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DOE OSTI2013

A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images

Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Low-complexity atlas-based prostate segmentation by combining global, regional, and local metrics

Purpose: To improve the efficiency of atlas-based segmentation without compromising accuracy, and to demonstrate the validity of the proposed method on MRI-based prostate segmentation application. Methods: Accurate and efficient automatic structure segmentation is an important task in medical image processing. Atlas-based methods, as the state-of-the-art, provide good segmentation at the cost of a large number of computationally intensive nonrigid registrations, for anatomical sites/structures that are subject to deformation. In this study, the authors propose to utilize a combination of global, regional, and local metrics to improve the accuracy yet significantly reduce the number of required nonrigid registrations. The authors first perform an affine registration to minimize the global mean squared error (gMSE) to coarsely align each atlas image to the target. Subsequently, atarget-specific regional MSE (rMSE), demonstrated to be a good surrogate for dice similarity coefficient (DSC), is used to select a relevant subset from the training atlas. Only within this subset are nonrigid registrations performed between the training images and the target image, to minimize a weighted combination of gMSE and rMSE. Finally, structure labels are propagated from the selected training samples to the target via the estimated deformation fields, and label fusion is performed based on a weighted combination of rMSE and local MSE (lMSE) discrepancy, with proper total-variation-based spatial regularization. Results: The proposed method was applied to a public database of 30 prostate MR images with expert-segmented structures. The authors’ method, utilizing only eight nonrigid registrations, achieved a performance with a median/mean DSC of over 0.87/0.86, outperforming the state-of-the-art full-fledged atlas-based segmentation approach of which the median/mean DSC was 0.84/0.82 when applying to their data set. Conclusions: The proposed method requires a fixed number of nonrigid registrations, independent of atlas size, providing desirable scalability especially important for a large or growing atlas. When applied to prostate segmentation, the method achieved better performance to the state-of-the-art atlas-based approaches, with significant improvement in computation efficiency. The proposed rationale of utilizing jointly global, regional, and local metrics, based on the information characteristic and surrogate behavior for registration and fusion subtasks, can be extended naturally to similarity metrics beyond MSE, such as correlation or mutual information types.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

SU-E-J-261: Statistical Analysis and Chaotic Dynamics of Respiratory Signal of Patients in BodyFix

Purpose: To quantify respiratory signal of patients in BodyFix undergoing 4DCT scan with and without immobilization cover. Methods: 20 pairs of respiratory tracks recorded with RPM system during 4DCT scan were analyzed. Descriptive statistic was applied to selected parameters of exhale-inhale decomposition. Standardized signals were used with the delay method to build orbits in embedded space. Nonlinear behavior was tested with surrogate data. Sample entropy SE, Lempel-Ziv complexity LZC and the largest Lyapunov exponents LLE were compared. Results: Statistical tests show difference between scans for inspiration time and its variability, which is bigger for scans without cover. The same is for variability of the end of exhalation and inhalation. Other parameters fail to show the difference. For both scans respiratory signals show determinism and nonlinear stationarity. Statistical test on surrogate data reveals their nonlinearity. LLEs show signals chaotic nature and its correlation with breathing period and its embedding delay time. SE, LZC and LLE measure respiratory signal complexity. Nonlinear characteristics do not differ between scans. Conclusion: Contrary to expectation cover applied to patients in BodyFix appears to have limited effect on signal parameters. Analysis based on trajectories of delay vectors shows respiratory system nonlinear character and its sensitive dependence on initial conditions. Reproducibility of respiratory signal can be evaluated with measures of signal complexity and its predictability window. Longer respiratory period is conducive for signal reproducibility as shown by these gauges. Statistical independence of the exhale and inhale times is also supported by the magnitude of LLE. The nonlinear parameters seem more appropriate to gauge respiratory signal complexity since its deterministic chaotic nature. It contrasts with measures based on harmonic analysis that are blind for nonlinear features. Dynamics of breathing, so crucial for 4D-based clinical technologies, can be better controlled if nonlinear-based methodology, which reflects respiration characteristic, is applied. Funding provided by Varian Medical Systems via Investigator Initiated Research Project.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-E-T-379: Concave Approximations of Target Volume Dose Metrics for Intensity- Modulated Radiotherapy Treatment Planning

