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Poster — Thur Eve — 44: Linearization of Compartmental Models for More Robust Estimates of Regional Hemodynamic, Metabolic and Functional Parameters using DCE-CT/PET Imaging

Quantitative analysis of dynamic positron emission tomography (PET) data usually involves minimizing a cost function with nonlinear regression, wherein the choice of starting parameter values and the presence of local minima affect the bias and variability of the estimated kinetic parameters. These nonlinear methods can also require lengthy computation time, making them unsuitable for use in clinical settings. Kinetic modeling of PET aims to estimate the rate parameter k{sub 3}, which is the binding affinity of the tracer to a biological process of interest and is highly susceptible to noise inherent in PET image acquisition. We have developed linearized kinetic models for kinetic analysis of dynamic contrast enhanced computed tomography (DCE-CT)/PET imaging, including a 2-compartment model for DCE-CT and a 3-compartment model for PET. Use of kinetic parameters estimated from DCE-CT can stabilize the kinetic analysis of dynamic PET data, allowing for more robust estimation of k{sub 3}. Furthermore, these linearized models are solved with a non-negative least squares algorithm and together they provide other advantages including: 1) only one possible solution and they do not require a choice of starting parameter values, 2) parameter estimates are comparable in accuracy to those from nonlinear models, 3) significantly reduced computational time. Our simulated data show that when blood volume and permeability are estimated with DCE-CT, the bias of k{sub 3} estimation with our linearized model is 1.97 ± 38.5% for 1,000 runs with a signal-to-noise ratio of 10. In summary, we have developed a computationally efficient technique for accurate estimation of k{sub 3} from noisy dynamic PET data.

60 APPLIED LIFE SCIENCES↗

Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients

Purpose: To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. Methods and Materials: Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. A modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. Results: A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. Conclusions: According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-T-671: Range-Modulation Effects of Carbon Ion Beams in Lung Tissue

Purpose: When particles traversing inhomogeneous materials like lung they show a characteristic range modulation which cannot be observed in homogeneous materials. It is possible to describe the range modulation by a convolution of an unperturbed Bragg-Curve and a normal distribution. The sigma of the normal distribution is a parameter for the strength of the modulation effect. A new material parameter (modulation power, P-mod) is introduced which is independent of the material thickness. It is defined as the square of sigma divided by the mean water equivalent thickness of the target (µ). Methods: The modulation power of lung tissue was determined by actual Bragg-peak measurements after traversing an ex-vivo porcine lung and by Monte-Carlo simulations with micro-CT data of human lung tissue. The determined modulation powers were used to show the effect of range modulation effects in a simplified treatment situation. A four centimeter spread-out Bragg-peak after traversing eight centimeter of lung tissue was simulated in FLUKA. The SOBP with and without consideration of range modulation effects were compared. Results: As well in the measurements as in the MC simulations range modulation effects of lung tissue were observed. The determined modulation powers showed a great range from 0.05 mm, in the micro-CT data, to 0.7 mm in the lung measurements. The SOBP comparison showed that range modulation effects Result in over- and underdosages at the distal and proximal edge of the SOBP. In the investigated case, the last 0.5 cm of the SOBP showed an underdosage of up to 50% at the distal edge, while 0.5 cm distal to the SOBP an overdosage of up to 50% was observed. Conclusion: Range modulation effects occur in inhomogeneous materials like lung. These modulation effects may Result in clinically relevant over- and underdosages but are currently not considered in commercially available treatment planning systems.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A Biomathematical Model of Lymphopoiesis and Its Application to Acute and Chronic Irradiation Assessment

After the events of September 11, 2001, there is an increasing concern of the occurrence of radiological terrorism that may result in significant casualties in densely populated areas. Much effort has been made to establish various biomarkers to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios, which are demanded for effective medical management and treatment of the exposed victims. Among these the count of lymphocytes in peripheral blood and their depletion kinetics are the most important early indicators of the severity of the radiation injury. In this study, we examine a biomathematical model of lymphopoiesis which has been successfully utilized to simulate and interpret experimental data of acute and chronic irradiations on rodents [1]. With revised parameters for humans, we find this model can reproduce several sets of clinical lymphocyte data of accident victims over a wide range of absorbed doses. In addition, the absolute lymphocyte counts and the depletion rate constants calculated by this model also show good correlation with the Guskova formula and the Goans model, the two empirical tools which have been widely recognized for early estimation of the exposed dose after radiation accidents [2]. We also use the model to analyze the hematological data of the Techa River residents which were exposed to chronic low-dose irradiation during 1950-1956 [3]. This model can serve as a computational tool in radiation accident management, military operations involving nuclear warfare, radiation therapy, and space radiation risk assessment.

