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Journal of Radiation Research Mar 2023While epidemiological data have greatly contributed to the estimation of the dose and dose-rate effectiveness factor (DDREF) for human populations, studies using animal... (Review)
Review
While epidemiological data have greatly contributed to the estimation of the dose and dose-rate effectiveness factor (DDREF) for human populations, studies using animal models have made significant contributions to provide quantitative data with mechanistic insights. The current article aims at compiling the animal studies, specific to rodents, with reference to the dose-rate effects of cancer development. This review focuses specifically on the results that explain the biological mechanisms underlying dose-rate effects and their potential involvement in radiation-induced carcinogenic processes. Since the adverse outcome pathway (AOP) concept together with the key events holds promise for improving the estimation of radiation risk at low doses and low dose-rates, the review intends to scrutinize dose-rate dependency of the key events in animal models and to consider novel key events involved in the dose-rate effects, which enables identification of important underlying mechanisms for linking animal experimental and human epidemiological studies in a unified manner.
Topics: Animals; Humans; Radiation Dosage; Neoplasms, Radiation-Induced; Risk Assessment; Radiation Exposure; Models, Animal; Liver; Lung; Hematopoietic System; Dose-Response Relationship, Radiation
PubMed: 36773331
DOI: 10.1093/jrr/rrad003 -
Journal of Radiation Research Sep 2021A microSilicon™ (PTW type 60023), a new unshielded diode detector succeeding Diode E (model 60017, PTW), was characterized for electron beam dosimetry and compared...
A microSilicon™ (PTW type 60023), a new unshielded diode detector succeeding Diode E (model 60017, PTW), was characterized for electron beam dosimetry and compared with other detectors. Electron beams generated from a TrueBeam linear accelerator were measured using the microSilicon, Diode E, and microDiamond synthetic single-crystal diamond detector. Positional accuracy of microSilicon was measured by data collected in air and water. The percent depth dose (PDD), off-center ratio (OCR), dose-response linearity, dose rate dependence, and cone factors were evaluated. The PDDs were compared with data measured using a PPC40 plane-parallel ionization chamber. The maximum variations of depth of 50% and 90% of the maximum dose, and practical depth among all detectors and energies were 0.9 mm. The maximum variations of the bremsstrahlung dose among all detectors and energies were within 0.3%. OCR showed good agreement within 1% for the flat and tail regions. The microSilicon detector showed a penumbra width similar to microDiamond, whereas Diode E showed the steepest penumbra shape. All detectors showed good dose-response linearity and stability against the dose rate; only Diode E demonstrated logarithmic dose rate dependency. The cone factor measured with microSilicon was within ±1% for all energies and cone sizes. We demonstrated that the characteristics of microSilicon is suitable for electron beam dosimetry. The microSilicon detector can be a good alternative for electron beam dosimetry in terms of providing an appropriate PDD curve without corrections, high spatial resolution for OCR measurements and cone factors.
PubMed: 34559877
DOI: 10.1093/jrr/rrab085 -
Emerging Infectious Diseases Jul 2022Despite extensive technological advances in recent years, objective and continuous assessment of physiologic measures after vaccination is rarely performed. We conducted... (Observational Study)
Observational Study
Despite extensive technological advances in recent years, objective and continuous assessment of physiologic measures after vaccination is rarely performed. We conducted a prospective observational study to evaluate short-term self-reported and physiologic reactions to the booster BNT162b2 mRNA (Pfizer-BioNTech, https://www.pfizer.com) vaccine dose. A total of 1,609 participants were equipped with smartwatches and completed daily questionnaires through a dedicated mobile application. The extent of systemic reactions reported after the booster dose was similar to that of the second dose and considerably greater than that of the first dose. Analyses of objective heart rate and heart rate variability measures recorded by smartwatches further supported this finding. Subjective and objective reactions after the booster dose were more apparent in younger participants and in participants who did not have underlying medical conditions. Our findings further support the safety of the booster dose from subjective and objective perspectives and underscore the need for integrating wearables in clinical trials.
Topics: BNT162 Vaccine; COVID-19; Humans; RNA, Messenger; Self Report; Vaccination
PubMed: 35654410
DOI: 10.3201/eid2807.212330 -
Neurosurgery Dec 2019Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further...
BACKGROUND
Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored.
OBJECTIVE
To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas.
METHODS
We retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression.
RESULTS
The study cohort included 227 patients with available follow-up. Following GKRS 2-yr and 4-yr clinical tumor control rates were 98% (95% CI: 95.6%-100%) and 96% (95% CI: 91.4%-99.6%), respectively. Among 177 patients with available radiographic follow-up, 2-yr and 4-yr radiographic progression-free survival rates were 97% (95% CI: 94.0%-100.0%) and 88% (95% CI: 81.2%-95.0%). The serviceable hearing preservation rate was 72.2% among patients with baseline Gardner-Robertson class I/II hearing and post-treatment audiological evaluations. Most patients experienced effective relief from prior headaches (94.7%), tinnitus (83.7%), balance issues (62.7%), FND (90.0%), and trigeminal nerve dysfunction (79.2%), but not hearing loss (1.0%). Whereas GKRS provided effective tumor control independently of dose rate, GKRS patients exposed to lower dose rates experienced significantly better freedom from post-treatment hearing loss and FND (P = .044).
