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SU-E-I-73: Clinical Evaluation of CT Image Reconstructed Using Interior Tomography

Purpose: Radiation dose reduction has been a long standing challenge in CT imaging of obese patients. Recent advances in interior tomography (reconstruction of an interior region of interest (ROI) from line integrals associated with only paths through the ROI) promise to achieve significant radiation dose reduction without compromising image quality. This study is to investigate the application of this technique in CT imaging through evaluating imaging quality reconstructed from patient data. Methods: Projection data were directly obtained from patients who had CT examinations in a Dual Source CT scanner (DSCT). Two detectors in a DSCT acquired projection data simultaneously. One detector provided projection data for full field of view (FOV, 50 cm) while another detectors provided truncated projection data for a FOV of 26 cm. Full FOV CT images were reconstructed using both filtered back projection and iterative algorithm; while interior tomography algorithm was implemented to reconstruct ROI images. For comparison reason, FBP was also used to reconstruct ROI images. Reconstructed CT images were evaluated by radiologists and compared with images from CT scanner. Results: The results show that the reconstructed ROI image was in excellent agreement with the truth inside the ROI, obtained from images from CT scanner, and the detailed features in the ROI were quantitatively accurate. Radiologists evaluation shows that CT images reconstructed with interior tomography met diagnosis requirements. Radiation dose may be reduced up to 50% using interior tomography, depending on patient size. Conclusion: This study shows that interior tomography can be readily employed in CT imaging for radiation dose reduction. It may be especially useful in imaging obese patients, whose subcutaneous tissue is less clinically relevant but may significantly increase radiation dose.

60 APPLIED LIFE SCIENCES↗

Comparative Analysis of Natural Gas Cogeneration Incentives on Electricity Production in Latin America

An analysis to assess the influence of country-dependent variables and incentives on the feasibility of natural gas cogeneration projects in Latin America is presented in this work. The analysis is performed using a hypothetical industrial plant, where the cogeneration solution consists in the recovery of waste heat from the power generation for steam production. The feasibility is evaluated by calculating the Return of Investment (ROI) and the Internal Rate of Return (IRR) of the project. Eight Latin American countries are studied considering their specific natural gas markets, regulation, and macroeconomic variables. Two scenarios, electricity production for self-consumption and electricity production with power surplus sale, are independently analyzed considering the effects of available incentives. In the countries where the project is feasible, the application of incentives leads to a significant reduction in the ROI and, consequently, to an increment in the IRR. The effect of the interest rate and environmental impact were also analyzed. In general terms, along the region, the regulation for cogeneration is incipient while incentives are very standard and similar respect to lowering of import, Value-Added Tax (VAT), and income taxes, which seems to be designed purely to promote capital investment. Following the results from this study, it is of paramount importance to create new policy instruments in the future to advance the regulatory framework for cogeneration in Latin America.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

SU-E-T-175: Evaluation of the Relative Output Ratio for Collimator Jaw and MLC Defined Small Static 6MV Photon Fields

Purpose: To evaluate relative output ratio of collimator jaw and MLC defined small photon fields. Methods: Relative output ratios were measured using Gafchromic EBT3 film for a 6 MV photon beam on a Novalis Tx with HD120 MLC. Beam collimation was achieved by the jaws for 1.0 cm and 3.0 cm and MLC defined square field sizes between 0.5 cm and 1.0 cm with varying jaw settings between 2.0 and 4.0 cm. Film pieces were exposed to 4 Gy. Experiments were repeated with each session consisting of five consecutive exposures for the given MLC and/or jaw collimation and with the MLC and the jaws reset for each exposure. Films were scanned using EPSON 10000XL flatbed scanner approximately 24 hours after exposure in 48 bit RGB format at 150 dpi. Film calibration data were corrected for daily linac output variations. Doses were evaluated using the green channel with square ROI sizes of 0.1 – 0.6 cm. Converted doses were normalised for output ratio calculation using the 3.0 cm field as a machine specific reference field size. Mean output ratio and coefficient of variation (CV) were calculated for each experimental session. Results: For the Novalis 6 MV photon beam the output ratios between 0.719 and 0.872 have been measured for the jaw/MLC combinations tested. For a jaw setting of 4.0 cm field, the mean CV of the output ratios increased from 0.77% to 1.48% with decreasing MLC field size from 1.0 cm to 0.5 cm. For a nominal MLC 1.0 cm field, the CV increased to 1.00% from 0.77% with reducing jaw field size from 4.0 cm to 2.0 cm. Conclusion: The relative output ratio and the associated CV were dependent on the collimator jaw and MLC settings. The field size dependent CV showed similar trends to those reported in the literature.

