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

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.

4D flow MRI for non-invasive measurement of blood flow in the brain: A systematic review

“…Not only does it possess excellent test–retest multisite reproducibility, 29 but has been used successfully on relatively large samples of elderly, clinically relevant subjects, 13,53 and has been used alongside other techniques such as hypoxia-induction to measure cerebrovascular reactivity. 54,55 Due to its ability to allow post-hoc quantification of blood flow, pulsatility and pressure changes in anatomically-defined vessels (as distinct from local tissue perfusion) in a non-invasive, low-risk manner, 4D flow arguably aids PC-MRI in filling a niche left by techniques such as arterial spin labelling, catheter angiography and Doppler US.…”

Cerebrovascular responses to graded exercise in young healthy males and females

“…They observed similar levels of total brain blood flow between the sexes and greater perfusion in females at rest (Zarrinkoob et al., 2015). When stress such as CO 2 is introduced, MCA dilation is similar between the sexes (Miller et al., 2019). Similarly, under hypoxic and hypercapnic breathing, Peltonen and colleagues found MCAv response to 90% and 80% SpO 2 were similar (Δ 5 vs. 8 cm/s and Δ 13 vs. 14 cm/s) and hypercapnia at 10 mmHg above EtCO 2 baseline was similar (Δ 19 vs. 23 cm/s, males and females, respectively) (Peltonen et al., 2015).…”

“…However, there have been many investigations that have examined cerebrovascular responses to changes in pressure or arterial CO 2 in isolation. 4D‐MRI analysis of the major cerebral arteries during hypercapnia has found young males to have a greater cerebral vascular reactivity than young females (Miller et al., 2019). However, this finding is not consistent especially in studies that have measured CBF with TCD (Fan et al., 2019; Madureira et al., 2017; Peltonen et al., 2015).…”

Integrative cardiovascular control in women: Regulation of blood pressure, body temperature, and cerebrovascular responsiveness

“…The above discussion suggests that sex influences cerebral artery structure and function, but sex differences in cerebrovascular control mechanisms in men and women are less clear. Some studies have reported higher cerebrovascular reactivity to hypercapnia in young women compared with young men 60,61 ; yet, more recent studies have reported higher cerebrovascular reactivity in young men compared with young women 58,77,80 or no change in cerebrovascular reactivity. 81 It is important to note that any potential sex differences in cerebrovascular reactivity may be influenced by alterations in chemosensitivity to hypercapnia between men and women.…”