Hu, Shaowen↗

Validation of columnar CsI x-ray detector responses obtained with hybridMANTIS, a CPU-GPU Monte Carlo code for coupled x-ray, electron, and optical transport

Purpose: hybridMANTIS is a Monte Carlo package for modeling indirect x-ray imagers using columnar geometry based on a hybrid concept that maximizes the utilization of available CPU and graphics processing unit processors in a workstation. Methods: The authors compare hybridMANTIS x-ray response simulations to previously published MANTIS and experimental data for four cesium iodide scintillator screens. These screens have a variety of reflective and absorptive surfaces with different thicknesses. The authors analyze hybridMANTIS results in terms of modulation transfer function and calculate the root mean square difference and Swank factors from simulated and experimental results. Results: The comparison suggests that hybridMANTIS better matches the experimental data as compared to MANTIS, especially at high spatial frequencies and for the thicker screens. hybridMANTIS simulations are much faster than MANTIS with speed-ups up to 5260. Conclusions: hybridMANTIS is a useful tool for improved description and optimization of image acquisition stages in medical imaging systems and for modeling the forward problem in iterative reconstruction algorithms.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

A self-adaptive case-based reasoning system for dose planning in prostate cancer radiotherapy

Purpose: Prostate cancer is the most common cancer in the male population. Radiotherapy is often used in the treatment for prostate cancer. In radiotherapy treatment, the oncologist makes a trade-off between the risk and benefit of the radiation, i.e., the task is to deliver a high dose to the prostate cancer cells and minimize side effects of the treatment. The aim of our research is to develop a software system that will assist the oncologist in planning new treatments. Methods: A nonlinear case-based reasoning system is developed to capture the expertise and experience of oncologists in treating previous patients. Importance (weights) of different clinical parameters in the dose planning is determined by the oncologist based on their past experience, and is highly subjective. The weights are usually fixed in the system. In this research, the weights are updated automatically each time after generating a treatment plan for a new patient using a group based simulated annealing approach. Results: The developed approach is analyzed on the real data set collected from the Nottingham University Hospitals NHS Trust, City Hospital Campus, UK. Extensive experiments show that the dose plan suggested by the proposed method is coherent with the dose plan prescribed by an experienced oncologist or even better. Conclusions: The developed case-based reasoning system enables the use of knowledge and experience gained by the oncologist in treating new patients. This system may play a vital role to assist the oncologist in making a better decision in less computational time; it utilizes the success rate of the previously treated patients and it can also be used in teaching and training processes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Source function from two-particle correlation function through entropy-regularized Richardson-Lucy deblurring

Source functions are obtained from p – p and d – α correlation functions by applying the Richardson-Lucy (RL) deblurring to the Koonin-Pratt (KP) equation. To prevent fitting of noise in the correlation function, total-variation (TV) regularization is employed that has been effective in ordinary image restoration. TV alone cannot ensure normalization of the source functions. To ensure the latter, we propose a maximum-entropy regularized RL algorithm (MEM-RL). We outline the MEM-RL formalism and optimization strategy for the KP equation, demonstrating its effectiveness on both simulated and experimental data, including the p – p and d – α correlation functions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Threat Sources for Creating Synthetic Urban Search Data

Equivalent point source energy emission distributions were computed for various threat sources for use in simulating the detector responses for urban search scenarios. The sources include standard isotopic sources used in detector testing, medical and industrial sources occasionally encountered in urban searches, and several types of special nuclear materials. Most of the equivalent point source distributions represent small sources inside some amount of shielding, but the special nuclear material sources represent volumetrically distributed sources in spheres of metal. Text-based inputs for emission distributions are available for the Monte Carlo transport codes Monte Carlo N-Particle, SCALE/MAVRIC, and Omnibus/Shift, any of which can easily be converted to other formats. These sources were developed for use in the Radiological Anomaly Detection and Identification (RADAI) project and the follow-on project, the RADAI-Extended project, sponsored by the National Nuclear Security Administration Office of Defense Nuclear Nonproliferation Research and Development.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment

Purpose: The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate the RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials: Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results: We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton biological effectiveness. Data were also used to validate a parameterized RBE model. Conclusions: The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

