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.
Public Health Relevance Statement: The diagnosis of prostate cancer relies on centuries-old pathology technology, which has flaws that lead to undetected carcinoma in biopsy specimens. This project aims to develop innovative open-top light-sheet microscopy methods for prostate cancer pathology in two ways: 1) to demonstrate non-interference with the current standard of care methods, and 2) to provide preliminary evidence supporting the clinical value of the technology. The objectives of this proposal are consistent with the goals of the NCI IMAT SBIR program, which aims to support the early-stage development and validation of highly innovative technologies relevant to cancer diagnosis in the context of commercial use.
Project Terms: 3-Dimensional; Address; Adoption; Age; Algorithm Design; Algorithmic Analysis; Antibodies; Archives; base; Biological Assay; Biopsy; Biopsy Specimen; Blinded; Blood; Cancer Detection; cancer diagnosis; Cancer Patient; cancer risk; Carcinoma; Cell Nucleus; Clinical; Clinical Research; clinically relevant; clinically significant; Color Perception; Communities; Core Biopsy; cost; Cytokeratin 8; Data Set; density; design; Development; Diagnosis; Diagnostic; digital; Disease; Disease Progression; Evaluation; Family; Formalin; Gleason Grade for Prostate Cancer; Goals; Grant; Hematoxylin and Eosin Staining Method; Histologic; Histology; Histopathology; Human; Image; Image Analysis; image archival system; Immunohistochemistry; improved; Individual; innovation; innovative technologies; Keratin; Label; Laboratories; Lead; Light; lightspeed; Malignant neoplasm of prostate; Malignant Neoplasms; Manuals; Methods; Microscope; Microscopy; Minority; Molecular; Molecular Weight; NKX3-1 gene; novel; novel strategies; Optics; Paraffin Embedding; Pathologist; Pathology; Pathway interactions; patient subsets; Patients; PECAM1 gene; Performance; Phase; Procedures; Process; programs; prospective; Prostate; prostate biopsy; Prostate carcinoma; Prostate-Specific Antigen; Prostatectomy; Protocols documentation; PSA level; Recording of previous events; rectal; Sampling; Screening for Prostate Cancer; Sectioning technique; Slide; Small Business Innovation Research Grant; Specimen; Stains; standard of care; Standardization; Technology; Technology Assessment; Thinness; Time; Tissue Embedding; Tissues; treatment optimization; Treatment Protocols; Uncertainty; Validation
