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Reproductive Biology Dec 2023Low-dose radiation is generally considered less harmful than high-dose radiation. However, its impact on ovaries remains debated. Since previous reports predominantly...
Low-dose radiation is generally considered less harmful than high-dose radiation. However, its impact on ovaries remains debated. Since previous reports predominantly employed low-dose radiation delivered at a high dose rate on the ovary, the effect of low-dose radiation at a low dose rate on the ovary remains unknown. We investigated the effect of low-dose ionizing radiation delivered at a low dose rate on murine ovaries. Three- and ten-week-old mice were exposed to 0.1 and 0.5 Gy of radiation at a rate of 6 mGy/h and monitored after 3 and 30 days. While neither body weight nor ovarian area showed significant changes, ovarian cells were damaged, showing apoptosis and a decrease in cell proliferation after exposure to 0.1 and 0.5 Gy radiation. Follicle numbers decreased over time in both age groups proportionally to the radiation dose. Younger mice were more susceptible to radiation damage, as evidenced by decreased follicles in 3-week-old mice after 30 days of 0.1 Gy exposure, while 10-week-old mice showed reduced follicles only following 0.5 Gy exposure. Primordial or primary follicles were the most vulnerable to radiation. These findings suggest that even low-dose radiation, delivered at a low dose rate, can adversely affect ovarian function, particularly in the early follicles of younger mice.
Topics: Female; Mice; Animals; Ovarian Follicle; Ovary
PubMed: 37890397
DOI: 10.1016/j.repbio.2023.100817 -
Radiation and Environmental Biophysics Aug 2020Many experimental studies are carried out to compare biological effectiveness of high dose rate (HDR) with that of low dose rate (LDR). The rational for this is the...
Many experimental studies are carried out to compare biological effectiveness of high dose rate (HDR) with that of low dose rate (LDR). The rational for this is the uncertainty regarding the value of the dose rate effectiveness factor (DREF) used in radiological protection. While a LDR is defined as 0.1 mGy/min or lower, anything above that is seen as HDR. In cell and animal experiments, a dose rate around 1 Gy/min is usually used as representative for HDR. However, atomic bomb survivors, the reference cohort for radiological protection, were exposed to tens of Gy/min. The important question is whether gamma radiation delivered at very high dose rate (VHDR-several Gy/min) is more effective in inducing DNA damage than that delivered at HDR. The aim of this investigation was to compare the biological effectiveness of gamma radiation delivered at VHDR (8.25 Gy/min) with that of HDR (0.38 Gy/min or 0.79 Gy/min). Experiments were carried out with human peripheral mononuclear cells (PBMC) and the human osteosarcoma cell line U2OS. Endpoints related to DNA damage response were analysed. The results show that in PBMC, VHDR is more effective than HDR in inducing gene expression and micronuclei. In U2OS cells, the repair of 53BP1 foci was delayed after VHDR indicating a higher level of damage complexity, but no VHDR effect was observed at the level of micronuclei and clonogenic cell survival. We suggest that the DREF value may be underestimated when the biological effectiveness of HDR and LDR is compared.
Topics: Adult; Cell Line; Cesium Radioisotopes; DNA Damage; Dose-Response Relationship, Radiation; Female; Gamma Rays; Humans; Leukocytes, Mononuclear; Micronuclei, Chromosome-Defective; Radiation Protection; Relative Biological Effectiveness; Young Adult
PubMed: 32488310
DOI: 10.1007/s00411-020-00852-z -
Journal of Dairy Science Nov 2021Transition dairy cows experience a decline in immune function that increases the risk of peripartum disease. One strategy to improve peripartum immune function involves...
Transition dairy cows experience a decline in immune function that increases the risk of peripartum disease. One strategy to improve peripartum immune function involves the use of a commercially available cytokine: bovine granulocyte-colony stimulating factor, with the addition of polyethylene glycol to increase duration of effectiveness. Treatment with Imrestor (15 mg pegbovigrastim; Elanco) one week before expected calving date (d -7) and again on the day of calving (d 0) was previously reported to increase the neutrophil number and improve neutrophil function; as a result, the incidence of clinical mastitis was reduced. We conducted 2 experiments over consecutive years to investigate the effect of a lower dose rate (half or quarter dose rate) of Imrestor in grazing dairy cattle and reduced administration frequency: one dose instead of the recommended 2. White blood cell counts were measured to determine changes in relative cell populations in response to treatment. Neutrophil function was assessed by measuring myeloperoxidase activity. Imrestor treatment increased the numbers of neutrophils, band cells, lymphocytes, and monocytes until 14 d postcalving in a dose-dependent manner; it also increased neutrophil myeloperoxidase activity. One dose of Imrestor increased white blood cell counts and myeloperoxidase activity, but the timing, degree, and duration of the response were different relative to the recommended 2 doses and were also dependent upon when Imrestor treatment was given. One dose at d -7 relative to expected calving date did not have a lasting effect postcalving, whereas one dose only on d 0 caused a delayed effect relative to cows that received 2 doses. There was no effect of Imrestor on milk yield or on blood indicators of transition cow health. A lower dose rate of Imrestor or a single dose of Imrestor on the day of calving may be sufficient to improve neutrophil function during the early postpartum in grazing dairy cows. Large-scale field studies are required to determine whether the smaller response from lower dose rates or the timing of the immunological response to drug delivery affect animal health in early lactation.
