Low Dose Rate Irradiation Research Articles

Total Ionizing Dose Effect and Failure Mechanism of Digital Signal Processor

Ionizing radiation effect and failure mechanism of Digital signal processor (DSP) is studied through test-board and automatic test equipment to find the relationship between system function failure and parameter degradation. Static bias is more sensitive than dynamic bias when DSP is tested on-line during radiation. Core current, high-Z leakage current and timing parameter are sensitive to ionizing radiation. No enhanced low-dose-rate sensitivity is found by comparing experiment results under high and low dose rate radiation. External memory interface and Timer are deduced to be the sensitive module by step radiation and analysis basing full parameter test in Verigy 93000. The timing parameter degradation have a strong correlation to these module functions. And the degeneration mechanism is analysed on inverter through Hspice simulation which indicate the leakage circuit caused by radiation can lead a delay to the digital signal propagating. The parasitical capacitance among long connections make it worse to the data transmission around DSP, field programmable gate array and memory. Then an early function failure occurs in test board than Verigy 93000. This work provide support to systematic radiation hardness design and hardness assurance/lot acceptance testing in space applications.

Pulsed low-dose rate radiotherapy has an improved therapeutic effect on abdominal and pelvic malignancies.

Until now, there has been a lack of standard and effective treatments for patients with recurrent malignant tumors or abdominal and pelvic malignancies with extensive invasion (Morris, 2000). Generally, these patients face problems such as inability to undergo surgery or chemotherapy resistance (Combs et al., 2016). Re-radiotherapy has achieved a prominent place in the treatment of patients who have received radiotherapy previously and developed in-field recurrences (Straube et al., 2018). However, re-radiotherapy is very complicated, requiring comprehensive consideration of appropriate radiation dose, interval from first radiotherapy, boundary of the radiotherapy target area, and damage to surrounding normal tissues (Straube et al., 2019). In other words, it is necessary to focus on the protection of surrounding normal tissues while maximizing the efficacy of re-radiotherapy in such patients.

Perturbed transcriptional profiles after chronic low dose rate radiation in mice.

Adverse health outcomes of ionizing radiation given chronically at low dose rates are highly debated, a controversy also relevant for other stressors. Increased knowledge is needed for a more comprehensive understanding of the damaging potential of ionizing radiation from all dose rates and doses. There is a lack of relevant low dose rate data that is partly ascribed to the rarity of exposure facilities allowing chronic low dose rate exposures. Using the FIGARO facility, we assessed early (one day post-radiation) and late (recovery time of 100-200 days) hepatic genome-wide transcriptional profiles in male mice of two strains (CBA/CaOlaHsd and C57BL/6NHsd) exposed chronically to a low dose rate (2.5 mGy/h; 1200h, LDR), a mid-dose rate (10 mGy/h; 300h, MDR) and acutely to a high dose rate (100 mGy/h; 30h, HDR) of gamma irradiation, given to an equivalent total dose of 3 Gy. Dose-rate and strain-specific transcriptional responses were identified. Differently modulated transcriptional responses across all dose rate exposure groups were evident by the representation of functional biological pathways. Evidence of changed epigenetic regulation (global DNA methylation) was not detected. A period of recovery markedly reduced the number of differentially expressed genes. Using enrichment analysis to identify the functional significance of the modulated genes, perturbed signaling pathways associated with both cancer and non-cancer effects were observed, such as lipid metabolism and inflammation. These pathways were seen after chronic low dose rate and were not restricted to the acute high dose rate exposure. The transcriptional response induced by chronic low dose rate ionizing radiation suggests contribution to conditions such as cardiovascular diseases. We contribute with novel genome wide transcriptional data highlighting dose-rate-specific radiation responses and emphasize the importance of considering both dose rate, duration of exposure, and variability in susceptibility when assessing risks from ionizing radiation.

