The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study

Abstract

Moyamoya disease (MMD) is a rare cerebro-occlusive disease with unknown etiology that can cause both ischemic and hemorrhagic stroke. MMD is characterized by progressive stenosis of the terminal internal carotid artery (ICA) and development of basal brain collaterals. Early-stage MMD is known to cause hemodynamic insufficiency despite mild or moderate stenosis of the intracranial arteries, but the exact mechanism underlying this pathophysiological condition is undetermined. We used highresolution Large eddy Simulations to investigate multiple complex hemodynamic phenomena that led to cerebral ischemia in five patients with early-stage MMD. The effects of transitional flow, coherent flow structures and blood shear-thinning properties through regions of tortuous and stenosed arteries were explored and linked to symptomatology. It is evidently shown that in some cases complex vortex structures, such as Rankine-type vortices, redirects blood flow away from some arteries causing significant reduction in blood flow. Moreover, partial blood hammer (PBH) phenomenon was detected in some cases and led to significant hemodynamic insufficiency. PBH events were attributed to the interaction between shear-thinning properties, transitional flow structures and loss of upstream pressure-velocity phase lag. We clearly show that the hemodynamic complexities in early-stage MMD could induce ischemia and explain the non-responsiveness to antiplatelet therapy.Moyamoya disease (MMD) is a rare cerebrovascular disease, characterized by bilateral occlusive changes at the internal carotid artery (ICA) terminus and an abnormal collaterals development at the base of the brain 1 . MMD is more prevalent in East Asian populations and can present as either ischemic or hemorrhagic stroke 2 . MMD can occur in pediatric or adult populations 2-4 and can present as bilateral or unilateral disease involvement 5 . The basic pathology of MMD, including its temporal profile, is clearly indicated by Suzuki's angiographic staging 1 , demonstrating the pathologic conversion of the cerebral vascular supply from internal carotid (IC) to the external carotid (EC) system 6 . Insufficiency of this 'IC-EC conversion system' could result in either ischemic or hemorrhage MMD presentations.Recent advance in high resolution magnetic resonance (HR-MR) vascular wall imaging enabled us to diagnose MMD even in its early stage, by demonstrating the characteristic vascular wall structure such as outer-diameter narrowing and the concentric stenosis of the affected intracranial arteries 7-9 . All of these characteristic findings by HR-MR vascular wall imaging are precisely reflected by vascular wall pathology of MMD including medial layer thinning and the waving of internal elastic lamina 10,11 . Accurate diagnosis of the early-stage MMD is clinically important because it could manifest as transient ischemic attacks (TIA) and/or cerebral infarction due to the significant hemodynamic compromise, despite its mild or moderate stenosis. Nonetheless, the mechanism

RNF213 loss of function reshapes vascular transcriptome and spliceosome leading to disrupted angiogenesis and aggravated vascular inflammatory responses

“…This interaction causes and modulates many vascular pathologies such as stenosis, aneurysms, and atherosclerosis 16,24,25 . We have previously shown that MMD symptomatology is impacted by complex hemodynamics arising from the complex morphology of the MMD associated ICA stenosis in early stage MMD 26 . However, our previous work does not provide a causal link between vascular hemodynamics and MMD initiation, but it was rather focused on the impact of MMD induced ICA stenosis on the hemodynamics leading to transient ischemic attacks (TIA).…”

“…A very interesting aspect of MMD is the exclusive occurrence of stenosis in the carotid terminus, despite being a genetic disease that, theoretically, should impact many vessels in the body. A way to explain this phenomenon is by looking at the blood hemodynamics in MMD patients 26 . However, traditional analysis methods utilizing wall shear stress or other common parameters fail to pinpoint the causality of MMD locality of pathogenesis 24,26 .…”

“…A way to explain this phenomenon is by looking at the blood hemodynamics in MMD patients 26 . However, traditional analysis methods utilizing wall shear stress or other common parameters fail to pinpoint the causality of MMD locality of pathogenesis 24,26 . Interestingly, in a previous unrelated work, our group was able to discover a new type of turbulence in the common and internal carotid arteries in healthy individuals 42 .…”

Time to peak and full width at half maximum in MR perfusion: valuable indicators for monitoring moyamoya patients after revascularization

“…One possible reason is that the deconvolution process is sensitive to AIF selection 23 . It is highly challenging for clinicians to select the optimal AIF at any DSC MRI scans consistently given the hemodynamic complexities in MMD 24 .…”

A Novel Method for Improving the Accuracy of MR-derived Patient-specific Vascular Models using X-ray Angiography

“…Computational fluid dynamics (CFD) simulation has been successfully used to evaluate hemodynamic quantities in the major arteries of the CoW 8, 12, 13 . As variations in vessel architecture can strongly influence local hemodynamics including WSR 14 , it is critically important that computational modeling accurately captures a patient’s vascular anatomy.…”