Evolution and status of bone and marrow dose models.

Investigations at the University of Leeds under the direction of F.W. Spiers in the early 1960s through the late 1970s established the first comprehensive assessment of marrow dose conversion factors (DCFs) for beta-emitting radionuclides within the volume or on the surface of trabecular bone. These DCFs were subsequently used in deriving radionuclide S values for skeletal tissues published in MIRD Pamphlet No. 11. Eckerman re-evaluated this work and extended the methods of Spiers to radionuclides within the marrow to provide DCFs for fifteen skeletal regions in computational models representing individuals of six different ages. These results were used in the MIRDOSE3 software. Bouchet et al. used updated information on regional bone and marrow masses, as well as 3D electron transport techniques, to derive radionuclide S values in skeletal regions of the adult. Although these two efforts are similar in most regards, the models differ in three respects in: (1) the definition of the red marrow region, (2) the definition of a surface source of activity, and (3) the assumption applied in transporting electrons through the trabecular endosteum. In this study, a review of chord-based skeletal models is given, followed by a description of the differences in the Eckerman and Bouchet et al. transport models. Finally, new data from NMR microscopy and radiation transport in trabecular bone is applied to address item (1) above. Dose conversion factors from MIRD 11, the Eckerman model, the Bouchet et al. model, and a revised model are compared for several radionuclides important to internal emitter therapy.

Comparisons of point and average organ dose within an anthropomorphic physical phantom and a computational model of the newborn patient.

Pediatric radiographic examinations yield medical benefits and/or diagnostic information that must be balanced against potential risk from patient radiation exposure. Consequently, clinical tools for measuring internal organ dose are needed for medical risk assessment. In this study, a physical phantom and Monte Carlo simulation model of the newborn patient were developed based upon their stylized mathematical expressions (ORNL and MIRD model series). The physical phantom was constructed using tissue equivalent substitutes for soft tissue, lung, and skeleton. Twenty metal-oxide-semiconductor field effect transistor (MOSFET) dosimeters were then inserted at three-dimensional positions representing the centroids of organs assigned in the ICRP's definition of the effective dose. MOSFET-derived point estimates of organ dose were shown to be in reasonable agreement with Monte Carlo estimates for representative newborn head, chest, and abdomen radiographic exams. Ratios of average organ dose assessed via MCNP simulations to the MOSFET-derived point doses (point-to-organ dose scaling factors, SF(POD)) are tabulated for subsequent use in clinical irradiations of the newborn phantom/MOSFET system. Values of SF(POD) indicate that MOSFET measurements of point dose for in-field exposures need to be adjusted only to within 10% to report volume-averaged organ dose. Larger adjustments to point doses are noted for organs out-of-field. For walled organs, point estimates of organ dose at the content centroid are shown to underestimate the average wall dose when the organ is within the primary field: SF(POD) of 1.19 for the stomach (AP chest exam), and SF(POD) of 1.15 for the urinary bladder (AP abdomen exam).

Isotropic beam bouquets for shaped beam linear accelerator radiosurgery.

In stereotactic radiosurgery and radiotherapy treatment planning, the steepest dose gradient is obtained by using beam arrangements with maximal beam separation. We propose a treatment plan optimization method that optimizes beam directions from the starting point of a set of isotropically convergent beams, as suggested by Webb. The optimization process then individually steers each beam to the best position, based on beam's-eye-view (BEV) critical structure overlaps with the target projection and the target's projected cross sectional area at each beam position. This final optimized beam arrangement maintains a large angular separation between adjacent beams while conformally avoiding critical structures. As shown by a radiosurgery plan, this optimization method improves the critical structure sparing properties of an unoptimized isotropic beam bouquet, while maintaining the same degree of dose conformity and dose gradient. This method provides a simple means of designing static beam radiosurgery plans with conformality indices that are within established guidelines for radiosurgery planning, and with dose gradients that approach those achieved in conventional radiosurgery planning.

Beta-particle dosimetry of the trabecular skeleton using Monte Carlo transport within 3D digital images.