Purpose: The widely used treatment plan metric Dx (mimimum dose to the hottest x% by volume of the target volume) is simple to interpret and use, but is computationally poorly behaved (non-convex), this impedes its use in computationally efficient intensity-modulated radiotherapy (IMRT) treatment planning algorithms. We therefore searched for surrogate metrics that are concave, computationally efficient, and accurately correlated to Dx values in IMRT treatment plans. Methods: To find concave surrogates of D95—and more generally, Dx values with variable x values—we tested equations containing one or two generalized equivalent uniform dose (gEUD) functions. Fits were obtained by varying gEUD ‘a’ parameter values, as well as the linear equation coefficients. Fitting was performed using a dataset of dose-volume histograms from 498 de-identified head and neck IMRT treatment plans. Fit characteristics were tested using a crossvalidation process. Reported root-mean-square error values were averaged over the cross-validation shuffles. Results: As expected, the two-gEUD formula provided a superior fit, compared to the single-gEUD formula. The best approximation uses two gEUD terms: 16.25 x gEUD[a=0.45] – 15.30 x gEUD[a=1.75] – 0.69. The average root-mean-square error on repeated (70/30) cross validation was 0.94 Gy. In addition, a formula was found that reasonably approximates Dx for x between 80% and 96%. Conclusion: A simple concave function using two gEUD terms was found that correlates well with PTV D95s for these head and neck treatment plans. More generally, a formula was found that represents well the Dx for x values from 80% to 96%, thus providing a computationally efficient formula for use in treatment planning optimization. The formula may need to be adjusted for other institutions with different treatment planning protocols. We conclude that the strategy of replacing Dx values with gEUD-based formulas is promising.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-E-QI-15: Single Point Dosimetry by Means of Cerenkov Radiation Energy Transfer (CRET)

Purpose: Cerenkov light is generated when a charged particles with energy greater then 250 keV, moves faster than the speed of light in a given medium. Both x-ray photons and electrons produce optical Cerenkov photons during the static megavoltage linear accelerator (LINAC) operational mode. Recently, Cerenkov radiation gained considerable interest as possible candidate as a new imaging modality. Optical signals generated by Cerenkov radiation may act as a surrogate for the absorbed superficial radiation dose. We demonstrated a novel single point dosimetry method for megavoltage photon and electron therapy utilizing down conversion of Cerenkov photons. Methods: The custom build signal characterization system was used: a sample holder (probe) with adjacent light tight compartments was connected via fiber-optic cables to a photon counting photomultiplier tube (PMT). One compartment contains a medium only while the other contains medium and red-shifting nano-particles (Q-dots, nanoclusters). By taking the difference between the two signals (Cerenkov photons and CRET photons) we obtain a measure of the down-converted light, which we expect to be proportional to dose as measured with an adjacent ion chamber. Experimental results are compared to Monte Carlo simulations performed using the GEANT4 code. Results: The signal correlation between CR signal, CRET readings and dose produced by LINAC at a single point were investigated. The experimental results were compared with simulations. The dose linearity, signal to noise ratio and dose rate dependence were tested with custom build CRET based probe. Conclusion: Performance characteristics of the proposed single point CRET based probe were evaluated. The direct use of the induced Cerenkov emission and CRET in an irradiated single point volume as an indirect surrogate for the imparted dose was investigated. We conclude that CRET is a promising optical based dosimetry method that offers advantages over those already proposed.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-E-CAMPUS-J-01: TG142 Complied Comprehensive Commissioning and Quality Assurance Procedure for Respiratory Gating

Purpose: To develop and establish a comprehensive gating commissioning and quality assurance procedure in compliance with TG142. Methods: Quality assurance tests on three Varian LINACs included beam output and energy constancy, calibration of surrogate, as well as phase and amplitude gating temporal accuracy. A diode array (MapCHECK 2) and film (Gafchromic EBT2) were used to measure the temporal accuracy of phase and amplitude gating windows. A motion simulation device (MotionSim) was used to simulate respiratory motion for both detectors. An end-to-end test was also performed on all three machines. The overall accuracy and uncertainty was analyzed and compared. Results: The end-to-end test using an anthropomorphic lung phantom (CIRS) results in an OSL dose difference reading within 5% (within measurement uncertainty) for both phase and amplitude gated treatment. Film results showed < 1% agreement between profiles for gated delivery and predicted dose. The diode array demonstrated an 80% passing rate for gamma criteria of 2%/0.2 mm, which results in a 111 msec temporal accuracy. However, the diode array is limited by its spatial resolution of measurements, due to its 7.07 mm diode spacing. Film provided higher measuring resolution, thus demonstrated a temporal accuracy of <100 msec. Conclusion: Results showed consistent respiratory gating stability and accuracy. MapCHECK 2 may not be sufficient for the temporal accuracy test in the respiratory gating treatment in order to meet the corresponding tolerance in TG142. One would need to decrease respiratory motion speed from the surrogate or tighten the gating window in order to be within tolerance of 100 msec temporal accuracy per TG-142. The end-to-end test offers insight to the overall accuracy and uncertainties with a gated protocol. Compared to static delivery, respiratory motion increases the overall uncertainty of treatment delivery from 3% to 5% dose difference.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-C-19A-04: Evaluation of Patient Positioning Reproducibility with Three Supine Breast Boards