60 APPLIED LIFE SCIENCES↗

SU-F-BRF-04: Evaluation of Five Commercially-Available Algorithms for Deformable Image Registration

Purpose: Deformable image registration (DIR) is increasingly being used in various clinical applications. Although there are several DIR packages all making successful attempts at modeling complex anatomical changes using even more complex mathematical approximations, they are all subject to various uncertainties. Many studies have attempted to quantify the spatial uncertainty with DIR. This is the first study to compare the uncertainty for interfraction DIR for 5 different commercially-available algorithms. The aim of this study was to benchmark the performance of the most commonlyused DIR algorithms offered through these 5 software packages: Eclipse, MIM, Pinnacle, RaySearch, and Velocity. Methods: A set of 10 virtual H'N phantoms [Pukala et al. MedPhys. 40(11) 2013] with known deformations were used to determine the spatial errors that might be seen when performing DIR. The “ground-truth” deformation vector field (DVF) was compared to the DVF output of the 5 commercially-available algorithms in order to evaluate spatial errors for six regions of interest (ROIs): brainstem, cord, mandible, left parotid, right parotid, and the external body contour. Results: We found that each software package had varying uncertainties with the various ROIs, but were generally all comparable to one another – with mean spatial errors for each algorithm below 3.5 mm for each ROI (averaged across all phantoms). We also found that no single algorithm was the clear winner over the other 4 algorithms. However, at times, we found huge maximum errors in our results (e.g. phantom #9 maximum errors: right parotid = 22.9 mm, external contour = 30.5mm) with the varying DIR algorithms. Conclusion: Although our evaluation was limited to H'N patients, we show that our methods are a single-assessment analysis tool that could be used by any physicist, within any type of facility, to compare their DIR software before initiating widespread use within their daily radiotherapy practice.

60 APPLIED LIFE SCIENCES↗

Assessment of ROI for Workforce Development Efforts National & Homeland Security

The IDEAL Professional Engagement project at Idaho National Laboratory (INL) aims to enhance the laboratory's workforce diversity and inclusivity efforts, focusing on the U.S. National and Homeland Security mission areas. This project involves researching and evaluating opportunities for INL to engage in various professional events, particularly cyber conferences, to support recruitment and professional development. The project involved several key tasks: compiling comprehensive information on national laboratories and their mission statements, developing a deep understanding of INL’s role and efforts in national and homeland security, and identifying and engaging key stakeholders. Interviews were conducted with a set of targeted questions, and the findings were analyzed to identify common themes, insights, and actionable recommendations. Additionally, relevant upcoming cyber conferences were identified, various sponsorship levels and their associated benefits were evaluated, and the recruitment potential of these conferences was assessed. A detailed cost analysis was performed, including registration fees and travel expenses, and a cost-benefit analysis was conducted to evaluate the financial viability and potential return on investment (ROI) of conference participation and sponsorship. Based on the research and analysis, actionable recommendations for conference participation and sponsorship were formulated, ensuring alignment with INL’s mission and diversity goals. Preliminary results include a comprehensive list of relevant cyber conferences, a detailed cost analysis, and a set of actionable recommendations for future conference participation and sponsorship. The analysis highlights the financial requirements and geographical distribution of these conferences, providing valuable insights for INL's engagement strategies. This project underscores the importance of strategic engagement in professional events to attract and develop a diverse and skilled workforce, ultimately supporting INL’s mission areas in U.S. National and Homeland Security.

