SGER: In Vivo Hemodynamic Mapping Using DPIV

California Institute Of Technology, Pasadena CA

Investigators

Abstract

Normal heart development is a result of a complex interplay between the genetic program, hemodynamic forces and the inter- and intracellular processes that link them. Steady progress is being made in unraveling the role of genetics in both normal and pathophysiological cardiogenesis but investigations into the effects of hemodynamics on heart development are far less common. This discrepancy is likely due to recently acquired genetic accessibility of several animal models and to the difficulty in making sufficiently detailed flow measurements inside a living, beating heart. The primary goal of this study is to break through existing technological barriers by applying a powerful new flow visualization technique (digital particle image velocimetry [DPIV]) and state-of-the-art confocal imaging to create a map of the intracardiac hemodynamic environment in the most genetically accessible vertebrate model, the zebrafish (Danio rerio). To accomplish this objective the standard DPIV technique will need to be substantially modified: i) for application in microscopy; ii) for collection of micro-EKG data concomitantly with flow data in order to temporally "gait" the system; iii) for separation of the motions of red blood cells from the moving chamber walls and; iv) for better accounting of the use of a planar measurement on a 3-dimensional flow. The constrictions delineating the boundaries between the early zebrafish heart chambers are small in cross-section and will experience the most dynamic flow conditions. In addition, they are the sites of predictable, future heart remodeling (i.e. valve formation) and thus represent a logical anatomical location to apply our flow mapping technique. The embryos appropriate for this developmental stage will be approximately 2 days post-fertilization (dpf) and maintained at 28.5 C. Successful redefinition of DPIV technique to in vivo use will offer an unprecedented look into the heart as it develops, and will provide us with a tool for beginning to understand how epigenetic factors influence the timing and eventual morphology of Natures most celebrated pump.