nasal cavity, and thyroid gland with volume ranging from 72.0 cm{sup 3} to 602.0 cm{sup 3}. The identified LLGEP differed between patients. It ranged from 183.9% to 457.7% with a mean of 368.6%. For the majority of the patients, the LLGEP distributions peaked at non-zero positions and showed no obvious dependence on gantry rotations. Kurtosis and skewness, with minimum/maximum of 66.6/217.9 and 6.5/12.6, respectively, suggested relatively more peaked while right-skewed leaf error distribution pattern. Conclusion: The results indicate pattern of MLC leaf gap error differs between patients of lesion located at similar anatomic site. Understanding the systemic mechanisms underlying these observed error patterns necessitates examining more patient-specific plan parameters in a large patient cohort setting.« less

Antimicrobial Activity and Biocompatibility of the Psidium cattleianum Extracts for Endodontic Purposes.

PubMed

Massunari, Loiane; Novais, Renata Zoccal; Oliveira, Márcio Teixeira; Valentim, Diego; Dezan Junior, Eloi; Duque, Cristiane

2017-01-01

Psidium cattleianum (PC) has been displaying inhibitory effect against a variety of microorganisms, but this effect has not yet been tested against endodontic pathogens. The aim of this study was to evaluate the antimicrobial activity and biocompatibility of the aqueous (PCAE) and hydroethanolic (PCHE) extracts from Psidium cattleianum (PC) leaves. Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) were determined using the microdilution broth method in order to analyze the antimicrobial effect against Enterococcus faecalis, Pseudomonas aeruginosa, Actinomyces israelii and Candida albicans in planktonic conditions. Biofilm assays were conducted only with the extracts that were able to determine the MLC for microorganisms in planktonic conditions. Immediate and late tissue reactions against PC extracts were evaluated using edemogenic test and histological analysis of subcutaneous implants in Wistar rats. The results showed that the MIC and MLC values ranged between 0.25 and 4 mg/mL. The MLC obtained for PCHE inhibited 100% growth of all the tested strains, except for C. albicans. PCAE had the same effect for E. faecalis and P. aeruginosa. Both PC extracts were able to eliminate E. faecalis biofilms and only the PCHE eliminated P. aeruginosa biofilms. The positive controls inhibited the growth of all tested strains in MIC and MLC essays, but no CHX tested concentrations were able to eliminate A. israelii biofilm. PCAE caused a discrete increase in the edema over time, while PCHE caused a higher initial edema, which decreased progressively. Both PCAE and PCHE extracts were biocompatible, but PCHE showed better results with slight levels of inflammation at 28 days. In conclusion, PCHE was biocompatible and presented better antimicrobial effect against important pathogens associated with persistent endodontic infections.

Development, physical properties and clinical applicability of a mechanical Multileaf Collimator for the use in Cobalt-60 radiotherapy

NASA Astrophysics Data System (ADS)

Langhans, Marco; Echner, Gernot; Runz, Armin; Baumann, Martin; Xu, Mark; Ueltzhöffer, Stefan; Häring, Peter; Schlegel, Wolfgang

2015-04-01

According to the Directory of Radiotherapy Centres (DIRAC) there are 2348 Cobalt-60 (Co-60) teletherapy units worldwide, most of them in low and middle income countries, compared to 11046 clinical accelerators. To improve teletherapy with Co-60, a mechanical Multi-Leaf Collimator (MLC) was developed, working with pneumatic pressure and thus independent of electricity supply. Instead of tungsten, brass was used as leaf material to make the mechanical MLC more affordable. The physical properties and clinical applicability of this mechanical MLC are presented here. The leakage strongly depends on the fieldsize of the therapy unit due to scatter effects. The maximum transmission through the leaves measured 2.5 cm from the end-to-end gap, within a field size of 20 cm × 30 cm defined by jaws of the therapy unit at 80 cm SAD, amounts 4.2%, normalized to an open 10 cm × 10 cm field, created by the mechanical MLC. Within a precollimated field size of 12.5 cm × 12.5 cm, the end-to-end leakage is 6.5% normalized to an open 10 cm × 10 cm field as well. This characteristic is clinically acceptable considering the criteria for non-IMRT MLCs of the International Electrotechnical Commission (IEC 60601-2-1). The penumbra for a 10 cm × 10 cm field was measured to be 9.14 mm in plane and 8.38 mm cross plane. The clinical applicability of the designed mechanical MLC was affirmed by measurements relating to all relevant clinical properties such as penumbra, leakage, output factors and field widths. Hence this novel device presents an apt way forward to make radiotherapy with conformal fields possible in low-infrastructure environments, using gantry based Co-60 therapy units.

Poster — Thur Eve — 19: Performance assessment of a 160-leaf beam collimation system

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

Ali, E. S. M.; La Russa, D. J.; Vandervoort, E.

2014-08-15

In this study, the performance of the new beam collimation system with 160 leaves, each with a 5 mm leaf width projected at isocenter, is evaluated in terms of positional accuracy and plan/delivery quality. Positional accuracy was evaluated using a set of static and dynamic MLC/jaw delivery patterns at different gantry angles, dose rates, and MLC/jaw speeds. The impact on IMRT plan quality was assessed by comparing against a previous generation collimation system using the same optimization parameters, while delivery quality was quantified using a combination of patient-specific QA measurements with ion chambers, film, and a bi-planar diode array. Positionalmore » accuracy for four separate units was comparable. The field size accuracy, junction width, and total displacement over 16 cm leaf travel are 0.3 ± 0.2 mm, 0.4 ± 0.3 mm, and 0.5 ± 0.2 mm, respectively. The typical leaf minor offset is 0.05 ± 0.04 mm, and MLC hysteresis effects are 0.2 ± 0.1 mm over 16 cm travel. The dynamic output is linear with MU and MLC/jaw speed, and is within 0.7 ± 0.3 % of the planning system value. Plan quality is significantly improved both in terms of target coverage and OAR sparing due, in part, to the larger allowable MLC and jaw speeds. γ-index pass rates for the patient-specific QA measurements exceeded 97% using criteria of 2%/2 mm. In conclusion, the performance of the Agility system is consistent among four separate installations, and is superior to its previous generations of collimation systems.« less

Effect of conductance linearity and multi-level cell characteristics of TaOx-based synapse device on pattern recognition accuracy of neuromorphic system

NASA Astrophysics Data System (ADS)

Sung, Changhyuck; Lim, Seokjae; Kim, Hyungjun; Kim, Taesu; Moon, Kibong; Song, Jeonghwan; Kim, Jae-Joon; Hwang, Hyunsang

2018-03-01

To improve the classification accuracy of an image data set (CIFAR-10) by using analog input voltage, synapse devices with excellent conductance linearity (CL) and multi-level cell (MLC) characteristics are required. We analyze the CL and MLC characteristics of TaOx-based filamentary resistive random access memory (RRAM) to implement the synapse device in neural network hardware. Our findings show that the number of oxygen vacancies in the filament constriction region of the RRAM directly controls the CL and MLC characteristics. By adopting a Ta electrode (instead of Ti) and the hot-forming step, we could form a dense conductive filament. As a result, a wide range of conductance levels with CL is achieved and significantly improved image classification accuracy is confirmed.

Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration.

PubMed

Croft, Daniel R; Coleman, Mathew L; Li, Shuixing; Robertson, David; Sullivan, Teresa; Stewart, Colin L; Olson, Michael F

2005-01-17

Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization.

Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration

PubMed Central

Croft, Daniel R.; Coleman, Mathew L.; Li, Shuixing; Robertson, David; Sullivan, Teresa; Stewart, Colin L.; Olson, Michael F.

2005-01-01

Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization. PMID:15657395

The Enhancement of Phototropin-Induced Phototropic Curvature in Arabidopsis Occurs via a Photoreversible Phytochrome A-Dependent Modulation of Auxin Responsiveness1

PubMed Central

Stowe-Evans, Emily L.; Luesse, Darron R.; Liscum, Emmanuel

2001-01-01

The induction of phototropism in etiolated (dark-grown) seedlings exposed to an unidirectional pulse or extended irradiation with low fluence rate blue light (BL) requires the action of the phototropin (nph1) BL receptor. Although cryptochromes and phytochromes are not required for phototropic induction, these photoreceptors do modulate the magnitude of curvature resulting from phototropin activation. Modulatory increases in the magnitude of phototropic curvature have been termed “enhancement.” Here, we show that phototropic enhancement is primarily a phytochrome A (phyA)-dependent red/far-red-reversible low fluence response. This phyA-dependent response is genetically separable from the basal phototropin-dependent response, as demonstrated by its retention under extended irradiation conditions in the nph4 mutant background, which normally lacks the basal BL-induced response. It is interesting that the nph4 mutants fail to exhibit the basal phototropin-dependent and phyA-dependent enhancement responses under limiting light conditions. Given that NPH4 encodes a transcriptional activator, auxin response factor 7 (ARF7), we hypothesize that the ultimate target(s) of phyA action during the phototropic enhancement response is a rate-limiting ARF-containing transcriptional complex in which the constituent ARFs can vary in identity or activity depending upon the irradiation condition. PMID:11402210

Near-surface density profiling of Fe ion irradiated Si (100) using extremely asymmetric x-ray diffraction by variation of the wavelength

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

Khanbabaee, B., E-mail: khanbabaee@physik.uni-siegen.de; Pietsch, U.; Facsko, S.

2014-10-20

In this work, we report on correlations between surface density variations and ion parameters during ion beam-induced surface patterning process. The near-surface density variations of irradiated Si(100) surfaces were investigated after off-normal irradiation with 5 keV Fe ions at different fluences. In order to reduce the x-ray probing depth to a thickness below 5 nm, the extremely asymmetrical x-ray diffraction by variation of wavelength was applied, exploiting x-ray refraction at the air-sample interface. Depth profiling was achieved by measuring x-ray rocking curves as function of varying wavelengths providing incidence angles down to 0°. The density variation was extracted from the deviationsmore » from kinematical Bragg angle at grazing incidence angles due to refraction of the x-ray beam at the air-sample interface. The simulations based on the dynamical theory of x-ray diffraction revealed that while a net near-surface density decreases with increasing ion fluence which is accompanied by surface patterning, there is a certain threshold of ion fluence to surface density modulation. Our finding suggests that the surface density variation can be relevant with the mechanism of pattern formation.« less

A study on the application of Fourier series in IMRT treatment planning.

PubMed

Almeida-Trinidad, R; Garnica-Garza, H M

2007-12-01

In intensity-modulated radiotherapy, a set of x-ray fluence profiles is iteratively adjusted until a desired absorbed dose distribution is obtained. The purpose of this article is to present a method that allows the optimization of fluence profiles based on the Fourier series decomposition of an initial approximation to the profile. The method has the advantage that a new fluence profile can be obtained in a precise and controlled way with the tuning of only two parameters, namely the phase of the sine and cosine terms of one of the Fourier components, in contrast to the point-by-point tuning of the profile. Also, because the method uses analytical functions, the resultant profiles do not exhibit numerical artifacts. A test case consisting of a mathematical phantom with a target wrapped around a critical structure is discussed to illustrate the algorithm. It is shown that the degree of conformality of the absorbed dose distribution can be tailored by varying the number of Fourier terms made available to the optimization algorithm. For the test case discussed here, it is shown that the number of Fourier terms to be modified depends on the number of radiation beams incident on the target but it is in general in the order of 10 terms.

