Open-top light-sheet microscopy for non-destructive 3D pathology of prostate biopsies

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Abstract We are proposing a new approach for prostate cancer pathology using 3D open-top light-sheet (OTLS) microscopy and optical clearing. Approximately 20% of patients with an initial negative prostate biopsy procedure are found to have prostate cancer on a subsequent biopsy procedure. Previous studies have shown that examination of 100% of biopsy tissue improved prostate cancer detection rate, but these studies used labor-intensive manual sectioning techniques that are practical for a clinical laboratory. We hypothesize that imaging 100% of prostate biopsy tissue using OTLS microscopy, rather than 1-2% of the biopsy using current pathology technology, can detect occult carcinoma that would have otherwise been missed in a subset of patients. Furthermore, we intend to show that 3D OTLS can be seamlessly integrated into the current clinical laboratory workflow. The specific aims of this proposal are: 1) Validate that our OTLS methods do not interfere with the current pathology practice of formalin-fixed paraffin-embedded (FFPE) tissue sections, hematoxylin and eosin (H&E) histology, and immunohistochemistry (IHC), and 2) To show that 3D pathology can detect occult cancer missed by traditional microscopy, we will compare diagnosis of “pseudo-H&E” 3D OTLS images to traditional H&E pathology. We will use archived FFPE biopsy blocks from patients with prostate cancer who had a negative initial biopsy result. Through the studies in this proposal, we will validate the non-interference of our innovative 3D OTLS methods with standard pathology practice, a necessary prerequisite for adoption within the pathology community and for regulatory considerations. We will also provide preliminary evidence to support the clinical value of 3D pathology. This project addresses the IMAT goal of developing substantially improved cancer detection and risk assessment technologies.