Non-invasive contrast enhanced ultrasound molecular imaging of inflammation in autoimmune myocarditis for prediction of left ventricular fibrosis and remodeling

BACKGROUND: Myocarditis can lead to myocyte loss and myocardial fibrosis resulting in dilated cardiomyopathy (DCMP). Currently employed methods for assessing the risk for development of DCMP are inaccurate or rely on invasive myocardial biopsies. We hypothesized that molecular imaging of tissue inflammation with contrast enhanced ultrasound during peak inflammation in myocarditis could predict development of fibrosis and impaired left ventricular function. METHODS AND RESULTS: Experimental autoimmune myocarditis (EAM) was induced in Balbc mice by injection of the α-myosin heavy chain peptide. Contrast enhanced ultrasound (CEU) using microbubbles targeted to leukocytes (MB(Lc)), to CD4+ lymphocytes (MB(CD4)), and to the endothelial cell adhesion molecule P-selectin (MB(PSel)) was performed during the expected EAM peak inflammatory activity 21 days after induction. High resolution ultrasound, invasive hemodynamic measurements and fibrosis quantification were done 63 days after EAM assessment. All tested microbubbles correlated to fibrosis (MB(Lc) spearman r 0.28, p 0.047, MB(CD4) r 0.44, p 0.01, MB(PSel) r 0.73, p 0.02), however, correlations were weak overall and the spread of data was considerable. Also, targeted CEU data on day 21 did not correlate to hemodynamic and functional data on day 63. CONCLUSIONS: Ultrasound molecular imaging using targeted microbubbles during the peak inflammatory activity of myocarditis correlates weakly with later development of fibrosis but not with hemodynamic or left ventricular functional parameters.