Interface Message Processors for the ARPA Computer Network

DTIC Science & Technology

1975-04-01

Pluribus IMP construction and checkout; sizeable changes to the i*4P message-processing algorithms: and Satellite IMP issues. The IMP message...extremely low cost modification design. We have begun to consider changes to the MLC design which would enable the MLC to suppress continuous breaks...existing authentication mechanisms need not make these changes . 2.7 Other Topics During the first quarter BBN constructed an environmental test chamber

Kidney protection against ischemia/reperfusion injury by myofibrillogenesis regulator-1.

PubMed

Wang, Xiaoreng; Tao, Tianqi; Ding, Rui; Song, Dandan; Liu, Mi; Xie, Yuansheng; Liu, Xiuhua

2014-01-01

Ischemia/reperfusion (I/R) injury is characterized by cytoskeletal reorganization and loss of polarity in proximal tubule epithelial cells. Previously, we showed that myofibrillogenesis regulator (MR)-1 promoted actin organization in cardiomyocytes. MR-1 is also expressed in the kidney. In this study, we investigated MR-1 expression in acute renal failure induced by I/R in Sprague-Dawley rats. We determined the MR-1 expression and the ratio of fibrous actin (F-actin) to globular actin (G-actin). HK-2 cells were treated with or without hypoxia/reoxygenation (H/R), and MR-1 levels were increased by adenoviral overexpression or silenced by RNA interference. I/R and H/R resulted in cellular injury and decreases of MR-1, the F-/G-actin ratio, and myosin light chain (MLC)-2. MR-1 overexpression attenuated H/R-induced cell injury and loss of surface membrane polarity of actin. MR-1 overexpression also increased the expression and phosphorylation of MLC-2 and MLC kinase, which were decreased in MR-1-silenced and H/R-treated cells. Together, these data show that MR-1 promoted actin polarity on the membrane surface and protected HK-2 cells from H/R injury. The mechanism might involve the rapid organization of F-actin through the upregulation and phosphorylation of MLC-2.

Aspects of cooling tower biocides and protozoa

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

Berk, S.G.; Ashburn, R.J.; Ting, R.S.

1998-12-31

Previous work has shown that certain cooling tower amoebae and ciliated protozoa are resistant to several cooling tower biocides, even at the manufacturer`s recommended dosages. For the present study, an Acunthumoeba species was isolated from a cooling tower in Australia. Suspensions of the trophozoites (feeding stages) were exposed to isothiazolones. Cysts were tested separately. The minimum lethal concentration (MLC) for trophozoites was between 31-62 ppm of the biocide product, which is slightly less than the MLC for an amoebae species from the United States; and cyst forms were twofold more resistant than those of the US species, with a MLCmore » of 62,500 ppm. A ciliate and an amoeba species were also exposed to bromochlorodimethylhydantoin. The MLC for the ciliate species was 1 ppm of the biocide product, and the MLC was 30--40 ppm for the amoeba trophozoites. Since amoebae can expel vesicles containing live Legionella, experiments were conducted to determine whether exposure of Acunthamoebu polyphugu to biocides influenced release of such potentially infectious particles. Vesicle release was not inhibited by any of the three biocides: quaternary ammonium compounds (QACs), isothiazolones, and a thiocarbamate compound. These results suggest that amoebae from various sources are resistant to recommended levels of biocides, and the amoebae may continue to release potentially infectious vesicles in the presence of biocides.« less

Monte Carlo calculation of the radiation field at aircraft altitudes.

PubMed

Roesler, S; Heinrich, W; Schraube, H

2002-01-01

Energy spectra of secondary cosmic rays are calculated for aircraft altitudes and a discrete set of solar modulation parameters and rigidity cut-off values covering all possible conditions. The calculations are based on the Monte Carlo code FLUKA and on the most recent information on the interstellar cosmic ray flux including a detailed model of solar modulation. Results are compared to a large variety of experimental data obtained on the ground and aboard aircraft and balloons, such as neutron, proton, and muon spectra and yields of charged particles. Furthermore, particle fluence is converted into ambient dose equivalent and effective dose and the dependence of these quantities on height above sea level, solar modulation, and geographical location is studied. Finally, calculated dose equivalent is compared to results of comprehensive measurements performed aboard aircraft.

Dynamic temperature response of electrocaloric multilayer capacitors

NASA Astrophysics Data System (ADS)

Kwon, Beomjin; Roh, Im-Jun; Baek, Seung-Hyub; Keun Kim, Seong; Kim, Jin-Sang; Kang, Chong-Yun

2014-05-01

We measure and model the dynamic temperature response of electrocaloric (EC) multilayer capacitors (MLCs) which have been recently highlighted as novel solid-state refrigerators. The MLC temperature responses depend on the operation voltage waveform, thus we consider three types of voltage waveforms, which include square, triangular, and trapezoidal. Further, to implement an effective refrigeration cycle, the waveform frequency and duty cycle should be carefully chosen. First, our model is fitted to the measurements to evaluate an effective EC power and thermal properties, and calculates an effective cooling power for an EC MLC. The prediction shows that for a MLC with a thermal relaxation time for cooling, trc, a square voltage waveform with a duty cycle of 0 < d ≤ 0.3 and a period of trc < P ≤ 1.4trc provides the maximum cooling power. This work will help to improve the implementing methods for EC refrigeration cycles.

Ultrafast dynamics of Al-doped zinc oxide under optical excitation (Presentation Recording)

NASA Astrophysics Data System (ADS)

Kinsey, Nathaniel; DeVault, Clayton T.; Kim, Jongbum; Ferrera, Marcello; Kildishev, Alexander V.; Shalaev, Vladimir M.; Boltasseva, Alexandra

2015-09-01

There is a continual need to explore new and promising dynamic materials to power next-generation switchable devices. In recent years, transparent conducting oxides have been shown to be vital materials for such systems, allowing for both optical and electrical tunability. Using a pump-probe technique, we investigate the optical tunability of CMOS-compatible, highly aluminum doped zinc oxide (AZO) thin films. The sample was pumped at 325 nm and probed with a weak beam at 1.3 μm to determine the timescale and magnitude of the changes by altering the temporal delay between the pulses with a delay line. For an incident fluence of 3.9 mJ/cm2 a change of 40% in reflection and 30% (max 6.3dB/μm modulation depth) in transmission is observed which is fully recovered within 1ps. Using a computational model, the experimental results were fitted for the given fluence allowing the recombination time and induced carrier density to be extracted. For a fluence of 3.9 mJ/cm2 the average excess carrier density within the material is 0.7×10^20cm-3 and the recombination time is 88fs. The ultrafast temporal response is the result of Auger recombination due to the extremely high carrier concentration present in our films, ~10^21 cm-3. By measuring and fitting the results at several incident fluence levels, the recombination time versus carrier density was determined and fitted with an Auger model resulting in an Auger coefficient of C = 1.03×10^20cm6/sec. Consequently, AZO is shown to be a unique, promising, and CMOS-compatible material for high performance dynamic devices in the near future.

Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1α and MMP-2*

PubMed Central

Cury, Vivian; Moretti, Ana Iochabel Soares; Assis, Lívia; Bossini, Paulo; de Souza Crusca, Jaqueline; Neto, Carlos Benatti; Fangel, Renan; de Souza, Heraldo Possolo; Hamblin, Michael R; Parizotto, Nivaldo Antonio

2013-01-01

It is known that low level laser therapy is able to improve skin flap viability by increasing angiogenesis. However, the mechanism for new blood vessel formation is not completely understood. Here, we investigated the effects of 660 nm and 780 nm lasers at fluences of 30 and 40 J/cm2 on three important mediators activated during angiogenesis. Sixty male Wistar rats were used and randomly divided into five groups with twelve animals each. Groups were distributed as follows: skin flap surgery non-irradiated group as a control; skin flap surgery irradiated with 660 nm laser at a fluence of 30 or 40 J/cm2 and skin flap surgery irradiated with 780 nm laser at a fluence of 30 or 40 J/cm2. The random skin flap was performed measuring 10 × 4 cm, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was performed on 24 points covering the flap and surrounding skin immediately after the surgery and for 7 consecutive days thereafter. Tissues were collected, and the number of vessels, angiogenesis markers (vascular endothelial growth factor, VEGF and hypoxia inducible factor, HIF-1α) and a tissue remodeling marker (matrix metalloproteinase, MMP-2) were analyzed. LLLT increased an angiogenesis, HIF-1α and VEGF expression and decrease MMP-2 activity. These phenomena were dependent on the fluences, and wavelengths used. In this study we showed that LLLT may improve the healing of skin flaps by enhancing the amount of new vessels formed in the tissue. Both 660 nm and 780 nm lasers were able to modulate VEGF secretion, MMP-2 activity and HIF-1α expression in a dose dependent manner. PMID:23831843

SU-F-T-604: Dosimetric Evaluation of Intracranial Stereotactic Radiotherapy Plans On a LINAC

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

Sheth, N; Tabibian, A; Rose, J

2016-06-15

Purpose: To evaluate the dosimetry of cranial stereotactic radiotherapy (SRT) plans of varying techniques on linac that meets appropriate TG-142 tolerances using 1 cm leaf width multileaf collimator (MLC). Methods: Seventeen spherical targets were generated in the center of a head phantom with diameters ranging 8 mm to 40 mm. SRT plans used 100° non-coplanar arcs and 5 couch angles with 35° spacing. The field size was target plus 1 mm margin. Four plans were created for each target: symmetrical jaws blocking for 5 arcs with 0° collimator (J1C), symmetrical jaws blocking with 5 clockwise arcs with 0° collimator andmore » 5 counter-clockwise arcs with 45° collimator (J2C), MLC blocking for 5 dynamic conformal arcs with 0° collimator (M1C), and MLC blocking for 5 clockwise dynamic conformal arcs with 0° collimators and 5 counter-clockwise dynamic conformal arcs with 45° collimator (M2C).Conformity was evaluated using a ratio of Rx to target volume (PITV). Heterogeneity was determined using a ratio of maximum dose to Rx dose. Falloff was scored using CGIg: difference of effective radii of spheres equal to half and full Rx volumes. Results: All plans met RTOG SRS criteria for conformity and heterogeneity. The mean PITV was 1.52±0.07, 1.49±0.08, 1.39±0.05, and 1.37±0.04 for J1C, J2C, M1C, and M2C plans respectively. The mean CGIg was 75.35±15.79, 74.19±16.66, 77.14±15.12, and 76.28±15.78 for J1C, J2C, M1C, and M2C plans respectively. The mean MDPD was 1.25±0.00 for all techniques. Conclusion: Clinically acceptable SRT plans for spherical targets were created on a linac with 1 cm MLC. Adding two collimator angles and MLC to arcs each improved conformity. The MLC improved the dose falloff while two collimator angles degraded it. This technique can expand the availability of SRT to patients especially to those who cannot travel to a facility with a dedicated stereotactic radiosurgery machine.« less

Magnetic decoupling of the linac in a low field biplanar linac-MR system.

