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Wesley E Bolch

Publications and source records attributed to Wesley E Bolch.

33 records · Page 2Linked to original sources
PubMed2005

The UF series of tomographic computational phantoms of pediatric patients.

Two classes of anthropomorphic computational phantoms exist for use in Monte Carlo radiation transport simulations: tomographic voxel phantoms based upon three-dimensional (3D) medical images, and stylized mathematical phantoms based upon 3D surface equations for internal organ definition. Tomographic phantoms have shown distinct advantages over the stylized phantoms regarding their similarity to real human anatomy. However, while a number of adult tomographic phantoms have been developed since the early 1990s, very few pediatric tomographic phantoms are presently available to support dosimetry in pediatric diagnostic and therapy examinations. As part of a larger effort to construct a series of tomographic phantoms of pediatric patients, five phantoms of different ages (9-month male, 4-year female, 8-year female, 11-year male, and 14-year male) have been constructed from computed tomography (CT) image data of live patients using an IDL-based image segmentation tool. Lungs, bones, and adipose tissue were automatically segmented through use of window leveling of the original CT numbers. Additional organs were segmented either semiautomatically or manually with the aid of both anatomical knowledge and available image-processing techniques. Layers of skin were created by adding voxels along the exterior contour of the bodies. The phantoms were created from fused images taken from head and chest-abdomen-pelvis CT exams of the same individuals (9-month and 4-year phantoms) or of two different individuals of the same sex and similar age (8-year, 11-year, and 14-year phantoms). For each model, the resolution and slice positions of the image sets were adjusted based upon their anatomical coverage and then fused to a single head-torso image set. The resolutions of the phantoms for the 9-month, 4-year, 8-year, 11-year, and 14-year are 0.43 x 0.43 x 3.0 mm, 0.45 x 0.45 x 5.0 mm, 0.58 x 0.58 x 6.0 mm, 0.47 X 0.47 x 6.00 mm, and 0.625 x 0.625 x 6.0 mm, respectively. While organ masses can be matched to reference values in both stylized and tomographic phantoms, side-by-side comparisons of organ doses in both phantom classes indicate that organ shape and positioning are equally important parameters to consider in accurate determinations of organ absorbed dose from external photon irradiation. Preliminary studies of external photon irradiation of the 11-year phantom indicate significant departures of organ dose coefficients from that predicted by the existing stylized phantom series. Notable differences between pediatric stylized and tomographic phantoms include anterior-posterior (AP) and right lateral (RLAT) irradiation of the stomach wall, left lateral (LLAT) and right lateral (RLAT) irradiation of the thyroid, and AP and posterior-anterior (PA) irradiation of the urinary bladder.

Adolescent↗
PubMed2005

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.

Aged↗
PubMed2005

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.

Adult↗
PubMed2004

A revised stylized model of the adult extrathoracic and thoracic airways for use with the ICRP-66 human respiratory tract model.

The extrathoracic airways and lymph nodes have not yet been represented explicitly in mathematical or stylized models of the human body utilized in the transport of photons internally between source and target organs. Currently, the ICRP assumes that the extrathoracic airways are reasonably approximated by using the thyroid or brain as the surrogate source and target region within the ICRP 66 respiratory tract model. In the present study, a new mathematical model was created to explicitly consider the extrathoracic airways, as well as other respiratory structures in the thorax of the adult. The model incorporates the MIRD model of the adult head and neck, and the ORNL model of the adult torso/legs. Additional defining equations are established for the external nose, nasal cavity, nasal sinuses (frontal, ethmoid, sphenoid, and maxillary sinuses), oral cavity, larynx, pharynx, trachea, and main bronchi. Use of the thyroid as a surrogate source for photon emissions in the ET1 and ET2 tissues is shown to provide either close or conservative values of specific absorbed fraction to target organs such as the lungs or breasts at energies exceeding 50-100 keV. At lower energies, surrogate-region values of SAF underestimate dose to target organs in ways highly dependent upon the source/target configuration. The use of the brain as a surrogate source for ET1 and ET2 tissues irradiating the thyroid is shown to result in SAF values that are lower than values of SAF(thyroid<--ET1) by factors of approximately 2-3, and lower than values of SAF(thyroid<--ET2) by factors of approximately 30 at photon energies >50 keV. At energies <50 keV, values of SAF(thyroid<--ET2) are shown to be orders of magnitude higher than the ICRP 66 default given by SAF(thyroid<--brain).

Adult↗
PubMed2004

Bone marrow dosimetry using blood-based models for radiolabeled antibody therapy: a multiinstitutional comparison.

