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Cerebral Hemodynamics Underlying Artery-to-Artery Embolism in Symptomatic Intracranial Atherosclerotic Disease

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Abstract

Artery-to-artery embolism (AAE) is a common stroke mechanism in intracranial atherosclerotic disease (ICAD), associated with a considerable risk of recurrent stroke. We aimed to investigate cerebral hemodynamic features associated with AAE in symptomatic ICAD. Patients with anterior-circulation, symptomatic ICAD confirmed in CT angiography (CTA) were recruited. We classified probable stroke mechanisms as isolated parent artery atherosclerosis occluding penetrating artery, AAE, hypoperfusion, and mixed mechanisms, largely based on infarct topography. CTA-based computational fluid dynamics (CFD) models were built to simulate blood flow across culprit ICAD lesions. Translesional pressure ratio (PR = Pressurepost-stenotic/Pressurepre-stenotic) and wall shear stress ratio (WSSR = WSSstenotic-throat/WSSpre-stenotic) were calculated, to reflect the relative, translesional changes of the two hemodynamic metrics. Low PR (PR ≤ median) and high WSSR (WSSR ≥ 4th quartile) respectively indicated large translesional pressure and elevated WSS upon the lesion. Among 99 symptomatic ICAD patients, 44 had AAE as a probable stroke mechanism, 13 with AAE alone and 31 with coexisting hypoperfusion. High WSSR was independently associated with AAE (adjusted OR = 3.90; P = 0.022) in multivariate logistic regression. There was significant WSSR-PR interaction on the presence of AAE (P for interaction = 0.013): high WSSR was more likely to associate with AAE in those with low PR (P = 0.075), but not in those with normal PR (P = 0.959). Excessively elevated WSS in ICAD might increase the risk of AAE. Such association was more prominent in those with large translesional pressure gradient. Hypoperfusion, commonly coexisting with AAE, might be a therapeutic indicator for secondary stroke prevention in symptomatic ICAD with AAE.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by the General Research Fund (Reference No. 14106019 & 14138416), Hong Kong Research Grants Council; Health and Medical Research Fund (Reference No. 07180366), Hong Kong Food and Health Bureau; the NHC Key Laboratory of Prevention and treatment of Cerebrovascular Disease, Henan Key Laboratory of Cerebrovascular Diseases (Zhengzhou University), the Non-profit Central Research Institute and Major Science to Yuming Xu (Grant No. 2020-PT310-01).

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Authors and Affiliations

  1. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Xueyan Feng

  2. Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China

    Xueyan Feng, Bonaventure Y. M. Ip, Shuang Li, Xuan Tian, Lina Zheng, Yuying Liu, Sze Ho Ma, Florence S. Y. Fan, Vincent H. L. Ip, Yannie O. Y. Soo, Vincent C. T. Mok, Thomas W. Leung & Xinyi Leng

  3. Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Hui Fang, Bo Song & Yuming Xu

  4. NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, China

    Hui Fang, Bo Song & Yuming Xu

  5. Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou, China

    Ka Lung Chan

  6. Department of Neurology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Linfang Lan

  7. Research Centre for Intelligent Healthcare, Faculty of Health and Life Sciences, Coventry University, Coventry, UK

    Haipeng Liu

  8. Department of Imaging and Interventional Radiology, the Chinese University of Hong Kong, Hong Kong SAR, China

    Jill Abrigo

Authors
  1. Xueyan Feng
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  2. Hui Fang
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  3. Bonaventure Y. M. Ip
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  4. Ka Lung Chan
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  8. Yuying Liu
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  9. Linfang Lan
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  10. Haipeng Liu
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  11. Jill Abrigo
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  14. Vincent H. L. Ip
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  15. Yannie O. Y. Soo
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  17. Bo Song
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  19. Yuming Xu
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Contributions

T.L, Y.X, and X.L conceptualize the research project. X.F, H.F, B.I, K.L.C, L.L, J.A, S.M, F.F, V.I, and Y.S curated data. X.F, H.F, S.L, X.T, L.Z, Y.L, and H.L conducted statistical analysis and methodology. X.F, S.L, and X.T prepared Figs. 1–2. X.F, H.F, K.L.C, and X.L validated the assessment of stroke mechanisms. T.L, Y.X, and X.L supervised the study. X.F and H.F wrote the original draft. X.F, V.M, B.S, T.L, and X.L edited the draft. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Yuming Xu or Xinyi Leng.

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Ethical Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committee (No. 2014.329).

Competing Interests

The authors declare no competing interests.

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Dr. X Feng and H Fang contributed equally.

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Feng, X., Fang, H., Ip, B.Y.M. et al. Cerebral Hemodynamics Underlying Artery-to-Artery Embolism in Symptomatic Intracranial Atherosclerotic Disease. Transl. Stroke Res. (2023). https://doi.org/10.1007/s12975-023-01146-4

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