Spatio-temporal cell cycle phase analysis using level sets and fast marching methods
Spatio-temporal cell cycle phase analysis using level sets and fast marching methods
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DOI：
10.1016/j.media.2008.06.018
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发表时间：
2009-02-01
影响因子：
10.9
通讯作者：
Roysam, Badrinath
中科院分区：
文献类型：
--
作者：
Padfield, Dirk;Rittscher, Jens;Roysam, Badrinath
通过新型分子标记，荧光显微镜能够使用活细胞测定来监测多种细胞功能。自动图像分析是必要的，以监测这样的模型系统在高通量和高内容的环境。在这里，我们展示了在单细胞水平上同时跟踪细胞周期阶段和细胞运动的能力。使用最近推出的细胞周期标记物，我们提出了一套图像分析工具，用于在较长的时间内对活细胞进行自动细胞时相分析。我们的基于模型的方法能够表征细胞周期G1，S，G2和M的四个阶段，这使得能够研究抑制剂化合物的作用，这些抑制剂化合物旨在阻止癌细胞在任何阶段的复制。我们接近跟踪问题作为一个时空体积分割任务，其中的2D切片堆叠成一个体积与时间作为z维。G2和S阶段的分割是使用水平集完成的，我们设计了一个基于模型的形状/大小约束来控制水平集的演化。我们的主要贡献是设计了一个速度函数，再加上一个快速行进的路径规划方法，用于跟踪细胞在G1期的细胞核的外观变化的基础上。我们的方法的可行性证明了控制和情况下，其中细胞与细胞周期抑制剂治疗的定量结果。(C)2008 Elsevier B. V.保留所有权利。
Enabled by novel molecular markers, fluorescence microscopy enables the monitoring of multiple cellular functions using live cell assays. Automated image analysis is necessary to monitor such model systems in a high-throughput and high-content environment. Here, we demonstrate the ability to simultaneously track cell cycle phase and cell motion at the single cell level. Using a recently introduced cell cycle marker, we present a set of image analysis tools for automated cell phase analysis of live cells over extended time periods. Our model-based approach enables the characterization of the four phases of the cell cycle G1, S, G2, and M, which enables the study of the effect of inhibitor compounds that are designed to block the replication of cancerous cells in any of the phases. We approach the tracking problem as a spatio-temporal volume segmentation task, where the 2D slices are stacked into a volume with time as the z dimension. The segmentation of the G2 and S phases is accomplished using level sets, and we designed a model-based shape/size constraint to control the evolution of the level set. Our main contribution is the design of a speed function coupled with a fast marching path planning approach for tracking cells across the G1 phase based on the appearance change of the nuclei. The viability of our approach is demonstrated by presenting quantitative results on both controls and cases in which cells are treated with a cell cycle inhibitor. (C) 2008 Elsevier B.V. All rights reserved.