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Novel methodologies for investigating the pathophysiology of cerebral aneurysms.

Zeng, Zijing (2011) Novel methodologies for investigating the pathophysiology of cerebral aneurysms. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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An intracranial aneurysm (IA) is a pathological state of a cerebral artery in which the elastin and smooth muscle cells found in the healthy arterial wall are absent. Rupture of an IA is a major cause of subarachnoid hemorrhage. Cerebral aneurysms are most commonly found at arterial bifurcations and the outer bends of curved vessels. The nature of blood flow in these regions is believed to play an important role in initiation, development and rupture of the IA. However, the coupling between hemodynamics and aneurysm pathophysiology is complex and remains poorly understood. The initiation of cerebral aneurysms is believed to be caused by a breakdown in the homeostatic mechanism of healthy arteries, leading to destructive wall remodeling and damage. Due to its complex nature, there is a need for both controlled in vitro and in vivo studies of IA initiation. We have designed an in vitro flow chamber that can be used to reproduce specific magnitudes of wall shear stress and wall shear stress gradients found at the apices of arterial bifurcations, where aneurysms tend to form. Particular attention is given to reproducing spatial distributions of these functions that have been shown to induce pre-aneurysmal changes in vivo. Animal models provide a mechanism for fundamental studies of the coupling between hemodynamics and pathophysiology in diseases such as saccular aneurysms. We conducted a sensitivity study to develop an accurate CFD model for an elastase induced rabbit aneurysm model. We then used this computational model to evaluate the capability of the rabbit model to reproduce hemodynamic features typical of human intracranial aneurysms. Geometric and hemodynamic features of 51 rabbit aneurysm models were analyzed and shown to fall within the range reported for human IAs. This model was also used to study the relationship between aspect ratio and hemodynamics in the aneurysm sac. An "in silico design" approach was then used to explore the possibility of extending the rabbit model to capture more of the flow categories identified in human IAs. Based on a previously developed parametric model for human arterial bifurcations, we created and validated a parametric model for intracranial aneurysms. This parametric model captures important geometric and flow features of both the aneurysm and neighboring vasculature. The model is currently being used for studies of the coupling between geometry and hemodynamics in intracranial aneurysms. It can also be used to guide 3D reconstruction of poor quality clinical data or construct in vitro experimental models.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Zeng, Zijingziz3@pitt.eduZIZ3
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairRobertson, Anne M.rbertson@pitt.eduRBERTSON
Committee MemberTakahashi,
Committee MemberKallmes, David
Committee MemberGaldi, Giovanni P.galdi@pitt.eduGALDI
Committee MemberSacks, Michael S.msacks@pitt.eduMSACKS
Date: 19 September 2011
Date Type: Completion
Defense Date: 12 July 2011
Approval Date: 19 September 2011
Submission Date: 13 April 2011
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Mechanical Engineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Aneurysm; Geometry; Hemodynamics; In Vitro Flow Device; CFD; Parametric Model
Other ID:, etd-04132011-104941
Date Deposited: 10 Nov 2011 19:37
Last Modified: 15 Nov 2016 13:40


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