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All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Hepatitis B e Antigen-Negative Single Hepatocyte Analysis Shows Transcriptional Silencing and Slow Decay of Infected Cells With Treatment

Background Nucleos(t)ide analogues (NUCs) rarely cure chronic hepatitis B (CHB) because they do not eliminate covalently closed circular deoxyribonucleic acid, the stable replication template. In hepatitis B e antigen (HBeAg)-positive CHB during NUCs, HBV-infected cells decline slowly and are transcriptionally silenced. Whether these occur in HBeAg-negative CHB is unknown. Methods Using paired liver biopsies separated by 2.7–3.7 years in 4 males with HIV and HBeAg-negative CHB at both biopsies and 1 male with HIV who underwent HBeAg seroconversion between biopsies, we quantified amounts of viral nucleic acids in hundreds of individual hepatocytes. Results In the 4 persistently HBeAg-negative participants, HBV-infected hepatocytes ranged from 6.2% to 17.7% (biopsy 1) and significantly declined in 3 of 4 by biopsy 2. In the HBeAg seroconverter, the proportion was 97.4% (biopsy 1) and declined to 81.9% at biopsy 2 (P < .05). Here, we extrapolated that HBV eradication with NUCs would take >100 years. At biopsy 1 in the persistently HBeAg-negative participants, 23%–56.8% of infected hepatocytes were transcriptionally inactive—higher than we observed in HBeAg-positive CHB—and significantly declined in 1 of 4 at biopsy 2. Conclusions In HBeAg-negative CHB on NUCs, the negligible decline in infected hepatocytes is similar to HBeAg-positive CHB, supporting the need for more potent therapeutics to achieve functional cure.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Post-Transcriptional Mechanisms Respond Rapidly to Ecologically Relevant Thermal Fluctuations During Temperature-Dependent Sex Determination

An organism’s ability to integrate transient environmental cues experienced during development into molecular and physiological responses forms the basis for adaptive shifts in phenotypic trajectories. During temperature-dependent sex determination (TSD), thermal cues during discrete periods in development coordinate molecular changes that ultimately dictate sexual fate and contribute to patterns of inter- and intra-sexual variation. How these mechanisms interface with dynamic thermal environments in nature remain largely unknown. By deploying thermal loggers in wild nests of the American alligator (Alligator mississippiensis) over two consecutive breeding seasons, we observed that 80% of nests exhibit both male- and female-promoting thermal cues during the thermosensitive period, and of these nests, all exhibited both male- and female-promoting temperatures within the span of a single day. These observations raise a critical question—how are opposing environmental cues integrated into sexually dimorphic transcriptional programs across short temporal scales? To address this question, alligator embryos were exposed to fluctuating temperatures based on nest thermal profiles and sampled over the course of a daily thermal fluctuation. We examined the expression dynamics of upstream genes in the temperature-sensing pathway and find that post-transcriptional alternative splicing and transcript abundance of epigenetic modifier genes JARID2 and KDM6B respond rapidly to thermal fluctuations while transcriptional changes of downstream effector genes, SOX9 and DMRT1, occur on a delayed timescale. Our findings reveal how the basic mechanisms of TSD operate in an ecologically relevant context. We present a hypothetical hierarchical model based on our findings as well as previous studies, in which temperature-sensitive alternative splicing incrementally influences the epigenetic landscape to affect the transcriptional activity of key sex-determining genes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

A new pinnotherid crab of the genus Pinnixulala Palacios Theil, Cuesta & Felder, 2016 from uncertain infaunal hosts in the northern Gulf of Mexico, with a rediagnosis and updated synonymy for the polychaete symbiont Pinnixulala retinens (Rathbun, 1918) (Decapoda: Brachyura: Pinnotheridae)

