BME Seminar Series: Dr. Nozomi Nishimura

Goergen Hall 101 (Sloan Auditorium)

Multiphoton Microscopy of the Microvasculature in the Brain and Beyond

Assistant Professor, Department of Biomedical Engineering, Cornell University

Abstract:

Multiphoton microscopy is a powerful tool for investigating the contribution of multiple physiological systems to disease. Our goal is to study how the vascular, immune, and inflammatory systems interact in a tissue during disease. We develop experimental and analysis tools for in vivo imaging studies in several organ systems with a focus on the role of the microvasculature. In brain, we have been investigating the relationship between Alzheimer's disease and dysfunctional microvasculature. Vascular health is increasingly being recognized as a critical factor in Alzheimer's. In both humans with Alzheimer's disease and mouse models of Alzheimer's, cerebral blood flow is decreased by as much as 30% relative to age-matched controls. We have identified one mechanism that contributes to the perfusion reduction. We found an elevation in the number of brain capillaries plugged by leukocytes in transgenic AD mice as compared to age-matched controls. Although the fraction of capillaries that are plugged is small, our models suggest that these plugged capillaries are the cause of the blood flow reduction in the brains of Alzheimer's disease patients. This blood flow change could accelerate dementia in Alzheimer's disease. Before the use of multiphoton microscopy, these microscopic disturbances in blood flow went unrecognized. In other organs, motion makes microscopy difficult, but recent innovations enable studies with similar resolution as in brain. We can now study microvascular dynamics in the intestine as well as the beating heart in mice.