Dimitrios E. Kiousis Stephan F. Rubinigg Institute of Biomechanics, Center of Biomedical Engineering, Graz University of Technology, Kronesgasse 5-I, 8010 Graz, Austria Martin Auer Department of Solid Mechanics, School of Engineering Sciences, Royal Institute of Technology (KTH), 10044 Stockholm, Sweden Gerhard A. Holzapfel 1 Institute of Biomechanics, Center of Biomedical Engineering, Graz University of Technology, Kronesgasse 5-I, 8010 Graz, Austria; Department of Solid Mechanics, School of Engineering Sciences, Royal Institute of Technology (KTH), 10044 Stockholm, Sweden e-mail: holzapfel@tugraz.at A Methodology to Analyze Changes in Lipid Core and Calcification Onto Fibrous Cap Vulnerability: The Human Atherosclerotic Carotid Bifurcation as an Illustratory Example A lipid core that occupies a high proportion of the plaque volume in addition to a thin fibrous cap is a predominant indicator of plaque vulnerability. Nowadays, noninvasive imaging modalities can identify such structural components, however, morphological criteria alone cannot reliably identify high-risk plaques. Information, such as stresses in the lesion’s components, seems to be essential. This work presents a methodology able to analyze the effect of changes in the lipid core and calcification on the wall stresses, in particular, on the fibrous cap vulnerability. Using high-resolution magnetic resonance imaging and histology of an ex vivo human atherosclerotic carotid bifurcation, a patient- specific three-dimensional geometric model, consisting of four tissue components, is gen- erated. The adopted constitutive model accounts for the nonlinear and anisotropic tissue behavior incorporating the collagen fiber orientation by means of a novel and robust algorithm. The material parameters are identified from experimental data. A novel stress- based computational cap vulnerability index is proposed to assess quantitatively the rupture-risk of fibrous caps. Nonlinear finite element analyses identify that the highest stress regions are located at the vicinity of the shoulders of the fibrous cap and in the stiff calcified tissue. A parametric analysis reveals a positive correlation between the increase in lipid core portion and the mechanical stress in the fibrous cap and, hence, the risk for cap rupture. The highest values of the vulnerability index, which correlate to more vul- nerable caps, are obtained for morphologies for which the lipid cores were severe; heavily loaded fibrous caps were thus detected. The proposed multidisciplinary method- ology is able to investigate quantitatively the mechanical behavior of atherosclerotic plaques in patient-specific stenoses. The introduced vulnerability index may serve as a more quantitative tool for diagnosis, treatment and prevention. DOI: 10.1115/1.4000078 Keywords: artery, calcification, carotid bifurcation, fibrous cap, lipid core, MRI, vulnerability 1 Introduction Atherosclerosis is the main determinant of cardiovascular dis- eases, the leading cause of cardiovascular morbidity and mortality around the globe 1,2. Although luminal narrowing and exagger- ated or anomalous vasoconstriction contribute to some of the clinical manifestations of arterial diseases, it is the superimposi- tion of an arterial thrombus over an underlying ruptured or eroded plaque that is responsible for the vast majority of acute ischemic syndromes such as myocardial infarction or cerebrovascular acci- dent 3–5. Cerebrovascular atherosclerosis, for example, is the result of half of the stroke events including carotid plaques; plaque rupture is a critical event in the evolution of atherosclero- sis. Hence, it is crucial to determine whether a plaque is vulner- able 6, and therefore life-threatening with the risk of stroke, or resistant and innocuous. The ability to identify rupture-prone high-risk plaques and to intervene successfully before acute plaque rupture occurs has been an elusive goal of clinicians over the past decades. A series of postmortem observations in patients with acute is- chemic syndromes revealed that predominant features of plaque vulnerability include increased numbers of macrophages, in- creased expression of tissue factor, reduced number of smooth muscle cells, a lipid core that occupies a high proportion of the overall plaque volume, and a thin fibrous cap see, e.g., Refs. 6–9. The rapid development in the area of arterial wall imaging made the detection of the lipid core and the fibrous cap feasible. A review of the invasive and noninvasive imaging modalities is given in Ref. 10. High-resolution magnetic resonance imaging represents the best promise of in vivo quantitative characterization of plaque morphology 11–13, and appears to be a favorable 1 Corresponding author. Contributed by the Bioengineering Division of ASME for publication in the JOUR- NAL OF BIOMECHANICAL ENGINEERING. Manuscript received August 25, 2008; final manuscript received February 19, 2009; accepted manuscript posted September 1, 2009; published online October 29, 2009. Editor: Michael Sacks. Journal of Biomechanical Engineering DECEMBER 2009, Vol. 131 / 121002-1 Copyright © 2009 by ASME Downloaded 31 Oct 2009 to 84.115.151.25. Redistribution subject to ASME license or copyright; see http://www.asme.org/terms/Terms_Use.cfm