S-values for radium-223 and absorbed doses estimates for 223RACL2 using three computational phantoms.

Radium-223 dichloride (223RaCl2), approved by FDA (Food and Drug Administration) in 2013 and in Brazil by ANVISA (Agência Nacional de Vigilância Sanitária) in 2016, offers a new therapeutic option for bone metastases from castration-resistant prostate cancer (CRPC). The advantages of radionuclide therapy for bone metastases include the simultaneous treatment of multiple lesions at the same time. The activity prescription is based on the patient's body weight, disregarding the absorbed dose limit of 2 Gy in the organ at risk: bone marrow. This study focuses on Internal Dosimetry for 223RaCl2 therapy aiming to apply biokinetic models described in the literature to estimate absorbed doses in the organs of interests, especially for the bone marrow. For this purpose, the present paper compares and validates the GATE Monte Carlo simulation with the Radioactive Decay Module (RDM) and calculates a set of S-values for Radium-223 radionuclide using male and female XCAT computational models. Moreover, a comparison of S-values for Radium-223 for three male computational models with different anatomies is also evaluated, Male (standard), Pat1 (lower body weight) and Pat2 (highest body weight). A comprehensive set of S-values was calculated for the Male model, 30 source-regions and 47 target-regions, and for Female model, 30 source-regions and 42 target-regions for Radium-223 and its decay scheme: Radon-219, Polonium-215, Lead-211, Bismuth- 211, Polonium-211 and Thallium-207. The new set of S-values will facilitate absorbed dose calculations for Radium-223 therapy. In addition, Absorbed Dose Evaluation for 223RaCl2 therapy was estimated for three different biodistributions described in the literature within three male computational models. For all biodistributions, the Pat2 phantom has a greatest absorbed dose within the red marrow, when compared with Male and Pat1.

Development of a Computerized 4-D MRI Phantom for Liver Motion Study.

PURPOSE: To develop a 4-dimensional computerized magnetic resonance imaging phantom with image textures extracted from real patient scans for liver motion studies. METHODS: The proposed phantom was developed based on the current version of 4-dimensional extended cardiac-torso computerized phantom and a clinical magnetic resonance scan. Initially, the extended cardiac-torso phantom was voxelized in abdominal-chest region at the end of exhalation phase. Structures/tissues were classified into 4 categories: (1) Seven key textured organs, including liver, gallbladder, spleen, stomach, heart, kidneys, and pancreas, were mapped from a clinical T1-weighted liver magnetic resonance scan using deformable registration. (2) Large textured soft tissue volumes were simulated via an iterative pattern generation method using the same magnetic resonance scan. (3) Lung and intestine structures were generated by assigning uniform intensity with proper noise modeling. (4) Bony structures were generated by assigning the magnetic resonance values. A spherical hypointensity tumor was inserted into the liver. Other respiratory phases of the 4-dimensional phantom were generated using the backward deformation vector fields exported by the extended cardiac-torso program, except that bony structures were generated separately for each phase. A weighted image filtering process was utilized to improve the overall tissue smoothness at each phase. RESULTS: Three 4-dimensional series with different motion amplitudes were generated. The developed motion phantom produced good illustrations of abdominal-chest region with anatomical structures in key organs and texture patterns in large soft tissue volumes. In a standard series, the tumor volume was measured as 13.90 ± 0.11 cm3 in a respiratory cycle and the tumor's maximum center-of-mass shift was 2.95 cm/1.84 cm on superior-inferior/anterior-posterior directions. The organ motion during the respiratory cycle was well rendered. The developed motion phantom has the flexibility of motion pattern variation, organ geometry variation, and tumor modeling variation. CONCLUSIONS: A 4-D computerized phantom was developed and could be used to produce image series with synthetic magnetic resonance textures for magnetic resonance imaging research of liver motion.

Finite-element modeling of compression and gravity on a population of breast phantoms for multimodality imaging simulation.

