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Interindividual registration and dose mapping for voxelwise population analysis of rectal toxicity in prostate cancer radiotherapy

Purpose: Recent studies revealed a trend toward voxelwise population analysis in order to understand the local dose/toxicity relationships in prostate cancer radiotherapy. Such approaches require, however, an accurate interindividual mapping of the anatomies and 3D dose distributions toward a common coordinate system. This step is challenging due to the high interindividual variability. In this paper, the authors propose a method designed for interindividual nonrigid registration of the rectum and dose mapping for population analysis. Methods: The method is based on the computation of a normalized structural description of the rectum using a Laplacian-based model. This description takes advantage of the tubular structure of the rectum and its centerline to be embedded in a nonrigid registration-based scheme. The performances of the method were evaluated on 30 individuals treated for prostate cancer in a leave-one-out cross validation. Results: Performance was measured using classical metrics (Dice score and Hausdorff distance), along with new metrics devised to better assess dose mapping in relation with structural deformation (dose-organ overlap). Considering these scores, the proposed method outperforms intensity-based and distance maps-based registration methods. Conclusions: The proposed method allows for accurately mapping interindividual 3D dose distributions toward a single anatomical template, opening the way for further voxelwise statistical analysis.

60 APPLIED LIFE SCIENCES↗

Motion tracking in the liver: Validation of a method based on 4D ultrasound using a nonrigid registration technique

Purpose: Treatments like radiotherapy and focused ultrasound in the abdomen require accurate motion tracking, in order to optimize dosage delivery to the target and minimize damage to critical structures and healthy tissues around the target. 4D ultrasound is a promising modality for motion tracking during such treatments. In this study, the authors evaluate the accuracy of motion tracking in the liver based on deformable registration of 4D ultrasound images. Methods: The offline analysis was performed using a nonrigid registration algorithm that was specifically designed for motion estimation from dynamic imaging data. The method registers the entire 4D image data sequence in a groupwise optimization fashion, thus avoiding a bias toward a specifically chosen reference time point. Three healthy volunteers were scanned over several breathing cycles (12 s) from three different positions and angles on the abdomen; a total of nine 4D scans for the three volunteers. Well-defined anatomic landmarks were manually annotated in all 96 time frames for assessment of the automatic algorithm. The error of the automatic motion estimation method was compared with interobserver variability. The authors also performed experiments to investigate the influence of parameters defining the deformation field flexibility and evaluated how well the method performed with a lower temporal resolution in order to establish the minimum frame rate required for accurate motion estimation. Results: The registration method estimated liver motion with an error of 1 mm (75% percentile over all datasets), which was lower than the interobserver variability of 1.4 mm. The results were only slightly dependent on the degrees of freedom of the deformation model. The registration error increased to 2.8 mm with an eight times lower temporal resolution. Conclusions: The authors conclude that the methodology was able to accurately track the motion of the liver in the 4D ultrasound data. The authors believe that the method has potential in interventions on moving abdominal organs such as MR or ultrasound guided focused ultrasound therapy and radiotherapy, pending the method is enabled to run in real-time. The data and the annotations used for this study are made publicly available for those who would like to test other methods on 4D liver ultrasound data.

