Nonlinear Optics in Vivo: Using Light to Study and Perturb Blood Flow in the Living Brain Chris Schaffer Department of Physics University of California San Diego   Blood flow to the brain is supplied through a highly interconnected vascular network containing loops and redundant connections at all levels. Although this redundancy likely provides some protection against vascular blockages, clinical evidence nonetheless implicates the occlusion of small blood vessels in the progression of neurodegenerative diseases such as Alzheimer's and vascular dementia. Understanding this link between microvessel occlusion and neurodegeneration requires characterization of the blood flow changes that result from the occlusion of a single microvessel, a task well suited to optical methods. We use linear and nonlinear optical effects to induce clot formation in single surface and sub-surface vessels in the cortex of live rats. Surface vessels are occluded using photochemically-induced clots, while clot formation in deep-lying vessels is triggered using a novel technique based on nonlinear absorption of femtosecondlaser pulses. We visualize the vascular architecture and measure blood flow in individual vessels before and after clot formation using two-photon excitation fluorescence microscopy. We find that the redundancy of the cortical vasculature provides alternate paths for blood flow following an occlusion, but the speed of this reestablished flow depends on the locationof the clot in the vascular hierarchy. For example, we observe that blood flow is maintained downstream from an occluded surface arteriole through a reversal in the direction of flow at the first branch downstream from the clot. This reestablished flow is approximately 60% of the initial value, which is likely to maintain neural viability. In contrast, after clotting a deep-lying vessel we find that downstream flow is nearly stalled. This difference is likely due to distinct surface and sub-surface vascular architectures, and highlights the importance of the location of the blockage in the vascular hierarchy for determining cellular survival. Refreshments 1:30pm Faculty Lounge