Development of Respiratory Tract Organs for ICRP Pediatric Mesh-type Reference Computational Phantoms.

ABSTRACT: As part of the activities of the International Commission on Radiological Protection (ICRP) Task Group 103, the present study developed a new set of respiratory tract organs consisting of the extrathoracic, bronchial, bronchiolar, and alveolar-interstitial regions for newborn, 1-, 5-, 10-, and 15-y-old males and females for use in pediatric mesh-type reference computational phantoms. The developed respiratory tract organs, while preserving the original topologies of those of the pediatric voxel-type reference computational phantoms of ICRP Publication 143, have improved anatomy and detailed structure and also include µm-thick target and source regions prescribed in ICRP Publication 66. The dosimetric impact of the developed respiratory tract organs was investigated by calculating the specific absorbed fraction for internal electron exposures, which were then compared with the ICRP Task Group 96 values. The results showed that except for the alveolar-interstitial region as a source region, the pediatric mesh phantoms showed larger specific absorbed fractions than the Task Group 96 values. The maximum difference was a factor of ~3.5 for the extrathoracic-2 basal cell and surface as target and source regions, respectively. These results reflect the differences in the target masses and geometry caused by the anatomical enhancement of the pediatric mesh phantoms. For the alveolar-interstitial region as a source region, the pediatric mesh phantoms showed larger values for low energy ranges and lower values with increasing energies, owing to the differences in the size and shape of the alveolar-interstitial region.

MIRD Pamphlet No. 28, Part 2: Comparative Evaluation of MIRDcalc Dosimetry Software Across a Compendium of Diagnostic Radiopharmaceuticals.

Radiopharmaceutical dosimetry is usually estimated via organ-level MIRD schema-style formalisms, which form the computational basis for commonly used clinical and research dosimetry software. Recently, MIRDcalc internal dosimetry software was developed to provide a freely available organ-level dosimetry solution that incorporates up-to-date models of human anatomy, addresses uncertainty in radiopharmaceutical biokinetics and patient organ masses, and offers a 1-screen user interface as well as quality assurance tools. The present work describes the validation of MIRDcalc and, secondarily, provides a compendium of radiopharmaceutical dose coefficients obtained with MIRDcalc. Biokinetic data for about 70 currently and historically used radiopharmaceuticals were obtained from the International Commission on Radiological Protection (ICRP) publication 128 radiopharmaceutical data compendium. Absorbed dose and effective dose coefficients were derived from the biokinetic datasets using MIRDcalc, IDAC-Dose, and OLINDA software. The dose coefficients obtained with MIRDcalc were systematically compared against the other software-derived dose coefficients and those originally presented in ICRP publication 128. Dose coefficients computed with MIRDcalc and IDAC-Dose showed excellent overall agreement. The dose coefficients derived from other software and the dose coefficients promulgated in ICRP publication 128 both were in reasonable agreement with the dose coefficients computed with MIRDcalc. Future work should expand the scope of the validation to include personalized dosimetry calculations.

MIRD Pamphlet No. 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry.

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, along with the ability to interpolate between models for patient-specific dosimetry. The software also includes sphere models of various composition for tumor dosimetry. MIRDcalc offers several noteworthy features for organ-level dosimetry, including modeling of blood source regions and dynamic source regions defined by user input, integration of tumor tissues, error propagation, quality control checks, batch processing, and report-preparation capabilities. MIRDcalc implements an immediate, easy-to-use single-screen interface. The MIRDcalc software is available for free download (www.mirdsoft.org) and has been approved by the Society of Nuclear Medicine and Molecular Imaging.

Development of alimentary tract organs for ICRP pediatric mesh-type reference computational phantoms.

