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All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

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

Purpose: To develop and validate a volume-modulated arc therapy (VMAT) quality assurance (QA) tool that takes as input a time-resolved, low-density ({approx}10 mm) cylindrical surface dose map from a commercial helical diode array, and outputs a high density, volumetric, time-resolved dose matrix on an arbitrary patient dataset. This first validation study is limited to a homogeneous 'patient.'Methods: A VMAT treatment is delivered to a diode array phantom (ARCCHECK, Sun Nuclear Corp., Melbourne, FL). 3DVH software (Sun Nuclear) derives the high-density volumetric dose using measurement-guided dose reconstruction (MGDR). MGDR cylindrical phantom results are then used to perturb the three-dimensional (3D) treatment planning dose on the patient dataset, producing a semiempirical volumetric dose grid. Four-dimensional (4D) dose reconstruction on the patient is also possible by morphing individual sub-beam doses instead of the composite. For conventional (3D) dose comparison two methods were developed, using the four plans (Multi-Target, C-shape, Mock Prostate, and Head and Neck), including their structures and objectives, from the AAPM TG-119 report. First, 3DVH and treatment planning system (TPS) cumulative point doses were compared to ion chamber in a cube water-equivalent phantom ('patient'). The shape of the phantom is different from the ARCCHECK and furthermore the targets were placed asymmetrically. Second, coronal and sagittal absolute film dose distributions in the cube were compared with 3DVH and TPS. For time-resolved (4D) comparisons, three tests were performed. First, volumetric dose differences were calculated between the 3D MGDR and cumulative time-resolved patient (4D MGDR) dose at the end of delivery, where they ideally should be identical. Second, time-resolved (10 Hz sampling rate) ion chamber doses were compared to cumulative point dose vs time curves from 4D MGDR. Finally, accelerator output was varied to assess the linearity of the 4D MGDR with global fluence change. Results: Across four TG-119 plans, the average PTV point dose difference in the cube between 3DVH and ion chamber is 0.1 {+-} 1.0%. Average film vs TPS {gamma}-analysis passing rates are 83.0%, 91.1%, and 98.4% for 1%/2 mm, 2%/2 mm, and 3%/3 mm threshold combinations, respectively, while average film vs 3DVH {gamma}-analysis passing rates are 88.6%, 96.1%, and 99.5% for the same respective criteria. 4D MGDR was also sufficiently accurate. First, for 99.5% voxels in each case, the doses from 3D and 4D MGDR at the end of delivery agree within 0.5%local dose-error/1 mm distance. Moreover, all failing voxels are confined to the edge of the cylindrical reconstruction volume. Second, dose vs time curves track between the ion chamber and 4D MGDR within 1%. Finally, 4D MGDR dose changes linearly with the accelerator output: the difference between cumulative ion chamber and MGDR dose changed by no more than 1% (randomly) with the output variation range of 10%. Conclusions: Even for a well-commissioned TPS, comparison metrics show better agreement on average to MGDR than to TPS on the arbitrary-shaped measurable 'patient.' The method requires no more accelerator time than standard QA, while producing more clinically relevant information. Validation in a heterogeneous thoracic phantom is under way, as is the ultimate application of 4D MGDR to virtual motion studies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Magnitude of speed of sound aberration corrections for ultrasound image guided radiotherapy for prostate and other anatomical sites

Purpose: The purpose of this work is to assess the magnitude of speed of sound (SOS) aberrations in three-dimensional ultrasound (US) imaging systems in image guided radiotherapy. The discrepancy between the fixed SOS value of 1540 m/s assumed by US systems in human soft tissues and its actual nonhomogeneous distribution in patients produces small but systematic errors of up to a few millimeters in the positions of scanned structures. Methods: A correction, provided by a previously published density-based algorithm, was applied to a set of five prostate, five liver, and five breast cancer patients. The shifts of the centroids of target structures and the change in shape were evaluated. Results: After the correction the prostate cases showed shifts up to 3.6 mm toward the US probe, which may explain largely the reported positioning discrepancies in the literature on US systems versus other imaging modalities. Liver cases showed the largest changes in volume of the organ, up to almost 9%, and shifts of the centroids up to more than 6 mm either away or toward the US probe. Breast images showed systematic small shifts of the centroids toward the US probe with a maximum magnitude of 1.3 mm. Conclusions: The applied correction in prostate and liver cancer patients shows positioning errors of several mm due to SOS aberration; the errors are smaller in breast cancer cases, but possibly becoming more important when breast tissue thickness increases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Liver motion during cone beam computed tomography guided stereotactic body radiation therapy