PURPOSE: The authors are developing a series of computational breast phantoms based on breast CT data for imaging research. In this work, the authors develop a program that will allow a user to alter the phantoms to simulate the effect of gravity and compression of the breast (craniocaudal or mediolateral oblique) making the phantoms applicable to multimodality imaging. METHODS: This application utilizes a template finite-element (FE) breast model that can be applied to their presegmented voxelized breast phantoms. The FE model is automatically fit to the geometry of a given breast phantom, and the material properties of each element are set based on the segmented voxels contained within the element. The loading and boundary conditions, which include gravity, are then assigned based on a user-defined position and compression. The effect of applying these loads to the breast is computed using a multistage contact analysis in FEBio, a freely available and well-validated FE software package specifically designed for biomedical applications. The resulting deformation of the breast is then applied to a boundary mesh representation of the phantom that can be used for simulating medical images. An efficient script performs the above actions seamlessly. The user only needs to specify which voxelized breast phantom to use, the compressed thickness, and orientation of the breast. RESULTS: The authors utilized their FE application to simulate compressed states of the breast indicative of mammography and tomosynthesis. Gravity and compression were simulated on example phantoms and used to generate mammograms in the craniocaudal or mediolateral oblique views. The simulated mammograms show a high degree of realism illustrating the utility of the FE method in simulating imaging data of repositioned and compressed breasts. CONCLUSIONS: The breast phantoms and the compression software can become a useful resource to the breast imaging research community. These phantoms can then be used to evaluate and compare imaging modalities that involve different positioning and compression of the breast.

The development of a population of 4D pediatric XCAT phantoms for imaging research and optimization.

PURPOSE: We previously developed a set of highly detailed 4D reference pediatric extended cardiac-torso (XCAT) phantoms at ages of newborn, 1, 5, 10, and 15 yr with organ and tissue masses matched to ICRP Publication 89 values. In this work, we extended this reference set to a series of 64 pediatric phantoms of varying age and height and body mass percentiles representative of the public at large. The models will provide a library of pediatric phantoms for optimizing pediatric imaging protocols. METHODS: High resolution positron emission tomography-computed tomography data obtained from the Duke University database were reviewed by a practicing experienced radiologist for anatomic regularity. The CT portion of the data was then segmented with manual and semiautomatic methods to form a target model defined using nonuniform rational B-spline surfaces. A multichannel large deformation diffeomorphic metric mapping algorithm was used to calculate the transform from the best age matching pediatric XCAT reference phantom to the patient target. The transform was used to complete the target, filling in the nonsegmented structures and defining models for the cardiac and respiratory motions. The complete phantoms, consisting of thousands of structures, were then manually inspected for anatomical accuracy. The mass for each major tissue was calculated and compared to linearly interpolated ICRP values for different ages. RESULTS: Sixty four new pediatric phantoms were created in this manner. Each model contains the same level of detail as the original XCAT reference phantoms and also includes parameterized models for the cardiac and respiratory motions. For the phantoms that were 10 yr old and younger, we included both sets of reproductive organs. This gave them the capability to simulate both male and female anatomy. With this, the population can be expanded to 92. Wide anatomical variation was clearly seen amongst the phantom models, both in organ shape and size, even for models of the same age and sex. The phantoms can be combined with existing simulation packages to generate realistic pediatric imaging data from different modalities. CONCLUSIONS: This work provides a large cohort of highly detailed pediatric phantoms with 4D capabilities of varying age, height, and body mass. The population of phantoms will provide a vital tool with which to optimize 3D and 4D pediatric imaging devices and techniques in terms of image quality and radiation-absorbed dose.

Organ localization: toward prospective patient-specific organ dosimetry in computed tomography.