In line with the activities of Task Group 103 under the International Commission on Radiological Protection (ICRP), the present study was conducted to develop a new set of alimentary tract organs consisting of the oral cavity, oesophagus, stomach, small intestine, and colon for the newborn, 1 year-old, 5 year-old, 10 year-old, and 15 year-old males and females for use in the pediatric mesh-type reference computational phantoms (MRCPs). The developed alimentary tract organs of the pediatric MRCPs, while nearly preserving the original topology and shape of those of the pediatric voxel-type reference computational phantoms (VRCPs) of ICRPPublication 143, present considerable anatomical improvement and include all micrometre-scale target and source regions as prescribed in ICRPPublication 100. To investigate the dosimetric impact of the developed alimentary tract organs, organ doses and specific absorbed fractions were computed for certain external exposures to photons and electrons and internal exposures to electrons, respectively, which were then compared with the values computed using the current ICRP models (i.e. pediatric VRCPs and ICRP-100 stylised models). The results showed that for external exposures to penetrating radiations (i.e. photons >0.04 MeV), there was generally good agreement between the compared values, within a 10% difference, except for the oral mucosa. For external exposures to weakly penetrating radiations (i.e. low-energy photons and electrons), there were significant differences, up to a factor of ∼8300, owing to the geometric difference caused by the anatomical enhancement in the MRCPs. For internal exposures of electrons, there were significant differences, the maximum of which reached a factor of ∼73 000. This was attributed not only to the geometric difference but also to the target mass difference caused by the different luminal content mass and organ shape.

Improved accuracy of S-value-based dosimetry: a guide to transition from Cristy-Eckerman to ICRP adult phantoms.

BACKGROUND: In 2016, the International Commission on Radiological Protection (ICRP) published the results of Monte Carlo simulations performed using updated and anatomically realistic voxelized phantoms. The resulting specific absorbed fractions are based on more realistic human anatomy than those computed in the stylized, geometrical Cristy-Eckerman (CE) phantom. Despite this development, the ICRP-absorbed fractions have not been widely adopted for radiopharmaceutical dosimetry. To help make the transition, we have established a correspondence between source and target tissues defined in the CE phantom and those defined in the ICRP phantoms. RESULTS: The ICRP phantom has 79 source regions and 43 target regions in comparison with the 23 source and 18 target tissue regions defined in the CE phantom. The ICRP phantom provides tissue regions with greater anatomical detail. Some of this additional detail is focused on radiation protection and dosimetry of inhaled/ingested radioactivity. Some, but not all, of this detail is useful and appropriate for radiopharmaceutical therapy. We have established the correspondence between CE and ICRP phantom source and target regions and attempted to highlight the ICRP source tissues relevant to radiopharmaceutical therapy (RPT). This paper provides tables and figures highlighting the correspondences established. CONCLUSION: The results provide assistance in transitioning from CE-stylized phantoms to the anatomically accurate voxelized ICRP phantoms. It provides specific guidance for porting the total absorbed activity for regions as defined in the CE phantom to regions within the ICRP phantoms.

Specific Absorbed Fractions for Spontaneous Fission Neutron Emitters in the ICRP Reference Pediatric Voxel Phantom Series.

ABSTRACT: Specific absorbed fractions (SAFs) are key components in the workflow of internal exposure assessment following the intake of a radionuclide, allowing quick conversion of particle energy released in a source region to the expected absorbed dose in target regions throughout the body. For data completeness, SAFs for spontaneous fission neutron emitters are currently needed for the recently adopted ICRP reference pediatric voxel phantom series. With 77 source regions within each reference individual and 28 radionuclides decaying via spontaneous fission, full Monte Carlo simulation requires significant computation time. In order to reduce this burden, a novel method for neutron SAF estimation was undertaken. The Monte Carlo N-Particle version 6.1 (MCNP6) simulation package was chosen to simulate the 252 Cf Watt fission neutron spectrum originating from 15 source regions in each phantom; dose estimation within 41 target tissues allowed for assessment of the SAF value for each source-target pair. For the remaining source regions, chord length distributions were computed using MATLAB code to determine the separation between the source-target pairs within the pediatric phantom series. These distance distributions were used in conjunction with a 252 Cf neutron dose point kernel calculated in soft tissue, which was modified to account for the source region's depth from the surface of the body. Lastly, the 252 Cf SAF dataset was extended to the other 27 spontaneous fission neutron emitters based on differences in the Watt fission spectrum parameters of each radionuclide. This methodology has been shown to accurately estimate spontaneous fission neutron SAFs to within 20% of the Monte Carlo estimated value for most source-target pairs in the ICRP reference pediatric series.