Purpose: Understanding motion characteristics of liver such as, interfractional and intrafractional motion variability, difference in motion within different locations in the organ, and their complex relationship with the breathing cycles are particularly important for image-guided liver SBRT. The purpose of this study was to investigate such motion characteristics based on fiducial markers tracked with the x-ray projections of the CBCT scans, taken immediately prior to the treatments. Methods: Twenty liver SBRT patients were analyzed. Each patient had three fiducial markers (2 Multiplication-Sign 5-mm gold) percutaneously implanted around the gross tumor. The prescription ranged from 2 to 8 fractions per patient. The CBCT projections data for each fraction ({approx}650 projections/scan), for each patient, were analyzed and the 2D positions of the markers were extracted using an in-house algorithm. In total, >55 000 x-ray projections were analyzed from 85 CBCT scans. From the 2D extracted positions, a 3D motion trajectory of the markers was constructed, from each CBCT scans, resulting in left-right (LR), anterior-posterior (AP), and cranio-caudal (CC) location information of the markers with >55 000 data points. The authors then analyzed the interfraction and intrafraction liver motion variability, within different locations in the organ, and as a function of the breathing cycle. The authors also compared the motion characteristics against the planning 4DCT and the RPM Trade-Mark-Sign (Varian Medical Systems, Palo Alto, CA) breathing traces. Variations in the appropriate gating window (defined as the percent of the maximum range at which 50% of the marker positions are contained), between fractions were calculated as well. Results: The range of motion for the 20 patients were 3.0 {+-} 2.0 mm, 5.1 {+-} 3.1 mm, and 17.9 {+-} 5.1 mm in the planning 4DCT, and 2.8 {+-} 1.6 mm, 5.3 {+-} 3.1 mm, and 16.5 {+-} 5.7 mm in the treatment CBCT, for LR, AP, and CC directions, respectively. The range of respiratory period was 3.9 {+-} 0.7 and 4.2 {+-} 0.8 s during the 4DCT simulation and the CBCT scans, respectively. The authors found that breathing-induced AP and CC motions are highly correlated. That is, all markers moved cranially also moved posteriorly and vice versa, irrespective of the location. The LR motion had a more variable relationship with the AP/CC motions, and appeared random with respect to the location. That is, when the markers moved toward cranial-posterior direction, 58% of the markers moved to the patient-right, 22% of the markers moved to the patient-left, and 20% of the markers had minimal/none motion. The absolute difference in the motion magnitude between the markers, in different locations within the liver, had a positive correlation with the absolute distance between the markers (R{sup 2}= 0.69, linear-fit). The interfractional gating window varied significantly for some patients, with the largest having 29.4%-56.4% range between fractions. Conclusions: This study analyzed the liver motion characteristics of 20 patients undergoing SBRT. A large variation in motion was observed, interfractionally and intrafractionally, and that as the distance between the markers increased, the difference in the absolute range of motion also increased. This suggests that marker(s) in closest proximity to the target be used.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Objected constrained registration and manifold learning: A new patient setup approach in image guided radiation therapy of thoracic cancer

