Introduction Directory UMM :Data Elmu:jurnal:A:Atherosclerosis:Vol150.Issue2.Jun2000:

Atherosclerosis 150 2000 321 – 329 High resolution ex vivo magnetic resonance imaging of in situ coronary and aortic atherosclerotic plaque in a porcine model Stephen G. Worthley a , Ge´rard Helft a , Valentin Fuster b , Zahi A. Fayad b,c , John T. Fallon b,d , Julio I. Osende a , Merce` Roque´ a , Meir Shinnar b,c , Azfar G. Zaman a , Oswaldo J. Rodriguez a , Peter Verhallen e , Juan J. Badimon a, a Cardio6ascular Biology Research Laboratory, Zena and Michael A. Wiener Cardio6ascular Institute, One Gusta6e L. Le6y Place, P.O. Box 1030 , New York, NY 10029 - 6574 , USA b Zena and Michael A. Wiener Cardio6ascular Institute, One Gusta6e L. Le6y Place, P.O. Box 1030 , New York, NY 10029 - 6574 , USA c Department of Radiology, The Mount Sinai Medical Center, New York, NY 10029 , USA d Department of Pathology, The Mount Sinai Medical Center, New York, NY 10029 , USA e Berlex Sciences, Richmond, CA 94804 , USA Received 8 June 1999; received in revised form 23 August 1999; accepted 3 September 1999 Abstract Atherosclerotic plaque composition is central to the pathogenesis of plaque disruption and acute thrombosis. Thus, there is a need for accurate imaging and characterization of atherosclerotic lesions. Even though there is no ideal animal model of atherosclerosis, the porcine model is considered to most closely resemble human atherosclerosis. We report the feasibility of MR imaging and characterizing of atherosclerotic lesions from in situ coronary arteries and aortas in an ex vivo setting and validate this with histopathology. Coronary and aortic atherosclerosis was induced in Yucatan mini-swine n = 4 by a combination of atherogenic diet 6 months and balloon injury. All coronary arteries were imaged ex vivo on the intact heart, preserving the curvature of their course. The aorta also underwent MR imaging. The MR images were correlated with the matched histopathology sections for both the coronary arteries n = 54 and the aortas n = 43. MR imaging accurately characterized complex atherosclerotic lesions, including calcified, lipid rich, fibrocellular and hemorrhagic regions. Mean wall thickness for the coronary arteries r = 0.94, slope: 0.81 and aortas r = 0.94, slope: 0.81 as well as aortic plaque area r = 0.97, slope: 0.90 was accurately determined by MR imaging P B 0.0001. Coronary artery MR imaging is not limited by the curvature of the coronary arteries in the heart. MR imaging accurately quantifies and characterizes coronary and aortic atherosclerotic lesions, including the vessel wall, in this experimental porcine model of complex atherosclerosis. This model may be useful for future study of MR imaging of atherosclerosis in vivo. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords : Magnetic resonance imaging; Atherosclerosis; Coronary; Aorta; Porcine www.elsevier.comlocateatherosclerosis

1. Introduction

Coronary artery disease is the single leading cause of mortality in the Western world [1 – 3]. The acute clinical complications of coronary artery disease are associated with atherosclerotic plaque disruption and thrombosis [1 – 7]. Atherosclerotic plaque composition rather than stenotic severity predicts the risk of plaque rupture and its thrombogenicity [1 – 3,7 – 9]. Thus imaging tech- niques that can characterize the plaque and its compo- nents will potentially allow risk stratification in asymptomatic, as well as symptomatic, patients with coronary artery disease and potentially select the most appropriate therapies to help attenuate this risk. Magnetic resonance MR imaging has been shown in ex vivo models of atherosclerosis to be effective in identifying both normal vessel wall components [10] and atherosclerotic plaque composition [10,11]. These studies have usually required high field research MR systems [10,11]. Recently, in vivo MR imaging in ani- mal models of atherosclerosis including mice [12], rats Corresponding author. Tel.: + 1-212-241-8484; fax: + 1-212-426- 6962. E-mail address : jbadimosmtplink.mssm.edu J.J. Badimon 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 3 8 6 - X [13], rabbits [14] and pigs [15], has been demonstrated. However, to date, only linear arteries have been suc- cessfully imaged. The in-plane resolution in 1.5 T clini- cal systems using standard surface coils has generally been greater than 300 × 300 mm, in both in and ex vivo studies [14,16]. Imaging the coronary artery wall with magnetic resonance techniques in vivo provides added levels of difficulty due to cardiac and respira- tory motion, as well as its curvi-linear course [17,18]. Given the predilection of coronary atherosclerotic le- sions for more tortuous sites in the vessel, associated with lower shear stress [19], it is important to confirm that MR imaging can accurately identify and charac- terize atherosclerotic lesions in the curved coronary arteries. Additional data, confirming the unique re- sponse of the coronary arterial system to injury, in comparison to other arterial beds [20], highlight the importance of being able to serially and noninvasively characterize atherosclerotic lesions within the coronary system. The ability to accurately identify and quantify the coronary wall components ex vivo on the intact heart in an atherosclerotic model has yet to be docu- mented. Despite the many animal models of atherosclerosis available, there is no perfect model of human coro- nary atherosclerosis [21]. Cholesterol feeding with bal- loon denudation of the proximal coronary arteries in pigs has been associated with high mortality [22]. Bal- loon angioplasty in normal porcine vessels, in the ab- sence of an atherogenic diet, leads to intimal hyperplasia and occasionally vessel wall hematoma, but no other components of complex atherosclerotic plaque i.e. lipid cores, fibrous caps, calcification [23,24]. We investigated the use of Yucatan mini-swine fed an atherogenic diet combined with balloon angio- plasty of the coronary arteries and balloon denudation of the abdominal aorta as a potential new experimen- tal model for complex atherosclerotic lesions. Our data show that MR imaging of coronary atherosclerotic lesions is not limited by the architec- tural curvature of the arteries. We have been able to characterize the composition of coronary and aortic atherosclerotic lesions. This suggests the possible fu- ture use of MR imaging for noninvasive serial studies of atherosclerotic plaque in an in vivo setting.

2. Methods