Presently, skeletal dosimetry models utilized in clinical medicine simulate electron path lengths through skeletal regions based upon distributions of linear chords measured across bone trabeculae and marrow cavities. In this work, a human thoracic vertebra has been imaged via nuclear magnetic resonance (NMR) spectroscopy yielding a three-dimensional voxelized representation of this skeletal site. The image was then coupled to the radiation transport code EGS4 allowing for 3D tracing of electron paths within its true 3D structure. The macroscopic boundaries of the trabecular regions, as well as the cortex of cortical bone surrounding the bone site, were explicitly considered in the voxelized transport model. For the case of a thoracic vertebra, energy escape to the cortical bone became significant at source energies exceeding approximately 2 MeV. Chord-length distributions were acquired from the same NMR image, and subsequently used as input for a chord-based dosimetry model. Differences were observed in the absorbed fractions given by the chord-based model and the voxel transport model, suggesting that some of the input chord distributions for the chord-based models may not be accurate. Finally, this work shows that skeletal mass estimates can be made from the same NMR image in which particle transport is performed. This feature allows one to determine a skeletal S-value using absorbed fraction and mass data taken from the same anatomical tissue sample. The techniques developed in this work may be applied to a variety of skeletal sites, thus allowing for the development of skeletal dosimetry models at all skeletal sites for both males and females and as a function of subject age.

Calibration of three-dimensional ultrasound images for image-guided radiation therapy.

A new technique of patient positioning for radiotherapy/radiosurgery of extracranial tumours using three-dimensional (3D) ultrasound images has been developed. The ultrasound probe position is tracked within the treatment room via infrared light emitting diodes (IRLEDs) attached to the probe. In order to retrieve the corresponding room position of the ultrasound image, we developed an initial ultrasound probe calibration technique for both 2D and 3D ultrasound systems. This technique is based on knowledge of points in both room and image coordinates. We first tested the performance of three algorithms in retrieving geometrical transformations using synthetic data with different noise levels. Closed form solution algorithms (singular value decomposition and Horn's quaternion algorithms) were shown to outperform the Hooke and Jeeves iterative algorithm in both speed and accuracy. Furthermore, these simulations show that for a random noise level of 2.5, 5, 7.5 and 10 mm, the number of points required for a transformation accuracy better than 1 mm is 25, 100, 200 and 500 points respectively. Finally, we verified the tracking accuracy of this system using a specially designed ultrasound phantom. Since ultrasound images have a high noise level, we designed an ultrasound phantom that provides a large number of points for the calibration. This tissue equivalent phantom is made of nylon wires, and its room position is optically tracked using IRLEDs. By obtaining multiple images through the nylon wires, the calibration technique uses an average of 300 points for 3D ultrasound volumes and 200 for 2D ultrasound images, and its stability is very good for both rotation (standard deviation: 0.4 degrees) and translation (standard deviation: 0.3 mm) transformations. After this initial calibration procedure, the position of any voxel in the ultrasound image volume can be determined in world space, thereby allowing real-time image guidance of therapeutic procedures. Finally, the overall tracking accuracy of our 3D ultrasound image-guided positioning system was measured to be on average 0.2 mm, 0.9 mm and 0.6 mm for the AP, lateral and axial directions respectively.

Ultrasonographic guidance for spinal extracranial radiosurgery: technique and application for metastatic spinal lesions.

OBJECT: The relatively stationary anatomy of the intracranial compartment has allowed the development of stereotactic radiosurgery as an effective treatment option for many intracranial lesions. Difficulty in accurately tracking extracranial targets has limited its development in the treatment of these lesions. The ability to track extracranial structures in real time with ultrasound images allows a system to upgrade and interface pretreatment volumetric images for extracranial applications. In this report the authors describe this technique as applied to the treatment of localized metastatic spinal disease. METHODS: The extracranial stereotactic system consists of an optically tracked ultrasonography unit that can be registered to a linear accelerator coordinate system. Stereotactic ultrasound images are acquired following patient positioning, based on a pretreatment computerized tomography (CT) simulation. The soft-tissue shifts between the virtual CT-based treatment plan and the actual treatment are determined. The degree of patient offset is tracked and used to correct the treatment plan. The ultrasonography-based stereotactic navigation system is accurate to within an approximate means of 1.5 mm based on testing with an absolute coordinate phantom. A radiosurgical treatment was delivered using the system for localization of a metastatic spinal lesion. Compared with the virtual CT simulation, the actual treatment plan isocenter was shifted 12.2 mm based on the stereotactic ultrasound image. The patient was treated using noncoplanar beams to a dose of 15.0 Gy to the 80% isodose shell in a single fraction. CONCLUSIONS: A system for high-precision radiosurgical treatment of metastatic spinal tumors has been developed, tested, and applied clinically. Optical tracking of the ultrasonography probe provides real-time tracking of the patient anatomy and allows computation of the target displacement prior to treatment delivery. The results reported here suggest the feasibility and safety of the technique.