Topics: Animals; Cattle; Female; Granulocyte Colony-Stimulating Factor; Lactation; Milk; Neutrophils; Recombinant Proteins
PubMed: 34419282
DOI: 10.3168/jds.2021-20630 -
Medical Physics Jun 2024Although the FLASH radiotherapy (FLASH) can improve the sparing of organs-at-risk (OAR) via the FLASH effect, it is generally a tradeoff between the physical dose...
BACKGROUND
Although the FLASH radiotherapy (FLASH) can improve the sparing of organs-at-risk (OAR) via the FLASH effect, it is generally a tradeoff between the physical dose coverage and the biological FLASH coverage, for which the concept of FLASH effective dose (FED) is needed to quantify the net improvement of FLASH, compared to the conventional radiotherapy (CONV).
PURPOSE
This work will develop the first-of-its-kind treatment planning method called simultaneous dose and dose rate optimization via dose modifying factor modeling (SDDRO-DMF) for proton FLASH that directly optimizes FED.
METHODS
SDDRO-DMF models and optimizes FED using FLASH dose modifying factor (DMF) models, which can be classified into two categories: (1) the phenomenological model of the FLASH effect, such as the FLASH effectiveness model (FEM); (2) the mechanistic model of the FLASH radiobiology, such as the radiolytic oxygen depletion (ROD) model. The general framework of SDDRO-DMF will be developed, with specific DMF models using FEM and ROD, as a demonstration of general applicability of SDDRO-DMF for proton FLASH via transmission beams (TB) or Bragg peaks (BP) with single-field or multi-field irradiation. The FLASH dose rate is modeled as pencil beam scanning dose rate. The solution algorithm for solving the inverse optimization problem of SDDRO-DMF is based on iterative convex relaxation method.
RESULTS
SDDRO-DMF is validated in comparison with IMPT and a state-of-the-art method called SDDRO, with demonstrated efficacy and improvement for reducing the high dose and the high-dose volume for OAR in terms of FED. For example, in a SBRT lung case of the dose-limiting factor that the max dose of brachial plexus should be no more than 26 Gy, only SDDRO-DMF met this max dose constraint; moreover, SDDRO-DMF completely eliminated the high-dose (V70%) volume to zero for CTV10mm (a high-dose region as a 10 mm ring expansion of CTV).
CONCLUSION
We have proposed a new proton FLASH optimization method called SDDRO-DMF that directly optimizes FED using phenomenological or mechanistic models of DMF, and have demonstrated the efficacy of SDDO-DMF in reducing the high-dose volume or/and the high-dose value for OAR, compared to IMPT and a state-of-the-art method SDDRO.
PubMed: 38873848
DOI: 10.1002/mp.17251 -
Clinical NeuropharmacologyThe objective of our study was to evaluate the relationship between the loading dose and efficacy of lacosamide (LCM), when used in seizure clusters (SCs).
PURPOSE
The objective of our study was to evaluate the relationship between the loading dose and efficacy of lacosamide (LCM), when used in seizure clusters (SCs).
METHODS
A cohort of patients with SC treated with intravenous (IV)-LCM between September 2017 and September 2019 was retrospectively examined. Demographic data, type of seizure emergency, etiology, response rate, previous oral antiepileptic drugs used, total LCM loading dose, and side effects were reviewed.
RESULTS
Thirty-nine cases of epileptic emergencies treated with IV LCM were collected. The mean age was 59.25 years (18-88 years), and the median loading dose was 136.5 mg (100-300 mg) with a response rate in the whole population of 29.2%. Nine patients received a loading dose of 200 to 300 mg, and their response rate was 89%. Common side effects (drowsiness and dizziness) were mild. No electrocardiogram changes or other cardiovascular side effects, or unexpected side effects were seen.
