Noninvasive Assessment of Myocardial Inflammation by Cardiovascular Magnetic Resonance in a Rat Model of Experimental Autoimmune Myocarditis

• Published in: Circulation (New York, N.Y.) Vol. 125; no. 21; pp. 2603 - 2612
• Main Authors: MOON, Hyeyoung, EUN PARK, Hyo, KIYUK CHANG, KWAN SOO HONG, JONGEUN KANG, HYUNSEUNG LEE, CHEONG, Chaejoon, TAIK LIM, Yong, IHM, Sang-Hyun, SEUNG, Ki-Bae, JAFFER, Farouc A, NARULA, Jagat
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 29.05.2012
• Subjects: Animals; Autoimmune Diseases - diagnosis; Autoimmune Diseases - pathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary heart disease; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Feasibility Studies; Gadolinium; Heart; Magnetic Resonance Imaging - methods; Medical sciences; Myocarditis - diagnosis; Myocarditis - immunology; Myocarditis - pathology; Nanoparticles; Rats; Rats, Inbred Lew; Severity of Illness Index; Autoimmunity; magnetic resonance imaging; Rat; Magnetic resonance; Rodentia; Cardiovascular disease; Inflammation; Myocardial disease; Nuclear magnetic resonance imaging; Myocarditis; Vertebrata; Mammalia; Heart disease; Animal; Contrast media; Macrophage
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.111.075283

Limited availability of noninvasive and biologically precise diagnostic tools poses a challenge for the evaluation and management of patients with myocarditis. The feasibility of cardiovascular magnetic resonance (CMR) imaging with magneto-fluorescent nanoparticles (MNPs) for detection of myocarditis and its effectiveness in discriminating inflammation grades were assessed in experimental autoimmune myocarditis (EAM) (n=65) and control (n=10) rats. After undergoing CMR, rats were administered with MNPs, followed by a second CMR 24 hours later. Head-to-head comparison of MNP-CMR with T(2)-weighted, early and late gadolinium enhancement CMR was performed in additional EAM (n=10) and control (n=5) rats. Contrast-to-noise ratios were measured and compared between groups. Flow cytometry and microscopy demonstrated that infiltrating inflammatory cells engulfed MNPs, resulting in altered myocardial T(2)* effect. Changes in contrast-to-noise ratio between pre- and post-MNP CMR were significantly greater in EAM rats (1.08 ± 0.10 versus 0.48 ± 0.20; P<0.001). In addition, contrast-to-noise ratio measurement in MNP-CMR clearly detected the extent of inflammation (P<0.001) except for mild inflammation. Compared with conventional CMR, MNP-CMR provided better image contrast (CNR change 8% versus 46%, P<0.001) and detectability of focal myocardial inflammation. Notably, MNP-CMR successfully tracked the evolution of myocardial inflammation in the same EAM rats. Magneto-fluorescent nanoparticle CMR permitted effective visualization of myocardial inflammatory cellular infiltrates and distinction of the extent of inflammation compared with conventional CMR in a preclinical model of EAM. Magneto-fluorescent nanoparticle CMR performs best in EAM rats with at least moderate inflammatory response.