Abstract
To induce a rabbit model of atherosclerosis at carotid artery, to visualize the lesion evolution with magnetic resonance imaging (MRI), and to characterize the lesion types by histopathology. Atherosclerosis at the right common carotid artery (RCCA) was induced in 23 rabbits by high-lipid diet following balloon catheter injury to the endothelium. The rabbits were examined in vivo with a 1.5-T MRI and randomly divided into three groups of 6 weeks (n=6), 12 weeks (n=8) and 15 weeks (n=9) for postmortem histopathology. The lesions on both MRI and histology were categorized according to the American Heart Association (AHA) classifications of atherosclerosis. Type I and type II of atherosclerotic changes were detected at week 6, i.e., nearly normal signal intensity (SI) of the injured RCCA wall without stenosis on MRI, but with subendothelial inflammatory infiltration and proliferation of smooth muscle cells on histopathology. At week 12, 75.0% and 62.5% of type III changes were encountered on MRI and histopathology respectively with thicker injured RCCA wall of increased SI on T1-weighted and proton density (PD)-weighted MRI and microscopically a higher degree of plaque formation. At week 15, carotid atherosclerosis became more advanced, i.e., type IV and type V in 55.6% and 22.2% of the lesions with MRI and 55.6% and 33.3% of the lesions with histopathology, respectively. Statistical analysis revealed a significant agreement (p<0.05) between the MRI and histological findings for lesion classification (r=0.96). A rabbit model of carotid artery atherosclerosis has been successfully induced and noninvasively visualized. The atherosclerotic plaque formation evolved from type I to type V with time, which could be monitored with 1.5-T MRI and confirmed with histomorphology. This experimental setting can be applied in preclinical research on atherosclerosis.
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Yach D, Hawkes C, Gould CL, Hofman KJ (2004) The global burden of chronic diseases: overcoming impediments to prevention and control. JAMA 291:2616–2622
Duvall WL, Vorchheimer DA (2004) Multi-bed vascular disease and atherothrombosis: scope of the problem. J Thromb Thrombolvsis 17:51–61
Cullen P, Rauterberg J, Lorkowski S (2005) The pathogenesis of atherosclerosis. Handb Exp Pharmacol 170:3–70
Goldschmidt-Clermont PJ, Creager MA, Lorsordo DW, Lam JK, Wassef M, Dzau VJ (2005) Atherosclerosis: 2005 recent discoveries and novel hypotheses. Circulation 112:3348–3353
Chu B, Phan BA, Balu N, Yuan C, Brown BG, Zhao XQ (2006) Reproducibility of carotid atherosclerotic lesion type characterization using high resolution multicontrast weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson 8:793–799
Yuan C, Miller ZE, Cai J, Hatsukami T (2002) Carotid atherosclerotic wall imaging by MRI. Neuroimaging Clin N Am 12:391–401
Cai J, Hatsukami TS, Ferguson MS, Kerwin WS, Saam T, Chu B, Takaya N, Polissar NL, Yuan C (2005) In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque: comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology. Circulation 112:3437–3444
Babiarz LS, Astor B, Mohamed MA, Wasserman BA (2007) Comparison of gadolinium-enhanced cardiovascular magnetic resonance angiography with high-resolution black blood cardiovascular magnetic resonance for assessing carotid artery stenosis. J Cardiovasc Magn Reson 9:63–70
Leiner T, Gerretsen S, Botnar R, Lutgens E, Cappendijk V, Kooi E (2005) Magnetic resonance imaging of atherosclerosis. Eur Radiol 15(6):1087–1099
Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C (2002) Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 106:1368–1373
Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W Jr, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW (1994) A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 89:2462–3353
Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW (1995) A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 92:1355–1374
Hegyi L, Hockings PD, Benson MG, Overend P, Grimsditch DC, Burton KJ, Lioyd H, Whelan GA, Skepper JN, Vidgeon-Hart MP, Carpenter AT, Reid DG, Suckling KE, Weissberg PL et al (2004) Short term arterial remodelling in the aorta of cholesterol fed New Zealand white rabbits shown in vivo by high-resolution magnetic resonance imaging - implications for human pathology. Pathol Oncol Res 10:159–165
Spence JD (2006) Technology Insight: ultrasound measurement of carotid plaque–patient management, genetic research, and therapy evaluation. Nat Clin Pract Neurol 2:611–619
Nighoghossian N, Derex L, Douek P (2005) The vulnerable carotid artery plaque: current imaging methods and new perspectives. Stroke 36:2764–2772
Brown BG, Zhao XQ (2007) Is intravascular ultrasound the gold standard surrogate for clinically relevant atherosclerosis progression? J Am Coll Cardiol 49:933–938
Manninen HI, Vanninen RL, Laitnen M, Rasanen H, Vainio P, Luoma JS, Pakkanen T, Tulla H, Yla-Herttuala S (1998) Intravascular ultrasound and magnetic resonance imaging in the assessment of atherosclerotic lesions in rabbit aorta: correlation to histopathologic findings. Invest Radiol 33:464–471
Briley-Saebo KC, Mulder WJ, Mani V, Hyafil F, Amirbekian V, Aguinaldo JG, Fisher EA, Fayad ZA (2007) Magnetic resonance imaging of vulnerable atherosclerotic plaques: current imaging strategies and molecular imaging probes. J Magn Reson Imaging 26:460–479
Jaffer FA, Libby P, Weissleder R (2007) Molecular imaging of cardiovascular disease. Circulation 116:1052–1–61
Wiesmann F, Szimtenings M, Frydrychowicz A, Illinger R, Hunecke A, Rommel E, Neubauer S, Haase A (2003) High-resolution MRI with cardiac and respiratory gating allows for accurate in vivo atherosclerotic plaque visualization in the murine aortic arch. Magn Reson Med 50:69–74
Chaabane L, Soulas EC, Contard F, Salah A, Guerrier D, Briguet A, Douek P (2003) High-resolution magnetic resonance imaging at 2 Tesla: potential for atherosclerotic lesions exploration in the apolipoprotein E knockout mouse. Invest Radiol 38:532–538
Kramer CM (2002) Magnetic resonance imaging to identify the high-risk plaque. Am J Cardiol 90:15L–17L
Wang YX, Kuribayashi H, Wagberg M, Holmes AP, Tessier JJ, Waterton JC (2006) Gradient echo MRI characterization of development of atherosclerosis in the abdominal aorta in Watanabe Heritable Hyperlipidemic rabbits. Cardiovasc Intervent Radiol 29:605–612
Hanni M, Edvardsson H, Wagberg M, Pettersson K, Smedby O (2004) Quantification of atherosclerosis with MRI and image processing in spontaneously hyperlipidemic rabbits. J Cardiovasc Magn Reson 6:675–684
McMahon AC, Kritharides L, Lowe HC (2005) Animal models of atherosclerosis progression: current concepts. Curr Drug Targets Cardiovasc Haematol Disord 5:433–440
Bengel FM (2006) Atherosclerosis imaging on the molecular level. J Nucl Cardiol 13:111–118
Yarnykh VL, Terashima M, Hayes CE, Shimakawa A, Takaya N, Nguyen PK, Brittain JH, McConnel MV, Yuan C (2006) Multicontrast black-blood MRI of carotid arteries: comparison between 1.5 and 3 Tesla magnetic field strengths. J Magn Reson Imaging 23:691–698
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This research project was partially supported by the National Natural Science Foundation of China 90606007 and an award by the Hwa Ying Education and Culture Foundation 2007.
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Ma, ZL., Teng, GJ., Chen, J. et al. A rabbit model of atherosclerosis at carotid artery: MRI visualization and histopathological characterization. Eur Radiol 18, 2174–2181 (2008). https://doi.org/10.1007/s00330-008-0978-x
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DOI: https://doi.org/10.1007/s00330-008-0978-x