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Abstract: Both abdominal radiotherapy and a nuclear event can result in gastrointestinal symptoms, including acute radiation syndrome (GI-ARS). GI-ARS is characterized by compromised intestinal barrier integrity increasing the risk for infectious complications. Physiologically relevant animal models are crucial for elucidating host responses and therapeutic targets. We aimed to determine the radiation dose requirements for creating GI-ARS in the Sinclair minipig. Male, sexually mature swine were randomly divided into sham (n = 6) and three lower hemibody radiation dosage groups of 8, 10, and 12 Gy (n = 5/group) delivered using linear accelerator-derived x-rays (1.9 Gy/min). Animals were monitored for GI-ARS symptoms for 14 days with rectal swab and blood collection at days 0-3, 7, 10, and 14 followed by necropsy for western blotting and histology. Dose-dependent increases in weight loss, diarrhea severity, and mortality (log-rank test, P = 0.041) were seen. Villi length was significantly reduced in all irradiated animals compared to controls ( P < 0.001). Serum citrulline decreased and bacterial translocation increased after irradiation compared to controls. Increased NLRP3 levels in post-mortem jejunum were seen ( P = 0.0043) as well as increased IL-1β levels in the 12 Gy group ( P = 0.041). Radiation dose and survival were associated with significant gut microbial community shifts in beta diversity. Moreover, decedents had increased Porphyromonas, Campylobacter, Bacteroides , Parvimonas , and decreased Fusobacterium and decreased Aerococcus, Lactobacillus, Prevotella, and Streptococcus . Our novel Sinclair minipig model showed dose-dependent clinical symptoms of GI-ARS. These findings provide invaluable insights into the intricate interplay between GI-ARS, intestinal inflammation, and gut microbiota alterations offering potential targets for therapeutic and diagnostic interventions after radiation exposure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government"œ for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Purpose: Scientific Committee 6-9 was established by the National Council on Radiation Protection and Measurements (NCRP), charged to provide guidance in the derivation of organ doses and their uncertainty, and produced a report, NCRP Report No. 178, Deriving Organ Doses and their Uncertainty for Epidemiologic Studies with a focus on the Million Person Study of Low-Dose Radiation Health Effects (MPS). This review summarizes the conclusions and recommendations of NCRP Report No. 178, with a concentration on and overview of the dosimetry and uncertainty approaches for the cohorts in the MPS, along with guidelines regarding the essential approaches used to estimate organ doses and their uncertainties (from external and internal sources) within the framework of an epidemiologic study., Conclusions: The success of the MPS is tied to the validity of the dose reconstruction approaches to provide realistic estimates of organ-specific radiation absorbed doses that are as accurate and precise as possible and to properly evaluate their accompanying uncertainties. The dosimetry aspects for the MPS are challenging in that they address diverse exposure scenarios for diverse occupational groups being studied over a period of up to 70 y. Specific dosimetric reconstruction issues differ among the varied exposed populations that are considered: atomic veterans, U.S. Department of Energy workers exposed to both penetrating radiation and intakes of radionuclides, nuclear power plant workers, medical radiation workers, and industrial radiographers. While a major source of radiation exposure to the study population comes from external gamma- or x-ray sources, for some of the study groups, there is also a meaningful component of radionuclide intakes that requires internal radiation dosimetry assessments.