Purpose: To evaluate positioning reproducibility using three commercially available breast board immobilization systems for whole breast radiation therapy. Methods: Weekly pre-treatment cone beam CT images from 18 free-breathing breast radiotherapy patients, each immobilized with one of three breast boards, were retrospectively registered to the planning CT. Relative shifts between breast tissue and sternum/chest wall (CW), and breast tissue and spine compared to planning CT were obtained for each board. Positioning reproducibility, inter-patient variation and intra-patient variation were evaluated by group mean (M), standard deviation of group mean (Σ) and standard deviation of random shift (σ). Margins to account for setup uncertainties were calculated based on shift uncertainties in x, y, and z directions. Results: For breast positioning relative to sternum/CW, the average shift from planned positioning was 4.5mm (95% CI: 3.5 – 5.3), 3.3mm (CI: 2.9 - 3.8) and 2.6mm (CI: 1.8 - 3.5) for Breast Boards I, II, and III, respectively. The respective numbers for breast positioning relative to spine were 7.2 mm (CI: 4.1 – 10.3), 6.4 mm (CI: 4.3 – 8.3) and 4.3 mm (CI: 2.5 – 6.2). Localizing to the sternum/CW as a surrogate for the breast tissue, margins for setup uncertainties were 5.7mm, 5.5mm, and 6.0mm for Breast Board I, 5.0mm, 4.0mm and 4.3mm for Breast Board II, and 3.8mm, 3.5mm and 4.8mm for Breast Board III, in the lateral, anterior/posterior, and superior/inferior directions, respectively. Conclusion: Better patient positioning reproducibility was observed with Boards II and III compared to Board I. Inter- and intra-patient set-up uncertainties were also improved with Boards II and III, which requires smaller PTV margins. Independent of breast board, breast cancer patient positioning to the sternum/CW is a better surrogate than the spine. Our findings have potential dosimetric consequences from set-up uncertainties when employing IMRT or proton treatments, and further analyses are on-going.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina

Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (L)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Methods: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Results: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. Conclusions: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-C-304-04: A Compact Modular Computational Platform for Automated On-Board Imager Quality Assurance

Purpose: Traditionally, the assessment of X-ray tube output and detector positioning accuracy of on-board imagers (OBI) has been performed manually and subjectively with rulers and dosimeters, and typically takes hours to complete. In this study, we have designed a compact modular computational platform to automatically analyze OBI images acquired with in-house designed phantoms as an efficient and robust surrogate. Methods: The platform was developed as an integrated and automated image analysis-based platform using MATLAB for easy modification and maintenance. Given a set of images acquired with the in-house designed phantoms, the X-ray output accuracy was examined via cross-validation of the uniqueness and integration minimization of important image quality assessment metrics, while machine geometric and positioning accuracy were validated by utilizing pattern-recognition based image analysis techniques. Results: The platform input was a set of images of an in-house designed phantom. The total processing time is about 1–2 minutes. Based on the data acquired from three Varian Truebeam machines over the course of 3 months, the designed test validation strategy achieved higher accuracy than traditional methods. The kVp output accuracy can be verified within +/−2 kVp, the exposure accuracy within 2%, and exposure linearity with a coefficient of variation (CV) of 0.1. Sub-millimeter position accuracy was achieved for the lateral and longitudinal positioning tests, while vertical positioning accuracy within +/−2 mm was achieved. Conclusion: This new platform delivers to the radiotherapy field an automated, efficient, and stable image analysis-based procedure, for the first time, acting as a surrogate for traditional tests for LINAC OBI systems. It has great potential to facilitate OBI quality assurance (QA) with the assistance of advanced image processing techniques. In addition, it provides flexible integration of additional tests for expediting other OBI quality assurance tests, such as 2D/3D image quality, making completely automated QA possible. Research Funding from Varian Medical Systems Inc. . Dr. Sasa Mutic receives compensation for providing patient safety training services from Varian Medical Systems, the sponsor of this study.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-235: Audiovisual Biofeedback Improves the Correlation Between Internal and External Respiratory Motion