CONCLUSION
Whereas GKRS provides excellent tumor control and effective symptomatic relief for vestibular schwannomas, dose-rate effects may impact post-treatment functional outcomes. Further research remains warranted.
Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Follow-Up Studies; Hearing; Hearing Loss; Hearing Tests; Humans; Male; Middle Aged; Neuroma, Acoustic; Radiation Dosage; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 31270543
DOI: 10.1093/neuros/nyz229 -
Medical Physics Sep 2022To provide ultrahigh dose rate (UHDR) pencil beam scanning (PBS) proton dosimetry comparison of clinically used plane-parallel ion chambers, PTW (Physikalisch-Technische...
PURPOSE
To provide ultrahigh dose rate (UHDR) pencil beam scanning (PBS) proton dosimetry comparison of clinically used plane-parallel ion chambers, PTW (Physikalisch-Technische Werkstaetten) Advanced Markus and IBA (Ion Beam Application) PPC05, with a proton graphite calorimeter in a support of first in-human proton FLASH clinical trial.
METHODS
Absolute dose measurement intercomparison of the plane-parallel plate ion chambers and the proton graphite calorimeter was performed at 5-cm water-equivalent depth using rectangular 250-MeV single-layer treatment plans designed for the first in-human FLASH clinical trial. The dose rate for each field was designed to remain above 60 Gy/s. The ion recombination effects of the plane-parallel plate ion chambers at various bias voltages were also investigated in the range of dose rates between 5 and 60 Gy/s. Two independent model-based extrapolation methods were used to calculate the ion recombination correction factors k to compare with the two-voltage technique from most widely used clinical protocols.
RESULTS
The mean measured dose to water with the proton graphite calorimeter across all the predefined fields is 7.702 ± 0.037 Gy. The average ratio over the predefined fields of the PTW Advanced Markus chamber dose to the calorimeter reference dose is 1.002 ± 0.007, whereas the IBA PPC05 chamber shows ∼3% higher reading of 1.033 ± 0.007. The relative differences in the k values determined from between the linear and quadratic extrapolation methods and the two-voltage technique for the PTW Advanced Markus chamber are not statistically significant, and the trends of dose rate dependence are similar. The IBA PPC05 shows a flat response in terms of ion recombination effects based on the k values calculated using the two-voltage technique. Differences in k values for the PPC05 between the two-voltage technique and other model-based extrapolation methods are not statistically significant at FLASH dose rates. Some of the k values for the PPC05 that were extrapolated from the three-voltage linear method and the semiempirical model were reported less than unity possibly due to the charge multiplication effect, which was negligible compared to the volume recombination effect in FLASH dose rates.
CONCLUSIONS
The absolute dose measurements of both PTW Advanced Markus and IBA PPC05 chambers are in a good agreement with the National Physical Laboratory graphite calorimeter reference dose considering overall uncertainties. Both ion chambers also demonstrate good reproducibility as well as stability as reference dosimeters in UHDR PBS proton radiotherapy. The dose rate dependency of the ion recombination effects of both ion chambers in cyclotron generated PBS proton beams is acceptable and therefore, both chambers are suitable to use in clinical practice for the range of dose rates between 5 and 60 Gy/s.
Topics: Clinical Protocols; Graphite; Humans; Protons; Radiometry; Reproducibility of Results; Water
PubMed: 35780318
DOI: 10.1002/mp.15844 -
Scientific Reports May 2024The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We...
The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DR)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8-12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DR). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.
PubMed: 38773165
DOI: 10.1038/s41598-024-62148-2 -
Gels (Basel, Switzerland) Apr 2023Tetrazolium salts provide an appealing candidate for 3D gel dosimeters as they exhibit a low intrinsic color, no signal diffusion and excellent chemical stability....
Tetrazolium salts provide an appealing candidate for 3D gel dosimeters as they exhibit a low intrinsic color, no signal diffusion and excellent chemical stability. However, a previously developed commercial product (the ClearView 3D Dosimeter) based on a tetrazolium salt dispersed within a gellan gum matrix presented a noticeable dose rate effect. The goal of this study was to find out whether ClearView could be reformulated in order to minimize the dose rate effect by optimizing of the tetrazolium salt and gellan gum concentrations and by the addition a thickening agent, ionic crosslinkers, and radical scavengers. To that goal, a multifactorial design of experiments (DOE) was conducted in small-volume samples (4-mL cuvettes). It showed that the dose rate could be effectively minimized without sacrificing the integrity, chemical stability, or dose sensitivity of the dosimeter. The results from the DOE were used to prepare candidate formulations for larger-scale testing in 1-L samples to allow for fine-tuning the dosimeter formulation and conducting more detailed studies. Finally, an optimized formulation was scaled-up to a clinically relevant volume of 2.7 L and tested against a simulated arc treatment delivery with three spherical targets (diameter 3.0 cm), requiring different doses and dose rates. The results showed excellent geometric and dosimetric registration, with a gamma passing rate (at 10% minimum dose threshold) of 99.3% for dose difference and distance to agreement criteria of 3%/2 mm, compared to 95.7% in the previous formulation. This difference may be of clinical importance, as the new formulation may allow the quality assurance of complex treatment plans, relying on a variety of doses and dose rates; thus, expanding the potential practical application of the dosimeter.
