International journal of radiation biology最新文献

Purpose: Phosphorylation of the histone H2AX (γ-H2AX) is a rapid response to radiation-induced DNA double strand breaks (DSBs) and is a good biomarker for exposure to ionizing radiation. The signal has traditionally been detected by microscopy (spot counting) or by flow cytometry (fluorescent intensity). An imaging flow cytometry (IFC) method has been developed, which combines the high resolution of microscopy with the statistical power of flow cytometry methods to measure γ-H2AX in human lymphocytes.

Materials and methods: The assay was optimized and validated for both sample acquisition and data analysis, in the dose range of 0-10 Gy. For data analysis, mean fluorescence intensity (MFI), spot count (foci per cell), and average area of the spots were used with the supervised machine learning (SML) K-Nearest Neighbors (K-NN) algorithm to estimate doses. These dose estimates were compared to the traditional flow cytometry method of estimating doses from an MFI-based dose response curve.

Results: A statistical analysis of both methodologies showed that SML K-NN method was able to determine the dose delivered to blind, irradiated samples more accurately than when using a linear fit of the MFI response alone, especially in the 7-10 Gy dose range.

Conclusions: The efficiency of the γ-H2AX-IFC assay, 1 hour post-exposure, has been improved and validated using the SML K-NN methodology for dose estimation. This study could help establish the γ-H2AX assay as a triage tool for the rapid screening of a large number of samples.

Purpose: To apply electron spin resonance (ESR) dosimetry to wild Japanese macaques captured in the ex-evacuation area during the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, the improvement of the detection limit is crucial. In this study, we optimized the microwave power in ESR measurements to suppress the noise of native radicals and enhanced the signals of radiation-induced carbonate radicals.

Materials and methods: Tooth enamels of a Japanese macaque captured in a control area were prepared and irradiated with gamma rays from ⁶⁰Co source. The ESR spectra of the enamel samples with different absorbed doses ranging from 0 to 1800 mGy were measured with varying microwave power. The ESR spectra were analyzed by an in-house multi-component decomposition code using a simulated annealing method.

Results: Intensities of both components originating from carbonate and native radicals saturated and decayed as the microwave power increased. The intensity ratio of carbonate radicals to native radicals, i.e., signal to noise ratio, increased monotonically at microwave powers below 30 mW. We also examined the linearity of the intensity of carbonate radicals against the absorbed doses and recommended a microwave power range of 5-25 mW.

Conclusion: In this study, we showed that optimizing the microwave power is an effective way to improve the quantitation accuracy of carbonate radicals in samples with low absorbed doses. The improved measurement conditions will expand the applicable range of ESR dosimetry for research on the effects of radiation on wild animals related to the FDNPP accident.

Purpose: This paper characterizes types of biodosimetric tools used for response and treatment in a large-scale nuclear event. Using US official documents to define dangerous zones and centers for triage and treatment, the types of biodosimetry needed in various circumstances, based on likely volumes, types of radiation and extent of combined injuries of people arriving at different center locations, are defined.

Conclusions: Appropriate biodosimetry methods should consider the type of radiation received (predominantly prompt mixed gamma-neutron irradiation or gamma rays from fallout), probability of physical injury/burns, the likelihood of receiving a significant dose, and the location and number of likely victims. The types of parameters needed for using biodosimetric techniques most effectively in a nuclear event, including for methods to be developed, are denoted for seven distinct situations that would occur with a large-scale nuclear event. The analysis leads to the conclusion that the benefit of using qualitative biodosimetry for stage 1 triage of people who were in dangerous zones is low and not recommended in a nuclear detonation. For this cohort, stage 2 triage will be very important but the type of biodosimetry depends on whether the irradiation occurred immediately or from fallout, because anyone from the detonation zones would more likely have physical injuries and/or burns and have received neutron exposures. Biodosimetry in stage 3 (medical care) would have only a modest role. Biodosimetry for people nearby but outside of the detonation and fallout zones requires a different approach, perhaps also benefitting from new methods.

Purpose: The development of AI-assisted biodosimetry systems brings significant advances in cytogenetic dosimetry. The introduction of deep learning algorithms has improved the accuracy and speed of chromosome detection and classification in input images, addressing the incomplete reproducibility and time-consuming of manual evaluation. An advanced molecular cytogenetic technique, PNA-FISH, has further improved the clarity and reliability of chromosome identification. We have been developing a deep learning algorithm to automate the detection of chromosomal aberrations in PNA-FISH images, resulting in a more efficient approach to dose assessment, particularly in large-scale nuclear disasters.

