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DOE OSTI2015

Specific heat investigation for line nodes in heavily overdoped Ba 1-x K x Fe 2 As 2

Previous research has found that the pairing symmetry in the iron-based superconductor Ba 1-x K x Fe 2 As 2 changes from nodeless s-wave near optimally doped, x≈0.4-0.55 and T c >30 K, to nodal (either d-wave or s-wave) at the pure endpoint, x=1 and T c <4 K. Intense theoretical interest has been focused on this possibility of changing pairing symmetry, where in the transition region both order parameters would be present and time reversal symmetry would be broken. Here we report specific heat measurements in zero and applied magnetic fields down to 0.4 K of three individual single crystals, free of low temperature magnetic anomalies, of heavily overdoped Ba 1-x K x Fe 2 As 2 , x= 0.91, 0.88, and 0.81. The values for T c mid are 5.6, 7.2 and 13 K and for H c2 ≈ 4.5, 6, and 20 T respectively. Furthermore, the data can be analyzed in a two gap scenario, Δ 2 /Δ 1 ≈ 4, with the magnetic field dependence of γ (=C/T as T→0) showing an anisotropic ‘S-shaped’ behavior vs H, with the suppression of the lower gap by 1 T and γ ≈ H 1/2 overall. Although such a non-linear γ vs H is consistent with deep minima or nodes in the gap structure, it is not clear evidence for one, or both, of the gaps being nodal in these overdoped samples. Thus, following the established theoretical analysis of the specific heat of d-wave cuprate superconductors containing line nodes, we present the specific heat normalized by H 1/2 plotted vs T/H 1/2 of these heavily overdoped Ba 1-x K x Fe 2 As 2 samples which – thanks to the absence of magnetic impurities in our sample - convincingly shows the expected scaling for line node behavior for the larger gap for all three compositions. There is however no clear observation of the nodal behavior C ∝ αT 2 in zero field at low temperatures, with α ≤ 2 mJ/molK 3 being consistent with the data. Together with the scaling, this leaves open the possibility of extreme anisotropy in a nodeless larger gap, Δ 2 , such that the scaling works for fields above 0.25 – 0.5 T (0.2 – 0.4 K in temperature units), where this an estimate for the size of the deep minima in the Δ 2 ~ 20-25 K gap. Furthermore, the location of the change from nodeless→nodal gaps between optimally doped and heavily overdoped Ba 1-x K x Fe 2 As 2 based on the present work may be closer to the KFe 2 As 2 endpoint than x=0.91.

36 MATERIALS SCIENCE↗

DOE OSTI2024

Specific heats for quantum BTZ black holes in extended thermodynamics

It was shown recently that extended black hole thermodynamics, where the cosmological constant is a dynamical variable, giving rise to a pressure p and its conjugate volume V , can be given a natural setting in the context of braneworld models. We study the specific heat capacities C p ( T ) and C V ( T ) of the quantum version of the Bañados, Teitelboim, and Zanelli (BTZ) black hole that lives in the induced gravity theory on the brane. There are multiple branches of solutions, and we explore and characterize key features of the possible behavior. We identify and study a critical point in the space of solutions where both specific heats diverge. In the regime of weak backreaction where we are close to an ordinary theory of gravity, the black hole is “subentropic,” but as backreaction is increased we note that there are parts of parameter space that has regions where it is “superentropic.” While a study of the sign of the specific heats does not always show a corresponding instability (conjectured in the literature), the presence of strong backreaction makes interpretation unclear. Published by the American Physical Society 2024

Johnson, Clifford V. (ORCID:0000000189645830)↗

DOE OSTI2018

Decoupling Thin Film CdTe Growth from Packaging: Toward Record Specific Power in Low Cost Polycrystalline PV

There are critical material and scientific barriers to producing high efficiency, flexible, lightweight solar cells that maximize specific power in a cost-effective manner. III-V solar cells have produced the highest specific power of any photovoltaic technology due to their extremely high efficiency, however, they are also among the most expensive to produce. This work explores a novel lift-off approach with thin-film solar cells, particularly CdTe, to achieve high specific power at low costs. Thin-film devices can be delaminated from their heavy, glass growth substrates post-growth by exploiting a mismatch in coefficient of thermal expansion between the two. This allows thin-film PV to be decoupled from high temperature growth requirements and repackaged using lightweight materials. In this work we evaluate different materials and approaches for achieving large area delamination of CdTe films from their glass superstrates. It is found that epoxy bonded to a rigid handle provides robust and reproducible delamination at the TCO/CdS interface upon submersion in liquid nitrogen. Following delamination, a transparent front contact is re-deposited and selectively etched to expose the back contact to produce a functioning device. Effects of delamination and contributions to device functionality from CdCl 2 and CdS layers are discussed. Reproducible delamination of high efficiency, thin-film solar cells over large areas will enable work to further improve device efficiency through passivation and reconstruction of the previously buried interface between the transparent contact and CdS.