PubMed

St Aubin, J; Steciw, S; Fallone, B G

2010-09-01

The integration of a low field biplanar magnetic resonance (MR) imager and linear accelerator (linac) causes magnetic interference at the linac due to the MR fringe fields. In order to eliminate this interference, passive and active magnetic shielding designs are investigated. The optimized design of passive magnetic shielding was performed using the finite element method. The design was required to achieve no greater than a 20% electron beam loss within the linac waveguide and electron gun, no greater than 0.06 T at the multileaf collimator (MLC) motors, and generate a distortion of the main MR imaging volume of no greater than 300 ppm. Through the superposition of the analytical solution for a single current carrying wire loop, active shielding designs in the form of three and four sets of coil pairs surrounding the linac waveguide and electron gun were also investigated. The optimized current and coil center locations that yielded the best cancellation of the MR fringe fields at the linac were determined using sequential quadratic programming. Optimized passive shielding in the form of two steel cylinders was designed to meet the required constraints. When shielding the MLC motors along with the waveguide and electron gun, the thickness of the cylinders was less than 1 mm. If magnetically insensitive MLC motors are used, no MLC shielding would be required and the waveguide shield (shielding the waveguide and electron gun) became 1.58 mm thick. In addition, the optimized current and coil spacing for active shielding was determined for both three and four coil pair configurations. The results of the active shielding optimization produced no beam loss within the waveguide and electron gun and a maximum MR field distortion of 91 ppm over a 30 cm diameter spherical volume. Very simple passive and active shielding designs have been shown to magnetically decouple the linac from the MR imager in a low field biplanar linac-MR system. The MLC passive shielding produced the largest distortion of the MR field over the imaging volume. With the use of magnetically insensitive motors, the MR field distortion drops substantially since no MLC shield is required. The active shielding designs yielded no electron beam loss within the linac.

Effect of tertiary multileaf collimator (MLC) on foetal dose during three-dimensional conformal radiation therapy (3DCRT) of a brain tumour during pregnancy.

PubMed

Sharma, Dayananda S; Jalali, Rakesh; Tambe, Chandrashekhar M; Animesh; Deshpande, Deepak D

2004-01-01

The aim of this work was to measure the dose to foetus both in vivo and in vitro during three-dimensional conformal radiation therapy (3DCRT) in a pregnant patient with a pituitary adenoma. The study was then extended to assess the components contributing to the foetal dose such as collimator scatter, internal scatter, head leakage, wedge scatter and multileaf collimator (MLC) effect. A 30-year-old pregnant woman with a non-functioning pituitary macroadenoma was planned for 3DCRT with 6MV X-ray using four equally weighted MLC-shaped non-coplanar wedged portals. In vivo dosimetry was carried out using thermoluminescent (TL) phosphor powder, which was placed at different positions on the patient, corresponding to different locations in the uterus and also at external os. In vitro measurements were also performed on a simulated phantom using the same set-up parameters and beam arrangement to verify the in vivo measured dose. Experiments were carried out to measure the respective contributions of different components towards peripheral dose. In vitro measured dose to foetus was found to be slightly more than that of in vivo measurement with a maximum of 0.044% of the prescribed dose of 45Gy, which corresponded to 0.0199+/-0.0008Gy. Thermoluminescence dosimeter (TLD) kept at the external os of the patient showed a dose of 0.031% of the prescribed dose. Among the various components of the peripheral dose (foetal dose) measured, head leakage was found to be the leading cause contributing 52%, followed by wedge scatter (31%), collimator scatter (14%) and internal scatter (13%). The use of MLC reduced not only the volume of normal brain irradiation as compared to open fields but also the peripheral dose by 10%. Radiotherapy of brain tumours during pregnancy poses a unique clinical situation and decisions to deliver radiotherapy should be taken after detailed in vitro and in vivo dosimetric measurements. Our findings suggest that the beam arrangement using 3-4-fields generally used for 3DCRT of brain tumour with MLC for optimal coverage can be employed for pregnant patients even in early trimester. A possible increase in foetal dose from wedges to a large extent can be compensated with the use of MLC.

Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study.

PubMed

Venketasubramanian, Narayanaswamy; Lee, Chun Fan; Young, Sherry H; Tay, San San; Umapathi, Thirugnanam; Lao, Annabelle Y; Gan, Herminigildo H; Baroque Ii, Alejandro C; Navarro, Jose C; Chang, Hui Meng; Advincula, Joel M; Muengtaweepongsa, Sombat; Chan, Bernard P L; Chua, Carlos L; Wijekoon, Nirmala; de Silva, H Asita; Hiyadan, John Harold B; Suwanwela, Nijasri C; Wong, K S Lawrence; Poungvarin, Niphon; Eow, Gaik Bee; Chen, Christopher L H

2017-01-01

The Chinese Medicine NeuroAiD Efficacy on Stroke recovery - Extension (CHIMES-E) study is among the few acute stroke trials with long-term outcome data. We aimed to evaluate the recovery pattern and the influence of prognostic factors on treatment effect of MLC601 over 2 years. The CHIMES-E study evaluated the 2 years outcome of subjects aged ≥18 years with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score 6-14, pre-stroke modified Rankin Scale (mRS) score ≤1 included in a multicenter, randomized, double-blind, placebo-controlled trial of MLC601 for 3 months. Standard stroke care and rehabilitation were allowed during follow-up with mRS score being assessed in-person at month (M) 3 and by telephone at M1, M6, M12, M18 and M24. Data from 880 subjects were analyzed. There was no difference in baseline characteristics between treatment groups. The proportion of subjects with mRS score 0-1 increased over time in favor of MLC601 most notably from M3 to M6, thereafter remaining stable up to M24, while the proportion deteriorating to mRS score ≥2 remained low at all time points. Older age (p < 0.01), female sex (p = 0.06), higher baseline NIHSS score (p < 0.01) and longer onset to treatment time (OTT; p < 0.01) were found to be predictors of poorer outcome at M3. Greater treatment effect, with more subjects improving on MLC601 than placebo, was seen among subjects with 2 or more prognostic factors (OR 1.65 at M3, 1.78 at M6, 1.90 at M12, 1.65 at M18, 1.39 at M24), especially in subjects with more severe stroke or longer OTT. The sustained benefits of MLC601 over 2 years were due to more subjects improving to functional independence at M6 and beyond compared to placebo. Selection of subjects with poorer prognosis, particularly those with more severe NIHSS score and longer OTT delay, as well as a long follow-up period, may improve the power of future trials investigating the treatment effect of neuroprotective or neurorestorative therapies. © 2016 The Author(s) Published by S. Karger AG, Basel.

Species differences in the effects of prostanoids on MAP kinase phosphorylation, myosin light chain phosphorylation and contraction in bovine and cat iris sphincter smooth muscle.

PubMed

Kaddour-Djebbar, I; Ansari, H R; Akhtar, R A; Abdel-Latif, A A

2005-01-01

There is evidence from our own laboratory and that of others that EP-receptor ligands are strong contractile agonists in bovine iris sphincter and that FP-receptor agonists are strong contractile agonists in cat iris sphincter. Here, we have investigated the effects of prostaglandin (PG) receptor agonists of the FP-, EP-, TP- and DP-class on myosin light chain (MLC) phosphorylation, p42/p44 MAP kinase phosphorylation and contraction in the iris sphincter of bovine and cat. Using three signal transduction mechanism assays, namely MLC phosphorylation, MAP kinase phosphorylation and contraction, we demonstrated that in bovine iris sphincter the rank order of potency of the PG agonists in the contractile and MLC phosphorylation assays is as follows: E2>U46619>F2alpha>D2, and in cat F2alpha>D2>E2>U46619. In the MAP kinase assay, in bovine iris sphincter the rank order of potency is E2>F2alpha and in cat F2alpha>E2. These conclusions are supported by the following findings: (1) In the contractile assay, in the bovine sphincter the EC50s for PGF2alpha, PGE2, U46619 and PGD2 were found to be 1.4x10(-7), 5.0x10(-9), 9.0x10(-9) and 1.3x10(-6)M, respectively, and the corresponding values in the cat were 1.9x10(-8), 2.3x10(-7), 1.5x10(-6) and 6.9x10(-8)M, respectively. (2) In the MLC phophorylation assay, in the bovine sphincter PGF2alpha, PGE2, U46619 and PGD2 increased MLC phophorylation by 118%, 165%, 153% and 72%, respectively, and the corresponding values in cat were 175%, 99%, 90% and 95%, respectively. (3) In the MAP kinase assay, in the bovine iris sphincter PGF2alpha and PGE2, increased MAP kinase phosphorylation by 276% and 328%, respectively, and the corresponding values in cat were 308% and 245%, respectively. The data presented demonstrate pronounced species differences in the effects of the prostanoids on the MLC kinase signaling pathway in bovine and cat irides and furthermore confirm the existence of FP-receptors in that of the bovine.

Apigenin Alleviates Endotoxin-Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy

PubMed Central

Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chunxiao

2017-01-01

Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF-α, IL-1β, MIP-1α, and MIP-2) along with their master regulator NFκB. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries. PMID:28828145

Apigenin Alleviates Endotoxin-Induced Myocardial Toxicity by Modulating Inflammation, Oxidative Stress, and Autophagy.

PubMed

Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Zhai, Chunxiao; Hao, Enkui

2017-01-01

Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID)). Apigenin also alleviated endotoxin-induced myocardial injury by modulating oxidative stress (nitrotyrosine and protein carbonyl) and inflammatory cytokines (TNF- α , IL-1 β , MIP-1 α , and MIP-2) along with their master regulator NF κ B. Apigenin modulated redox homeostasis, and its anti-inflammatory role might be associated with its ability to control autophagy. Autophagy (determined by LAMP1, ATG5, and p62), its transcriptional regulator transcription factor EB (TFEB), and downstream target genes including vacuolar protein sorting-associated protein 11 (Vps11) and microtubule-associated proteins 1A/1B light chain 3B (Map1lc3) were modulated by apigenin. Thus, our study demonstrated that apigenin may lead to potential development of new target in sepsis treatment or other myocardial oxidative and/or inflammation-induced injuries.

Using narrow beam profiles to quantify focal spot size, for accurate Monte Carlo simulations of SRS/SRT systems

NASA Astrophysics Data System (ADS)

Kairn, T.; Crowe, S. B.; Charles, P. H.; Trapp, J. V.

2014-03-01

This study investigates the variation of photon field penumbra shape with initial electron beam diameter, for very narrow beams. A Varian Millenium MLC (Varian Medical Systems, Palo Alto, USA) and a Brainlab m3 microMLC (Brainlab AB. Feldkirchen, Germany) were used, with one Varian iX linear accelerator, to produce fields that were (nominally) 0.20 cm across. Dose profiles for these fields were measured using radiochromic film and compared with the results of simulations completed using BEAMnrc and DOSXYZnrc, where the initial electron beam was set to FWHM = 0.02, 0.10, 0.12, 0.15, 0.20 and 0.50 cm. Increasing the electron-beam FWHM produced increasing occlusion of the photon source by the closely spaced collimator leaves and resulted in blurring of the simulated profile widths from 0.24 to 0.58 cm, for the MLC, from 0.11 to 0.40 cm, for the microMLC. Comparison with measurement data suggested that the electron spot size in the clinical linear accelerator was between FWHM = 0.10 and 0.15 cm, encompassing the result of our previous output-factor based work, which identified a FWHM of 0.12 cm. Investigation of narrow-beam penumbra variation has been found to be a useful procedure, with results varying noticeably with linear accelerator spot size and allowing FWHM estimates obtained using other methods to be verified.

