title: Simultaneous imaging of blood flow dynamics and vascular remodelling during development.
abstract: Normal vascular development requires blood flow. Time-lapse imaging techniques have revolutionised our understanding of developmental biology, but measuring changes in blood flow dynamics has met with limited success. Ultrasound biomicroscopy and optical coherence tomography can concurrently image vascular structure and blood flow velocity, but these techniques lack the resolution to accurately calculate fluid forces such as shear stress. This is important because hemodynamic forces are biologically active and induce changes in the expression of genes important for vascular development. Regional variations in shear stress, rather than the overall level, control processes such as vessel enlargement and regression during vascular remodelling. We present a technique to concurrently visualise vascular remodelling and blood flow dynamics. We use an avian embryonic model and inject an endothelial-specific dye and fluorescent microspheres. The motion of the microspheres is captured with a high-speed camera and the velocity of the blood flow in and out of the region of interest is quantified by micro-particle image velocitymetry (µPIV). The vessel geometry and flow are used to numerically solve the flow physics with computational fluid dynamics (CFD). Using this technique, we can analyse changes in shear stress, pressure drops and blood flow velocities over a period of 10 to 16 h. We apply this to study the relationship between shear stress and chronic changes in vessel diameter during embryonic development, both in normal development and after TGFβ stimulation. This technique allows us to study the interaction of biomolecular and biomechanical signals during vascular remodelling using an in vivo developmental model.
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, 3755 Chemin de la Côte-Ste-Catherine, Montréal, Quebec H3T 1E2, Canada Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, Quebec H3A 0C5, Canada.
authors.forename: Siavash
authors.initials: S
authors.lastname: Ghaffari
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, Quebec H3A 0C5, Canada.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Leask
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, 3755 Chemin de la Côte-Ste-Catherine, Montréal, Quebec H3T 1E2, Canada Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, Quebec H3A 0C5, Canada Department of Cardiovascular Science, KU Leuven, UZ Herestraat 49, Box 911, Leuven 3000, Belgium liz.jones@med.kuleuven.be.
authors.forename: Elizabeth A V
authors.initials: EA
authors.lastname: Jones
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001783:Blood Flow Velocity / Q000502:physiology; D003198:Computer Simulation; D003370:Coturnix; D006400:Hematocrit; D006439:Hemodynamics / Q000502:physiology*; D008863:Microspheres; D008955:Models, Cardiovascular; D012212:Rheology; D033081:Shear Strength; D013314:Stress, Mechanical; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D066253:Vascular Remodeling / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta
keywords: Angiogenesis; Arteriogenesis; Computational fluid dynamics; Hemodynamics; Micro-particle image velocimetry; Time-lapse microscopy