PubMed: 37102946
DOI: 10.3390/gels9040334 -
International Journal of Molecular... Nov 2021The adverse effects of radiation are proportional to the total dose and dose rate. We aimed to investigate the effects of radiation dose rate on different organs in...
The adverse effects of radiation are proportional to the total dose and dose rate. We aimed to investigate the effects of radiation dose rate on different organs in mice. The mice were subjected to low dose rate (LDR, ~3.4 mGy/h) and high dose rate (HDR, ~51 Gy/h) radiation. LDR radiation caused severe tissue toxicity, as observed in the histological analysis of testis. It adversely influenced sperm production, including sperm count and motility, and induced greater sperm abnormalities. The expression of markers of early stage spermatogonial stem cells, such as Plzf, c-Kit, and Oct4, decreased significantly after LDR irradiation, compared to that following exposure of HDR radiation, in qPCR analysis. The compositional ratios of all stages of spermatogonia and meiotic cells, except round spermatid, were considerably reduced by LDR in FACS analysis. Therefore, LDR radiation caused more adverse testicular damage than that by HDR radiation, contrary to the response observed in other organs. Therefore, the dose rate of radiation may have differential effects, depending on the organ; it is necessary to evaluate the effect of radiation in terms of radiation dose, dose rate, organ type, and other conditions.
Topics: Animals; Dose-Response Relationship, Radiation; Gamma Rays; Male; Mice; Models, Animal; Radiation Dosage; Spermatids; Spermatogenesis; Spermatogonia; Spermatozoa; Testis
PubMed: 34884637
DOI: 10.3390/ijms222312834 -
Radiation Protection Dosimetry Oct 2022External dose rates were measured 1 m away from 230 Lu-177 patients to characterise the variability in normalised dose rates as a function of administered activity,...
External dose rates were measured 1 m away from 230 Lu-177 patients to characterise the variability in normalised dose rates as a function of administered activity, body mass index (BMI) and sex. The largest dose rate observed was 0.07 mSv/h associated with an administered activity of 7.2 GBq. Substantial variability was found in the distribution of the normalised dose rate associated that had an average of 0.0037 mSv/h per GBq and a 95% confidence interval of 0.0024-0.0058 mSv/h per GBq. Based on this study, estimating the patient dose rate based on the Lu-177 gamma exposure factor overestimates the dose rate by a factor of 2. A statistically significant inverse relationship was found between the patient dose rate and patient BMI and an empirically derived equation relating these two quantities was reported. On average, male patient dose rates were 3.5% lower than female dose rates, which may be attributed to the larger average BMI of the male patient group.
Topics: Humans; Male; Female; Lutetium; Radioisotopes; Body Mass Index; Cohort Studies
PubMed: 36138119
DOI: 10.1093/rpd/ncac187 -
Antioxidants (Basel, Switzerland) Jan 2023Low dose-rate radiation exposure can occur in medical imaging, as background from environmental or industrial radiation, and is a hazard of space travel. In contrast...
Low dose-rate radiation exposure can occur in medical imaging, as background from environmental or industrial radiation, and is a hazard of space travel. In contrast with high dose-rate radiation exposure that can induce acute life-threatening syndromes, chronic low-dose radiation is associated with Chronic Radiation Syndrome (CRS), which can alter environmental sensitivity. Secondary effects of chronic low dose-rate radiation exposure include circulatory, digestive, cardiovascular, and neurological diseases, as well as cancer. Here, we investigated 1-2 Gy, 0.66 cGy/h, Co radiation effects on primary human mesenchymal stem cells (hMSC). There was no significant induction of apoptosis or DNA damage, and cells continued to proliferate. Gene ontology (GO) analysis of transcriptome changes revealed alterations in pathways related to cellular metabolism (cholesterol, fatty acid, and glucose metabolism), extracellular matrix modification and cell adhesion/migration, and regulation of vasoconstriction and inflammation. Interestingly, there was increased hypoxia signaling and increased activation of pathways regulated by iron deficiency, but Nrf2 and related genes were reduced. The data were validated in hMSC and human lung microvascular endothelial cells using targeted qPCR and Western blotting. Notably absent in the GO analysis were alteration pathways for DNA damage response, cell cycle inhibition, senescence, and pro-inflammatory response that we previously observed for high dose-rate radiation exposure. Our findings suggest that cellular gene transcription response to low dose-rate ionizing radiation is fundamentally different compared to high-dose-rate exposure. We hypothesize that cellular response to hypoxia and iron deficiency are driving processes, upstream of the other pathway regulation.
PubMed: 36829800
DOI: 10.3390/antiox12020241