60 APPLIED LIFE SCIENCES↗

Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors

As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estimates for upper digestive tract cancers. In this study, we added 11 years of follow-up (1958–2009), used improved radiation dose estimates, considered effects of smoking and alcohol consumption and performed dose-response analyses by anatomical sub-site. In examining 52 years'worth of data, we ascertained the occurrence of 394 oral cavity/pharyngeal cancers, 486 esophageal cancers and 5,661 stomach cancers among 105,444 subjects. The radiation risk for oral cavity/pharyngeal cancer, other than salivary gland, was elevated but not significantly so. In contrast, salivary gland cancer exhibited a strong linear dose response with excess relative risk (ERR) of 2.54 per Gy [95% confidence interval (CI): 0.69 to 6.1]. Radiation risk decreased considerably with increasing age at time of exposure (–66% per decade, 95% CI: –88% to –32%). The dose response for esophageal cancer was statistically significant under a simple linear, linear-quadratic and quadratic model. Both linear-quadratic and quadratic models described the data better than a simple linear model and, of the two, the quadratic model showed a marginally better fit based on the Akaike Information Criteria. Sex difference in linear ERRs was not statistically significant; however, when the dose-response shape was allowed to vary by sex, statistically significant curvature was found among males, with no evidence of quadratic departure from linearity among females. The risk for stomach cancer increased significantly with dose and there was little evidence for quadratic departure from linearity among either males or females. The sex-averaged ERR at age 70 was 0.33 per Gy (95% CI: 0.20 to 0.47). The ERR decreased significantly (–1.93 power of attained age, 95% CI: –2.94 to –0.82) with increasing attained age, but not with age at exposure, and was higher in females than males (P = 0.02). Our results are largely consistent with the results of prior LSS analyses. Salivary gland, esophageal and stomach cancers continue to show significant increases in risk with radiation dose. Adjustment for lifestyle factors had almost no impact on the radiation effect estimates. Further follow-up of the LSS cohort is important to clarify the nature of radiation effects for upper digestive tract cancers, especially for oral cavity/pharyngeal and esophageal cancers, for which detailed investigation for dose-response shape could not be conducted due to the small number of cases.

60 APPLIED LIFE SCIENCES↗

Diffusion processes in tumors: A nuclear medicine approach

The number of counts used in nuclear medicine imaging techniques, only provides physical information about the desintegration of the nucleus present in the the radiotracer molecules that were uptaken in a particular anatomical region, but that information is not a real metabolic information. For this reason a mathematical method was used to find a correlation between number of counts and {sup 18}F-FDG mass concentration. This correlation allows a better interpretation of the results obtained in the study of diffusive processes in an agar phantom, and based on it, an image from the PETCETIX DICOM sample image set from OsiriX-viewer software was processed. PET-CT gradient magnitude and Laplacian images could show direct information on diffusive processes for radiopharmaceuticals that enter into the cells by simple diffusion. In the case of the radiopharmaceutical {sup 18}F-FDG is necessary to include pharmacokinetic models, to make a correct interpretation of the gradient magnitude and Laplacian of counts images.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Modelling kidney disease using ontology: insights from the Kidney Precision Medicine Project

An important need exists to better understand and stratify kidney disease according to its underlying pathophysiology in order to develop more precise and effective therapeutic agents. National collaborative efforts such as the Kidney Precision Medicine Project are working towards this goal through the collection and integration of large, disparate clinical, biological and imaging data from patients with kidney disease. Ontologies are powerful tools that facilitate these efforts by enabling researchers to organize and make sense of different data elements and the relationships between them. Ontologies are critical to support the types of big data analysis necessary for kidney precision medicine, where heterogeneous clinical, imaging and biopsy data from diverse sources must be combined to define a patient’s phenotype. Here, the development of two new ontologies — the Kidney Tissue Atlas Ontology and the Ontology of Precision Medicine and Investigation — will support the creation of the Kidney Tissue Atlas, which aims to provide a comprehensive molecular, cellular and anatomical map of the kidney. These ontologies will improve the annotation of kidney-relevant data, and eventually lead to new definitions of kidney disease in support of precision medicine.

60 APPLIED LIFE SCIENCES↗

A novel approach to assess the treatment response using Gaussian random field in PET

Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128{sup 2} pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response assessment utilizing local average method based on random field. The accuracy of the estimation was validated in terms of Euler distance and correlation coefficient. Results: It is shown that the performance of therapy response assessment is significantly improved by the introduction of variance with a higher area under the curve (97.3%) than SUVmean (91.4%) and SUVmax (82.0%). In addition, the FPR estimation serves as a good prediction for the specificity of the proposed method, consistent with simulation outcome with ∼1 correlation coefficient. Conclusions: In this work, the authors developed a method to evaluate therapy response from PET images, which were modeled as Gaussian random field. The digital phantom simulations demonstrated that the proposed method achieved a large reduction in statistical variability through incorporating knowledge of the variance of the original Gaussian random field. The proposed method has the potential to enable prediction of early treatment response and shows promise for application to clinical practice. In future work, the authors will report on the robustness of the estimation theory for application to clinical practice of therapy response evaluation, which pertains to binary discrimination tasks at a fixed location in the image such as detection of small and weak lesion.