A million persons, a million dreams: a vision for a national center of radiation epidemiology and biology.

BACKGROUND: Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. MATERIALS AND METHODS: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautics and Space Administration (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. RESULTS: The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. CONCLUSIONS: The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.

Radium dial workers: back to the future.

PURPOSE: This paper reviews the history of the radium dial workers in the United States, summarizes the scientific progress made since the last evaluation in the early 1990s, and discusses current progress in updating the epidemiologic cohort and applying new dosimetric models for radiation risk assessment. BACKGROUND: The discoveries of radiation and radioactivity led quickly to medical and commercial applications at the turn of the 20th century, including the development of radioluminescent paint, made by combining radium with phosphorescent material and adhesive. Workers involved with the painting of dials and instruments included painters, handlers, ancillary workers, and chemists who fabricated the paint. Dial painters were primarily women and, prior to the mid to late 1920s, would use their lips to give the brush a fine point, resulting in high intakes of radium. The tragic experience of the dial painters had a significant impact on industrial safety standards, including protection measures taken during the Manhattan Project. The dial workers study has formed the basis for radiation protection standards for intakes of radionuclides by workers and the public. EPIDEMIOLOGIC APPROACH: The mortality experience of 3,276 radium dial painters and handlers employed between 1913 and 1949 is being determined through 2019. The last epidemiologic follow-up was 30 years ago when most of these workers were still alive. Nearly 65% were born before 1920, 37.5% were teenagers when first hired, and nearly 50% were hired before 1930 when the habit of placing brushes in mouths essentially stopped. Comprehensive dose reconstruction techniques are being applied to estimate organ doses for each worker related to the intake of 226Ra, 228Ra, and associated photon exposures. Time dependent dose-response analyses will estimate lifetime risks for specific causes of death. DISCUSSION: The study of radium dial workers is part of the Million Person Study of low-dose health effects that is designed to evaluate radiation risks among healthy American workers and veterans. Despite being one of the most important and influential radiation effects studies ever conducted, shifting programmatic responsibilities and declining funding led to the termination of the radium program of studies in the early 1990s. Renewed interest and opportunity have arisen. With scientific progress made in dosimetric methodology and models, the ability to perform a study over the entire life span, and the potential applicability to other scenarios such as medicine, environmental contamination and space exploration, the radium dial workers have once again come to the forefront.

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal electron sources.

In both the International Commission on Radiological Protection (ICRP) and Medical Internal Radiation Dose (MIRD) schemata of internal dosimetry, the S-value is defined as the absorbed dose to a target organ per nuclear decay of the radionuclide in a source organ. Its computation requires data on the energies and yields of all radiation emissions from radionuclide decay, the mass of the target organ, and the value of the absorbed fraction-the fraction of particle energy emitted in the source organ that is deposited in the target organ. The specific absorbed fraction (SAF) is given as the ratio of the absorbed fraction and the target mass. Historically, in the early development of both schemata, computational simplifications were made to the absorbed fraction in considering both organ self-dose ([Formula: see text]) and organ cross-dose ([Formula: see text]). In particular, the value of the absorbed fraction was set to unity for all 'non-penetrating' particle emissions (electrons and alpha particles) such that they contributed only to organ self-dose. As radiation transport codes for charged particles became more widely available, it became increasingly possible to abandon this distinction and to explicitly consider the transport of internally emitted electrons in a manner analogous to that for photons. In this present study, we report on an extensive series of electron SAFs computed in a revised series of the UF/NCI pediatric phantoms. A total of 28 electron energies-0-10 MeV-along a logarithmic energy grid are provided in electronic annexes, where 0 keV is associated with limiting values of the SAF. Electron SAFs were computed independently for collisional energy losses (SAFCEL) and radiation energy losses (SAFREL) to the target organ. A methodology was employed in which values of SAFREL were compiled by first assembling organ-specific and electron energy-specific bremsstrahlung x-ray spectra, and then using these x-ray spectra to re-weight a previously established monoenergetic database of photon SAFs for all phantoms and source-target combinations. Age-dependent trends in the electron SAF were demonstrated for the majority of the source-target organ pairs, and were consistent to values given for the ICRP adult phantoms. In selected cases, however, anticipated age-dependent trends were not seen, and were attributed to anatomical differences in relative organ positioning at specific phantom ages. Both the electron SAFs of this study, and the photon SAFs from our companion study, are presently being used by ICRP Committee 2 in its upcoming pediatric extension to ICRP Publication 133.