Purpose: The management of thoracic malignancies with radiation therapy is complicated by continuous target motion. In this study, a real time motion analysis approach is proposed to improve the accuracy of patient setup. Methods: For 11 lung cancer patients a long training fluoroscopy was acquired before the first treatment, and multiple short testing fluoroscopies were acquired weekly at the pretreatment patient setup of image guided radiotherapy (IGRT). The data analysis consisted of three steps: first a 4D target motion model was constructed from 4DCT and projected to the training fluoroscopy through deformable registration. Then the manifold learning method was used to construct a 2D subspace based on the target motion (kinetic) and location (static) information in the training fluoroscopy. Thereafter the respiratory phase in the testing fluoroscopy was determined by finding its location in the subspace. Finally, the phase determined testing fluoroscopy was registered to the corresponding 4DCT to derive the pretreatment patient position adjustment for the IGRT. The method was tested on clinical image sets and numerical phantoms. Results: The registration successfully reconstructed the 4D motion model with over 98% volume similarity in 4DCT, and over 95% area similarity in the training fluoroscopy. The machine learning method derived the phase values in over 98% and 93% test images of the phantom and patient images, respectively, with less than 3% phase error. The setup approach achieved an average accumulated setup error less than 1.7 mm in the cranial-caudal direction and less than 1 mm in the transverse plane. All results were validated against the ground truth of manual delineations by an experienced radiation oncologist. The expected total time for the pretreatment setup analysis was less than 10 s. Conclusions: By combining the registration and machine learning, the proposed approach has the potential to improve the accuracy of pretreatment setup for patients with thoracic malignancy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Evaluation of multiple image-based modalities for image-guided radiation therapy (IGRT) of prostate carcinoma: A prospective study

Purpose: Setup errors and prostate intrafraction motion are main sources of localization uncertainty in prostate cancer radiation therapy. This study evaluates four different imaging modalities 3D ultrasound (US), kV planar images, cone-beam computed tomography (CBCT), and implanted electromagnetic transponders (Calypso/Varian) to assess inter- and intrafraction localization errors during intensity-modulated radiation therapy based treatment of prostate cancer. Methods: Twenty-seven prostate cancer patients were enrolled in a prospective IRB-approved study and treated to a total dose of 75.6 Gy (1.8 Gy/fraction). Overall, 1100 fractions were evaluated. For each fraction, treatment targets were localized using US, kV planar images, and CBCT in a sequence defined to determine setup offsets relative to the patient skin tattoos, intermodality differences, and residual errors for each patient and patient cohort. Planning margins, following van Herk's formalism, were estimated based on error distributions. Calypso-based localization was not available for the first eight patients, therefore centroid positions of implanted gold-seed markers imaged prior to and immediately following treatment were used as a motion surrogate during treatment. For the remaining 19 patients, Calypso transponders were used to assess prostate intrafraction motion. Results: The means ({mu}), and standard deviations (SD) of the systematic ({Sigma}) and random errors ({sigma}) of interfraction prostate shifts (relative to initial skin tattoo positioning), as evaluated using CBCT, kV, and US, averaged over all patients and fractions, were: [{mu}{sub CBCT}= (-1.2, 0.2, 1.1) mm, {Sigma}{sub CBCT}= (3.0, 1.4, 2.4) mm, {sigma}{sub CBCT}= (3.2, 2.2, 2.5) mm], [{mu}{sub kV}= (-2.9, -0.4, 0.5) mm, {Sigma}{sub kV}= (3.4, 3.1, 2.6) mm, {sigma}{sub kV}= (2.9, 2.0, 2.4) mm], and [{mu}{sub US}= (-3.6, -1.4, 0.0) mm, {Sigma}{sub US}= (3.3, 3.5, 2.8) mm, {sigma}{sub US}= (4.1, 3.8, 3.6) mm], in the anterior-posterior (A/P), superior-inferior (S/I), and the left-right (L/R) directions, respectively. In the treatment protocol, adjustment of couch was guided by US images. Residual setup errors as assessed by kV images were found to be: {mu}{sub residual}= (-0.4, 0.2, 0.2) mm, {Sigma}{sub residual}= (1.0, 1.0,0.7) mm, and {sigma}{sub residual}= (2.5, 2.3, 1.8) mm. Intrafraction prostate motion, evaluated using electromagnetic transponders, was: {mu}{sub intrafxn}= (0.0, 0.0, 0.0) mm, {Sigma}{sub intrafxn}= (1.3, 1.5, 0.6) mm, and {sigma}{sub intrafxn}= (2.6, 2.4, 1.4) mm. Shifts between pre- and post-treatment kV images were: {mu}{sub kV(post-pre)}= (-0.3, 0.8, -0.2), {Sigma}{sub kV(post-pre)}= (2.4, 2.7, 2.1) mm, and {sigma}{sub kV(post-pre)}= (2.7, 3.2, 3.1) mm. Relative to skin tattoos, planning margins for setup error were within 10-11 mm for all image-based modalities. The use of image guidance was shown to reduce these margins to less than 5 mm. Margins to compensate for both residual setup (interfraction) errors as well as intrafraction motion were 6.6, 6.8, and 3.9 mm in the A/P, S/I, and L/R directions, respectively. Conclusions: Analysis of interfraction setup errors, performed with US, CBCT, planar kV images, and electromagnetic transponders, from a large dataset revealed intermodality shifts were comparable (within 3-4 mm). Interfraction planning margins, relative to setup based on skin marks, were generally within the 10 mm prostate-to-planning target volume margin used in our clinic. With image guidance, interfraction residual planning margins were reduced to approximately less than 4 mm. These findings are potentially important for dose escalation studies using smaller margins to better protect normal tissues.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Progressive cone beam CT dose control in image-guided radiation therapy

