Smart microscope system for radiation biodosimetry

Abstract

Automation of microscopic pathological diagnosis relies on digital image quality, which, in turn, affects the rates of false positive and negative cellular objects designated as abnormalities. Cytogenetic biodosimetry is a genotoxic assay that detects dicentric chromosomes (DCs) arising from exposure to ionizing radiation. The frequency of DCs is related to radiation dose received, so the inferred radiation dose depends on the accuracy of DC detection. To improve this accuracy, image segmentation methods are used to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data in a sample based on novel quality measures. When sufficient numbers of high quality images are found, the microscope system is directed to terminate metaphase image collection for a sample. The International Atomic Energy Agency recommends at least 500 images be used to estimate radiation dose, however often many more images are collected in order to select the metaphase cells with good morphology for analysis. Improvements in DC recognition increase the accuracy of dose estimates, by reducing false positive (FP) DC detection. A set of chromosome morphology segmentation methods selectively filtered out false DCs, arising primarily from extended prometaphase chromosomes, sister chromatid separation and chromosome fragmentation. This reduced FPs by 55% and was highly specific to the abnormal structures (≥97.7%). Additional procedures were then developed to fully automate image review, resulting in 6 image-level filters that, when combined, selectively remove images with consistently unparsable or incorrectly segmented chromosome morphologies. Overall, these filters can eliminate half of the FPs detected by manual image review. Optimal image selection and FP DCs are minimized by combining multiple feature based segmentation filters and a novel image sorting procedure based on the known distribution of chromosome lengths. Consequently, the average dose estimation error was reduced from 0.4 Gy to <0.2 Gy with minimal manual review required. Automated image selection with these filters reduces the number of images that are required to capture metaphase cells, thus decreasing the number of images and time required for each sample. A microscope system integrates image selection procedures controls with an automated digitally controlled microscope then determines at what point a sufficient number of metaphase cell images have been acquired to accurately determine radiation dose, which then terminates data collection by the microscope. These image filtering approaches constitute a reliable and scalable solution that results in more accurate and rapid radiation dose estimates.