Grant: Canada Research Chairs

The objective of the chair program is to pursue the development of innovative optical imaging technologies and state of the art simulations to investigate the causative role of vascular dysfunction in brain damage. Blood vessels form a plumbing network used to carry oxygen to tissue using red blood cells as a transporter. From a simple network in larger arterial segments to the complex topological structure of capillary beds, the vascular system plays a fundamental role in the delivery of oxygen molecules to cells. With age and disease, larger pipes in the system degrade both becoming more rigid and less responsive to hemodynamic stress while the smaller pipes (arterioles, capillaries) see connections and functional changes modifying their tissue footprint and their ability to deliver oxygen. First and foremost, impaired oxygen delivery affects the brain due to constant metabolic demand that needs to be met at every point in time to avoid damage. This chair program aims to develop novel technology to measure and accurately model microvascular function, oxygen delivery and potential associations with neural damage in complex and realistic environments. We will exploit combined 2/3-photon and Optical Coherence Tomography (OCT) microscopy imaging instruments to assess in vivo, how vascular properties modulate neural tissue oxygenation and neural death. With ground truth from in-vivo measures and ex-vivo structural information, we will then build and validate whole-brain first-principles vascular mechanistic models quantifying blood flow and oxygen delivery to tissue based on O2 advection/diffusion principles. These models will serve to simulate conditions associated with vascular dysfunction and allow modelling its impact on oxygen delivery and macroscopic signals measured with Magnetic Resonance Imaging (MRI). This will provide a unique tool to model the impact of microvascular dysfunction and to identify signatures of vascular diseases. With this research program we hope to develop technology that will help elucidate the role of vascular and micro-vascular network dysfunction in brain damage. With modelling developments, we aim to assess the manifestations/biomarker-signatures of these changes when measured with large clinical imaging instruments. Finally, new imaging technology developed to reach our goals is expected to provide instruments that can be disseminated and used beyond the investigations planned here.