Purpose: Cone beam CT (CBCT) in image-guided radiotherapy (IGRT) offers a tremendous advantage for treatment guidance. The associated imaging dose is a clinical concern. One unique feature of CBCT-based IGRT is that the same patient is repeatedly scanned during a treatment course, and the contents of CBCT images at different fractions are similar. The authors propose a progressive dose control (PDC) scheme to utilize this temporal correlation for imaging dose reduction. Methods: A dynamic CBCT scan protocol, as opposed to the static one in the current clinical practice, is proposed to gradually reduce the imaging dose in each treatment fraction. The CBCT image from each fraction is processed by a prior-image based nonlocal means (PINLM) module to enhance its quality. The increasing amount of prior information from previous CBCT images prevents degradation of image quality due to the reduced imaging dose. Two proof-of-principle experiments have been conducted using measured phantom data and Monte Carlo simulated patient data with deformation. Results: In the measured phantom case, utilizing a prior image acquired at 0.4 mAs, PINLM is able to improve the image quality of a CBCT acquired at 0.2 mAs by reducing the noise level from 34.95 to 12.45 HU. In the synthetic patient case, acceptable image quality is maintained at four consecutive fractions with gradually decreasing exposure levels of 0.4, 0.1, 0.07, and 0.05 mAs. When compared with the standard low-dose protocol of 0.4 mAs for each fraction, an overall imaging dose reduction of more than 60% is achieved. Conclusions: PINLM-PDC is able to reduce CBCT imaging dose in IGRT utilizing the temporal correlations among the sequence of CBCT images while maintaining the quality.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2013

MR-CT registration using a Ni-Ti prostate stent in image-guided radiotherapy of prostate cancer

Purpose: In image-guided radiotherapy of prostate cancer defining the clinical target volume often relies on magnetic resonance (MR). The task of transferring the clinical target volume from MR to standard planning computed tomography (CT) is not trivial due to prostate mobility. In this paper, an automatic local registration approach is proposed based on a newly developed removable Ni-Ti prostate stent.Methods: The registration uses the voxel similarity measure mutual information in a two-step approach where the pelvic bones are used to establish an initial registration for the local registration.Results: In a phantom study, the accuracy was measured to 0.97 mm and visual inspection showed accurate registration of all 30 data sets. The consistency of the registration was examined where translation and rotation displacements yield a rotation error of 0.41 Degree-Sign {+-} 0.45 Degree-Sign and a translation error of 1.67 {+-} 2.24 mm.Conclusions: This study demonstrated the feasibility for an automatic local MR-CT registration using the prostate stent.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

MR-guided focused ultrasound surgery, present and future

MR-guided focused ultrasound surgery (MRgFUS) is a quickly developing technology with potential applications across a spectrum of indications traditionally within the domain of radiation oncology. Especially for applications where focal treatment is the preferred technique (for example, radiosurgery), MRgFUS has the potential to be a disruptive technology that could shift traditional patterns of care. While currently cleared in the United States for the noninvasive treatment of uterine fibroids and bone metastases, a wide range of clinical trials are currently underway, and the number of publications describing advances in MRgFUS is increasing. However, for MRgFUS to make the transition from a research curiosity to a clinical standard of care, a variety of challenges, technical, financial, clinical, and practical, must be overcome. This installment of the Vision 20/20 series examines the current status of MRgFUS, focusing on the hurdles the technology faces before it can cross over from a research technique to a standard fixture in the clinic. It then reviews current and near-term technical developments which may overcome these hurdles and allow MRgFUS to break through into clinical practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