Improving a scissor-action couch for conformal arc radiotherapy and radiosurgery.

PubMed

Li, Kaile; Yu, Cedric X; Ma, Lijun

2004-01-01

We have developed a method to improve the setup accuracy of a Varian Clinac 6/100 couch for delivering conformal arc therapy using a tertiary micro multileaf collimator (MLC) system. Several immobilization devices have been developed to improve the mechanical stability and isocenter alignment of the couch: turn-knob harnesses, double-track alignment plates, and a drop-in rod that attaches the couch to the concrete floor. These add-on components minimize the intercomponent motion of the couch's scissor elevator, which allows consistent treatment setup. The accuracy of our isocenter couch alignment is an improvement over the above devices, within 1 mm of their accuracy. The couch has been used with over 15 patients and with over 50 modulated conformal arc treatment deliveries at our institution.

A Dosimetric Evaluation of The Eclipse and Pinnacle Treatment Planning Systems in Treatment of Vertebral Bodies Using IMRT and VMAT with Modeled and Commissioned Flattening Filter Free (FFF) Fields

NASA Astrophysics Data System (ADS)

Ajo, Ramzi, Jr.

Modern treatment planning systems (TPS's) utilize different algorithms in computing dose within the patient medium. The algorithms rely on properly modeled clinical setups in order to perform optimally. Aside from various parameters of the beam, modifiers, such as multileaf collimators (MLC's), must also be modeled properly. That could not be more true today, where dynamic delivery such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) are being increasingly utilized due to their ability to deliver higher dose precisely to the target while sparing more surrounding normal tissue. Two of the most popular TPS's, Pinnacle (Philips) and Eclipse (Varian), were compared, with special emphasis placed on parameterization of the dosimetric leaf gap (DLG) in Eclipse. The DLG is a parameter that accounts for Varian's rounded MLC leaf ends. While Pinnacle accounts for the rounded leaf end by modeling the MLC's, Eclipse uses a measured parameter. This study investigated whether a single value measured DLG is sufficient for dynamic delivery. Using five planning volumes for vertebral body SBRT treatments, each prescribed for 3000 cGy in 5 fractions, an array of 20 treatment plans was generated using varying energies of 6MV-FFF and 10MV-FFF. Treatment techniques consisted of 9-field Step-and-shoot IMRT, and dual-arc VMAT using patient specific optimization criteria in the Pinnacle TPS v9.8. Each plan was normalized to ensure coverage of 3000cGy to 95% of the target volume. The dose was computed in Pinnacle v9.8, with the Collapsed Cone Convolution Superposition algorithm and Eclipse v11, with the Acuros XB algorithm, using a dose grid resolution of 2 mm in both systems. Dose volume histograms (DVH's) were generated for a comparison of max and mean dose to the targets and spinal cord, as well as 95% coverage of the targets and the volume of the spinal cord receiving 14.5 Gy (V14.5). Patient specific quality assurance (PSQA) fields were generated and then delivered, using a Varian Edge linear accelerator, to a 4D QA phantom for a gamma analysis and distance to agreement (DTA) comparison. All Eclipse calculations were made for both measured and optimized DLG parameters. Calculated vs. measured point dose for the Pinnacle TPS had an average difference of 2.79 +/- 2.00%. Gamma analysis using a 3% and 3 mm DTA had 99/100 fields passing at > 95%. Using measured values of the DLG in Eclipse, calculated vs. measured point dose was -4.44 +/- 1.97%, and DTA had 33/110 fields passing at > 95%. After an optimization of the DLG in Eclipse, calculated vs. measured point dose had an average difference of 2.20 +/- 2.23%, and DTA with 95/110 fields passing at > 95%. This study looked at the performance of the Pinnacle and Eclipse TPS's, with special consideration given to the DLG parameterization used by Eclipse. The results support the idea that a single valued DLG is not sufficient for dynamic delivery. An optimization of the parameter is necessary to account for the high modulation of IMRT and VMAT techniques.

Ultra-high modulation depth exceeding 2,400% in optically controlled topological surface plasmons

PubMed Central

Sim, Sangwan; Jang, Houk; Koirala, Nikesh; Brahlek, Matthew; Moon, Jisoo; Sung, Ji Ho; Park, Jun; Cha, Soonyoung; Oh, Seongshik; Jo, Moon-Ho; Ahn, Jong-Hyun; Choi, Hyunyong

2015-01-01

Modulating light via coherent charge oscillations in solids is the subject of intense research topics in opto-plasmonics. Although a variety of methods are proposed to increase such modulation efficiency, one central challenge is to achieve a high modulation depth (defined by a ratio of extinction with/without light) under small photon-flux injection, which becomes a fundamental trade-off issue both in metals and semiconductors. Here, by fabricating simple micro-ribbon arrays of topological insulator Bi2Se3, we report an unprecedentedly large modulation depth of 2,400% at 1.5 THz with very low optical fluence of 45 μJ cm−2. This was possible, first because the extinction spectrum is nearly zero due to the Fano-like plasmon–phonon-destructive interference, thereby contributing an extremely small denominator to the extinction ratio. Second, the numerator of the extinction ratio is markedly increased due to the photoinduced formation of massive two-dimensional electron gas below the topological surface states, which is another contributor to the ultra-high modulation depth. PMID:26514372

Magnetically-induced forces on a ferromagnetic HT-9 first wall/blanket module

NASA Astrophysics Data System (ADS)

Lechtenberg, T. A.; Dahms, C. F.; Attaya, H.

1984-05-01

A model of the Starfire commercial tokamak reactor was used as the basis for calculating magnetic loads induced on typical fusion reactor first wall components fabricated of ferromagnetic material. The component analyzed was the first wall/blanket module because this structure experiences the greatest neutron fluence level and is the component for which the low swelling ferromagnetic Sandvik alloy, HT-9, may have the greatest benefit. The magnitudes of the magnetic body forces calculated were consistent with analyses performed on structures within other types of reactors. The loads generated within the module structure by the magnetic forces were found to be of the same order of magnitude as those arising from other sources such as pressure differential, dead weight, temperature distribution. Only small structural design modifications would be required if the magnetic alloy, Sandvik HT-9 were utilized.

Inherent smoothness of intensity patterns for intensity modulated radiation therapy generated by simultaneous projection algorithms

NASA Astrophysics Data System (ADS)

Xiao, Ying; Michalski, Darek; Censor, Yair; Galvin, James M.

2004-07-01

The efficient delivery of intensity modulated radiation therapy (IMRT) depends on finding optimized beam intensity patterns that produce dose distributions, which meet given constraints for the tumour as well as any critical organs to be spared. Many optimization algorithms that are used for beamlet-based inverse planning are susceptible to large variations of neighbouring intensities. Accurately delivering an intensity pattern with a large number of extrema can prove impossible given the mechanical limitations of standard multileaf collimator (MLC) delivery systems. In this study, we apply Cimmino's simultaneous projection algorithm to the beamlet-based inverse planning problem, modelled mathematically as a system of linear inequalities. We show that using this method allows us to arrive at a smoother intensity pattern. Including nonlinear terms in the simultaneous projection algorithm to deal with dose-volume histogram (DVH) constraints does not compromise this property from our experimental observation. The smoothness properties are compared with those from other optimization algorithms which include simulated annealing and the gradient descent method. The simultaneous property of these algorithms is ideally suited to parallel computing technologies.

Computer-aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli

PubMed Central

Nishio, Yousuke; Usuda, Yoshihiro; Matsui, Kazuhiko; Kurata, Hiroyuki

2008-01-01

The phosphotransferase system (PTS) is the sugar transportation machinery that is widely distributed in prokaryotes and is critical for enhanced production of useful metabolites. To increase the glucose uptake rate, we propose a rational strategy for designing the molecular architecture of the Escherichia coli glucose PTS by using a computer-aided design (CAD) system and verified the simulated results with biological experiments. CAD supports construction of a biochemical map, mathematical modeling, simulation, and system analysis. Assuming that the PTS aims at controlling the glucose uptake rate, the PTS was decomposed into hierarchical modules, functional and flux modules, and the effect of changes in gene expression on the glucose uptake rate was simulated to make a rational strategy of how the gene regulatory network is engineered. Such design and analysis predicted that the mlc knockout mutant with ptsI gene overexpression would greatly increase the specific glucose uptake rate. By using biological experiments, we validated the prediction and the presented strategy, thereby enhancing the specific glucose uptake rate. PMID:18197177

SU-G-TeP4-07: Automatic EPID-Based 2D Measurement of MLC Leaf Offset as a Quality Control Tool

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

Ritter, T; Moran, J; Schultz, B

Purpose: The MLC dosimetric leaf gap (DLG) and transmission are measured parameters which impact the dosimetric accuracy of IMRT and VMAT plans. This investigation aims to develop an efficient and accurate routine constancy check of the physical DLG in two dimensions. Methods: The manufacturer’s recommended DLG measurement method was modified by using 5 fields instead of 11 and by utilizing the Electronic Portal Imaging Device (EPID). Validations were accomplished using an ion chamber (IC) in solid water and a 2D IC array. EPID data was collected for 6 months on multiple TrueBeam linacs using both Millennium and HD MLCs atmore » 5 different clinics in an international consortium. Matlab code was written to automatically analyze the images and calculate the 2D results. Sensitivity was investigated by introducing deliberate leaf position errors. MLC calibration and initialization history was recorded to allow quantification of their impact. Results were analyzed using statistical process control (SPC). Results: The EPID method took approximately 5 minutes. Due to detector response, the EPID measured DLG and transmission differed from the IC values but were reproducible and consistent with changes measured using the ICs. For the Millennium MLC, the EPID measured DLG and transmission were both consistently lower than IC results. The EPID method was implemented as leaf offset and transmission constancy tests (LOC and TC). Based on 6 months of measurements, the initial leaf-specific action thresholds for changes from baseline were set to 0.1 mm. Upper and lower control limits for variation were developed for each machine. Conclusion: Leaf offset and transmission constancy tests were implemented on Varian HD and Millennium MLCs using an EPID and found to be efficient and accurate. The test is effective for monitoring MLC performance using dynamic delivery and performing process control on the DLG in 2D, thus enhancing dosimetric accuracy. This work was supported by a grant from Varian Medical Systems.« less

Mechanistic studies of a cell-permeant peptide designed to enhance myosin light chain phosphorylation in polarized intestinal epithelia.