UNLABELLED: Standardization of marrow dosimetry is of considerable importance when estimating dose-response for a multicentered clinical trial involving radionuclide therapy. However, it is only within the past five years that the intercomparison of marrow dosimetry results among separate clinical trials that use the same agent has become scientifically feasible. In this work, we have analyzed reported marrow dosimetry results from radioimmunotherapy trials and recalculated marrow absorbed doses at a central facility using a standard blood model with patient-specific source data. The basic approach used in the American Association of Physicists in Medicine (AAPM)/Sgouros marrow dosimetry methodology was common to calculation performed at all participating institutions, including the central facility. Differences in dose estimates associated with starting assumptions and the exact implementation of the AAPM/Sgouros calculation methodology used by the source institutions and the central facility were quantified and compared. METHODS: Data from 22 patients enrolled in radiolabeled antibody clinical trials were randomly selected from 7 participating institutions for the assessment of marrow dose. The analysis was restricted to those patients who were treated with 131I- or 186Re-labeled antibody and had no marrow involvement. Calculation of bone marrow dose at each participating institution was unique to the trial or institution, but all used some form of the AAPM/Sgouros blood model approach. The central facility adopted a marrow dosimetry model based on the AAPM/Sgouros model for radiolabeled antibodies using the standard MIRD approach to the remainder-of-body contribution. A standardized approach to account for variations in patient mass was used for the remainder-of-body component. To simplify clinical implementation, regional marrow uptake and time-dependent changes in the marrow-to-blood concentration ratio were not included. Methods of formatting the collection of standard datasets useful in defining dose-response parameters are also presented. RESULTS: Bone marrow doses were calculated according to the method described for each of the 22 patients based on the patient-specific data supplied by the participating institutions. These values were then individually compared with the marrow doses originally reported by each institution. Comparison of the two calculation methods was expressed as a ratio of the marrow doses for each patient. The mean ratio for the dose estimates at the participating institution calculation compared with the central laboratory value was 0.920 +/- 0.259 (mean +/- SD), with a range from 0.708 to 1.202. CONCLUSION: The independent use of the AAPM/Sgouros method blood model approach to marrow dosimetry has brought these dose estimates to within 30% of the results obtained centrally compared with substantially higher uncertainties reported previously. Variations in calculation methodology or initial assumptions adopted by individual institutions may still contribute significant uncertainty to dose estimates, even when the same data are used as a starting point for the calculation comparison shown here. A clinically relevant, standard method for marrow dosimetry for radiolabeled antibodies is proposed as a benchmark for intercomparison purposes. A parameter sensitivity analysis and a summary discussion of the use of this model for potentially improving dose-response data correlation are also presented.

Adult↗
PubMed2003

Voxeldoes: a computer program for 3-D dose calculation in therapeutic nuclear medicine.

A computer program, VoxelDose, was developed to calculate patient specific 3-D-dose maps at the voxel level. The 3-D dose map is derived in three steps: (i) The SPECT acquisitions are reconstructed using a filtered back projection method, with correction for attenuation and scatter; (ii) the 3-D cumulated activity map is generated by integrating the SPECT data; and (iii) a 3-D dose map is computed by convolution (using the Fourier Transform) of the cumulated activity map and corresponding MIRD voxel S values. To validate the VoxelDose software, a Liqui-Phil abdominal phantom with four simulated organ inserts and one spherical tumor (radius 4.2 cm) was filled with known activity concentrations of 111In. Four cylindrical calibration tubes (from 3.7 to 102 kBq/mL) were placed on the phantom. Thermoluminescent mini-dosimeters (mini-TLDs) were positioned on the surface of the organ inserts. Percent differences between the known and measured activity concentrations were determined to be 12.1 (tumor), 1.8 (spleen), 1.4, 8.1 (right and left kidneys), and 38.2% (liver), leading to percent differences between the calculated and TLD measured doses of 41, 16, 3, 5, and 62%. Large differences between the measured and calculated dose in the tumor and the liver may be attributed to several reasons, such as the difficulty in precisely associating the position of the TLD to a voxel and limits of the quantification method (mainly the scatter correction and partial volume effect). Further investigations should be performed to better understand the impact of each effect on the results and to improve absolute quantification. For all other organs, activity concentration measurements and dose calculations agree well with the known activity concentrations.

Humans↗
PubMed2003

Influences of parameter uncertainties within the ICRP-66 respiratory tract model: particle clearance.

