Optical metabolic imaging quantifies heterogeneous cell populations

Biomedical Optics Express
Alex Walsh, Melissa C Skala

Abstract

The genetic and phenotypic heterogeneity of cancers can contribute to tumor aggressiveness, invasion, and resistance to therapy. Fluorescence imaging occupies a unique niche to investigate tumor heterogeneity due to its high resolution and molecular specificity. Here, heterogeneous populations are identified and quantified by combined optical metabolic imaging and subpopulation analysis (OMI-SPA). OMI probes the fluorescence intensities and lifetimes of metabolic enzymes in cells to provide images of cellular metabolism, and SPA models cell populations as mixed Gaussian distributions to identify cell subpopulations. In this study, OMI-SPA is characterized by simulation experiments and validated with cell experiments. To generate heterogeneous populations, two breast cancer cell lines, SKBr3 and MDA-MB-231, were co-cultured at varying proportions. OMI-SPA correctly identifies two populations with minimal mean and proportion error using the optical redox ratio (fluorescence intensity of NAD(P)H divided by the intensity of FAD), mean NAD(P)H fluorescence lifetime, and OMI index. Simulation experiments characterized the relationships between sample size, data standard deviation, and subpopulation mean separation distance required f...Continue Reading

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Citations

Jan 8, 2016·Scientific Reports·Alex J WalshMelissa C Skala
Dec 24, 2015·Neoplasia : an International Journal for Oncology Research·Amy T ShahMelissa C Skala
Mar 19, 2016·Journal of Biophotonics·Sviatlana KalininaAngelika Rück
Oct 13, 2016·Journal of Biophotonics·Amy T ShahMelissa C Skala
May 10, 2017·Journal of Biophotonics·Tiffany M HeasterMelissa C Skala
Dec 23, 2017·Antioxidants & Redox Signaling·Olivia I Kolenc, Kyle P Quinn
Nov 16, 2017·Nature Reviews. Gastroenterology & Hepatology·Alex J ThompsonGuang-Zhong Yang
Oct 9, 2018·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Jenu V Chacko, Kevin W Eliceiri
Jan 4, 2019·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Ruofan CaoAmmasi Periasamy
Jul 29, 2020·Nature Biomedical Engineering·Alex J WalshMelissa C Skala
Jan 19, 2017·PloS One·Amy T ShahMelissa C Skala
Nov 19, 2019·Frontiers in Oncology·Tiffany M HeasterMelissa C Skala
Jun 6, 2020·Biomedical Optics Express·Peter F FavreauMelissa C Skala
Nov 30, 2016·Biomedical Optics Express·Kinan AlhallakNarasimhan Rajaram
Jun 21, 2017·Scientific Reports·Chiara StringariEmmanuel Beaurepaire
May 11, 2019·Nature Biomedical Engineering·Alex J WalshMelissa C Skala
Jul 1, 2017·Biomedical Optics Express·Mohammad A YaseenSava Sakadžić
Jun 6, 2020·Frontiers in Oncology·Joe T SharickMelissa C Skala
Apr 25, 2020·Current Treatment Options in Oncology·Katherine A JohnsonDustin A Deming
Oct 10, 2020·Integrative Biology : Quantitative Biosciences From Nano to Macro·Sheena C KerrDavid J Beebe
Nov 15, 2018·Molecular Cancer Therapeutics·Stephanie L FrickeDustin A Deming
Jun 9, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cheri A PaschDustin A Deming
Nov 24, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Andreas E Vasdekis, Abhyudai Singh
May 8, 2021·Frontiers in Bioengineering and Biotechnology·Tiffany M HeasterMelissa C Skala
Jun 8, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Alex J WalshMelissa C Skala
Jun 3, 2021·International Journal of Molecular Sciences·Sviatlana KalininaAngelika Rueck

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