PubMed

Almansour, Khaled; Taverner, Alistair; Eggleston, Ian M; Mrsny, Randall J

2018-06-10

Tight junction (TJ) structures restrict the movement of solutes between adjacent epithelial cells to maintain homeostatic conditions. A peptide, termed PIP 640, with the capacity to regulate the transient opening of intestinal TJ structures through an endogenous mechanism involving the induction of myosin light chain (MLC) phosphorylation at serine 19 (MLC-pS 19 ) has provided a promising new method to enhance the in vivo oral bioavailability of peptide therapeutics. PIP 640 is a decapeptide composed of all D-amino acids (rrdykvevrr-NH 2 ) that contains a central sequence designed to emulates a specific domain of C-kinase potentiated protein phosphatase-1 inhibitor-17 kDa (CPI-17) surrounded by positively-charged amino acids that provide a cell penetrating peptide (CPP)-like character. Here, we examine compositional requirements of PIP 640 with regard to its actions on MLC phosphorylation, its intracellular localization to TJ structures, and its interactions with MLC phosphatase (MLCP) elements that correlate with enhanced solute uptake. These studies showed that a glutamic acid and tyrosine within this peptide are critical for PIP 640 to retain its ability to increase MLC-pS 19 levels and enhance the permeability of macromolecular solutes of the size range of therapeutic peptides without detectable cytotoxicity. On the other hand, exchange of the aspartic acid for alanine and then arginine resulted in an increasingly greater bias toward protein phosphatase-1 (PP1) relative to MLCP inhibition, an outcome that resulted in increased paracellular permeability for solutes in the size range of therapeutic peptides, but with a significant increase in cytotoxicity. Together, these data further our understanding of the composition requirements of PIP 640 with respect to the desired goal of transiently altering the intestinal epithelial cell paracellular barrier properties through an endogenous mechanism, providing a novel approach to enhance the oral bioavailability of poorly absorbed therapeutic agents of < ~ 5 kDa. Copyright © 2018 Elsevier B.V. All rights reserved.

Role of Telokin in Regulating Murine Gastric Fundus Smooth Muscle Tension

PubMed Central

An, Changlong; Bhetwal, Bhupal P.; Sanders, Kenton M.; Somlyo, Avril V.; Perrino, Brian A.

2015-01-01

Telokin phosphorylation by cyclic GMP-dependent protein kinase facilitates smooth muscle relaxation. In this study we examined the relaxation of gastric fundus smooth muscles from basal tone, or pre-contracted with KCl or carbachol (CCh), and the phosphorylation of telokin S13, myosin light chain (MLC) S19, MYPT1 T853, T696, and CPI-17 T38 in response to 8-Bromo-cGMP, the NO donor sodium nitroprusside (SNP), or nitrergic neurotransmission. We compared MLC phosphorylation and the contraction and relaxation responses of gastric fundus smooth muscles from telokin-/- mice and their wild-type littermates to KCl or CCh, and 8-Bromo-cGMP, SNP, or nitrergic neurotransmission, respectively. We compared the relaxation responses and telokin phosphorylation of gastric fundus smooth muscles from wild-type mice and W/W V mice which lack ICC-IM, to 8-Bromo-cGMP, SNP, or nitrergic neurotransmission. We found that telokin S13 is basally phosphorylated and that 8-Bromo-cGMP and SNP increased basal telokin phosphorylation. In muscles pre-contracted with KCl or CCh, 8-Bromo-cGMP and SNP had no effect on CPI-17 or MYPT1 phosphorylation, but increased telokin phosphorylation and reduced MLC phosphorylation. In telokin-/- gastric fundus smooth muscles, basal tone and constitutive MLC S19 phosphorylation were increased. Pre-contracted telokin-/- gastric fundus smooth muscles have increased contractile responses to KCl, CCh, or cholinergic neurotransmission and reduced relaxation to 8-Bromo-cGMP, SNP, and nitrergic neurotransmission. However, basal telokin phosphorylation was not increased when muscles were stimulated with lower concentrations of SNP or when the muscles were stimulated by nitrergic neurotransmission. SNP, but not nitrergic neurotransmission, increased telokin Ser13 phosphorylation in both wild-type and W/W V gastric fundus smooth muscles. Our findings indicate that telokin may play a role in attenuating constitutive MLC phosphorylation and provide an additional mechanism to augment gastric fundus mechanical responses to inhibitory neurotransmission. PMID:26258553

SU-E-I-49: The Evaluation of Usability of Multileaf Collimator for Diagnostic Radiation in Cephalometric Exposure

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

Han, S; Kim, K; Jung, H

Purpose: This study evaluated usability of Multileaf collimator (MLC) for diagnostic radiation in cephalometric exposure using optical stimulated luminance dosimeters (OSLDs) Methods: The MLC material was made alloy tool steel (SKD-11) and the density of it is 7.89g/m3 that is similar to it of steel (Fe, 7.85 g/m3) and the MLC was attached to general radiography unit (Rex-650R, Listem Inc, Korea) for cephalometric exposure. The OSLDs that used were nanoDotTM Dosimeter (Landauer Inc, Glenwood, USA) and we read out OSLDs with micro star system (Landauer Inc, Glenwood, USA). The Optical annealing system contained fluorescent lamps (Osram lumilux, 24 W, 280more » ∼780 nm). To measure absorbed dose using OSLDs, was carried out dosimetric characteristics of OSLDs. Based on these, we evaluated dose reduction of critical organ (Eyes, Thyroids) with MLC in cephalometric exposure Results: The dosimetric characteristics were following that batch homogeneity was 1.21% and reproducibility was 0.96% of the coefficient of variation The linearity was that the correlation of between dose and count was fitted by linear function (dose,mGy = 0.00029 × Count, R2 =0.997). The range of angular dependence was from −3.6% to 3.7% variation when each degree was normalized by zero degree. The organ dose of Rt. eye, Lt eye, thyroids were 77.8 μGy, 337.0 μGy, 323.1μGy, respectively in open field and the dose reduction of organ dose was 10.6%(8.3μGy), 12.4 %(42 μGy), 87.1%(281.4μGy) with MLC Conclusion: We certified dose reduction of organ dose in cephalometric exposure. The dose reduction of Eye was 11% because of reduction of field size and it of thyroids was 87% by primary beam shielding.« less

SU-E-T-774: Use of a Scintillator-Mirror-Camera System for the Measurement of MLC Leakage Radiation with the CyberKnife M6 System

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

Goggin, L; Kilby, W; Noll, M

2015-06-15

Purpose: A technique using a scintillator-mirror-camera system to measure MLC leakage was developed to provide an efficient alternative to film dosimetry while maintaining high spatial resolution. This work describes the technique together with measurement uncertainties. Methods: Leakage measurements were made for the InCise™ MLC using the Logos XRV-2020A device. For each measurement approximately 170 leakage and background images were acquired using optimized camera settings. Average background was subtracted from each leakage frame before filtering the integrated leakage image to replace anomalous pixels. Pixel value to dose conversion was performed using a calibration image. Mean leakage was calculated within an ROImore » corresponding to the primary beam, and maximum leakage was determined by binning the image into overlapping 1mm x 1mm ROIs. 48 measurements were performed using 3 cameras and multiple MLC-linac combinations in varying beam orientations, with each compared to film dosimetry. Optical and environmental influences were also investigated. Results: Measurement time with the XRV-2020A was 8 minutes vs. 50 minutes using radiochromic film, and results were available immediately. Camera radiation exposure degraded measurement accuracy. With a relatively undamaged camera, mean leakage agreed with film measurement to ≤0.02% in 92% cases, ≤0.03% in 100% (for maximum leakage the values were 88% and 96%) relative to reference open field dose. The estimated camera lifetime over which this agreement is maintained is at least 150 measurements, and can be monitored using reference field exposures. A dependency on camera temperature was identified and a reduction in sensitivity with distance from image center due to optical distortion was characterized. Conclusion: With periodic monitoring of the degree of camera radiation damage, the XRV-2020A system can be used to measure MLC leakage. This represents a significant time saving when compared to the traditional film-based approach without any substantial reduction in accuracy.« less

Inhibition of the AMP-activated protein kinase-α2 accentuates agonist-induced vascular smooth muscle contraction and high blood pressure in mice.

PubMed

Wang, Shuangxi; Liang, Bin; Viollet, Benoit; Zou, Ming-Hui

2011-05-01

The aim of the present study was to determine the effects and molecular mechanisms by which AMP-activated protein kinase (AMPK) regulates smooth muscle contraction and blood pressure in mice. In cultured human vascular smooth muscle cells, we observed that activation of AMPK by 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside inhibited agonist-induced phosphorylation of myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1). Conversely, AMPK inhibition with pharmacological or genetic means potentiated agonist-induced the phosphorylation of MLC and MYPT1, whereas it inhibited both Ras homolog gene family member A and Rho-associated kinase activity. In addition, AMPK activation or Rho-associated kinase inhibition with Y27632 abolished agonist-induced phosphorylation of MLC and MYPT1. Gene silencing of p190-guanosine triphosphatase-activating protein abolished the effects of AMPK activation on MLC, MYPT1, and Ras homolog gene family member A in human smooth muscle cells. Ex vivo analyses revealed that agonist-induced contractions of the mesenteric artery and aortas were stronger in both AMPKα1(-/-) and AMPKα2(-/-) knockout mice than in wild-type mice. Inhibition of Rho-associated kinase with Y27632 normalized agonist-induced contractions of AMPKα1(-/-) and AMPKα2(-/-) vessels. AMPKα2(-/-) mice had higher blood pressure along with decreased serine phosphorylation of p190-guanosine triphosphatase-activating protein. Finally, inhibition of the Ras homolog gene family member A/Rho-associated kinase pathway with Y27632, which suppressed MYPT1 and MLC phosphorylation, lowered blood pressure in AMPKα2(-/-) mice. In conclusion, AMPK decreases vascular smooth muscle cell contractility by inhibiting p190-GTP-activating protein-dependent Ras homolog gene family member A activation, indicating that AMPK may be a new therapeutic target in lowering high blood pressure.

Peripheral doses from pediatric IMRT

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

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

Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 tomore » 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged from 0.47-0.94) doses {approx}[0.4-1.8 cGy]/[0.9-2.9 cGy]/fraction, respectively. Prior phantom reports are for fields 10 cm or greater, while pediatric central nervous system fields range from 4 to 7 cm, and effectively much smaller for IMRT (2-6 cm). Peripheral dose in close proximity (<10 cm from the field edge) is dominated by internal scatter; therefore, field-size differences overwhelm phantom size affects and increased MU. Distant peripheral dose, dominated by head leakage, was higher than predicted, even when accounting for MUs ({approx}factor of 3) likely due to the pediatric phantom size. The ratio of the testes dose ranged from 3.3-5.3 for IMRT/conventional. PD to OAR for pediatric IMRT cannot be predicted from large-field full phantom studies. For regional OAR, doses are likely lower than predicted by existing ''large field'' data, while the distant PD is higher.« less

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% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When {+-}20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. Conclusions: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.« less

Zinc supplementation induces CD4+CD25+Foxp3+ antigen-specific regulatory T cells and suppresses IFN-γ production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1.