99 GENERAL AND MISCELLANEOUS↗

Automated Voxel-Based Analysis of Volumetric Dynamic Contrast-Enhanced CT Data Improves Measurement of Serial Changes in Tumor Vascular Biomarkers

Objectives: Development of perfusion imaging as a biomarker requires more robust methodologies for quantification of tumor physiology that allow assessment of volumetric tumor heterogeneity over time. This study proposes a parametric method for automatically analyzing perfused tissue from volumetric dynamic contrast-enhanced (DCE) computed tomography (CT) scans and assesses whether this 4-dimensional (4D) DCE approach is more robust and accurate than conventional, region-of-interest (ROI)-based CT methods in quantifying tumor perfusion with preliminary evaluation in metastatic brain cancer. Methods and Materials: Functional parameter reproducibility and analysis of sensitivity to imaging resolution and arterial input function were evaluated in image sets acquired from a 320-slice CT with a controlled flow phantom and patients with brain metastases, whose treatments were planned for stereotactic radiation surgery and who consented to a research ethics board-approved prospective imaging biomarker study. A voxel-based temporal dynamic analysis (TDA) methodology was used at baseline, at day 7, and at day 20 after treatment. The ability to detect changes in kinetic parameter maps in clinical data sets was investigated for both 4D TDA and conventional 2D ROI-based analysis methods. Results: A total of 7 brain metastases in 3 patients were evaluated over the 3 time points. The 4D TDA method showed improved spatial efficacy and accuracy of perfusion parameters compared to ROI-based DCE analysis (P<.005), with a reproducibility error of less than 2% when tested with DCE phantom data. Clinically, changes in transfer constant from the blood plasma into the extracellular extravascular space (K{sub trans}) were seen when using TDA, with substantially smaller errors than the 2D method on both day 7 post radiation surgery (±13%; P<.05) and by day 20 (±12%; P<.04). Standard methods showed a decrease in K{sub trans} but with large uncertainty (111.6 ± 150.5) %. Conclusions: Parametric voxel-based analysis of 4D DCE CT data resulted in greater accuracy and reliability in measuring changes in perfusion CT-based kinetic metrics, which have the potential to be used as biomarkers in patients with metastatic brain cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Feasibility Analysis of Converter-Interfaced Combined Heat and Power System

As a promising new design concept, the converter-interfaced combined heat and power (CHP) system is coupled to the bulk grid through a rectifier and a grid-ready tied inverter. Compared to the traditional directly-coupled CHP system, it removes the requirement for oversizing the CHP generator, limits the short-circuit contribution of the generator and simplifies the grid integration process of CHP system. This paper evaluates the economic benefits of this concept by calculating the annualized Return-on-Investment (ROI) and comparing it to the directly-coupled system. The economic analysis includes timeseries simulations to compute energy transactions with the bulk grid as well as sizing the equipment to calculate the capital and operational costs. Obtained results indicate that in majority of user cases evaluated, the converter-interfaced CHP systems can provide better ROI than directly-coupled systems. Given the additional technical benefits provided by inverter-based distributed energy resources (DERs), the proposed concept is proved to be technically viable and economically feasible.

03 NATURAL GAS↗

Are State-Sponsored New Radiation Therapy Facilities Economically Viable in Low- and Middle-Income Countries?

Purpose: The economic viability of establishing a state-funded radiation therapy (RT) infrastructure in low- and middle-income countries (LMICs) in accordance with the World Bank definition has been assessed through computation of a return on investment (ROI). Methods and Materials: Of the 139 LMICs, 100 were evaluated according to their RT facilities, gross national income (GNI) per capita, and employment/population ratio. The assumption was an investment of US$5 million for a basic RT center able to treat 1000 patients annually. The national breakeven points and percentage of ROI (%ROI) were calculated according to the GNI per capita and patient survival rates of 10% to 50% at 2 years. It was assumed that 50% of these patients would be of working age and that, if employed and able to work after treatment, they would contribute to the country's GNI for at least 2 years. The cumulative GNI after attaining the breakeven point until the end of the 15-year lifespan of the teletherapy unit was calculated to estimate the %ROI. The recurring and overhead costs were assumed to vary from 5.5% to 15% of the capital investment. Results: The %ROI was dependent on the GNI per capita, employment/population ratio and 2-year patient survival (all P<.001). Accordingly, none of the low-income countries would attain an ROI. If 50% of the patients survived for 2 years, the %ROI in the lower-middle and upper-middle income countries could range from 0% to 159.9% and 11.2% to 844.7%, respectively. Patient user fees to offset recurring and overhead costs could vary from “nil” to US$750, depending on state subsidies. Conclusions: Countries with a greater GNI per capita, higher employment/population ratio, and better survival could achieve a faster breakeven point, resulting in a higher %ROI. Additional factors such as user fees have also been considered. These can be tailored to the patient's ability to pay to cover the recurring costs. Certain pragmatic steps that could be undertaken to address these issues are discussed in the present study.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