14 SOLAR ENERGY↗

DOE OSTI2013

Structure of NADP + -dependent glutamate dehydrogenase from Escherichia coli - reflections on the basis of coenzyme specificity in the family of glutamate dehydrogenases

Glutamate dehydrogenases catalyse the oxidative deamination of L -glutamate to α-ketoglutarate, using NAD + and/or NADP + as a cofactor. Subunits of homo-hexameric bacterial enzymes comprise a substrate-binding domain I followed by a nucleotide-binding domain II. The reaction occurs in a catalytic cleft between the two domains. Although conserved residues in the nucleotide-binding domains of various dehydrogenases have been linked to cofactor preferences, the structural basis for specificity in the GDH family remains poorly understood. Here, the refined crystal structure of Escherichia coli GDH in the absence of reactants is described at 2.5-Å resolution. Modelling of NADP + in domain II reveals the potential contribution of positively charged residues from a neighbouring α-helical hairpin to phosphate recognition. In addition, a serine that follows the P7 aspartate is presumed to form a hydrogen bond with the 2'-phosphate. Mutagenesis and kinetic analysis confirms the importance of these residues in NADP + recognition. Surprisingly, one of the positively charged residues is conserved in all sequences of NAD + -dependent enzymes, but the conformations adopted by the corresponding regions in proteins whose structure has been solved preclude their contribution to the coordination of the 2'-ribose phosphate of NADP + . These studies clarify the sequence–structure relationships in bacterial GDHs, revealing that identical residues may specify different coenzyme preferences, depending on the structural context. Primary sequence alone is therefore not a reliable guide for predicting coenzyme specificity. We also consider how it is possible for a single sequence to accommodate both coenzymes in the dual-specificity GDHs of animals.

Sharkey, Michael A.↗

DOE OSTI2025

Species‐Specific Epigenetic Signature Associates With Heat Stress Tolerance in the Perennial Tree Species Populus

Epigenetic regulation in annual plants is recognized as a key component of recurring stress acclimation and adaptation, but reports on perennial tree species are limited. In this study, two contrasting tree species, Populus trichocarpa and Populus deltoides, and an F1 hybrid cross between them showed species-specific epigenetic and physiological responses to heat stress (42°C) following priming (35°C). By analyzing whole-genome methylation, transcriptomics, proteomics, metabolomics, and photosynthesis parameters, we found that P. deltoides expresses specific epigenetic signatures in response to heat, resulting in improved photosynthetic efficiency compared to P. trichocarpa. Conversely, P. trichocarpa displayed stress signaling and defense mechanisms that could not sustain a net assimilation rate despite maintaining higher gas exchange. Heat stress following priming in hybrid plants increased transcript levels of thermotolerance-related transcription factors, such as SPL12. Selected regions in the promoter of SPL12 showed differential methylation between direct heat stress and priming followed by heat stress. As a result, upregulation of downstream genes and associated increases in protein and metabolite abundance for stress adaptation were exhibited. Consequently, hybrid plants showed enhanced photosynthesis and gas exchange rates, a trait lacking in P. trichocarpa. These results imply that priming may not be universally effective in enhancing plant performance under stress, particularly in perennial tree species. However, priming can acclimate the perennial tree species P. deltoides to withstand elevated temperature stress better. Our study has demonstrated that priming-based stress adaptation is species-specific but can be attained through crossbreeding, indicating its potential use in breeding programs.

