Mitosis detection of hematopoietic stem cell populations in time-lapse phase-contrast microscopy images

Abstract

Understanding the heterogeneous behavior of hematopoietic stem cells (HSCs) is required for the expansion of the cells without loss of their regenerative capacity. As such, it is essential to establish their lineage relationships by tracking the history of individual cells in a cell population. However, the quality of lineage relationships is often degraded because of undetected or misdetected mitotic events, which lead to missed or inaccurate mother-daughter cell relationships. In this paper, we present an automated mitosis detection method for HSCs in time-lapse phase-contrast microscopy images. Since HSCs are nonadherent, i.e., free-floating in the culture medium, the method is distinguished from the recent mitosis detection methods developed for adherent cells that are attached to the surface of a petri dish. The proposed mitosis detection method detects individual cells in each image frame and subsequently tracks them over time and in so doing identifies newly appeared cells, each of which is considered as a candidate of a newborn cell. Each candidate is then examined to determine whether it is indeed a newborn cell based on temporal change of cell sizes of potential mother and daughter cells. Our method was quantitatively evaluated on 14 HSC populations, each of which is observed for four days, resulting in a precision of 97.4% and a recall of 96.6%.