Accurate Cytogenetic Biodosimetry Through Automation Of Dicentric Chromosome Curation And Metaphase Cell Selection
Jin Liu, Yaking Li, Ruth Wilkins, Farrah Flegal, Joan H. M. Knoll, Peter K. Rogan.
bioRxiv, doi: https://doi.org/10.1101/120410
Software to automate digital pathology relies on image quality and the rates of false positive and negative objects in these images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received from the frequency of DCs. We present image segmentation methods to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data based on novel quality measures. 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 0.4Gy to <0.2Gy with minimal manual review required. These image filtering approaches constitute a reliable and scalable solution that results in more accurate radiation dose estimates.
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