Yueshan Feng, Jiaxing Yu, Lixin Xu, Haohan Lu, Hongyun Zhang, Zhengsong Li, Roberta Kungulli, Tao Hong, Mo Zhang, Jie Lu, Hongqi Zhang, Sishi Xiang
{"title":"Development of an Experimental Platform for Gamma Knife Radiosurgery in Mouse Brains.","authors":"Yueshan Feng, Jiaxing Yu, Lixin Xu, Haohan Lu, Hongyun Zhang, Zhengsong Li, Roberta Kungulli, Tao Hong, Mo Zhang, Jie Lu, Hongqi Zhang, Sishi Xiang","doi":"10.1667/RADE-24-00198.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00198.1","url":null,"abstract":"<p><p>The limited availability of post-Gamma Knife radiosurgery (GKRS) samples and the unsuitability of clinical GKRS devices for small animals highlight the need to develop devices that enable the application of a clinical GKRS device in mouse models. This study introduces a novel platform specifically designed for utilizing the Leksell Gamma Knife in mouse studies. The 3D-printed device comprises a positioning platform and a head fixation device. Six-week-old C57BL/6N mice underwent irradiation targeting the left caudate putamen (CPu) or left anterior frontobase areas. Clinical Gamma Knife prescription doses (central radiation doses of 80 Gy, 60 Gy, 50 Gy, 40 Gy, 20 Gy, and 10 Gy) were administered as single exposures. Dose conversion experiments confirmed that the actual radiation dose delivered to mice was consistently 1.5-fold higher than the planned clinical dose. MRI and H&E staining revealed clear radiation necrosis (RN) in the targeted areas when the planned clinical dose of 80 Gy was applied to the CPu and anterior frontobase, confirming the device's accuracy. γ-H2AX staining showed significant DNA double-strand breaks in the targeted region, particularly after a planned clinical dose of 40 Gy and higher. H&E staining also indicated parenchymal hemorrhage, tissue loss, and edema in the targeted areas among groups exposed to the planned clinical central doses of 80 Gy, 60 Gy, and 50 Gy. Immunofluorescence staining of CD68, IBA1, and NeuN showed significant neuroinflammation in the targeted areas of the high-dose groups (planned clinical doses of 80 Gy, 60 Gy, 50 Gy, or 40 Gy), characterized by increased microglia activation, macrophage infiltration, and neuronal death. This study developed a novel mouse platform for the Leksell Gamma Knife, enabling precise GKRS in mouse brains. For adult C57BL/6N mice, a planned clinical central dose of 40 Gy may be considered a suitable threshold for radiation-induced brain injury.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeffrey C Buchsbaum, Henry F VanBrocklin, Reinier Hernandez, Ellen M O'Brien, Heather M Hennkens, Dmitri G Medvedev, Roger W Howell, Freddy E Escorcia, Yuni K Dewaraja, Abhinav K Jha, Anuj J Kapadia, Greeshma Agasthya, Arman Rahmim, Babak Saboury, Kristian Myhre, Sandra Davern
{"title":"Computational Modeling to Advance Novel Medical Isotopes for Radiotheranostics: A DOE-NIH Joint Workshop Executive Summary.","authors":"Jeffrey C Buchsbaum, Henry F VanBrocklin, Reinier Hernandez, Ellen M O'Brien, Heather M Hennkens, Dmitri G Medvedev, Roger W Howell, Freddy E Escorcia, Yuni K Dewaraja, Abhinav K Jha, Anuj J Kapadia, Greeshma Agasthya, Arman Rahmim, Babak Saboury, Kristian Myhre, Sandra Davern","doi":"10.1667/RADE-25-00MR1.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00MR1.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Satoshi Omiya, Juan Dalo, Yuki Ueda, Uma Shankavaram, Elisa Baldelli, Valerie Calvert, Michelle Bylicky, Emanuel F Petricoin, Molykutty J Aryankalayil
{"title":"The EGFR Pathway as a Potential Therapeutic Target for Modulation of Radiation-induced Liver Injury.","authors":"Satoshi Omiya, Juan Dalo, Yuki Ueda, Uma Shankavaram, Elisa Baldelli, Valerie Calvert, Michelle Bylicky, Emanuel F Petricoin, Molykutty J Aryankalayil","doi":"10.1667/RADE-24-00203.1","DOIUrl":"10.1667/RADE-24-00203.1","url":null,"abstract":"<p><p>Radiation exposure can result in various complications influenced by factors such as dose, the amount of tissue exposed, and the type of tissue exposed. Radiation-induced liver injury (RILI) is a concern in cancer patients receiving thoracic and upper abdominal radiation, but it can also be a risk for civilians exposed to radiation in a nuclear event. RILI can lead to organ dysfunction or death; a deeper understanding of how radiation causes damage to normal tissue could pave the way for new treatments. In our study, we focused on the effects of radiation on the two main liver cell types: liver sinusoidal endothelial cells (LSECs) and hepatocytes. We exposed these cells to different doses of radiation (2, 4 or 8 Gy) as well as a sham irradiation (0 Gy) control. Proteins were extracted at 30 min, 6 h and 24 h postirradiation and analyzed using reverse phase