DNA methylation↗

DOE OSTI2022

Genetically-determined variations in photosynthesis indicate roles for specific fatty acid species in chilling responses

Using a population of recombinant inbred lines (RILs) cowpea (Vigna unguiculata. L. Walp), we tested for co-linkages between lipid contents and chilling responses of photosynthesis. Under low-temperature conditions (19°C/13°C, day/night), we observed co-linkages between quantitative trait loci intervals for photosynthetic light reactions and specific fatty acids, most strikingly, the thylakoid-specific fatty acid 16:1 Δ3trans found exclusively in phosphatidylglycerol (PG 16:1t). By contrast, we did not observe co-associations with bulk polyunsaturated fatty acids or high-melting-point-PG (sum of PG 16:0, PG 18:0 and PG 16:1t) previously thought to be involved in chilling sensitivity. These results suggest that in cowpea, chilling sensitivity is modulated by specific lipid interactions rather than bulk properties. We were able to recapitulate the predicted impact of PG 16:1t levels on photosynthetic responses at low temperature using mutants and transgenic Arabidopsis lines. Because PG 16:1t synthesis requires the activity of peroxiredoxin-Q, which is activated by H 2 O 2 and known to be involved in redox signalling, here we hypothesise that the accumulation of PG 16:1t occurs as a result of upstream effects on photosynthesis that alter redox status and production of reactive oxygen species.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2013

Characterization of a novel 2D array dosimeter for patient-specific quality assurance with volumetric arc therapy

Purpose: In this study, the authors are evaluating a new, commercially available 2D array that offers 3D dose reconstruction for patient specific intensity modulated radiation therapy quality assurance (IMRT QA).Methods: The OCTAVIUS 4D system and its accompanying software (VERISOFT) by PTW were evaluated for the accuracy of the dose reconstruction for patient specific pretreatment IMRT QA. OCTAVIUS 4D measures the dose plane at the linac isocenter as the phantom rotates synchronously with the gantry, maintaining perpendicularity with the beam, by means of an inclinometer and a motor. The measurements collected during a volumetric modulated arc therapy delivery (VMAT) are reconstructed into a 3D dose volume. The VERISOFT application is used to perform the analysis, by comparing the reconstructed dose against the 3D dose matrix from the treatment planning system (TPS) that is computed for the same geometry and beam arrangement as that of the measurement. In this study, the authors evaluated the 3D dose reconstruction algorithm of this new system using a series of tests. Using the Octavius 4D phantom as the patient, dose distributions for various field sizes, beam orientations, shapes, and combination of fields were calculated using the Pinnacle3, TPS, and the respective DICOMRT dose was exported to the VERISOFT analysis software. Measurements were obtained by delivering the test treatment plans and comparisons were made based on gamma index, dose profiles, and isodose distribution analysis. In addition, output factors were measured and the dose linearity of the array was assessed. Those measurements were compared against measurements in water using a single, calibrated ionization chamber as well as calculations from Pinnacle for the same delivery geometries.Results: The number of voxels that met the 3%/3 mm criteria for the volumetric 3D gamma index analysis ranged from 92.3% to 98.9% for all the patient plans that the authors evaluated. 2D gamma analysis in the axial, sagittal, and coronal planes produced similar results to those in the 3D gamma analysis. The new detector system does not require an angular dependence correction because it rotates in synchrony with the gantry and the detector array maintains a constant SAD while always perpendicular to the beam axis. Output factors were within 2% when compared to ionization chamber measurements and Pinnacle calculations. Similar agreement was observed when testing the MU linearity (for MU values above 2) as well as dose rate effect.Conclusions: The OCTAVIUS 4D system has some unique characteristics that can potentially improve the patient specific pretreatment IMRT QA data collection and analysis. The ability of the software to reconstruct from the measurements the true 3D dose distribution in the phantom, provides a unique perspective for the medical physicist that evaluates a patient's QA plan.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2013

Comparison of Gafchromic EBT2 and EBT3 for patient-specific quality assurance: Cranial stereotactic radiosurgery using volumetric modulated arc therapy with multiple noncoplanar arcs

