Label-free virtual-histology of skin tissues using a Photoacoustic Remote Sensing (PARS) microscope is explored. The PARS captures optical absorption contrast facilitating label-free imaging of numerous biomolecules. Combined with AI-based image processing, PARS provides virtual histology images label-free directly from unprocessed tissues. The label-free contrast means several virtual stains may be applied to each tissue section. Subsequent results are explored in unprocessed human skin with basal cell carcinoma, and squamous cell carcinoma. Clinical comparison studies indicate there is similar diagnostic quality between the PARS and gold-standard histology preparations. This represents a significant milestone in the development of a clinically ready microscope for label-free skin cancer histology.
A Photoacoustic Remote Sensing (PARS) microscopy system is presented for label-free histological imaging of skin tissues. PARS captures label-free optical absorption contrast visualizing cell nuclei, connective tissues, lipids, and other structures with contrast analogous to common histochemical stains. Imaging is demonstrated in unprocessed human skin with basal cell carcinoma, squamous cell carcinoma, and melanoma. Visualizations are compared against traditional tissue preparation with histochemical staining. Preliminary clinical studies show comparable diagnostic quality between PARS histology and standard histology preparations. The proposed method is a milestone in this translational research project, aiming towards clinical deployment of a PARS microscope for skin cancer imaging.
Nonmelanoma skin cancers (NSMC) are among the most common malignancies in the US today. Mohs micrograph surgery (MMS) is the gold standard for most NSMC. However, MMS is time-consuming as it employs frozen section analysis (FSA) for intraoperative assessment. Each FSA can require up to 60 minutes per excision. Using photoacoustic remote sensing (PARS™) we demonstrate first results of imaging tissue morphology on human skin with a non-contact reflection-mode method, enabling rapid label-free pathological assessment. These images are validated against toluidine blue stained sections. The authors believe the proposed method represents a vital step towards an in-situ assessment of NSMC.
Here we explore the use of Photoacoustic Remote Sensing (PARS™) microscopy, a recently developed non-contact photoacoustic imaging modality, for visualizing subcellular structures label-free in tissues. Operating in an all-optical reflection-mode architecture PARS captures optical absorption contrast within bulk tissue samples. Presented here, by visualizing endogenous optical absorption of DNA and cytochromes, cellular morphology is captured with contrast analogous to the industry standard hematoxylin and eosin (H&E) staining. Subcellular features are recovered from human and murine, brain and gastrointestinal tissues. This work represents a significant step towards the development of a real-time microscopy system for label-free histopathological assessment of tissues in-situ.
Histopathology remains the gold standard for assessing tissue microanatomy. Presently, specimens are examined with bright-field microscopes that require thin stained sections of tissue specimens. However, this requires extensive tissue processing and long turnaround times. Frozen sectioning is commonly used during surgery to assess margin status. However, this method can be unreliable as the slides can be difficult to interpret. Employing photoacoustic remote sensing (PARS), we emulate H and E micrographs by visualizing nuclear and cytoplasm contrast directly. These contrasts are visualized in a variety of human tissue samples and fresh thick unprocessed tissue specimens.
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