61 RADIATION PROTECTION AND DOSIMETRY↗

BrachyView, A novel inbody imaging system for HDR prostate brachytherapy: Design and Monte Carlo feasibility study

Purpose: High dose rate (HDR) brachytherapy is a form of radiation therapy for treating prostate cancer whereby a high activity radiation source is moved between predefined positions inside applicators inserted within the treatment volume. Accurate positioning of the source is essential in delivering the desired dose to the target area while avoiding radiation injury to the surrounding tissue. In this paper, HDR BrachyView, a novel inbody dosimetric imaging system for real time monitoring and verification of the radioactive seed position in HDR prostate brachytherapy treatment is introduced. The current prototype consists of a 15 Multiplication-Sign 60 mm{sup 2} silicon pixel detector with a multipinhole tungsten collimator placed 6.5 mm above the detector. Seven identical pinholes allow full imaging coverage of the entire treatment volume. The combined pinhole and pixel sensor arrangement is geometrically designed to be able to resolve the three-dimensional location of the source. The probe may be rotated to keep the whole prostate within the transverse plane. The purpose of this paper is to demonstrate the efficacy of the design through computer simulation, and to estimate the accuracy in resolving the source position (in detector plane and in 3D space) as part of the feasibility study for the BrachyView project.Methods: Monte Carlo simulations were performed using the GEANT4 radiation transport model, with a {sup 192}Ir source placed in different locations within a prostate phantom. A geometrically accurate model of the detector and collimator were constructed. Simulations were conducted with a single pinhole to evaluate the pinhole design and the signal to background ratio obtained. Second, a pair of adjacent pinholes were simulated to evaluate the error in calculated source location.Results: Simulation results show that accurate determination of the true source position is easily obtainable within the typical one second source dwell time. The maximum error in the estimated projection position was found to be 0.95 mm in the imaging (detector) plane, resulting in a maximum source positioning estimation error of 1.48 mm.Conclusions: HDR BrachyView is a feasible design for real-time source tracking in HDR prostate brachytherapy. It is capable of resolving the source position within a subsecond dwell time. In combination with anatomical information obtained from transrectal ultrasound imaging, HDR BrachyView adds a significant quality assurance capability to HDR brachytherapy treatment systems.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-T-73: Commissioning of a Treatment Planning System for Proton Spot Scanning

Purpose: A treatment planning system (TPS) was commissioned for clinical use with a fixed beam line proton delivery system. An outline of the data collection, modeling, and verification is provided. Methods: Beam data modeling for proton spot scanning in CMS Xio TPS requires the following measurements: (i) integral depth dose curves (IDDCs); (ii) absolute dose calibration; and (iii) beam spot characteristics. The IDDCs for 18 proton energies were measured using an integrating detector in a single spot field in a water phantom. Absolute scaling of the IDDCs were performed based on ion chamber measurements in mono-energetic 10×10 cm{sup 2} fields in water. Beam spot shapes were measured in air using a flat panel scintillator detector at multiple planes. For beam model verification, more than 45 uniform dose phantom and patient plans were generated. These plans were used to measure range, point dose, and longitudinal and lateral profiles. Tolerances employed for verification are: point dose and longitudinal profiles, ±2%; range, ±1 mm; FWHM for lateral profiles, ±2 mm; and patient plan dose distribution, gamma index of >90% at 3%/3 mm criteria. Results: More than 97% of the point dose measurements out of 115 were within +/-2% with maximum deviation of 3%. 98% of the ranges measured were within 1 mm with maximum deviation of 1.4mm. The normalized depth doses were within 2% at all depths. The maximum error in FWHM of lateral profiles was found to be less than 2mm. For 5 patient plans representing different anatomic sites, a total of 38 planes for 12 beams were analyzed for gamma index with average value of 99% and minimum of 94%. Conclusions: The planning system is successfully commissioned and can be safely deployed for clinical use. Measurements of IDDCs on user beam are highly recommended instead of using standard beam IDDCs.

