<p>Animal models of stroke are used extensively to study the mechanisms involved in the acute and chronic phases of recovery following stroke. A translatable animal model that closely mimics the mechanisms of a human stroke is essential in understanding recovery processes as well as developing therapies that improve functional outcomes. We describe a photothrombosis stroke model that is capable of targeting a single distal pial branch of the middle cerebral artery with minimal damage to the surrounding parenchyma in awake head-fixed mice. Mice are implanted with chronic cranial windows above one hemisphere of the brain that allow optical access to study recovery mechanisms for over a month following occlusion. Additionally, we study the effect of laser spot size used for occlusion and demonstrate that a spot size with small axial and lateral resolution has the advantage of minimizing unwanted photodamage while still monitoring macroscopic changes to cerebral blood flow during photothrombosis. We show that temporally guiding illumination using real-time feedback of blood flow dynamics also minimized unwanted photodamage to the vascular network. Finally, through quantifiable behavior deficits and chronic imaging we show that this model can be used to study recovery mechanisms or the effects of therapeutics longitudinally.</p>
Optical coherence tomography angiography (OCTA) has been widely used for en face visualization of the microvasculature, but is challenged for real three-dimensional (3-D) topologic imaging due to the “tail” artifacts that appear below large vessels. Further, OCTA is generally incapable of differentiating descending arterioles from ascending venules. We introduce a normalized field autocorrelation function-based OCTA (g1-OCTA), which minimizes the tail artifacts and is capable of distinguishing penetrating arterioles from venules in the 3-D image. g1 ( τ ) is calculated from repeated optical coherence tomography (OCT) acquisitions for each spatial location. The decay amplitude of g1 ( τ ) is retrieved to represent the dynamics for each voxel. To account for the small g1 ( τ ) decay in capillaries where red blood cells are flowing slowly and discontinuously, Intralipid is injected to enhance the OCT signal. We demonstrate that the proposed technique realizes 3-D OCTA with negligible tail projections and the penetrating arteries are readily identified. In addition, compared to regular OCTA, the proposed g1-OCTA largely increased the depth-of-field. This technique provides a more accurate rendering of the vascular 3-D anatomy and has the potential for more quantitative characterization of vascular networks.