Rapid population biological dose evaluation system used under large-scale ionizing radiation exposure condition

Abstract

The invention relates to the technical field of nuclear radiation evaluation, in particular to a rapid population biological dose evaluation system used under the condition of large-scale ionizing radiation exposure. According to the rapid evaluation method, the analysis efficiency can be improved, the dose can be accurately estimated, and the rapid and effective method can replace manual DCA dose estimation. The method and the curve can be potentially applied to a triage mode and serve as an alternative scheme for manual analysis under large-scale radioactive events, and rapid dose evaluation is achieved.

Description

Technical Field

[0001] This invention relates to the field of nuclear radiation assessment technology, and in particular to a rapid biological dose assessment system for populations under large-scale ionizing radiation exposure. Background Technology

[0002] With the rapid development of nuclear energy and nuclear technology utilization, the possibility of large-scale ionizing radiation exposure has increased. Radiation dose estimation is of great significance for health risk assessment and treatment planning for overexposed populations.

[0003] Currently, the internationally recognized "gold standard" method for assessing biodosimetry is based on the analysis of chromosomal aberrations in human peripheral blood lymphocytes, especially the detection of dicentric chromosome assays (DCA). Dicentric chromosomes are radiation-induced, highly specific, and dose-dependent unstable chromosomal aberrations with an extremely low spontaneous frequency in the normal population, and are therefore considered the most reliable biodosimetric marker.

[0004] However, traditional dicentric chromosome analysis methods have significant limitations in practical applications, especially for rapid assessment of large populations: First, these methods heavily rely on manual microscopic examination by skilled technicians. The examiner observes, identifies, and counts dicentric chromosomes cell by cell under a microscope, a process that is extremely time-consuming and labor-intensive, with very low throughput; a skilled technician can analyze only dozens to hundreds of cells per day. When faced with hundreds or thousands of samples, traditional manual methods cannot meet the time requirements for rapid response. Second, the accuracy and consistency of manual analysis are limited by the operator's experience and subjective judgment, potentially leading to missed detections or misjudgments, affecting the accuracy of dosage estimation.

[0005] To improve analytical efficiency, automated chromosome scanning and image analysis systems (such as the Metafer platform) have been introduced into this field. These systems can automatically locate metaphase, acquire images, and use algorithms to initially identify dicentric chromosomes. However, current technology indicates that automated identification has a high false-positive rate; the system may misclassify closely contacting chromosomes, crossed chromosomes, monosomy breaks, or other complex conformations as dicentric chromosomes. Directly using uncorrected automated counting results to establish dose-response curves or evaluate test samples will lead to systematic biases in dose estimations, which may, in severe cases, mislead clinical decisions.

[0006] Therefore, how to construct a biodosimetry system that ensures both analytical throughput and assessment accuracy, overcoming the contradiction between the low efficiency of manual analysis and the insufficient reliability of automatic identification in existing technologies, has become a pressing technical challenge in the fields of radiation biology and nuclear emergency medicine. This invention aims to provide an innovative solution to this problem. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention provides a system for rapid biological dose assessment of a large-scale population exposed to ionizing radiation, comprising: Sample processing module: used to prepare blood samples with different radiation doses, and to culture and prepare chromosome slides from the blood samples to obtain chromosome specimens; Aberration Analysis Module: Used to automatically identify and count dicentric chromosome aberrations in the chromosome specimens, and to manually verify the automatic identification results to obtain dicentric chromosome frequency data corresponding to different radiation doses; Dose-response curve establishment module: used to establish a dose-response relationship model based on the different radiation doses and the corresponding dicentric chromosome frequency data through curve fitting; Dose estimation module: Used to receive dicentric chromosome frequency data of blood samples from the individual to be tested after the same processing, and substitute it into the dose-response relationship model to estimate the radiation biological dose of the blood sample.

[0008] In some preferred embodiments, the different radiation doses in the sample processing module cover the range of 0 Gy to 5 Gy, and include at least dose points of 0.0 Gy, 0.1 Gy, 0.25 Gy, 0.5 Gy, 0.75 Gy, 1.0 Gy, 2.0 Gy, 3.0 Gy, 4.0 Gy, and 5.0 Gy.

[0009] In some preferred embodiments, the dose rate of the different radiation doses in the sample processing module is between 0.3 Gy / min and 0.4 Gy / min, preferably 0.353 Gy / min.

[0010] In some preferred embodiments, the distortion analysis module includes: The automatic scanning unit is used to scan chromosome specimens through an automatic chromosome image scanning and analysis system, to preliminarily identify and record dicentric chromosome candidates and analyze the total number of cells; The manual verification unit is used to manually verify the results of the initial identification by the automatic scanning unit, eliminate false positive identification objects, and confirm the final number of dicentric chromosomes.

[0011] In some preferred embodiments, the false positive identification objects include one or more of the following types: contact chromosomes, crossed chromosomes, twisted chromosomes, single broken chromosomes, and misidentified normal chromosomes.