PURPOSE: With increased focus on radiation dose from medical imaging, prospective radiation dose estimates are becoming increasingly desired. Using available populations of adult and pediatric patient phantoms, radiation dose calculations can be catalogued and prospectively applied to individual patients that best match certain anatomical characteristics. In doing so, the knowledge of organ size and location is a required element. Here, the authors develop a predictive model of organ locations and volumes based on an analysis of adult and pediatric computed tomography (CT) data. METHODS: Fifty eight adult and 69 pediatric CT datasets were segmented and utilized in the study. The maximum and minimum points of the organs were recorded with respect to the axial distance from the tip of the sacrum. The axial width, midpoint, and volume of each organ were calculated. Linear correlations between these three organ parameters and patient age, BMI, weight, and height were determined. RESULTS: No statistically significant correlations were found in adult patients between the axial width, midpoint, and volume of the organs versus the patient age or BMI. Slight, positive linear trends were found for organ midpoint versus patient weight (max r(2) = 0.382, mean r(2) = 0.236). Similar trends were found for organ midpoint versus height (max r(2) = 0.439, mean r(2) = 0.200) and for organ volume versus height (max r(2) = 0.410, mean r(2) = 0.153). Gaussian fits performed on probability density functions of the adult organs resulted in r(2)-values ranging from 0.96 to 0.996. The pediatric patients showed much stronger correlations overall. Strong correlations were observed between organ axial midpoint versus age, height, and weight (max r(2) = 0.842, mean r(2) = 0.790; max r(2) = 0.949, mean r(2) = 0.894; and max r(2) = 0.870, mean r(2) = 0.847, respectively). Moderate linear correlations were also observed for organ axial width versus height (max r(2) = 0.772, mean r(2) = 0.562) and for organ volume versus height (max r(2) = 0.781, mean r(2) = 0.601). CONCLUSIONS: Adult patients exhibited small variations in organ volume and location with respect to height and weight, but no meaningful correlation existed between these parameters and age or BMI. Once adulthood is reached, organ morphology and positioning seem to remain static. However, clear trends are evident between pediatric organ locations versus age, height, and weight. Such information can be incorporated into a matching methodology that may provide the highest probability of representing the anatomy of a patient undergoing a clinical exam to prospectively estimate the radiation dose.

A set of 4D pediatric XCAT reference phantoms for multimodality research.

PURPOSE: The authors previously developed an adult population of 4D extended cardiac-torso (XCAT) phantoms for multimodality imaging research. In this work, the authors develop a reference set of 4D pediatric XCAT phantoms consisting of male and female anatomies at ages of newborn, 1, 5, 10, and 15 years. These models will serve as the foundation from which the authors will create a vast population of pediatric phantoms for optimizing pediatric CT imaging protocols. METHODS: Each phantom was based on a unique set of CT data from a normal patient obtained from the Duke University database. The datasets were selected to best match the reference values for height and weight for the different ages and genders according to ICRP Publication 89. The major organs and structures were segmented from the CT data and used to create an initial pediatric model defined using nonuniform rational B-spline surfaces. The CT data covered the entire torso and part of the head. To complete the body, the authors manually added on the top of the head and the arms and legs using scaled versions of the XCAT adult models or additional models created from cadaver data. A multichannel large deformation diffeomorphic metric mapping algorithm was then used to calculate the transform from a template XCAT phantom (male or female 50th percentile adult) to the target pediatric model. The transform was applied to the template XCAT to fill in any unsegmented structures within the target phantom and to implement the 4D cardiac and respiratory models in the new anatomy. The masses of the organs in each phantom were matched to the reference values given in ICRP Publication 89. The new reference models were checked for anatomical accuracy via visual inspection. RESULTS: The authors created a set of ten pediatric reference phantoms that have the same level of detail and functionality as the original XCAT phantom adults. Each consists of thousands of anatomical structures and includes parameterized models for the cardiac and respiratory motions. Based on patient data, the phantoms capture the anatomic variations of childhood, such as the development of bone in the skull, pelvis, and long bones, and the growth of the vertebrae and organs. The phantoms can be combined with existing simulation packages to generate realistic pediatric imaging data from different modalities. CONCLUSIONS: The development of patient-derived pediatric computational phantoms is useful in providing variable anatomies for simulation. Future work will expand this ten-phantom base to a host of pediatric phantoms representative of the public at large. This can provide a means to evaluate and improve pediatric imaging devices and to optimize CT protocols in terms of image quality and radiation dose.

Evaluation of the effect of respiratory and anatomical variables on a Fourier technique for markerless, self-sorted 4D-CBCT.