Chartered by the U.S. Congress in 1961, the Armed Forces Radiobiology Research Institute (AFRRI) is a Joint Department of Defense (DoD) entity with the mission of carrying out the Medical Radiological Defense Research Program in support of our military forces around the globe. In the last 60 years, the investigators at AFRRI have conducted exploratory and developmental research with broad application to the field of radiation sciences. As the only DoD facility dedicated to radiation research, AFRRI's Medical Radiobiology Advisory Team provides deployable medical and radiobiological subject matter expertise, advising commanders in the response to a U.S. nuclear weapon incident and other nuclear or radiological material incidents. AFRRI received the DoD Joint Meritorious Unit Award on February 17, 2004, for its exceptionally meritorious achievements from September 11, 2001 to June 20, 2003, in response to acts of terrorism and nuclear/radiological threats at home and abroad. In August 2009, the American Nuclear Society designated the institute a nuclear historic landmark as the U.S.'s primary source of medical nuclear and radiological research, preparedness and training. Since then, research has continued, and core areas of study include prevention, assessment and treatment of radiological injuries that may occur from exposure to a wide range of doses (low to high). AFRRI collaborates with other government entities, academic institutions, civilian laboratories and other countries to research the biological effects of ionizing radiation. Notable early research contributions were the establishment of dose limits for major acute radiation syndromes in primates, applicable to human exposures, followed by the subsequent evolution of radiobiology concepts, particularly the importance of immune collapse and combined injury. In this century, the program has been essential in the development and validation of prophylactic and therapeutic drugs, such as Amifostine, Neupogen®, Neulasta®, Nplate® and Leukine®, all of which are used to prevent and treat radiation injuries. Moreover, AFRRI has helped develop rapid, high-precision, biodosimetry tools ranging from novel assays to software decision support. New drug candidates and biological dose assessment technologies are currently being developed. Such efforts are supported by unique and unmatched radiation sources and generators that allow for comprehensive analyses across the various types and qualities of radiation. These include but are not limited to both 60Co facilities, a TRIGA® reactor providing variable mixed neutron and γ-ray fields, a clinical linear accelerator, and a small animal radiation research platform with low-energy photons. There are five major research areas at AFRRI that encompass the prevention, assessment and treatment of injuries resulting from the effects of ionizing radiation: 1. biodosimetry; 2. low-level and low-dose-rate radiation; 3. internal contamination and metal toxicity; 4. radiation combined injury; and 5. radiation medical countermeasures. These research areas are bolstered by an educational component to broadcast and increase awareness of the medical effects of ionizing radiation, in the mass-casualty scenario after a nuclear detonation or radiological accidents. This work provides a description of the military medical operations as well as the radiation facilities and capabilities present at AFRRI, followed by a review and discussion of each of the research areas., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

Neutron metrology in the United States must be based on traceability to standards maintained by the National Institute of Standards and Technology (NIST). This article reviews the history of NIST's neutron-metrology efforts, the loss of those capabilities, and attempts to restore them. Recommendations are made to ensure that neutron dosimetry performed in the United States meets the requirements set forth by the International Standards Organization and other international and national authorities.

Organ and effective dose coefficients have been calculated for the International Commission on Radiological Protection (ICRP) reference pediatric phantoms externally exposed to mono-energetic photon radiation (x- and gamma-rays) from 0.01 to 20 MeV. Calculations used Monte Carlo radiation transport techniques. Organ dose coefficients, i.e., organ absorbed dose per unit air kerma (Gy/Gy), were calculated for 28 organs and tissues including the active marrow (or red bone marrow) for 10 phantoms (newborn, 1 year, 5 year, 10 year, and 15 year old male and female). Radiation exposure was simulated for 33 photon mono-energies (0.01-20 MeV) in six irradiation geometries: antero-posterior (AP), postero-anterior, right lateral, left lateral, rotational, and isotropic. Organ dose coefficients for different ages closely agree in AP geometry as illustrated by a small coefficient of variation (COV) (the ratio of the standard deviation to the mean) of 4.4% for the lungs. The small COVs shown for the effective dose and AP irradiation geometry reflect that most of the radiosensitive organs are located in the front part of the human body. In contrast, we observed differences in organ dose coefficients across the ages of the phantoms for lateral irradiation geometries. We also observed variation in dose coefficients across different irradiation geometries, where the COV ranges from 18% (newborn male) to 38% (15 year old male) across idealised whole body irradiation geometries for the major organs (active marrow, colon, lung, stomach wall, and breast) at the energy of 0.1 MeV. Effective dose coefficients were also derived for applicable situations, e.g., radiation protection or risk projection. Our results are the first comprehensive set of organ and effective dose coefficients applicable to children and adolescents based on the newly adopted ICRP pediatric phantom series. Our tabulated organ and effective dose coefficients for these next-generation phantoms should provide more accurate estimates of organ doses in children than earlier dosimetric models allowed.