Abstract A new infaunal pinnotherid crab, Pinnixulala heardin. sp., is described from muddy substrates of the middle to inner continental shelf of the northern Gulf of Mexico. Molecular genetic analysis supports its separation from P. retinens (Rathbun, 1918), the only other western Atlantic member of the genus and a species most commonly found living as a symbiont of large polychaete worms. Both western Atlantic species are clearly separated from several described and undescribed populations of congeners occurring along shorelines of the eastern Pacific. We herein include a rediagnosis of P. retinens to facilitate morphological comparisons with P. heardin. sp. Unlike P. retinens, which is more common in shallow inshore waters and reaches larger sizes, the new species lacks development of a strong distally directed spine on the fourth pereopod ischium and has chelae that are at least as heavily developed as the second and third pereopods. In addition, the mature male first gonopods in P. heardin. sp. are tapered over their terminal one-third and directed distally, rather than being curved in their terminal one-third with the tips directed mesially, as they are in P. retinens. The new species is invariably collected from samples including infaunal worms and other invertebrates, but the specific hosts remain to be determined

Marine & Freshwater Biology↗
DOE OSTI2020

Benefits of colorectal cancer screening using fecal immunochemical testing with varying positivity thresholds by age and sex

Background Fecal immunochemical test (FIT) performance for colorectal cancer screening varies by age and sex, yet most FIT-based screening programs use uniform positivity thresholds. This study assessed the potential benefits of stratifying FIT thresholds based on age and sex. Methods We conducted a meta-analysis of FIT sensitivity and specificity at various positivity thresholds by age and sex. We then used these estimates in 2 microsimulation models of colorectal cancer and projected lifetime clinical outcomes, incremental costs, and quality-adjusted life-years (QALYs) gained from age- and sex-stratified FIT strategies. FIT thresholds ranged from 10 to 50 µg hemoglobin per gram of feces. Results For current uniform FIT screening (20 µg hemoglobin/gram of feces), models projected 85.67 to 122.15 QALYs gained at incremental costs of ‒$982 to $504 per 1000 individuals compared with no screening. At equivalent costs to current uniform screening, only 1 model found stratified FIT approaches cost-effective, yielding a marginal increase of 1.04 and 1.10 QALYs gained/1000 female and male individuals, respectively. At a willingness-to-pay threshold of $100 000/QALYs gained, both models found stratified FIT cutoffs to be the best strategy, with cutoffs being equal to or higher for males and lowest at older ages (70-75 years). Uniform strategies showed comparable effectiveness, falling within 1 quality-adjusted life-day per person of efficient strategies at up to $112 more per person. Results were sensitive to FIT test performance characteristics and 1-time setup costs. Conclusion Stratifying FIT thresholds by age and sex may be cost-effective compared to current screening. The gain in expected health benefits with stratified FIT screening, however, is likely small.

Harlass, Matthias↗
DOE OSTI2021

URINARY EXCRETION OF PLUTONIUM IN MAYAK WORKERS DURING AND AFTER CA-DTPA ADMINISTRATION

Chelation therapy is sometimes used after potential exposures to plutonium to increase urinary excretion of the radionuclide to improve the accuracy of bioassay measurements. The purpose of this report is to describe the enhancement of urinary excretion of plutonium during and after the administration of the trisodium salt of calcium diethylenetriaminepentaacetate (Ca-DTPA) daily for 3 d to a group of male and female plutonium workers from the Mayak Production Association in Ozyorsk, Russia. One-hundred and two cases (18 females and 84 males) were selected where urinary contents of plutonium, prior to chelation, exceeded the detection threshold. Daily urine collections were obtained during the 3 d of Ca-DTPA treatments. In addition, 58 of these cases had urine bioassays at 1–45 d after chelation. The daily enhancement over baseline values excretion of plutonium was found to be 50.4×/1.4 (geometric mean and geometric standard deviation); 58.9×/1.2; 72.9×/1.4 in the first, second and third days of Ca-DTPA administration. The mean enhancement for the 3-d period was 60.1×/1.7. The rate of plutonium excretion from 1 to 45 d after chelation decreased with a half-period of 3.9 d and the chelation enhancement factor (Кenh-i) is described by the function Кenh-i = (0.79 ± 0.24) + (42.9 ± 1.2) × e-(0.18 ± 0.01) × day.