Comparison of 186Re to 662 keV photon radiation concerning biological radiation effect on the human B-cell line BV-173

Zellen der humanen Leukämie-Zelllinie BV-173 wurden mit 662keV-Photonenstrahlung respektive 186Re bestrahlt. In einem Inkubationszeitraum von 7 Tagen wurden Zahl und Vitalität der Zellen täglich bestimmt und als Dosiseffektkurven basierend auf der Vitalität dargestellt. Hierfür wurde der Zeitpunkt mit minimalem Überleben verwendet (72h 186Re und 24h Photonenstrahlung). Beide Strahlenarten zeigen am Auswertezeitpunkt (72h nach Versuchsbeginn für 186Re und 24h nach Versuchsbeginn für Photonenstrahlung) eine Überlebenskurve mit biexponentiellem Verlauf. Für Photonenstrahlung ist dies erklärbar durch eine Hypersensitivität im niedrigen Dosisbereich bis 1Gy, für die sich eine D0 von 3,3Gy ergibt, für Dosen über 1,0Gy liegt die D0 bei 10Gy. Für die 186Re-Inkubation ergibt sich eine D0 von 11,1Gy bei niedrigen Dosen verursacht durch die Reparatur subletaler Schäden, durch welche die biologische Wirkung abgeschwächt wird. Ab einer akkumulierten Dosis von etwa 1,6Gy zeichnet sich für 186Re ein wesentlich steilerer Kurvenverlauf mit einer D0 von 4,0Gy ab, der eine in diesem Bereich 2,5-fach stärkere biologische Wirkung als akute Photonenstrahlung wiedergibt (D0 4Gy für 186Re bzw. 10Gy für Photonen). Strahlung niedriger Dosisleistung zeigt eine geringere biologische Wirkung als eine akute Bestrahlung. Es existiert aber ein Grenzwert der akkumulierten Dosis, ab dem die biologische Wirkung von β-Strahlung die der Photonenstrahlung sogar übertrifft.

Late Radiation Related Brachial Plexopathy After Pulsed Reduced Dose Rate Reirradiation of an Axillary Breast Cancer Recurrence

Radiation induced brachial plexopathy (RIBP) is an unfortunate complication of radiation involving the axilla and supraclavicular fossa. This case report highlights development of RIBP in a patient 15 years after initial radiation and 11 years after pulsed low dose rate (PRDR) re-irradiation for recurrent disease. PRDR is a radiation technique believed to lower normal tissue toxicity due to improved sublethal intrafraction damage repair of these tissues at low radiation dose rates with good reported long term locoregional control in the re-irradiation setting. However, RIBP, as seen in this patient, is a devastating side effect of high dose radiation to this region, with no effective treatment options outside of symptom management and control. In this case, the patient has remained disease free following her recurrence but has had continued RIBP with minimal improvement using pentoxyfilline for management.

Evaluation of DNA damage and stress in wildlife chronically exposed to low-dose, low-dose rate radiation from the Fukushima Dai-ichi Nuclear Power Plant accident

The health effects associated with chronic low-dose, low-dose rate (LD-LDR) exposures to environmental radiation are uncertain. All dose-effect studies conducted outside controlled laboratory conditions are challenged by inherent complexities of ecological systems and difficulties quantifying dose to free-ranging organisms in natural environments. Consequently, the effects of chronic LD-LDR radiation exposures on wildlife health remain poorly understood and much debated. Here, samples from wild boar (Sus scrofa leucomystax) and rat snakes (Elaphe spp.) were collected between 2016 and 2018 across a gradient of radiation exposures in Fukushima, Japan. In vivo biomarkers of DNA damage and stress were evaluated as a function of multiple measurements of radiation dose. Specifically, we assessed frequencies of dicentric chromosomes (Telomere-Centromere Fluorescence in situ Hybridization: TC-FISH), telomere length (Telo-FISH, qPCR), and cortisol hormone levels (Enzyme Immunoassay: EIA) in wild boar, and telomere length (qPCR) in snakes. These biological parameters were then correlated to robust calculations of radiation dose rate at the time of capture and plausible upper bound lifetime dose, both of which incorporated internal and external dose. No significant relationships were observed between dicentric chromosome frequencies or telomere length and dose rate at capture or lifetime dose (p value range: 0.20–0.97). Radiation exposure significantly associated only with cortisol, where lower concentrations were associated with higher dose rates (r2 = 0.58; p < 0.0001), a relationship that was likely due to other (unmeasured) factors. Our results suggest that wild boar and snakes chronically exposed to LD-LDR radiation sufficient to prohibit human occupancy were not experiencing significant adverse health effects as assessed by biomarkers of DNA damage and stress.

