TY - JOUR
T1 - Aging-related cerebral microvascular changes visualized using ultrasound localization microscopy in the living mouse
AU - Lowerison, Matthew R.
AU - Sekaran, Nathiya Vaithiyalingam Chandra
AU - Zhang, Wei
AU - Dong, Zhijie
AU - Chen, Xi
AU - Llano, Daniel A.
AU - Song, Pengfei
N1 - The study was partially supported by the National Cancer Institute, the National Institute of Biomedical Imaging and Bioengineering, the National Institute on Deafness and Other Communication Disorders, and the National Institute on Aging of the National Institutes of Health under grant numbers R00CA214523, R21EB030072, R21DC019473 and R03AG059103, as well as a grant to DL from the Kiwanis Neuroscience Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NCS is supported by a Beckman Institute Postdoctoral Fellowship.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-04712-8
DO - 10.1038/s41598-021-04712-8
M3 - Article
C2 - 35022482
AN - SCOPUS:85122786077
SN - 2045-2322
VL - 12
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 619
ER -