Cerebrovascular Reactivity Following Spinal Cord Injury
Authors: Weber Alexander Mark , Nightingale Tom E. , Jarrett Michael , Lee Amanda H. X. , Campbell Olivia , Walter Matthias , Lucas Samuel J.E. , Phillips Aaron , Rauscher Alexander , Krassioukov Andrei 
Published: June 2022

Cervical and upper-thoracic spinal cord injury (SCI) commonly results in autonomic cardiovascular impairments. These impairments can lead to alterations in blood flow, cerebral perfusion pressure and ultimately tissue perfusion, which can lead to an elevated risk of stroke and global cognitive deficits. The aim of this study was to assess cerebrovascular reactivity (CVR) in both the grey matter (GM) and brainstem using functional magnetic resonance imaging (fMRI) in participants with SCI compared to non-injured controls. CVR represents the capacity of brain parenchyma to change cerebral blood flow in response to a vasoactive stimulus (e.g. carbon dioxide, CO2) or altered metabolic demand [e.g. neurovascular coupling (NVC)]. Thirteen participants (7 chronic SCI (all male, median age of 42 years), 6 controls (all male, median age of 33 years) were studied cross-sectionally. CVR was measured by assessing the MRI-blood oxygen level–dependent signal with hypercapnic challenge (controlled CO2 inhalation). The CVR outcome measure was assessed in three ways. Initially, CVR was calculated as is standard, via the linear, least-squares ﬁt across the whole gas challenge protocol (CVRwhole). In addition, CVR was further decomposed into its dynamic (tau) and static components (steady state CVR; ssCVR). A 24-hour ambulatory blood pressure monitor was worn to capture free-living blood pressure outcomes. Our results showed a longer tau in the GM of SCI participants compared to controls (median of the difference = 3.0 seconds; p<0.05). Time since injury (TSI) displayed negative correlations with ssCVR in the GM and brainstem of SCI participants: RS=-0.77, p=0.041 and RS=-0.76, p=0.049, respectively, where RS is the Spearman’s rank Correlation Coefficient. Neurological level of injury (NLI), modified into an ascending, continuous numeric variable, was positively correlated with GM CVRwhole (RS=0.85, p=0.016), GM ssCVR (RS=0.95, p=0.001) and brainstem ssCVR (RS=0.90, p=0.006). Lower CVRwhole and ssCVR in the SCI-cohort was significantly (P<0.05) correlated with lower daytime blood pressure (RS≥ 0.81) and a higher frequency of hypotensive episodes (RS≥ -0.83). Thus, living with a SCI for a longer period of time, having a higher NLI and lower blood pressure are linked with poorer CVR outcomes. Our preliminary findings reveal an important difference between the cohorts in the dynamic CVR component, tau. Collectively, these results may partially explain the increased cerebrovascular health burden in individuals with SCI.

Highlights

CVR is the change in blood flow in response to a vasodilatory stimulus (e.g., hypercapnia).

Impaired CVR is linked with increased stroke risk and cognitive deficits.

We investigated the dynamic and steady-state components of CVR using fMRI in individuals with a SCI.

The dynamic component was significantly different compared to non-injured controls.

CVR is significantly correlated with time since injury, level of injury and ambulatory daytime blood pressure.