Clinical Applications of Pulsed Low Dose-Rate Radiation Therapy

Clinical Applications of Pulsed Low Dose-Rate Radiation Therapy

Phase II study of combining immunotherapy and pulsed low dose rate radiotherapy for abdominal metastasis of gastric cancer.

e16099 Background: Immune-mediated responses against tumor antigens by checkpoint inhibitors (CPIs) may be enhanced by radiotherapy and the combination may hold therapeutic promise. Pulsed low dose rate radiotherapy (PLDR) is an effective strategy for abdominal tumor by taking advantage of low dose hyper-radiosensitivity with maximizing tumor response and minimizing adverse events by radiotherapy. In this phase II study, we prospectively analyzed the response and adverse events of the combination strategy of CPIs and PLDR for abdominal metastasis of gastric cancer. Methods: Eligibility criteria included pathologically confirmed advanced gastric adenocarcinoma with abdominal metastasis. Patients received XELOX regimen chemotherapy, anti-PD-1 toripalimab, and PLDR for abdominal metastasis, prescription dose was 50-56Gy/25-28f. The primary endpoint was objective response rate (ORR) and safety. Secondary endpoints were regional response rate (RRR) and regional controlled rate (RCR) for radiotherapy target tumor, progression-free survival (PFS), and overall survival (OS). Results: Between November 2018 and June 2020, 24 patients were enrolled and included in the efficacy analysis. 13 of them were first line therapy, and 11 of them were second line therapy. The ORR was 70.8% and the combination regimen were tolerable. The RRR was 83.3% and the RCR was 95.8%. The median PFS was 11.1 months and the median OS was not yet reached. Conclusions: In this phase II clinical trial, the combination of Immunotherapy and radiotherapy provided good response and toleration for abdominal metastasis of gastric cancer. It suggested clinical efficacy of this regimen in patients with advanced gastric cancer. Clinical trial information: NCT03061162.

Inter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise

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.

Influence of enhanced low dose rate sensitivity on single-event transient degradation in the LM158 bipolar operational amplifier

The synergistic effect of enhanced low dose rate sensitivity and single-event transients (SETs) in the bipolar dual operational amplifier LM158 is studied. The test results show a significant reduction in the SET amplitude and broadening in the SET waveform upon exposure to total ionizing dose radiation. These results are much more prominent for a low dose rate (LDR) irradiation of 0.01 rad(Si)/s than for a high dose rate irradiation of 10 rad(Si)/s. The greater gain degradation in the LM158 with LDR irradiation could be the direct cause of the reduction in the SET amplitude and broadening in the SET waveform, and this is corroborated through HSPICE simulations.

PO53: A Novel Unidirectional Permanent Device for Intraoperative Brachytherapy in Patients with Early Stage Lung Cancer Who Undergo Sub-Lobar Resection

Purpose: While complete surgical resection is considered standard of care for early stage lung cancer, many patients are unable to tolerate radical lung procedures due to poor cardiopulmonary function. In these patients, sub-lobar resection with radiotherapy may be a safe and efficacious compromise. Implanted brachytherapy at the time of surgery is highly conformal and may spare cardiopulmonary toxicity. The CivaSheet (CivaTech Oncology) is a planar, uni-directional device designed to deliver a therapeutic dose of low dose rate radiation.

Conclusions and Suggestions on Low-Dose and Low-Dose Rate Radiation Risk Estimation Methodology

Background: For radiological protection and control, the International Commission on Radiological Protection (ICRP) provides the nominal risk coefficients related to radiation exposure, which can be extrapolated using the excess relative risk and excess absolute risk obtained from the Life Span Study of atomic bomb survivors in Hiroshima and Nagasaki with the dose and dose-rate effectiveness factor (DDREF). Materials and Methods: Since it is impossible to directly estimate the radiation risk at doses less than approximately 100 mSv only from epidemiological knowledge and data, support from radiation biology is absolutely imperative, and thus, several national and international bodies have advocated the importance of bridging knowledge between biology and epidemiology. Because of the accident at the Tokyo Electric Power Company (TEPCO)’s Fukushima Daiichi Nuclear Power Station in 2011, the exposure of the public to radiation has become a major concern and it was considered that the estimation of radiation risk should be more realistic to cope with the prevailing radiation exposure situation. Results and Discussion: To discuss the issues from wide aspects related to radiological protection, and to realize bridging knowledge between biology and epidemiology, we have established a research group to develop low-dose and low-dose-rate radiation risk estimation methodology, with the permission of the Japan Health Physics Society. Conclusion: The aim of the research group was to clarify the current situation and issues related to the risk estimation of low-dose and low-dose-rate radiation exposure from the viewpoints of different research fields, such as epidemiology, biology, modeling, and dosimetry, to identify a future strategy and roadmap to elucidate a more realistic estimation of risk against low-dose and low-dose-rate radiation exposure.