Purpose: External respiratory surrogates are often used to predict internal lung tumor motion for beam gating but the assumption of correlation between external and internal surrogates is not always verified resulting in amplitude mismatch and time shift. To test the hypothesis that audiovisual (AV) biofeedback improves the correlation between internal and external respiratory motion, in order to improve the accuracy of respiratory-gated treatments for lung cancer radiotherapy. Methods: In nine lung cancer patients, 2D coronal and sagittal cine-MR images were acquired across two MRI sessions (pre- and mid-treatment) with (1) free breathing (FB) and (2) AV biofeedback. External anterior-posterior (AP) respiratory motions of (a) chest and (b) abdomen were simultaneously acquired with physiological measurement unit (PMU, 3T Skyra, Siemens Healthcare Erlangen, Germany) and real-time position management (RPM) system (Varian, Palo Alto, USA), respectively. Internal superior-inferior (SI) respiratory motions of (c) lung tumor (i.e. centroid of auto-segmented lung tumor) and (d) diaphragm (i.e. upper liver dome) were measured from individual cine-MR images across 32 dataset. The four respiratory motions were then synchronized with the cine-MR image acquisition time. Correlation coefficients were calculated in the time variation of two nominated respiratory motions: (1) chest-abdomen, (2) abdomen-diaphragm and (3) diaphragm-lung tumor. The three combinations were compared between FB and AV biofeedback. Results: Compared to FB, AV biofeedback improved chest-abdomen correlation by 17% (p=0.005) from 0.75±0.23 to 0.90±0.05 and abdomen-diaphragm correlation by 4% (p=0.058) from 0.91±0.11 to 0.95±0.05. Compared to FB, AV biofeedback improved diaphragm-lung tumor correlation by 12% (p=0.023) from 0.65±0.21 to 0.74±0.16. Conclusions: Our results demonstrated that AV biofeedback significantly improved the correlation of internal and external respiratory motion, thus suggesting the need of AV biofeedback in respiratory-gated treatments.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-T-183: Clinical Quality Assurance Workflow for Dynamic Tumor Tracking Radiation Dose Delivery

Purpose: One of the most important aspects of implementation of new treatment modalities is an ‘end-to-end’ verification of the treatment process. Radiation treatment based on dynamic tracking of a tumor is highly patient-specific, therefore, special attention should be paid to quality assurance of the treatment delivery. Our goal was to design the clinical workflow that ensures accurate delivery of the planned dose using the Dynamic Target Tracking option of VeroTM (BrainLab,MHI) linac. Methods: A patient simulation is designed to include a pre-treatment session to verify whether the system can reliably track the motion of the implanted marker and build the 4D model of the target motion. The external surrogate and target motion patterns are recorded in the ExactracTM log files. In this work, a spectrum of custom marker and external surrogate motion trajectories closely resembling the patient specific motion patterns was used. 1mm thick/11mm long VisicoilTM marker was placed 15 and 20mm from the center of the spherical tissue equivalent target (centroid to centroid distance) in the 4D motion phantom (CIRSTM). 3D conformal (3 mm block margin) SBRT plans were delivered to 2 moving targets in the phantom: 1) 20mm diameter target that allows ion chamber dose measurement and 2) 25mm target that allows using film to measure CAX dose (GafchromicTM EBT3 used). The measured dose was compared to the iPlanTM TPS results using MonteCarlo algorithm (1% variance, Dose-to-water). Results: On average, film shows 98.9% pass using gamma criterion for 2% and 2mm DTA, 94.3% match for 2% and 1 mm DTA, 98% pass for 1% and 2 mm DTA however only 88% points passing for 1% and 1 mm DTA. Ion chamber measurements agreed with the calculation within 1.5%. Conclusion: The clinical QA workflow was designed for SBRT delivery using real-time tumor tracking on VeroTM linac.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-T-359: Emulation of Yb-169 Gamma-Ray Spectrum Using Metal-Filtered 250 KVp X-Rays for Pre-Clinical Studies of Gold Nanoparticle-Aided Radiation Therapy