SU-C-213-07: Fabrication and Testing of a 3D-Printed Small Animal Rectal Cooling Device to Evaluate Local Hypothermia as a Radioprotector During Prostate SBRT

Purpose: The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to SBRT treatments. Relevant to prostate SBRT, this work details the fabrication and testing of a 3D-printed cooling device to facilitate the investigation of the radioprotective effect of local hypothermia on the rat rectum. Methods: A 3cm long, two-channel rectal cooling device was designed in SOLIDWORKS CAD for 3D printing. The water intake nozzle is connected to a 1mm diameter brass pipe from which water flows and circulates back around to the exit nozzle. Both nozzles are connected by plastic tubing to a water chiller pump. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within a rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. CBCT images from a small-animal irradiator were evaluated for imaging artifacts which could affect Monte Carlo dose calculations during treatment planning. Results: The rectal temperature adjacent to the cooling device decreased from body temperature (37°C) to 15°C in 10–20 minutes from device insertion. Rectal temperature was maintained at 15±3°C during active cooling. MRI thermometry tests revealed a steep temperature gradient with increasing distance from the cooling device, with the desired temperature range maintained within the surrounding few millimeters. Conclusion: A 3D printed rectal cooling device was fabricated for the purpose of inducing local hypothermia in rat rectums. Rectal cooling capabilities were characterized in-vivo to facilitate an investigation of the radioprotective effect of hypothermia for late rectal toxicity following a single large dose of radiation. Funding support provided by RSNA research seed grant.

60 APPLIED LIFE SCIENCES↗

SU-F-T-440: The Feasibility Research of Checking Cervical Cancer IMRT Pre- Treatment Dose Verification by Automated Treatment Planning Verification System

Purpose: To assess the preliminary feasibility of automated treatment planning verification system in cervical cancer IMRT pre-treatment dose verification. Methods: The study selected randomly clinical IMRT treatment planning data for twenty patients with cervical cancer, all IMRT plans were divided into 7 fields to meet the dosimetric goals using a commercial treatment planning system(PianncleVersion 9.2and the EclipseVersion 13.5). The plans were exported to the Mobius 3D (M3D)server percentage differences of volume of a region of interest (ROI) and dose calculation of target region and organ at risk were evaluated, in order to validate the accuracy automated treatment planning verification system. Results: The difference of volume for Pinnacle to M3D was less than results for Eclipse to M3D in ROI, the biggest difference was 0.22± 0.69%, 3.5±1.89% for Pinnacle and Eclipse respectively. M3D showed slightly better agreement in dose of target and organ at risk compared with TPS. But after recalculating plans by M3D, dose difference for Pinnacle was less than Eclipse on average, results were within 3%. Conclusion: The method of utilizing the automated treatment planning system to validate the accuracy of plans is convenientbut the scope of differences still need more clinical patient cases to determine. At present, it should be used as a secondary check tool to improve safety in the clinical treatment planning.