Characterization of a novel large area microdosimeter system for low dose rate radiation environments

A feasibility study is presented on a newly developed microdosimetry system named Octobox, for its application in low dose rate, mixed radiation environments. A full characterization of the device was performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan, out-of-field of various heavy ion radiation fields — 290 MeV/u 12C, 230 MeV/u and 490 MeV/u 28Si and 400 MeV/u 20Ne ions, as well as a low dose rate 222Rn environment at the Australian Nuclear Sciences and Technology Organization (ANSTO). The device was shown to collect adequate statistics in a short period of time when compared to the MicroPlus probe with a single microdosimeter, while accurately measuring microdosimetric quantities and the corresponding average quality factor (Q¯) and dose equivalent (H) of the mixed radiation field. Good agreement of the microdosimetric spectra was also shown with Geant4 simulations for all presented ion fields. Based on the findings in this study, the Octobox is capable of being applied in mixed, low dose rate, radiation environments such as those encountered in space and aviation, as well as in underground mines for radiation protection purposes.

Low dose gamma irradiation attenuates cyclophosphamide-induced cardiotoxicity in rats: role of NF-κB signaling pathway

Purpose Cyclophosphamide (Cyp) is one of the most commonly used, wide spectrum chemotherapeutic agents. Cyp has multi-organ toxicities that are dose limiting, thus it’s mostly used in chemotherapeutic combinations. Radiation is well known as a hazardous sort of energy, recent studies are interested in studying the beneficial therapeutic effects of low-dose gamma radiation. This study examined the protective effect of two different doses/dose-rates of irradiation either alone or combined with telmisartan against Cyp-induced cardiotoxicity. Materials and methods Rats were divided into seven groups; (1): Control, (2): Cyp, (3–4): 0.05 Gy low dose rate (LDR) irradiation, 0.25 Gy high dose rate (HDR) irradiation, respectively, prior to Cyp dose, (5–7): telmisartan either alone or with 0.05 Gy LDR-irradiation or 0.25 Gy HDR-irradiation, respectively, prior to Cyp dose. The current investigation studied the effect of Cyp alone or combined with different treatment regimens on serum cTn-I and LDH, nuclear factor-κB (NF-κB) pathway (p65/IκB/IKK-α/IKK-ß) in the myocardium. Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were assessed in addition to histopathological examination of the heart. Results Low-dose irradiation attenuated cardiac enzymes, pro-inflammatory cytokines, NF-κB content, and histology, in both low and HDRs. Furthermore, the combination of low-dose irradiation with telmisartan (an angiotensin-II receptor type-1 blocker and a known cardio-protective drug) offered the best histological results. Conclusions Low-dose irradiation-induced amelioration is partially but not completely through canonical activation of NF-κB, and may have another atypical pathway. While telmisartan probably ameliorates NF-κB totally through canonical pathway.

Study on the uncertainty of passive area dosimetry systems for environmental radiation monitoring in the framework of the EMPIR “Preparedness” project

One of the objectives of the EMPIR project 16ENV04 “Preparedness” is the harmonization of methodologies for the measurement of doses with passive dosimetry systems for environmental radiation monitoring in the aftermath of a nuclear or radiological event. In such cases, measurements are often performed at low radiation dose rates, close to the detection limit of the passive systems.The parameters which may affect the dosimetric results of a passive dosimetry system are analyzed and four laboratories quantitatively evaluate the uncertainties of their passive dosimetry systems. Typical uncertainties of five dosimetric systems in four European countries are compared and the main sources of uncertainty are analyzed using the results of a questionnaire compiled for this specific purpose.To compute the characteristic limits of a passive dosimetry system according to standard ISO 11929, the study of the uncertainty of the system is the first step. In this work the uncertainty budget as well as the characteristic limits (decision thresholds and detection limits) are evaluated and the limitations and strengths of a complete analysis of all parameters are presented.

Striking effect of solute elements (Mn, Ni) on radiation-induced segregation/precipitation in iron-based model alloys

The evolution of radiation damage in steels is a major issue for the safe operation of nuclear power plants. Mn and Ni contribution to the formation and evolution of microstructural features remains a controversial issue. The present study aims at investigating their effects on microstructure by irradiating undersaturated BCC Fe-3.3at.%Ni and Fe-2.8at.%Mn model alloys. Two different ion irradiation conditions have been applied to study the effect of irradiation dose rate in both of these Fe-based alloys at a temperature of 673 K. In all cases, irradiation promotes the formation of dislocation loops. In the FeNi alloy, radiation-induced segregation is observed on loops, leading to precipitation of a FCC phase in the low dose rate irradiation condition only. In the case of FeMn, even if no precipitation was revealed, highly enriched decorated dislocation loops are observed, with a higher Mn segregation at radiation defects than Ni.