Purpose: Patient-specific quality assurance in volumetric modulated arc therapy (VMAT) brain stereotactic radiosurgery raises specific issues on dosimetric procedures, mainly represented by the small radiation fields associated with the lack of lateral electronic equilibrium, the need of small detectors and the high dose delivered (up to 30 Gy). Gafchromic{sup TM} EBT2 and EBT3 films may be considered the dosimeter of choice, and the authors here provide some additional data about uniformity correction for this new generation of radiochromic films.Methods: A new analysis method using blue channel for marker dye correction was proposed for uniformity correction both for EBT2 and EBT3 films. Symmetry, flatness, and field-width of a reference field were analyzed to provide an evaluation in a high-spatial resolution of the film uniformity for EBT3. Absolute doses were compared with thermoluminescent dosimeters (TLD) as baseline. VMAT plans with multiple noncoplanar arcs were generated with a treatment planning system on a selected pool of eleven patients with cranial lesions and then recalculated on a water-equivalent plastic phantom by Monte Carlo algorithm for patient-specific QA. 2D quantitative dose comparison parameters were calculated, for the computed and measured dose distributions, and tested for statistically significant differences.Results: Sensitometric curves showed a different behavior above dose of 5 Gy for EBT2 and EBT3 films; with the use of inhouse marker-dye correction method, the authors obtained values of 2.5% for flatness, 1.5% of symmetry, and a field width of 4.8 cm for a 5 × 5 cm{sup 2} reference field. Compared with TLD and selecting a 5% dose tolerance, the percentage of points with ICRU index below 1 was 100% for EBT2 and 83% for EBT3. Patients analysis revealed statistically significant differences (p < 0.05) between EBT2 and EBT3 in the percentage of points with gamma values <1 (p= 0.009 and p= 0.016); the percent difference as well as the mean difference between calculated and measured isodoses (20% and 80%) were found not to be significant (p= 0.074, p= 0.185, and p= 0.57).Conclusions: Excellent performances in terms of dose homogeneity were obtained using a new blue channel method for marker-dye correction on both EBT2 and EBT3 Gafchromic{sup TM} films. In comparison with TLD, the passing rates for the EBT2 film were higher than for EBT3; a good agreement with estimated data by Monte Carlo algorithm was found for both films, with some statistically significant differences again in favor of EBT2. These results suggest that the use of Gafchromic{sup TM} EBT2 and EBT3 films is appropriate for dose verification measurements in VMAT stereotactic radiosurgery; taking into account the uncertainty associated with Gafchromic film dosimetry, the use of adequate action levels is strongly advised, in particular, for EBT3.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2014

Isotope specific resolution recovery image reconstruction in high resolution PET imaging

Purpose: Measuring and incorporating a scanner-specific point spread function (PSF) within image reconstruction has been shown to improve spatial resolution in PET. However, due to the short half-life of clinically used isotopes, other long-lived isotopes not used in clinical practice are used to perform the PSF measurements. As such, non-optimal PSF models that do not correspond to those needed for the data to be reconstructed are used within resolution modeling (RM) image reconstruction, usually underestimating the true PSF owing to the difference in positron range. In high resolution brain and preclinical imaging, this effect is of particular importance since the PSFs become more positron range limited and isotope-specific PSFs can help maximize the performance benefit from using resolution recovery image reconstruction algorithms. Methods: In this work, the authors used a printing technique to simultaneously measure multiple point sources on the High Resolution Research Tomograph (HRRT), and the authors demonstrated the feasibility of deriving isotope-dependent system matrices from fluorine-18 and carbon-11 point sources. Furthermore, the authors evaluated the impact of incorporating them within RM image reconstruction, using carbon-11 phantom and clinical datasets on the HRRT. Results: The results obtained using these two isotopes illustrate that even small differences in positron range can result in different PSF maps, leading to further improvements in contrast recovery when used in image reconstruction. The difference is more pronounced in the centre of the field-of-view where the full width at half maximum (FWHM) from the positron range has a larger contribution to the overall FWHM compared to the edge where the parallax error dominates the overall FWHM. Conclusions: Based on the proposed methodology, measured isotope-specific and spatially variant PSFs can be reliably derived and used for improved spatial resolution and variance performance in resolution recovery image reconstruction. The benefits are expected to be more substantial for more energetic positron emitting isotopes such as Oxygen-15 and Rubidium-82.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

SU-E-T-69: Cloud-Based Monte Carlo Patient-Specific Quality Assurance (QA) Method for Volumetric Modulated Arc Therapy (VMAT)