60 APPLIED LIFE SCIENCES↗

A Technique for Generating Volumetric Cine-Magnetic Resonance Imaging

Purpose: The purpose of this study was to develop a techique to generate on-board volumetric cine-magnetic resonance imaging (VC-MRI) using patient prior images, motion modeling, and on-board 2-dimensional cine MRI. Methods and Materials: One phase of a 4-dimensional MRI acquired during patient simulation is used as patient prior images. Three major respiratory deformation patterns of the patient are extracted from 4-dimensional MRI based on principal-component analysis. The on-board VC-MRI at any instant is considered as a deformation of the prior MRI. The deformation field is represented as a linear combination of the 3 major deformation patterns. The coefficients of the deformation patterns are solved by the data fidelity constraint using the acquired on-board single 2-dimensional cine MRI. The method was evaluated using both digital extended-cardiac torso (XCAT) simulation of lung cancer patients and MRI data from 4 real liver cancer patients. The accuracy of the estimated VC-MRI was quantitatively evaluated using volume-percent-difference (VPD), center-of-mass-shift (COMS), and target tracking errors. Effects of acquisition orientation, region-of-interest (ROI) selection, patient breathing pattern change, and noise on the estimation accuracy were also evaluated. Results: Image subtraction of ground-truth with estimated on-board VC-MRI shows fewer differences than image subtraction of ground-truth with prior image. Agreement between normalized profiles in the estimated and ground-truth VC-MRI was achieved with less than 6% error for both XCAT and patient data. Among all XCAT scenarios, the VPD between ground-truth and estimated lesion volumes was, on average, 8.43 ± 1.52% and the COMS was, on average, 0.93 ± 0.58 mm across all time steps for estimation based on the ROI region in the sagittal cine images. Matching to ROI in the sagittal view achieved better accuracy when there was substantial breathing pattern change. The technique was robust against noise levels up to SNR = 20. For patient data, average tracking errors were less than 2 mm in all directions for all patients. Conclusions: Preliminary studies demonstrated the feasibility of generating real-time VC-MRI for on-board localization of moving targets in radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Human Mars Landing Site and Impacts on Mars Surface Operations

This paper describes NASA's initial steps for identifying and evaluating candidate Exploration Zones (EZs) and Regions of Interests (ROIs) for the first human crews that will explore the surface of Mars. NASA's current effort to define the exploration of this planet by human crews, known as the Evolvable Mars Campaign (EMC), provides the context in which these EZs and ROIs are being considered. The EMC spans all aspects of a human Mars mission including launch from Earth, transit to and from Mars, and operations on the surface of Mars. Studies related to Mars surface operations and related system capabilities have led to the current definition of an EZ as well as ROIs. An EZ is a collection of ROIs that are located within approximately 100 kilometers of a centralized landing site. ROIs are areas that are relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. The EZ also contains one or more landing sites and a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. With the EMC as a conceptual basis, the EZ model has been refined to a point where specific site selection criteria for scientific exploration and in situ resource utilization can be defined. In 2015 these criteria were distributed to the planetary sciences community and the in situ resource utilization and civil engineering communities as part of a call for EZ proposals. The resulting "First Landing Site/Exploration Zone Workshop for Human Missions to the Surface of Mars" was held in October 2015 during which 47 proposals for EZs and ROIs were presented and discussed. Proposed locations spanned all longitudes and all allowable latitudes (+/- 50 degrees). Proposed justification for selecting one of these EZs also spanned a significant portion of the scientific and resource criteria provided to the community. Workshop results will be used to prepare for follow-on workshops to refine our understanding of proposed EZs and ultimately select a single location to be explored and utilized by human crews. Another significant workshop outcome was a recognition that new data will be needed to refine our understanding of the value of proposed EZs. These new data will come in part from existing spacecraft at Mars and may come from future robotic Mars missions as appropriate consideration is given to these new data needs during mission definition and development.

