Calcification is highly prevalent in cerebral aneurysms and differs in presentation in ruptured and unruptured aneurysms

 In All Presenters, Robertson, Anne M.

Presenting Author: Anne M. Robertson1

1Department of Mechanical Engineering and Materials Science and Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Additional Authors: Piyusha Gade1, Juan Raul Cebral2

2Bioengineering and Mechanical Engineering Departments, George Mason University

Fairfax, Virginia, USA

BACKGROUND/PURPOSE:  Vascular calcifications are known to alter the mechanical stiffness and strength of vascular tissues.  It is now clear they do not originate from a single disease process, but rather arise as either a non-atherosclerotic phosphate-dependent, rapid mineralization in the media or a slower, inflammation driven, atherosclerotic type change in the intima.  However, studies of calcification in intra-cranial aneurysms (IAs) have been limited, likely due to clinical reports of low prevalence as well as difficulties obtaining human IA tissue for ex-vivo study.  In this talk, we summarize our recent work using high resolution micro-CT to evaluate calcification in human IA tissue [1].

METHODS:  For these studies, sixty-five cerebral aneurysm domes were harvested following clipping during open brain surgery (48 unruptured, 17 ruptured)  and calcification and lipid pools were imagined  non-destructively  in the intact samples using high resolution micro-CT.

RESULTS: Calcification was found in 78%  of IA specimens in the form of micro (<500μm), meso (500μm – 1mm) and macro-calcifications (>1mm), without an associated specific visible changes to wall color.  Of these, 24% had atherosclerotic calcification, located in or adjacent to a lipid pool.  The other 76% only contained non-atherosclerotic calcification (found in the absence of lipid pools).   Ruptured aneurysms never presented with macro calcifications nor atherosclerotic type calcification.  In contrast, unruptured aneurysms displayed all sizes of calcification and both atherosclerotic and non-atherosclerotic calcification.  Furthermore, ruptured aneurysms had significantly lower calcification fraction compared with unruptured aneurysms.

CONCLUSIONS:  Calcification in IAs is more prevalent than previously reported and differs in presentation in ruptured and unruptured aneurysms.  Prior studies on extracerebral plaques suggest micro-calcifications can be more dangerous than macro-calcifications [2,3], underscoring the importance of further investigation in IAs.  Current efforts to develop therapies to reverse or prevent micro-calcifications may have relevance for clinical treatment of cerebral aneurysms.

[1] Gade, Tulamo, Lee, Mut, Ollikainen, Chuang, Chung, Niemelä, Jahromi, Aziz, Yu, Charbel, Amin-Hanjani, Frösen, Cebral, Robertson, ATVB, 39(10), 2157–2167, (2019).

[2]  Cardoso, Weinbaum, Changing views of the biomechanics of vulnerable plaque rupture: A review, Ann. Biomed. Eng. 42, 415–431, (2014).

[3]  Tang, Kamm, Yang, Zheng, Canton, Bach, Huang, Hatsukami, Zhu, Ma, Maehara, Mintz, Yuan, J. Biomech,47, 834–846 (2014).

 

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