[0012] In some preferred embodiments, in the sample processing module, the blood sample is cultured for 48 to 52 hours after irradiation, and chromosomes are harvested and prepared as slides.

[0013] In some preferred embodiments, in the dose-response curve establishment module, the curve fitting is a quadratic curve fitting, and the established dose-response relationship model is as follows: Y = c + αD + βD 2 , In the formula, y The number of dicentric mitochondria per cell; c This represents the background level of bicentromeres; D For absorbed dose, Gy; α The coefficient of the linear term; β coefficient of the quadratic term In some preferred embodiments, the dose estimation module is also used to assess the statistical uncertainty of dicentromere chromosome counting results when estimating biological doses, so as to provide a confidence interval for the dose estimation value.

[0014] In some preferred embodiments, the dicentric chromosome frequency data is calculated by dividing the number of manually verified dicentric chromosomes by the total number of analyzed cells.

[0015] The present invention also provides a computer-readable storage medium having a computer program stored thereon, characterized in that the program, when executed by a processor, implements the functions of various modules of the system.

[0016] The technical solution adopted in this invention can achieve the following beneficial effects: The system disclosed in this invention subjectes extracted human peripheral venous blood to different doses of radiation, obtaining results based on the Metafer system and combined with manual verification methods. 60 COγ-ray induced dicentric chromosome dose-response curves Y = c + αD + βD 2 The method and curves provided by this invention significantly improve the efficiency and accuracy of biological dose estimation, which can meet the needs of dose estimation for a large number of people under large-scale ionizing radiation exposure events, and assess individual exposure doses in the shortest possible time to effectively guide medical intervention strategies. Attached Figure Description

[0017] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below, forming part of the present invention. The illustrative embodiments of the present invention and their descriptions explain the present invention and do not constitute an improper limitation of the present invention. In the accompanying drawings: Figure 1 This is a flowchart of Example 1.

[0018] Figure 2 This is the dose-response curve of dicentromere chromosomes fitted after γ-ray irradiation in Example 1. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below in conjunction with specific embodiments and corresponding drawings. In the description of this invention, it should be noted that the term "or" is generally used to include the meaning of "and / or," unless otherwise expressly indicated.

[0020] Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0021] Example 1 (1) Draw peripheral venous blood and administer different doses of the drawn peripheral venous blood. 60 COγ-ray irradiation was performed, and blood samples from each dose group were collected to prepare dicentric chromosome aberration specimens. The dose-response model is Y =0.0009 (±0.0005) +0.0108 (±0.0026) D +0.0087 (±0.0010) D 2 .

[0022] (3) Three healthy adult volunteers, aged 24-30 years (mean 26 years), who had not undergone diagnostic or occupational radiation exposure within the past year, were selected. Peripheral venous blood was collected and anticoagulated using heparin sodium anticoagulant tubes. [The following text appears to be incomplete and requires further context: "Administered..."] 60 Co-γ ray irradiation was performed at a dose rate of 0.353 Gy / min. Ten dose points were set: 0.0, 0.1, 0.25, 0.5, 0.75, 1.0, 2.0, 3.0, 4.0, and 5.0 Gy. Chromosomes were harvested and prepared after 52 hours of blood culture following irradiation.

[0023] (3) Images were acquired and dic were automatically identified using Metafer chromosome scanning analysis software, and then manually verified to obtain data on dic distribution and frequency: The slides were scanned and analyzed using the Metafer automated scoring system. First, the system automatically located metaphases under low magnification (MSearch software). Then, the AutoCapt tool was used to acquire high-resolution images under 63x magnification. Automatic detection of dicentric chromosomes was performed using DCScore software. The system automatically recorded the number of detected dicentric chromosomes (dic) and the number of analyzed cells for subsequent analysis. The candidate dic images obtained from the automated analysis were manually verified, and false positives were eliminated. False positive dic types included contact chromosomes, crossed chromosomes, twisted chromosomes, chromosomes with single-cell breaks, and normal chromosomes. The number of manually verified dic and the number of analyzed cells were recorded.

[0024] Table 1 shows the distribution and frequency of dichotomyc (dic) in human peripheral blood lymphocytes at doses of 0-5 Gy after gamma ray irradiation.

[0025] Table 1. Cell count and DIC frequency at different dose points after γ-ray irradiation.

[0026] As shown in Table 1, within the dose range of 0–5 Gy, the dic rate in human peripheral blood lymphocytes increases with increasing dose, and the spontaneous aberration rate of dic is 0.10%.

[0027] (4) Establish the dose-response curve based on the dic distribution and frequency data. The Dose Estimate (Version 5.3) software is used to construct the automatic dose-response curve for Dic, which employs an iterative reweighted least squares method. Figure 1 The dose-response curves generated from pooled data from 3 volunteers are shown, with the dashed lines representing the 95% lower and upper confidence limits. The fitted curve equation is as follows: Y =0.0009 (±0.0005) +0.0108 (±0.0026) D +0.0087 (±0.0010) D 2 ( χ 2 =58.10, df =7, r =0.9916, P <0.0001), correlation coefficient ( r =0.9916) is close to 1, indicating that there is a strong correlation between the fitted data points.

