Dataset Information

High-Spatiotemporal-Resolution Ultrasound Flow Imaging to Determine Cerebrovascular Hemodynamics in Alzheimer's Disease Mice Model.

ABSTRACT: Although the relationships of cerebrovascular hemodynamic dysfunction with neurodegenerative diseases remain unclear, many studies have indicated that poor cerebral perfusion accelerates the progression of neurodegenerative diseases, such as Alzheimer's disease (AD). Small animal models are widely used in AD research. However, providing an imaging modality with a high spatiotemporal resolution and sufficiently large field of view to assess cerebrovascular hemodynamics in vivo remains a challenge. The present study proposes a novel technique for high-spatiotemporal-resolution vector micro-Doppler imaging (HVμDI) based on contrast-free ultrafast high frequency ultrasound imaging to visualize the cerebrovascular hemodynamics of the mouse, with a data acquisition time of 0.4 s, a minimal detectable vessel size of 38 µm, and a temporal resolution of 500 Hz. In vivo experiments are conducted on wild-type and AD mice. Cerebrovascular hemodynamics are quantified using the cerebral vascular density, diameter, velocity, tortuosity, cortical flow pulsatility, and instant flow direction variations. Results reveal that AD significantly change the cerebrovascular hemodynamics. HVμDI offers new opportunities for in vivo analysis of cerebrovascular hemodynamics in neurodegenerative pathologies in preclinical animal research.

SUBMITTER: Huang H

PROVIDER: S-EPMC10724386 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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High-Spatiotemporal-Resolution Ultrasound Flow Imaging to Determine Cerebrovascular Hemodynamics in Alzheimer's Disease Mice Model.

Huang Hsin H Hsu Pei-Ling PL Tsai Sheng-Feng SF Chuang Yi-Hsiang YH Chen De-Quan DQ Xu Guo-Xuan GX Chen Chien C Kuo Yu-Min YM Huang Chih-Chung CC

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231114 35

Although the relationships of cerebrovascular hemodynamic dysfunction with neurodegenerative diseases remain unclear, many studies have indicated that poor cerebral perfusion accelerates the progression of neurodegenerative diseases, such as Alzheimer's disease (AD). Small animal models are widely used in AD research. However, providing an imaging modality with a high spatiotemporal resolution and sufficiently large field of view to assess cerebrovascular hemodynamics in vivo remains a challenge ...[more]

PMID: 37964413

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Project description:BackgroundVascular dysfunction is closely associated with the progression of Alzheimer's disease (AD). A critical research gap exists that no studies have explored the in vivo temporal changes of cerebrovascular alterations with AD progression in mouse models, encompassing both structure and flow dynamics at micron-scale resolution across the early, middle, and late stages of the disease.MethodsIn this study, ultrasound localisation microscopy (ULM) was applied to image the cerebrovascular alterations of the transgenic female 5×FAD mouse model across different stages of disease progression: early (4 months), moderate (7 months), and late (12 months). Age-matched non-transgenic (non-Tg) littermates were used as controls. Immunohistology examinations were performed to evaluate the influence of disease progression on the β-amyloid (Aβ) load and microvascular alterations, including morphological changes and the blood-brain barrier (BBB) leakage.FindingsOur findings revealed a significant decline in both vascular density and flow velocity in the retrosplenial cortex of 5×FAD mice at an early stage, which subsequently became more pronounced in the visual cortex and hippocampus as the disease progressed. Additionally, we observed a reduction in vascular length preceding diminished flow velocities in cortical penetrating arterioles during the early stages. The quantification of vascular metrics derived from ULM imaging showed significant correlations with those obtained from vascular histological images. Immunofluorescence staining identified early vascular abnormalities in the retrosplenial cortex. As the disease advanced, there was an exacerbation of Aβ accumulation and BBB disruption in a regionally variable manner. The vascular changes observed through ULM imaging exhibited a negative correlation with amyloid load and were associated with the compromise of the BBB integrity.InterpretationThrough high-resolution, in vivo imaging of cerebrovasculature, this study reveals significant spatiotemporal dysfunction in cerebrovascular dynamics accompanying disease progression in a mouse model of AD, enhancing our understanding of its pathophysiology.FundingThis study is supported by grants from National Key Research and Development Program of China (2020YFA0908800), National Natural Science Foundation of China (12074269, 82272014, 82327804, 62071310), Shenzhen Basic Science Research (20220808185138001, JCYJ20220818095612027, JCYJ20210324093006017), STI 2030-Major Projects (2021ZD0200500) and Guangdong Natural Science Foundation (2024A1515012591, 2024A1515011342).

Project description:To validate a prospectively triggered spiral phase-contrast magnetic resonance (MR) sequence accelerated with sensitivity encoding (SENSE) in a population of children and adults with congenital heart disease.The local research ethics committee approved this study, and written consent was obtained from all patients or guardians. Stroke volumes were quantified in 40 patients (mean age ± standard deviation: 21.4 years ± 13.8, age range: 3.0-61.3 years; 22 male patients aged 3.0-38.0 years [mean age, 17.2 years ± 10.5], 18 female patients aged 4.7-61.3 years [mean age, 26.6 years ± 15.9]) with congenital heart disease in the aorta (n = 40), main pulmonary artery (n = 38), right pulmonary artery (n = 22), and left pulmonary artery (n = 24). Stroke volumes were obtained with (a) breath-hold spiral phase-contrast MR imaging with SENSE, (b) conventional breath-hold cartesian phase-contrast MR imaging, and (c) reference free-breathing phase-contrast MR imaging. Stroke volumes were compared by using repeated-measures analysis of variance, Bland-Altman analysis, and correlation coefficients.Imaging time with the breath-hold spiral phase-contrast MR sequence was significantly lower than that with the conventional breath-hold phase-contrast MR sequence (~5 seconds vs ~16 seconds, respectively; P < .0001). There was excellent agreement in stroke volumes in all vessels between the reference free-breathing sequence (mean volume, 60.3 mL ± 27.3) and the two breath-hold sequences-spiral SENSE phase-contrast MR imaging (mean volume, 59.5 mL ± 27.1; P < .001) and conventional cartesian phase-contrast MR imaging (mean volume, 59.8 mL ± 27.6; P = .268). The limits of agreement were smaller with the spiral breath-hold sequence than with the conventional breath-hold sequence (-4.4 mL, 2.9 mL vs -10.3 mL, 9.3 mL, respectively); correlation was similar (r = 0.998 vs r = 0.984, respectively).Flow volumes can be accurately and reliably quantified by using a spiral SENSE phase-contrast MR sequence, with high spatiotemporal resolution obtained in a short breath hold.

Dataset Information

High-Spatiotemporal-Resolution Ultrasound Flow Imaging to Determine Cerebrovascular Hemodynamics in Alzheimer's Disease Mice Model.

Publications

High-Spatiotemporal-Resolution Ultrasound Flow Imaging to Determine Cerebrovascular Hemodynamics in Alzheimer's Disease Mice Model.

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