Environmental Sciences & Ecology↗
DOE OSTI2016

Comparison of monoenergetic photon organ dose rate coefficients for stylized and voxel phantoms submerged in air

As part of a broader effort to calculate effective dose rate coefficients for external exposure to photons and electrons emitted by radionuclides distributed in air, soil or water, age-specific stylized phantoms have been employed to determine dose coefficients relating dose rate to organs and tissues in the body. In this article, dose rate coefficients computed using the International Commission on Radiological Protection reference adult male voxel phantom are compared with values computed using the Oak Ridge National Laboratory adult male stylized phantom in an air submersion exposure geometry. Monte Carlo calculations for both phantoms were performed for monoenergetic source photons in the range of 30 keV to 5 MeV. Furthermore, these calculations largely result in differences under 10 % for photon energies above 50 keV, and it can be expected that both models show comparable results for the environmental sources of radionuclides.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2017

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms are provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2019

Efficacy of Midazolam and Ketamine Combination Therapy over Midazolam Monotherapy against Soman Exposure in Carboxylesterase Knockout Mice

Introduction Chemical warfare nerve agents (CWNAs) inhibit acetylcholinesterase (AChE), which leads to status epilepticus (SE), spontaneous recurrent seizures (SRS) and severe neuropathology when treatment is delayed. In addition to binding to AChE, some organophosphorus (OP) CWNAs such as soman (GD) also inhibit carboxylesterase (CaE), which acts as a bioscavenger and can thus reduce the severity of the toxicity of OP agent exposure. Unlike humans, rodents have plasma CaE activity. The CaE knockout (ES1−/−) mouse specifically lacks plasma CaE and might better model human GD exposure compared to wildtype rodents. Delayed treatment of CWNA‐induced SE with midazolam leads to benzodiazepine‐refractory SE. We evaluated combination therapy of midazolam and the NMDA antagonist ketamine in male and female mice for efficacy against soman‐induced lethality, SE and epileptogenesis. Methods Mice implanted with telemetry transmitters for electroencephalography (EEG) seizure identification were exposed to 82 μg/kg GD (~4LD 50 ) and treated with an admix (ip) of atropine sulfate (4 mg/kg) and HI‐6 (50 mg/kg) 1 min after exposure, and with midazolam (3 mg/kg; ip) alone or in combination with ketamine (30 mg/kg, ip) at 40 min after seizure onset. Mice were continuously recorded to evaluate initial seizure duration and SRS and then euthanized 2 weeks after exposure for neuropathology assessment. Results Delayed treatment with midazolam resulted in poor survival, was unable to rapidly terminate behavioral or EEG seizure activity and did not prevent the development of SRS or neuronal loss following GD exposure. Combination therapy of midazolam and ketamine resulted in improved outcome, including an increase in survival from 30% to 78% in female and from 57% to 77% in males compared to midazolam monotherapy. In addition, the incidence of epileptogenesis was lower in mice treated with ketamine and midazolam dual therapy compared to midazolam monotherapy. Conclusions This study demonstrates that delayed treatment of SE with midazolam is not fully protective against the GD‐induced epileptogenesis and neuropathology, exemplifying the need for adjunct treatment to midazolam to prevent or reduce effects of GD‐induced SE. Ketamine combination with midazolam improves outcome. Support or Funding Information Research was supported by the CounterACT Program, NIH OD, and the NINDS (Grant 1R21NS103820‐01 to LA Lumley‐Lange) and by DTRA‐JSTO. Erica Kundrick, Katie Walker, and Sean O'Brien were supported in part by an appointment to the Research Participation Program for the U.S. Army Medical Research and Materiel Command administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and U.S. Army Medical Research and Materiel Command. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Marrero‐Rosado, Brenda↗
DOE OSTI2023

Maternal provisioning interacts with incubation temperature to affect hatchling mercury exposure in an oviparous reptile

