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Published April 7, 2023 | Supplemental Material + Published
Journal Article Open

Automatic detection of circulating tumor cells and cancer associated fibroblasts using deep learning

Abstract

Circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) from whole blood are emerging as important biomarkers that potentially aid in cancer diagnosis and prognosis. The microfilter technology provides an efficient capture platform for them but is confounded by two challenges. First, uneven microfilter surfaces makes it hard for commercial scanners to obtain images with all cells in-focus. Second, current analysis is labor-intensive with long turnaround time and user-to-user variability. Here we addressed the first challenge through developing a customized imaging system and data pre-processing algorithms. Utilizing cultured cancer and CAF cells captured by microfilters, we showed that images from our custom system are 99.3% in-focus compared to 89.9% from a top-of-the-line commercial scanner. Then we developed a deep-learning-based method to automatically identify tumor cells serving to mimic CTC (mCTC) and CAFs. Our deep learning method achieved precision and recall of 94% (± 0.2%) and 96% (± 0.2%) for mCTC detection, and 93% (± 1.7%) and 84% (± 3.1%) for CAF detection, significantly better than a conventional computer vision method, whose numbers are 92% (± 0.2%) and 78% (± 0.3%) for mCTC and 58% (± 3.9%) and 56% (± 3.5%) for CAF. Our custom imaging system combined with deep learning cell identification method represents an important advance on CTC and CAF analysis.

Additional Information

© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. We thank all colleagues in the C.Y. and R.J.C. labs for helpful suggestions and feedback. We thank Dr. Dorraya El-Ashry for providing CAF23 cells. We acknowledge Prof. S. Joshua Swamidass from Washington University, St. Louis for helpful advice and experimental design suggestions. This work was supported by the following grants: NIH U01 Funding (U01CA233363), Caltech Center for Sensing to Intelligence (S2I) Funding (13520296), Heritage Research Institute for the Advancement of Medicine and Science at Caltech (HMRI) Funding (HMRI-15-09-01) and Merkin Translational Research Grant 2021. Contributions. C.S. was responsible for planning the project direction, building up imaging system, and developing data preprocessing algorithm as well as DL model. S.R. was responsible for model sample preparation and human annotation on fluorescence images. The project was conceived and supervised by R.J.C. and C.Y. The manuscript was written by C.S. and S.R. and all authors participated in editing the manuscript. Data availability. The datasets generated and/or analysed during the current study are available in the Google Drive repository, https://drive.google.com/drive/folders/1hsxoi5tr3_3e-tldonrWFRbi1B7J4Pcz?usp=sharing. Code availability. The training and testing code for the ensemble DL mCTC and CAF detection models are available at https://github.com/Scott-Sheen/AI4CTCCAF. Competing interests. R.J.C. and S.R. are co-founders and principals at Circulogix Inc. The other authors declare that there are no competing interests.

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Supplemental Material - 41598-2023-Article-32955-MOESM1-ESM.docx

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Additional details

Created:
September 28, 2023
Modified:
December 21, 2023