A geometrically based method for automated radiosurgery planning.

PURPOSE: A geometrically based method of multiple isocenter linear accelerator radiosurgery treatment planning optimization was developed, based on a target's solid shape. METHODS AND MATERIALS: Our method uses an edge detection process to determine the optimal sphere packing arrangement with which to cover the planning target. The sphere packing arrangement is converted into a radiosurgery treatment plan by substituting the isocenter locations and collimator sizes for the spheres. RESULTS: This method is demonstrated on a set of 5 irregularly shaped phantom targets, as well as a set of 10 clinical example cases ranging from simple to very complex in planning difficulty. Using a prototype implementation of the method and standard dosimetric radiosurgery treatment planning tools, feasible treatment plans were developed for each target. The treatment plans generated for the phantom targets showed excellent dose conformity and acceptable dose homogeneity within the target volume. The algorithm was able to generate a radiosurgery plan conforming to the Radiation Therapy Oncology Group (RTOG) guidelines on radiosurgery for every clinical and phantom target examined. CONCLUSIONS: This automated planning method can serve as a valuable tool to assist treatment planners in rapidly and consistently designing conformal multiple isocenter radiosurgery treatment plans.

Improvement of internal dose calculations using mathematical models of different adult heights.

In internal dosimetry for both nuclear medicine and radiation protection, the adult morphology is represented by a limited number of anthropomorphic models that may not be suitable for all patients. To develop more patient-specific dosimetry, we derived six mathematical models for adults of different height. Three male models (160 cm, 170 cm and 180 cm) and three female models (150 cm, 160 cm and 170 cm), based on the MIRD model design, were developed from the statistical analysis of anthropometric data gathered from autopsies. Monte Carlo calculations were used to provide an example of estimations of S value for these new models for iodine 131 uniformly distributed successively in the stomach or in the urinary bladder. On average, for both male and female models, an increase in the model height of 10 cm leads to a mean reduction in the S value for iodine-131 by 20% and 29% when the stomach and the urinary bladder respectively are selected as source regions. Similarly, when the model height increases by 20 cm, the S values decrease on average by 35% and 48%. This study presents the use of anthropometric data to develop new mathematical models for adults of different height, and shows the significant influence of the morphology on dosimetric parameters.

Marrow toxicity of 33P-versus 32P-orthophosphate: implications for therapy of bone pain and bone metastases.

UNLABELLED: Several bone-seeking radiopharmaceuticals, such as 32P-orthophosphate, 89Sr-chloride, 186Re-1,1 hydroxyethylidene diphosphonate (HEDP), and 153Sm-ethylene diamine tetramethylene phosphonic acid (EDTMP), have been used to treat bone pain. The major limiting factor with this modality is bone marrow toxicity, which arises from the penetrating nature of the high-energy beta particles emitted by the radionuclides. It has been hypothesized that marrow toxicity can be reduced while maintaining therapeutic efficacy by using radionuclides that emit short-range beta particles or conversion electrons. In view of the significant clinical experience with 32P-orthophosphate, and the similarity in pain relief afforded by 32P-orthophosphate and 89Sr-chloride, this hypothesis is examined in this study using 32P- and 33P-orthophosphate in a mouse femur model. METHODS: Survival of granulocyte macrophage colony-forming cells (GM-CFCs) in femoral marrow was used as a biologic dosimeter for bone marrow. 32P- and 33P-orthophosphate were administered intravenously, and GM-CFC survival was determined as a function of time after injection and, at the nadir, as a function of injected activity. The kinetics of radioactivity in the marrow, muscle, and femoral bone were also determined. The biologic dosimeter was calibrated by assessing GM-CFC survival at its nadir after chronic irradiation of Swiss Webster mice with exponentially decreasing dose rates of gamma rays (relative biologic effectiveness equivalent to that of beta particles) from a low-dose rate 137Cs irradiator. Dose-rate decrease half-times (Td) (time required for 137Cs gamma ray dose rate to decrease by one half) of 62, 255, and 425 h and infinity were used to simulate the dose rate patterns delivered by the radiopharmaceuticals as dictated by their effective clearance half-times from the mouse femurs. These data were used to experimentally determine the mean absorbed dose to the femoral marrow per unit injected activity. Finally, a theoretical dosimetry model of the mouse femur was developed, and the absorbed doses to the femoral marrow, bone, and endosteum were calculated using the EGS4 Monte Carlo code. RESULTS: When the animals were irradiated with exponentially decreasing dose rates of 137Cs gamma rays, initial dose rates required to achieve 37% survival were 1.9, 0.98, 0.88, and 0.79 cGy/h for dose rate decrease half-times of 62, 255, and 425 h and infinity, respectively. The D37 values were 144 +/- 15, 132 +/- 12, 129 +/- 3, and 133 +/- 10 cGy, respectively, compared with a value of 103 cGy for acute irradiation. When 32P and 33P were administered, the injected activities required to achieve 37% survival were 313 and 2,820 kBq, respectively. Theoretical dosimetry calculations show that 33P offers a 3- to 6-fold therapeutic advantage over 32P, depending on the source and target regions assumed. CONCLUSION: The low-energy beta-particle emitter 33P appears to offer a substantial dosimetric advantage over energetic beta-particle emitters (e.g., 32p, 89Sr, 186Re) for irradiating bone and minimizing marrow toxicity. This suggests that low-energy beta or conversion electron emitters may offer a substantial advantage for alleviation of bone pain as well as for specifically irradiating metastatic disease in bone.