The thermal environment experienced by developing embryos can influence the utilization of maternally provisioned resources. Despite being particularly consequential for oviparous ectotherms, these dynamics are largely unexplored within ecotoxicological frameworks. Here, we test if incubation temperature interacts with maternally transferred mercury to affect subsequent body burdens and tissue distributions of mercury in hatchling American alligators (Alligator mississippiensis). Nine clutches of alligator eggs were collected from a mercury-contaminated reservoir and incubated at either female- or male-promoting temperatures. Total mercury (THg) concentration was measured in egg yolk collected during incubation and in a suite of tissues collected from hatchlings. THg concentrations in residual yolk and blood were higher in hatchlings incubated at cooler, female-promoting temperatures compared to the warmer, male-promoting temperatures. THg concentrations in most tissues were positively correlated with THg concentrations in blood and dermis, and egg yolk THg concentration was the best predictor of THg concentration in many resultant tissues. Furthermore, our results highlight a hereto unknown role of the developmental environment in mediating tissue specific uptake of contaminants in an oviparous reptile.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Analysis of implant loss risk factors after simultaneous guided bone regeneration: A retrospective study of 5404 dental implants

Abstract Purpose The purpose was to analyze the risk factors for implant loss after simultaneous guided bone regeneration (GBR). Materials and Methods Patients who underwent implant placement with simultaneous GBR between January 2011 and December 2018 were screened for this study. The cumulative survival rate (CSR) was calculated using the life table method. Log‐rank test and Kaplan–Meier survival estimates were used to identify potential risk factors for implant loss. The association between the investigated variables and implant loss was determined using hazard ratios (HRs) obtained from a multivariate Cox regression analysis. Results A total of 3973 patients with 5404 implants were included in this study. The CSRs of the implants at 1, 5, and 10 years were 99.6%, 98.9%, and 98.7%, respectively. Male patient (HR = 2.94, 95% CI: 1.41–6.14), periodontitis (HR = 4.26, 95% CI: 2.05–9.86), tissue‐level implants (HR = 3.02, 95% CI: 1.30–6.98), narrow implants (HR = 2.71, 95% CI: 1.12–6.57), and implant length ≤10 mm (HR = 2.91, 95% CI: 1.41–6.02) significantly increased the risk of implant loss ( p < 0.05). The risk of implant loss was significantly higher in the maxillary posterior region (HR = 2.26, 95% CI: 1.04–4.90) than in the maxillary anterior region ( p < 0.05). Compared to Straumann, Nobel (HR = 4.07, 95% CI: 1.75–9.44) and other implant systems (HR = 14.23, 95% CI: 4.32–46.85) showed a significantly higher risk of implant loss ( p < 0.05). Conclusion Male patient, periodontitis, maxillary posterior region, Nobel implant system, other implant systems, tissue‐level implants, narrow implants, and implant length ≤10 mm were considered risk factors for implant loss after simultaneous GBR.

Shen, Xiaoting↗
DOE OSTI2016

Quantification of cerivastatin toxicity supports organismal performance assays as an effective tool during pharmaceutical safety assessment

A major problem in pharmaceutical development is that adverse effects remain undetected during preclinical and clinical trials, but are later revealed after market release when prescribed to many patients. We have developed a fitness assay known as the organismal performance assay (OPA), which evaluates individual performance by utilizing outbred wild mice ( Mus musculus ) that are assigned to an exposed or control group, which compete against each other for resources within semi-natural enclosures. Performance measurements included reproductive success, survival, and male competitive ability. Our aim was to utilize cerivastatin (Baycol ® , Bayer), a pharmaceutical with known adverse effects, as a positive control to assess OPAs as a potential tool for evaluating the safety of compounds during preclinical trials. Mice were exposed to cerivastatin (~4.5 mg/kg/day) into early adulthood. Exposure ceased and animals were released into semi-natural enclosures. Within enclosures, cerivastatin-exposed females had 25% fewer offspring and cerivastatin-exposed males had 10% less body mass, occupied 63% fewer territories, sired 41% fewer offspring, and experienced a threefold increase in mortality when compared to controls. OPAs detected several cerivastatin-nduced adverse effects indicating that fitness assays, commonly used in ecology and evolutionary biology, could be useful as an additional tool in safety testing during pharmaceutical development.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2010

