Intravital optical imaging and microscopy are essential tools to study the pathophysiology of disease in small animal models in the neurosciences, immunology, and cancer research. The ability to visualize and measure dynamic physiology at cellular resolution in vivo using confocal and multiphoton microscopy provides a critical bridge between molecular measurements made using in vitro assays and assessments of whole-organ function using traditional imaging approaches such as ultrasound or MRI. Due to technical challenges in imaging the mouse heart beating at several hundred times per minute, it has not previously been possible to perform intravital imaging of cardiac structure and function at the cellular level.
This talk will describe new microscopy methods that overcome limitations in cardiac imaging to enable cellular imaging in vivo in the heart. We have developed high-speed scanning, tissue stabilization, and cardiac gating approaches that enable motion-artifact free imaging of the contracting heart at microscopic resolution in animal models. This allows quantitative measurement of the structure and function of individual working cardiomyocytes and immune cells in their native environment. We apply these methods in transgenic mouse models to characterize cellular physiology during myocardial infarction, or heart attack, and the response of the injured heart to drug therapies. New engineering advances in microscopy techniques, fluorescent reporters, and quantitative image analysis promise important insights into the complex physiology of ischemic heart disease, which remains the world’s number one cause of death.
Aaron Aguirre is a physician-scientist and cardiologist at the Massachusetts General Hospital (MGH). He received a B.S.E. in Electrical Engineering from the University of Michigan in 2000, an S.M. in Electrical Engineering from MIT in 2003, and a Ph.D. in Electrical and Medical Engineering from the Harvard-MIT Division of Health Sciences and Technology (HST) in 2008. He also received an M.D. from Harvard Medical School in 2008. Dr. Aguirre’s graduate research was in the areas of ultrafast optics and biomedical imaging, with a focus on new methods for endoscopic imaging and neuroimaging. He subsequently completed clinical training in cardiology and critical care at the Brigham and Women’s Hospital and a post-doctoral research fellowship in cardiovascular imaging at the Center for Systems Biology at MGH before joining the faculty at MGH in 2015. Dr. Aguirre’s clinical practice concentrates on critical care cardiology, and he is also a clinical affiliate at the MGH Healthcare Transformation Lab. His current research focuses on the development of new microscopy techniques to investigate the physiology of ischemic heart disease and is funded by a Fellow-to-Faculty Transition Award from the American Heart Association.