Bussey, Ben↗

Human Mars Landing Site and Impacts on Mars Surface Operations

This paper describes NASA's initial steps for identifying and evaluating candidate Exploration Zones (EZs) and Regions of Interests (ROIs) for the first human crews that will explore the surface of Mars. NASA's current effort to define the exploration of this planet by human crews, known as the Evolvable Mars Campaign (EMC), provides the context in which these EZs and ROIs are being considered. The EMC spans all aspects of a human Mars mission including launch from Earth, transit to and from Mars, and operations on the surface of Mars. An EZ is a collection of ROIs located within approximately 100 kilometers of a centralized landing site. ROIs are areas relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. The EZ also contains one or more landing sites and a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. With the EMC as a conceptual basis, the EZ model has been refined to a point where specific site selection criteria for scientific exploration and in situ resource utilization can be defined. In 2015 these criteria were distributed to the planetary sciences community and the in situ resource utilization and civil engineering communities as part of a call for EZ proposals. The resulting "First Landing Site/Exploration Zone Workshop for Human Missions to the Surface of Mars" was held in October 2015 during which 47 proposals for EZs and ROIs were presented and discussed. Proposed locations spanned all longitudes and all allowable latitudes (+/- 50 degrees). Proposed justification for selecting one of these EZs also spanned a significant portion of the scientific and resource criteria provided to the community. Several important findings resulted from this Workshop including: (a) a strong consensus that, at a scale of 100 km (radius), multiple places on Mars exist that have both sufficient scientific interest to sustain multiple crews of exploring astronauts, AND potential resource deposits for ISRU indicating the current EZ definition is viable and should be retained for now, (b) new data types (needed for more definitive analysis of EZs) argued strongly for a new orbiter mission, and possibly one or more surface missions, to obtain these data, (c) a general consensus that this Workshop was an excellent start to identifying a place where future human missions to Mars can productively explore this planet and learn to live and work there for the long term. Building on these findings, HEOMD and SMD are: (a) refining the EZ selection criteria and overall selection process to improve on lessons learned from the first EZ workshop, (b) using these proposed locations to develop "reference EZs" for assessment purposes (primarily engineering assessments), (c) gathering data and conducting analyses to better understanding the different potential sources for water, including the ease of extraction and purification, and (d) assessing trends in additional data that are needed to better characterize EZs proposed at the workshop and how these data needs impact the design and operation of future robotic Mars missions.

Hoffman, Stephen J.↗

Method for simulating dose reduction in digital mammography using the Anscombe transformation

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.

60 APPLIED LIFE SCIENCES↗

SU-E-I-96: A Study About the Influence of ROI Variation On Tumor Segmentation in PET

Purpose: To study the influence of different regions of interest (ROI) on tumor segmentation in PET. Methods: The experiments were conducted on a cylindrical phantom. Six spheres with different volumes (0.5ml, 1ml, 6ml, 12ml, 16ml and 20 ml) were placed inside a cylindrical container to mimic tumors of different sizes. The spheres were filled with 11C solution as sources and the cylindrical container was filled with 18F-FDG solution as the background. The phantom was continuously scanned in a Biograph-40 True Point/True View PET/CT scanner, and 42 images were reconstructed with source-to-background ratio (SBR) ranging from 16:1 to 1.8:1. We took a large and a small ROI for each sphere, both of which contain the whole sphere and does not contain any other spheres. Six other ROIs of different sizes were then taken between the large and the small ROI. For each ROI, all images were segmented by eitht thresholding methods and eight advanced methods, respectively. The segmentation results were evaluated by dice similarity index (DSI), classification error (CE) and volume error (VE). The robustness of different methods to ROI variation was quantified using the interrun variation and a generalized Cohen's kappa. Results: With the change of ROI, the segmentation results of all tested methods changed more or less. Compared with all advanced methods, thresholding methods were less affected by the ROI change. In addition, most of the thresholding methods got more accurate segmentation results for all sphere sizes. Conclusion: The results showed that the segmentation performance of all tested methods was affected by the change of ROI. Thresholding methods were more robust to this change and they can segment the PET image more accurately. This work was supported in part by National Natural Science Foundation of China (NNSFC), under Grant Nos. 60971112 and 61375018, and Fundamental Research Funds for the Central Universities, under Grant No. 2012QN086. Wei Lu was supported in part by the National Institutes of Health (NIH) Grant No. R01 CA172638.

60 APPLIED LIFE SCIENCES↗

TH-EF-BRA-08: A Novel Technique for Estimating Volumetric Cine MRI (VC-MRI) From Multi-Slice Sparsely Sampled Cine Images Using Motion Modeling and Free Form Deformation