A novel class of peptide pheromone precursors in ascomycetous fungi

Recently, sexual development in the heterothallic ascomycete Trichoderma reesei (anamorph of Hypocrea jecorina) has been achieved and thus initiated attempts to elucidate regulation and determinants of this process. While the α-type pheromone of this fungus fits the consensus known from other fungi, the assumed a-type peptide pheromone precursor shows remarkably unusual characteristics: it comprises three copies of the motif (LI)GC(TS)VM thus constituting a CAAX domain at the C-terminus and two Kex2-protease sites. This structure shares characteristics of both a- and α-type peptide pheromone precursors. Presence of hybrid-type peptide pheromone precursor 1 (hpp1) is essential for male fertility, thus indicating its functionality as a peptide pheromone precursor, while its phosphorylation site is not relevant for this process. However, sexual development in a female fertile background is not perturbed in the absence of hpp1, which rules out a higher order function in this process. Open reading frames encoding proteins with similar characteristics to HPP1 were also found in Fusarium spp., of which Fusarium solani still retains a putative a-factor-like protein, but so far in no other fungal genome available. We therefore propose the novel class of h-type (hybrid) peptide pheromone precursors with H. jecorina HPP1 as the first member of this class.Recently, sexual development in the heterothallic ascomycete Trichoderma reesei (anamorph of Hypocrea jecorina) has been achieved and thus initiated attempts to elucidate regulation and determinants of this process. While the α-type pheromone of this fungus fits the consensus known from other fungi, the assumed a-type peptide pheromone precursor shows remarkably unusual characteristics: it comprises three copies of the motif (LI)GC(TS)VM thus constituting a CAAX domain at the C-terminus and two Kex2-protease sites. This structure shares characteristics of both a- and α-type peptide pheromone precursors. Presence of hybrid-type peptide pheromone precursor 1 (hpp1) is essential for male fertility, thus indicating its functionality as a peptide pheromone precursor, while its phosphorylation site is not relevant for this process. However, sexual development in a female fertile background is not perturbed in the absence of hpp1, which rules out a higher order function in this process. Open reading frames encoding proteins with similar characteristics to HPP1 were also found in Fusarium spp., of which Fusarium solani still retains a putative a-factor-like protein, but so far in no other fungal genome available. We therefore propose the novel class of h-type (hybrid) peptide pheromone precursors with H. jecorina HPP1 as the first member of this class.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

Reverse genetic characterization of two paralogous acetoacetyl CoA thiolase genes in Arabidopsis reveals their importance in plant growth and development

Acetoacetyl CoA thiolase (AACT, EC 2.3.1.9) catalyzes the condensation of two acetyl CoA molecules to form acetoacetyl CoA. Two AACT-encoding genes, At5g47720 (AACT1) and At5g48230 (AACT2), were functionally identified in the Arabidopsis genome by direct enzymological assays and functional expression in yeast. Promoter::GUS fusion experiments indicated that AACT1 is primarily expressed in the vascular system and AACT2 is highly expressed in root tips, young leaves, top stems and anthers. Characterization of T-DNA insertion mutant alleles at each AACT locus established that AACT2 function is required for embryogenesis and for normal male gamete transmission. In contrast, plants lacking AACT1 function are completely viable and show no apparent growth phenotypes, indicating that AACT1 is functionally redundant with respect to AACT2 function. RNAi lines that express reduced levels of AACT2 show pleiotropic phenotypes, including reduced apical dominance, elongated life span and flowering duration, sterility, dwarfing, reduced seed yield and shorter root length. Microscopic analysis reveals that the reduced stature is caused by a reduction in cell size and fewer cells, and male sterility is caused by loss of the pollen coat and premature degeneration of the tapetal cells. Biochemical analyses established that the roots of AACT2 RNAi plants show quantitative and qualitative alterations in phytosterol profiles. These phenotypes and biochemical alterations are reversed when AACT2 RNAi plants are grown in the presence of mevalonate, which is consistent with the role of AACT2 in generating the bulk of the acetoacety CoA precursor required for the cytosol-localized, mevalonate-derived isoprenoid biosynthetic pathway.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Close‐kin mating, but not inbred parents, reduces hatching rates and offspring quality in a threatened tortoise

