CAREER: MOEMS-based Head-mounted NIR-II Microscopy for Molecular Imaging of Brain Tumor in Freely Behaving Small Animal Models

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Brain diseases represent a considerable social and economic burden in US. With yearly costs of about 800 billion and an estimated 50 million people afflicted per year, brain diseases are a grand challenge for scientists. Presently, there is no effective cure for brain diseases (especially glioblastoma) despite the efforts of many investigators and significant financial investment. There is a pressing and unmet need for miniaturized deep tissue imaging tools that can help neuro-oncologist study the fundamental mechanism of brain tumor and the dynamics in the ligand-receptor interactions. This project will be focused on the development of a tiny microscope for molecularly targeted imaging on freely behaving small animals. The ultimate goal of this research is to provide advanced biomedical tools to drive advancements in both scientific understanding and future clinical applications. The techniques may lead to new imaging-guided surgery and therapies for clinicians to improve the quality of life for a sizable population. The generalized molecular imaging strategies will be applied to other organs, such as the breast, lung, and colon. Interdisciplinary educational activities will be developed for MSU and surrounding communities (Greater Lansing) with emphasis on increasing participation by women and underrepresented minorities.This project aims to conduct research leading to head-mounted near-infrared-II confocal fluorescence microscope that allows in vivo longitudinal cellular resolution imaging of brain tumor with deep penetration (1000µm) for studying molecular contrast agents targeting tumor biomarkers associated with brain diseases, including glioblastoma. Fiber-coupled superconductive nanowire single photon detector enables deep imaging in the biological transparency window (1000-1700nm). Based on magnetic field-compatible ultra-low power thin-film piezoelectrical materials and all-dielectric metamaterials-based flat lens, micro-system enabled three-dimensional laser scan engine with long-range focus tunability deep in the turbid solid brain tumor will be developed. Integration of monolithic focus tuning and beam steering devices on a tiny platform allows broad-bandwidth scan with ultra-low power consumption, which is currently impossible with macro-scale instrumentation. The development of microscopic system will help exploit new knowledge of opto-electronics on single photon detection. In-depth understanding of multimodal imaging on biomarkers will lay the foundation for developing new imaging modalities for applications in basic cancer biology studies and translational medicine.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.