Imaging of cortical oxygen tension and blood flow following targeted photothrombotic stroke

Journal of Neuroscience Methods

et al. 2018

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Background Despite significant advancements of optical imaging techniques for mapping hemodynamics in small animal models, it remains challenging to combine imaging with spatially resolved electrical recording of individual neurons especially for longitudinal studies. This is largely due to the strong invasiveness to the living brain from the penetrating electrodes and their limited compatibility with longitudinal imaging. New Method We implant arrays of ultraflexible nanoelectronic threads (NETs) in mice for neural recording both at the brain surface and intracortically, which maintain great tissue compatibility chronically. By mounting a cranial window atop of the NET arrays that allows for chronic optical access, we establish a multimodal platform that combines spatially resolved electrical recording of neural activity and laser speckle contrast imaging (LSCI) of cerebral blood flow (CBF) for longitudinal studies. Results We induce peri-infarct depolarizations (PIDs) by targeted photothrombosis, and show the ability to detect its occurrence and propagation through spatiotemporal variations in both extracellular potentials and CBF. We also demonstrate chronic tracking of single-unit neural activity and CBF over days after photothrombosis, from which we observe reperfusion and increased firing rates. Comparison with Existing Method(s) This multimodal platform enables simultaneous mapping of neural activity and hemodynamic parameters at the microscale for quantitative, longitudinal comparisons with minimal perturbation to the baseline neurophysiology. Conclusion The ability to spatiotemporally resolve and chronically track CBF and neural electrical activity in the same living brain region has broad applications for studying the interplay between neural and hemodynamic responses in health and in cerebrovascular and neurological pathologies.

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanoelectronics enabled chronic multimodal neural platform in a mouse ischemic model

Luan

Journal of Neuroscience Methods

et al. 2018

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“…Simultaneously, laser light (200 mW, AixiZ) at 532 nm was patterned by a digital micromirror device (DMD, DLP3000, Texas Instruments). A small fraction of the light that scaled with the number of DMD pixels in the "on" state was delivered to the craniotomy to induce user-defined photothrombotic occlusions (16,46) in the cortical vasculature using Rose Bengal. The projected DMD pattern was co-registered with the LSCI camera via an affine image transformation.…”

Section: Laser Speckle Contrast Imaging and Targeted Photothrombosismentioning

confidence: 99%

“…We combined multi-shank, multidepth neural recording with multi-exposure speckle imaging (MESI), a refinement of speckle contrast imaging that enables quantification of CBF for longitudinal and cross-animal comparisons with high resolution at large field of view (14,15). By patterned illumination using a digital micromirror device (DMD), we induced targeted photothrombotic occlusion within individual or multiple surface arteriole branches to provide fine control over lesion location, size and onset time (16). In addition, by confining photodamage to arteries on the cortical surface, this modified technique produces a more graded penumbra than traditional photothrombosis (17).…”

Section: Introductionmentioning

confidence: 99%

Multimodal mapping of neural activity and cerebral blood flow reveals long-lasting neurovascular dissociations after small-scale strokes

Zhu

et al. 2020

Preprint

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Neurovascular coupling, the close spatial and temporal relationship between neural activity and hemodynamics, is disrupted in pathological brain states. To understand the altered neurovascular relationship in brain disorders, longitudinal, simultaneous mapping of neural activity and hemodynamics is critical yet challenging to achieve. Here, we employ a multimodal neural platform in a mouse model of stroke and realize long-term, spatially-resolved tracking of intracortical neural activity and cerebral blood flow in the same brain regions. We observe a pronounced neurovascular dissociation that occurs immediately after small-scale strokes, becomes the most severe a few days after, lasts into chronic periods, and varies with the level of ischemia. Neuronal deficits extend spatiotemporally whereas restoration of cerebral blood flow occurs sooner and reaches a higher relative value. Our findings reveal the neurovascular impact of mini-strokes and inform the limitation of neuroimaging techniques that infer neural activity from hemodynamic responses.

“…LSCI's advantage lies in its ability to rapidly image blood flow over a large field-of-view (FOV) with relatively simple and cost-effective instrumentation. LSCI has been widely adopted in a variety of biomedical applications, such as in skin flap monitoring [1,2], neurovascular blood flow imaging in small animal models [3,4], and more recently, clinical applications in real-time intra-operative cerebral blood flow monitoring during surgery [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Establishing the Effect of Vascular Structure on Laser Speckle Contrast Imagining

Jafari

Miller

et al. 2020

Preprint

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Laser Speckle Contrast Imaging (LSCI) is a powerful tool for non-invasive, real-time imaging of blood flow in tissue. However, the effect of tissue geometry on the form of the electric field autocorrelation function and speckle contrast values is yet to be investigated. In this paper, we present an ultrafast forward model for simulating a speckle contrast image with the ability to rapidly update the image for a desired illumination pattern and flow perturbation. We demonstrate the first simulated speckle contrast image and compare it against experimental results. We simulate three mouse-specific cerebral cortex decorrelation time images and implement three different schemes for analyzing the effects of homogenization of vascular structure on correlation decay times. Our results indicate that dissolving structure and assuming homogeneous geometry creates up to ∼ 10x shift in the correlation function decay times and alters its form compared with the case for which the exact geometry is simulated. These effects are more pronounced for point illumination and detection imaging schemes. Further analysis indicates that correlated multiple scattering events, on average, account for 50% of all dynamic scattering events for a detector over a vessel region and 31% that of a detector over parenchyma region, highlighting the significance of accurate modeling of the three-dimensional vascular geometry for accurate blood flow estimates.