Abstract
Moyamoya disease (MMD) is characterized by narrowing of the distal internal carotid artery and the circle of Willis (CoW) and leads to recurring ischemic and hemorrhagic stroke. A retrospective review of data from 50 pediatric MMD patients revealed that among the 24 who had a unilateral stroke and were surgically treated, 11 (45.8%) had a subsequent, contralateral stroke. There is no reliable way to predict these events. After a pilot study in Acta−/− mice that have features of MMD, we hypothesized that local hemodynamics are predictive of contralateral strokes and sought to develop a patient-specific analysis framework to noninvasively assess this stroke risk. A pediatric MMD patient with an occlusion in the right middle cerebral artery and a right-sided stroke, who was surgically treated and then had a contralateral stroke, was selected for analysis. By using an unsteady Navier–Stokes solver within an isogeometric analysis framework, blood flow was simulated in the CoW model reconstructed from the patient’s postoperative imaging data, and the results were compared with those from an age- and sex-matched control subject. A wall shear rate (WSR) > 60,000 s−1 (about 12 × higher than the coagulation threshold of 5000 s−1 and 9 × higher than control) was measured in the terminal left supraclinoid artery; its location coincided with that of the subsequent postsurgical left-sided stroke. A parametric study of disease progression revealed a strong correlation between the degree of vascular morphology altered by MMD and local hemodynamic environment. The results suggest that an occlusion in the CoW could lead to excessive contralateral WSRs, resulting in thromboembolic ischemic events, and that WSR could be a predictor of future stroke.
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Acknowledgements
The authors gratefully acknowledge the assistance of Stephanie Wallace in providing patient imaging data, and the Texas Advanced Computing Center (TACC) at the University of Texas at Austin for providing high-performance computing (HPC) resources that have contributed to the research results reported in this paper. Stephen N. Palmer, PhD, ELS, of the Department of Scientific Publications at the Texas Heart Institute, contributed to the editing of the manuscript. James Philpot of the Department of Visual Communications at the Texas Heart Institute created the artwork in Fig. 1.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute of Health [grant number R03NS110442]. AA acknowledges funding from the National Institutes of Health (U01DE028233, R01HD094347). DMM has funding for MMD studies from the American Heart Association Merit Award.
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SSH planned and supervised the project, wrote the manuscript, ran the simulations, and interpreted data. ZS and SSH conducted the retrospective review of patient data; ZS performed image analysis; ZS and TS performed image segmentation; TS and MJJ reconstructed the NURBS-based computational models from the segmented imaging data; MCH and MW conducted the numerical implementation of the flow model in a parallelized numerical code; TS, MJJ, and SSH performed post-processing of simulation results; DM advised on the clinical relevance of the research and edited the manuscript; and AA helped with the conceptualization of the project and data interpretation. All authors provided critical feedback, commented on the manuscript, and approved the final submission.
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AA is a consultant to, and a founder and stockholder in, Alzeca Biosciences and a shareholder in Sensulin LLC. ZS is a stockholder in Alzeca Biosciences and a consultant for InContext.ai. All other authors declare that they have no conflict of interest.
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There was no direct involvement of human subjects or protected health information (PHI). All patient imaging data used in analysis and modeling were collected retrospectively from medical records and de-identified at Texas Children’s Hospital. Institutional review board (IRB) approval was obtained with a waiver of written authorization for consent. No animals were involved in this study. Mouse cerebrovascular images used in this work were taken from a previous study conducted by (Starosolski et al. 2015).
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Hossain, S.S., Starosolski, Z., Sanders, T. et al. Image-based patient-specific flow simulations are consistent with stroke in pediatric cerebrovascular disease. Biomech Model Mechanobiol 20, 2071–2084 (2021). https://doi.org/10.1007/s10237-021-01495-9
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DOI: https://doi.org/10.1007/s10237-021-01495-9