ArticleScience advances2018
Mapping metabolic changes by noninvasive, multiparametric, high-resolution imaging using endogenous contrast.
Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed.
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- Multi-modal label-free imaging of cellular metabolism and oxidative stress in 3D brain tissue models.Communications biology · 2025Article
- Label-free nonlinear microscopy probes cellular metabolism and myelin dynamics in live tissue.Communications biology · 2025Article
- Light and metabolism: label-free optical imaging of metabolic activities in biological systems [Invited].Biomedical optics express · 2025Review
- Integrating nonlinear optical and Raman spectral imaging for label-free pathological examinations.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2025Article
- Accelerating biopharmaceutical cell line selection with label-free multimodal nonlinear optical microscopy and machine learning.Communications biology · 2025Article
- Consensus guidelines for cellular label-free optical metabolic imaging: ensuring accuracy and reproducibility in metabolic profiling.Journal of biomedical optics · 2025Article
- Frontiers in mechanobiology and mechanomedicine.Med-X · 2025Article
- Multiphoton microscopy imaging of fibrous meningiomas based on the combination of multichannel mode and lambda mode.Frontiers in neuroscience · 2025Article
- Synergistic label-free fluorescence imaging and miRNA studies reveal dynamic human neuron-glial metabolic interactions following injury.Science advances · 2024Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Monitoring subcellular functional and structural changes associated with metabolism is essential for understanding healthy tissue development and the progression of numerous diseases, including cancer, diabetes, and cardiovascular and neurodegenerative disorders. Unfortunately, established methods for this purpose either are destructive or require the use of exogenous agents. Recent work has highlighted the potential of endogenous two-photon excited fluorescence (TPEF) as a method to monitor subtle metabolic changes; however, mechanistic understanding of the connections between the detected optical signal and the underlying metabolic pathways has been lacking. We present a quantitative approach to detecting both functional and structural metabolic biomarkers noninvasively, relying on endogenous TPEF from two coenzymes, NADH (reduced form of nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide). We perform multiparametric analysis of three optical biomarkers within intact, living cells and three-dimensional tissues: cellular redox state, NADH fluorescence lifetime, and mitochondrial clustering. We monitor the biomarkers in cells and tissues subjected to metabolic perturbations that trigger changes in distinct metabolic processes, including glycolysis and glutaminolysis, extrinsic and intrinsic mitochondrial uncoupling, and fatty acid oxidation and synthesis. We demonstrate that these optical biomarkers provide complementary insights into the underlying biological mechanisms. Thus, when used in combination, these biomarkers can serve as a valuable tool for sensitive, label-free identification of changes in specific metabolic pathways and characterization of the heterogeneity of the elicited responses with single-cell resolution.
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