protein array (RPPA). We observed changes to the Hepatic fibrosis signaling pathway, IL-8 signaling, and S100 family signaling pathways across multiple doses and time points in LSECs. In hepatocytes, radiation affected different pathways; we see changes in the Th1 and Th2 signaling pathways and the IL-10 signaling pathway. These pathways are critical in mediating the immune response, with Th1 being associated with pro-inflammatory responses and Th2 with anti-inflammatory responses. Hub proteins from protein-protein interaction (PPI) networks across all time points for both LSECs and hepatocytes highlighted EGFR as a top-ranked protein, indicating the potential role in mitigating radiation damage in liver cells. Herein, we showed alterations in protein expression after RILI using RPPA at early time points (hours to days) to determine potentially targetable molecular pathways. We further highlighted potential therapeutic protein markers, including EGFR, as an example of the potential utility of RPPA in target discovery.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"293-303"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthesis and Evaluation of Novel 18F-labeled Oxadiazole-based Positron Emission Tomography Tracers for β-Amyloid.","authors":"Zhongyuan Qi, Wantong Guo, Mengchao Cui, Jie Lu","doi":"10.1667/RADE-25-00035.1","DOIUrl":"10.1667/RADE-25-00035.1","url":null,"abstract":"<p><p>This research details the synthesis, structure-activity evaluation, and analysis of novel oxadiazole-based compounds for visualizing β-amyloid (Aβ) in Alzheimer's disease (AD). The derivatives exhibited binding affinities to Aβ aggregates in vitro. The [18F]-labeled compounds, [18F]4-(5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)-N, N-dimethylaniline (compound [18F] 3) and [18F] 4-(5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)-N-methylaniline (compound [18F]4), effectively labeled Aβ plaques in brain sections from Alzheimer's disease patients and APP/PS1 mice. In dynamic positron emission tomography (PET) studies on healthy mice, these compounds demonstrated favorable brain uptake followed by clearance. Additional structural alterations to compounds [18F] 3 and [18F] 4 may lead to the development of more efficient PET tracers for precise visualization of Aβ plaques.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"357-365"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Symbolic Regression: A Versatile Approach for Constructing Phenomenological Models of Radiobiological Effects.","authors":"Ankang Hu, Wanyi Zhou, Rui Qiu, Junli Li","doi":"10.1667/RADE-24-00213.1","DOIUrl":"10.1667/RADE-24-00213.1","url":null,"abstract":"<p><p>The development of quantitative models that correlate physical, chemical, and biological parameters with radiobiological effects is imperative in the domains of radiotherapy and radiation protection. Due to the challenges associated with quantifying underlying mechanisms, phenomenological models are frequently established in preference to mechanistic models. However, the lack of a universal methodology for constructing phenomenological models presents a significant challenge in the field. We employ symbolic regression as a method for constructing phenomenological models. We attempt to develop models for the survival fraction, microdosimetric parameters, the radiation oxygen effect, and the FLASH effect. Additionally, we compare the results obtained from our symbolic regression approach with existing formulas in the scientific literature to assess the efficacy and validity of our method. Symbolic regression yields multiple simple formulas for each modeling task undertaken. These formulas demonstrate a comparable ability to predict radiobiological effects as the formulas presented in previous scientific publications. Our findings propose that symbolic regression is an automated and flexible strategy for constructing phenomenological models of radiobiological effects. Additionally, they underscore that the interpretability of a model is as crucial as its goodness of fit, as symbolic regression can identify various distinct formulas that adequately fit the provided data points.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"333-340"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peiquan Liu, Min Fu, Dong Liu, Tengfei Chao, Jiaxuan Zhang