The primary aim of the epidemiologic study of one million U.S. radiation workers and veterans [the Million Worker Study (MWS)] is to provide scientifically valid information on the level of radiation risk when exposures are received gradually over time and not within seconds, as was the case for Japanese atomic bomb survivors. The primary outcome of the epidemiologic study is cancer mortality, but other causes of death such as cardiovascular disease and cerebrovascular disease will be evaluated. The success of the study is tied to the validity of the dose reconstruction approaches to provide realistic estimates of organ-specific radiation absorbed doses that are as accurate and precise as possible and to properly evaluate their accompanying uncertainties. The dosimetry aspects for the MWS are challenging in that they address diverse exposure scenarios for diverse occupational groups being studied over a period of up to 70 y. The dosimetric issues differ among the varied exposed populations that are considered: atomic veterans, U.S. Department of Energy workers exposed to both penetrating radiation and intakes of radionuclides, nuclear power plant workers, medical radiation workers, and industrial radiographers. While a major source of radiation exposure to the study population comes from external gamma- or x-ray sources, for some of the study groups, there is a meaningful component of radionuclide intakes that requires internal radiation dosimetry assessments. Scientific Committee 6-9 has been established by the National Council on Radiation Protection and Measurements (NCRP) to produce a report on the comprehensive organ dose assessment (including uncertainty analysis) for the MWS. The NCRP dosimetry report will cover the specifics of practical dose reconstruction for the ongoing epidemiologic studies with uncertainty analysis discussions and will be a specific application of the guidance provided in NCRP Report Nos. 158, 163, 164, and 171. The main role of the Committee is to provide guidelines to the various groups of dosimetrists involved in the MWS to ensure that certain dosimetry criteria are considered: calculation of annual absorbed doses in the organs of interest, separation of low and high linear-energy transfer components, evaluation of uncertainties, and quality assurance and quality control. It is recognized that the MWS and its approaches to dosimetry are a work in progress and that there will be flexibility and changes in direction as new information is obtained with regard to both dosimetry and the epidemiologic features of the study components. This paper focuses on the description of the various components of the MWS, the available dosimetry results, and the challenges that have been encountered. It is expected that the Committee will complete its report in 2016.

Availability, reliability, and technical improvements have led to continued expansion of computed tomography (CT) imaging. During a CT scan, there is substantially more exposure to ionizing radiation than with conventional radiography. This has led to questions and critical conclusions about whether the continuous growth of CT scans should be subjected to review and potentially restraints or, at a minimum, closer investigation. This is particularly pertinent to populations in emergency departments, such as children and patients who receive repeated CT scans for benign diagnoses. During the last several decades, among national medical specialty organizations, the American College of Emergency Physicians and the American College of Radiology have each formed membership working groups to consider value, access, and expedience and to promote broad acceptance of CT protocols and procedures within their disciplines. Those efforts have had positive effects on the use criteria for CT by other physician groups, health insurance carriers, regulators, and legislators., (Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

A comparative study of electron paramagnetic resonance dosimetry in Q- and X-bands has shown that Q-band is able to provide accurate measurements of radiation doses even below 0.5 Gy with tooth enamel samples as small as 2 mg. The optimal amount of tooth enamel for dose measurements in Q-band was found to be 4 mg. This is less than 1% of the total amount of tooth enamel in one molar tooth. Such a small amount of tooth enamel can be harmlessly obtained in an emergency requiring after-the-fact radiation dose measurement. The other important advantage of Q-band is full resolution of the radiation-induced EPR signal from the native, background signal. This separation makes dose response measurements much easier in comparison to conventional X-band measurements in which these overlapping signals necessitate special methods for doses below 0.5 Gy. The main disadvantages of Q-band measurements are a higher level of noise and lower spectral reproducibility than in X-band. The effect of these negative factors on the precision of dose measurements in Q-band could probably be reduced by improvement of sample fixation in the resonance cavity and better optimization of signal filtration to reduce high-frequency noise.