Abstract Inbreeding depression, the reduction in fitness due to mating of related individuals, is of particular conservation concern in species with small, isolated populations. Although inbreeding depression is widespread in natural populations, long‐lived species may be buffered from its effects during population declines due to long generation times and thus are less likely to have evolved mechanisms of inbreeding avoidance than species with shorter generation times. However, empirical evidence of the consequences of inbreeding in threatened, long‐lived species is limited. In this study, we leverage a well‐studied population of gopher tortoises, Gopherus polyphemus , to examine the role of inbreeding depression and the potential for behavioural inbreeding avoidance in a natural population of a long‐lived species. We tested the hypothesis that increased parental inbreeding leads to reduced hatching rates and offspring quality. Additionally, we tested for evidence of inbreeding avoidance. We found that high parental relatedness results in offspring with lower quality and that high parental relatedness is correlated with reduced hatching success. However, we found that hatching success and offspring quality increase with maternal inbreeding, likely due to highly inbred females mating with more distantly related males. We did not find evidence for inbreeding avoidance in males and outbred females, suggesting sex‐specific evolutionary trade‐offs may have driven the evolution of mating behaviour. Our results demonstrate inbreeding depression in a long‐lived species and that the evolution of inbreeding avoidance is shaped by multiple selective forces.

Yuan, Michael L.↗
DOE OSTI2011

Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

Purpose: Current methods for estimating and reporting radiation dose from CT examinations are largely patient-generic; the body size and hence dose variation from patient to patient is not reflected. Furthermore, the current protocol designs rely on dose as a surrogate for the risk of cancer incidence, neglecting the strong dependence of risk on age and gender. The purpose of this study was to develop a method for estimating patient-specific radiation dose and cancer risk from CT examinations. Methods: The study included two patients (a 5-week-old female patient and a 12-year-old male patient), who underwent 64-slice CT examinations (LightSpeed VCT, GE Healthcare) of the chest, abdomen, and pelvis at our institution in 2006. For each patient, a nonuniform rational B-spine (NURBS) based full-body computer model was created based on the patient's clinical CT data. Large organs and structures inside the image volume were individually segmented and modeled. Other organs were created by transforming an existing adult male or female full-body computer model (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. A Monte Carlo program previously developed and validated for dose simulation on the LightSpeed VCT scanner was used to estimate patient-specific organ dose, from which effective dose and risks of cancer incidence were derived. Patient-specific organ dose and effective dose were compared with patient-generic CT dose quantities in current clinical use: the volume-weighted CT dose index (CTDI{sub vol}) and the effective dose derived from the dose-length product (DLP). Results: The effective dose for the CT examination of the newborn patient (5.7 mSv) was higher but comparable to that for the CT examination of the teenager patient (4.9 mSv) due to the size-based clinical CT protocols at our institution, which employ lower scan techniques for smaller patients. However, the overall risk of cancer incidence attributable to the CT examination was much higher for the newborn (2.4 in 1000) than for the teenager (0.7 in 1000). For the two pediatric-aged patients in our study, CTDI{sub vol} underestimated dose to large organs in the scan coverage by 30%-48%. The effective dose derived from DLP using published conversion coefficients differed from that calculated using patient-specific organ dose values by -57% to 13%, when the tissue weighting factors of ICRP 60 were used, and by -63% to 28%, when the tissue weighting factors of ICRP 103 were used. Conclusions: It is possible to estimate patient-specific radiation dose and cancer risk from CT examinations by combining a validated Monte Carlo program with patient-specific anatomical models that are derived from the patients' clinical CT data and supplemented by transformed models of reference adults. With the construction of a large library of patient-specific computer models encompassing patients of all ages and weight percentiles, dose and risk can be estimated for any patient prior to or after a CT examination. Such information may aid in decisions for image utilization and can further guide the design and optimization of CT technologies and scan protocols.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Development of 5- and 10-year-old pediatric phantoms based on polygon mesh surfaces