A novel technique based on Fourier transform theory has been developed that directly extracts respiratory information from projections without the use of external surrogates. While the feasibility has been demonstrated with three patients, a more extensive validation is necessary. Therefore, the purpose of this work is to investigate the effects of a variety of respiratory and anatomical scenarios on the performance of the technique with the 4D digital extended cardiac torso phantom. FT-phase and FT-magnitude methods were each applied to identify peak-inspiration projections and quantitatively compared to the gold standard of visual identification. Both methods proved to be robust across the studied scenarios with average differences in respiratory phase <10% and percentage of projections assigned within 10% of the gold standard >90%, when incorporating minor modifications to region-of-interest (ROI) selection and/or low-frequency location for select cases of DA and lung percentage in the field of view of the projection. Nevertheless, in the instance where one method initially faltered, the other method prevailed and successfully identified peak-inspiration projections. This is promising because it suggests that the two methods provide complementary information to each other. To ensure appropriate clinical adaptation of markerless, self-sorted four-dimensional cone-beam CT (4D-CBCT), perhaps an optimal integration of the two methods can be developed.

Population of anatomically variable 4D XCAT adult phantoms for imaging research and optimization.

PURPOSE: The authors previously developed the 4D extended cardiac-torso (XCAT) phantom for multimodality imaging research. The XCAT consisted of highly detailed whole-body models for the standard male and female adult, including the cardiac and respiratory motions. In this work, the authors extend the XCAT beyond these reference anatomies by developing a series of anatomically variable 4D XCAT adult phantoms for imaging research, the first library of 4D computational phantoms. METHODS: The initial anatomy of each phantom was based on chest-abdomen-pelvis computed tomography data from normal patients obtained from the Duke University database. The major organs and structures for each phantom were segmented from the corresponding data and defined using nonuniform rational B-spline surfaces. To complete the body, the authors manually added on the head, arms, and legs using the original XCAT adult male and female anatomies. The structures were scaled to best match the age and anatomy of the patient. A multichannel large deformation diffeomorphic metric mapping algorithm was then used to calculate the transform from the template XCAT phantom (male or female) to the target patient model. The transform was applied to the template XCAT to fill in any unsegmented structures within the target phantom and to implement the 4D cardiac and respiratory models in the new anatomy. Each new phantom was refined by checking for anatomical accuracy via inspection of the models. RESULTS: Using these methods, the authors created a series of computerized phantoms with thousands of anatomical structures and modeling cardiac and respiratory motions. The database consists of 58 (35 male and 23 female) anatomically variable phantoms in total. Like the original XCAT, these phantoms can be combined with existing simulation packages to simulate realistic imaging data. Each new phantom contains parameterized models for the anatomy and the cardiac and respiratory motions and can, therefore, serve as a jumping point from which to create an unlimited number of 3D and 4D variations for imaging research. CONCLUSIONS: A population of phantoms that includes a range of anatomical variations representative of the public at large is needed to more closely mimic a clinical study or trial. The series of anatomically variable phantoms developed in this work provide a valuable resource for investigating 3D and 4D imaging devices and the effects of anatomy and motion in imaging. Combined with Monte Carlo simulation programs, the phantoms also provide a valuable tool to investigate patient-specific dose and image quality, and optimization for adults undergoing imaging procedures.

Realistic reference adult and paediatric phantom series for internal and external dosimetry.

A new generation of realistic, image-based anthropomorphic phantoms has been developed based on the reference masses and organ definitions given in the International Commission on Radiological Protection Publication 89. Specific absorbed fractions for internal radiation sources have been calculated for photon and electron sources for many body organs. Values are similar to those from the previous generation of 'stylized' (mathematical equation-based) models, but some differences are seen, particularly at low particle or photon energies, due to the more realistic organ geometries, with organs generally being closer together, and with some touching and overlapping. Extension of this work, to use these phantoms in Monte Carlo radiation transport simulation codes with external radiation sources, is an important area of investigation that should be undertaken.

4D XCAT phantom for multimodality imaging research.

