(PQC4) Towards In Vivo, 3D Cytotyping By Stimulated Raman Spectroscopic Imaging-Ba

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DESCRIPTION (provided by applicant): Technologies that can help make accurate, objective and automated decisions to aid the pathologist are sorely needed in clinical practice to improve cancer outcomes. While it is known that the tumor microenvironment plays a strong role, its potential to address this need cannot be assessed as we don't have facile methods for 3D, in situ cytotyping. A major stumbling block in cancer research today is not being able to fully appreciate or normalize for the role of the tumor microenvironment. The major goal of this project is to provide a practical imaging instrument for clinical and research use that can be operated by any trained person in pathology laboratories. The instrument will provide 3D location and identity of all cells in an optimal and fast manner. The approach is based; first, on developing novel instrumentation and analytical methods for stimulate Raman scattering (SRS) microscopy. The instrument presents a departure from the current state of the art using standoff optics to allow non-perturbative imaging and advanced control algorithms. The integration of spectral analysis algorithms makes generation of molecular pathology data facile - without any dyes, stains or human supervision. The developed instrument and algorithms are tested in against histologic standards and quantitative measures of performance obtained. As opposed to current practice that largely relies only on epithelial cells, overcoming the inability to cytotypethe tumor microenvironment with this project has the potential to transform decision-making for patients and alter the standard practice of histologic assessment in research.