Application of functional optical coherence tomography angiography in neurovascular research

Abstract

Optical coherence tomography (OCT) is a revolutionary non-invasive imaging technique that can perform high-resolution, cross-sectional tomographic imaging of the internal microstructure in biological tissues by measuring backscattered or backreflected light. Its functional extension, OCT angiography (OCTA), analyzes the intrinsic scattering property of the heterogenous tissue bed to extract dynamic blood flow signals to the capillary level without a need of contrast agents. Aside from the commonly known application of OCTA in clinical ophthalmology for imaging the retinal blood flow in human subjects, the technique has recently emerged as a useful tool in pre-clinical neuroscience for imaging cerebral microcirculation and dynamics in rodent models. The main goal of this thesis is to progress with the application of OCT/OCTA in neurovascular research and solve questions in neurovascular functions and associated disorders, including ischemic stroke, aging, and Alzheimer’s disease. To achieve this goal, firstly, novel mouse cranial window techniques will be developed together with series of OCTA algorithms to image the cerebral blood flow in mouse brain that covers capillary, pial and penetrating vessels. Then, a newly developed method, OCTA capillary velocimetry, will be applied to investigate the capillary flow pattern adjustment during neurovascular coupling and brain oxygenation. Next, vasodynamics of pial and penetrating arterioles of the cerebral collateral network will be unraveled in rodent models of ischemic stroke, upon which new details of a vascular self-protective mechanism will be revealed. Lastly, the multifunctional OCTA will be applied for a comprehensive investigation of aging-associated cerebral vasculature and blood flow changes that give indications to Alzheimer’s disease.