PURPOSE: The authors develop the 4D extended cardiac-torso (XCAT) phantom for multimodality imaging research. METHODS: Highly detailed whole-body anatomies for the adult male and female were defined in the XCAT using nonuniform rational B-spline (NURBS) and subdivision surfaces based on segmentation of the Visible Male and Female anatomical datasets from the National Library of Medicine as well as patient datasets. Using the flexibility of these surfaces, the Visible Human anatomies were transformed to match body measurements and organ volumes for a 50th percentile (height and weight) male and female. The desired body measurements for the models were obtained using the PEOPLESIZE program that contains anthropometric dimensions categorized from 1st to the 99th percentile for US adults. The desired organ volumes were determined from ICRP Publication 89 [ICRP, "Basic anatomical and physiological data for use in radiological protection: reference values," ICRP Publication 89 (International Commission on Radiological Protection, New York, NY, 2002)]. The male and female anatomies serve as standard templates upon which anatomical variations may be modeled in the XCAT through user-defined parameters. Parametrized models for the cardiac and respiratory motions were also incorporated into the XCAT based on high-resolution cardiac- and respiratory-gated multislice CT data. To demonstrate the usefulness of the phantom, the authors show example simulation studies in PET, SPECT, and CT using publicly available simulation packages. RESULTS: As demonstrated in the pilot studies, the 4D XCAT (which includes thousands of anatomical structures) can produce realistic imaging data when combined with accurate models of the imaging process. With the flexibility of the NURBS surface primitives, any number of different anatomies, cardiac or respiratory motions or patterns, and spatial resolutions can be simulated to perform imaging research. CONCLUSIONS: With the ability to produce realistic, predictive 3D and 4D imaging data from populations of normal and abnormal patients under various imaging parameters, the authors conclude that the XCAT provides an important tool in imaging research to evaluate and improve imaging devices and techniques. In the field of x-ray CT, the phantom may also provide the necessary foundation with which to optimize clinical CT applications in terms of image quality versus radiation dose, an area of research that is becoming more significant with the growing use of CT.

Investigation of Respiratory Gating in Quantitative Myocardial SPECT.

The purpose of this study is to investigate optimal respiratory gating schemes using different numbers of gates and placements within the respiratory cycle for reduction of respiratory motion (RM) artifacts in myocardial SPECT. The 4D NCAT phantom with its realistic respiratory model was used to generate 96 3D phantoms equally spaced over a complete respiratory cycle modeling the activity distribution from a typical Tc-99m Sestamibi study with the maximum movement of the diaphragm set at 2 cm. The 96 time frames were grouped to simulate various gating schemes (1, 3, 6, and 8 equally spaced gates) and different placements of the gates within a respiratory cycle. Projection data, including effects of attenuation, collimator-detector response and scatter, from each respiratory gate and each gating scheme were generated and reconstructed using the OS-EM algorithm with correction for attenuation. Attenuation correction was done with average attenuation maps for each gate and over the entire respiratory cycle. Bull's-eye polar plots generated from the reconstructed images for each gate were analyzed and compared to assess the effect of RM. RM artifacts were found to be reduced the most when going from the ungated to the gated case. No significant difference was found in attenuation compensated images between the use of gated and average attenuation maps. Our results indicate that the extent of RM artifacts is dependent on the placement of the gates in a gating scheme. Artifacts are less prominent in gates near end-expiration and more prominent near end-inspiration. This dependence on gate placement decreases when going to higher numbers of gates (6 and higher). However, it is possible to devise a non-uniform time interval gating scheme with 3 gates that will produce results similar to those using a higher number of gates. We conclude that respiratory gating is an effective way to reduce RM artifacts. Effective implementation of respiratory gating to further improve quantitative myocardial SPECT requires optimization of the gating scheme based on the amount of respiratory motion of the heart during each gate and the placement of the gates within the respiratory cycle.

Realistic CT simulation using the 4D XCAT phantom.