As a result of terrorism, accident, or war, populations potentially can be exposed to doses of ionizing radiation that could cause direct clinical effects within days or weeks. There is a critical need to determine the magnitude of the exposure to individuals so that those with significant risk have appropriate procedures initiated immediately, while those without a significant probability of acute effects can be reassured and removed from the need for further consideration in the medical/emergency system. In many of the plausible scenarios there is an urgent need to make the determination very soon after the event and while the subject is still present. In vivo EPR measurements of radiation-induced changes in the enamel of teeth is a method, perhaps the only such method, which can differentiate among doses sufficiently for classifying individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. In its current state, the in vivo EPR dosimeter can provide estimates of absorbed dose with an error approximately +/- 50 cGy over the range of interest for acute biological effects of radiation, assuming repeated measurements of the tooth in the mouth of the subject. The time required for acquisition, the lower limit, and the precision are expected to improve, with improvements in the resonator and the algorithm for acquiring and calculating the dose. The magnet system that is currently used, while potentially deployable, is somewhat large and heavy, requiring that it be mounted on a small truck or trailer. Several smaller magnets, including an intraoral magnet are under development, which would extend the ease of use of this technique.

Biological monitoring of dose can contribute important, independent estimates of cumulative radiation exposure in epidemiological studies, especially in studies in which the physical dosimetry is lacking. Three biodosimeters that have been used in epidemiological studies to estimate past radiation exposure from external sources will be highlighted: chromosome painting or FISH (fluorescence in situ hybridization), the glycophorin A somatic mutation assay (GPA), and electron paramagnetic resonance (EPR) with teeth. All three biodosimeters have been applied to A-bomb survivors, Chernobyl clean-up workers, and radiation workers. Each biodosimeter has unique advantages and limitations depending upon the level and type of radiation exposure. Chromosome painting has been the most widely applied biodosimeter in epidemiological studies of past radiation exposure, and results of these studies provide evidence that dose-related translocations persist for decades. EPR tooth dosimetry has been used to validate dose models of acute and chronic radiation exposure, although the present requirement of extracted teeth has been a disadvantage. GPA has been correlated with physically based radiation dose after high-dose, acute exposures but not after low-dose, chronic exposures. Interindividual variability appears to be a limitation for both chromosome painting and GPA. Both of these techniques can be used to estimate the level of past radiation exposure to a population, whereas EPR can provide individual dose estimates of past exposure. This paper will review each of these three biodosimeters and compare their application in selected epidemiological studies.

Determination of mean glandular dose (MGD) to breast tissue is an essential aspect of mammography equipment evaluations and exposure controls. The American College of Radiology (ACR) Quality Control Manual outlines the procedure for MGD determination in screen-film mammography based upon conversions of entrance skin exposures (ESEs) measured with an ionization chamber (IC). The development of digital mammography has increased with the demand for improved object resolution and tissue contrast. This change in image receptor from screen-film to a solid-state detector has led to questions about the applicability of the ACR MGD methodology to digital mammography. This research has validated the applicability of the ACR MGD methodology to digital mammography in the GE digital mammography system Senographe 2000D. MGD was determined using light output measurements from thermoluminescent dosimeters (MGDTL), exposure measurements from an IC (MGD(IC)) and conversion factors from the ACR Mammography Quality Control Manual. MGD(TL) and MGD(IC) data indicate that there is a statistically significant difference between the two measurements with the Senographe 2000D. However, the applicability of the ACR's methodology was validated by calculating MGD at various depths in a 50/50 breast phantom. Additionally, the results of backscatter measurements from the image receptors of both mammography modalities indicate there is a difference (all P values < 0.001) in the radiation backscattered from each image receptor.