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal photon sources.

Assessment of radiation absorbed dose to internal organs of the body from the intake of radionuclides, or in the medical setting through the injection of radiopharmaceuticals, is generally performed based upon reference biokinetic models or patient imaging data, respectively. Biokinetic models estimate the time course of activity localized to source organs. The time-integration of these organ activity profiles are then scaled by the radionuclide S-value, which defines the absorbed dose to a target tissue per nuclear transformation in various source tissues. S-values are computed using established nuclear decay information (particle energies and yields), and a parameter termed the specific absorbed fraction (SAF). The SAF is the ratio of the absorbed fraction-fraction of particle energy emitted in the source tissue that is deposited in the target tissue-and the target organ mass. While values of the SAF may be computed using patient-specific or individual-specific anatomic models, they have been more widely available through the use of computational reference phantoms. In this study, we report on an extensive series of photon SAFs computed in a revised series of the University of Florida and the National Cancer Institute pediatric reference phantoms which have been modified to conform to the specifications embodied in the ICRP reference adult phantoms of Publication 110 (e.g. organs modeled, organ ID numbers, blood contribution to elemental compositions). Following phantom anatomical revisions, photon radiation transport simulations were performed using MCNPX v2.7 in each of the ten phantoms of the series-male and female newborn, 1 year old, 5 year old, 10 year old, and 15 year old-for 60 different tissues serving as source and/or target regions. A total of 25 photon energies were considered from 10 keV to 10 MeV along a logarithm energy grid. Detailed analyses were conducted of the relative statistical errors in the Monte Carlo target tissue energy deposition tallies at low photon energies and over all energies for source-target combinations at large intra-organ separation distances. Based on these analyses, various data smoothing algorithms were employed, including multi-point weighted data smoothing, and log-log interpolation at low energies (1 keV and 5 keV) using limiting SAF values based upon target organ mass to bound the interpolation interval. The final dataset is provided in a series of ten electronic supplemental files in MS Excel format. The results of this study were further used as the basis for assessing the radiative component of internal electron source SAFs as described in our companion paper (Schwarz et al 2021) for this same pediatric phantom series.

Suggested reference values for regional blood volumes in children and adolescents.

Estimates of regional blood volumes (BVs) in humans are needed in dosimetric models of radionuclides and radiopharmaceuticals that decay in the circulation to a significant extent. These values are also needed to refine models of tissue elemental composition in computational human phantoms of both patients and exposed members of the general public. The International Commission on Radiological Protection (ICRP) in its Publication 89 provides reference values for total blood content in the full series of their reference individuals, to include the male and female newborn, 1 year-old, 5 year-old, 10 year-old, 15 year-old, and adult. Furthermore, Publication 89 provides reference values for the percentage distribution of total blood volume in 27 different blood-filled organs and tissues of the reference adult male and adult female. However, no similar distribution values are provided for non-adults. The goal of the present study is to present a volumetric scaling methodology to derive these values for the same organs and tissues at ages younger than the reference adult. Literature data on organ-specific vascular growth in the brain, kidneys, and skeletal tissues are also considered.

Response functions for computing absorbed dose to skeletal tissues from neutron irradiation.

