Chronic Monitoring of Vascular Progression after Ischemic Stroke Using Multiexposure Speckle Imaging and Two-Photon Fluorescence Microscopy

Abstract

Monitoring the progression of the vascular structure and cerebral blood flow (CBF) after brain injury is vital to understand the neurovascular recovery process. Multiexposure speckle imaging (MESI) provides a quantitatively accurate technique for chronically measuring the postocclusion CBF perfusion of the infarct and peri-infarct regions in rodent stroke models, while multiphoton microscopy offers direct visualization of the microvascular structure. In this paper, we present imaging outcomes extending 35 days after photo-thrombotic occlusion, tracking the progression of the vasculature throughout this period. We compare MESI flow estimates within the unresolvable parenchyma with subsurface microvascular volume fractions taken with two-photon microscopy in the same regions to assess how the vascular density influences the surface-integrated MESI flow values. The MESI flow measurements and volume fractions are shown to have high correlations (r = 0.90) within areas of recovering vasculature in the peri-infarct region. We also observe vascular reorientation occurring within the microvascular structure throughout the 35-day postocclusion period. With the combination of a chronic mouse model and relatively noninvasive optical imaging techniques, we present an imaging protocol for monitoring long-term vascular progression after photo-thrombotic occlusion with the potential to test the efficacy of rehabilitation and pharmacological therapies.

Infarct prediction by intraoperative laser speckle imaging in patients with malignant hemispheric stroke

“…Nevertheless, the quantitative accuracy of iLSI could be further improved by intraoperative implementation of multiexposure LSI, 28 as recently demonstrated in quantitative monitoring of ischemic lesion evolution in rodent models of focal stroke. 29,30 Also, motion artifacts from cardiac, respiratory and brain shifting activity can influence perfusion measurements in continuously acquired optical image sets. 27 In the present study, the following steps were taken to minimize motion artifacts as much as possible: first, blood pressure and PaCO 2 during the iLSI measurement were maintained at a constant level.…”

Nanoelectronics enabled chronic multimodal neural platform in a mouse ischemic model

“…Here we took advantages of targeted photothrombosis where we controlled the lesion size and location, and chose to target partial branches of arterioles near one NET shank. From our previous experience, such small occlusions typically lead to ischemic penumbra in mouse brain spanning 1 – 2 mm[30], matching the spatial distribution of the NET electrodes. The inter-shank spacing and the intra-shank distribution of NET electrodes can be adjusted for lesions of various sizes and severity.…”

“…Laser speckle contrast imaging (LSCI) is used as a cost-effective method for visualizing and quantifying neurovascular blood flows particularly in small animals[26, 27]. Multi-exposure speckle imaging (MESI), a refined method of LSCI to eliminate artifacts, allows for quantitative measurement of CBF for longitudinal studies and cross-animal comparisons[28–30]. In contrast, electrical recording in stroke models mostly relies on techniques developed decades ago that offers one or few recording sites either subdural[6, 31–33] or intra-cortical[34], with electrode dimensions and distance from the infarct often both on millimeter scales, lacking the necessary spatial resolution and specificity.…”

Spatial and temporal identification of cerebral infarctions based on multiphoton microscopic imaging

“…However, these techniques require exogenous fluorescence markers to produce the necessary labeling and contrast. A key advantage of MPM is that it does not require the use of such external markers, which has permitted the study of various functional aspects of the brain at the cellular and molecular level including the structural dynamics of microtubule and cortical vasculature after ischemia [38][39][40][41]. Despite the power and extent of information that MPM can provide, some limitations still exist for applying MPM imaging to cerebral ischemia in the clinic, especially in imaging depth and miniaturization.…”