PubMed

Maywald, Martina; Rink, Lothar

2017-08-01

The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures (MLC), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. Cell proliferation and pro-inflammatory cytokine production were monitored by [ 3 H]-thymidine proliferation assay and ELISA, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and mRNA analysis were used for Foxp3, KLF-10, and IRF-1 expression. Zinc supplementation on antigen-specific T cells in physiological doses (50 µM) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on MLC results in an increased induction and stabilization of CD4 + CD25 + Foxp3 + and CD4 + CD25 + CTLA-4 + T cells (p < 0.05). The effect is based on zinc-induced upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. However, in resting lymphocytes zinc increases IRF-1. In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific iTreg cells due to modulation of essential molecular targets: Foxp3, KLF-10, and IRF-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions.

A spectroscopic ellispometric study of the tunability of the optical constants and thickness of GeO{sub x} films with swift heavy ions

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

Vijayarangamuthu, K.; Singh, Chaman; Rath, Shyama

2011-09-15

Sub-stoichiometric GeO{sub x} films were fabricated by electron-beam evaporation method. The films were irradiated with 100 MeV Ag{sup 7+} ions at fluences between 1 x 10{sup 12} and 1 x 10{sup 14} ions-cm{sup -2}. Spectroscopic ellipsometric measurements were performed in air at room temperature. The values of the layer thickness and refractive index were extracted from ellipsometry using a multilayer analysis and the Tauc Lorentz model. The refractive index (at 633 nm) of the as-deposited GeO{sub x} film was estimated to be 1.860 and decreased to 1.823 for films irradiated at an ion fluence of 1 x 10{sup 14} ions-cm{supmore » -2}. The thickness of the films also decreased after irradiation and is due to a sputtering induced by the ion beam. The change in the refractive index with ion fluence is attributed to a stoichiometric change and structural transformation represented by GeO{sub x}{yields} Ge + GeO{sub y} (y > x) occurring due to a thermal spike induced by ion irradiation. Swift heavy ions thus provide a scope for modulating the refractive index of GeO{sub x} films. The thickness and stoichiometric changes are supported by Rutherford backscattering measurements.« less

Derivative-free generation and interpolation of convex Pareto optimal IMRT plans

NASA Astrophysics Data System (ADS)

Hoffmann, Aswin L.; Siem, Alex Y. D.; den Hertog, Dick; Kaanders, Johannes H. A. M.; Huizenga, Henk

2006-12-01

In inverse treatment planning for intensity-modulated radiation therapy (IMRT), beamlet intensity levels in fluence maps of high-energy photon beams are optimized. Treatment plan evaluation criteria are used as objective functions to steer the optimization process. Fluence map optimization can be considered a multi-objective optimization problem, for which a set of Pareto optimal solutions exists: the Pareto efficient frontier (PEF). In this paper, a constrained optimization method is pursued to iteratively estimate the PEF up to some predefined error. We use the property that the PEF is convex for a convex optimization problem to construct piecewise-linear upper and lower bounds to approximate the PEF from a small initial set of Pareto optimal plans. A derivative-free Sandwich algorithm is presented in which these bounds are used with three strategies to determine the location of the next Pareto optimal solution such that the uncertainty in the estimated PEF is maximally reduced. We show that an intelligent initial solution for a new Pareto optimal plan can be obtained by interpolation of fluence maps from neighbouring Pareto optimal plans. The method has been applied to a simplified clinical test case using two convex objective functions to map the trade-off between tumour dose heterogeneity and critical organ sparing. All three strategies produce representative estimates of the PEF. The new algorithm is particularly suitable for dynamic generation of Pareto optimal plans in interactive treatment planning.

Diffraction-assisted micropatterning of silicon surfaces by ns-laser irradiation

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

Haro-Poniatowski, E., E-mail: haro@xanum.uam.mx; Acosta-Zepeda, C.; Mecalco, G.

2014-06-14

Single-pulse (532 nm, 8 ns) micropatterning of silicon with nanometric surface modulation is demonstrated by irradiating through a diffracting pinhole. The irradiation results obtained at fluences above the melting threshold are characterized by scanning electron and scanning force microscopy and reveal a good agreement with Fresnel diffraction theory. The physical mechanism is identified and discussed on basis of both thermocapillary and chemicapillary induced material transport during the molten state of the surface.

Plan averaging for multicriteria navigation of sliding window IMRT and VMAT

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

Craft, David, E-mail: dcraft@partners.org; Papp, Dávid; Unkelbach, Jan

2014-02-15

Purpose: To describe a method for combining sliding window plans [intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT)] for use in treatment plan averaging, which is needed for Pareto surface navigation based multicriteria treatment planning. Methods: The authors show that by taking an appropriately defined average of leaf trajectories of sliding window plans, the authors obtain a sliding window plan whose fluence map is the exact average of the fluence maps corresponding to the initial plans. In the case of static-beam IMRT, this also implies that the dose distribution of the averaged plan is the exact dosimetricmore » average of the initial plans. In VMAT delivery, the dose distribution of the averaged plan is a close approximation of the dosimetric average of the initial plans. Results: The authors demonstrate the method on three Pareto optimal VMAT plans created for a demanding paraspinal case, where the tumor surrounds the spinal cord. The results show that the leaf averaged plans yield dose distributions that approximate the dosimetric averages of the precomputed Pareto optimal plans well. Conclusions: The proposed method enables the navigation of deliverable Pareto optimal plans directly, i.e., interactive multicriteria exploration of deliverable sliding window IMRT and VMAT plans, eliminating the need for a sequencing step after navigation and hence the dose degradation that is caused by such a sequencing step.« less

Production of clinically useful positron emitter beams during carbon ion deceleration.

PubMed

Lazzeroni, M; Brahme, A

2011-03-21

In external beam radiation therapy, radioactive beams offer the best clinical solution to simultaneously treat and in vivo monitor the dose delivery and tumor response using PET or PET-CT imaging. However, difficulties mainly linked to the low production efficiency have so far limited their use. This study is devoted to the analysis of the production of high energy (11)C fragments, preferably by projectile fragmentation of a stable monodirectional and monoenergetic primary (12)C beam in different absorbing materials (decelerators) in order to identify the optimal elemental composition. The study was performed using the Monte Carlo code SHIELD-HIT07. The track length and fluence of generated secondary particles were scored in a uniform absorber of 300 cm length and 10 cm radius, divided into slices of 1 cm thickness. The (11)C fluence build-up and mean energy variation with increasing decelerator depth are presented. Furthermore, the fluence of the secondary (11)C beam was studied as a function of its mean energy and the corresponding remaining range in water. It is shown that the maximum (11)C fluence build-up is high in compounds where the fraction by weight of hydrogen is high, being the highest in liquid hydrogen. Furthermore, a cost effective alternative solution to the single medium initially envisaged is presented: a two-media decelerator that comprises a first liquid hydrogen section followed by a second decelerating section made of a hydrogen-rich material, such as polyethylene (C(2)H(4)). The purpose of the first section is to achieve a fast initial (11)C fluence build-up, while the second section is primarily designed to modulate the mean energy of the generated (11)C beam in order to reach the tumor depth. Finally, it was demonstrated that, if the intensity of the primary (12)C beam can be increased by an order of magnitude, a sufficient intensity of the secondary (11)C beam is achieved for therapy and subsequent therapeutic PET imaging sessions. Such an increase in the intensity might be easily achieved with a superconducting cyclotron.

Metal nanostructures with complex surface morphology: The case of supported lumpy Pd and Pt nanoparticles produced by laser processing of metal films

NASA Astrophysics Data System (ADS)

Ruffino, F.; Maugeri, P.; Cacciato, G.; Zimbone, M.; Grimaldi, M. G.

2016-09-01

In this work we report on the formation of lumpy Pd and Pt nanoparticles on fluorine-doped tin oxide/glass (FTO/glass) substrate by a laser-based approach. In general, complex-surface morphology metal nanoparticles can be used in several technological applications exploiting the peculiarities of their physical properties as modulated by nanoscale morphology. For example plasmonic metal nanoparticles presenting a lumpy morphology (i.e. larger particles coated on the surface by smaller particles) can be used in plasmonic solar cell devices providing broadband scattering enhancement over the smooth nanoparticles leading, so, to the increase of the device efficiency. However, the use of plasmonic lumpy nanoparticles remains largely unexplored due to the lack of simply, versatile, low-cost and high-throughput methods for the controllable production of such nanostructures. Starting from these considerations, we report on the observation that nanoscale-thick Pd and Pt films (17.6 and 27.9 nm, 12.1 and 19.5 nm, respectively) deposited on FTO/glass surface irradiated by nanosecond pulsed laser at fluences E in the 0.5-1.5 J/cm2 range, produce Pd and Pt lumpy nanoparticles on the FTO surface. In addition, using scanning electron microscopy analyses, we report on the observation that starting from each metal film of fixed thickness h, the fraction F of lumpy nanoparticles increases with the laser fluence E and saturates at the higher fluences. For each fixed fluence, F was found higher starting from the Pt films (at each starting film thickness h) with respect to the Pd films. For each fixed metal and fluence, F was found to be higher decreasing the starting thickness of the deposited film. To explain the formation of the lumpy Pd and Pt nanoparticles and the behavior of F as a function of E and h both for Pd and Pt, the thermodynamic behavior of the Pd and Pt films and nanoparticles due to the interaction with the nanosecond laser is discussed. In particular, the photothermal vaporization and Coulomb explosion processes of the Pd and Pt nanoparticles are invoked as possible mechanisms for the lumpy nanoparticles formation.

Neutron Radiation Damage Estimation in the Core Structure Base Metal of RSG GAS

NASA Astrophysics Data System (ADS)

Santa, S. A.; Suwoto

2018-02-01

Radiation damage in core structure of the Indonesian RGS GAS multi purpose reactor resulting from the reaction of fast and thermal neutrons with core material structure was investigated for the first time after almost 30 years in operation. The aim is to analyze the degradation level of the critical components of the RSG GAS reactor so that the remaining life of its component can be estimated. Evaluation results of critical components remaining life will be used as data ccompleteness for submission of reactor operating permit extension. Material damage analysis due to neutron radiation is performed for the core structure components made of AlMg3 material and bolts reinforcement of core structure made of SUS304. Material damage evaluation was done on Al and Fe as base metal of AlMg3 and SUS304, respectively. Neutron fluences are evaluated based on the assumption that neutron flux calculations of U3Si8-Al equilibrium core which is operated on power rated of 15 MW. Calculation result using SRAC2006 code of CITATION module shows the maximum total neutron flux and flux >0.1 MeV are 2.537E+14 n/cm2/s and 3.376E+13 n/cm2/s, respectively. It was located at CIP core center close to the fuel element. After operating up to the end of #89 core formation, the total neutron fluence and fluence >0.1 MeV were achieved 9.063E+22 and 1.269E+22 n/cm2, respectively. Those are related to material damage of Al and Fe as much as 17.91 and 10.06 dpa, respectively. Referring to the life time of Al-1100 material irradiated in the neutron field with thermal flux/total flux=1.7 which capable of accepting material damage up to 250 dpa, it was concluded that RSG GAS reactor core structure underwent 7.16% of its operating life span. It means that core structure of RSG GAS reactor is still capable to receive the total neutron fluence of 9.637E+22 n/cm2 or fluence >0.1 MeV of 5.672E+22 n/cm2.

