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

Background—Limited availability of noninvasive and biologically precise diagnostic tools poses a challenge for the evaluation and management of patients with myocarditis. Methods and Results—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) (nϭ65) and control (nϭ10) 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 (nϭ10) and control (nϭ5) 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 (1.08Ϯ0.10 versus 0.48Ϯ0.20; PϽ0.001). In addition, contrast-to-noise ratio measurement in MNP-CMR clearly detected the extent of inflammation (PϽ0.001) except for mild inflammation. Compared with conventional CMR, MNP-CMR provided better image contrast (CNR change 8% versus 46%, PϽ0.001) and detectability of focal myocardial inflammation. Notably, MNP-CMR successfully tracked the evolution of myocardial inflammation in the same EAM rats. Conclusions—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. M yocarditis is defined as inflammation of myocardial tissue with characteristic inflammatory cell infiltration into myocardium. 1,2 Clinically, myocarditis is a major cause of sudden death in young adults 3 and is an important underlying cause of both dilated cardiomyopathy 2 and ar-rhythmogenic right ventricular cardiomyopathy. 4 Despite these serious consequences, there is no single confirmatory tool to diagnose myocarditis with absolute certainty, resulting in limited consensus on clinical practice guidelines for its evaluation and treatment. 5,6 The introduction of endomyocardial biopsy combined with immunohistochemistry (IHC) and cardiovascular magnetic resonance (CMR) imaging has helped to overcome the major drawbacks of traditional diagnostic methodologies. 7,8 Whereas the invasive nature and poor standardization of endomyocardial biopsy have limited its widespread use, noninvasive CMR has emerged as a leading imaging tool in the diagnosis of myocarditis. 9 However, myocardial inflammation , a critical pathogenic factor in myocarditis, cannot be directly visualized by CMR: T 2-weighted (T2W) imaging of tissue edema and myocardial early gadolinium enhancement (EGE) …