Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas.

Microcalcifications (MCs) are routinely used to detect breast cancer in mammography. Little is known, however, about their materials properties and associated organic matrix, or their correlation to breast cancer prognosis. We combine histopathology, Raman microscopy, and electron microscopy to image MCs within snap-frozen human breast tissue and generate micron-scale resolution correlative maps of crystalline phase, trace metals, particle morphology, and organic matrix chemical signatures within high grade ductal carcinoma in situ (DCIS) and invasive cancer. We reveal the heterogeneity of mineral-matrix pairings, including punctate apatitic particles (<2 µm) with associated trace elements (e.g., F, Na, and unexpectedly Al) distributed within the necrotic cores of DCIS, and both apatite and spheroidal whitlockite particles in invasive cancer within a matrix containing spectroscopic signatures of collagen, non-collagen proteins, cholesterol, carotenoids, and DNA. Among the three DCIS samples, we identify key similarities in MC morphology and distribution, supporting a dystrophic mineralization pathway. This multimodal methodology lays the groundwork for establishing MC heterogeneity in the context of breast cancer biology, and could dramatically improve current prognostic models.

Integrated semiconductor optical sensors for cellular and neural imaging.

We review integrated optical sensors for functional brain imaging, localized index-of-refraction sensing as part of a lab-on-a-chip, and in vivo continuous monitoring of tumor and cancer stem cells. We present semiconductor-based sensors and imaging systems for these applications. Measured intrinsic optical signals and tissue optics simulations indicate the need for high dynamic range and low dark-current neural sensors. Simulated and measured reflectance spectra from our guided resonance filter demonstrate the capability for index-of-refraction sensing on cellular scales, compatible with integrated biosensors. Finally, we characterized a thermally evaporated emission filter that can be used to improve sensitivity for in vivo fluorescence sensing.