Purpose: To develop an external beam surrogate of the Yb-169 brachytherapy source applying a filter-based spectrum modulation technique to 250 kVp x-rays. In-vitro/vivo studies performed with the modulated 250 kVp beam will help gauge the benefits of implementing gold nanoparticle-aided radiotherapy with the Yb-169 source. Methods: A previously validated MCNP5 model of the Phillips RT-250 orthovoltage unit was used to obtain the percentage depth dose (PDD) and filtered photon spectra for a variety of filtration and irradiation conditions. Photon spectra were obtained using the average flux F4 tally in air right after all collimation. A 30 x 30 x 30 cm{sup 3} water phantom was used to compute the PDD along the central axis (CAX) under the standards conditions of a 10 x 10 cm{sup 2} field size at 50 cm SSD. Cylindrical cells of 4 cm in diameter and the energy deposition F6 tally were used along the CAX to score the doses down to 20 cm depth. The number of particle history was set to 2 x 10{sup 8} in order to keep the relative uncertainty within each cell < 0.3%. The secondary electron spectrum within a gold-loaded tissue due to each photon spectrum was also calculated using EGSnrc and compared with that due to Yb-169 gamma rays. Results: Under the practical constraints for the spectrum modulation task, 250 kVp x-rays filtered by a 0.25 mm Erbium (Er) foil produced the best match with Yb-169 gamma rays, in terms of PDD and, more importantly, secondary electron spectrum. Conclusion: Modulation of 250kVp x-ray spectrum by an Er-filter was found effective in emulating the gamma ray spectrum of Yb-169. Possible benefits as predicted from the current MC model such as enhanced radiosensitization with the Er-filtered beam (as a surrogate of Yb-169) was confirmed with a separate in-vitro study. Supported by DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-F-BRA-08: An Investigation of Well-Chamber Responses for An Electronic Brachytherapy Source

Purpose: The aim of this study was to investigate the variation of well-type ionization chamber response between a Xoft Axxent™ electronic brachytherapy (EBT) source and a GE Oncoseed™ 6711 I-125 seed. Methods: A new EBT air-kerma standard has recently been introduced by the National Institute of Standards and Technology (NIST). Historically, the Axxent source strength has been based on a well chamber calibration from an I-125 brachytherapy source due to the lack of a primary standard. Xoft utilizes a calibration procedure that employs a GE 6711 seed calibration as a surrogate standard to represent the air-kerma strength of an Axxent source. This method is based on the premise that the energies of the two sources are similar and thus, a conversion factor would be a suitable interim solution until a NIST standard was established. For this investigation, a number of well chambers of the same model type and three different EBT sources were used to determine NIST-traceable calibration coefficients for both the GE 6711 seed and the Axxent source. The ratio of the two coefficients was analyzed for consistency and also to identify any possible correlations with chamber vintage or the sources themselves. Results: For all well chambers studied, the relative standard deviation of the ratio of calibration coefficients between the two standards is less than 1%. No specific trends were found with the well chamber vintage or between the three different EBT sources used. Conclusion: The variation of well chamber calibration coefficients between a Xoft Axxent™ EBT source versus a GE 6711 Oncoseed™ are consistent across well chamber vintage and between sources. The results of this investigation confirm the underlying assumptions and stability of the surrogate standard currently in use by Xoft, and establishes a migration path for future implementation of the new NIST air kerma standard. This research is supported in part by Xoft, a subsidiary of iCAD.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2015

MO-FG-204-02: Reference Image Selection in the Presence of Multiple Scan Realizations

Purpose: Fusing information from multiple correlated realizations (e.g., 4DCT) can improve image quality. This process often involves ill-conditioned and asymmetric nonlinear registration and the proper selection of a reference image is important. This work proposes to examine post-registration variation indirectly for such selection, and develops further insights to reduce the number of cross-registrations needed. Methods: We consider each individual scan as a noisy point in the vicinity of an image manifold, related by motion. Nonrigid registration “transports” a scan along the manifold to the reference neighborhood, and the residual is a surrogate for local variation. To test this conjecture, 10 thoracic scans from the same session were reconstructed from a recently developed low-dose helical 4DCT protocol. Pairwise registration was repeated bi-directionally (81 times) and fusion was performed with each candidate reference. The fused image quality was assessed with SNR and CNR. Registration residuals in SSD, harmonic energy, and deformation Jacobian behavior were examined. The semi-symmetry is further utilized to reduce the number of registration needed. Results: The comparison of image quality between single image and fused ones identified reduction of local intensity variance as the major contributor of image quality, boosting SNR and CNR by 5 to 7 folds. This observation further suggests the criticality of good agreement across post-registration images. Triangle inequality on the SSD metric provides a proficient upper-bound and surrogate on such disagreement. Empirical observation also confirms that fused images with high residual SSD have lower SNR and CNR than the ones with low or intermediate SSDs. Registration SSD is structurally close enough to symmetry for reduced computation. Conclusion: Registration residual is shown to be a good predictor of post-fusion image quality and can be used to identify good reference centers. Semi-symmetry of the registration residual further reduces computation cost. Supported by in part by NIH R01 CA096679.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