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

Purpose: Recent advances in preclinical radiotherapy systems have provided the foundation for scaling many of the elements of clinical radiation therapy practice to the dimensions and energy demanded in small animal studies. Such systems support the technical capabilities to accurately deliver highly complex dose distributions, but methods to optimize and deliver such distributions remain in their infancy. This study developed an optimization method based on empirically measured two-dimensional dose kernel measurements to deliver arbitrary planar dose distributions on a recently developed small animal radiotherapy platform.Methods: A two-dimensional dose kernel was measured with repeated radiochromic film measurements for the circular 1 mm diameter fixed collimator of the small animal radiotherapy system at 1 cm depth in a solid water phantom. This kernel was utilized in a sequential quadratic programming optimization framework to determine optimal beam positions and weights to deliver an arbitrary desired dose distribution. The positions and weights were then translated to a set of stage motions to automatically deliver the optimized dose distribution. End-to-end efficacy of the framework was quantified through five repeated deliveries of two dosimetric challenges: (1) a 5 mm radius bullseye distribution, and (2) a “sock” distribution contained within a 9 × 13 mm bounding box incorporating rectangular, semicircular, and exponentially decaying geometric constructs and a rectangular linear dose gradient region. These two challenges were designed to gauge targeting, geometric, and dosimetric fidelity.Results: Optimization of the bullseye and sock distributions required 2.1 and 5.9 min and utilized 50 and 77 individual beams for delivery, respectively. Automated delivery of the resulting optimized distributions, validated using radiochromic film measurements, revealed an average targeting accuracy of 0.32 mm, and a dosimetric delivery error along four line profiles taken through the sock distribution of 3.9%. Mean absolute delivery error across the 0–1 Gy linear dose gradient over 7.5 mm was 0.01 Gy.Conclusions: The work presented here demonstrates the potential for complex dose distributions to be planned and automatically delivered with millimeter scale heterogeneity at submillimeter accuracy. This capability establishes the technical foundation for preclinical validation of biologically guided radiotherapy investigations and development of unique radiobiological experiments.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2014

Multi-institutional dosimetric and geometric commissioning of image-guided small animal irradiators

Purpose: To compare the dosimetric and geometric properties of a commercial x-ray based image-guided small animal irradiation system, installed at three institutions and to establish a complete and broadly accessible commissioning procedure. Methods: The system consists of a 225 kVp x-ray tube with fixed field size collimators ranging from 1 to 44 mm equivalent diameter. The x-ray tube is mounted opposite a flat-panel imaging detector, on a C-arm gantry with 360° coplanar rotation. Each institution performed a full commissioning of their system, including half-value layer, absolute dosimetry, relative dosimetry (profiles, percent depth dose, and relative output factors), and characterization of the system geometry and mechanical flex of the x-ray tube and detector. Dosimetric measurements were made using Farmer-type ionization chambers, small volume air and liquid ionization chambers, and radiochromic film. The results between the three institutions were compared. Results: At 225 kVp, with 0.3 mm Cu added filtration, the first half value layer ranged from 0.9 to 1.0 mm Cu. The dose-rate in-air for a 40 × 40 mm{sup 2} field size, at a source-to-axis distance of 30 cm, ranged from 3.5 to 3.9 Gy/min between the three institutions. For field sizes between 2.5 mm diameter and 40 × 40 mm{sup 2}, the differences between percent depth dose curves up to depths of 3.5 cm were between 1% and 4% on average, with the maximum difference being 7%. The profiles agreed very well for fields >5 mm diameter. The relative output factors differed by up to 6% for fields larger than 10 mm diameter, but differed by up to 49% for fields ≤5 mm diameter. The mechanical characteristics of the system (source-to-axis and source-to-detector distances) were consistent between all three institutions. There were substantial differences in the flex of each system. Conclusions: With the exception of the half-value layer, and mechanical properties, there were significant differences between the dosimetric and geometric properties of the three systems. This underscores the need for careful commissioning of each individual system for use in radiobiological experiments.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2014

