Kozlowski Cleopatra, Fullerton Aaron, Cain Gary, Katavolos Paula, Bravo Joseph, Tarrant Jacqueline M
1 Safety Assessment, Development Sciences, Genentech Inc., South San Francisco, California, USA.
2 Gilead Sciences, Foster City, California, USA.
Toxicol Pathol. 2018 Apr;46(3):336-347. doi: 10.1177/0192623318766458.
The bone marrow is an important site for assessment of the hematopoietic toxicity of new drug candidates. Here, we extended our previous work, where we developed a computer algorithm to automatically quantitate overall bone marrow cell density by analyzing digitized images of standard hematoxylin and eosin (H&E) slides of rat bone marrow and further evaluated the capability to quantify myeloid: erythroid + lymphoid (M:EL) ratio and megakaryocyte cell density. We tested the algorithm in a toxicity study, where rats were dosed with two molecules known to affect bone marrow composition, monomethyl auristatin E, and a Bcl-xL inhibitor. The image analysis method detected significant changes in M:EL and megakaryocyte number that were either not found or semiquantitatively described by manual microscopic observation of the same slides. The image analysis results were consistent with other more established but time-consuming methods that measure changes in bone marrow cell composition: smear cytology, flow cytometry, and microscopic assessment. Our work demonstrates the feasibility of a rapid and more quantitative assessment of changes in bone marrow cell lineage composition using a computer algorithm compared to microscopic examination of H&E-stained bone marrow sections.
骨髓是评估新药候选物造血毒性的重要部位。在此，我们扩展了之前的工作，在之前的工作中我们开发了一种计算机算法，通过分析大鼠骨髓标准苏木精和伊红（H&E）染色玻片的数字化图像来自动定量总体骨髓细胞密度，并进一步评估量化髓系：红系+淋巴系（M:EL）比值和巨核细胞密度的能力。我们在一项毒性研究中测试了该算法，在该研究中给大鼠施用了两种已知会影响骨髓组成的分子，单甲基澳瑞他汀E和一种Bcl-xL抑制剂。图像分析方法检测到了M:EL和巨核细胞数量的显著变化，而这些变化在对同一张玻片进行手动显微镜观察时未被发现或只是半定量描述。图像分析结果与其他更成熟但耗时的测量骨髓细胞组成变化的方法一致：涂片细胞学、流式细胞术和显微镜评估。我们的工作证明了与对H&E染色的骨髓切片进行显微镜检查相比，使用计算机算法对骨髓细胞谱系组成变化进行快速且更定量评估的可行性。