{"title":"Mechanisms of Radiation-induced Brain Injury in Mice Based on Bioinformatics Analysis.","authors":"Peiquan Liu, Min Fu, Dong Liu, Tengfei Chao, Jiaxuan Zhang","doi":"10.1667/RADE-24-00204.1","DOIUrl":"10.1667/RADE-24-00204.1","url":null,"abstract":"<p><p>Radiation therapy is a crucial adjunct treatment for head and neck tumors, as well as primary or metastatic brain tumors. Radiation-induced brain injury is one of the most severe complications, postirradiation, in patients with head and neck tumors, and significantly impacts their quality of life. Currently, there are no effective treatments for radiation-induced brain injury, making the study of radiation-induced molecular mechanisms and the identification of early damage biomarkers critical for the early diagnosis and treatment of such injuries. In this study, twelve male C57 mice aged 6-8 weeks were randomly divided into a control group, a 15 Gy irradiation group, and a 30 Gy irradiation group. Mice were exposed to 6 MV X rays. The control group underwent the same anesthesia procedure as the irradiated groups but did not receive radiation. General health and weight changes were monitored and recorded. Four months postirradiation, mice were subjected to intracranial magnetic resonance imaging [T2-weighted imaging (T2WI)], open field test (OFT), novel object recognition (NOR), followed by a collection of brain tissues for immunofluorescence, SA-β-gal staining, and transcriptomic and metabolomic analyses. Compared to the control group, the 15 Gy and 30 Gy irradiated mice showed reduced activity and weight loss. The irradiated mice exhibited impaired recognition memory in the NOR test and decreased body weight, but radiation had no significant effect on weight or performance in the OFT. Electron microscopy reveals significant demyelination of mouse cortex after irradiation, and MRI T2-weighted imaging demonstrated varying degrees of brain atrophy and ventricular enlargement in irradiated mice compared to the control group. Immunofluorescence staining showed a significant increase in astrocytes and microglia activated after irradiation. SA-β-gal staining revealed significant increases in the numbers of β-gal+ cells in irradiated mice compared to those in untreated control mice. Bioinformatics analysis identified enriched pathways primarily related to lipid metabolism and neuroinflammatory responses; associated metabolites and genes were variously upregulated or downregulated. The findings suggest that radiation-induced brain injury involves complex biological processes, with lipid metabolism disorders and neuroinflammation being the predominant pathological changes observed. Further studies on these metabolic pathways and genes could enhance our understanding of the pathogenic mechanisms underlying radiation-induced brain injury and identify potential therapeutic targets.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"321-332"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Issa Melendez-Miranda, Oluseyi O Fatanmi, Stephen Y Wise, Sarah A Petrus, Alana D Carpenter, Cara Olsen, Artur A Serebrenik, Luis A Lugo-Roman, Thomas M Seed, Michael D Kaytor, Vijay K Singh
{"title":"Lethality Assessments for Acutely Irradiated Cynomolgus Macaques Under Subject-based Care.","authors":"Issa Melendez-Miranda, Oluseyi O Fatanmi, Stephen Y Wise, Sarah A Petrus, Alana D Carpenter, Cara Olsen, Artur A Serebrenik, Luis A Lugo-Roman, Thomas M Seed, Michael D Kaytor, Vijay K Singh","doi":"10.1667/RADE-24-00223.1","DOIUrl":"10.1667/RADE-24-00223.1","url":null,"abstract":"<p><p>Well-characterized animal models of acute radiation syndrome are needed for the development of radiation medical countermeasures to mitigate injury due to acute exposure to high doses of total- or partial-body radiation. Such animal models must reveal a radiation dose- and time-dependent relationship, pathogenesis of injury, and clinical presentation similar to humans. The focus of this study was to investigate clinical responses, principally lethality patterns, of cynomolgus macaques acutely exposed to relatively high doses of total-body radiation. Such investigations are currently relevant due to the limited availability of rhesus macaques, the dominant and preferred macaque subspecies, due to limited supply and their use in other high-priority areas. In this study employing cynomolgus macaques, a preliminary dose-response relationship was determined using three different radiation doses (4.7, 5.8 and 6.5 Gy, n = 24, n = 8/radiation dose) at a dose rate of 0.6 Gy/min. Animals were provided subject-based supportive care excluding blood products and were monitored for 60 days postirradiation for survival, which was the primary endpoint and the secondary endpoint was hematopoietic recovery. The lethality curve suggested LD30/60, LD50/60, and LD70/60 values as 4.8, 5.3, and 5.8 Gy, respectively. The initial results of this study are deemed critical for future efficacy assessments of newly developed medical countermeasures for acute radiation injuries by making use of an alternative subspecies of macaques, namely cynomolgus macaques (Macaca fascicularis).</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"304-320"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juliann G Kiang, Georgetta Cannon, Min Zhai, Matthew G Olson, Akeylah K Woods, Katherine S Cleveland, Hengying Ellery, Feng Xu, Mang Xiao