Between 1949 and 1989 the Semipalatinsk nuclear test site (SNTS), an area of 19,000 square km in northeastern Kazakhstan, was the location of over 400 nuclear test explosions with a total explosive energy of 6.6 Mt TNT (trinitrotoluene or trotyl) equivalent. It is estimated that the bulk of the radiation exposure to the population resulted from three tests, conducted in 1949, 1951, and 1953 although estimations of radiation doses received by the local population have varied significantly. Analysis of the published ESR dose reconstruction results for residents of the villages near the SNTS show that they do not correlate well with other methods of dose assessment (e.g. model dose calculation and thermo luminescence dosimetry (TLD) in bricks). The most significant difference in dose estimations was found for the population of Dolon, which was exposed as result of the first Soviet nuclear test in 1949. Published results of ESR measurements in tooth enamel are considerably lower than other dose estimations. Detailed analysis of these results is provided and a possible explanation for this discrepancy and ways to eliminate it are suggested.

The aim of this paper is to analyze the lower limit of detection (LLD), linearity of dose response, variation of radiation sensitivity between different tooth enamel samples, and time/temperature stability of EPR biodosimetry in tooth enamel. The theoretical LLD is shown to be 0.46 mGy, which is far lower than the measured value of about 30 mGy. The main issues to lowering LLD are the differentiation of the radiation-induced component against the total EPR spectrum and the complex nature of the dose dependence of the EPR signal. The following questions are also discussed in detail: need for exfoliated or extracted teeth from persons of interest, accounting for background radiation contribution; conversion of tooth enamel absorbed dose to effective dose; accounting for internal exposure specifically from bone-seeking radionuclides. Conclusions on future development of EPR retrospective biodosimetry are made.

Spectral acquisition time is one of the limiting factors in electron paramagnetic resonance (EPR) retrospective biodosimetry in teeth. Acquisition times for one sample can be from 2 to 4h. This problem is even more acute for in vivo EPR measurements in L-band. Patients cannot be expected to remain stationary for these lengths of time. In order to overcome this limitation, we investigated the dependence of EPR dose measurements on the number of data points in an EPR spectrum. We have shown that this number could be reduced from 1024 to 256 (factor of 4 reduction in spectral acquisition time) at 5 mT magnetic field sweep without a loss of precision in the dose measurements.

This study examined the feasibility of performing radiographic studies on patients wearing standard-issue body armor. The Kevlar helmet, fragmentation vest, demining suit sleeve, and armor plate were studied with plain film and computed tomography in a simulated casualty situation. We found that the military helmet contains metal screws and metal clips in the headband, but diagnostic computed tomographic images can be obtained. Kevlar, the principal component of soft armor, has favorable photon attenuation characteristics. Plate armor of composite material also did not limit radiographic studies. Therefore, when medically advantageous, patients can be examined radiographically while wearing standard military body armor. Civilian emergency rooms should be aware of these observations because law enforcement officers wear similar protective armor.

On 11 December 1991 a radiation accident occurred at an industrial accelerator facility. A description of the facility and details of the accident are reported in Schauer et al., 1993a). In brief, during maintenance on the lower window pressure plate of a 3 MV potential drop accelerator, an operator placed his hands, head, and feet in the radiation beam. The filament voltage of the electron source was turned 'off', but the full accelerating potential was on the high voltage terminal. The operator's body, especially his extremities and head, were exposed to electron dark current. At approx. 3 months post-irradiation, the four digits of the victim's right hand and most of the four digits of his left hand were amputated. Electron paramagnetic resonance (EPR) spectrometry was used to estimate the radiation dose to the victim's extremities. Extremity dose estimates ranged from 55.0 Gy (+/- 4.7 Gy) to 108 Gy (+/- 24.1 Gy).