Spongiosa in the adult human skeleton consists of three tissues-active marrow (AM), inactive marrow (IM) and trabecularized mineral bone (TB). AM is considered to be the target tissue for assessment of both long-term leukemia risk and acute marrow toxicity following radiation exposure. The total shallow marrow (TM(50)), defined as all tissues lying within the first 50 µm of the bone surfaces, is considered to be the radiation target tissue of relevance for radiogenic bone cancer induction. For irradiation by sources external to the body, kerma to homogeneous spongiosa has been used as a surrogate for absorbed dose to both of these tissues, as direct dose calculations are not possible using computational phantoms with homogenized spongiosa. Recent micro-CT imaging of a 40 year old male cadaver has allowed for the accurate modeling of the fine microscopic structure of spongiosa in many regions of the adult skeleton (Hough et al 2011 Phys. Med. Biol. 56 2309-46). This microstructure, along with associated masses and tissue compositions, was used to compute specific absorbed fraction (SAF) values for protons originating in axial and appendicular bone sites (Jokisch et al 2011 Phys. Med. Biol. 56 6857-72). These proton SAFs, bone masses, tissue compositions and proton production cross sections, were subsequently used to construct neutron dose-response functions (DRFs) for both AM and TM(50) targets in each bone of the reference adult male. Kerma conditions were assumed for other resultant charged particles. For comparison, AM, TM(50) and spongiosa kerma coefficients were also calculated. At low incident neutron energies, AM kerma coefficients for neutrons correlate well with values of the AM DRF, while total marrow (TM) kerma coefficients correlate well with values of the TM(50) DRF. At high incident neutron energies, all kerma coefficients and DRFs tend to converge as charged-particle equilibrium is established across the bone site. In the range of 10 eV to 100 MeV, substantial differences are observed among the kerma coefficients and DRF. As a result, it is recommended that the AM kerma coefficient be used to estimate the AM DRF, and that the TM kerma coefficient be used to estimate the TM(50) DRF below 10 eV. Between 10 eV and 100 MeV, the appropriate DRF should be used as presented in this study. Above 100 MeV, spongiosa kerma coefficients apply well for estimating skeletal tissue doses. DRF values for each bone site as a function of energy are provided in an electronic annex to this article available at http://stacks.iop.org/0031-9155/56/6873/mmedia.

Linear regression model for predicting patient-specific total skeletal spongiosa volume for use in molecular radiotherapy dosimetry.

UNLABELLED: The toxicity of red bone marrow is widely considered to be a key factor in restricting the activity administered in molecular radiotherapy to suboptimal levels. The assessment of marrow toxicity requires an assessment of the dose absorbed by red bone marrow which, in many cases, requires knowledge of the total red bone marrow mass in a given patient. Previous studies demonstrated, however, that a close surrogate-spongiosa volume (combined tissues of trabecular bone and marrow)-can be used to accurately scale reference patient red marrow dose estimates and that these dose estimates are predictive of marrow toxicity. Consequently, a predictive model of the total skeletal spongiosa volume (TSSV) would be a clinically useful tool for improving patient specificity in skeletal dosimetry. METHODS: In this study, 10 male and 10 female cadavers were subjected to whole-body CT scans. Manual image segmentation was used to estimate the TSSV in all 13 active marrow-containing skeletal sites within the adult skeleton. The age, total body height, and 14 CT-based skeletal measurements were obtained for each cadaver. Multiple regression was used with the dependent variables to develop a model to predict the TSSV. RESULTS: Os coxae height and width were the 2 skeletal measurements that proved to be the most important parameters for prediction of the TSSV. The multiple R(2) value for the statistical model with these 2 parameters was 0.87. The analysis revealed that these 2 parameters predicted the estimated the TSSV to within approximately +/-10% for 15 of the 20 cadavers and to within approximately +/-20% for all 20 cadavers in this study. CONCLUSION: Although the utility of spongiosa volume in estimating patient-specific active marrow mass has been shown, estimation of the TSSV in active marrow-containing skeletal sites via patient-specific image segmentation is not a simple endeavor. However, the alternate approach demonstrated in this study is fairly simple to implement in a clinical setting, as the 2 input measurements (os coxae height and width) can be made with either pelvic CT scanning or skeletal radiography.

