Tumor drug resistance due to heterogeneous cell populations remains a significant challenge for cancer treatment. Optical imaging of the fluorescence lifetimes of NADH and FAD, coenzymes of metabolism, can be used to track anti-cancer drug response in a label-free, non-contact manner. This imaging technique, “optical metabolic imaging,” can be performed on cancer cells and tumors to evaluate novel anti-cancer drugs or investigate mechanisms of resistance. Furthermore, multiphoton microscopy provides depth imaging of 3D samples such as patient derived primary tumor organoids. Optical metabolic imaging of organoids provides a predictive screen for individualized patient cancer treatment.
Optical metabolic microscopy can be combined with image segmentation for quantification of intra-population heterogeneity. Our work measuring and modeling cellular population dynamics reveals inherent and drug induced heterogeneity within cancer cells, providing a unique identification method of drug resistant cells.
Recent Papers:
- POSEA: A novel algorithm to evaluate the performance of multi-object instance image segmentation, Nianchao Wang, Linghao Hu, Alex J Walsh, PlosOne 18(3): e0283692.=, 2023.
- Evolution of cisplatin resistance through coordinated metabolic reprogramming of the cellular reductive state, Yu, W., Y. Chen, N. Putluri, A. Osman, C. Coarfa, V. Putluri, A. H. M. Kamal, J. K. Asmussen, P. Katsonis, J. N. Myers, S. Y. Lai, W. Lu, C. C. Stephan, R. T. Powell, F. M. Johnson, H. D. Skinner, J. Kazi, K. M. Ahmed, L. Hu, A. Threet, M. D. Meyer, J. A. Bankson, T. Wang, J. Davis, K. R. Parker, M. A. Harris, M. L. Baek, G. V. Echeverria, X. Qi, J. Wang, A. I. Frederick, A. J. Walsh, O. Lichtarge, M. J. Frederick and V. C. Sandulache, British Journal of Cancer, 2023.
- Identification of rare cell populations in autofluorescence lifetime image data. Elizabeth Cardona, Alex J. Walsh, Cytometry Part A, 2022.
- Autofluorescence Imaging to Evaluate Cellular Metabolism. Anna Theodossiou, Linghao Hu, Nianchao Wang, Uyen Nguyen, Alex J. Walsh, J. Vis. Exp. (177), e63282.