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.

Public Health Relevance

The goal of this project is to provide a new chemical imaging-based approach to in situ cytotyping. We advance a new technology - stimulated Raman scattering microscopy - with control algorithms for optimal data acquisition. Data acquired from every voxel in 3D is converted to corresponding cellular identity in human breast tissue using computer algorithms. The instrument addresses a contemporary problem in cancer in which we know that multiple cell types are involved in cancer progress but cannot understand their role since we don't have the tools to do so. This project provides the tools. If successful, establishment of the instrumentation and analytical methods here would alter the standard practice in histologic assessment of future research and clinical practice in cancer. The developed tools will also be widely applicable beyond cancer and help understand the interplay of different cells in human development and disease.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZCA1-GRB-P (A1))
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Ossandon, Miguel
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University of Illinois Urbana-Champaign
Engineering (All Types)
Schools of Engineering
United States
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