Chord-based versus voxel-based methods of electron transport in the skeletal tissues.

Anatomic models needed for internal dose assessment have traditionally been developed using mathematical surface equations to define organ boundaries, shapes, and their positions within the body. Many researchers, however, are now advocating the use of tomographic models created from segmented patient computed tomography (CT) or magnetic resonance (MR) scans. In the skeleton, however, the tissue structures of the bone trabeculae, marrow cavities, and endosteal layer are exceedingly small and of complex shape, and thus do not lend themselves easily to either stylistic representations or in-vivo CT imaging. Historically, the problem of modeling the skeletal tissues has been addressed through the development of chord-based methods of radiation particle transport, as given by studies at the University of Leeds (Leeds, U.K.) using a 44-year male subject. We have proposed an alternative approach to skeletal dosimetry in which excised sections of marrow-intact cadaver spongiosa are imaged directly via microCT scanning. The cadaver selected for initial investigation of this technique was a 66-year male subject of nominal body mass index (22.7 kg m(-2)). The objectives of the present study were to compare chord-based versus voxel-based methods of skeletal dosimetry using data from the UF 66-year male subject. Good agreement between chord-based and voxel-based transport was noted for marrow irradiation by either bone surface or bone volume sources up to 500-1000 keV (depending upon the skeletal site). In contrast, chord-based models of electron transport yielded consistently lower values of the self-absorbed fraction to marrow tissues than seen under voxel-based transport at energies above 100 keV, a feature directly attributed to the inability of chord-based models to account for nonlinear electron trajectories. Significant differences were also noted in the dosimetry of the endosteal layer (for all source tissues), with chord-based transport predicting a higher fraction of energy deposition than given by voxel-based transport (average factor of about 1.6). The study supports future use of voxel-based skeletal models which (1) permit nonlinear electron trajectories across the skeletal tissues, (2) do not rely on mathematical algorithms for treating the endosteal tissue layer, and (3) do not implicitly assume independence of marrow and bone trajectories as is the case for chord-based skeletal models.

A comparison of skeletal chord-length distributions in the adult male.

In radiation protection, skeletal dose estimates are required for the tissues of the hematopoietically active bone marrow and the osteogenic cells of the trabecular and cortical endosteum. Similarly, skeletal radiation dose estimates are required in therapy nuclear medicine in order to develop dose-response functions for myelotoxicity where active bone marrow is generally the dose-limiting organ in cancer radioimmunotherapy. At the present time, skeletal dose models in both radiation protection and medical dosimetry are fundamentally reliant on a single set of chord-length distribution measurements performed at the University of Leeds in the late 1970's for a 44-y-old male subject. These distributions describe the relative frequency at which linear pathlengths are seen across both the marrow cavities and bone trabeculae in seven individual bone sites: vertebrae (cervical and lumbar), proximal femur (head and neck), ribs, cranium (parietal bone), and pelvis (iliac crest). In the present study, we present an alternative set of chord-length distribution data acquired within a total of 14 skeletal sites of a 66-y-old male subject. The University of Florida (UF) distributions are assembled via 3D image processing of microCT scans of physical sections of trabecular spongiosa at each skeletal site. In addition, a tri-linear interpolation Marching Cube algorithm is employed to smooth the digital surfaces of the bone trabeculae while chord-length measurements are performed. A review of mean chord lengths indicate that larger marrow cavities are noted on average in the UF individual for the cervical vertebrae (1,038 vs. 910 microm), lumbar vertebrae (1,479 vs. 1,233 microm), ilium (1,508 vs. 904 microm), and parietal bone (812 vs. 389 microm), while smaller marrow cavities are noted in the UF individual for the femoral head (1,043 microm vs. 1,157 microm), the femoral neck (1,454 microm vs. 1,655 microm), and the ribs (1,630 microm vs. 1,703 microm). The mean chord-lengths for the bone trabeculae show close agreement for both individuals in the ilium (approximately 240 microm) and cervical vertebrae (approximately 280 microm). Thicker trabeculae were seen on average in the UF individual for the femoral head (ratio of 1.50), femoral neck (ratio of 1.10), lumbar vertebrae (ratio of 1.29), and ribs (ratio of 1.14), while thinner trabeculae were seen on average in the UF individual for the parietal bone of the cranium (ratio of 0.92). In two bone sites, prominent discrepancies in chord distribution shape were noted between the Leeds 44-y-old male and the UF 66-y-old male: (1) the bone trabeculae in the ribs, and (2) the marrow cavities and bone trabeculae within the cranium.