Quantifying radiological risk following the inhalation of radioactive aerosols entails not only an assessment of particle deposition within respiratory tract regions but a full accounting of clearance mechanisms whereby particles may be translocated to adjacent respiratory tissue regions, absorbed to blood, or released to the gastrointestinal tract. The model outlined in ICRP Publication 66 represents to date one of the most complete overall descriptions of particle deposition and clearance, as well as localized radiation dosimetry, within the respiratory tract. In this study, a previous review of the ICRP-66 deposition model is extended to the study of the subsequent clearance model. A systematic review of the clearance component within the ICRP 66 respiratory tract model was conducted in which probability density functions were assigned to all input parameters for both 239PuO2 and 238UO2/238U3O8. These distributions were subsequently incorporated within a computer code LUDUC (Lung Dose Uncertainty Code) in which Latin hypercube sampling techniques are used to generate multiple (e.g., 1,000) sets of input vectors (i.e., trials) for all model parameters needed to assess mechanical clearance and particle dissolution/absorption. Integral numbers of nuclear disintegrations, U(s), in various lung regions were shown to be well-described by lognormal probability distributions. Of the four extrathoracic clearance compartments of the respiratory tract, uncertainties in U(s), expressed as the ratio of its 95% to 5% confidence levels, were highest within the LN(ET) tissues for 239PuO2 (ratio of 50 to 130) and within the ET(seq) tissues for 238UO2/238U3O8 (ratio of 12 to 50). Peak uncertainties in U(s) in these respiratory regions occurred at particle sizes of approximately 0.5-0.6 microm where uncertainties in ET2 particle deposition fractions accounted for only approximately 10% of the total U(s) uncertainty for 239PuO2, and only approximately 30% of the total U(s) uncertainty for 238UO2/238U3O8 (the remainder is attributed to the clearance model alone). Of the eight clearance compartments within the thoracic regions of the respiratory tract, and for particle sizes below approximately 5 microm, uncertainties in U(s) were highest within the LN(TH) tissues for 239PuO2 (ratio of 60 to 80) and within the BB(seq) tissues for 238UO2/238U3O8 (ratio of 20 and 60). At particle sizes exceeding approximately 5 microm in aerodynamic diameter, peak uncertainties in U(s) are noted for the AI, bb(seq), and bb1 clearance compartments. As the particle size approaches 10 microm in size, uncertainties in U(s) within these three thoracic tissue regions approach a factor of 1,000 and are dominated by corresponding uncertainties in particle deposition.

Aerosols↗
PubMed2003

Influences of parameter uncertainties within the ICRP-66 respiratory tract model: regional tissue doses for 239PuO2 and 238UO2/238U3O8.

This paper extends an examination of the influence of parameter uncertainties on regional doses to respiratory tract tissues for short-ranged alpha particles using the ICRP-66 respiratory tract model. Previous papers examined uncertainties in the deposition and clearance aspects of the model. The critical parameters examined in this study included target tissue depths, thicknesses, and masses, particularly within the thoracic or lung regions of the respiratory tract. Probability density functions were assigned for the parameters based on published data. The probabilistic computer code LUDUC (Lung Dose Uncertainty Code) was used to assess regional and total lung doses from inhaled aerosols of 239PuO2 and 238UO2/238U3O8. Dose uncertainty was noted to depend on the particle aerodynamic diameter. Additionally, dose distributions were found to follow a lognormal distribution pattern. For 239PuO2 and 238UO2/238U3O8, this study showed that the uncertainty in lung dose increases by factors of approximately 50 and approximately 70 for plutonium and uranium oxides, respectively, over the particle size range from 0.1 to 20 microm. For typical exposure scenarios involving both radionuclides, the ratio of the 95% dose fractile to the 5% dose fractile ranged from approximately 8-10 (corresponding to a geometric standard deviation, or GSD, of about 1.7-2) for particle diameters of 0.1 to 1 microm. This ratio increased to about 370 for plutonium oxide (GSD approximately 4.5) and to about 600 for uranium oxide (GSD approximately 5) as the particle diameter approached 20 microm. However, thoracic tissue doses were quite low at larger particle sizes because most of the deposition occurred in the extrathoracic airways. For 239PuO2, median doses from LUDUC were found be in general agreement with those for Reference Man (via deterministic LUDEP 2.0 calculations) in the particle range of 0.1 to 5 microm. However, median doses to the basal cell nuclei of the bronchial airways (BB(bas)) calculated by LUDUC were found to be approximately 6 times higher than LUDEP reference doses. The higher BB(bas) doses were directly attributed to discrepancies between the ICRP default thickness for the bronchial epithelium (55 microm) and the probability density function assumed within LUDUC (uniform distribution from 20 to 60 microm based upon detailed literature reviews).