TOPAS: An innovative proton Monte Carlo platform for research and clinical applications

Purpose: While Monte Carlo particle transport has proven useful in many areas (treatment head design, dose calculation, shielding design, and imaging studies) and has been particularly important for proton therapy (due to the conformal dose distributions and a finite beam range in the patient), the available general purpose Monte Carlo codes in proton therapy have been overly complex for most clinical medical physicists. The learning process has large costs not only in time but also in reliability. To address this issue, we developed an innovative proton Monte Carlo platform and tested the tool in a variety of proton therapy applications. Methods: Our approach was to take one of the already-established general purpose Monte Carlo codes and wrap and extend it to create a specialized user-friendly tool for proton therapy. The resulting tool, TOol for PArticle Simulation (TOPAS), should make Monte Carlo simulation more readily available for research and clinical physicists. TOPAS can model a passive scattering or scanning beam treatment head, model a patient geometry based on computed tomography (CT) images, score dose, fluence, etc., save and restart a phase space, provides advanced graphics, and is fully four-dimensional (4D) to handle variations in beam delivery and patient geometry during treatment. A custom-designed TOPAS parameter control system was placed at the heart of the code to meet requirements for ease of use, reliability, and repeatability without sacrificing flexibility. Results: We built and tested the TOPAS code. We have shown that the TOPAS parameter system provides easy yet flexible control over all key simulation areas such as geometry setup, particle source setup, scoring setup, etc. Through design consistency, we have insured that user experience gained in configuring one component, scorer or filter applies equally well to configuring any other component, scorer or filter. We have incorporated key lessons from safety management, proactively removing possible sources of user error such as line-ordering mistakes. We have modeled proton therapy treatment examples including the UCSF eye treatment head, the MGH stereotactic alignment in radiosurgery treatment head and the MGH gantry treatment heads in passive scattering and scanning modes, and we have demonstrated dose calculation based on patient-specific CT data. Initial validation results show agreement with measured data and demonstrate the capabilities of TOPAS in simulating beam delivery in 3D and 4D. Conclusions: We have demonstrated TOPAS accuracy and usability in a variety of proton therapy setups. As we are preparing to make this tool freely available for researchers in medical physics, we anticipate widespread use of this tool in the growing proton therapy community.

60 APPLIED LIFE SCIENCES↗

Effect of respiratory motion on internal radiation dosimetry

Purpose: Estimation of the radiation dose to internal organs is essential for the assessment of radiation risks and benefits to patients undergoing diagnostic and therapeutic nuclear medicine procedures including PET. Respiratory motion induces notable internal organ displacement, which influences the absorbed dose for external exposure to radiation. However, to their knowledge, the effect of respiratory motion on internal radiation dosimetry has never been reported before. Methods: Thirteen computational models representing the adult male at different respiratory phases corresponding to the normal respiratory cycle were generated from the 4D dynamic XCAT phantom. Monte Carlo calculations were performed using the MCNP transport code to estimate the specific absorbed fractions (SAFs) of monoenergetic photons/electrons, the S-values of common positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82, Y-86, and I-124), and the absorbed dose of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) in 28 target regions for both the static (average of dynamic frames) and dynamic phantoms. Results: The self-absorbed dose for most organs/tissues is only slightly influenced by respiratory motion. However, for the lung, the self-absorbed SAF is about 11.5% higher at the peak exhale phase than the peak inhale phase for photon energies above 50 keV. The cross-absorbed dose is obviously affected by respiratory motion for many combinations of source-target pairs. The cross-absorbed S-values for the heart contents irradiating the lung are about 7.5% higher in the peak exhale phase than the peak inhale phase for different positron-emitting radionuclides. For {sup 18}F-FDG, organ absorbed doses are less influenced by respiratory motion. Conclusions: Respiration-induced volume variations of the lungs and the repositioning of internal organs affect the self-absorbed dose of the lungs and cross-absorbed dose between organs in internal radiation dosimetry. The dynamic anatomical model provides more accurate internal radiation dosimetry estimates for the lungs and abdominal organs based on realistic modeling of respiratory motion. This work also contributes to a better understanding of model-induced uncertainties in internal radiation dosimetry.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-C-BRE-03: Dual Compartment Mathematical Modeling of Glioblastoma Multiforme (GBM)