CONCLUSIONS
In adults with SC, a loading dose of IV LCM of 200 mg or more achieved 89% response rate in this cohort. Loading doses of less than 300 mg caused mild side effects only.
Topics: Acetamides; Adult; Anticonvulsants; Humans; Lacosamide; Middle Aged; Retrospective Studies; Seizures; Treatment Outcome
PubMed: 33811195
DOI: 10.1097/WNF.0000000000000445 -
Physics in Medicine and Biology Jun 2021Cancer radiotherapy (RT) with the irradiation at ultra-high dose rates, namely FLASH-RT, can substantially reduce radiation-induced normal tissue toxicities while...
Cancer radiotherapy (RT) with the irradiation at ultra-high dose rates, namely FLASH-RT, can substantially reduce radiation-induced normal tissue toxicities while maintaining tumor response. Currently, clinical FLASH-RT on deep-seated tumors can only be performed with proton beams. One way to achieve ultra-high dose rates at depth is through the use of high-energy transmission beams (TB), where the Bragg peaks (BP) fall outside the body. However, planning with TB alone does not fully leverage the degrees of freedom for dose shaping as traditional intensity modulated proton therapy (IMPT) which uses the BP of multi-energy proton beams at the tumor target. This work will develop a simultaneous dose and dose rate optimization (SDDRO) method with the joint use of TB and BP, namely SDDRO-Joint. Specifically, BP are placed inside tumor targets to improve the target dose conformality and sparse the normal-tissue dose, while TB primarily cover the tumor boundary to achieve ultra-high dose rate coverage of organs-at-risk (OAR) close to tumor targets. The sparing of OAR and other normal tissues via SDDRO-Joint is jointly by TB and BP, i.e. the FLASH sparing by TB and the dose sparing by BP. The results suggest that the addition of BP substantially increased the target dose conformality for SDDRO. Noticeably SDDRO-Joint also provided slightly higher conformal index values than the conventional IMPT method with BP alone.
Topics: Organs at Risk; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 34010818
DOI: 10.1088/1361-6560/ac02d8 -
Clinical Oncology (Royal College of... Mar 2020The management of high-risk prostate cancer is challenging, as patients have a high risk of both local and distant relapse. Although adjuvant systemic treatment remains... (Review)
Review
The management of high-risk prostate cancer is challenging, as patients have a high risk of both local and distant relapse. Although adjuvant systemic treatment remains an important component of management, for those receiving radiotherapy, optimal local treatment should include a brachytherapy boost. This may be given by low dose rate (LDR) or high dose rate (HDR) techniques, but HDR has several advantages over LDR by virtue of more consistent dose optimisation, ability to treat outside the prostate and lower toxicity. A significant body of evidence now supports the use of HDR brachytherapy in addition to supplementary pelvic external beam radiotherapy for men with high-risk disease. Consistent evidence has emerged from randomised clinical trials, meta-analyses, and from institutional and multicentre cohort studies. It has been shown to improve local disease control and possibly reduce metastases and improve cancer-specific survival compared with external beam radiotherapy alone. It should be considered as standard treatment.
Topics: Brachytherapy; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage
PubMed: 31791573
DOI: 10.1016/j.clon.2019.11.003 -
Journal of Applied Clinical Medical... Oct 2022Interventional cardiology involves catheter-based treatment of heart disease, generally through fluoroscopically guided interventional procedures. Patients can be...
Interventional cardiology involves catheter-based treatment of heart disease, generally through fluoroscopically guided interventional procedures. Patients can be subject to considerable radiation dose due to prolonged fluoroscopy time and radiographic exposure, and therefore efforts to minimize patient dose should always be undertaken. Developing standardized, effective quality control programs for these systems is a difficult task owing to cross-vendor differences and automated control of imaging protocols. Furthermore, analyses of radiation dose should be performed in the context of its associated effects on image quality. The aim of the study is to investigate radiation dose and image quality in two fluoroscopic systems used for interventional cardiology procedures. Image quality was assessed in terms of spatial resolution and modulation transfer function, signal-to-noise and contrast-to-noise ratios, and spatial-temporal resolution of fluoroscopy and cineradiography images with phantoms simulating various patient thicknesses under routine cardiology protocols. The entrance air kerma (or air kerma rate) was measured and used to estimate entrance surface dose (or dose rate) in the phantoms.