{"title":"A Combined Therapy of Pegylated G-CSF with Ciprofloxacin Mitigates Damage Induced by Lethal Ionizing Radiation to the Bone Marrow, Spleen, and Ileum by Increasing AKT Activation but Decreasing IL-18, C3, and miR-34a.","authors":"Juliann G Kiang, Georgetta Cannon, Min Zhai, Matthew G Olson, Akeylah K Woods, Katherine S Cleveland, Hengying Ellery, Feng Xu, Mang Xiao","doi":"10.1667/RADE-24-00266.1","DOIUrl":"10.1667/RADE-24-00266.1","url":null,"abstract":"<p><p>Ciprofloxacin (CIP) was found to enhance pegylated G-CSF therapy (PEG, Neulasta®)-induced survival from 30% to 85% after ionizing radiation exposure. This combined therapy significantly mitigated radiation-induced brain hemorrhage through its capability to improve platelet recovery. This study tested whether this combined treatment also mitigated gastrointestinal damage from radiation. B6D2F1 female mice were exposed to 60Co γ radiation. CIP was fed daily to mice for up to 14 days. PEG was injected on day 1, and then weekly up to day 14. For the early time point study, blood, femurs, spleen, and ileum were collected on days 2, 4, 9, and 15 postirradiation. Bone marrow cells were counted; spleen weights and splenocyte counts were measured; and ileum histopathology was examined and analyzed. AKT, ERK, JNK, p38, claudin 2, NF-kB, Bax, Bcl-2, and gasdermin D were measured in ileum lysates using Western blotting while miR-34a was measured by reverse transcription followed by real-time-PCR, and citrulline was measured by colorimetric assay. In serum, interleukin-18 (IL-18) was measured by Luminex assay and complement protein 3 (C3) was detected by ELISA. The bacterial DNA load in livers was measured by real-time PCR. Radiation depleted bone marrow cells in femurs beginning day 2 through day 15 postirradiation, which was mitigated by PEG or CIP+PEG on day 9 through day 15 and by CIP on day 15, respectively. Radiation exposure led to decreased spleen weight on day 2 through day 15, while PEG or CIP+PEG significantly mitigated the reduction on day 9 through day 15. Radiation exposure reduced splenocyte counts on day 2 through day 15 postirradiation, but that was mitigated by PEG or CIP+PEG on day 15. Ileum histology showed that radiation decreased villus height on day 2 through day 15; CIP mitigated the reduction on day 15, whereas PEG+CIP mitigated it on day 2 through 15. Villus widths were increased on day 2 through day 15, while PEG+CIP effectively decreased them on day 4 through day 15. Crypt depth was reduced by radiation on day 2, but returned to the baseline on day 4 through 15. CIP or CIP+PEG transiently increased the depth only on day 4. Crypt counts were reduced by radiation on days 2 and 4, but returned to the baseline on days 9 and 15, regardless of individual drugs or combinations. Citrulline data confirmed the villus height recovery. Radiation significantly increased pro-inflammatory cytokine IL-18 on days 4 and 9, which was mitigated by PEG alone or PEG+CIP, but not by CIP alone. Radiation increased C3 on day 9 in ileum and serum. The serum C3 was positively associated with the serum IL-18 levels and negatively correlated with the crypt depth. Radiation-induced decreases in claudin 2 (a tight junction marker) in ileum and increases in bacterial DNA in livers were mitigated by PEG+CIP. Radiation did not reduce NF-kB and its activation but reduced Bcl-2 expression, which was not significantly recovered by any individual drug or combinat","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"341-356"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haytham H Effarah, Trevor Reutershan, Michael W L Seggebruch, Martin Algots, Alexander Amador, Janet Baulch, Olivia G G Drayson, Frederic V Hartemann, Yoonwoo Hwang, Agnese Lagzda, Ferenc Raksi, Charles L Limoli, Christopher P J Barty
