Abstract

Background: Label-free molecular profiling, imaging, and analysis are of particular interest in cancer biology for detecting subtle biochemical changes during cancer progression and potentially during cancer treatment. Multimodal, multiphoton imaging that combines diverse molecular contrasts derived from different physical mechanisms can improve our understanding of the tumor microenvironment. Methods: A label-free optical molecular profiling technique has been developed based on penta-modal multiphoton imaging to investigate mammary tumor progression in a pre-clinical rat model. Pulses from a coherent supercontinuum were tailored for two-photon (2PF) and three-photon fluorescence (3PF), second (SHG) and third harmonic generation (THG), and hyperspectral coherent anti-Stokes Raman scattering (CARS)-based imaging. A graphic multiphoton molecular profiling model was constructed to intuitively combine the co-registered quantitative, chemical, functional, and structural tissue information, enabling longitudinal in situ biomolecular analysis. Results: Over a 9-week period of tumor progression, and even before the formation of solid tumor, we observed lipid-protein transitions, microenvironmental reorganization, and a shift from FAD to NAD(P)H fluorescence, which reflects the reprogramming of cellular metabolism in carcinogenesis. Conclusions: Multimodal multiphoton imaging reveals and interrelates diverse carcinogenic signatures, identifying biomarkers that could serve as early molecular indicators for breast cancer diagnosis. This quantitative multimodal imaging methodology for molecular profiling of associated cancer biomarkers may have a broader impact in fundamental cancer research and future clinical applications.

Original languageEnglish (US)
Pages (from-to)742-756
Number of pages15
JournalQuantitative Imaging in Medicine and Surgery
Volume9
Issue number5
DOIs
StatePublished - Jan 1 2019

Fingerprint

Multimodal Imaging
Carcinogenesis
Biomarkers
Neoplasms
Photons
Fluorescence
Breast Neoplasms
Rubiaceae
Flavin-Adenine Dinucleotide
Molecular Imaging
Molecular Models
Tumor Microenvironment
Raman Spectrum Analysis
Tumor Biomarkers
NAD
Lipids
Research

Keywords

  • Cancer biomarkers
  • Mammary tumor
  • Microenvironment
  • Molecular profiling
  • Multimodal multiphoton imaging
  • Nonlinear optical imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Label-free molecular profiling for identification of biomarkers in carcinogenesis using multimodal multiphoton imaging. / Liu, Yuan; Tu, Haohua; You, Sixian; Chaney, Eric J.; Marjanovic, Marina; Boppart, Stephen A.

In: Quantitative Imaging in Medicine and Surgery, Vol. 9, No. 5, 01.01.2019, p. 742-756.

Research output: Contribution to journalArticle

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abstract = "Background: Label-free molecular profiling, imaging, and analysis are of particular interest in cancer biology for detecting subtle biochemical changes during cancer progression and potentially during cancer treatment. Multimodal, multiphoton imaging that combines diverse molecular contrasts derived from different physical mechanisms can improve our understanding of the tumor microenvironment. Methods: A label-free optical molecular profiling technique has been developed based on penta-modal multiphoton imaging to investigate mammary tumor progression in a pre-clinical rat model. Pulses from a coherent supercontinuum were tailored for two-photon (2PF) and three-photon fluorescence (3PF), second (SHG) and third harmonic generation (THG), and hyperspectral coherent anti-Stokes Raman scattering (CARS)-based imaging. A graphic multiphoton molecular profiling model was constructed to intuitively combine the co-registered quantitative, chemical, functional, and structural tissue information, enabling longitudinal in situ biomolecular analysis. Results: Over a 9-week period of tumor progression, and even before the formation of solid tumor, we observed lipid-protein transitions, microenvironmental reorganization, and a shift from FAD to NAD(P)H fluorescence, which reflects the reprogramming of cellular metabolism in carcinogenesis. Conclusions: Multimodal multiphoton imaging reveals and interrelates diverse carcinogenic signatures, identifying biomarkers that could serve as early molecular indicators for breast cancer diagnosis. This quantitative multimodal imaging methodology for molecular profiling of associated cancer biomarkers may have a broader impact in fundamental cancer research and future clinical applications.",
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AU - You, Sixian

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AU - Boppart, Stephen A.

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N2 - Background: Label-free molecular profiling, imaging, and analysis are of particular interest in cancer biology for detecting subtle biochemical changes during cancer progression and potentially during cancer treatment. Multimodal, multiphoton imaging that combines diverse molecular contrasts derived from different physical mechanisms can improve our understanding of the tumor microenvironment. Methods: A label-free optical molecular profiling technique has been developed based on penta-modal multiphoton imaging to investigate mammary tumor progression in a pre-clinical rat model. Pulses from a coherent supercontinuum were tailored for two-photon (2PF) and three-photon fluorescence (3PF), second (SHG) and third harmonic generation (THG), and hyperspectral coherent anti-Stokes Raman scattering (CARS)-based imaging. A graphic multiphoton molecular profiling model was constructed to intuitively combine the co-registered quantitative, chemical, functional, and structural tissue information, enabling longitudinal in situ biomolecular analysis. Results: Over a 9-week period of tumor progression, and even before the formation of solid tumor, we observed lipid-protein transitions, microenvironmental reorganization, and a shift from FAD to NAD(P)H fluorescence, which reflects the reprogramming of cellular metabolism in carcinogenesis. Conclusions: Multimodal multiphoton imaging reveals and interrelates diverse carcinogenic signatures, identifying biomarkers that could serve as early molecular indicators for breast cancer diagnosis. This quantitative multimodal imaging methodology for molecular profiling of associated cancer biomarkers may have a broader impact in fundamental cancer research and future clinical applications.

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