Topics: Humans; Radiation Dosage; Fluoroscopy; Phantoms, Imaging
PubMed: 35950644
DOI: 10.1002/acm2.13741 -
International Journal of Radiation... Jun 2022To investigate a plasmid DNA nicking assay approach for isolating and quantifying the DNA-damaging effects of ultrahigh-dose-rate (ie, FLASH) irradiation relative to...
PURPOSE
To investigate a plasmid DNA nicking assay approach for isolating and quantifying the DNA-damaging effects of ultrahigh-dose-rate (ie, FLASH) irradiation relative to conventional dose-rate irradiation.
METHODS AND MATERIALS
We constructed and irradiated phantoms containing plasmid DNA to nominal doses of 20 Gy and 30 Gy using 16 MeV electrons at conventional (0.167 Gy/s) and FLASH (46.6 Gy/s and 93.2 Gy/s) dose rates. We delivered conventional dose rates using a standard clinical Varian iX linear accelerator and FLASH dose rates (FDRs) using a modified Varian 21EX C-series linear accelerator. We ran the irradiated DNA and controls (0 Gy) through an agarose gel electrophoresis procedure that sorted and localized the DNA into bands associated with single strand breaks (SSBs), double strand breaks (DSBs), and undamaged DNA. We quantitatively analyzed the gel images to compute the relative yields of SSBs and DSBs and applied a mathematical model of plasmid DNA damage as a function of dose to compute the relative biological effectiveness (RBE) of SSB and DSB (RBE and RBE) damage for a given endpoint and FDR.
RESULTS
Both RBE and RBE were less than unity with the FDR irradiations, indicating FLASH sparing. With regard to the more deleterious DNA DSB damage, the DSB RBEs of FLASH beams at dose rates of 46.6 Gy/s and 93.2 Gy/s relative to the conventional 16 MeV beam dose rate were 0.54 ± 0.15 and 0.55 ± 0.17, respectively.
CONCLUSIONS
This study demonstrated the feasibility of using a DNA-based phantom to isolate and assess the FLASH sparing effect on DNA. We also found that FLASH irradiation causes less damage to DNA compared with a conventional dose rate. This result supports the notion that the protective effect of FLASH irradiation occurs at least partially via fundamental biochemical processes.
Topics: DNA; DNA Damage; Electrons; Humans; Particle Accelerators; Plasmids; Relative Biological Effectiveness
PubMed: 35124135
DOI: 10.1016/j.ijrobp.2022.01.049 -
Physics in Medicine and Biology Aug 2020Dose distributions have become more complex with the introduction of image-guided brachytherapy in high-dose-rate (HDR) brachytherapy treatments. Therefore, to correctly...
Dose distributions have become more complex with the introduction of image-guided brachytherapy in high-dose-rate (HDR) brachytherapy treatments. Therefore, to correctly execute HDR, conducting a quality assurance programme for the remote after-loading system and verifying the dose distribution in the patient treatment plan are necessary. The characteristics of the dose distribution of HDR brachytherapy are that the dose is high near the source and rapidly drops when the distance from the source increases. Therefore, a measurement tool corresponding to the characteristic is required. In this study, using an Iridium-192 (Ir-192) source, we evaluated the basic characteristics of a nanoclay-based radio-fluorogenic gel (NC-RFG) dosimeter that is a fluorescent gel dosimeter using dihydrorhodamine 123 hydrochloride as a fluorescent probe. The two-dimensional dose distribution measurements were performed at multiple source positions to simulate a clinical plan. Fluorescence images of the irradiated NC-RFG were obtained at a high resolution (0.04 mm pixel) using a gel scanner with excitation at 465 nm. Good linearity was confirmed up to a dose range of 100 Gy without dose rate dependence. The dose distribution measurement at the five-point source position showed good agreement with the treatment planning system calculation. The pass ratio by gamma analysis was 92.1% with a 2%/1 mm criterion. The NC-RFG dosimeter demonstrates to have the potential of being a useful tool for quality assurance of the dose distribution delivered by HDR brachytherapy. Moreover, compared with conventional gel dosimeters such as polymer gel and Fricke gel dosimeters it solves the problems of diffusion, dose rate dependence and inhibition of oxygen-induced reactions. Furthermore, it facilitates dose data to be read in a short time after irradiation, which is useful for clinical use.
Topics: Brachytherapy; Fluorescent Dyes; Gels; Humans; Iridium Radioisotopes; Radiation Dosage; Radiometry; Radiotherapy Dosage; Rhodamines
PubMed: 32485693
DOI: 10.1088/1361-6560/ab98d2