[0028] (5) Validation of the dose-response curve Peripheral blood samples were collected from three additional healthy volunteers, with the same screening criteria as above. Blood samples were irradiated under the same conditions, with dose settings divided into clinically relevant low-exposure groups (0.3, 0.8 Gy), moderate-exposure groups (1.5 Gy, 2 Gy), and high-exposure groups (3.6, 4.8 Gy) (7,16). The dose-response curves were automatically analyzed using the DIC method established in this study. 60 Dose estimation was performed on validation samples irradiated with CO2 and γ-rays. After automated analysis using DScore and manual verification, the resulting dose (dic) per cell was substituted into a fitted semi-automatic curve for dose estimation, and compared with the actual irradiation dose of the samples. The results are shown in Table 2. Except for sample R1 (0.3 Gy), the error rates between the other doses and the actual irradiation dose were all within 20%. This demonstrates that the dose curve fitted based on semi-automatic dic analysis can accurately estimate the dose.

[0029] Table 2 Validation Results of “DIC Chromosome Semi-Automatic Analysis Dose-Effect Curve”

[0030] As shown in Table 2, the established bicentromere semi-automatic analysis dose-response curve can accurately estimate biological doses.

[0031] (6) Results Analysis The present invention establishes 60 An automated dose-response curve analysis of Co-γ ray-induced dicentric chromosome aberrations in human peripheral blood lymphocytes provides a rapid bio-dose assessment system for populations under large-scale ionizing radiation exposure. This rapid assessment method improves analytical efficiency and can accurately estimate dose, offering a fast and effective alternative to manual dose estimation (DCA). This method and curve can potentially be applied to triage models and serve as a replacement for manual analysis in large-scale radiological events, enabling rapid dose assessment.

[0032] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims, and all of these forms are within the protection scope of the present invention.

Claims

1. A system for rapid biological dose assessment in large-scale populations exposed to ionizing radiation, characterized in that, include: Sample processing module: used to prepare blood samples with different radiation doses, and to culture and prepare chromosome slides from the blood samples to obtain chromosome specimens; Aberration Analysis Module: Used to automatically identify and count dicentric chromosome aberrations in the chromosome specimens, and to manually verify the automatic identification results to obtain dicentric chromosome frequency data corresponding to different radiation doses; Dose-response curve establishment module: used to establish a dose-response relationship model based on the different radiation doses and the corresponding dicentric chromosome frequency data through curve fitting; Dose estimation module: Used to receive dicentric chromosome frequency data of blood samples from the individual to be tested after the same processing, and substitute it into the dose-response relationship model to estimate the radiation biological dose of the blood sample.

2. The system according to claim 1, characterized in that, In the sample processing module, the different radiation doses cover the range from 0 Gy to 5 Gy, and include at least the dose points of 0.0 Gy, 0.1 Gy, 0.25 Gy, 0.5 Gy, 0.75 Gy, 1.0 Gy, 2.0 Gy, 3.0 Gy, 4.0 Gy, and 5.0 Gy.

3. The system according to claim 1 or 2, characterized in that, In the sample processing module, the dose rate of the different radiation doses is between 0.3 Gy / min and 0.4 Gy / min, preferably 0.353 Gy / min.

4. The system according to claim 1, characterized in that, The distortion analysis module includes: The automatic scanning unit is used to scan chromosome specimens through an automatic chromosome image scanning and analysis system, to preliminarily identify and record dicentric chromosome candidates and analyze the total number of cells; The manual verification unit is used to manually verify the results of the initial identification by the automatic scanning unit, eliminate false positive identification objects, and confirm the final number of dicentric chromosomes.

5. The system according to claim 4, characterized in that, The false positive identification objects include one or more of the following types: contact chromosomes, crossed chromosomes, twisted chromosomes, single broken chromosomes, and normal chromosomes that are misidentified.

6. The system according to claim 1, characterized in that, In the sample processing module, the blood sample is cultured for 48 to 52 hours after irradiation, and the chromosomes are harvested and prepared as slides.

7. The system according to claim 1, characterized in that, In the dose-response curve establishment module, the curve fitting is a quadratic curve fitting, and the established dose-response relationship model is as follows: Y = c + αD + βD 2 , In the formula, Y The number of dicentric mitochondria per cell; c This represents the background level of bicentromeres; D For absorbed dose, Gy; α The coefficient of the linear term; β The coefficient of the quadratic term.

8. The system according to claim 1, characterized in that, When estimating biological doses, the dose estimation module is also used to assess the statistical uncertainty of dicentric chromosome counting results to provide a confidence interval for the dose estimation value.

9. The system according to claim 1, characterized in that, The dicentric chromosome frequency data was calculated by dividing the number of dicentric chromosomes confirmed by manual verification by the total number of analyzed cells.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that, When executed by the processor, the program implements the functions of the various modules of the system as described in any one of claims 1-9.

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