The authors develop a unique CT simulation tool based on the 4D extended cardiac-torso (XCAT) phantom, a whole-body computer model of the human anatomy and physiology based on NURBS surfaces. Unlike current phantoms in CT based on simple mathematical primitives, the 4D XCAT provides an accurate representation of the complex human anatomy and has the advantage, due to its design, that its organ shapes can be changed to realistically model anatomical variations and patient motion. A disadvantage to the NURBS basis of the XCAT, however, is that the mathematical complexity of the surfaces makes the calculation of line integrals through the phantom difficult. They have to be calculated using iterative procedures; therefore, the calculation of CT projections is much slower than for simpler mathematical phantoms. To overcome this limitation, the authors used efficient ray tracing techniques from computer graphics, to develop a fast analytic projection algorithm to accurately calculate CT projections directly from the surface definition of the XCAT phantom given parameters defining the CT scanner and geometry. Using this tool, realistic high-resolution 3D and 4D projection images can be simulated and reconstructed from the XCAT within a reasonable amount of time. In comparison with other simulators with geometrically defined organs, the XCAT-based algorithm was found to be only three times slower in generating a projection data set of the same anatomical structures using a single 3.2 GHz processor. To overcome this decrease in speed would, therefore, only require running the projection algorithm in parallel over three processors. With the ever decreasing cost of computers and the rise of faster processors and multi-processor systems and clusters, this slowdown is basically inconsequential, especially given the vast improvement the XCAT offers in terms of realism and the ability to generate 3D and 4D data from anatomically diverse patients. As such, the authors conclude that the efficient XCAT-based CT simulator developed in this work will have applications in a broad range of CT imaging research.

Impact of respiratory motion on the detection of small pulmonary nodules in SPECT imaging.

The objective of this investigation is to determine the impact of respiratory motion on the detection of small solitary pulmonary nodules (SPN) in single photon emission computed tomographic (SPECT) imaging. We have previously modeled the respiratory motion of SPN based on the change of location of anatomic structures within the lungs identified on breath-held CT images of volunteers acquired at two different stages of respiration. This information on respiratory motion within the lungs was combined with the end-expiration and time-averaged NCAT phantoms to allow the creation of source and attenuation maps for the normal background distribution of Tc-99m NeoTect. With the source and attenuation distribution thus defined, the SIMIND Monte Carlo program was used to produce SPECT projection data for the normal background and separately for each of 150 end-expiration and time-averaged simulated 1.0 cm tumors. Normal and tumor SPECT projection sets each containing one lesion were combined with a clinically realistic noise level and counts. These were reconstructed with RBI-EM using 1) no correction (NC), 2) attenuation correction (AC), 3) detector response correction (RC), and 4) attenuation correction, detector response correction, and scatter correction (AC_RC_SC). The post-reconstruction parameters of number of iterations and 3-D Gaussian filtering were optimized by human-observer studies. Comparison of lesion detection by human-observer LROC studies reveals that respiratory motion degrades tumor detection for all four reconstruction strategies, and that the magnitude of this effect is greatest for NC and RC, and least for AC_RC_SC. Additionally, the AC_RC_SC strategy results in the best detection of lesions.

Fast modelling of the collimator-detector response in Monte Carlo simulation of SPECT imaging using the angular response function.

Interactions of incident photons with the collimator and detector, including septal penetration, scatter and x-ray fluorescence, are significant sources of image degradation in applications of SPECT including dual isotope imaging and imaging using radioisotopes that emit high- or medium-energy photons. Modelling these interactions using full Monte Carlo (MC) simulations is computationally very demanding. We present a new method based on the use of angular response functions (ARFs). The ARF is a function of the incident photon's direction and energy and represents the probability that a photon will either interact with or pass through the collimator, and be detected at the intersection of the photon's direction vector and the detection plane in an energy window of interest. The ARFs were pre-computed using full MC simulations of point sources that include propagation through the collimator-detector system. We have implemented the ARF method for use in conjunction with the SimSET/PHG MC code to provide fast modelling of both interactions in the patient and in the collimator-detector system. Validation results in the three cases studied show that there was good agreement between the projections generated using the ARF method and those from previously validated full MC simulations, but with hundred to thousand fold reductions in simulation time.