Morphological reproductive characteristics of testes and fertilization capacity of cryopreserved sperm after the Fukushima accident in raccoon (Procyon lotor).

Since the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, we have established an archive system of livestock and wild animals from the surrounding ex-evacuation zone. Wildlife within the alert zone have been exposed to low-dose-rate (LDR) radiation for a long continuous time. In this study, we analysed the morphological characteristics of the testes and in vitro fertilization (IVF) capacity of cryopreserved sperm of racoons from the ex-evacuation zone of the FDNPP accident. The radioactivity of caesium-137 (137 Cs) was measured by gamma-ray spectrometry, and the measured radioactivity concentration was 300-6,630Bq/kg in the Fukushima raccoons. Notably, normal spermatogenesis was observed in the seminiferous tubules of the testes, with the germinal epithelium composed of a spermatogenic cell lineage with no evident ultrastructural alterations; freeze-thawing sperm penetration ability was confirmed using the interspecific zona pellucida-free mouse oocytes IVF assays. This study revealed that the chronic and LDR radiation exposure associated with the FDNPP accident had no adverse effect on the reproductive characteristics and functions of male raccoons.

Radioprotective effect of melatonin against radiotherapy-induced cerebral cortex and cerebellum damage in rat

Purpose The present study aims to investigate the radioprotective effect of melatonin (MEL) against early period brain damage caused by different dose rate beams in the experimental rat model. Materials and methods Forty-eight Sprague Dawley rats were randomly divided into six groups; the control, only melatonin, low dose rate-radiotherapy (LDR-RT), high dose rate-radiotherapy (HDR-RT) groups and (LDR-RT) + MEL and (HDR-RT) + MEL radiotherapy plus melatonin groups. Each rat administered melatonin was given a dose of 10 mg/kg through intraperitoneal injection, 15 minutes before radiation exposure. The head and neck region of each rat in only radiotherapy and radiotherapy plus melatonin groups was irradiated with a single dose of 16 Gy in LDR-RT and HDR-RT beams. Rats in all groups were examined for histopathology and biochemistry analysis 10 days after radiotherapy. Results Comparing the findings for LDR-RT and HDR-RT only radiotherapy groups and the control group, there was a statistically significant difference in histopathological and biochemical parameters, however, melatonin administered in radiotherapy plus melatonin groups contributed improving these parameters (p < .05). There was no statistically significant difference between LDR-RT and HDR-RT beams (p > .05). Conclusions It was concluded that melatonin applied before LDR-RT and HDR-RT radiotherapy protected early period radiotherapy-induced brain damage. The effects of clinically low and high dose beams on the cerebral cortex and cerebellum were investigated histopathologically for the first time. HDR beams can be safely applied in brain radiotherapy. However, more experimental rat and clinical studies are needed to explain the radiobiological uncertainties about the clinic dose rate on different cancerous and healthy tissues.

Possible relationship between mitochondrial changes and oxidative stress under low dose-rate irradiation

ABSTRACT Objectives: High dose-rate ionizing radiation (IR) causes severe DSB damage, as well as reactive oxygen species (ROS) accumulation and oxidative stress. However, it is unknown what biological processes are affected by low dose-rate IR; therefore, the molecular relationships between mitochondria changes and oxidative stress in human normal cells was investigated after low dose-rate IR. Methods: We compared several cellular response between high and low dose-rate irradiation using cell survival assay, ROS/RNS assay, immunofluorescence and western blot analysis. Results: Reduced DSB damage and increased levels of ROS, with subsequent oxidative stress responses, were observed in normal cells after low dose-rate IR. Low dose-rate IR caused several mitochondrial changes, including morphology mass, and mitochondrial membrane potential, suggesting that mitochondrial damage was caused. Although damaged mitochondria were removed by mitophagy to stop ROS leakage, the mitophagy-regulatory factor, PINK1, was reduced following low dose-rate IR. Although mitochondrial dynamics (fission/fusion events) are important for the proper mitophagy process, some mitochondrial fusion factors decreased following low dose-rate IR. Discussion: The dysfunction of mitophagy pathway under low dose-rate IR increased ROS and the subsequent activation of the oxidative stress response.

Biological Effects of Low Dose and Low Dose Rate Irradiation

Biological Effects of Low Dose and Low Dose Rate Irradiation