Absorbed fractions for alpha-particles in tissues of trabecular bone: considerations of marrow cellularity within the ICRP reference male.

UNLABELLED: Alpha-particles are of current interest in radionuclide therapy due to their short range and high rates of energy transfer to target tissues. Published values of alpha-particle absorbed fraction phi in the skeletal tissues, as needed for patient-specific dosimetry under the MIRD schema, do not generally account for its variation with particle energy or skeletal site. Furthermore, variations in alpha-particle absorbed fraction with marrow cellularity have yet to be fully considered. METHODS: In this study, a 3-dimensional (3D) chord-based radiation transport model (or 3D-CBIST) is presented, which combines (a) chord-based techniques for tracking alpha-particles across bone trabeculae, endosteum, and marrow cavities and (b) a spatial model of the marrow tissues that explicitly considers the presence of marrow adipocytes. Chord-length distributions are taken from a 44-y male subject (ICRP [International Commission on Radiological Protection] Reference Male) and are identical to those used currently for clinical dose estimates for beta-particle emitters. RESULTS: Values of phi(active marrow<--active marrow) given by the 3D-CBIST model are shown to be considerably lower than phi = 1.0 assumed under the ICRP Publication 30 and 2003 Eckerman bone models. For example, values of absorbed fraction for the self-dose to active bone marrow in the ribs, cervical vertebra, and parietal bone are 0.81, 0.80, and 0.55 for 6-MeV alpha-particles and are 0.74, 0.72, and 0.43 for 9-MeV alpha-particles, where each is evaluated at ICRP reference cellularities in the 3D-CBIST model (72%, 72%, and 42%, respectively, at age 25 y). CONCLUSION: Improvements in patient-specific dosimetry of skeletal tissues require explicit consideration of not only changes in target mass with variable patient marrow cellularity (i.e., active marrow) but also corresponding changes in values of the absorbed fraction. The data given in this study provide a more-firm basis for application of the MIRD schema to patient-specific dosimetry for newly developing therapies using alpha-particle emitters.

Accounting for beta-particle energy loss to cortical bone via paired-image radiation transport (PIRT).

Current methods of skeletal dose assessment in both medical physics (radionuclide therapy) and health physics (dose reconstruction and risk assessment) rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model which provides a more realistic three-dimensional (3D) geometry for particle transport in the skeletal site at both microscopic and macroscopic levels of its histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and individual ribs excised from a 66-year male cadaver (BMI of 22.7 kg m(-2)). For the three skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were taken and subjected to microCT imaging. Voxels within the resulting microCT images were then segmented and labeled as regions of bone trabeculae, endosteum, active marrow, and inactive marrow through application of image processing algorithms. The PIRT methodology was then implemented within the EGSNRC radiation transport code whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the CT microimage of the skeletal site. At initial electron energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow are noted between PIRT model simulations and those estimated under existing techniques of infinite spongiosa transport. Calculations of radionuclide S values under both methodologies imply that current chord-based models may overestimate the absorbed dose to active bone marrow in these skeletal sites by 0% to 27% for low-energy beta emitters (33P, 169Er, and 177Lu), by approximately 4% to 49% for intermediate-energy beta emitters (153Sm, 186Re, and 89Sr), and by approximately 14% to 76% for high-energy beta emitters (32p, 188Re, and 90Y). The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high energy beta emitters.

