Large-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples were exposed to an Iridium-192 source (1.36 TBq, Tech-Ops 880 Sentinal) at varying distances and geometries. This resulted in protracted doses ranging between 0.2 and 2.4 Gy using dose rates of 1.5–40 mGy/min and exposure times of 1 or 2.5 h. Blood samples were exposed in thermo bottles that maintained temperatures between 39 and 27.7 °C. After exposure, EDTA-blood samples were transferred into PAXGene tubes to preserve RNA. RNA was isolated in one laboratory and aliquots of four blinded RNA were sent to another five teams for dose estimation based on gene expression changes. Using an X-ray machine, samples for two calibration curves (first: constant dose rate of 8.3 mGy/min and 0.5–8 h varying exposure times; second: varying dose rates of 0.5–8.3 mGy/min and 4 h exposure time) were generated for distribution. Assays were run in each laboratory according to locally established protocols using either a microarray platform (one team) or quantitative real-time PCR (qRT-PCR, five teams). The qRT-PCR measurements were highly reproducible with coefficient of variation below 15% in ≥ 75% of measurements resulting in reported dose estimates ranging between 0 and 0.5 Gy in all samples and in all laboratories. Up to twofold reductions in RNA copy numbers per degree Celsius relative to 37 °C were observed. However, when irradiating independent samples equivalent to the blinded samples but increasing the combined exposure and incubation time to 4 h at 37 °C, expected gene expression changes corresponding to the absorbed doses were observed. Clearly, time and an optimal temperature of 37 °C must be allowed for the biological response to manifest as gene expression changes prior to running the gene expression assay. In conclusion, dose reconstructions based on gene expression measurements are highly reproducible across different techniques, protocols and laboratories. Even a radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min) can be identified. These results demonstrate the importance of the incubation conditions and time span between radiation exposure and measurements of gene expression changes when using this method in a field exercise or real emergency situation.
Objectives: With the aging population and thus rising numbers of orthopedic implants (OIs), metal artifacts (MAs) increasingly pose a problem for computed tomography (CT) examinations. In the study presented here, different MA reduction techniques (iterative metal artifact reduction software [iMAR], tin prefilter technique, and dual-energy CT [DECT]) were compared. Materials and Methods: Four human cadaver pelvises with OIs were scanned on a third-generation DECT scanner using tin prefilter (Sn), dual-energy (DE), and conventional protocols. Virtual monoenergetic CT images were generated from DE data sets. Postprocessing of CT images was performed using iMAR. Qualitative (bony structures, MA, image noise) image analysis using a 6-point Likert scale and quantitative image analysis (contrast-to-noise ratio, standard deviation of background noise) were performed by 2 observers. Statistical testing was performed using Friedman test with Nemenyi test as a post hoc test. Results: The iMAR Sn 150 kV protocol provided the best overall assessability of bony structures and the lowest subjective image noise. The iMAR DE protocol and virtual monochromatic image (VMI) ± iMAR achieved the most effective metal artifact reduction (MAR) (P < 0.05 compared with conventional protocols). Bony structures were rated worse in VMI ± iMAR (P < 0.05) than in tin prefilter protocols ± iMAR. The DE protocol ± iMAR had the lowest contrast-to-noise ratio (P < 0.05 compared with iMAR standard) and the highest image noise (P < 0.05 compared with iMAR VMI). The iMAR reduced MA very efficiently. Conclusions: When considering MAR and image quality, the iMAR Sn 150 kV protocol performed best overall in CT images with OI. The iMAR generated new artifacts that impaired image quality. The DECT/VMI reduced MA best, but experienced from a lack of resolution of bony fine structures.
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In a nuclear or radiological event, an early diagnostic or prognostic tool is needed to distinguish unexposed from low-and highly-exposed individuals with the latter requiring early and intensive medical care. Radiation-induced gene expression (GE) changes observed within hours and days after irradiation have shown potential to serve as biomarkers for either dose reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of GE markers lies in their capability for early (1-3 day after irradiation), high-throughput, and point-of-care diagnosis required for the prediction of the acute radiation syndrome (ARS). ConclusionsAs a key session of the ConRad conference in 2021, experts from different institutions were invited to provide state-of-the-art information on a range of topics including: (1) Biodosimetry: What are the current efforts to enhance the applicability of this method to perform retrospective biodosimetry? (2) Effect Prediction: Can we apply radiation-induced GE changes for prediction of acute health effects as an approach, complementary to and integrating retrospective dose estimation? (3) High-throughput and Point-of-Care Diagnostics: What are the current developments to make the GE approach applicable as a high-throughput as well as a point-of-care diagnostic platform? (4) Low Level Radiation: What is the lowest dose range where GE can be used for biodosimetry purposes? (5) Methodological Considerations: Different aspects of radiation-induced GE related to more detailed analysis of exons, transcripts and next-generation sequencing (NGS) were reported.
Radiation-induced biological changes occurring within hours and days after irradiation can be potentially used for either exposure reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of molecular protein or gene expression (GE) (mRNA) marker lies in their capability for early (1–3 days after irradiation), high-throughput and point-of-care diagnosis, required for the prediction of the acute radiation syndrome (ARS) in radiological or nuclear scenarios. These molecular marker in most cases respond differently regarding exposure characteristics such as e.g. radiation quality, dose, dose rate and most importantly over time. Changes over time are in particular challenging and demand certain strategies to deal with. With this review, we provide an overview and will focus on already identified and used mRNA GE and protein markers of the peripheral blood related to the ARS. These molecules are examined in light of ‘ideal’ characteristics of a biomarkers (e.g. easy accessible, early response, signal persistency) and the validation degree. Finally, we present strategies on the use of these markers considering challenges as their variation over time and future developments regarding e.g. origin of samples, point of care and high-throughput diagnosis.
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