Validation of a method for in vivo 3D dose reconstruction for IMRT and VMAT treatments using on-treatment EPID images and a model-based forward-calculation algorithm

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

Van Uytven, Eric, E-mail: eric.vanuytven@cancercare.mb.ca; Van Beek, Timothy; McCowan, Peter M.

2015-12-15

Purpose: Radiation treatments are trending toward delivering higher doses per fraction under stereotactic radiosurgery and hypofractionated treatment regimens. There is a need for accurate 3D in vivo patient dose verification using electronic portal imaging device (EPID) measurements. This work presents a model-based technique to compute full three-dimensional patient dose reconstructed from on-treatment EPID portal images (i.e., transmission images). Methods: EPID dose is converted to incident fluence entering the patient using a series of steps which include converting measured EPID dose to fluence at the detector plane and then back-projecting the primary source component of the EPID fluence upstream of themore » patient. Incident fluence is then recombined with predicted extra-focal fluence and used to calculate 3D patient dose via a collapsed-cone convolution method. This method is implemented in an iterative manner, although in practice it provides accurate results in a single iteration. The robustness of the dose reconstruction technique is demonstrated with several simple slab phantom and nine anthropomorphic phantom cases. Prostate, head and neck, and lung treatments are all included as well as a range of delivery techniques including VMAT and dynamic intensity modulated radiation therapy (IMRT). Results: Results indicate that the patient dose reconstruction algorithm compares well with treatment planning system computed doses for controlled test situations. For simple phantom and square field tests, agreement was excellent with a 2%/2 mm 3D chi pass rate ≥98.9%. On anthropomorphic phantoms, the 2%/2 mm 3D chi pass rates ranged from 79.9% to 99.9% in the planning target volume (PTV) region and 96.5% to 100% in the low dose region (>20% of prescription, excluding PTV and skin build-up region). Conclusions: An algorithm to reconstruct delivered patient 3D doses from EPID exit dosimetry measurements was presented. The method was applied to phantom and patient data sets, as well as for dynamic IMRT and VMAT delivery techniques. Results indicate that the EPID dose reconstruction algorithm presented in this work is suitable for clinical implementation.« less

Evaluation of the dose calculation accuracy for small fields defined by jaw or MLC for AAA and Acuros XB algorithms.

PubMed

Fogliata, Antonella; Lobefalo, Francesca; Reggiori, Giacomo; Stravato, Antonella; Tomatis, Stefano; Scorsetti, Marta; Cozzi, Luca

2016-10-01

Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis. Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 ; MLC-defined: 0.5 × 0.5 cm 2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 . MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed. Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm 2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm 2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the best agreement averaged over all the energies, of -3.9% and 0.2% for a 1 × 1 cm 2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 0 mm for both directions and both algorithms. For optimal setting applied in the algorithm configuration phase, the agreement of Acuros calculations with measurements could achieve the 3% for MLC-defined fields as small as 0.5 × 0.5 cm 2 . Similar agreement was found for AAA for fields as small as 1 × 1 cm 2 .

Minimizing dose variation from the interplay effect in stereotactic radiation therapy using volumetric modulated arc therapy for lung cancer.

PubMed

Kubo, Kazuki; Monzen, Hajime; Tamura, Mikoto; Hirata, Makoto; Ishii, Kentaro; Okada, Wataru; Nakahara, Ryuta; Kishimoto, Shun; Kawamorita, Ryu; Nishimura, Yasumasa

2018-03-01

It is important to improve the magnitude of dose variation that is caused by the interplay effect. The aim of this study was to investigate the impact of the number of breaths (NBs) to the dose variation for VMAT-SBRT to lung cancer. Data on respiratory motion and multileaf collimator (MLC) sequence were collected from the cases of 30 patients who underwent radiotherapy with VMAT-SBRT for lung cancer. The NBs in the total irradiation time with VMAT and the maximum craniocaudal amplitude of the target were calculated. The MLC sequence complexity was evaluated using the modulation complexity score for VMAT (MCSv). Static and dynamic measurements were performed using a cylindrical respiratory motion phantom and a micro ionization chamber. The 1 standard deviation which were obtained from 10 dynamic measurements for each patient were defined as dose variation caused by the interplay effect. The dose distributions were also verified with radiochromic film to detect undesired hot and cold dose spot. Dose measurements were also performed with different NBs in the same plan for 16 patients in 30 patients. The correlations between dose variations and parameters assessed for each treatment plan including NBs, MCSv, the MCSv/amplitude quotient (TMMCSv), and the MCSv/amplitude quotient × NBs product (IVS) were evaluated. Dose variation was decreased with increasing NBs, and NBs of >40 times maintained the dose variation within 3% in 15 cases. The correlation between dose variation and IVS which were considered NBs was shown stronger (R 2  = 0.43, P < 0.05) than TMMCSv (R 2  = 0.32, P < 0.05). The NBs is an important factor to reduce the dose variation. The patient who breathes >40 times during irradiation of two partial arcs VMAT (i.e., NBs = 16 breaths per minute) may be suitable for VMAT-SBRT for lung cancer. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Adaptive intensity modulated radiotherapy for advanced prostate cancer

NASA Astrophysics Data System (ADS)

Ludlum, Erica Marie

The purpose of this research is to develop and evaluate improvements in intensity modulated radiotherapy (IMRT) for concurrent treatment of prostate and pelvic lymph nodes. The first objective is to decrease delivery time while maintaining treatment quality, and evaluate the effectiveness and efficiency of novel one-step optimization compared to conventional two-step optimization. Both planning methods are examined at multiple levels of complexity by comparing the number of beam apertures, or segments, the amount of radiation delivered as measured by monitor units (MUs), and delivery time. One-step optimization is demonstrated to simplify IMRT planning and reduce segments (from 160 to 40), MUs (from 911 to 746), and delivery time (from 22 to 7 min) with comparable plan quality. The second objective is to examine the capability of three commercial dose calculation engines employing different levels of accuracy and efficiency to handle high--Z materials, such as metallic hip prostheses, included in the treatment field. Pencil beam, convolution superposition, and Monte Carlo dose calculation engines are compared by examining the dose differences for patient plans with unilateral and bilateral hip prostheses, and for phantom plans with a metal insert for comparison with film measurements. Convolution superposition and Monte Carlo methods calculate doses that are 1.3% and 34.5% less than the pencil beam method, respectively. Film results demonstrate that Monte Carlo most closely represents actual radiation delivery, but none of the three engines accurately predict the dose distribution when high-Z heterogeneities exist in the treatment fields. The final objective is to improve the accuracy of IMRT delivery by accounting for independent organ motion during concurrent treatment of the prostate and pelvic lymph nodes. A leaf-shifting algorithm is developed to track daily prostate position without requiring online dose calculation. Compared to conventional methods of adjusting patient position, adjusting the multileaf collimator (MLC) leaves associated with the prostate in each segment significantly improves lymph node dose coverage (maintains 45 Gy compared to 42.7, 38.3, and 34.0 Gy for iso-shifts of 0.5, 1 and 1.5 cm). Altering the MLC portal shape is demonstrated as a new and effective solution to independent prostate movement during concurrent treatment.

Modulation of smooth muscle tonus in the lower urinary tract: interplay of myosin light-chain kinase (MLCK) and MLC phosphatase (MLCP).

PubMed

Lin, Guiting; Fandel, Thomas M; Shindel, Alan W; Wang, Guifang; Banie, Lia; Ning, Hongxiu; Lue, Tom F; Lin, Ching-Shwun

2011-07-01

To assess and compare the expression and activity of myosin light-chain kinase (MLCK) and MLC phosphatase (MLCP) in rat bladder and urethra. Bladder and urethral smooth muscles were obtained from 2-month-old female Sprague-Dawley rats. They were analysed by real-time polymerase chain reaction for the mRNA expression of MLCK and myosin phosphatase-targeting subunit of protein phosphatase type 1 (MYPT1, a subunit of MLCP). Levels of MLCK and MYPT1 mRNA expression were determined as a ratio to the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The tissues were also analysed by Western blotting for MLCK and MYPT1 protein expression as a ratio to the expression of β-actin. A two-step enzymatic activity assay using phosphorylated and dephosphorylated smooth muscle myosin was used to assess MLCK and MLCP activity. MLCK mRNA expression was higher in the bladder than in the urethra [mean (sd) ratio to GAPDH: 0.26 (0.17) vs 0.14 (0.12); P = 0.09]. MYPT1 mRNA expression was significantly higher in the bladder than in the urethra [mean (sd) ratio to GAPDH: 2.31 (1.04) vs 0.56 (0.36); P = 0.001]. Expression of both MLCK and MYPT1 protein was significantly higher in the bladder compared with the urethra [mean (sd) ratio to β-actin: 1.63 (0.25) vs 0.91 (0.29) and 0.97 (0.10) vs 0.37 (0.29), respectively; both P < 0.001]. Enzymatic assay identified significantly greater MLCK activity in the bladder than in the urethra. While, MLCP activity was lower in the bladder than in the urethra. In healthy young female rats, MLCK activity is higher and MLCP activity is lower in the bladder relative to the urethra. These differences probably play a role in modulating the functional differences between bladder and urethral smooth muscle tone. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

[Ambulatory laparoscopic cholecystectomy by minilaparoscopy versus traditional multiport ambulatory laparoscopic cholecystectomy. Prospective randomized trial].

PubMed

Planells Roig, Manuel; Arnal Bertomeu, Consuelo; Garcia Espinosa, Rafael; Cervera Delgado, Maria; Carrau Giner, Miguel

2016-02-01

Difference analysis of ambulatorization rate, pain, analgesic requirements and daily activities recovery in patients undergoing laparoscopic cholecystectomy with standard multiport access (CLMP) versus a minilaparoscopic, 3mm size, technique. Prospective randomized trial of 40 consecutive patients undergoing laparoscopic cholecystectomy. Comparison criteria included predictive ultrasound factors of difficult cholecystectomy, previous history of complicated biliary disease and demographics. Results are analyzed in terms of ambulatorization rate, pain, analgesic requirements, postoperative recovery, technical difficulty, hemorrhage intensity, overnight stay, readmission rate and total or partial conversion. Both procedures were similar in surgery time, technical score and hemorrhage score. MLC was associated with similar ambulatorization rate, 85%, and over-night stay 15%, with only 15% partial conversion rate. MLC showed less postoperative pain (P=.026), less analgesic consumption (P=.006) and similar DAR (P=.879). MLC is similar to CLMP in terms of ambulatorization with less postoperative pain and analgesic requirements without differences in postoperative recovery. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Trastuzumab Alters the Expression of Genes Essential for Cardiac Function and Induces Ultrastructural Changes of Cardiomyocytes in Mice

PubMed Central

ElZarrad, M. Khair; Mukhopadhyay, Partha; Mohan, Nishant; Hao, Enkui; Dokmanovic, Milos; Hirsch, Dianne S.; Shen, Yi; Pacher, Pal; Wu, Wen Jin

2013-01-01

Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity. PMID:24255707

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

Duan, J

Purpose: The aim of this work is to study the dosimetric impact of leaf interdigitation in prostate cancer dynamic IMRT treatment planning. Methods: Fifteen previously treated prostate cancer patients were replanned for dynamic IMRT (dMLC) with and without leaf interdigitation using Monaco 3.3 TPS on the Elekta Synergy linear accelerator. The prescription dose of PTV was 70Gy/35 fractions. Various dosimetric variables, such as PTV coverage, OAR sparing, delivery efficiency and optimization time, were evaluated for each plan. Results: Interdigitation did not improve the coverage, HI and CI for PTV. Regarding OARs, sparing was equivalent with and without interdigitation. Interdigitation shownmore » an increase in MUs and segments. It was worth noting that leaf interdigitation saved the optimization time. Conclusion: This study shows that leaf interdigitation does not improve plan quality when performing dMLC treatment plan for prostate cancer. However, it influences delivery efficiency and optimization time. Interdigitation may gain efficiency for dosimetrist when designing the prostate cancer dMLC plans.« less

Comparison of two Classification methods (MLC and SVM) to extract land use and land cover in Johor Malaysia

NASA Astrophysics Data System (ADS)

Rokni Deilmai, B.; Ahmad, B. Bin; Zabihi, H.

