Keyvon Rashidi

Background: Cerebral aneurysms (CAs) affect 2-4% of the general population, have an annual rupture rate of ~0.36%, and are associated with up to 50% mortality^1,2. Unfortunately, the process of aneurysm development and rupture risk determination remains poorly understood. Similarly, no consensus exists on the appropriate time for CA intervention which carries high rates of morbidity ^4–6.  CAs tend to form at locations where arteries branch, with 36% of CAs affecting the MCA^1,3, suggesting that cerebrovascular fluid dynamics play a role in aneurysm development. Yet, attempts to quantify aneurysm development and rupture risk using computational fluid dynamics (CFD) have yielded seemingly contradictory conclusions, with both high and low WSS being conjectured as essential mediators of this process⁷.

Research Objective: As such, it is the purpose of this work to examine the role of WSS in the development of MCA aneurysms from the perspectives of MCA morphology, the effect of arterial flow rate on vessel wall remodeling, and patient-specific CFD modeling of MCA aneurysms.

Methods: The scientific literature for MCA aneurysms were examined using the following search terms: “MCA aneurysm,” Wall shear stress,” “CFD modeling,” “Newtonian fluid,” and “non-Newtonian fluid” in PubMed’.

Results: With respect to MCA morphology, WSS depends on vessel radius and bifurcation angle; deviations in cerebrovascular morphology from those predicted by the Principle of Minimum Work (PMW) may thus be an essential determinant in aneurysm formation⁸. Whereas high flow conditions are associated with high WSS at vessel bifurcations, inflammation, aneurysm rupture, and degenerative remodeling; low flow conditions are associated with degeneration of vessel walls and loss of smooth muscle mural cells^8–10. Furthermore, patient-specific CFD analyses reveal that while high WSS may mediate aneurysm initiation, a positive WSS gradient may mediate aneurysm development, and WSS alone cannot lead to the progression of MCA aneurysm development⁵. Moreover, in estimating WSS, Newtonian rheological models to simulate patient-specific MCA aneurysms were found to have estimation errors between -27% to +30% compared to non-Newtonian rheological models, thereby demonstrating the assumption of Newtonian blood viscosity to be limiting¹¹.

Conclusion: A well-established foundation of aneurysm hemodynamics knowledge may not be clinically reliable as many studies employ the Newtonian blood viscosity assumption in WSS calculations. Such shortcomings may be addressed by using Patient-specific whole-blood viscosity measurements. Nevertheless, as CFD simulations become more advanced, such techniques reveal their utility in identifying the precise mechanism of MCA aneurysm development and their potential use in quantifying aneurysm rupture risk.

References

1.  Zhang XJ, Hao WL, Zhang DH, Gao BL. Asymmetrical middle cerebral artery bifurcations are more vulnerable to aneurysm formation. Sci Rep. 2019;9(1):15255. doi:10.1038/s41598-019-51734-4
2. Long B, Koyfman A, Runyon MS. Subarachnoid Hemorrhage: Updates in Diagnosis and Management. Emerg Med Clin North Am. 2017;35(4):803-824. doi:10.1016/j.emc.2017.07.001
3. Toth G, Cerejo R. Intracranial aneurysms: Review of current science and management. Vasc Med. 2018;23(3):276-288. doi:10.1177/1358863X18754693
4. Darsaut TE, Keough MB, Sagga A, et al. Surgical or Endovascular Management of Middle Cerebral Artery Aneurysms: A Randomized Comparison. World Neurosurgery. 2021;149:e521-e534. doi:10.1016/j.wneu.2021.01.142
5. Zimny M, Kawlewska E, Hebda A, Wolański W, Ładziński P, Kaspera W. Wall shear stress gradient is independently associated with middle cerebral artery aneurysm development: a case-control CFD patient-specific study based on 77 patients. BMC Neurology. 2021;21(1):281. doi:10.1186/s12883-021-02251-3
6. Gholampour S, Mehrjoo S. Effect of bifurcation in the hemodynamic changes and rupture risk of small intracranial aneurysm. Neurosurg Rev. 2021;44(3):1703-1712. doi:10.1007/s10143-020-01367-3
7. Zhou G, Zhu Y, Yin Y, Su M, Li M. Association of wall shear stress with intracranial aneurysm rupture: systematic review and meta-analysis. Sci Rep. 2017;7:5331. doi:10.1038/s41598-017-05886-w
8. Ćmiel-Smorzyk K, Kawlewska E, Wolański W, Hebda A, Ładziński P, Kaspera W. Morphometry of cerebral arterial bifurcations harbouring aneurysms: a case-control study. BMC Neurol. 2022;22:49. doi:10.1186/s12883-022-02559-8
9. Mu L, Liu X, Liu M, et al. In Vitro Study of Endothelial Cell Morphology and Gene Expression in Response to Wall Shear Stress Induced by Arterial Stenosis. Front Bioeng Biotechnol. 2022;10:854109. doi:10.3389/fbioe.2022.854109
10. Cebral J, Ollikainen E, Chung BJ, et al. Flow Conditions in the Intracranial Aneurysm Lumen Are Associated with Inflammation and Degenerative Changes of the Aneurysm Wall. American Journal of Neuroradiology. 2017;38(1):119-126. doi:10.3174/ajnr.A4951
11. Saqr KM, Mansour O, Tupin S, Hassan T, Ohta M. Evidence for non-Newtonian behavior of intracranial blood flow from Doppler ultrasonography measurements. Med Biol Eng Comput. 2019;57(5):1029-1036. doi:10.1007/s11517-018-1926-9