60 APPLIED LIFE SCIENCES↗

Clinical effects of 3D printing-assisted posterolateral incision in the treatment of ankle fractures involving the posterior malleolus

Objective To explore the clinical outcomes of a 3D printing-assisted posterolateral approach for the treatment of ankle fractures involving the posterior malleolus. Methods A total of 51 patients with ankle fractures involving the posterior malleolus admitted to our hospital from January 2018 to December 2019 were selected. The patients were divided into 3D printing group (28 cases) and control group (23 cases). 3D printing was performed for ankle fractures, followed by printing of a solid model and simulation of the operation on the 3D model. The operation was then performed according to the preoperative plan, including open reduction and internal fixation via the posterolateral approach with the patient in the prone position. Routine x-ray and CT examinations of the ankle joint were performed, and ankle function was evaluated using the American Foot and Ankle Surgery Association (AOFAS) ankle-hindfoot score. Results All patients underwent x-ray and CT examinations. All fractures healed clinically, without loss of reduction or failure of internal fixation. Good clinical effects were achieved in both groups of patients. The operation time, intraoperative blood loss and intraoperative fluoroscopy frequency in the 3D printing group were significantly less than those in the control group ( p < 0.05). There was no significant difference between the two groups in the anatomical reduction rate of fractures or the incidence of surgical complications ( p > 0.05). Conclusion The 3D printing-assisted posterolateral approach is effective in the treatment of ankle fractures involving the posterior malleolus. The approach can be well planned before the operation, is simple to perform, yields good fracture reduction and fixation, and has good prospects for clinical application.

Zheng, Hongming↗

TU-CD-BRB-09: Prediction of Chemo-Radiation Outcome for Rectal Cancer Based On Radiomics of Tumor Clinical Characteristics and Multi-Parametric MRI

Purpose: To evaluate the tumor clinical characteristics and quantitative multi-parametric MR imaging features for prediction of response to chemo-radiation treatment (CRT) in locally advanced rectal cancer (LARC). Methods: Forty-three consecutive patients (59.7±6.9 years, from 09/2013 – 06/2014) receiving neoadjuvant CRT followed by surgery were enrolled. All underwent MRI including anatomical T1/T2, Dynamic Contrast Enhanced (DCE)-MRI and Diffusion-Weighted MRI (DWI) prior to the treatment. A total of 151 quantitative features, including morphology/Gray Level Co-occurrence Matrix (GLCM) texture from T1/T2, enhancement kinetics and the voxelized distribution from DCE-MRI, apparent diffusion coefficient (ADC) from DWI, along with clinical information (carcinoembryonic antigen CEA level, TNM staging etc.), were extracted for each patient. Response groups were separated based on down-staging, good response and pathological complete response (pCR) status. Logistic regression analysis (LRA) was used to select the best predictors to classify different groups and the predictive performance were calculated using receiver operating characteristic (ROC) analysis. Results: Individual imaging category or clinical charateristics might yield certain level of power in assessing the response. However, the combined model outperformed than any category alone in prediction. With selected features as Volume, GLCM AutoCorrelation (T2), MaxEnhancementProbability (DCE-MRI), and MeanADC (DWI), the down-staging prediciton accuracy (area under the ROC curve, AUC) could be 0.95, better than individual tumor metrics with AUC from 0.53–0.85. While for the pCR prediction, the best set included CEA (clinical charateristics), Homogeneity (DCE-MRI) and MeanADC (DWI) with an AUC of 0.89, more favorable compared to conventional tumor metrics with an AUC ranging from 0.511–0.79. Conclusion: Through a systematic analysis of multi-parametric MR imaging features, we are able to build models with improved predictive value over conventional imaging or clinical metrics. This is encouraging, suggesting the wealth of imaging radiomics should be further explored to help tailor the treatment into the era of personalized medicine. This work is supported by the National Science Foundation of China (NSFC Grant No. 81201091), National High Technology Research and Development Program of China (863 program, Grant No. 2015AA020917), and Fund Project for Excellent Abroad Scholar Personnel in Science and Technology.