Purpose: To explore the aggressive recurrence and radioresistence of GBM with a dual compartment tumor survival mathematical model based on intrinsic tumor heterogeneity, cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The repopulation and differentiation responses to radiotherapy of a solid tumor were simulated using an Ordinary Differential Equation (ODE). To obtain the tumor radiobiological parameters, we assumed that a tumor consists of two subpopulations, each with its distinctive linear quadratic parameters. The dual compartment cell survival model was constructed as SF(D)=F × exp(-α{sub 1} D-β{sub 1}D{sup 2}) + (1-F) × exp(-α{sub 2}D-β{sub 2}D{sup 2}) for a single fraction of treatment, with F as the fraction of CSC, and α and β describing the radiological properties of each population. Robust least square fitting was performed on clonogenic survival data from one GBM (U373MG) and one NSCLC (H460) cell line. The fit parameters were then used in the ODE model to predict treatment outcome of various treatment schemes. Results: The fit parameters from GBM cell survival data were (F, α{sub 1}, β{sub 1}, α{sub 2}, β{sub 2})=(0.0396, 0.0801, 0.0006, 0.1363, 0.0279), exhibiting two populations with distinctive radiological properties, CSC more radioresistant than DCC. The GBM cell line exhibited significantly poorer tumor control than its single compartment model prediction and NSCLC, which responded well to hypofrationation. The increased radioresistance was due to rapid regrowth of the DCC compartment triggered by its depletion while maintaining a viable CSC population. The rapid regrowth can be reduced by treating dose fractions ≤ 2 Gy with a prolonged treatment period. Conclusion: The interaction between a radioresistant CSC compartment and DCC compartment can explain the poor clinical outcome of GBM after radiotherapy despite dose escalation and hypofractionation attempts. Lower dose fractions result in better treatment outcome but still eventually recurs. Dose escalation beyond 100 Gy and/or differentiation therapy will be vital in achieving GBM tumor control.

60 APPLIED LIFE SCIENCES↗

SU-E-T-648: Quality Assurance Using the RADPOS System for 4D Radiotherapy with CyberKnife

Purpose: The CyberKnife robotic radiosurgery system uses Synchrony respiratory motion compensation, which requires independent performance verification. In this work, the RADPOS 4D dosimetry system’s motion measurements are compared with internal fiducial position measurements. In addition, RADPOS measurements are compared with Synchrony’s predictive correlation model, which is based on internal fiducial and external LED marker position measurements. Methods: A treatment plan was created for a lung insert containing fiducials, RADPOS detector, and Solid Water tumor phantom. Two Quasar Respiratory Motion Phantoms (Q1 and Q2) and two RADPOS detectors (R1 and R2) were used: Q1 simulated lung motion with a lung insert moving in the superior/inferior direction, while Q2 simulated chest motion with a chest platform moving in the anterior/posterior direction. Before treatment, R1 was secured inside of the tumor phantom within Q1, while LED markers and R2 were positioned on the chest platform of Q2. Two treatment delivery cases were studied: isocentric plan (I) and non-isocentric patient plan (P). Four motion cases were studied: no motion (0), sinusoidal and in-phase (1), sinusoidal and out-of-phase (2), patient waveform and out-of-phase (3). A coordinate alignment algorithm was implemented, allowing RADPOS and model position data to be compared within the fiducial coordinate system. Results: The standard deviation of the differences between RADPOS and fiducial position measurements was below 0.6 mm for all experimental cases. The standard deviation of the differences between RADPOS and model position data was 1.0, 1.5, and 1.6 mm along the primary direction of motion for case I1, I2, and P3, respectively. Conclusion: Our work demonstrates that RADPOS is a useful tool for independent quality assurance of CyberKnife treatment with Synchrony respiratory compensation. RADPOS and fiducial position measurement closely match, and RADPOS confirms the effectiveness of CyberKnife’s Synchrony motion tracking. This work was supported by OCAIRO (Ontario Consortium for Adaptive Interventions in Radiation Oncology) grant.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Organ doses for reference pediatric and adolescent patients undergoing computed tomography estimated by Monte Carlo simulation

