Assessment of cerebrovascular responses to physiological stimuli in identical twins using multimodal imaging and computational fluid dynamics

Abstract

There is acknowledged variability in the Circle of Willis in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. We aimed to demonstrate the feasibility of combining high resolution imaging techniques and computational fluid dynamics (CFD) to describe cerebrovascular structure and function in vivo. We examined the null hypothesis that monozygotic (MZ) twins (18-30yrs) would exhibit similar CoW structure and function. Six twin pairs underwent 3T magnetic resonance angiography of the head and neck and B-mode Doppler ultrasound for velocity and diameter recordings in the vertebral and internal carotid arteries under three conditions (rest, hypercapnia and exercise). Artery diameter, length, tortuosity and bifurcation angle were assessed in regions of interest of the CoW. CFD simulated hemodynamics to determine the cardiac-cycle time averaged wall shear stress (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT). We observed low and insignificant intra-class correlations (ICC) between twins in all regions for diameter (ICC range 0.000-0.657, P>0.05), two of four regions for length (ICC range 0.355-0.368, P>0.05), all regions for tortuosity (ICC range 0.270-0.505, P>0.05), and all bifurcation angles (ICC range 0.000-0.547, P> 0.05). Similarly, no significant correlations were apparent for cerebral blood flow or CFD-derived measures of TAWSS, OSI and RRT, at rest or in response to hypercapnia or exercise. Therefore differences exist in CoW structure and associated shear stress in response to physiological stimulation. These data suggest that the structure, function and health of cerebrovascular arteries are not primarily genetically dependent.

Comparison of Transcranial Doppler Ultrasound with Computational Fluid Dynamics: Responses to Physiological Stimuli

“…Participants were exposed to conditions previously described by Thomas et al . 41 , consisting of rest (5 minutes recumbent), hypercapnia (5 min of 6% CO 2 via Douglas bag recumbent) and submaximal exercise (5 min recumbent cycling at 90 Watts) conditions respectively. Each session was conducted in the morning for all participants, who were instructed to fast (no food, tea or coffee) and abstain from consumption of alcohol or performing exercise in the 24 hours prior to the session.…”

“…The duplex ultrasound measurements of diameter and velocity at the ICAs and VAs over three cardiac cycles 20 were converted to time varying volume flow rate and waveform averaged and processed as described previously 41 . This resulted in spline fitted and peak aligned data.…”

“…In addition, we prescribed extrusions at the fluid boundaries equal to 11 times the boundary diameter to ensure adequate development of parabolic flow upstream and downstream of the fluid domain 6 . Mesh core density was set proportional to local vessel diameter and the mesh settings were prescribed as per previously published work 41 . These settings had been optimized to ensure mesh independence using the grid convergence index 31 and used the subject with the greatest inlet velocity measurements for this optimization.…”

“…These settings had been optimized to ensure mesh independence using the grid convergence index 31 and used the subject with the greatest inlet velocity measurements for this optimization. Optimal mesh size was deemed sufficient when the grid convergence index for wall shear stress within the CoW was found to fall below 3% 41 . Final mesh sizes ranged from 9.1 to 16.7 million cells per geometry.…”

“…It has also been used to assess prognosis and diagnosis of life-threating conditions such as sickle cell anemia, stenosis, hemorrhage and ischemia across a spectrum of patient ages 25, 29 . TCD is also used extensively in healthy populations to better understand cerebrovascular responses to physiological stimuli including hypercapnia, hypocapnia, exercise, vessel occlusion, shear-mediated endothelial responses and neurovascular coupling 5, 11, 15, 28, 41 . In addition, measurement of blood flow velocity using TCD has been used to infer volumetric cerebral blood flow – however the absence of diameter measurement is a limitation in this regard.…”