Evaluation of image guided motion management methods in lung cancer radiotherapy

Purpose: To evaluate the accuracy and reliability of three target localization methods for image guided motion management in lung cancer radiotherapy. Methods: Three online image localization methods, including (1) 2D method based on 2D cone beam (CB) projection images, (2) 3D method using 3D cone beam CT (CBCT) imaging, and (3) 4D method using 4D CBCT imaging, have been evaluated using a moving phantom controlled by (a) 1D theoretical breathing motion curves and (b) 3D target motion patterns obtained from daily treatment of 3 lung cancer patients. While all methods are able to provide target mean position (MP), the 2D and 4D methods can also provide target motion standard deviation (SD) and excursion (EX). For each method, the detected MP/SD/EX values are compared to the analytically calculated actual values to calculate the errors. The MP errors are compared among three methods and the SD/EX errors are compared between the 2D and 4D methods. In the theoretical motion study (a), the dependency of MP/SD/EX error on EX is investigated with EX varying from 2.0 cm to 3.0 cm with an increment step of 0.2 cm. In the patient motion study (b), the dependency of MP error on target sizes (2.0 cm and 3.0 cm), motion patterns (four motions per patient) and EX variations is investigated using multivariant linear regression analysis. Results: In the theoretical motion study (a), the MP detection errors are −0.2 ± 0.2, −1.5 ± 1.1, and −0.2 ± 0.2 mm for 2D, 3D, and 4D methods, respectively. Both the 2D and 4D methods could accurately detect motion pattern EX (error < 1.2 mm) and SD (error < 1.0 mm). In the patient motion study (b), MP detection error vector (mm) with the 2D method (0.7 ± 0.4) is found to be significantly less than with the 3D method (1.7 ± 0.8,p < 0.001) and the 4D method (1.4 ± 1.0, p < 0.001) using paired t-test. However, no significant difference is found between the 4D method and the 3D method. Based on multivariant linear regression analysis, the variances of MP error in SI direction explained by target sizes, motion patterns, and EX variations are 9% with the 2D method, 74.4% with the 3D method, and 27% with the 4D method. The EX/SD detection errors are both < 1.0 mm for the 2D method and < 2.0 mm for the 4D method. Conclusions: The 2D method provides the most accurate MP detection regardless of the motion pattern variations, while its performance is limited by the accuracy of target identification in the projection images. The 3D method causes the largest error in MP determination, and its accuracy significantly depends on target sizes, motion patterns, and EX variations. The 4D method provides moderate MP detection results, while its accuracy relies on a regular motion pattern. In addition, the 2D and 4D methods both provide accurate measurement of the motion SD/EX, providing extra information for motion management.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Model-based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR-guided endorectal HIFU ablation array

Purpose: Feasibility of targeted and volumetric hyperthermia (40–45 °C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy. Methods: The simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm{sup 2}, ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W). Results: Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (T{sub max} < 45 °C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity I{sub SATA} < 3.4 W/cm{sup 2}). Tissue volumes with therapeutic temperature levels (T > 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13–23 cm{sup 3} volumes for sonications with planar or diverging beam patterns at 0.9–1.2 W/cm{sup 2}, in 4.5–5.8 cm{sup 3} volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm{sup 2}, and in ∼6.0 cm{sup 3} for curvilinear (cylindrical) beam patterns at 0.75 W/cm{sup 2}. Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous-wave sonications (∼0.88 W/cm{sup 2}, 15 min) were performed in tissue-mimicking material with real-time MR-based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations. Conclusions: The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Magnetization curves of sintered heavy tungsten alloys for applications in MRI-guided radiotherapy