Adolescent↗
PubMed2003

Influences of parameter uncertainties within the ICRP-66 respiratory tract model: a parameter sensitivity analysis.

An important aspect in model uncertainty analysis is the evaluation of input parameter sensitivities with respect to model outcomes. In previous publications, parameter uncertainties were examined for the ICRP-66 respiratory tract model. The studies were aided by the development and use of a computer code LUDUC (Lung Dose Uncertainty Code) which allows probabilities density functions to be specified for all ICRP-66 model input parameters. These density functions are sampled using Latin hypercube techniques with values subsequently propagated through the ICRP-66 model. In the present study, LUDUC has been used to perform a detailed parameter sensitivity analysis of the ICRP-66 model using input parameter density functions specified in previously published articles. The results suggest that most of the variability in the dose to a given target region is explained by only a few input parameters. For example, for particle diameters between 0.1 and 50 microm, about 50% of the variability in the total lung dose (weighted sum of target tissue doses) for 239PuO2 is due to variability in the dose to the alveolar-interstitial (AI) region. In turn, almost 90% of the variability in the dose to the AI region is attributable to uncertainties in only four parameters in the model: the ventilation rate, the AI deposition fraction, the clearance rate constant for slow-phase absorption of deposited material to the blood, and the clearance rate constant for particle transport from the AI2 to bb1 compartment. A general conclusion is that many input parameters do not significantly influence variability in final doses. As a result, future research can focus on improving density functions for those input variables that contribute the most to variability in final dose values.

Absorption↗
PubMed2003

A video analysis technique for organ dose assessment in pediatric fluoroscopy: applications to voiding cystourethrograms (VCUG).

The time-sequence videotape-analysis methodology, originally developed by Sulieman et al. [Radiol. 178, 653-658 (1991)] for use in tissue dose estimation in adult fluoroscopy exams, has been adapted to the study of the newborn voiding cystourethrogram (VCUG). Individual frames of fluoroscopic and radiographic video were analyzed with respect to unique combinations of field size, field center, projection, tube potential, and mA or mAs, respectively. A modified version of the stylized ORNL newborn model was coupled to the MCNP4C radiation transport code to report organ doses per unit entrance air kerma (free-in-air) for each identified x-ray field. A series of urinary bladder models was additionally developed representing the organ at differing stages of contrast filling. The technique was subsequently applied to two patients, a 3-month male and a 1-month female, examined via a conventional fluoroscopy system used just prior to departmental conversion to digital systems. The effective dose to these patients was estimated as 0.47 mSv and 1.36 mSv, respectively (ratio of 2.9). Corresponding ratios of cumulative fluoroscopy time and entrance air kerma were 2.2 and 1.6, respectively. For the male patient, the mean percent dose contribution from fluoroscopy for all irradiated organs was 71 +/- 12%, while that value for the female patient was 88 +/- 4%.

Computer Simulation↗
PubMed2003

Adipocyte spatial distributions in bone marrow: implications for skeletal dosimetry models.

UNLABELLED: Few studies have been conducted to quantify the spatial distributions of adipocytes in the marrow cavities of trabecular bone. Nevertheless, such data are needed for the development of 3-dimensional (3D) voxel skeletal models where marrow cellularity is explicitly considered as a model parameter for dose assessment. In this investigation, bone marrow biopsies of the anterior iliac crest were examined to determine the size distribution of adipocyte cell clusters, the percentage of perimeter coverage of trabecular surfaces, and the presence or absence of adipocyte density gradients in the marrow space, all as a function of the biopsy marrow cellularity (5%-95%). METHODS: Biopsy slides from 42 patients were selected as designated by the hematopathologist as either normocellular or with no evidence of disease. Still-frame video image captures were made of 1-3 regions of interest per biopsy specimen, with subsequent image analysis of adipocyte spatial characteristics performed via a user-written MATLAB routine. RESULTS: A predictable shift was found in cluster size with decreasing marrow cellularity from single adipocytes to clusters of >or=3 cells; the percentage of 2-cell clusters remained relatively constant with changing cellularity. Also, a nonlinear increase in trabeculae perimeter coverage was found with increasing fat tissue fraction at marrow cellularities between 50% and 80%. Finally, it was demonstrated that only in the range of 20%-50% marrow cellularity was a slight gradient in adipocyte concentration indicated with adipocytes localized preferentially toward the trabecular surfaces. CONCLUSION: Electron transport simulations were conducted in 4 different 3D voxel models of trabecular bone for sources localized in the active marrow (TAM), bone volume (TBV), bone endosteum (TBE), and bone surfaces (TBS). Voxel model simulations demonstrated that absorbed fractions to active marrow given by the ICRP 30 model (MIRDOSE2) are exceedingly conservative for both TBV and TBS sources, except in the case of high-energy particles (>500 keV) at high values of marrow cellularity (>70%). Values of both phi(TAM<--TBV) and phi(TAM<--TBS) given by the Eckerman and Stabin model (MIRDOSE3) were shown to be reasonably consistent with 3D voxel model simulations at the reference cellularity of 25%, except in the case of low-energy emitters (<100 keV) on the bone surfaces.