Purpose: To establish an organ dose database for pediatric and adolescent reference individuals undergoing computed tomography (CT) examinations by using Monte Carlo simulation. The data will permit rapid estimates of organ and effective doses for patients of different age, gender, examination type, and CT scanner model. Methods: The Monte Carlo simulation model of a Siemens Sensation 16 CT scanner previously published was employed as a base CT scanner model. A set of absorbed doses for 33 organs/tissues normalized to the product of 100 mAs and CTDI{sub vol} (mGy/100 mAs mGy) was established by coupling the CT scanner model with age-dependent reference pediatric hybrid phantoms. A series of single axial scans from the top of head to the feet of the phantoms was performed at a slice thickness of 10 mm, and at tube potentials of 80, 100, and 120 kVp. Using the established CTDI{sub vol}- and 100 mAs-normalized dose matrix, organ doses for different pediatric phantoms undergoing head, chest, abdomen-pelvis, and chest-abdomen-pelvis (CAP) scans with the Siemens Sensation 16 scanner were estimated and analyzed. The results were then compared with the values obtained from three independent published methods: CT-Expo software, organ dose for abdominal CT scan derived empirically from patient abdominal circumference, and effective dose per dose-length product (DLP). Results: Organ and effective doses were calculated and normalized to 100 mAs and CTDI{sub vol} for different CT examinations. At the same technical setting, dose to the organs, which were entirely included in the CT beam coverage, were higher by from 40 to 80% for newborn phantoms compared to those of 15-year phantoms. An increase of tube potential from 80 to 120 kVp resulted in 2.5-2.9-fold greater brain dose for head scans. The results from this study were compared with three different published studies and/or techniques. First, organ doses were compared to those given by CT-Expo which revealed dose differences up to several-fold when organs were partially included in the scan coverage. Second, selected organ doses from our calculations agreed to within 20% of values derived from empirical formulae based upon measured patient abdominal circumference. Third, the existing DLP-to-effective dose conversion coefficients tended to be smaller than values given in the present study for all examinations except head scans. Conclusions: A comprehensive organ/effective dose database was established to readily calculate doses for given patients undergoing different CT examinations. The comparisons of our results with the existing studies highlight that use of hybrid phantoms with realistic anatomy is important to improve the accuracy of CT organ dosimetry. The comprehensive pediatric dose data developed here are the first organ-specific pediatric CT scan database based on the realistic pediatric hybrid phantoms which are compliant with the reference data from the International Commission on Radiological Protection (ICRP). The organ dose database is being coupled with an adult organ dose database recently published as part of the development of a user-friendly computer program enabling rapid estimates of organ and effective dose doses for patients of any age, gender, examination types, and CT scanner model.

61 RADIATION PROTECTION AND DOSIMETRY↗

Evaluation of material heterogeneity dosimetric effects using radiochromic film for COMS eye plaques loaded with {sup 125}I seeds (model I25.S16)

Purpose: (1) To measure absolute dose distributions in eye phantom for COMS eye plaques with {sup 125}I seeds (model I25.S16) using radiochromic EBT film dosimetry. (2) To determine the dose correction function for calculations involving the TG-43 formalism to account for the presence of the COMS eye plaque using Monte Carlo (MC) method specific to this seed model. (3) To test the heterogeneous dose calculation accuracy of the new version of Plaque Simulator (v5.3.9) against the EBT film data for this seed model. Methods: Using EBT film, absolute doses were measured for {sup 125}I seeds (model I25.S16) in COMS eye plaques (1) along the plaque's central axis for (a) uniformly loaded plaques (14-20 mm in diameter) and (b) a 20 mm plaque with single seed, and (2) in off-axis direction at depths of 5 and 12 mm for all four plaque sizes. The EBT film calibration was performed at {sup 125}I photon energy. MC calculations using MCNP5 code for a single seed at the center of a 20 mm plaque in homogeneous water and polystyrene medium were performed. The heterogeneity dose correction function was determined from the MC calculations. These function values at various depths were entered into PS software (v5.3.9) to calculate the heterogeneous dose distributions for the uniformly loaded plaques (of all four sizes). The dose distributions with homogeneous water assumptions were also calculated using PS for comparison. The EBT film measured absolute dose rate values (film) were compared with those calculated using PS with homogeneous assumption (PS Homo) and heterogeneity correction (PS Hetero). The values of dose ratio (film/PS Homo) and (film/PS Hetero) were obtained. Results: The central axis depth dose rate values for a single seed in 20 mm plaque measured using EBT film and calculated with MCNP5 code (both in ploystyrene phantom) were compared, and agreement within 9% was found. The dose ratio (film/PS Homo) values were substantially lower than unity (mostly between 0.8 and 0.9) for all four plaque sizes, indicating dose reduction by COMS plaque compared with homogeneous assumption. The dose ratio (film/PS Hetero) values were close to unity, indicating the PS Hetero calculations agree with those from the film study. Conclusions: Substantial heterogeneity effect on the {sup 125}I dose distributions in an eye phantom for COMS plaques was verified using radiochromic EBT film dosimetry. The calculated doses for uniformly loaded plaques using PS with heterogeneity correction option enabled were corroborated by the EBT film measurement data. Radiochromic EBT film dosimetry is feasible in measuring absolute dose distributions in eye phantom for COMS eye plaques loaded with single or multiple {sup 125}I seeds. Plaque Simulator is a viable tool for the calculation of dose distributions if one understands its limitations and uses the proper heterogeneity correction feature.