Purpose: Due to the current interest in MRI-guided radiotherapy, the magnetic properties of the materials commonly used in radiotherapy are becoming increasingly important. In this paper, measurement results for the magnetization (BH) curves of a range of sintered heavy tungsten alloys used in radiation shielding and collimation are presented. Methods: Sintered heavy tungsten alloys typically contain >90 % tungsten and <10 % of a combination of iron, nickel, and copper binders. Samples of eight different grades of sintered heavy tungsten alloys with varying binder content were investigated. Using a superconducting quantum interference detector magnetometer, the induced magnetic momentm was measured for each sample as a function of applied external field H{sub 0} and the BH curve derived. Results: The iron content of the alloys was found to play a dominant role, directly influencing the magnetizationM and thus the nonlinearity of the BH curve. Generally, the saturation magnetization increased with increasing iron content of the alloy. Furthermore, no measurable magnetization was found for all alloys without iron content, despite containing up to 6% of nickel. For two samples from different manufacturers but with identical quoted nominal elemental composition (95% W, 3.5% Ni, 1.5% Fe), a relative difference in the magnetization of 11%–16% was measured. Conclusions: The measured curves show that the magnetic properties of sintered heavy tungsten alloys strongly depend on the iron content, whereas the addition of nickel in the absence of iron led to no measurable effect. Since a difference in the BH curves for two samples with identical quoted nominal composition from different manufacturers was observed, measuring of the BH curve for each individual batch of heavy tungsten alloys is advisable whenever accurate knowledge of the magnetic properties is crucial. The obtained BH curves can be used in FEM simulations to predict the magnetic impact of sintered heavy tungsten alloys.

36 MATERIALS SCIENCE↗
DOE OSTI2014

A DVH-guided IMRT optimization algorithm for automatic treatment planning and adaptive radiotherapy replanning

Purpose: To develop a novel algorithm that incorporates prior treatment knowledge into intensity modulated radiation therapy optimization to facilitate automatic treatment planning and adaptive radiotherapy (ART) replanning. Methods: The algorithm automatically creates a treatment plan guided by the DVH curves of a reference plan that contains information on the clinician-approved dose-volume trade-offs among different targets/organs and among different portions of a DVH curve for an organ. In ART, the reference plan is the initial plan for the same patient, while for automatic treatment planning the reference plan is selected from a library of clinically approved and delivered plans of previously treated patients with similar medical conditions and geometry. The proposed algorithm employs a voxel-based optimization model and navigates the large voxel-based Pareto surface. The voxel weights are iteratively adjusted to approach a plan that is similar to the reference plan in terms of the DVHs. If the reference plan is feasible but not Pareto optimal, the algorithm generates a Pareto optimal plan with the DVHs better than the reference ones. If the reference plan is too restricting for the new geometry, the algorithm generates a Pareto plan with DVHs close to the reference ones. In both cases, the new plans have similar DVH trade-offs as the reference plans. Results: The algorithm was tested using three patient cases and found to be able to automatically adjust the voxel-weighting factors in order to generate a Pareto plan with similar DVH trade-offs as the reference plan. The algorithm has also been implemented on a GPU for high efficiency. Conclusions: A novel prior-knowledge-based optimization algorithm has been developed that automatically adjust the voxel weights and generate a clinical optimal plan at high efficiency. It is found that the new algorithm can significantly improve the plan quality and planning efficiency in ART replanning and automatic treatment planning.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

SU-D-9A-07: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

Purpose: To systematically evaluate the imaging doses and cancer risks associated with various imaging procedures involving ionizing radiation during image-guided radiotherapy of an increasingly large number of cancer patients. Methods: 141 patients (52 brain cases, 47 thoracic cases, 42 abdominal cases, aged 3 to 91 years old) treated between October 2009 and March 2010 were included in this IRB-approved retrospective study. During the whole radiotherapy course, each patient underwent at least one type of imaging procedures, i.e., kV portal, MV portal and kVCBCT, besides CT simulations. Based on Monte Carlo modeling and particle transport in human anatomy of various dimensions, the correlations between the radiation doses to the various organs-at-risk (OARs) at the head, the thoracic and the abdominal regions and one's weight, circumference, scan mAs and kVp have been obtained and used to estimate the radiation dose from a specific imaging procedure. The radiation-induced excess relative risk (ERR) was then estimated with BEIR VII formulism based on one's gender, age and radiation dose. 1+ ERR was reported in this study as relative cancer risk. Results: For the whole cohort of 141 patients, the mean imaging doses from various imaging procedures were 8.3 cGy to the brain, 10.5 cGy to the lungs and 19.2 cGy to the red bone marrow, respectively. Accordingly, the cancer risks were 1.140, 1.369 and 2.671, respectively. In comparison, MV portal deposited largest doses to the lungs while kVCBCT delivered the highest doses to the red bone marrow. Conclusion: The compiled imaging doses to a patient during his/her treatment course were patient-specific and site-dependent, varying from 1.2 to 263.5 cGy on average, which were clinically significant and should be included in the treatment planning and overall decision-making. Our results indicated the necessity of personalized imaging to maximize its clinical benefits while reducing the associated cancer risks. Sichuan University Scholarship.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-J-14: A Novel Approach to Evaluate the Dosimetric Effect of Rectal Variation During Image Guided Prostate Radiotherapy