Conclusion: Integrating AI-assisted biodosimetry systems into the cooperative framework among Advanced Radiation Emergency Medical Support Centers in Japan is expected to support dose assessment in the events of nuclear disasters with mass casualties. However, there are still challenges in the integration of the system into our cooperative framework. Temperature management during blood transport is crucial to prevent coagulation and ensure adequate lymphocyte counts. To improve performance of our AI model, it is necessary to standardize experimental procedures for chromosome image preparations among network members and to further train the learning model. The development of secure and convenient data sharing system is also essential to improve the integrated and practical operation of the network and reduce its running costs. Additionally, development of a user-friendly interface is helpful for all the network members to operate the AI model. We will continue to develop web-based applications for AI-based biodosimetry by considering these requirements to enhance the effectiveness of the biodosimetry network of Japan.

Purpose: Cytogenetic biodosimetry of the Partial Body Irradiation (PBI) requires a dose response curve (DRC) for chromosome aberrations (ChA) but also an exponential coefficient D₀ of the interphase cell survival (ICS) of irradiated lymphocytes. The aim of the present work was to construct joint DRCs in vitro for ChA and ICS and validate them in a setting with a limited number of blood donors.

Materials & methods: Blood samples from three healthy volunteers were irradiated in vitro with 6 MV Linac photons to a range of acute doses up to 5.46 Gy. Cytogenetic preparations were stained with Fluorescence-plus-Giemsa; ChA were scored in the first division metaphases. The ICS was assessed in PBI simulations, mixing irradiated and unirradiated blood 1:1 at each dose point; D₀ was estimated by regression analysis.

Results: The DRC for dicentrics had linear and quadratic coefficients, respectively, 0.031 × cell^-1 × Gy^-1 and 0.070 × cell^-1 × Gy^-2; for dicentrics plus centric rings - respectively, 0.033 × cell^-1 × Gy^-1 and 0.083 × cell^-1 × Gy^-2. The ICS parameter D₀ varied within 3.18 - 3.54 Gy, depending on the end-point used for the assessment. DRCs were successfully validated in a biodosimetry exercise with uniform irradiation and PBI simulations in vitro and using in vivo data from four breast cancer patients after their first radiotherapy dose fraction.

Conclusions: Generating joint DRCs for ChA and ICS in a single experiment can be recommended as a rational methodology for laboratories practicing cytogenetic biodosimetry.

Purpose: Dr. Richard Hill performed pioneering work in the field of radiation-induced normal tissue injury to the lung including noninvasive imaging studies aimed at identifying imaging biomarkers of radiation-induced lung injury (RILI). RILI is a life-threatening toxicity of radiation exposure relevant to both cancer patients undergoing thoracic radiation therapy (RT) and victims of accidental radiation exposure. The ability to detect RILI noninvasively has the potential to guide treatment planning for RT and, in the case of victims of acute radiation exposures, inform the decision to start mitigative therapies. As part of this special issue of IJRB honoring Dr. Hill's many contributions to the field of radiation biology, this article reviews current advances in noninvasive imaging of RILI including computed tomography (CT), magnetic resonance (MR), hyperpolarized MR, nuclear medicine (PET and SPECT), and optical imaging with near-infrared (NIR) probes. Conclusion: The imaging modalities reviewed have potential to not only provide early identification of RILI but may also provide mechanistic insights into the progression of RILI via noninvasive detection of characteristic RILI mechanisms including: inflammation, vascular damage, cell death, oxidative stress, and fibrosis.

Purpose: Optimization of automated dicentric evaluation in the BIR laboratory is necessary to improve and accelerate individual biological dosimetry in radiation accident scenarios. Therefore, two different DCScore classifiers were analyzed for their suitability for use with laboratory-specific protocols, including two different lymphocyte culture conditions, 3-hour or 24-hour colcemid treatment.

Materials and methods: Dicentric formation was compared in 3 h and 24 h colcemid-treated cultures by fully- and semi-automated dicentric scoring using two different classifiers. Various calibration curves were constructed and absorbed doses of blinded X-irradiated blood samples were estimated after 24 h of colcemid treatment using both classifiers and scoring modes.

Results: 24 h colcemid treatment results in twice as many metaphases as 3 h colcemid treatment and the courses of dicentric frequencies after short- and long-term colcemid treatment differ, especially > 1 Gy. The "short-term colcemid classifier" detects more dicentric candidates and true positive dicentrics, respectively, especially > 2 Gy than the "long-term classifier" on the same slides.

