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A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
Patient-Specific Modeling Could Predict Occurrence of Pediatric Stroke
John D Horn1, Michael J Johnson2, Zbigniew Starosolski3,4
1Molecular Cardiology Research Laboratory, Texas Heart Institute, Houston, TX, United States.
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.
Insights
Hemodynamic wall shear rate metrics show promise in predicting future strokes in pediatric Moyamoya disease patients. Regular hemodynamic analysis may improve secondary stroke prevention strategies.
Area of Science:
- Biomedical Engineering
- Neurology
- Medical Imaging
Background:
- Moyamoya disease (MMD) is a progressive cerebrovascular condition causing recurrent strokes.
- Current biomarkers are insufficient for predicting contralateral stroke risk in unilateral MMD patients.
- Understanding local hemodynamics is crucial for assessing stroke progression.
Purpose of the Study:
- To noninvasively assess stroke risk in pediatric MMD patients using hemodynamic analysis.
- To identify reliable biomarkers for predicting contralateral stroke in MMD.
- To evaluate the predictive value of wall shear rate (WSR) metrics for future stroke events.
Main Methods:
- Patient-specific circle of Willis models were created from MR and X-ray angiography.
- Navier-Stokes blood flow simulations were performed using an isogeometric analysis framework.
- Wall shear rate (WSR) metrics, including critical WSR coverage and WSR score, were derived and compared with clinical outcomes.
Main Results:
- High WSR (>5,000 s⁻¹) regions indicated increased thrombus formation probability.
- Critical WSR coverage >50% and WSR score >6x control predicted early contralateral stroke in two patients.
- WSR metrics showed less clear prediction for strokes occurring 3-5 years later, but longitudinal analysis suggested predictive value.
Conclusions:
- WSR-based metrics show potential for predicting future stroke risk in pediatric MMD patients post-initial stroke.
- Patient-specific hemodynamic analysis at multiple timepoints may enhance stroke risk prediction.
- Regular follow-up and hemodynamic monitoring are warranted for secondary stroke prevention in MMD.