Previous investigators have reported that the radiation-induced EPR signal intensity in compact or cortical bone increases up to a factor of two with decreasing photon energy for a given absorbed dose. If the EPR signal intensity was dependent on energy, it could limit the application of EPR spectrometry and the additive reirradiation method to obtain dose estimates. We have recently shown that errors in the assumptions governing conversion of measured exposure to absorbed dose can lead to similar "apparent" energy-dependence results. We hypothesized that these previous results were due to errors in the estimated dose in bone, rather than the effects of energy dependence per se. To test this hypothesis we studied human adult cortical bone from male and female donors ranging in age from 23 to 95 years, and bovine tooth enamel, using 34 and 138 keV average energy X-ray beams and 137Cs (662 keV) and 60Co (1250 keV) gamma rays. In a femur from a 47-year-old male (subject 1), there was a difference of borderline significance at the alpha = 0.05 level in the mean radiation-induced hydroxyapatite signal intensities as a function of photon energy. No other statistically significant differences in EPR signal intensity as a function of photon energy were observed in this subject, or in the tibia from a 23-year-old male (subject 2) and the femur from a 75-year-old female (subject 3). However, there was a trend toward a decrease (12-15%) in signal intensity at the lowest energy compared with the highest energy in subjects 1 and 3. Further analysis of the data from subject 1 revealed that this trend, which is in the opposite direction of previous reports but is consistent with theory, is statistically significant. There were no effects of energy dependence in the tooth samples.

On 11 December 1991, a radiation overexposure occurred at an industrial radiation facility in Maryland. The radiation source was a 3-MV potential drop accelerator designed to produce high electron beam currents for materials-processing applications. This accelerator is capable of producing a 25 milliampere swept electron beam that is scanned over a width of 112.5 cm and which emerges from the accelerator vacuum system through a titanium double window assembly. During maintenance on the lower window pressure plate, an operator placed his hands, head, and feet in the beam. This was done with the filament voltage of the electron source turned "off," but with the full accelerating potential on the high voltage terminal. The operator's body, especially his extremities and head, were exposed to electron dark current. In an attempt to reconstruct the accident, radiochromic film and alanine measurements were made with the accelerator operated at two beam currents. Measured dose rates ranged from approximately 40 cGy s-1 inside the victim's shoe to 1,300 cGy s-1 at the hand position. Approximately 3 mo after the accident, it was necessary to amputate the four digits of the victim's right hand and most of the four digits of his left hand. Electron paramagnetic resonance spectrometry, which measures the concentration of radiation-induced paramagnetic centers in calcified tissues, was used to estimate the dose to the victim's extremities. A mean dose estimate of 55.0 +/- 3.5 Gy (95% confidence level) averaged over the mass of the bone was obtained for the victim's left middle finger (middle phalanx).

The conversion of measured exposure to absorbed dose at a point in bone, under conditions of electron equilibrium, involves a factor (the f-factor) which is proportional to the ratio of the spectrum-averaged photon energy-absorption coefficient for bone to that for air. This paper gives mass energy-absorption coefficients and f-factors for three compositions of human adult compact or cortical bone recommended in publications by the ICRU and the ICRP, for photon energies from 1 keV to 1.5 MeV. Spectrum-averaged f-factors for a number of calibration x-ray beams ranging from 10 to 250 kVp have been calculated and compared to corresponding results obtained with the use of an equivalent photon energy derived from the measured thickness of the half-value layer. At low photon energies (approximately less than 200 keV), the new f-factor results reflect: (a) the rather large differences due to the differing calcium contents among the recommended compositions for bone: and (b) the generally poor predictions obtained when replacing a broad energy spectrum by an equivalent photon energy.

Therapeutic and palliative uses of bone-seeking radiopharmaceuticals are undergoing clinical trials for human subjects. Radiation dosimetry for these applications is based on the Medical Internal Radiation Dosimetry (MIRD) schema. An experimental method for dosimetry of bone tissue based on electron paramagnetic resonance (EPR) spectrometry is described. Preliminary results for beagle bone exposed to radiopharmaceuticals under clinical conditions have indicated that the EPR dose measurements give approximately the calculated dose, but suggest that the dose distribution may be non-uniform.

A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage to isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 ke V X radiation. Electrophysiological recordings were made before, during, and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrate that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction.

A 50 kVp molybdenum target/filter x-ray tube has been installed inside a lead-shielded Faraday cage. High-dose rates of up to 1.54 Gy min-1 (17.4 keV weighted average photons) have been used to conduct local in vitro irradiations of the hippocampal region of guinea pig brains. Electrophysiological recordings of subtle changes in neuronal activity indicate this system is suitable for this application.