Purpose: Patient-specific QA for VMAT is incapable of providing full 3D dosimetric information and is labor intensive in the case of severe heterogeneities or small-aperture beams. A cloud-based Monte Carlo dose reconstruction method described here can perform the evaluation in entire 3D space and rapidly reveal the source of discrepancies between measured and planned dose. Methods: This QA technique consists of two integral parts: measurement using a phantom containing array of dosimeters, and a cloud-based voxel Monte Carlo algorithm (cVMC). After a VMAT plan was approved by a physician, a dose verification plan was created and delivered to the phantom using our Varian Trilogy or TrueBeam system. Actual delivery parameters (i.e., dose fraction, gantry angle, and MLC at control points) were extracted from Dynalog or trajectory files. Based on the delivery parameters, the 3D dose distribution in the phantom containing detector were recomputed using Eclipse dose calculation algorithms (AAA and AXB) and cVMC. Comparison and Gamma analysis is then conducted to evaluate the agreement between measured, recomputed, and planned dose distributions. To test the robustness of this method, we examined several representative VMAT treatments. Results: (1) The accuracy of cVMC dose calculation was validated via comparative studies. For cases that succeeded the patient specific QAs using commercial dosimetry systems such as Delta- 4, MAPCheck, and PTW Seven29 array, agreement between cVMC-recomputed, Eclipse-planned and measured doses was obtained with >90% of the points satisfying the 3%-and-3mm gamma index criteria. (2) The cVMC method incorporating Dynalog files was effective to reveal the root causes of the dosimetric discrepancies between Eclipse-planned and measured doses and provide a basis for solutions. Conclusion: The proposed method offers a highly robust and streamlined patient specific QA tool and provides a feasible solution for the rapidly increasing use of VMAT treatments in the clinic.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-E-T-153: Establish a Comprehensive Patient-Specific Plan QA Database for Instituitional Quality Control Program

Purpose: Since the publication of TG-119, several new treatment techniques requiring new QA devices have been implemented in the clinic. To monitor and analyze our institutional QA performance, we have created a comprehensive QA database using Research Electronic Data Capture (REDCap). The database will also assist us in creating IMRT QA Analysis practice guidelines. Methods: Since Oct. 2013, 336 patient plan QA results were entered into the database. Plan parameters such as plan ID, treatment site, technique, energy, optimization constraints, modulation factor, leaf speed, leaf opening.etc were automatically extracted from the Varian Eclipse database to allow us to refine our evaluation and analysis method. Specific QA device, LINAC-related information, and measurement and analysis results were manually entered by the QA team. IMRT plans were measured using MapCHECK2 while RapidArc plans were measured using ArcCHECK. Distance-To-Agreement 3%/3mm without global maximum normalization was used. Results: The data indicates that different treatment techniques might benefit from a different site-specific action level(AL) depending on the complexity of the plan and optimization parameter used (e.g., breast IMRT QA= 97.8% and pelvis IMRT QA=93.1%). Different QA devices may also benefit from a different AL (MapCHECK2 = 94.1% while ArcCHECK = 83.0%). The relationship between the parameters and passing rate suggests that the complexity of each plan, characterized by leaf travel, leaf opening and modulation factor, affect the passing rate significantly. The database is reviewed regularly, and any abnormal point of the QA result or a trend of lower QA passing rate on a specific LINAC is further investigated. Conclusion: Establishing a comprehensive QA database provides an overview of the quality assurance program. It not only helps in answering the question “what is a reasonable and achievable standard for each institution”, but also saves time in monitoring and investigating the daily machine and QA performance.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2014

SU-E-T-305: Study of the Eclipse Electron Monte Carlo Algorithm for Patient Specific MU Calculations

Purpose: To evaluate the Eclipse electron Monte Carlo (eMC) algorithm based on patient specific monitor unit (MU) calculations, and to propose a new factor which quantitatively predicts the discrepancy of MUs between the eMC algorithm and hand calculations. Methods: Electron treatments were planned for 61 patients on Eclipse (Version 10.0) using the eMC algorithm for Varian TrueBeam linear accelerators. For each patient, the same treatment beam angle was kept for a point dose calculation at dmax performed with the reference condition, which used an open beam with a 15×15 cm2 size cone and 100 SSD. A patient specific correction factor (PCF) was obtained by getting the ratio between this point dose and the calibration dose, which is 1 cGy per MU delivered at dmax. The hand calculation results were corrected by the PCFs and compared with MUs from the treatment plans. Results: The MU from the treatment plans were in average (7.1±6.1)% higher than the hand calculations. The average MU difference between the corrected hand calculations and the eMC treatment plans was (0.07±3.48)%. A correlation coefficient of 0.8 was found between (1-PCF) and the percentage difference between the treatment plan and hand calculations. Most outliers were treatment plans with small beam opening (< 4 cm) and low energy beams (6 and 9 MeV). Conclusion: For CT-based patient treatment plans, the eMC algorithm tends to generate a larger MU than hand calculations. Caution should be taken for eMC patient plans with small field sizes and low energy beams. We hypothesize that the PCF ratio reflects the influence of patient surface curvature and tissue inhomogeneity to patient specific percent depth dose (PDD) curve and MU calculations in eMC algorithm.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-E-T-316: The Design of a Risk Index Method for 3D Patient Specific QA