60 APPLIED LIFE SCIENCES↗

Heel effect adaptive flat field correction of digital x-ray detectors

Purpose: Anode heel effect renders large-scale background nonuniformities in digital radiographs. Conventional offset/gain calibration is performed at mono source-to-image distance (SID), and disregards the SID-dependent characteristic of heel effect. It results in a residual nonuniform background in the corrected radiographs when the SID settings for calibration and correction differ. In this work, the authors develop a robust and efficient computational method for digital x-ray detector gain correction adapted to SID-variant heel effect, without resorting to physical filters, phantoms, complicated heel effect models, or multiple-SID calibration and interpolation.Methods: The authors present the Duo-SID projection correction method. In our approach, conventional offset/gain calibrations are performed only twice, at the minimum and maximum SIDs of the system in typical clinical use. A fast iterative separation algorithm is devised to extract the detector gain and basis heel patterns from the min/max SID calibrations. The resultant detector gain is independent of SID, while the basis heel patterns are parameterized by the min- and max-SID. The heel pattern at any SID is obtained from the min-SID basis heel pattern via projection imaging principles. The system gain desired at a specific acquisition SID is then constructed using the projected heel pattern and detector gain map.Results: The method was evaluated for flat field and anatomical phantom image corrections. It demonstrated promising improvements over interpolation and conventional gain calibration/correction methods, lowering their correction errors by approximately 70% and 80%, respectively. The separation algorithm was able to extract the detector gain and heel patterns with less than 2% error, and the Duo-SID corrected images showed perceptually appealing uniform background across the detector.Conclusions: The Duo-SID correction method has substantially improved on conventional offset/gain corrections for digital x-ray imaging in an SID-variant environment. The technique is relatively simple, and can be easily incorporated into multiple-point gain calibration/correction techniques. It offers a potentially valuable tool for preprocessing digital x-ray images to boost image quality of mammography, chest and cardiac radiography, as well as automated computer aided diagnostic radiology.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Core States of Neutron Stars from Anatomizing Their Scaled Structure Equations

Given an Equation of State (EOS) for neutron star (NS) matter, there is a unique mass–radius sequence characterized by a maximum mass ${M}_{\mathrm{NS}}^{\max}$ at radius $R$ max . We first show analytically that the ${M}_{\mathrm{NS}}^{\max}$ and $R$ max scale linearly with two different combinations of the NS central pressure $P$ $c$ and energy density $ε$ $c$ , by dissecting perturbatively the dimensionless Tolman–Oppenheimer–Volkoff (TOV) equations governing NS internal variables. The scaling relations are then verified via 87 widely used and rather diverse phenomenological as well as 17 microscopic NS EOSs with/without considering hadron–quark phase transitions and hyperons, by solving numerically the original TOV equations. The EOS of the densest NS matter allowed before it collapses into a black hole is then obtained. Using the universal ${M}_{\mathrm{NS}}^{\max}$ and $R$ max scalings and Neutron Star Interior Composition Explorer and XMM-Newton mass–radius observational data for PSR J0740+6620, a very narrow constraining band on the NS central EOS is extracted directly from the data for the first time, without using any specific input EOS model.

