Differential wall shear stress patterns in cerebral circulation of prediabetic adults: Possible evidence for increased stroke risk?

Abstract

Proper endothelial function is crucial to cerebral vascular health and is affected by wall shear stress (WSS) patterns. Metabolic syndrome (MetSyn) is a prediabetic state that contributes to endothelial dysfunction which can lead to clinical conditions, such as, stroke. The aim of this study was to quantify and compare resting WSS in multiple conduit cerebral arteries in healthy and MetSyn subjects. We hypothesized adults with Metsyn will display reduced WSS in cerebral arteries when compared to healthy controls. 7 healthy controls (29±2y) and 7 MetSyn (37±3y) underwent a single four‐dimensional (4D) flow MRI scan during quiet rest in the supine position. Data acquisition was based on a radial undersampling scheme named Phase Contrast Vastly‐undersampled Isotropic Projection Reconstruction (PC VIPR) used to generate a phase contrast (PC) angiogram, as well as, measure cerebral blood flow (CBF), and WSS non‐invasively without use of a contrast agent (three directional velocity encoding at a spatial and temporal resolution of 0.68 mm and 20 cardiac phases, respectively). Average scan time was ~ 5 minutes and produced large imaging volumes. Nine arteries were analyzed: Middle cerebral (MCA) ×2, anterior cerebral (ACA) ×2, internal carotid (ICA) ×2, vertebral (VA) ×2, and basilar. WSS was measured by segmenting the vascular tree from the PC angiograms and subsequently calculating the velocity gradient at the vessel wall from the 4D Flow MRI data over ~ 3 voxels. Total CBF was calculated as the sum of the left and right ICA and basilar artery. Resting total CBF was 577±45 ml· min−1 in healthy controls and 499±46 ml ·min−1 in MetSyn (p=0.25). Metsyn exhibited lower WSS (Pa) in the left MCA (3.7±0.2 vs. 3.0±0.2; p=0.01), right ACA (3.4±0.2 vs. 2.9±0.2; p=0.05), right ICA (2.7±0.3 vs. 1.8±0.1; p=0.01) and left ICA (2.8±0.3 vs. 1.5±0.1; p<0.01). This non‐invasive MRI approach provides new insight into local flow and shear patterns that might have a large impact on cerebral endothelial function. Younger adults with MetSyn exhibit lower WSS in anterior portions of the brain. Furthermore, these findings are consistent with the observation that stroke occurs most commonly in the anterior cerebral circulation. Given the young age (< 45 y) of these subjects, we propose chronically reduced WSS leads to endothelial dysfunction in middle/old age, thereby contributing to increased risk and severity of stroke in MetSyn.Support or Funding InformationFunded by the American Diabetes Association and an American Physiological Society Undergraduate Research Summer Fellowship.