Kozlowski Cleopatra, Brumm Jochen, Cain Gary
1 Safety Assessment Pathology, Genentech Inc., South San Francisco, California, USA.
2 Biostatistics, Genentech Inc., South San Francisco, California, USA.
Toxicol Pathol. 2018 Apr;46(3):324-335. doi: 10.1177/0192623318766457.
Bone marrow toxicity is a common finding when assessing safety of drug candidate molecules. Standard hematoxylin and eosin (H&E) marrow tissue sections are typically manually evaluated to provide a semiquantitative assessment of overall cellularity. Here, we developed an automated image analysis method that allows quantitative assessment of changes in bone marrow cell population in sternal bone. In order to test whether the method was repeatable and sensitive, we compared the automated method with manual subjective histopathology scoring of total cellularity in rat sternal bone marrow samples across 17 independently run studies. The automated method was consistent with manual scoring methodology for detecting altered bone marrow cellularity and, in multiple cases, identified changes at lower doses. The image analysis method allows rapid and more quantitative assessment of bone marrow toxicity compared to manual examination of H&E slides, making it an excellent tool to aid detection of bone marrow cell depletion in preclinical toxicologic studies.
在评估候选药物分子的安全性时，骨髓毒性是一个常见的发现。标准苏木精和伊红（H&E）骨髓组织切片通常通过人工评估，以提供对总体细胞密度的半定量评估。在此，我们开发了一种自动图像分析方法，可对胸骨骨髓细胞群体的变化进行定量评估。为了测试该方法是否具有可重复性和敏感性，我们在17项独立进行的研究中，将自动方法与大鼠胸骨骨髓样本中总细胞密度的人工主观组织病理学评分进行了比较。自动方法与检测骨髓细胞密度改变的人工评分方法一致，并且在多个案例中，能在较低剂量下识别出变化。与手动检查H&E玻片相比，图像分析方法能够快速且更定量地评估骨髓毒性，使其成为临床前毒理学研究中辅助检测骨髓细胞耗竭的优秀工具。