Adipocytes↗
PubMed2003

MIRD Pamphlet No 19: absorbed fractions and radionuclide S values for six age-dependent multiregion models of the kidney.

UNLABELLED: As one of the major organs of the excretory pathway, the kidneys represent a frequent source of radiopharmaceutical uptake in both diagnostic and therapeutic nuclear medicine. The unique organization of the functional tissues of the organ ensures transient changes in suborgan localization of renal activity. Current single-region dosimetric models of the kidneys, however, force the assumption of a uniform distribution of radioactivity across the entire organ. The average absorbed dose to the kidneys predicted by such models can misrepresent local regional doses to specific substructures. METHODS: To facilitate suborgan dosimetry for the kidneys, 6 new age-dependent multiregion kidney models are presented. The outer dimensions of the models conform to those used currently in single-region kidney models, whereas interior structures are defined for the renal cortex, the medullary pyramids with papillae (2 vertical and 3 horizontal), and the renal pelvis. Absorbed fractions of energy were calculated for both photon and electron sources (10 keV to 4 MeV) located in each source region within the 6 age-dependent models. The absorbed fractions were then used to assemble S values for radionuclides of potential interest in suborgan kidney dosimetry. RESULTS: For the adult, the absorbed dose to the renal cortex for (90)Y-labeled compounds retained within that subregion is approximately 1.3 times that predicted by the single-region kidney model, whereas the medullary dose is only 26% of that same single-region value. For compounds that are rapidly filtered in the kidneys, the renal cortex dose is approximately one-half of that predicted under the single-region model, whereas the tissues of the medullary pyramids receive an absorbed dose 1.5-1.8 times larger. CONCLUSION: The multiregion model described here permits estimates of regional kidney dose not previously supported by current single-region models. Full utilization of the new model, however, requires serial imaging of the kidneys with regions of interest assigned to the renal cortex and medulla.

Aging↗
PubMed2002

Site-specific OH attack to the sugar moiety of DNA: a comparison of experimental data and computational simulation.

Little computational or experimental information is available on site-specific hydroxyl attack probabilities to DNA. In this study, an atomistic stochastic model of OH radical reactions with DNA was developed to compute relative OH attack probabilities at individual deoxyribose hydrogen atoms. A model of the self-complementary decamer duplex d(CCAACGTTGG) was created including Na(+) counter ions and the water molecules of the first hydration layer. Additionally, a method for accounting for steric hindrance from nonreacting atoms was implemented. The model was then used to calculate OH attack probabilities at the various C-H sites of the sugar moiety. Results from this computational model show that OH radicals exhibit preferential attack at different deoxyribose hydrogens, as suggested by their corresponding percentage solvent-accessible surface areas. The percentage OH attack probabilities for the deoxyribose hydrogens [1H(5')+2H(5'), H(4'), H(3'), 1H(2')+2H(2'), H(1')] were calculated as approximately 54.6%, 20.6%, 15.0%, 8.5% and 1.3%, respectively, averaged across the sequence. These results are in good agreement with the latest experimental site-specific DNA strand break data of Balasubramanian et al. [Proc. Natl. Acad. Sci. USA 95, 9738-9742 (1998)]. The data from this stochastic model suggest that steric hindrance from nonreacting atoms significantly influences site-specific hydroxyl radical attack probabilities in DNA. A number of previous DNA damage models have been based on the assumption that C(4') is the preferred site, or perhaps the only site, for OH-mediated DNA damage. However, the results of the present study are in good agreement the experimental results of Balasubramanian et al. in which OH radicals exhibit preferential initial attack at sugar hydrogen atoms in the order 1H(5')+2H(5') > H(4') > H(3') > 1H(2')+2H(2') > H(1').

Algorithms↗
PubMed2002

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.

Adipocytes↗