79 ASTRONOMY AND ASTROPHYSICS↗

TH-C-17A-12: Integrated CBCT and Optical Tomography System On-Board a Small Animal Radiation Research Platform (SARRP)

Purpose: We present a newly developed on-board optical tomography system for SARRP. Innovative features include the compact design and fast acquisition optical method to perform 3D soft tissue radiation guidance. Because of the on-board feature and the combination of the CBCT, diffusive optical tomography (DOT), bioluminescence and fluorescence tomography (BLT and FT), this integrated system is expected to provide more accurate soft tissue guidance than an off-line system as well as highly sensitive functional imaging in preclinical research. Methods: Images are acquired in the order of CBCT, DOT and then BLT/FT, where the SARRP CBCT and DOT are used to provide the anatomical and optical properties information to enhance the subsequent BLT/FT optical reconstruction. The SARRP stage is redesigned to include 9 imbedded optical fibers in contact with the animal's skin. These fibers, connected to a white light lamp or laser, serve as the light sources for the DOT or FT, respectively. A CCD camera with f/1.4 lens and multi-spectral filter set is used as the optical detector and is mounted on a portable cart ready to dock into the SARRP. No radiation is delivered during optical image acquisition. A 3-way mirror system capable of 180 degree rotation around the animal reflects the optical signal to the camera at multiple projection angles. A special black-painted dome covers the stage and provides the light shielding. Results: Spontaneous metastatic bioluminescent liver and lung tumor models will be used to validate the 3D BLT reconstruction. To demonstrate the capability of our FT system, GastroSense750 fluorescence agent will be used to imaging the mouse stomach and intestinal region in 3D. Conclusion: We expect that this integrated CBCT and optical tomography on-board a SARRP will present new research opportunities for pre-clinical radiation research. Supported by NCI RO1-CA 158100.

60 APPLIED LIFE SCIENCES↗

DEEPER: An Intergrated Platform for Deeper Roots

Crops with deeper roots would have multiple benefits, including better drought tolerance, reduced requirement for nitrogen fertilizer, and better sequestration of atmospheric CO 2 . DEEPER is an integrated platform of phenomic, genomic, and in silico technologies to generate maize lines with deeper roots. DEEPER is: LEADER (Leaf Elemental Accumulation from Deep Roots) is a breakthrough technology to nondestructively measure rooting depth by using the plant itself as a sensor. LEADER uses handheld X-ray Fluorescence spectrometry to quantify foliar accumulation of elements that are differentially distributed in the soil profile. LEADER is nondestructive and is orders of magnitude cheaper, faster, and more precise than any competing assay of rooting depth in the field. LEADER is able to distinguish deep-rooted from shallow-rooted maize lines in the field without the need for costly and noisy soil coring. RootRobot/DIRT3D, to automatically phenotype root architecture in any field, combining RootRobot, a mechatronics platform to excavate, clean, section, and image mature root crowns, with DIRT3D, software to quantify architectural traits in 3D. Anatomics, a high-throughput platform to phenotype root anatomy, combining LAT 2.0, a technology for 3D imaging of root anatomy and composition, with RootScan3D, software to automatically extract 3D anatomical and cell wall composition metrics from LAT 2.0 output. Using this platform we discovered two novel root traits, parenchyma cell wall thickness and multiseriate cortical sclerenchyma, that improve rooting depth and drought tolerance in maize and wheat. OpenSimRoot/Deep, software to simulate root interaction with hard subsoils. Using this platform we discovered novel concepts regarding how to increase crop rooting depth by modulating how individual root axes respond to hard soil. DeepGenes, a toolkit of genes, parent lines, and genomic selection strategies to enable breeding hybrids with deeper roots. We discovered 3 novel root genes that increase rooting depth in maize and wheat. DEEPER discovered novel root phenotypes for deeper rooting, and delivered validated ideotypes for deeper-rooted maize; novel technologies to rapidly assess root depth, root architecture and anatomy in field-grown plants; novel software tools for root modeling and 3D image analysis of root architecture and anatomy; and validated genes and genomic selection models to deploy traits for deeper rooting in maize breeding. Each DEEPER technology is transformative in its own right, and exceeds existing technologies. They are mutually synergistic, deployable for field-grown plants, and are ready for application. The phenotyping and modeling technologies are readily applicable to many crops, and genetic leads in maize may have utility in other grasses. Taken as a whole they represent a transformative platform to develop deeper-rooted crops, with greater drought tolerance, reduced fertilizer requirement, and greater carbon sequestration.

