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Significance: Histopathological analysis of tissues is an essential tool forgrading, staging, diagnosing and resecting cancers and other malignancies.Current histopathological techniques require substantial sample processingprior to staining with hematoxylin and eosin (H&E) dyes, to highlight nuclearand cellular morphology. Sample preparation and staining is resource-intensiveand introduces potential for variability during sample preparation.  Aim: We present a novel method for direct label-free histopathologicalassessment of formalin fixed paraffin embedded tissue blocks and thin tissuesections using a dual contrast photoacoustic remote sensing (PARS) microscopysystem.  Approach: To emulate the nuclear and cellular contrast of H&E staining, weleverage unique properties of the PARS system. Here the ultraviolet excitationof the PAARS microscope takes advantage of DNA's unique optical absorption toprovide nuclear contrast analogous to hematoxylin staining of cell nucelli.Concurrently, the optical scattering contrast of the PARS detection system isleveraged to provide bulk tissue contrast analogous to eosin staining of cellmembranes.  Results: We demonstrate the efficacy of this technique by imaging humanbreast tissue and human skin tissues in formalin fixed paraffin embedded tissueblocks and frozen sections respectively. Salient nuclear and extra-nuclearfeatures such as cancerous cells, glands and ducts, adipocytes, and stromalstructures such as collagen.  Conclusions. The presented dual contrast PARS microscope enables label-freevisualizations of tissue with contrast and quality analogous to the currentgold standard for histopathological analysis. Thus, the proposed system is wellpositioned to augment existing histopathological workflows, providinghistological imaging directly on unstained tissue blocks and sections.

Single Acquisition Label-free Histology-like Imaging with Dual Contrast Photoacoustic Remote Sensing Microscopy