MO-F-CAMPUS-J-03: Sorting 2D Dynamic MR Images Using Internal Respiratory Signal for 4D MRI

Purpose: To develop a novel algorithm to extract internal respiratory signal (IRS) for sorting dynamic magnetic resonance (MR) images in order to achieve four-dimensional (4D) MR imaging. Methods: Dynamic MR images were obtained with the balanced steady state free precession by acquiring each two-dimensional sagittal slice repeatedly for more than one breathing cycle. To generate a robust IRS, we used 5 different representative internal respiratory surrogates in both the image space (body area) and the Fourier space (the first two low-frequency phase components in the anterior-posterior direction, and the first two low-frequency phase components in the superior-inferior direction). A clustering algorithm was then used to search for a group of similar individual internal signals, which was then used to formulate the final IRS. A phantom study and a volunteer study were performed to demonstrate the effectiveness of this algorithm. The IRS was compared to the signal from the respiratory bellows. Results: The IRS computed by our algorithm matched well with the bellows signal in both the phantom and the volunteer studies. On average, the normalized cross correlation between the IRS and the bellows signal was 0.97 in the phantom study and 0.87 in the volunteer study, respectively. The average difference between the end inspiration times in the IRS and bellows signal was 0.18 s in the phantom study and 0.14 s in the volunteer study, respectively. 4D images sorted based on the IRS showed minimal mismatched artifacts, and the motion of the anatomy was coherent with the respiratory phases. Conclusion: A novel algorithm was developed to generate IRS from dynamic MR images to achieve 4D MR imaging. The performance of the IRS was comparable to that of the bellows signal. It can be easily implemented into the clinic and potentially could replace the use of external respiratory surrogates. This research was partially funded by the the Center for Radiation Oncology Research from UT MD Anderson Cancer Center.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Multivariate analysis for the estimation of target localization errors in fiducial marker-based radiotherapy

Purpose: To assess the target localization error (TLE) in terms of the distance between the target and the localization point estimated from the surrogates (|TMD|), the average of respiratory motion for the surrogates and the target (|aRM|), and the number of fiducial markers used for estimating the target (n). Methods: This study enrolled 17 lung cancer patients who subsequently underwent four fractions of real-time tumor tracking irradiation. Four or five fiducial markers were implanted around the lung tumor. The three-dimensional (3D) distance between the tumor and markers was at maximum 58.7 mm. One of the markers was used as the target (P{sub t}), and those markers with a 3D |TMD{sub n}| ≤ 58.7 mm at end-exhalation were then selected. The estimated target position (P{sub e}) was calculated from a localization point consisting of one to three markers except P{sub t}. Respiratory motion for P{sub t} and P{sub e} was defined as the root mean square of each displacement, and |aRM| was calculated from the mean value. TLE was defined as the root mean square of each difference between P{sub t} and P{sub e} during the monitoring of each fraction. These procedures were performed repeatedly using the remaining markers. To provide the best guidance on the answer with n and |TMD|, fiducial markers with a 3D |aRM ≥ 10 mm were selected. Finally, a total of 205, 282, and 76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n = 1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to evaluate TLE as a function of |TMD| and |aRM| in each n. Results: |TMD| for n = 1 was larger than that for n = 3. Moreover, |aRM| was almost constant for all n, indicating a similar scale for the marker’s motion near the lung tumor. MRA showed that |aRM| in the left–right direction was the major cause of TLE; however, the contribution made little difference to the 3D TLE because of the small amount of motion in the left–right direction. The TLE calculated from the MRA ({sup MRA}TLE) increased as |TMD| and |aRM| increased and adversely decreased with each increment of n. The median 3D {sup MRA}TLE was 2.0 mm (range, 0.6–4.3 mm) for n = 1, 1.8 mm (range, 0.4–4.0 mm) for n = 2, and 1.6 mm (range, 0.3–3.7 mm) for n = 3. Although statistical significance between n = 1 and n = 3 was observed in all directions, the absolute average difference and the standard deviation of the {sup MRA}TLE between n = 1 and n = 3 were 0.5 and 0.2 mm, respectively. Conclusions: A large |TMD| and |aRM| increased the differences in TLE between each n; however, the difference in 3D {sup MRA}TLEs was, at most, 0.6 mm. Thus, the authors conclude that it is acceptable to continue fiducial marker-based radiotherapy as long as |TMD| is maintained at ≤58.7 mm for a 3D |aRM| ≥ 10 mm.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-J-116: Clinical Experience-Based Verification and Improvement of a 4DCT Program

