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Aging-related cerebral microvascular changes visualized using ultrasound localization microscopy in the living mouse.

ABSTRACT: Aging-related cognitive decline is an emerging health crisis; however, no established unifying mechanism has been identified for the cognitive impairments seen in an aging population. A vascular hypothesis of cognitive decline has been proposed but is difficult to test given the requirement of high-fidelity microvascular imaging resolution with a broad and deep brain imaging field of view, which is restricted by the fundamental trade-off of imaging penetration depth and resolution. Super-resolution ultrasound localization microscopy (ULM) offers a potential solution by exploiting circulating microbubbles to achieve a vascular resolution approaching the capillary scale without sacrificing imaging depth. In this report, we apply ULM imaging to a mouse model of aging and quantify differences in cerebral vascularity, blood velocity, and vessel tortuosity across several brain regions. We found significant decreases in blood velocity, and significant increases in vascular tortuosity, across all brain regions in the aged cohort, and significant decreases in blood volume in the cerebral cortex. These data provide the first-ever ULM measurements of subcortical microvascular dynamics in vivo within the context of the aging brain and reveal that aging has a major impact on these measurements.

SUBMITTER: Lowerison MR

PROVIDER: S-EPMC8755738 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Aging-related cerebral microvascular changes visualized using ultrasound localization microscopy in the living mouse.

Lowerison Matthew R MR Sekaran Nathiya Vaithiyalingam Chandra NVC Zhang Wei W Dong Zhijie Z Chen Xi X Llano Daniel A DA Song Pengfei P

Scientific reports 20220112 1

Aging-related cognitive decline is an emerging health crisis; however, no established unifying mechanism has been identified for the cognitive impairments seen in an aging population. A vascular hypothesis of cognitive decline has been proposed but is difficult to test given the requirement of high-fidelity microvascular imaging resolution with a broad and deep brain imaging field of view, which is restricted by the fundamental trade-off of imaging penetration depth and resolution. Super-resolut ...[more]

PMID: 35022482

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Project description:BackgroundWe studied the microvascular structure and function of in situ glioblastoma using ultrasound localization microscopy (ULM).MethodsThe in vivo study was conducted via craniotomy in six Sprague-Dawley rats. Capillary pattern, capillary hemodynamics, and functional quantitative parameters were compared among tumor core, invasive zone, and normal brain tissue with ex vivo micro-computed tomography (micro-CT) and scanning electron microscopy. Correlations between quantitative parameters and histopathological vascular density (VD-H), proliferation index, and histopathological vascular maturity index (VMI-H) were evaluated. Kruskal-Wallis H, ANOVA, Mann-Whitney U, Pearson, and Spearman correlation statistics were used.ResultsCompared to the tumor core, the invasive zone exhibited higher microvascularity structural disorder and complexity, increased hemodynamic heterogeneity, higher local blood flow perfusion (p ≤ 0.033), and slightly lower average flow velocity (p = 0.873). Significant differences were observed between the invasive zone and normal brain tissue across all parameters (p ≤ 0.001). ULM demonstrated higher microstructural resolution compared to micro-CT and a nonsignificant difference compared to scanning electron microscopy. The invasive zone vascular density correlated with VD-H (r = 0.781, p < 0.001). Vessel diameter (r = 0.960, p < 0.001), curvature (r = 0.438, p = 0.047), blood flow velocity (r = 0.487, p = 0.025), and blood flow volume (r = 0.858, p < 0.001) correlated with proliferation index. Vascular density (r = -0.444, p = 0.044) and fractal dimension (r = -0.933, p < 0.001) correlated with VMI-H.ConclusionULM provided high-resolution, noninvasive imaging of glioblastoma microvascularity, offering insights into structural/functional abnormalities.Relevance statementULM technology based on ultrafast ultrasound can accurately quantify the microvessels of glioblastoma, providing a new method for evaluating the effectiveness of antiangiogenic therapy and visualizing disease progression. This method may facilitate early therapeutic assessment.Key pointsULM reliably captures the vascular structures and hemodynamic features of glioblastoma in rats. Micro-CT and scanning electron microscopy validated its effectiveness in microvascular non-invasion characterization. ULM is expected to effectively evaluate glioblastoma anti-vascular therapy response.

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Aging-related cerebral microvascular changes visualized using ultrasound localization microscopy in the living mouse.

Publications

Aging-related cerebral microvascular changes visualized using ultrasound localization microscopy in the living mouse.

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