Protection by DMSO against cell death caused by intracellularly localized iodine-125, iodine-131 and polonium-210.

The mechanisms by which DNA-incorporated radionuclides impart lethal damage to mammalian cells were investigated by examining the capacity of dimethyl sulfoxide (DMSO) to protect against lethal damage to Chinese hamster V79 cells caused by unbound tritium ((3)H(2)O), DNA-incorporated (125)I- and (131)I-iododeoxyuridine ((125)IdU, (131)IdU), and cytoplasmically localized (210)Po citrate. The radionuclides (3)H and (131)I emit low- and medium-energy beta particles, respectively, (125)I is a prolific Auger electron emitter, and (210)Po emits 5.3 MeV alpha particles. Cells were radiolabeled and maintained at 10.5 degrees C for 72 h in the presence of different concentrations of DMSO (5-12.5% v/v), and the surviving fraction compared to that of unlabeled controls was determined. DMSO afforded no protection against the lethal effects of the high-LET alpha particles emitted by (210)Po. Protection against lethal damage caused by unbound (3)H, (131)IdU and (125)IdU depended on the concentration of DMSO in the culture medium. Ten percent DMSO provided maximum protection in all cases. The dose modification factors obtained at 10% DMSO for (3)H(2)O, (131)IdU, (125)IdU and (210)Po citrate were 2.9 +/- 0.01, 2.3 +/- 0.5, 2.6 +/- 0.2 and 0.95 +/- 0.07, respectively. These results indicate that the toxicity of Auger electron and beta-particle emitters incorporated into the DNA of mammalian cells is largely radical-mediated and is therefore indirect in nature. This is also the case for the low-energy beta particles emitted by (3)H(2)O. In contrast, alpha particles impart lethal damage largely by direct effects. Finally, calculations of cellular absorbed doses indicate that beta-particle emitters are substantially more toxic when incorporated into the DNA of mammalian cells than when they are localized extracellularly.

Considerations in the selection of radiopharmaceuticals for palliation of bone pain from metastatic osseous lesions.