Purpose: To suggest a new guidance for the evaluation of 3D patient specific QA, a structure-specific risk-index (RI) method was designed and implemented. Methods: A new algorithm was designed to assign the score of Pass, Fail or Pass with Risk to all 3D voxels in each structure by improving a conventional Gamma Index (GI) algorithm, which implied the degree of the risk of under-dose to the treatment target or over-dose to the organ at risks (OAR). Structure-specific distance to agreement (DTOA), dose difference and minimum checkable dose were applied to the GI algorithm, and additional parameters such as dose gradient factor and dose limit of structures were used to the RI method. Maximum passing rate (PR) and minimum PR were designed and calculated for each structure with the RI method. 3D doses were acquired from a spine SBRT plan by simulating the shift of beam iso-center, and tested to show the feasibility of the suggested method. Results: When the iso-center was shifted by 1 mm, 2 mm, and 3 mm, the PR of conventional GI method between shifted and non-shifted 3D doses were 99.9%, 97.4%, and 89.7% for PTV, 99.8%, 84.8%, and 63.2% for spinal cord, and 100%, 99.5%, 91.7% for right lung. The minimum PRs from the RI method were 98.9%, 96.9%, and 89.5% for PTV, and 96.1%, 79.3%, 57.5% for spinal cord, and 92.5%, 92.0%, 84.4% for right lung, respectively. The maximum PRs from the RI method were equal or less than the PRs from the conventional GI evaluation. Conclusion: Designed 3D RI method showed more strict acceptance level than the conventional GI method, especially for OARs. The RI method is expected to give the degrees of risks in the delivered doses, as well as the degrees of agreements between calculated 3D doses and measured (or simulated) 3D doses.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

SU-E-T-345: Validation of a Patient-Specific Monte Carlo Targeted Radionuclide Therapy Dosimetry Platform

Purpose: There is a compelling need for personalized dosimetry in targeted radionuclide therapy given that conventional dose calculation methods fail to accurately predict dose response relationships. To address this need, we have developed a Geant4-based Monte Carlo patient-specific 3D dosimetry platform for TRT. This platform calculates patient-specific dose distributions based on serial CT/PET or CT/SPECT images acquired after injection of the TRT agent. In this work, S-values and specific absorbed fractions (SAFs) were calculated using this platform and benchmarked against reference values. Methods: S-values for 1, 10, 100, and 1000g spherical tumors with uniform activity distributions of I-124, I-125, I-131, F-18, and Ra-223 were calculated and compared to OLINDA/EXM reference values. SAFs for monoenergetic photons of 0.01, 0.1, and 1 MeV and S factors for monoenergetic electrons of 0.935 MeV were calculated for the liver, kidneys, lungs, pancreas, spleen, and adrenals in the Zubal Phantom and compared with previously published values. Sufficient particles were simulated to keep the voxel statistical uncertainty below 5%. Results: The calculated spherical S-values agreed within a few percent of reference data from OLINDA/EXM for each radionuclide and sphere size. The comparison of photon SAFs and electron S-values with previously published values showed good agreement with the previously published values. The S-values and SAFs of the source organs agreed within 1%. Conclusion: Our platform has been benchmarked against reference values for a variety of radionuclides and over a wide range of energies and tumor sizes. Therefore, this platform could be used to provide accurate patientspecific dosimetry for use in radiopharmaceutical clinical trials.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

TU-F-BRF-02: MR-US Prostate Registration Using Patient-Specific Tissue Elasticity Property Prior for MR-Targeted, TRUS-Guided HDR Brachytherapy

