Coupling Advanced Computational Analyses for Mammography and SHG Imaging for Early Detection of Breast Cancer Tissue Microenvironment Disruptions Accompanying Tumorigenesis

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Summary The breast tumor microenvironment plays a key role in the early development of cancer. An improved understanding of the tumor microenvironment will support the early detection of disease and the development of novel, more effective therapies. Current radiological interpretation of mammograms is based on identifying breast lesions and assessing their potential malignancy and lethality. The biomedical research community has yet to correlate the mammographic signatures of microenvironment alterations and loss of tissue homeostasis accompanying, or even preceding tumorigenesis. The PI recently used a novel and powerful computational technique to demonstrate that tissue disruption and loss of homeostasis can be quantitatively and objectively assessed from standard clinical mammography. These preliminary findings pertain only to single diagnostic mammograms; the proposed AREA project will analyze longitudinal sequences of mammograms over multiple years prior to, and approaching the year of diagnosis, thus revealing the progression of healthy breast tissue microenvironment towards a disrupted state. It is hypothesized that the tissue disorganization signature present in mammographic data is associated with tissue disruption and loss of tissue homeostasis in the microenvironment. Team members will verify this hypothesis by imaging breast tissue samples to characterize, at the cellular level, disruption of collagen structures associated to tumor microenvironment alterations accompanying tumorigenesis. This project's specific aims include: 1) verifying that mammographic tissue disruption accompanies and perhaps even precedes tumor development; 2) developing an in silico model of microcalcification growth into mammographic breast tissue environment, 3) improving the computational efficiency of our data analysis, and 4) linking morphological features of the breast tumor microenvironment imaged by mammography to cellular-scale alterations imaged by second harmonic generation microscopy. The proposed research will advance the education and career preparation of undergraduates within Maine's only biomedical engineering program, nurture a growing partnership among the University of Maine, Spectrum Healthcare Partners and Maine Medical Research Institute, introduce two UMaine faculty to biomedical research, and support the early career development of two assistant professors.