UNLABELLED: Bone pain is a common complication for terminal patients with bone metastases from prostate, lung, breast, and other malignancies. A multidisciplinary approach in treating bone pain is generally required, 1 which includes a combination of analgesic drug therapy, radiation therapy, hormonal therapy, and chemotherapy. Over the years, treatment of bone pain using bone-seeking radiopharmaceuticals has been explored extensively. Pharmaceuticals labeled with energetic 1-particle emitters such as 32p, 89Sr, 153Sm, and 186Re, in addition to the low-energy electron emitter 117mSn, have been studied for this purpose. Bone-marrow toxicity as a consequence of chronic irradiation by the energetic , particles is a general problem associated with this form of treatment. It is therefore desirable to identify radiochemicals that minimize the dose to the bone marrow and at the same time deliver therapeutic doses to the bone. METHODS: New S values (mean absorbed dose per unit cumulated activity) for target regions of human bone and marrow were used to ascertain the capacity of various radiochemicals to deliver a high bone dose while minimizing the marrow dose. The relative dosimetric advantage of a given radiopharmaceutical compared with a reference radiochemical was quantitated as a dosimetric relative advantage factor (RAF). Several radionuclides that emit energetic 1 particles (32p, 89Sr, 153Sm, 186Re, and 177Lu) and radionuclides that emit low-energy electrons or beta particles (169Er, 117mSn, and 33p) were evaluated. For these calculations, ratios of the cumulated activity in the bone relative to cumulated activity in the marrow alpha equal to 10 and 100 were used. RESULTS: When the radiopharmaceutical was assumed to be uniformly distributed in the endosteum and alpha was taken as 100 for both the reference and test radiochemicals, the RAF values compared with the reference radionuclide 32p were 1.0, 1.2, 1.4, 1.6, 1.7, 1.9, and 2.0 for 89Sr, 186Re, 153Sm, 177Lu, 169Er, 117mSn, and 33P, respectively. In contrast, when the radiopharmaceutical is assumed to be uniformly distributed in the bone volume, the RAF values for these 7 radionuclides were 1.1, 1.5, 2.4, 3.2, 4.5, 5.1, and 6.5, respectively. CONCLUSION: These results suggest that low-energy electron emitters such as 117mSn and 33P are more likely to deliver a therapeutic dose to the bone while sparing the bone marrow than are energetic beta emitters such as 32p and 89Sr. Therefore, radiochemicals tagged with low-energy electron or beta emitters are the radiopharmaceuticals of choice for treatment of painful metastatic disease in bone.

S values for radionuclides localized within the skeleton.

UNLABELLED: Calculations of radiation absorbed dose to the active marrow are important to radionuclide therapies such as radioimmunotherapy and bone pain palliation. In diagnostic nuclear medicine, calculations of the effective dose for radiopharmaceutical procedures also require the assessment of radiation dose to the skeletal endosteum. We have previously reported the development of 2 3-dimensional electron transport models for assessing absorbed fractions to both marrow and endosteum in trabecular and cortical bone, respectively. Here, we extend these calculations to the assignment of radionuclide S values. METHODS: Data published in International Commission on Radiological Protection Publication 70 were used to develop tables of masses for total marrow space, active and inactive marrow, endosteum, and bone matrix within 22 skeletal sites in the adult. Using our site-specific tissue masses, along with electron absorbed fractions given by our 3-dimensional transport models, radionuclide S values (electron and beta particle components only) were subsequently calculated using the MIRD schema for 32P, 33P, 89Sr, 90Sr, 90Y, 117mSn, 153Sm, 169Er, 177Lu, and 186Re. Specific consideration was given to the trabecular active marrow as both a source and a target region. RESULTS: Site-specific radionuclide S values are reported for 22 skeletal sites, for 9 source-target tissue combinations within trabecular bone, and for 6 source-target tissue combinations within cortical bone. Skeletal-averaged S values are also provided. CONCLUSION: A fully documented model is presented for the adult for use in radionuclide dosimetry of the skeleton. The model is based on both the latest international recommendations for skeletal tissue masses and results from three-dimensional electron transport calculations within the skeleton. Comparisons are additionally made against the radionuclide S values published in MIRD Pamphlet No. 11 and those calculated using the MIRDOSE2 and MIRDOSE3 computer codes. Differences in these datasets vary with the source-target combination considered and may be attributed to 1 of 3 causes: (a) assumptions on reference target masses, (b) transport models used to assign absorbed fractions, and (c) implicit assumptions made in considering the trabecular active marrow as both a source and a target tissue.

Marrow-sparing effects of 117mSn(4+)diethylenetriaminepentaacetic acid for radionuclide therapy of bone cancer.

