Metabolic light absorption, scattering, and emission (MetaLASE) microscopy

Optical imaging of metabolism can provide key information about health and disease progression in cells and tissues; however, current methods have lacked gold-standard information about histological structure. Conversely, histology and virtual histology methods have lacked metabolic contrast. Here, we present metabolic light absorption, scattering, and emission (MetaLASE) microscopy, which rapidly provides a virtual histology and optical metabolic readout simultaneously. Hematoxylin-like nucleic contrast and eosin-like cytoplasmic contrast are obtained using photoacoustic remote sensing and ultraviolet reflectance microscopy, respectively. The same ultraviolet source excites endogenous Nicotinamide adenine dinucleotide (phosphate), flavin adenine dinucleotide, and collagen autofluorescence, providing a map of optical redox ratios to visualize metabolic variations including in areas of invasive carcinoma. Benign chronic inflammation and glands also are seen to exhibit hypermetabolism. MetaLASE microscopy offers promise for future applications in intraoperative margin analysis and in research applications where greater insights into metabolic activity could be correlated with cell and tissue types.