Purpose: To demonstrate the role of continuous improvement fulfilled by the Medical Physicist in clinical 4DCT and CBCT scanning. Methods: Lung (SABR and Standard) patients’ 4D respiratory motion and image data were reviewed over a 3, 6 and 12 month period following commissioning testing. By identifying trends of clinically relevant parameters and respiratory motions, variables were tested with a programmable motion phantom and assessed. Patient traces were imported to a motion phantom and 4DCT and CBCT imaging were performed. Cos6 surrogate and sup-inf motion was also programmed into the phantom to simulate the long exhale of patients for image contrast tests. Results: Patient surrogate motion amplitudes were 9.9+5.2mm (3–35) at 18+6bpm (6–30). Expiration/Inspiration time ratios of 1.4+0.5second (0.6–2.9) showed image contrast effects evident in the AveCT and 3DCBCT images. Small differences were found for patients with multiple 4DCT data sets. Patient motion assessments were simulated and verified with the phantom within 2mm. Initial image reviews to check for reconstructed artefacts and data loss identified a small number of patients with irregularities in the automatic placement of inspiration and expiration points. Conclusion: The Physicist’s involvement in the continuous improvements of a clinically commissioned technique, processes and workflows continues beyond the commissioning stage of a project. Our experience with our clinical 4DCT program shows that Physics presence is required at the clinical 4DCT scan to assist with technical aspects of the scan and also for clinical image quality assessment prior to voluming. The results of this work enabled the sharing of information from the Medical Physics group with the Radiation Oncologists and Radiation Therapists. This results in an improved awareness of clinical patient respiration variables and how they may affect 4D simulation images and also may also affect the treatment verification images.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-T-202: An Evaluation Method of Lifetime Attributable Risk for Comparing Between Proton Beam Therapy and Intensity Modulated X-Ray Therapy for Pediatric Cancer Patients by Averaging Four Dose-Response Models for Carcinoma Induction

Purpose: To examine how much lifetime attributable risk (LAR) as an in silico surrogate marker of radiation-induced secondary cancer would be lowered by using proton beam therapy (PBT) in place of intensity modulated x-ray therapy (IMXT) in pediatric patients. Methods: From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: a) brain, head, and neck, b) thoracic, c) abdominal, and d) whole craniospinal (WCNS) irradiation. IMXT was re-planned using the same computed tomography and region of interest. Using dose volume histogram (DVH) of PBT and IMXT, the LAR of Schneider et al. was calculated for the same patient. The published four dose-response models for carcinoma induction: i) full model, ii) bell-shaped model, iii) plateau model, and ix) linear model were tested for organs at risk. In the case that more than one dose-response model was available, the LAR for this patient was calculated by averaging LAR for each dose-response model. Results: Calculation of the LARs of PBT and IMXT based on DVH was feasible for all patients. The mean±standard deviation of the cumulative LAR difference between PBT and IMXT for the four categories was a) 0.77±0.44% (n=7, p=0.0037), b) 23.1±17.2%,(n=8, p=0.0067), c) 16.4±19.8% (n=8, p=0.0525), and d) 49.9±21.2% (n=3, p=0.0275, one tailed t-test), respectively. The LAR was significantly lower by PBT than IMXT for the the brain, head, and neck region, thoracic region, and whole craniospinal irradiation. Conclusion: In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. This method was suggested to be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques. This research was supported by the Translational Research Network Program, JSPS KAKENHI Grant No. 15H04768 and the Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, founded by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.

60 APPLIED LIFE SCIENCES↗