Diversity in the Strength and Structure of Unruptured Cerebral Aneurysms
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Intracranial aneurysms are pathological enlargements of brain arteries that are believed to arise from progressive wall degeneration and remodeling. Earlier work using classical histological approaches identified variability in cerebral aneurysm mural content, ranging from layered walls with intact endothelium and aligned smooth muscle cells, to thin, hypocellular walls. Here, we take advantage of recent advances in multiphoton microscopy, to provide novel results for collagen fiber architecture in 15 human aneurysm domes without staining or fixation as well as in 12 control cerebral arteries. For all aneurysm samples, the elastic lamina was absent and the abluminal collagen fibers had similar diameters to control arteries. In contrast, the collagen fibers on the luminal side showed great variability in both diameter and architecture ranging from dense fiber layers to sparse fiber constructs suggestive of ineffective remodeling efforts. The mechanical integrity of eight aneurysm samples was assessed using uniaxial experiments, revealing two sub-classes (i) vulnerable unruptured aneurysms (low failure stress and failure pressure), and (ii) strong unruptured aneurysms (high failure stress and failure pressure). These results suggest a need to refine the end-point of risk assessment studies that currently do not distinguish risk levels among unruptured aneurysms. We propose that a measure of wall integrity that identifies this vulnerable wall subpopulation will be useful for interpreting future biological and structural data.
KeywordsSoft tissue Rupture risk Structural integrity Collagen Failure Multiphoton Remodeling
This work was supported, in part, by a grant from the National Institute of Neurological Disorders and Stroke of the National Institute of Health (1R21NS080031-01A1). We also wish to acknowledge Joshua Selling, a talented undergraduate student at the University of Pittsburgh, for his development and implementation of a meticulous protocol for fiber diameter measurements. The authors wish to thank the Alzheimers Disease Research Center (ADRC) of the University of Pittsburgh and Dr. Julia K. Kofler, Director of the Neuropathology Core of the ADRC for providing the cadaveric human cerebral vessels that were used in this study.
Conflict of interest
- 2.Broderick, J. P., R. D. Brown, L. Sauerbeck, R. Hornung, J. Huston, D. Woo, C. Anderson, G. Rouleau, D. Kleindorfer, M. L. Flaherty, I. Meissner, T. Foroud, E. C. J. Moomaw, and E. S. Connolly. Greater rupture risk for familial as compared to sporadic unruptured intracranial aneurysms. Stroke 40:1952–1957, 2009.PubMedCentralPubMedCrossRefGoogle Scholar
- 7.Costalat, V., M. Sanchez, D. Ambard, L. Thines, N. Lonjon, F. Nicoud, H. Brunel, J. P. Lejeune, H. Dufour, P. Bouillot, J. P. Lhaldky, K. Kouri, F. Segnarbieux, C. A. Maurage, K. Lobotesis, M. C. Villa-Uriol, C. Zhang, A. F. Frangi, G. Mercier, A. Bonafé, L. Sarry, and F. Jourdan. Biomechanical wall properties of human intracranial aneurysms resected following surgical clipping (IRRAs Project). J. Biomech. 44(15):2685–2691, 2011.PubMedCrossRefGoogle Scholar
- 8.Frösen, J., A. Piippo, A. Paetau, M. Kangasniemi, M. Niemelä, J. Hernesniemi, and J. Jääskeläinen. Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35(10):2287–2293, 2004.PubMedCrossRefGoogle Scholar
- 23.Robertson, A. M., M. R. Hill, and D. Li. Structurally motivated damage models for arterial walls—theory and application. In: Modelling of Physiological Flows, Modeling, Simulation and Applications, Vol. 5, edited by D. Ambrosi, A. Quarteroni, and G. Rozza. New York: Springer, 2011.Google Scholar
- 31.Stehbens, W. E. Pathology of the Cerebral Blood Vessels. St. Louis: C.V. Mosby Co., 1972.Google Scholar
- 36.Weir, B., and R. L. Macdonald. Intracranial aneurysms and subarachnoid hemorrhage: an overview. In: Neurosurgery, 2nd ed., edited by R. H. Wilkins, and S. S. Rengachany. New York: McGraw-Hill, 1996, pp. 2191–2213.Google Scholar