UNLABELLED: Several bone-seeking radionuclides (32P, 89Sr, 186Re, and 153Sm) have been used to treat bone pain. The limiting factor in this modality is marrow toxicity. Our hypothesis is that marrow toxicity can be reduced while maintaining therapeutic efficacy using radionuclides that emit short-range beta particles or conversion electrons (CEs). A recent study on 47 patients using the short-range CE emitter 117mSn(4+)diethylenetriaminepentaacetic acid (117mSn(4+)DTPA) supports this hypothesis. The hypothesis is now tested using 117mSn(4+)DTPA in a mouse femur model. METHODS: The survival of granulocyte-macrophage colony-forming cells (GM-CFCs) in femoral marrow is used as a biologic dosimeter for bone marrow. The dosimeter is calibrated by irradiating mice with exponentially decreasing dose rates of 137Cs gamma-rays with a dose-rate decrease half-time, Td, equal to the effective clearance half-time of 117mSn(4+)DTPA from the femur (222 h). When Td = 222 h, the mean absorbed dose required to achieve a survival fraction of 37% is 151 cGy. After calibration, 117mSn(4+)DTPA is administered and GM-CFC survival is determined as a function of injected activity. These data are used to experimentally determine the mean absorbed dose to the femoral marrow per unit injected activity. The kinetics of radioactivity in the marrow, muscle, and femoral bone are also determined. Finally, a theoretic dosimetry model of the mouse femur is used, and the absorbed doses to the femoral marrow and bone are calculated. RESULTS: The experimental mean absorbed dose to the femoral marrow per unit injected activity of 117mSn(4+)DTPA is 0.043 cGy/kBq. The theoretic mean absorbed dose to the femoral bone per unit injected activity is 1.07 cGy/kBq. If these data are compared with those obtained previously for 32P-orthophosphate, the radiochemical 117mSn(4+)DTPA yields up to an 8-fold therapeutic advantage over the energetic beta emitter 32P. CONCLUSION: The CE emitter 117mSn offers a large dosimetric advantage over energetic beta-particle emitters for alleviating bone pain, and possibly for other therapeutic applications, while minimizing marrow toxicity.

A three-dimensional transport model for determining absorbed fractions of energy for electrons within trabecular bone.

UNLABELLED: Bone marrow is generally the dose-limiting organ of concern in radioimmunotherapy and in radionuclide palliation of bone pain. However, skeletal dosimetry is complicated by the intricate nature of its microstructure, which can vary greatly throughout skeletal regions. In this article, a new three-dimensional electron transport model for trabecular bone is introduced, based on Monte Carlo transport and on bone microstructure information for several trabecular bone sites. METHODS: Marrow cavity and trabecular chord length distributions originally published by Spiers et al. were randomly sampled to create alternating regions of bone, endosteum and marrow during the three-dimensional transport of single electrons. For the marrow spaces, explicit consideration of the site-specific elemental composition was made in the transport calculations based on the percentage of active and inactive marrow in each region. The electron transport was performed with the EGS4 electron transport code and the parameter reduced electron-step transport algorithm. Electron absorbed fractions of energy were tabulated for seven adult trabecular bone sites, considering three source and target regions: the trabecular marrow space (TMS), the trabecular bone endosteum (TBE) and the trabecular bone volume (TBV). RESULTS: For all source-target combinations, the absorbed fraction was seen to vary widely within the skeleton. These variations can be directly attributed to the differences in the trabecular microstructure of the different skeletal regions. For many source-target combinations, substantial energy dependence was seen in the calculated absorbed fraction, a factor not considered in values recommended by the International Commission on Radiological Protection (ICRP). A one-dimensional model of electron transport in trabecular bone, based on range-energy relationships, was also developed to verify the three-dimensional transport model and to evaluate differences between the two modeling approaches. Differences of approximately 10%-15% were seen, particularly at low electron energies. In the case of a TBV source and a TMS target (or vice versa), differences >50% were seen in the absorbed fraction. CONCLUSION: The three-dimensional model of electron transport in trabecular bone allows improved estimates of skeletal absorbed fractions. The model highlights both the regional and the energy dependency of the absorbed fraction not previously considered in the ICRP model.

A new rectal model for dosimetry applications.