Purpose: Deformable registration establishes the spatial correspondence back to the reference image in order to accumulate dose. However, in prostate radiotherapy the changing shape and volume of the rectum present a challenge to accurate deformable registration and consequently calculation of delivered dose. We explored an alternative approach to calculating accumulated dose to the rectum, independent of deformable registration. Methods: This study was performed on three patients who received online image-guided radiotherapy (IGRT) with daily CBCT (XVI-system,Elekta) and target localization using intraprostatic fiducials. On each CBCT, the rectum was manually contoured and bulk density assignments were made allowing dose to be calculated for each fraction. Dose-surface maps (DSM) were generated (MATLAB,Mathworks,Natick,MA) by considering the rectum as a cylinder and sampling the dose at 21-equispaced points on each CT slice. The cylinder was “cut” at the posterior-most position on each CT and unfolded to generate a DSM. These were normalised in the longitudinal direction by interpolation creating maps of 21×21 pixels. A DSM was produced for each CBCT and the dose was accumulated. Results: The mean accumulated delivered rectal surface dose was on average 7.5(+/−3.5)% lower than the planned dose. The dose difference maps consistently show that the greatest variation in dose between planned and delivered dose is away from where the rectal surface is adjacent to the prostate. Conclusion: Estimation of dose accumulation using DSM provides an alternative method for determining actual delivered dose to the rectum. The dose difference is greatest in areas away from the region where the rectal surface abuts the prostate, the region where set-up is verified. The change in size and shape of the rectum was shown to resultin a change in the accumulated dose compared to the planned dose and this will have an impact on determining the relationships between dose delivered and toxicity. We acknowledge funding from CRUK and acknowledge NHS funding to the NIHR Biomedical Research Centre for Cancer. Patients were treated within the CHHiP IGRT sub-study (CRUK/06/016, ISRCTN:97182923) funded by CRUK. RayStation was used under an evaluation agreement with RaySearch Laboratories AB.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-J-47: Development of a High-Precision, Image-Guided Radiotherapy, Multi- Purpose Radiation Isocenter Quality-Assurance Calibration and Checking System

Purpose: To develop a system that can define the radiation isocenter and correlate this information with couch coordinates, laser alignment, optical distance indicator (ODI) settings, optical tracking system (OTS) calibrations, and mechanical isocenter walkout. Methods: Our team developed a multi-adapter, multi-purpose quality assurance (QA) and calibration device that uses an electronic portal imaging device (EPID) and in-house image-processing software to define the radiation isocenter, thereby allowing linear accelerator (Linac) components to be verified and calibrated. Motivated by the concept that each Linac component related to patient setup for image-guided radiotherapy based on cone-beam CT should be calibrated with respect to the radiation isocenter, we designed multiple concentric adapters of various materials and shapes to meet the needs of MV and KV radiation isocenter definition, laser alignment, and OTS calibration. The phantom's ability to accurately define the radiation isocenter was validated on 4 Elekta Linacs using a commercial ball bearing (BB) phantom as a reference. Radiation isocenter walkout and the accuracy of couch coordinates, ODI, and OTS were then quantified with the device. Results: The device was able to define the radiation isocenter within 0.3 mm. Radiation isocenter walkout was within ±1 mm at 4 cardinal angles. By switching adapters, we identified that the accuracy of the couch position digital readout, ODI, OTS, and mechanical isocenter walkout was within sub-mm. Conclusion: This multi-adapter, multi-purpose isocenter phantom can be used to accurately define the radiation isocenter and represents a potential paradigm shift in Linac QA. Moreover, multiple concentric adapters allowed for sub-mm accuracy for the other relevant components. This intuitive and user-friendly design is currently patent pending.

07 ISOTOPE AND RADIATION SOURCES↗