2014-06-01

Mapping is essential for the analysis of the land use and land cover, which influence many environmental processes and properties. For the purpose of the creation of land cover maps, it is important to minimize error. These errors will propagate into later analyses based on these land cover maps. The reliability of land cover maps derived from remotely sensed data depends on an accurate classification. In this study, we have analyzed multispectral data using two different classifiers including Maximum Likelihood Classifier (MLC) and Support Vector Machine (SVM). To pursue this aim, Landsat Thematic Mapper data and identical field-based training sample datasets in Johor Malaysia used for each classification method, which results indicate in five land cover classes forest, oil palm, urban area, water, rubber. Classification results indicate that SVM was more accurate than MLC. With demonstrated capability to produce reliable cover results, the SVM methods should be especially useful for land cover classification.

Irradiation at 660 nm modulates different genes central to wound healing in wounded and diabetic wounded cell models

NASA Astrophysics Data System (ADS)

Houreld, Nicolette N.

2014-02-01

Wound healing is a highly orchestrated process and involves a wide variety of cellular components, chemokines and growth factors. Laser irradiation has influenced gene expression and release of various growth factors, cytokines and extracellular matrix proteins involved in wound healing. This study aimed to determine the expression profile of genes involved in wound healing in wounded and diabetic wounded fibroblast cells in response to irradiation at a wavelength of 660 nm. Human skin fibroblast cells (WS1) were irradiated with a diode laser (wavelength 660 nm; fluence 5 J/cm2; power output 100 mW; power density 11 mW/cm2; spot size 9.1 cm2; exposure duration 7 min 35 s). Total RNA was isolated and 1 μg reverse transcribed into cDNA which was used as a template in real-time qualitative polymerase chain reaction (qPCR). Eighty four genes involved in wound healing (extracellular matrix and cell adhesion; inflammatory cytokines and chemokines; growth factors; and signal transduction) were evaluated in wounded and diabetic wounded cell models. Forty eight hours post-irradiation, 6 genes were significantly upregulated and 8 genes were down-regulated in irradiated wounded cells, whereas 1 gene was up-regulated and 33 genes down-regulated in irradiated diabetic wounded cells. Irradiation of stressed fibroblast cells to a wavelength of 660 nm and a fluence of 5 J/cm2 modulated the expression of different genes involved in wound healing in different cell models. Modulation of these genes leads to the effects of laser irradiation seen both in vivo and in vitro, and facilitates the wound healing process.

[Overexpression of LaeA enhances mevastatin production and reduces sporulation of Penicillium citrinum].

PubMed

Zheng, Yueliang; Cao, Shuang; Huang, Yuqi; Liao, Guojian; Hu, Changhua

2014-12-04

To study the regulation of laeA overexpression on mevastatin production and sporulation in Penicillium citrinum. We cloned the laeA gene from Penicillium citrinum and constructed the vector pGiHTGi-laeA. The plasmid pGiHTGi-laeA was transformed in Penicillium citrinum by agrobacterium tumefaciens-mediated transformation. Positive transformants were detected by cloning the hygromycin gene. The mevastatin production of the wild type and OE:: laeA was compared by HPLC. The conidia number was counted by blood counting chamber. The biosynthetic gene cluster expression quantity of mevastatin in the wild type and OE: :laeA were analyzed by qRT-PCR. We constructed the plasmid pGiHTGi-laeA, and screened the positive transformants that overexpress the laeA in Penicillium citrinum. With the overexpression of laeA, the mevastatin production was increased from (0.69 ± 0.12) mg/g to (4.02 ± 0.50) mg/g dry cell weight. Compared to the wild type strain, the laeA expression quantity in the OE :: laeA strain increased 29%, and the mlcB expression increased 72%, the mlcR expression increased 153%. Moreover, the overexpression of laeA would decrease the conidia number. Overexpression of LaeA enhances mevastatin production and reduces sporulation of Penicillium citrinum, with increases expression of pathway-regulator mlcR, and biosynthetic gene MlcR. These results could guide global regulatory mechanism of mevastatin biosynthesis and the exploitation of high-production strain.

Airborne particulate matter in vitro exposure induces cytoskeleton remodeling through activation of the ROCK-MYPT1-MLC pathway in A549 epithelial lung cells.

PubMed

Chirino, Yolanda I; García-Cuellar, Claudia María; García-García, Carlos; Soto-Reyes, Ernesto; Osornio-Vargas, Álvaro Román; Herrera, Luis A; López-Saavedra, Alejandro; Miranda, Javier; Quintana-Belmares, Raúl; Pérez, Irma Rosas; Sánchez-Pérez, Yesennia

2017-04-15

Airborne particulate matter with an aerodynamic diameter ≤10μm (PM 10 ) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM 10 is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM 10 exposure in A549 lung epithelial cells. Results showed that 10μg/cm 2 of PM 10 had no influence on cell viability but increased actin stress fibers, cytoplasmic ROCK expression, and phosphorylation of myosin phosphatase-targeting 1 (MYPT1) and myosin light chain (MLC) proteins, which are targeted by ROCK. The inhibition of ROCK prevented actin stress fiber formation and the phosphorylation of MYPT1 and MLC, suggesting that PM 10 activated the ROCK-MYPT1-MLC pathway in lung epithelial cells. The activation of ROCK1 has been involved in the acquisition of malignant phenotypes, and its induction by PM 10 exposure could contribute to the understanding of PM 10 as a risk factor for cancer development through the mechanisms associated with invasive phenotype. Copyright © 2017 Elsevier B.V. All rights reserved.

TH-AB-202-03: A Novel Tool for Computing Deliverable Doses in Dynamic MLC Tracking Treatments

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

Fast, M; Kamerling, C; Menten, M

2016-06-15

Purpose: In tracked dynamic multi-leaf collimator (MLC) treatments, segments are continuously adapted to the target centroid motion in beams-eye-view. On-the-fly segment adaptation, however, potentially induces dosimetric errors due to the finite MLC leaf width and non-rigid target motion. In this study, we outline a novel tool for computing the 4d dose of lung SBRT plans delivered with MLC tracking. Methods: The following automated workflow was developed: A) centroid tracking, where the initial segments are morphed to each 4dCT phase based on the beams-eye-view GTV shift (followed by a dose calculation on each phase); B) re-optimized tracking, in which all morphedmore » initial plans from (A) are further optimised (“warm-started”) in each 4dCT phase using the initial optimisation parameters but phase-specific volume definitions. Finally, both dose sets are accumulated to the reference phase using deformable image registration. Initial plans were generated according to the RTOG-1021 guideline (54Gy, 3-Fx, equidistant 9-beam IMRT) on the peak-exhale (reference) phase of a phase-binned 4dCT. Treatment planning and delivery simulations were performed in RayStation (research v4.6) using our in-house segment-morphing algorithm, which directly links to RayStation through a native C++ interface. Results: Computing the tracking plans and 4d dose distributions via the in-house interface takes 5 and 8 minutes respectively for centroid and re-optimized tracking. For a sample lung SBRT patient with 14mm peak-to-peak motion in sup-inf direction, mainly perpendicular leaf motion (0-collimator) resulted in small dose changes for PTV-D95 (−13cGy) and GTV-D98 (+18cGy) for the centroid tracking case compared to the initial plan. Modest reductions of OAR doses (e.g. spinal cord D2: −11cGy) were achieved in the idealized tracking case. Conclusion: This study presents an automated “1-click” workflow for computing deliverable MLC tracking doses in RayStation. Adding a non-deliverable re-optimized tracking scenario is expected to help quantify plan robustness for more challenging patients with anatomy deformations. We acknowledge support of the MLC tracking research from Elekta AB. MFF is supported by Cancer Research UK under Programme C33589/A19908. Research at ICR is also supported by Cancer Research UK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR.« less

SU-G-BRA-16: Target Dose Comparison for Dynamic MLC Tracking and Mid- Ventilation Planning in Lung Radiotherapy Subject to Intrafractional Baseline Drifts

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

Menten, MJ; Fast, MF; Nill, S

Purpose: Lung tumor motion during radiotherapy can be accounted for by expanded treatment margins, for example using a mid-ventilation planning approach, or by localizing the tumor in real-time and adapting the treatment beam with multileaf collimator (MLC) tracking. This study evaluates the effect of intrafractional changes in the average tumor position (baseline drifts) on these two treatment techniques. Methods: Lung stereotactic treatment plans (9-beam IMRT, 54Gy/3 fractions, mean treatment time: 9.63min) were generated for three patients: either for delivery with MLC tracking (isotropic GTV-to-PTV margin: 2.6mm) or planned with a mid-ventilation approach and delivered without online motion compensation (GTV-to-PTV margin:more » 4.4-6.3mm). Delivery to a breathing patient was simulated using DynaTrack, our in-house tracking and delivery software. Baseline drifts in cranial and posterior direction were simulated at a rate of 0.5, 1.0 or 1.5mm/min. For dose reconstruction, the corresponding 4DCT phase was selected for each time point of the delivery. Baseline drifts were accounted for by rigidly shifting the CT to ensure correct relative beam-to-target positioning. Afterwards, the doses delivered to each 4DCT phase were accumulated deformably on the mid-ventilation phase using research RayStation v4.6 and dose coverage of the GTV was evaluated. Results: When using the mid-ventilation planning approach, dose coverage of the tumor deteriorated substantially in the presence of baseline drifts. The reduction in D98% coverage of the GTV in a single fraction ranged from 0.4-1.2, 0.6-3.3 and 4.5-6.2Gy, respectively, for the different drift rates. With MLC tracking the GTV D98% coverage remained unchanged (+/− 0.1Gy) regardless of drift. Conclusion: Intrafractional baseline drifts reduce the tumor dose in treatments based on mid-ventilation planning. In rare, large target baseline drifts tumor dose coverage may drop below the prescription, potentially affecting clinical outcome in hypofractionated treatment protocols. Dynamic MLC tracking preserves tumor dose coverage even in the presence of extreme baseline drifts. We acknowledge financial and technical support of the MLC tracking research from Elekta AB. Research at ICR is supported by CRUK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR. MFF is supported by CRUK under Programme C33589/A19908.« less