Department of Computer Science, University of Central Florida, Orlando, FL 32816, USA.
Departments of Malignant Hematology and Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Bioinformatics. 2022 Aug 10;38(16):4002-4010. doi: 10.1093/bioinformatics/btac417.
Time-lapse microscopy is a powerful technique that relies on images of live cells cultured ex vivo that are captured at regular intervals of time to describe and quantify their behavior under certain experimental conditions. This imaging method has great potential in advancing the field of precision oncology by quantifying the response of cancer cells to various therapies and identifying the most efficacious treatment for a given patient. Digital image processing algorithms developed so far require high-resolution images involving very few cells originating from homogeneous cell line populations. We propose a novel framework that tracks cancer cells to capture their behavior and quantify cell viability to inform clinical decisions in a high-throughput manner.
The brightfield microscopy images a large number of patient-derived cells in an ex vivo reconstruction of the tumor microenvironment treated with 31 drugs for up to 6 days. We developed a robust and user-friendly pipeline CancerCellTracker that detects cells in co-culture, tracks these cells across time and identifies cell death events using changes in cell attributes. We validated our computational pipeline by comparing the timing of cell death estimates by CancerCellTracker from brightfield images and a fluorescent channel featuring ethidium homodimer. We benchmarked our results using a state-of-the-art algorithm implemented in ImageJ and previously published in the literature. We highlighted CancerCellTracker's efficiency in estimating the percentage of live cells in the presence of bone marrow stromal cells.
https://github.com/compbiolabucf/CancerCellTracker.
Supplementary data are available at Bioinformatics online.
延时显微镜技术是一种强大的技术,依赖于对活细胞进行体外培养的图像,这些图像每隔一定时间拍摄一次,以描述和量化它们在特定实验条件下的行为。这种成像方法在推进精准肿瘤学领域具有巨大潜力,可以定量评估癌细胞对各种疗法的反应,并为特定患者确定最有效的治疗方法。到目前为止,开发的数字图像处理算法需要涉及极少数细胞的高分辨率图像,这些细胞源自同质细胞系群体。我们提出了一种新的框架,可以跟踪癌细胞,捕捉它们的行为,并量化细胞活力,以便以高通量的方式为临床决策提供信息。
明场显微镜对在体外重建的肿瘤微环境中进行的 31 种药物处理的大量患者来源细胞进行成像,处理时间长达 6 天。我们开发了一个强大且用户友好的 CancerCellTracker 管道,用于在共培养物中检测细胞,跨时间跟踪这些细胞,并使用细胞属性的变化识别细胞死亡事件。我们通过将 CancerCellTracker 从明场图像和具有 ethidium homodimer 的荧光通道中估计细胞死亡的时间与荧光通道进行比较,验证了我们的计算管道。我们使用在 ImageJ 中实现的最先进算法和之前在文献中发表的算法对结果进行了基准测试。我们强调了 CancerCellTracker 在存在骨髓基质细胞的情况下估计活细胞百分比的效率。
https://github.com/compbiolabucf/CancerCellTracker。
补充数据可在 Bioinformatics 在线获取。