Conclusion: Neither classifier was significantly better suited for the lab-specific MP preparations with regard to triage dose estimates for blinded samples by fully- as well as semi-automated analysis. For accurate dose assessment, it is recommended to adapt an available classifier to laboratory-specific conditions and protocols to optimize the identification of true dicentrics by DCScore.

Purpose: The aim of this study is to investigate the stability of radiation-induced electron paramagnetic resonance (EPR) signals in sorbitol and to determine the spectroscopic characteristics of the radiation-induced radicals in sorbitol.

Materials and methods: Sorbitol samples were irradiated at 10 Gy using a 6 MV X-ray beam of medical linear accelerator (LINAC). EPR measurements were carried out using X-band (Bruker ESR5000X, and EMX-131) and Q-band (Bruker EMXplus) spectrometers. Isochronal and isothermal annealing experiments, as well as fading experiments, were carried out to assess the stability of radiation-induced signals. EasySpin simulation software was used to determine the spectroscopic and structural parameters of the radiation-induced radicals.

Results: The EPR spectrum of irradiated sorbitol consists of several overlapping components produced by stable and unstable radicals. X- and Q-band measurements revealed significant changes in the signal patterns during time fading and thermal annealing experiments. High-temperature annealing caused rapid decay of the unstable radicals, leaving behind a stable radical. Simulation calculations indicated that at least three components were required to reproduce the observed EPR spectra. Spectroscopic parameters derived from simulations showed consistent agreement across the different experimental conditions.

Conclusion: Sorbitol shows promising characteristics as an EPR dosimeter, with radiation-induced radicals exhibiting distinct thermal and time stability. High-temperature annealing can eliminate unstable radicals, enabling reliable dosimetric application shortly after irradiation. The identified stable radical is a promising marker for dose quantification. These findings support the feasibility of using sorbitol for retrospective and accidental dosimetry.

Purpose: Our prior results showed that in the most cases, radiation doses measured by electron paramagnetic resonance (EPR) in tooth enamel samples significantly exceeded worksite reported doses. In an effort to understand causes of this discrepancy, we carried out EPR dose measurements in additional tooth samples collected from individuals studied before.

Materials and methods: Tooth enamel samples from five tissue donors to the United States Transuranium and Uranium Registries were used in this study. EPR measurements were performed using ELEXYS 500 spectrometer and high purity germanium detectors were used to measure gamma-emitting radionuclides.

Results: Significant variation of the EPR measured doses among multiple teeth collected from the same individuals was observed. These variations are potentially due to an additional exposure of the head/neck region as compared to the other parts of the body, e.g. torso where personal dosimeters are typically worn. The latter could explain very significant discrepancy of the doses, derived from EPR measurements and reported by worksites. With gamma-spectroscopy, no ¹³⁷Cs was detected in tooth roots.

Conclusions: In several cases there was nonuniform exposure of the head of the teeth' donors which may explain the discrepancy between worksite reported and EPR reconstructed doses. Results of the gamma counting suggested that exposure from ¹³⁷Cs in the roots was not a factor in the observed discrepancy.

Purposes: Hadrontherapy with proton and carbon ion scanning beams is an advanced radiation treatment modality mainly exploiting the finite range of those particles in the matter, to better spare critical organs close to the tumor volume as compared to photons. However, its complexity requires careful management of dosimetric uncertainties to guarantee patient safety. This study aims to reassess the suitability of alanine-based dosimetry for modern hadrontherapy applications.

Materials and methods: Alanine pellets based on electron spin resonance (ESR) were used as dosimeters. The response was taken from the peak-to-peak amplitude and compared to the ionization chamber one. Dose response and dependence on energy, beam direction, and linear energy transfer (LET), for both pristine Bragg peak and spread-out Bragg peak (SOBP) were evaluated. The ESR ratio x/y was evaluated as a function of LET and microwave power. Photon irradiations were performed with a 6 MV linear accelerator at the San Matteo Hospital, while with charged particles at CNAO, both located in Pavia, Italy.

Results: Alanine showed a linear dose-response for both protons and carbon ions in the range of 10-45 Gy. For carbon ions, a pronounced quenching effect in the Bragg peak and energy dependence were observed. Alanine effectiveness was reduced by up to 30% due to LET effects. Moreover, the use of the x/y ratio showed potential for LET differentiation.

Conclusions: Alanine may be a promising dosimeter for hadrontherapy. However, further studies are required to investigate factors of correction due to the effects of LET and energy dependence.