Computerized spermatogenesis staging (CSS) of mouse testis sections via quantitative histomorphological analysis.
Computerized spermatogenesis staging (CSS) of mouse testis sections via quantitative histomorphological analysis.
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通过定量组织形态学分析对小鼠睾丸切片进行计算机化精子发生分期 (CSS)
DOI：
10.1016/j.media.2020.101835
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发表时间：
2021-05
影响因子：
10.9
通讯作者：
Xu EY
中科院分区：
文献类型：
--
作者：
Xu J;Lu H;Li H;Yan C;Wang X;Zang M;Rooij DG;Madabhushi A;Xu EY
哺乳动物的精子发生是生精上皮中生精细胞发育的一个循环过程，可分为12个阶段。睾丸切片的组织学分期分析，特别是曲细精管横截面，是唯一有效的方法来评估生精过程的质量，并确定导致不育的发育缺陷。然而，这样的分期分析是乏味和耗时的，并且可能需要很长时间才能变得熟练。我们现在已经开发了一个计算机化的精子发生分期系统（CSS）的小鼠睾丸切片，通过学习的专家与几十年的经验，在小鼠睾丸分期。CSS系统的开发包括三个主要部分：1）开发小鼠睾丸切片的计算机图像分析模型; 2）将每个生精小管横截面自动分类为三个阶段组：早期阶段（ES：I-V期），中期（MS：VI-VIII期）和晚期（LS：IV-XII期）; 3）基于新发展的组织形态学特征将MS自动分类为不同的VI期、VII-mVIII期和晚期VIII期。根据三个模块建立了40个H&E染色的正常小鼠睾丸切片的队列，其中28个横截面用于开发小管区域分割、生精细胞类型和多同心层分割模型。其余的12个睾丸横截面，大约2314个小管，其阶段由两名专家睾丸组织学家手动注释，作为开发CSS系统的基础。CSS系统对ES、MS和LS的平均值和标准差（MSD）的准确度分别为0.93 ± 0.03、0.94 ± 0.11和0.89 ± 0.05;对于具有5年经验的人，CSS系统对ES、MS和LS的平均值和标准差（MSD）的准确度分别为0.85 ± 0.12、0.88 ± 0.07和0.96 ± 0.04。CSS系统在识别VI期、VII-mVIII期和晚期VIII期时的MSD准确度分别为0.74 ± 0.03、0.85 ± 0.04和0.78 ± 0.06;对于具有5年经验的人，MSD准确度分别为0.34 ± 0.18、0.78 ± 0.16和0.44 ± 0.25。就收集这些数据所需的时间而言，组织学家平均需要3小时，CSS系统需要1.87小时才能完成整个睾丸切片的评估（使用PC（I7-6800k 4.0 GHz，32 GB RAM和256 G SSD）和Titan 1080Ti GPU计算）。因此，与人类组织学家相比，CSS系统在分期方面更准确，更快，进一步的优化和开发不仅可以对小鼠精子发生的所有12个阶段进行完整的分期，而且还可以帮助未来诊断人类不育症。此外，由CSS分类器识别的顶级组织形态学特征与组织学家在区分VI、VII-mVIII和晚期VIII时使用的主要特征一致。
Spermatogenesis in mammals is a cyclic process of spermatogenic cell development in the seminiferous epithelium that can be subdivided into 12 subsequent stages. Histological staging analysis of testis sections, specifically of seminiferous tubule cross-sections, is the only effective method to evaluate the quality of the spermatogenic process and to determine developmental defects leading to infertility. Such staging analysis, however, is tedious and time-consuming, and it may take a long time to become proficient. We now have developed a Computerized Staging system of Spermatogenesis (CSS) for mouse testis sections through learning of an expert with decades of experience in mouse testis staging. The development of the CSS system comprised three major parts: 1) Developing computational image analysis models for mouse testis sections; 2) Automated classification of each seminiferous tubule cross-section into three stage groups: Early Stages (ES: stages I-V), Middle Stages (MS: stages VI-VIII), and Late Stages (LS: stages IV-XII); 3) Automated classification of MS into distinct stages VI, VII-mVIII, and late VIII based on newly developed histomorphological features. A cohort of 40 H&E stained normal mouse testis sections was built according to three modules where 28 cross-sections were leveraged for developing tubule region segmentation, spermatogenic cells types and multi-concentric-layers segmentation models. The rest of 12 testis cross-sections, approximately 2314 tubules whose stages were manually annotated by two expert testis histologists, served as the basis for developing the CSS system. The CSS system’s accuracy of mean and standard deviation (MSD) in identifying ES, MS, and LS were 0.93 ± 0.03, 0.94 ± 0.11, and 0.89 ± 0.05 and 0.85 ± 0.12, 0.88 ± 0.07, and 0.96 ± 0.04 for one with 5 years of experience, respectively. The CSS system’s accuracy of MSD in identifying stages VI, VII-mVIII, and late VIII are 0.74 ± 0.03, 0.85 ± 0.04, and 0.78 ± 0.06 and 0.34 ± 0.18, 0.78 ± 0.16, and 0.44 ± 0.25 for one with 5 years of experience, respectively. In terms of time it takes to collect these data, it takes on average 3 hours for a histologist and 1.87 hours for the CSS system to finish evaluating an entire testis section (computed with a PC (I7–6800k 4.0 GHzwith 32GB of RAM & 256G SSD) and a Titan 1080Ti GPU). Therefore, the CSS system is more accurate and faster compared to a human histologist in staging, and further optimization and development will not only lead to a complete staging of all 12 stages of mouse spermatogenesis but also could aid in the future diagnosis of human infertility. Moreover, the top-ranking histomorphological features identified by the CSS classifier are consistent with the primary features used by histologists in discriminating stages VI, VII-mVIII, and late VIII.
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影响因子：
5.4
作者：
Lee G;Veltri RW;Zhu G;Ali S;Epstein JI;Madabhushi A
通讯作者：
Madabhushi A
DOI：
10.1038/s41374-018-0095-7
发表时间：
2018-11
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Lu C;Romo-Bucheli D;Wang X;Janowczyk A;Ganesan S;Gilmore H;Rimm D;Madabhushi A
通讯作者：
Madabhushi A
影响因子：
78.8
作者：
Bera, Kaustav;Schalper, Kurt A.;Madabhushi, Anant
通讯作者：
Madabhushi, Anant
影响因子：
--
作者：
OAKBERG, EF
通讯作者：
OAKBERG, EF
影响因子：
4.1
作者：
Fakhrzadeh, Azadeh;Sporndly-Nees, Ellinor;Hendriks, Cris L. Luengo
通讯作者：
Hendriks, Cris L. Luengo