Purpose: To develop a technique to estimate on-board VC-MRI using multi-slice sparsely-sampled cine images, patient prior 4D-MRI, motion-modeling and free-form deformation for real-time 3D target verification of lung radiotherapy. Methods: A previous method has been developed to generate on-board VC-MRI by deforming prior MRI images based on a motion model(MM) extracted from prior 4D-MRI and a single-slice on-board 2D-cine image. In this study, free-form deformation(FD) was introduced to correct for errors in the MM when large anatomical changes exist. Multiple-slice sparsely-sampled on-board 2D-cine images located within the target are used to improve both the estimation accuracy and temporal resolution of VC-MRI. The on-board 2D-cine MRIs are acquired at 20–30frames/s by sampling only 10% of the k-space on Cartesian grid, with 85% of that taken at the central k-space. The method was evaluated using XCAT(computerized patient model) simulation of lung cancer patients with various anatomical and respirational changes from prior 4D-MRI to onboard volume. The accuracy was evaluated using Volume-Percent-Difference(VPD) and Center-of-Mass-Shift(COMS) of the estimated tumor volume. Effects of region-of-interest(ROI) selection, 2D-cine slice orientation, slice number and slice location on the estimation accuracy were evaluated. Results: VCMRI estimated using 10 sparsely-sampled sagittal 2D-cine MRIs achieved VPD/COMS of 9.07±3.54%/0.45±0.53mm among all scenarios based on estimation with ROI-MM-ROI-FD. The FD optimization improved estimation significantly for scenarios with anatomical changes. Using ROI-FD achieved better estimation than global-FD. Changing the multi-slice orientation to axial, coronal, and axial/sagittal orthogonal reduced the accuracy of VCMRI to VPD/COMS of 19.47±15.74%/1.57±2.54mm, 20.70±9.97%/2.34±0.92mm, and 16.02±13.79%/0.60±0.82mm, respectively. Reducing the number of cines to 8 enhanced temporal resolution of VC-MRI by 25% while maintaining the estimation accuracy. Estimation using slices sampled uniformly through the tumor achieved better accuracy than slices sampled non-uniformly. Conclusions: Preliminary studies showed that it is feasible to generate VC-MRI from multi-slice sparsely-sampled 2D-cine images for real-time 3D-target verification. This work was supported by the National Institutes of Health under Grant No. R01-CA184173 and a research grant from Varian Medical Systems.

60 APPLIED LIFE SCIENCES↗

Single reader between-cases AUC estimator with nested data

The area under the receiver operating characteristic curve (AUC) is widely used in evaluating diagnostic performance for many clinical tasks. It is still challenging to evaluate the reading performance of distinguishing between positive and negative regions of interest (ROIs) in the nested-data problem, where multiple ROIs are nested within the cases. To address this issue, we identify two kinds of AUC estimators, within-cases AUC and between-cases AUC. We focus on the between-cases AUC estimator, since our main research interest is in patient-level diagnostic performance rather than location-level performance (the ability to separate ROIs with and without disease within each patient). Another reason is that as the case number increases, the number of between-cases paired ROIs is much larger than the number of within-cases ROIs. We provide estimators for the variance of the between-cases AUC and for the covariance when there are two readers. We derive and prove the above estimators’ theoretical values based on a simulation model and characterize their behavior using Monte Carlo simulation results. We also provide a real-data example. Moreover, we connect the distribution-based simulation model with the simulation model based on the linear mixed-effect model, which helps better understand the sources of variation in the simulated dataset.

Health Care Sciences & Services↗

Development of Training Materials for Pathologists to Provide Machine Learning Validation Data of Tumor-Infiltrating Lymphocytes in Breast Cancer

The High Throughput Truthing project aims to develop a dataset for validating artificial intelligence and machine learning models (AI/ML) fit for regulatory purposes. The context of this AI/ML validation dataset is the reporting of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and eosin-stained invasive breast cancer biopsy specimens. After completing the pilot study, we found notable variability in the sTILs estimates as well as inconsistencies and gaps in the provided training to pathologists. Using the pilot study data and an expert panel, we created custom training materials to improve pathologist annotation quality for the pivotal study. We categorized regions of interest (ROIs) based on their mean sTILs density and selected ROIs with the highest and lowest sTILs variability. In a series of eight one-hour sessions, the expert panel reviewed each ROI and provided verbal density estimates and comments on features that confounded the sTILs evaluation. We aggregated and shaped the comments to identify pitfalls and instructions to improve our training materials. From these selected ROIs, we created a training set and proficiency test set to improve pathologist training with the goal to improve data collection for the pivotal study. We are not exploring AI/ML performance in this paper. Instead, we are creating materials that will train crowd-sourced pathologists to be the reference standard in a pivotal study to create an AI/ML model validation dataset. The issues discussed here are also important for clinicians to understand about the evaluation of sTILs in clinical practice and can provide insight to developers of AI/ML models.

60 APPLIED LIFE SCIENCES↗