CancerCellTracker: a brightfield time-lapse microscopy framework for cancer drug sensitivity estimation.

Abstract

MOTIVATION:

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.

RESULTS:

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.

AVAILABILITY AND IMPLEMENTATION:

https://github.com/compbiolabucf/CancerCellTracker.

SUPPLEMENTARY INFORMATION:

Supplementary data are available at Bioinformatics online.

• Authors: Qibing Jiang, Praneeth Sudalagunta, Maria C Silva, Rafael R Canevarolo, Xiaohong Zhao, Khandakar Tanvir Ahmed, Raghunandan Reddy Alugubelli, Gabriel DeAvila, Alexandre Tungesvik, Lia Perez, Robert A Gatenby, Robert J Gillies, Rachid Baz, Mark B Meads, Kenneth H Shain, Ariosto S Silva, Wei Zhang
• Journal: Bioinformatics (Oxford, England) (Bioinformatics) Vol. 38 Issue 16 Pg. 4002-4010 (08 10 2022) ISSN: 1367-4811 [Electronic] England
• PMID: 35751591 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antineoplastic Agents

Topics

• Humans
• Microscopy (methods)
• Time-Lapse Imaging
• Software
• Neoplasms (diagnostic imaging, drug therapy)
• Precision Medicine
• Algorithms
• Antineoplastic Agents
• Tumor Microenvironment