Multimodal imaging of metabolic activities for distinguishing subtypes of breast cancer

Author:

Li Zhi1,Nguyen Chloe1,Jang Hongje1,Hoang David1,Min SoeSu2,Ackerstaff Ellen2,Koutcher Jason A.23,Shi Lingyan1ORCID

Affiliation:

1. University of California San Diego

2. Memorial Sloan Kettering Cancer Center

3. Cornell University

Abstract

Triple negative breast cancer (TNBC) is a highly aggressive form of cancer. Detecting TNBC early is crucial for improving disease prognosis and optimizing treatment. Unfortunately, conventional imaging techniques fall short in providing a comprehensive differentiation of TNBC subtypes due to their limited sensitivity and inability to capture subcellular details. In this study, we present a multimodal imaging platform that integrates heavy water (D2O)-probed stimulated Raman scattering (DO-SRS), two-photon fluorescence (TPF), and second harmonic generation (SHG) imaging. This platform allows us to directly visualize and quantify the metabolic activities of TNBC subtypes at a subcellular level. By utilizing DO-SRS imaging, we were able to identify distinct levels of de novo lipogenesis, protein synthesis, cytochrome c metabolic heterogeneity, and lipid unsaturation rates in various TNBC subtype tissues. Simultaneously, TPF imaging provided spatial distribution mapping of NAD[P]H and flavin signals in TNBC tissues, revealing a high redox ratio and significant lipid turnover rate in TNBC BL2 (HCC1806) samples. Furthermore, SHG imaging enabled us to observe diverse orientations of collagen fibers in TNBC tissues, with higher anisotropy at the tissue boundary compared to the center. Our multimodal imaging platform offers a highly sensitive and subcellular approach to characterizing not only TNBC, but also other tissue subtypes and cancers.

Funder

Hellman Foundation

National Institutes of Health

Publisher

Optica Publishing Group

Subject

Atomic and Molecular Physics, and Optics,Biotechnology

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