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

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthew R. Lowerison ◽  
Nathiya Vaithiyalingam Chandra Sekaran ◽  
Wei Zhang ◽  
Zhijie Dong ◽  
Xi Chen ◽  
...  

AbstractAging-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.

2021 ◽  
Author(s):  
Matthew R Lowerison ◽  
Nathiya Chandra Sekaran ◽  
Wei Zhang ◽  
Zhijie Dong ◽  
Xi Chen ◽  
...  

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 contradictory radiologic needs of high-fidelity microvascular imaging resolution and a broad and deep brain imaging field of view. 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 cortex. These data provide the first-ever measurements of subcortical microvascular dynamics in vivo and reveal that aging has a major impact on these measurements.


2020 ◽  
Vol 6 (3) ◽  
pp. 035019 ◽  
Author(s):  
David Espíndola ◽  
Ryan M DeRuiter ◽  
Francisco Santibanez ◽  
Paul A Dayton ◽  
Gianmarco Pinton

2021 ◽  
Author(s):  
Jihun Kim ◽  
Mathew R. Lowerison ◽  
Nathiya Chandra Sekaran ◽  
Zhengchang Kou ◽  
Zhijie Dong ◽  
...  

AbstractUltrasound localization microscopy (ULM) demonstrates great potential for visualization of tissue microvasculature at depth with high spatial resolution. The success of ULM heavily depends on the robust localization of isolated microbubbles (MBs), which can be challenging in vivo especially within larger vessels where MBs can overlap and cluster close together. While MB dilution alleviates the issue of MB overlap to a certain extent, it drastically increases the data acquisition time needed for MBs to populate the microvasculature, which is already on the order of several minutes using recommended MB concentrations. Inspired by optical super-resolution imaging based on stimulated emission depletion (STED), here we propose a novel ULM imaging sequence based on microbubble uncoupling via transmit excitation (MUTE). MUTE “silences” MB signals by creating acoustic nulls to facilitate MB separation, which leads to robust localization of MBs especially under high concentrations. The efficiency of localization accomplished via the proposed technique was first evaluated in simulation studies with conventional ULM as a benchmark. Then an in vivo study based on the chorioallantoic membrane (CAM) of chicken embryos showed that MUTE could reduce the data acquisition time by half thanks to the enhanced MB separation and localization. Finally, the performance of MUTE was validated in an in vivo mouse brain study. These results demonstrate the high MB localization efficacy of MUTE-ULM, which contributes to a reduced data acquisition time and improved temporal resolution for ULM.


Author(s):  
XIAOFENG YU ◽  
ZHILONG ZHU ◽  
SHUZHAN ZHENG ◽  
JIAN JIANG ◽  
JUANJUAN JIANG ◽  
...  

Subjective cognitive decline (SCD), characterized by self-perceived subtle cognitive impairment ahead of the appearance of explicit and measurable cognitive deficits, is regarded as the preclinical manifestation of the pathological change continuum of Alzheimer’s disease (AD). We were committed to exploring the amyloid and glucose metabolic signatures related to imminent brain metabolic changes in SCD subjects. This study included 39 subjects (mean age = 71.9 years; 14 males and 25 females) diagnosed with SCD disease and 39 gender-matched healthy controls (HCs) (mean age = 75.2; 16 males and 23 females) with brain [18F] fluorodeoxyglucose positron emission tomography (PET) images and [18F] florbetapir PET images. The standardized uptake value ratios (SUVRs) of PET images within the regions of interest (ROIs) were calculated. Inter-group SUVR differences were assessed by two-sample [Formula: see text]-testing and receiver operating characteristic curve (ROC) analyses. A generalized linear model (GLM) was employed to evaluate the correlations between amyloid and FDG uptake. Compared with HCs, SCD subjects showed significantly increased amyloid SUVR, as well as significantly increased glucose SUVR in the olfactory, amygdala, thalamus, heschl gyrus, superior and middle temporal gyrus and temporal pole (all [Formula: see text]). The amyloid SUVR of thalamus was found to have a better ROC result (area under the curve (AUC): 0.77, 95% confidence interval (CI): 0.66–0.86) in the HC group, as was the case with the glucose SUVR of the middle temporal gyrus (AUC: 0.83, 95% CI: 0.73–0.91). There were significant positive correlations between amyloid and glucose SUVRs ([Formula: see text]). The amyloid SUVR of the thalamus showed a significantly better main effect (odd ratio [Formula: see text] 2.91, 95% CI: 1.44–6.7, [Formula: see text]), and the glucose SUVR of the heschl gyrus indicated an enhanced main effect (odd ratio [Formula: see text] 5.08, 95% CI: 1.86–18.15, [Formula: see text]). SCD subjects demonstrated significant amyloid accumulation and glucose hypermetabolism in specific brain regions, and amyloid pathology overlapped with regions of glucose abnormality. These findings may advance the understanding of imminent pathological changes in the SCD stage and help to provide clinical guidelines for interventional management.


Nature ◽  
2015 ◽  
Vol 527 (7579) ◽  
pp. 499-502 ◽  
Author(s):  
Claudia Errico ◽  
Juliette Pierre ◽  
Sophie Pezet ◽  
Yann Desailly ◽  
Zsolt Lenkei ◽  
...  

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