Purpose: High-dose-rate (HDR) brachytherapy has become a popular treatment modality for prostate cancer. Conventional transrectal ultrasound (TRUS)-guided prostate HDR brachytherapy could benefit significantly from MR-targeted, TRUS-guided procedure where the tumor locations, acquired from the multiparametric MRI, are incorporated into the treatment planning. In order to enable this integration, we have developed a MR-TRUS registration with a patient-specific biomechanical elasticity prior. Methods: The proposed method used a biomechanical elasticity prior to guide the prostate volumetric B-spline deformation in the MRI and TRUS registration. The patient-specific biomechanical elasticity prior was generated using ultrasound elastography, where two 3D TRUS prostate images were acquired under different probe-induced pressures during the HDR procedure, which takes 2-4 minutes. These two 3D TRUS images were used to calculate the local displacement (elasticity map) of two prostate volumes. The B-spline transformation was calculated by minimizing the Euclidean distance between the normalized attribute vectors of the prostate surface landmarks on the MR and TRUS. This technique was evaluated through two studies: a prostate-phantom study and a pilot study with 5 patients undergoing prostate HDR treatment. The accuracy of our approach was assessed through the locations of several landmarks in the post-registration and TRUS images; our registration results were compared with the surface-based method. Results: For the phantom study, the mean landmark displacement of the proposed method was 1.29±0.11 mm. For the 5 patients, the mean landmark displacement of the surface-based method was 3.25±0.51 mm; our method, 1.71±0.25 mm. Therefore, our proposed method of prostate registration outperformed the surfaced-based registration significantly. Conclusion: We have developed a novel MR-TRUS prostate registration approach based on patient-specific biomechanical elasticity prior. Successful integration of multi-parametric MR and TRUS prostate images provides a prostate-cancer map for treatment planning, enables accurate dose planning and delivery, and potentially enhances prostate HDR treatment outcome.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

TH-A-BRF-10: Quantification of Subject-Specific Susceptibility-Related Geometric Distortion in Clinical Liver MRI for Radiation Therapy

Purpose: Subject-specific susceptibility-induced B0 inhomogeneity affects the geometric accuracy of MRI images, with potential impact on the accuracy of treatment planning and image guidance. This study quantifies individual distortions for patients with intrahepatic tumors. Methods: Liver MRI scans of 13 patients who were enrolled in an IRB approved study were acquired on a 3T scanner (Skyra, Siemens). Clinical contrast-enhanced images were acquired by a 3D Volume Interpolated Breath-Hold Examination (VIBE) sequence with TE/TR =1.65/4.3ms, voxel size = 2.5×2.5×3mm (axial sets) or 3.5×3.5×5mm (coronal sets), and frequency-encoding (FE) bandwidth of 440Hz/pixel. B0 inhomogeneity was evaluated by acquisition of dual gradient echoes (GRE) with TE1/TE2/TR =4.92/7.38/106ms, a voxel size of 3.5×3.5×3.75mm, a FE bandwidth of 290Hz/pixel and breath-hold. The phase difference maps from the two echoes were unwrapped using a quantitative MRI analysis software package (FSL, FMRIB, Oxford, UK). The resulting calculated B0 inhomogeneity maps (ΔB0 in Hz) were converted to voxel distortion maps in the FE direction (ΔX in mm) corresponding to the VIBE images. Results: Maximum susceptibility-induced distortions were observed in the liver dome near the diaphragm. Using results from coronal VIBE images in this study as examples, we observed clusters of voxels displaced close to or greater than ΔX=3.5mm (440 Hz in ΔB0) in the VIBE images of the liver in 3 patients, and greater than 2 mm but less than 3.5 mm in 12 patients. On average, approximately 14% of imaged liver voxels had distortions ΔX>±1mm (ΔB0>±125Hz) and 1% of the voxels had ΔX>±2mm (ΔB0>±250Hz). Conclusion: Although advanced MRI techniques, like VIBE, permit faster acquisitions allowing for breath-held examinations with limited motion-induced artifacts, this study suggests that localized distortions due to subject-specific susceptibility variations can occur and require additional advanced corrections based on measuring patient-specific B0 inhomogeneity maps. The authors would like to acknowledge funding support from NIH R01EB016079 and NIH/NCI RO1 CA132834.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

TH-C-BRD-05: Reducing Proton Beam Range Uncertainty with Patient-Specific CT HU to RSP Calibrations Based On Single-Detector Proton Radiography