60 APPLIED LIFE SCIENCES↗

Characterization of tissue magnetic susceptibility-induced distortions for MRIgRT

Purpose: MR image geometric integrity is one of the building blocks of MRI-guided radiotherapy. In particular, tissue magnetic susceptibility-induced effects are patient-dependent and their behavior is difficult to assess and predict. In this study, the authors investigated in detail the characteristics of susceptibility ({chi}) distortions in the context of MRIgRT, including the case of two common MR-linac system configurations. Methods: The magnetic field distortions were numerically simulated for several imaging parameters and anatomical sites, i.e., brain, lung, pelvis (with air pockets), and prostate. The simulation process consisted of (a) segmentation of patient CT data into susceptibility relevant anatomical volumes (i.e., soft-tissue, bone and air/lung), (b) conversion of CT data into susceptibility masks by assigning bulk {chi} values to the structures defined at (a), (c) numerical computations of the local magnetic fields by using a finite difference algorithm, and (d) generation of the geometric distortion maps from the magnetic field distributions. For each patient anatomy, the distortions were quantified at the interfaces of anatomical structures with significantly different {chi} values. The analysis was performed for two specific orientations of the external main magnetic field (B{sub 0}) characteristic to the MR-linac systems, specifically along the z-axis for a bore MR scanner and in the (x,y)-plane for a biplanner magnet. The magnetic field local perturbations were reported in ppm. The metrics used to quantify the geometric distortions were the maximum, mean, and range of distortions. The numerical simulation algorithm was validated using phantom data measurements. Results: Susceptibility-induced distortions were determined for both quadratic and patient specific geometries. The numerical simulations showed a good agreement with the experimental data. The measurements were acquired at 1.5 and 3 T and with an encoding gradient varying between 3 and 20 mT/m by using an annular phantom mimicking the water-air and water-oil {chi} interfaces. For quadratic geometries, the magnitude of field distortion increased rapidly with the size of the inhomogeneity up to about 10 mm and then tended to plateau. This trend became more evident for materials with a larger {Delta}{chi} relative to water. The simulations showed only a slight increase in the maximum distortion values when the B{sub 0} orientation was varied with regard to the shape of the {chi} inhomogeneity. In the case of patient anatomy, the largest distortion values arose at the air-soft-tissue interface. Considering the two MR-linac system configurations and comparing the field distortion values corresponding to all organ structures, the distortions tended to be larger for the biplanar magnet. The authors provide a reference table with ppm values which can be used to easily evaluate the geometric distortions for patient data as a function of B{sub 0} and the strength of the encoding gradient. Conclusions: The susceptibility distortions were quantified as a function of multiple parameters such as the {chi} inhomogeneity size and shape, the magnitude of B{sub 0} and the readout gradient, and the orientation of B{sub 0} with respect to the sample geometry. The analysis was performed for several anatomical sites and corresponding to two B{sub 0} orientations as featured by MR-linac systems.

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↗

Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure

Purpose: Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levels from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Methods: Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Results: Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the HDTV algorithm shows the best performance. At 50 mGy, the deviation from the reference obtained at 500 mGy were less than 4%. Also the LDPC algorithm provides reasonable results with deviation less than 10% at 50 mGy while PCF and MKB reconstruction show larger deviations even at higher dose levels. Conclusions: LDPC and HDTV increase CNR and allow for quantitative evaluations even at dose levels as low as 50 mGy. The left ventricular volumes exemplarily illustrate that cardiac parameters can be accurately estimated at lowest dose levels if sophisticated algorithms are used. This allows to reduce dose by a factor of 10 compared to today's gold standard and opens new options for longitudinal studies of the heart.

62 RADIOLOGY AND NUCLEAR MEDICINE↗