Purpose: The purpose of this study is the development of reference pediatric phantoms for 5- and 10-year-old children to be used for the calculation of organ and tissue equivalent doses in radiation protection. Methods: The study proposes a method for developing anatomically highly sophisticated pediatric phantoms without using medical images. The 5- and 10-year-old male and female phantoms presented here were developed using 3D modeling software applied to anatomical information taken from atlases and textbooks. The method uses polygon mesh surfaces to model body contours, the shape of organs as well as their positions, and orientations in the human body. Organ and tissue masses comply with the corresponding data given by the International Commission on Radiological Protection (ICRP) for the 5- and 10-year-old reference children. Bones were segmented into cortical bone, spongiosa, medullary marrow, and cartilage to allow for the use of micro computer tomographic ({mu}CT) images of trabecular bone for skeletal dosimetry. Results: The four phantoms, a male and a female for each age, and their organs are presented in 3D images and their organ and tissue masses in tables which show the compliance of the ICRP reference values. Dosimetric data, calculated for the reference pediatric phantoms by Monte Carlo methods were compared with corresponding data from adult mesh phantoms and pediatric stylized phantoms. The comparisons show reasonable agreement if the anatomical differences between the phantoms are properly taken into account. Conclusions: Pediatric phantoms were developed without using medical images of patients or volunteers for the first time. The models are reference phantoms, suitable for regulatory dosimetry, however, the 3D modeling method can also be applied to medical images to develop patient-specific phantoms.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2013

Organ S values and effective doses for family members exposed to adult patients following I-131 treatment: A Monte Carlo simulation study

Purpose: To calculate organ S values (mGy/Bq-s) and effective doses per time-integrated activity (mSv/Bq-s) for pediatric and adult family members exposed to an adult male or female patient treated with I-131 using a series of hybrid computational phantoms coupled with a Monte Carlo radiation transport technique.Methods: A series of pediatric and adult hybrid computational phantoms were employed in the study. Three different exposure scenarios were considered: (1) standing face-to-face exposures between an adult patient and pediatric or adult family phantoms at five different separation distances; (2) an adult female patient holding her newborn child, and (3) a 1-yr-old child standing on the lap of an adult female patient. For the adult patient model, two different thyroid-related diseases were considered: hyperthyroidism and differentiated thyroid cancer (DTC) with corresponding internal distributions of {sup 131}I. A general purpose Monte Carlo code, MCNPX v2.7, was used to perform the Monte Carlo radiation transport.Results: The S values show a strong dependency on age and organ location within the family phantoms at short distances. The S values and effective dose per time-integrated activity from the adult female patient phantom are relatively high at shorter distances and to younger family phantoms. At a distance of 1 m, effective doses per time-integrated activity are lower than those values based on the NRC (Nuclear Regulatory Commission) by a factor of 2 for both adult male and female patient phantoms. The S values to target organs from the hyperthyroid-patient source distribution strongly depend on the height of the exposed family phantom, so that their values rapidly decrease with decreasing height of the family phantom. Active marrow of the 10-yr-old phantom shows the highest S values among family phantoms for the DTC-patient source distribution. In the exposure scenario of mother and baby, S values and effective doses per time-integrated activity to the newborn and 1-yr-old phantoms for a hyperthyroid-patient source are higher than values for a DTC-patient source.Conclusions: The authors performed realistic assessments of {sup 131}I organ S values and effective dose per time-integrated activity from adult patients treated for hyperthyroidism and DTC to family members. In addition, the authors’ studies consider Monte Carlo simulated “mother and baby/child” exposure scenarios for the first time. Based on these results, the authors reconfirm the strong conservatism underlying the point source method recommended by the US NRC. The authors recommend that various factors such as the type of the patient's disease, the age of family members, and the distance/posture between the patient and family members must be carefully considered to provide realistic dose estimates for patient-to-family exposures.

61 RADIATION PROTECTION AND DOSIMETRY↗