UNLABELLED: A revised geometric representative model of the lower part of the colon, including the rectum, the urinary bladder and prostate, is proposed for use in the calculation of absorbed dose from injected radiopharmaceuticals. The lower segment of the sigmoid colon as described in the 1987 Oak Ridge National Laboratory mathematical phantoms does not accurately represent the combined urinary bladder/rectal/prostate geometry. In the revised model in this study, the lower part of the abdomen includes an explicitly defined rectum. The shape of sigmoid colon is more anatomically structured, and the diameters of the descending colon are modified to better approximate their true anatomic dimensions. To avoid organ overlap and for more accurate representation of the urinary bladder and the prostate gland (in the male), these organs are shifted from their originally defined positions. The insertion of the rectum and the shifting of the urinary bladder will not overlap with or displace the female phantom's ovaries or the uterus. In the adult male phantom, the prostatic urethra and seminal duct are also included explicitly in the model. The relevant structures are defined for the newborn and 1-, 5-, 10- and 15-y-old (adult female) and adult male phantoms. METHODS: Values of the specific absorbed fractions and radionuclide S values were calculated with the SIMDOS dosimetry package. Results for 99mTc and other radionuclides are compared with previously reported values. RESULTS: The new model was used to calculate S values that may be crucial to calculations of the effective dose equivalent. For 131I, the S (prostate<--urinary bladder contents) and S (lower large intestine [LLI] wall<--urinary bladder contents) are 6.7 x 10(-6) and 3.41 x 10(-6) mGy/MBq x s, respectively. Corresponding values given by the MIRDOSE3 computer program are 6.23 x 10(-6) and 1.53 x 10(-6) mGy/MBq x s, respectively. The value of S (rectum wall<--urinary bladder contents) is 4.84 x 10(-5) mGy/MBq x s. For 99mTc, we report S (testes<--prostate) and S (LLI wall<--prostate) of 9.41 x 10(-7) and 1.53 x 10(-7) mGy/MBq x s versus 1.33 x 10(-6) and 7.57 x 10(-6) mGy/MBq x s given by MIRDOSE3, respectively. The value of S (rectum wall<--prostate) for 99mTc is given as 4.05 x 10(-6) mGy/MBq x s in the present model. CONCLUSION: The new revised rectal model describes an anatomically realistic lower abdomen region, thus giving improved estimates of absorbed dose. Due to shifting the prostate gland, a 30%-45% reduction in the testes dose and the insertion of the rectum leads to 48%-55% increase in the LLI wall dose when the prostate is the source organ.

Five pediatric head and brain mathematical models for use in internal dosimetry.

UNLABELLED: Mathematical models of the head and brain currently used in pediatric neuroimaging dosimetry lack the anatomic detail needed to provide the necessary physical data for suborgan brain dosimetry. To overcome this limitation, the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine recently adopted a detailed dosimetric model of the head and brain for the adult. METHODS: New head and brain models have been developed for a newborn, 1, 5, 10 and 15 y old for use in internal dosimetry. These models are based on the MIRD adult head and brain model and on published head and brain dimensions. They contain the same eight brain subregions and the same head regions as the adult model. These new models were coupled with the Monte Carlo transport code EGS4, and absorbed fractions of energy were calculated for 14 sources of monoenergetic photons and electrons in the energy range of 10 keV-4 MeV. These absorbed fractions were then used along with radionuclide decay data to generate S values for all ages for 99mTc, considering 12 source and 15 target regions. RESULTS: Explicit transport of positrons was also considered with separation of the annihilation photons component to the absorbed fraction of energy in the calculation of S values for positron-emitting radionuclides. No statistically significant differences were found when S values were calculated for positron-emitting radionuclides under explicit consideration of the annihilation event compared with the traditional assumption of a uniform distribution of 0.511-MeV photons. CONCLUSION: The need for electron transport within the suborgan brain regions of these pediatric phantoms was reflected by the relatively fast decrease of the self-absorbed fraction within many of the brain subregions, with increasing particle energy. This series of five dosimetric head and brain models will allow more precise dosimetry of radiopharmaceuticals in pediatric nuclear medicine brain procedures.

MIRD Pamphlet No. 15: Radionuclide S values in a revised dosimetric model of the adult head and brain. Medical Internal Radiation Dose.

UNLABELLED: Current dosimetric models of the brain and head lack the anatomic detail needed to provide the physical data necessary for suborgan brain dosimetry. During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head for use in estimating regional absorbed dose within the brain and its adjacent structures. METHODS: A new brain model has been developed that includes eight subregions: the caudate nuclei, the cerebellum, the cerebral cortex, the lateral ventricles, the lentiform nuclei, the thalami, the third ventricle and the white matter. This brain model is incorporated within a total revision of the head model presented in MIRD Pamphlet No. 5 Revised. Modifications include the addition of the eyes, the teeth, the mandible, an upper facial region, a neck region and the cerebrospinal fluid within both the cranial and spinal regions. RESULTS: Absorbed fractions of energy for photon and electron sources located in 14 source regions within the new model were calculated using the EGS4 Monte Carlo radiation transport code for particles in the energy range 10 keV-4 MeV. These absorbed fractions were then used along with radionuclide decay data to generate S values for 24 radionuclides that are used in clinical or investigational studies of the brain, 12 radionuclides that localize within the cranium and spinal skeleton and 12 radionuclides that selectively localize in the thyroid gland. CONCLUSION: A substantial revision to the dosimetric model of the adult head and brain originally published in MIRD Pamphlet No. 5 Revised is presented. This revision supports suborgan brain dosimetry for a variety of radiopharmaceuticals used in neuroimaging. Dose calculations for the neuroimaging agent 1231-tropane provide an example of the new model and yield mean brain doses that are consistent with published values. However, the absorbed dose to subregions within the brain such as the caudate and lentiform nuclei may exceed the average brain dose by a factor of up to 5.

MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions--radionuclide S values at the voxel level. Medical Internal Radiation Dose Committee.

The availability of quantitative three-dimensional in vivo data on radionuclide distributions within the body makes it possible to calculate the corresponding nonuniform distribution of radiation absorbed dose in body organs and tissues. This pamphlet emphasizes the utility of the MIRD schema for such calculations through the use of radionuclide S values defined at the voxel level. The use of both dose point-kernels and Monte Carlo simulation methods is also discussed. PET and SPECT imaging can provide quantitative activity data in voxels of several millimeters on edge. For smaller voxel sizes, accurate data cannot be obtained using present imaging technology. For submillimeter dimensions, autoradiographic methods may be used when tissues are obtained through biopsy or autopsy. Sample S value tabulations for five radionuclides within cubical voxels of 3 mm and 6 mm on edge are given in the appendices to this pamphlet. These S values may be used to construct three-dimensional dose profiles for nonuniform distributions of radioactivity encountered in therapeutic and diagnostic nuclear medicine. Data are also tabulated for 131I in 0.1-mm voxels for use in autoradiography. Two examples illustrating the use of voxel S values are given, followed by a discussion of the use of three-dimensional dose distributions in understanding and predicting biologic response.

A three-dimensional transport model for determining absorbed fractions of energy for electrons within cortical bone.

UNLABELLED: Any radionuclide that is transported through the blood stream will also be carried through the haversian canals within cortical bone. These canals are lined with a layer of endosteum that contains radiosensitive cells. This paper introduces a new three-dimensional electron transport model for cortical bone based on Monte Carlo transport and on bone microstructural information for several cortical bone regions. METHODS: Previously published haversian cavity and bone matrix chord length distributions for cortical bone were randomly sampled to create alternating regions of bone matrix, endosteum and haversian canal tissues during the three-dimensional transport of single electrons. Electron transport was performed using the EGS4 transport code with the parameter reduced electron step transport algorithm. Electron-absorbed fractions of energy were tabulated for three adult cortical bone sites considering three source and target regions: the cortical haversian space, the cortical bone endosteum (CBE) and the cortical bone volume (CBV). RESULTS: Absorbed fractions assessed with the new model were shown to be highly energy dependent for most combinations of source-target regions in cortical bone. Although chord length data were available for three different bone sites (femur, humerus and tibia), very little variation with bone site was noted in the absorbed fraction data. CONCLUSION: International Commission on Radiation Protection (ICRP)-recommended absorbed fractions for cortical bone are given only for the CBE as target region and for the CBE and CBV as source regions. Comparisons of these recommended absorbed fractions with the absorbed fractions calculated in this study show large differences. For example, ratios of self-absorbed fractions to the CBE in this model and in the ICRP 30 model are approximately 0.25, approximately 4 and approximately 1.5 for initial electron energies of 10, 200 keV and 4 MeV, respectively. Consequently, this new transport model of electrons in cortical bone will improve the relatively energy-independent data recommended by the ICRP. This model will also allow consideration of the haversian canals as a potential radiation source.

NMR microscopy of trabecular bone and its role in skeletal dosimetry.

One of the more intractable problems in internal dosimetry is the assessment of energy deposition by alpha and beta particles within trabecular, or cancellous, bone. In the past few years, new technologies have emerged that allow for the direct and nondestructive 3D imaging of trabecular bone with sufficient spatial resolution to characterize trabecular bone structure in a manner needed for radiation dosimetry models. High-field proton nuclear magnetic resonance (NMR) imaging is one such technology. NMR is an ideal modality for imaging trabecular bone due to the sharp contrast in proton density between the bone matrix and bone marrow regions. In this study, images of the trabecular regions within the bodies of a human thoracic vertebra have been obtained at a field strength of 14.1 T. These images were digitally processed to measure chord length distribution data through both the bone trabeculae and marrow cavities. These distributions, which were found to be qualitatively consistent with those measured by F. W. Spiers and colleagues at the University of Leeds using physical sectioning and automated light microscopy, yielded a mean trabecular thickness of 201 microm and a mean marrow cavity thickness of 998 microm. The NMR techniques developed here for vertebral imaging may be extended to other skeletal sites, allowing for improved site-specific skeletal dosimetry.