Accurate cytogenetic biodosimetry through automated dicentric chromosome curation and metaphase cell selection.
Accurate cytogenetic biodosimetry through automated dicentric chromosome curation and metaphase cell selection.
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DOI：
10.12688/f1000research.12226.1
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Rogan PK
中科院分区：
文献类型：
--
作者：
Liu J;Li Y;Wilkins R;Flegal F;Knoll JHM;Rogan PK
异常显微结构的精确数字图像分析依赖于高质量的图像和最小化图像中假阳性（FP）和阴性对象的比率。细胞遗传学生物剂量学检测由电离辐射暴露引起的双着丝粒染色体（DC），并根据DC频率确定所接受的辐射剂量。通过将FP DC重新分类为单着丝粒染色体或染色体片段，自动DC识别的改进提高了剂量估计的准确性。我们还提出了图像分割方法，以排名高质量的数字中期图像和消除次优中期细胞。一组染色体形态分割方法选择性地过滤出主要由姐妹染色单体分离、染色体片段化和细胞碎片产生的FP DC。这使FP平均减少了55%，并且对三个样本中的这些异常结构具有高度特异性（≥97.7%）。额外的过滤器选择性地删除不完整、高度重叠或缺失中期细胞的图像，或增加FP率的整体染色体形态不佳的图像。图像选择的优化和FP DC最小化相结合的多个特征为基础的分割过滤器和一种新的图像排序程序的基础上已知的染色体长度分布。将相同的图像分割过滤程序应用于校准和测试样本，将平均剂量估计误差从0.4戈伊降低到<0.2戈伊，从而无需首先手动查看这些图像。这种可靠且可扩展的解决方案能够批量处理未知剂量的多个样品，并满足当前对高质量中期细胞制备物的分类辐射生物剂量测定的要求。
Accurate digital image analysis of abnormal microscopic structures relies on high quality images and on minimizing the rates of false positive (FP) and negative objects in images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received based on DC frequency. Improvements in automated DC recognition increase the accuracy of dose estimates by reclassifying FP DCs as monocentric chromosomes or chromosome fragments. We also present image segmentation methods to rank high quality digital metaphase images and eliminate suboptimal metaphase cells. A set of chromosome morphology segmentation methods selectively filtered out FP DCs arising primarily from sister chromatid separation, chromosome fragmentation, and cellular debris. This reduced FPs by an average of 55% and was highly specific to these abnormal structures (≥97.7%) in three samples. Additional filters selectively removed images with incomplete, highly overlapped, or missing metaphase cells, or with poor overall chromosome morphologies that increased FP rates. Image selection is optimized 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. Applying the same image segmentation filtering procedures to both calibration and test samples reduced the average dose estimation error from 0.4 Gy to <0.2 Gy, obviating the need to first manually review these images. This reliable and scalable solution enables batch processing for multiple samples of unknown dose, and meets current requirements for triage radiation biodosimetry of high quality metaphase cell preparations.