Age-Related Reductions in Cerebrovascular Reactivity Using 4D Flow MRI

Kathleen B Miller, Anna J Howery, Leonardo A Rivera-Rivera, Sterling C Johnson, Howard A Rowley, Oliver Wieben, Jill N Barnes, Kathleen B Miller, Anna J Howery, Leonardo A Rivera-Rivera, Sterling C Johnson, Howard A Rowley, Oliver Wieben, Jill N Barnes

Abstract

Cerebrovascular reactivity (CVR), is important for determining future risk of cerebrovascular disease. It is unclear if primary aging is associated with reductions in CVR because previous studies often include participants with vascular risk factors. Additionally, the inconsistency in the literature may be due to the inherent difficulty in quantifying intracranial cerebral blood flow and CVR. To address these limitations, we determined the effect of age on CVR in the large intracranial vessels in adults with low vascular risk using state-of-the-art MRI techniques. We also determined if the effect of age on CVR was sex-specific. Young (n = 20; 25 ± 3 years) and older (n = 19; 61 ± 5 years) healthy, physically active adults participated in the study. CVR was measured in response to hypercapnia using 4D flow MRI, which allows for simultaneous angiographic and quantitative blood flow measurements in the intracranial arteries. Older adults had lower global CVR and CVR in multiple intracranial arteries [right and left internal carotid arteries (ICA), right and left middle cerebral arteries (MCA), and basilar artery (BA)] compared with young adults (p < 0.05 for all). In addition, the MCA dilated significantly in response to hypercapnia in young (p < 0.05), but not older adults. Young men demonstrated higher global CVR and CVR in multiple intracranial arteries (ICAs, MCAs, and BA) compared with young women and older men (p < 0.05 for both); however, CVR did not differ between young women and older women. Our results demonstrate that, using 4D flow MRI, primary aging is associated with lower CVR in adults with low vascular risk. In addition, the effect of age on CVR may be driven by men. The 4D flow MRI technique may provide a promising new alternative to measure cerebrovascular physiology without the limitations of commonly used techniques. Future studies could utilize this MRI technique to examine interventions to maintain CVR with advancing age. This study was registered under clinicaltrials.gov # NCT02840851.

Keywords: cerebral blood flow; cerebrovascular conductance; middle cerebral artery; neuroimaging; sex differences.

Copyright © 2019 Miller, Howery, Rivera-Rivera, Johnson, Rowley, Wieben and Barnes.

Figures

FIGURE 1
FIGURE 1
This image shows an example participant’s 4D flow MRI scan during normocapnia. Warmer colors indicate higher flow. Blood flow and vessel cross sectional area (CSA) were averaged along the length of the vessel. The middle cerebral arteries (MCA) were measured along the M1 segment. The internal carotid arteries (ICA) were measured along the cervical and petrous portions below the carotid siphon. The basilar artery (BA) was measured below the superior cerebellar artery and above the bifurcation of the vertebral arteries. Global flow was calculated as the sum of the right and left ICA and the BA flows. End points or branches were removed from the vessel analysis.
FIGURE 2
FIGURE 2
This image displays cerebrovascular reactivity (CVR) to hypercapnia in young and older adults. (A) Global CVR in young and older adults. (B) CVR in each intracranial vessel of interest [basilar artery, left (L) and right (R) internal carotid arteries (ICA), and L and R middle cerebral arteries (MCA)]. CVR was calculated as the linear relationship between cerebrovascular conductance (CVC) (flow/mean arterial pressure × 100) and end-tidal carbon dioxide during 4 and 6% CO2 inhalation. Young adults are shown in black and older adults are shown in gray. Data are mean ± standard error. ∗p < 0.05. Global CVR was significantly lower in older adults compared with young adults. These results persisted in each vessel of interest (basilar artery, ICAs, and MCAs).
FIGURE 3
FIGURE 3
This image displays global cerebrovascular reactivity (CVR) to hypercapnia in young and older men and women. (A) Global CVR in young and older men and women. (B) CVR in each intracranial vessel of interest [basilar artery, left (L) and right (R) internal carotid arteries (ICA), and L and R middle cerebral arteries (MCA)]. CVR was calculated as the linear relationship between cerebrovascular conductance (CVC) (flow/mean arterial pressure × 100) and end-tidal carbon dioxide during 4 and 6% CO2 inhalation. Young men are shown in black, young women are shown in black stripes, older men are shown in gray and older women are shown in gray stripes. Data are mean ± standard error. ∗p < 0.05 compared with young of same sex. †p < 0.05 compared with men of same age. Young men demonstrated higher global CVR than younger women and older men. No sex-differences in global CVR were present in older adults. These results persisted in each vessel of interest (basilar artery, ICAs and MCAs).
FIGURE 4
FIGURE 4
This image displays the cross sectional area (CSA) of the left and right middle cerebral artery (MCA) during normocapnia and hypercapnia (6% CO2 inhalation) in (A) young and (B) older adults. The group average response is shown in black. Gray lines demonstrate individual responses. On average, the left MCA CSA significantly increased from normocapnia to 6% CO2 in young adults (p = 0.004) but the change in CSA was not significant in older adults (p = 0.08). The right MCA CSA significantly increased from normocapnia to 6% CO2 in young adults (p = 0.002) but the change in CSA was not significant in older adults (p = 0.19). There were no differences in the response to hypercapnia between the right MCA CSA compared with the left MCA CSA in young (p = 0.28) and older (p = 0.72) adults.

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