59 BASIC BIOLOGICAL SCIENCES↗

SU-F-E-03: PET/CT Guided Dose Boost to Hypoxic Sub-Volume in Nasopharyngeal Carcinomas Using Self-Optimizing Non-Uniform VMAT

Purpose: This study is to evaluate the feasibility of simultaneously integrated boost (SIB) to hypoxic subvolume (HTV) in nasopharyngeal carcinomas under the guidance of 18F-Fluoromisonidazole (FMISO) PET/CT using a novel non-uniform volumetric modulated arc therapy (VMAT)technique. Methods: Eight nasopharyngeal carcinoma patients treated with conventional uniform VMAT were retrospectively analyzed. For each treatment, actual conventional uniform VMAT plan with two or more arcs (2–2.5 arcs, totally rotating angle < 1000o) was designed with dose boost to hopxic subvolume (total dose, 84Gy) in the gross tumor volme (GTV) under the guidance of 18F- FMISO PET/CT. Based on the same dataset, experimental single arc non-uniform VAMT plans were generated with the same dose prescription using customized software tools. Dosimetric parameters, quality assurance and the efficiency of the treatment delivery were compared between the uniform and non-uniform VMAT plans. Results: To develop the non-uniform VMAT technique, a specific optimization model was successfully established. Both techniques generate high-quality plans with pass rate (>98%) with the 3mm, 3% criterion. HTV received dose of 84.1±0.75Gy and 84.1±1.2Gy from uniform and non-uniform VMAT plans, respectively. In terms of target coverage and dose homogeneity, there was no significant statistical difference between actual and experimental plans for each case. However, for critical organs at risk (OAR), including the parotids, oral cavity and larynx, dosimetric difference was significant with better dose sparing form experimental plans. Regarding plan implementation efficiency, the average machine time was 3.5 minutes for the actual VMAT plans and 3.7 minutes for the experimental nonuniform VMAT plans (p>0.050). Conclusion: Compared to conventional VMAT technique, the proposed non-uniform VMAT technique has the potential to produce efficient and safe treatment plans, especially in cases with complicated anatomical structures and demanding dose boost to subvolumes.

60 APPLIED LIFE SCIENCES↗

A hybrid reconstruction algorithm for fast and accurate 4D cone-beam CT imaging

Purpose: 4D cone beam CT (4D-CBCT) has been utilized in radiation therapy to provide 4D image guidance in lung and upper abdomen area. However, clinical application of 4D-CBCT is currently limited due to the long scan time and low image quality. The purpose of this paper is to develop a new 4D-CBCT reconstruction method that restores volumetric images based on the 1-min scan data acquired with a standard 3D-CBCT protocol. Methods: The model optimizes a deformation vector field that deforms a patient-specific planning CT (p-CT), so that the calculated 4D-CBCT projections match measurements. A forward-backward splitting (FBS) method is invented to solve the optimization problem. It splits the original problem into two well-studied subproblems, i.e., image reconstruction and deformable image registration. By iteratively solving the two subproblems, FBS gradually yields correct deformation information, while maintaining high image quality. The whole workflow is implemented on a graphic-processing-unit to improve efficiency. Comprehensive evaluations have been conducted on a moving phantom and three real patient cases regarding the accuracy and quality of the reconstructed images, as well as the algorithm robustness and efficiency. Results: The proposed algorithm reconstructs 4D-CBCT images from highly under-sampled projection data acquired with 1-min scans. Regarding the anatomical structure location accuracy, 0.204 mm average differences and 0.484 mm maximum difference are found for the phantom case, and the maximum differences of 0.3–0.5 mm for patients 1–3 are observed. As for the image quality, intensity errors below 5 and 20 HU compared to the planning CT are achieved for the phantom and the patient cases, respectively. Signal-noise-ratio values are improved by 12.74 and 5.12 times compared to results from FDK algorithm using the 1-min data and 4-min data, respectively. The computation time of the algorithm on a NVIDIA GTX590 card is 1–1.5 min per phase. Conclusions: High-quality 4D-CBCT imaging based on the clinically standard 1-min 3D CBCT scanning protocol is feasible via the proposed hybrid reconstruction algorithm.