{"title":"Preparations for Ultra-High Dose Rate 25-90 MeV Electron Radiation Experiments with a Compact, High-Peak-Current, X-band Linear Accelerator.","authors":"Haytham H Effarah, Trevor Reutershan, Michael W L Seggebruch, Martin Algots, Alexander Amador, Janet Baulch, Olivia G G Drayson, Frederic V Hartemann, Yoonwoo Hwang, Agnese Lagzda, Ferenc Raksi, Charles L Limoli, Christopher P J Barty","doi":"10.1667/RADE-24-00120.1","DOIUrl":"10.1667/RADE-24-00120.1","url":null,"abstract":"<p><p>The Distributed Charge Compton Source (DCCS) developed by Lumitron Technologies, Inc. has produced a 25-MeV electron beam with 1.7-nC macrobunches at a 100-Hz repetition rate from a compact, high-gradient X-band (11.424 GHz) accelerator. The DCCS is currently being commissioned to produce 100-MeV-class electrons, well within the very high energy electron (VHEE) energy regime, with macrobunch charges of up to 25 nC at repetition rates up to 400 Hz. The DCCS is also designed to produce imaging X rays through Laser Compton scattering. This work aims to describe the preparations for the first dosimetry experimental campaign using this accelerator system at energies ranging from 25 MeV to 90 MeV through hardware development and Monte Carlo (TOPAS) simulation studies. A significant goal of these preparations is to configure the machine so that it can be used to both image with X rays and subsequently treat with VHEEs without movement of the animal model under study. At ultra-high dose rates, this X-ray image-guided electron source could be used to investigate dose-rate dependent differential sparing of normal and malignant biological tissue, known as the FLASH effect. An indium-tin-oxide-coated, 100-μm-thick diamond window was obtained and installed in a custom flange assembly to act as the electron/X-ray vacuum exit window. Simulations at 25 MeV suggest that a scattering foil and collimator can shape the output of the accelerator to produce a 12-mm-diameter, flat-field, circular beam with a 1.7-nC macrobunch charge. This corresponds to an entrance dose of 10 Gy in less than 100 ms. These initial results highly motivate an experimental campaign toward investigating VHEE FLASH using the DCCS at Lumitron Technologies, Inc.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"223-235"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul J Villeneuve, Brianna Frangione, Robert Talarico, Tim Prendergast, Chenchung Yu, Gagan Gill, Lydia Zablotska
{"title":"Occupational Exposure to Low Dose Ionizing Radiation and the Incidence of Surgically Removed Cataracts and Glaucoma in a Cohort of Ontario Nuclear Power Plant Workers.","authors":"Paul J Villeneuve, Brianna Frangione, Robert Talarico, Tim Prendergast, Chenchung Yu, Gagan Gill, Lydia Zablotska","doi":"10.1667/RADE-24-00050.1","DOIUrl":"10.1667/RADE-24-00050.1","url":null,"abstract":"<p><p>Ionizing radiation is a human carcinogen and has been shown to increase the risk of non-cancerous ocular disorders. Specifically, findings from epidemiological studies suggest that ionizing radiation leads to the development of cataracts and to a lesser extent glaucoma, however, there are uncertainties of these risks at lower exposures. We analyzed data from a cohort of 60,874 Ontario Nuclear Power Plant (NPP) workers within the Canadian National Dose Registry (NDR). These workers were monitored for whole-body exposure to ionizing radiation using dosimeters, with exposure estimates derived for each year of employment. Incident cases of surgically removed cataracts and glaucoma were identified through the record linkage of occupational histories to administrative health data for Ontario between 1991 and 2022. We compared the incidence of surgically removed cataracts and glaucoma in the cohort to Ontario's general population using indirect age- and sex-standardization with matching by place of residence. We evaluated exposure-response relationships with internal cohort comparisons using age-, sex-, and calendar-period-adjusted Poisson regression. The relative risks of cataract and glaucoma were estimated across categorical measures of whole-body dose [Hp(10)] from exposure to radiation (lagged 5 years). In total, 32,855 of the 60,874 workers (58%) had a positive cumulative dose exceeding the minimum reportable threshold. Among these workers, the mean cumulative whole-body lifetime dose at end of follow-up was 23.7 mSv (interquartile range: 1.1-26.4 mSv, maximum = 959.3 mSv). Overall, 4,401 (7.2%) of workers developed glaucoma, while 2,939 (4.8%) underwent cataract-removal surgery. There was no evidence of a dose-response relationship between cumulative whole-body dose ionizing radiation (lagged 5 years) and glaucoma, but some for surgically removed cataracts. Specifically, among workers with a cumulative exposure of greater than 50 mSv relative to those with an exposure of less than 0.25 mSv, the relative risks of incident glaucoma and cataract removal surgery were 0.91 (95% CI: 0.81-1.05) and 1.13 (95% CI: 0.97-1.33), respectively. The linear excess risks per 100 mSv (lagged 5 years) for cataract removal surgery was 0.055 (95% CI: -0.042 to 0.163). Our findings provide some evidence that ionizing radiation increases the risk of cataracts but not glaucoma in an occupational cohort whose lifetime cumulative dose rarely exceeded 30 mSv.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"271-283"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}