A paired-image radiation transport model for skeletal dosimetry.

UNLABELLED: Toxicity of the hematopoietically active bone marrow continues to be a primary limitation in radionuclide therapies of cancer. Improved techniques for patient-specific skeletal dosimetry are thus crucial to the development of dose-response relationships needed to optimize these therapies (i.e., avoid both marrow toxicity and tumor underdosing). Current clinical methods of skeletal dose assessment rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model that can provide a more realistic 3-dimensional geometry for particle transport of the skeletal site at both microscopic and macroscopic levels of its histology. METHODS: Ex vivo CT scans were acquired of the lumbar vertebra and right proximal femur excised from a 66-y male cadaver (body mass index, 22.7 kg m(-2)). For both skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were then taken and subjected to nuclear magnetic resonance (NMR) microscopy. Voxels within the resulting NMR microimages were segmented and labeled into regions of bone trabeculae, endosteum, active marrow, and inactive marrow. The PIRT methodology was then implemented within the EGSnrc radiation transport code, whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the NMR microimage of the skeletal site. RESULTS: At electron initial energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow is noted between PIRT model simulations and those estimated under infinite spongiosa transport techniques. Calculations of radionuclide S values under both methodologies imply that current chord-based models used in clinical skeletal dosimetry can overestimate dose to active bone marrow in these 2 skeletal sites by approximately 4%-23% for low-energy beta-emitters ((33)P, (169)Er, and (177)Lu), by approximately 4%-25% for intermediate-energy beta-emitters ((153)Sm, (186)Re, and (89)Sr), and by approximately 11%-30% for high-energy beta-emitters ((32)P, (188)Re, and (90)Y). CONCLUSION: The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton, thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high beta-emitters.

Considerations of marrow cellularity in 3-dimensional dosimetric models of the trabecular skeleton.

UNLABELLED: Dose assessment to active bone marrow is a critical feature of radionuclide therapy treatment planning. Skeletal dosimetry models currently used to assign radionuclide S values for clinical marrow dose assessment are based on bone and marrow cavity chord-length distributions. Accordingly, these models cannot explicitly consider energy loss to inactive marrow (adipose tissue) during particle transport across the trabecular marrow space (TMS). One method to account for this energy loss is to uniformly scale the resulting TMS absorbed fractions by reference values of site-specific marrow cellularity. In doing so, however, the resulting absorbed fractions for self-irradiation of the trabecular active marrow (TAM) do not converge to unity at low electron source energies. This study attempts to address this issue by using nuclear magnetic resonance microscopy images of trabecular bone to define 3-dimensional (3D) dosimetric models in which explicit spatial distributions of adipose tissue are introduced. METHODS: Cadaveric sources of trabecular bone were taken from both the femoral heads and humeral epiphyses of a 51-y-old male subject. The bone sites were sectioned and subsequently imaged at a proton resonance frequency of 200 MHz (4.7 T) using a 3D spin-echo pulse sequence. After image segmentation, voxel clusters of adipocytes were inserted interior to the marrow cavities of the binary images, which were then coupled to the EGS4 radiation transport code for simulation of active marrow electron sources. RESULTS: Absorbed fractions for self-irradiation of the TAM were tabulated for both skeletal sites. Substantial variations in the absorbed fraction to active marrow are seen with changes in marrow cellularity, particularly in the energy range of 100-500 keV. These variations are seen to be more dramatic in the humeral epiphysis (larger marrow volume fraction) than in the femoral head. CONCLUSION: Results from electron transport in 3D models of the trabecular skeleton indicate that current methods to account for marrow cellularity in chord-based models are incomplete. At 10 keV, for example, the Eckerman and Stabin model underestimates the self-absorbed fraction to active marrow by 75%. At 1 MeV, the model of Bouchet et al. overestimates this same value by 40%. In the energy range of 20-200 keV, neither model accurately predicts energy loss to the active bone marrow. Thus, it is proposed that future extensions of skeletal dosimetry models use 3D transport techniques in which explicit delineation of active and inactive marrow is feasible.