Hemodynamics and stroke risk in intracranial atherosclerotic disease

Abstract

Objective: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model. Methods: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressure poststenotic /pressure prestenotic ) and translesional wall shear stress ratio (WSSR = WSS stenotic − throat /WSS prestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year. Results: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004). Interpretation: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. ANN NEUROL 2019;85:752-764 I ntracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke in Asian populations, contributing to 30 to 50% of ischemic stroke and transient ischemic attack (TIA). 1,2 In earlier pivotal trials on treatment of symptomatic ICAS (sICAS) patients, such as the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial, risk of recurrent stroke and death was up to 15% at 1 year among those with 50 to 99% sICAS treated with aspirin. 3 In the last few years, risk of recurrent stroke in such patients has decreased with better cardiovascular risk factor management, but still higher than stroke patients without ICAS. For instance, among minor stroke or high-risk TIA patients treated with aspirin plus clopidogrel for 21 days followed by clopidogrel mono therapy for days 22 to 90 in the View this article online at wileyonlinelibrary.com.

Characteristics of Wall Shear Stress and Pressure of Intracranial Atherosclerosis Analyzed by a Computational Fluid Dynamics Model: A Pilot Study

“…WSS, wall shear stress; WSS max , the maximum value of WSS; pressure terminal , the value of pressure at the terminal point; pressure origin , the value of pressure at the origin point. relapse in symptomatic ICAS patients (6). Our study initially demonstrates that the two indexes were not altered significantly until stenosis severity reached 50%.…”

“…From the proposed TOF-MRA-based CFD model, we also found that the WSS max was linearly correlated with pressure ratio (terminal/origin) and pressure drop (terminal−to−origin) in ICAS, accordingly with the result in coronary artery (27). Since WSSmax values beyond a critical value can induce atherosclerotic inflammation (6), our results also indicated that the plaque vulnerability induced by WSS max may be accompanied with the aggravation of mechanical load, and there was a possibility that plaque vulnerability and hypoperfusion collaboratively participate in the risk of stroke in ICAS.…”

“…The 3D geometric model was then reconstructed by a suite of software, Mimics (Materialize NV, Belgium), and then examined and manually revised by two neurologists, with the primary collaterals included. Further processing of the vascular surface and generation of the computational domain (volume mesh) was performed using the ANSYS ICEM CFD meshing software (ANSYS, Inc., USA) (6)(7)(8).…”

“…Considering the complexity of the cerebral artery geometry, we used the unstructured tetrahedral cell for domain discretization, and the mesh was finer nearby the area of stenosis where the flow field was of greater interest (6). The total number of elements was above one million, and the minimum volume of the elements was about 1.0 × 10 −8 cm 3 to capture the small-scale feature of the blood flow.…”

“…Several studies have applied computational fluid dynamics (CFD) to simulate and analyze the hemodynamics of ICAS (6)(7)(8). However, these studies relied on images of computed tomography angiography, which causes concerns in radioactivity and contrast administration, and applied with the hypothetical inlet flow condition.…”