Purpose: Beam range uncertainty in proton treatment comes primarily from converting the patient's X-ray CT (xCT) dataset to relative stopping power (RSP). Current practices use a single curve for this conversion, produced by a stoichiometric calibration based on tissue composition data for average, healthy, adult humans, but not for the individual in question. Proton radiographs produce water-equivalent path length (WEPL) maps, dependent on the RSP of tissues within the specific patient. This work investigates the use of such WEPL maps to optimize patient-specific calibration curves for reducing beam range uncertainty. Methods: The optimization procedure works on the principle of minimizing the difference between the known WEPL map, obtained from a proton radiograph, and a digitally-reconstructed WEPL map (DRWM) through an RSP dataset, by altering the calibration curve that is used to convert the xCT into an RSP dataset. DRWMs were produced with Plastimatch, an in-house developed software, and an optimization procedure was implemented in Matlab. Tests were made on a range of systems including simulated datasets with computed WEPL maps and phantoms (anthropomorphic and real biological tissue) with WEPL maps measured by single detector proton radiography. Results: For the simulated datasets, the optimizer showed excellent results. It was able to either completely eradicate or significantly reduce the root-mean-square-error (RMSE) in the WEPL for the homogeneous phantoms (to zero for individual materials or from 1.5% to 0.2% for the simultaneous optimization of multiple materials). For the heterogeneous phantom the RMSE was reduced from 1.9% to 0.3%. Conclusion: An optimization procedure has been designed to produce patient-specific calibration curves. Test results on a range of systems with different complexities and sizes have been promising for accurate beam range control in patients. This project was funded equally by the Engineering and Physical Sciences Research Council (UK) and Ion Beam Applications (Louvain-La-Neuve, Belgium)

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2014

Toward optimizing patient-specific IMRT QA techniques in the accurate detection of dosimetrically acceptable and unacceptable patient plans

Purpose: The authors investigated the performance of several patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA) dosimeters in terms of their ability to correctly identify dosimetrically acceptable and unacceptable IMRT patient plans, as determined by an in-house-designed multiple ion chamber phantom used as the gold standard. A further goal was to examine optimal threshold criteria that were consistent and based on the same criteria among the various dosimeters. Methods: The authors used receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of (1) a 2D diode array undergoing anterior irradiation with field-by-field evaluation, (2) a 2D diode array undergoing anterior irradiation with composite evaluation, (3) a 2D diode array using planned irradiation angles with composite evaluation, (4) a helical diode array, (5) radiographic film, and (6) an ion chamber. This was done with a variety of evaluation criteria for a set of 15 dosimetrically unacceptable and 9 acceptable clinical IMRT patient plans, where acceptability was defined on the basis of multiple ion chamber measurements using independent ion chambers and a phantom. The area under the curve (AUC) on the ROC curves was used to compare dosimeter performance across all thresholds. Optimal threshold values were obtained from the ROC curves while incorporating considerations for cost and prevalence of unacceptable plans. Results: Using common clinical acceptance thresholds, most devices performed very poorly in terms of identifying unacceptable plans. Grouping the detector performance based on AUC showed two significantly different groups. The ion chamber, radiographic film, helical diode array, and anterior-delivered composite 2D diode array were in the better-performing group, whereas the anterior-delivered field-by-field and planned gantry angle delivery using the 2D diode array performed less well. Additionally, based on the AUCs, there was no significant difference in the performance of any device between gamma criteria of 2%/2 mm, 3%/3 mm, and 5%/3 mm. Finally, optimal cutoffs (e.g., percent of pixels passing gamma) were determined for each device and while clinical practice commonly uses a threshold of 90% of pixels passing for most cases, these results showed variability in the optimal cutoff among devices. Conclusions: IMRT QA devices have differences in their ability to accurately detect dosimetrically acceptable and unacceptable plans. Field-by-field analysis with a MapCheck device and use of the MapCheck with a MapPhan phantom while delivering at planned rotational gantry angles resulted in a significantly poorer ability to accurately sort acceptable and unacceptable plans compared with the other techniques examined. Patient-specific IMRT QA techniques in general should be thoroughly evaluated for their ability to correctly differentiate acceptable and unacceptable plans. Additionally, optimal agreement thresholds should be identified and used as common clinical thresholds typically worked very poorly to identify unacceptable plans.

60 APPLIED LIFE SCIENCES↗