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Dysfunction in neurovascular coupling that results in a mismatch between cerebral blood flow and neuronal activity has been suggested to play a key role in the pathogenesis of Alzheimer's disease (AD). Meanwhile, physical exercise is a powerful approach for maintaining cognitive health and could play a preventive role against the progression of AD. Given the fundamental role of capillaries in oxygen transport to tissue, our pilot study aimed to characterize changes in capillary hemodynamics with AD and AD supplemented by exercise. Exploiting two-photon microscopy, intrinsic signal optical imaging, and magnetic resonance imaging, we found hemodynamic alterations and lower vascular density with AD that were reversed by exercise. We further observed that capillary properties were branch order-dependent and that stimulation-evoked changes were attenuated with AD but increased by exercise. Our study provides novel indications into cerebral microcirculatory disturbances with AD and the modulating role of voluntary exercise on these alterations.

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This article describes the generation of elastic shear waves in a soft medium using a laser beam. Our experiments show two different regimes depending on laser energy. Physical modeling of the underlying phenomena reveals a thermoelastic regime caused by a local dilatation resulting from temperature increase, and an ablative regime caused by a partial vaporization of the medium by the laser. Computed theoretical displacements are close to experimental measurements. A numerical study based on the physical modeling gives propagation patterns comparable to those generated experimentally. These results provide a physical basis for the feasibility of a shear wave elastography technique (a technique which measures a soft solid stiffness from shear wave propagation) by using a laser beam.When a laser beam of sufficient energy is incident on a medium, the absorption of the electromagnetic radiation leads to an increase in the local temperature. Due to thermal effects, displacements occur in the medium, which can then propagate as elastic waves. Elastic waves within a bulk can be separated into two components: compression waves, corresponding to a curl-free propagation, and shear waves, corresponding to a divergencefree propagation 1 . Measures of the transmission characteristics of compression and shear waves are useful for inspecting solids, such as a metal, to reveal potential cracks or defects 21 . In biological tissues, induction of compression waves by laser has been studied with the development of photoacoustic imaging 23 . Elastic waves used in photoacoustic imaging are typically of a few megahertz; at this frequency, shear waves are quickly attenuated in soft tissues, typically over a few microns, and only compression waves can propagate over a few centimeters.

Significance: Understanding how the brain recovers from cerebral tissue and vascular damage after an ischemic event can help develop new therapeutic strategies for the treatment of stroke. Aim: We investigated cerebral tissue repair and microvasculature regeneration and function after a targeted ischemic stroke. Approach: Following photothrombosis occlusion of microvasculature, chronic optical coherence tomography (OCT)-based angiography was used to track ischemic tissue repair and microvasculature regeneration at three different cortical depths and up to 28 days in awake animals. Capillary network orientation analysis was performed to study the structural pattern of newly formed microvasculature. Based on the time-resolved OCT-angiography, we also investigated capillary stalling, which is likely related to ischemic stroke-induced inflammation. Results: Deeper cerebral tissue was found to have a larger ischemic area than shallower regions at any time point during the course of poststroke recovery, which suggests that cerebral tissue located deep in the cortex is more vulnerable. Regenerated microvasculature had a highly organized pattern at all cortical depths with a higher degree of structural reorganization in deeper regions. Additionally, capillary stalling event analysis revealed that cerebral ischemia augmented stalling events considerably. Conclusion: Longitudinal OCT angiography reveals that regenerated capillary network has a highly directional pattern and an increased density and incidence of capillary stalling event.

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Recent studies suggested that cerebrovascular micro-occlusions, i.e. microstokes, could lead to ischemic tissue infarctions and cognitive deficits. Due to their small size, identifying measurable biomarkers of these microvascular lesions remains a major challenge. This work aims to simulate potential MRI signatures combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). Driving our hypothesis are recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially-oriented, and optical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n = 5) before and after inducing targeted photothrombosis, were analyzed. Computational vascular graphs combined with a 3D Monte-Carlo simulator were used to characterize the magnetic resonance (MR) response, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. We quantified the minimal intravoxel signal loss ratio when applying multiple gradient directions, at varying sequence parameters with and without ASL. With ASL, our results demonstrate a significant difference (p < 0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p < 0.005) using angiograms measured at week 4. Without ASL, no reliable signal change was found. We found that higher ratios, and accordingly improved significance, were achieved at lower magnetic field strengths (e.g., B0 = 3T) and shorter echo time TE (< 16 ms). Our simulations suggest that microstrokes might be characterized through ASL-DWI sequence, providing necessary insights for posterior experimental validations, and ultimately, future translational trials.