Monday  |  Conference Center A  |  09:00 AM–09:40 AM

#14084, Keynote: Understanding the Diverse Sources of Strength and Vulnerability in Cerebral Aneurysm Walls

Intracranial aneurysms (IAs) are pathological outpouching of the walls of brain arteries, found in 3-7% of the adult population using prospective autopsy and angiography studies [1]. While IA rupture risk is low, it is responsible for approximately 85% of non-traumatic subarachnoid hemorrhagic strokes, a disease with high mortality and disability rates [2]. Despite this dire situation, identification of tools to reliably assess IA rupture risk remain elusive. Such tools would enable patients with high risk IAs to be treated, while avoiding unnecessary treatment in others. We conjecture one reason this controversy remains is that efforts to identify patient characteristics associated with rupture risk do not account for diverse causes for rupture. The IA structural integrity rests on the effective remodeling of collagen fibers in response to changing IA size and shape [3,4]. This integrity can be altered by inclusions such as calcification and lipid pools. We previously found calcification to be present in over 75% of human IA samples and display a range of phenotypes [5]. Notably, calcification in ruptured IAs was never adjacent to or within lipid pools. Moreover, ruptured IAs did not present with macro calcifications. In the present work, we use an integrated in vitro, bioimaging, in silico approach to identify collagen organization responsible for structural integrity in the absence of calcification and contrast this with multiple physical mechanisms by which various calcification phenotypes alter this integrity. In particular, high resolution micro-CT data from IA specimens and patient specific 3D clinical imaging data were used to create 3D computational geometries of the IA and surrounding vasculature. Patient specific collagen and calcification structure were acquired for these models using previously developed multiphoton protocols that make it possible to co-image calcification and collagen fibers in intact samples [6]. A set of in silico tools, including an embedded fiber based finite element algorithm [7], were then used to identify the diverse mechanisms by which the coupled calcification-collagen fiber architecture impacts the structural integrity of the IA wall.

[1] Rinkel et al, Stroke, 29,1998.
[2] van Gijn et al, Brain,124,2001.
[3] Robertson et al, Ann Biomed Eng, 43, 2015.
[4] Sang et. al, Exp Mech, 61,2021.
[5] Gade et al, ATVB, 18,2019.
[6] Gade et al, Curr Protoc Cytom,87, 2019.
[4] Fortunato et al, Exp Mech, 61,2021.

Anne Robertson   University of Pittsburgh
Spandan Maiti   University of Pittsburgh
Ronald Fortunato   University of Pittsburgh
Mehdi Ramezanpour   University of Pittsburgh
Yasutaka Tobe   University of Pittsburgh
Juan Cebral   University of Pittsburgh