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Nonlinear Optics in Vivo: Using Light to Study and Perturb Function in the Living Brain
Chris Schaffer, Cornell University
February 9, 2007
Abstract
Blood flow to the brain is supplied through a highly interconnected vascular network containing loops and redundant connections at all levels. Although this redundancy provides some protection against vascular blockages, clinical evidence nonetheless implicates the occlusion of small blood vessels in the progression of neurodegenerative disorders such as Alzheimer's disease 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, anesthetized rodents. 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 femtosecond laser pulses. We visualize the vascular architecture and measure blood flow in individual vessels before and after clot formation using two-photon excited 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 location of 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 sufficient to maintain downstream neural viability. In contrast, after clotting a microvessel located deep within the brain we find that downstream flow is nearly stalled. This difference is 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.
Biography
Chris Schaffer received his undergraduate degree from the University of Florida in 1995 and Ph.D. from Harvard University in 2001, both in Physics. He is currently an Assistant Professor at Cornell University in the Department of Biomedical Engineering. His research focuses on the use of nonlinear optical interactions between femtosecond duration laser pulses and biological materials as a tool for precise ablation of structures and quantitative observation of dynamical processes in live biological samples. A current area of interest is the pathophysiology of small-scale stroke and studies of the changes in cerebral blood flow that result from localized, optically-induced occlusions in the microvasculature.