The mechanisms by which intracranial aneurysms develop, enlarge, and rupture are unknown, and it remains difficult to collect the longitudinal patient-based information needed to improve our understanding. We submit, therefore, that mathematical models hold promise by allowing us to propose and test competing hypotheses on potential mechanisms of aneurysmal enlargement and to compare predicted outcomes with limited clinical information—in this way, we may begin to narrow the possible mechanisms and thereby focus experimental studies. In this paper, we present a constrained mixture model of evolving thin-walled, fusiform aneurysms and compare multiple competing hypotheses with regard to the production, removal, and alignment of the collagen that provides the structural integrity of the wall. The results show that this type of approach has the capability to infer potential means by which lesions enlarge and whether such changes are likely to produce a stable or unstable process. Such information can better direct the requisite histopathological examinations, particularly on the need to quantify collagen orientations as a function of lesion geometry.

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