Patient-Specific Modeling Could Predict Occurrence of Pediatric Stroke.

John D Horn,Dianna M Milewicz,Shaolie S Hossain,Michael J Johnson,Zbigniew Starosolski,Avner Meoded,Ananth Annapragada

doi:10.3389/fphys.2022.846404

Abstract

Moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disease leading to recurrent stroke. There is a lack of reliable biomarkers to identify unilateral stroke MMD patients who are likely to progress to bilateral disease and experience subsequent contralateral stroke(s). We hypothesized that local hemodynamics are predictive of future stroke and set out to noninvasively assess this stroke risk in pediatric MMD patients. MR and X-ray angiography imaging were utilized to reconstruct patient-specific models of the circle of Willis of six pediatric MMD patients who had previous strokes, along with a control subject. Blood flow simulations were performed by using a Navier–Stokes solver within an isogeometric analysis framework. Vascular regions with a wall shear rate (WSR) above the coagulation limit (>5,000 s−1) were identified to have a higher probability of thrombus formation, potentially leading to ischemic stroke(s). Two metrics, namely, “critical WSR coverage” and “WSR score,” were derived to assess contralateral stroke risk and compared with clinical follow-up data. In two patients that suffered a contralateral stroke within 2 months of the primary stroke, critical WSR coverages exceeding 50% of vessel surface and WSR scores greater than 6× the control were present in multiple contralateral vessels. These metrics were not as clearly indicative of stroke in two additional patients with 3–5 year gaps between primary and contralateral strokes. However, a longitudinal study of one of these two cases, where a subsequent timepoint was analyzed, suggested disease stabilization on the primary stroke side and an elevated contralateral stroke risk, which was confirmed by patient outcome data. This indicates that post-stroke follow-up at regular intervals might be warranted for secondary stroke prevention. The findings of this study suggest that WSR-based metrics could be predictive of future stroke risk after an initial stroke in pediatric MMD patients. In addition, better predictions may be possible by performing patient-specific hemodynamic analysis at multiple timepoints during patient follow-up to monitor changes in the WSR-based metrics.

Highlights

Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by stenotic or occlusive lesions in the terminal internal carotid artery (ICA) and the proximal middle or anterior cerebral arteries (MCA and Anterior Cerebral Artery (ACA)), leading to recurrent transient ischemic attacks and stroke
Data from 50 pediatric Moyamoya Disease (MMD) patients were retrospectively reviewed and six cases were selected for computational fluid dynamics (CFD) analysis (Table 1) based on the following criteria: (1) patient age is less than 18 years, (2) no other cerebral or cerebrovascular disease is indicated, (3) history of at least one stroke, (4) availability of post-stroke MR TOF and X-ray angiography (XA) imaging taken within 6 months of each other, and (5) there is communication between posterior and anterior circulations in the Circle of Willis (CoW)
We performed blood flow analysis of patient-specific models of the CoW in pediatric MMD patients and showed that local hemodynamics are markedly different than those present in a healthy subject (Hossain et al, 2021). These differences, which are largely dependent on vessel morphology altered by MMD progression, may be indicative of future contralateral stroke risk in patients presenting with unilateral stroke

Summary

Introduction

Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by stenotic or occlusive lesions in the terminal internal carotid artery (ICA) and the proximal middle or anterior cerebral arteries (MCA and ACA), leading to recurrent transient ischemic attacks and stroke. A substantial number of patients presenting with unilateral lesions go on to form bilateral disease, and it is known to occur more commonly in pediatric patients (Hirotsune et al, 1997). In our retrospective review of data from 50 pediatric MMD patients, we found that 39.2% of the unilateral stroke patients, 82% of whom underwent ipsilateral dural inversion surgery, suffered a subsequent contralateral stroke (Hossain et al, 2021). There is a lack of reliable biomarkers to identify these at-risk patients and intervene before the subsequent stroke occurs. Progression of vasculopathy associated with MMD is highly variable from patient to patient, and patients with similar angiographic appearance can have varying degree of stroke risk (Zipfel et al, 2009). Several studies that have relied on angiographic appearance to predict progression to bilateral disease, produced conflicting conclusions (Yeon et al, 2011)

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