60 APPLIED LIFE SCIENCES↗

Population of 224 realistic human subject-based computational breast phantoms

Purpose: To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. Methods: A tissue classification and segmentation algorithm was used to create realistic and detailed 3D computational breast phantoms based on 230 + dedicated bCT datasets from normal human subjects. The breast volume was identified using a coarse three-class fuzzy C-means segmentation algorithm which accounted for and removed motion blur at the breast periphery. Noise in the bCT data was reduced through application of a postreconstruction 3D bilateral filter. A 3D adipose nonuniformity (bias field) correction was then applied followed by glandular segmentation using a 3D bias-corrected fuzzy C-means algorithm. Multiple tissue classes were defined including skin, adipose, and several fractional glandular densities. Following segmentation, a skin mask was produced which preserved the interdigitated skin, adipose, and glandular boundaries of the skin interior. Finally, surface modeling was used to produce digital phantoms with methods complementary to the XCAT suite of digital human phantoms. Results: After rejecting some datasets due to artifacts, 224 virtual breast phantoms were created which emulate the complex breast parenchyma of actual human subjects. The volume breast density (with skin) ranged from 5.5% to 66.3% with a mean value of 25.3% ± 13.2%. Breast volumes ranged from 25.0 to 2099.6 ml with a mean value of 716.3 ± 386.5 ml. Three breast phantoms were selected for imaging with digital compression (using finite element modeling) and simple ray-tracing, and the results show promise in their potential to produce realistic simulated mammograms. Conclusions: This work provides a new population of 224 breast phantoms based on in vivo bCT data for imaging research. Compared to previous studies based on only a few prototype cases, this dataset provides a rich source of new cases spanning a wide range of breast types, volumes, densities, and parenchymal patterns.

61 RADIATION PROTECTION AND DOSIMETRY↗

WE-H-BRC-05: Catastrophic Error Metrics for Radiation Therapy

Purpose: Intuitive evaluation of complex radiotherapy treatments is impractical, while data transfer anomalies create the potential for catastrophic treatment delivery errors. Contrary to prevailing wisdom, logical scrutiny can be applied to patient-specific machine settings. Such tests can be automated, applied at the point of treatment delivery and can be dissociated from prior states of the treatment plan, potentially revealing errors introduced early in the process. Methods: Analytical metrics were formulated for conventional and intensity modulated RT (IMRT) treatments. These were designed to assess consistency between monitor unit settings, wedge values, prescription dose and leaf positioning (IMRT). Institutional metric averages for 218 clinical plans were stratified over multiple anatomical sites. Treatment delivery errors were simulated using a commercial treatment planning system and metric behavior assessed via receiver-operator-characteristic (ROC) analysis. A positive result was returned if the erred plan metric value exceeded a given number of standard deviations, e.g. 2. The finding was declared true positive if the dosimetric impact exceeded 25%. ROC curves were generated over a range of metric standard deviations. Results: Data for the conventional treatment metric indicated standard deviations of 3%, 12%, 11%, 8%, and 5 % for brain, pelvis, abdomen, lung and breast sites, respectively. Optimum error declaration thresholds yielded true positive rates (TPR) between 0.7 and 1, and false positive rates (FPR) between 0 and 0.2. Two proposed IMRT metrics possessed standard deviations of 23% and 37%. The superior metric returned TPR and FPR of 0.7 and 0.2, respectively, when both leaf position and MUs were modelled. Isolation to only leaf position errors yielded TPR and FPR values of 0.9 and 0.1. Conclusion: Logical tests can reveal treatment delivery errors and prevent large, catastrophic errors. Analytical metrics are able to identify errors in monitor units, wedging and leaf positions with favorable sensitivity and specificity. In part by Varian.

60 APPLIED LIFE SCIENCES↗