Myocarditis is a significant cause of myocardial injury and has recently received increased attention following COVID-19 illness and vaccination. Cardiovascular Magnetic Resonance (CMR) plays an important role in diagnosing this condition, but its sensitivity may vary with disease progression, and it does not always reliably assess therapeutic response.

Our objective was to investigate the potential of cardiac immuno-MRI of VCAM-1 expression, an endothelial adhesion molecule over-expressed during inflammation, to improve the diagnosis and monitoring of myocardial inflammation.

Histological analysis of cardiac biopsies from myocarditis patients and ELISA assays in a cardiac inflammation model induced by intraperitoneal injection of LPS (5mg/kg) were performed to assess VCAM-1 expression in inflammatory tissue. An experimental autoimmune myocarditis model was induced in rats by subcutaneous injection of 0.25mg porcine cardiac myosin (day 0). CMR was performed on days 0, 7, 14, and 21 using a small animal 7T MRI. Cardiac immuno-MRI with MPIO@αVCAM-1 (2mg/kg) was performed using T2*-weighted sequences, and the inflammation signal was compared to late gadolinium enhancement (LGE) on T1-weighted sequences. Treatment with corticosteroids (dexamethasone, 1mg/kg, i.p., three times per week) or vehicle was initiated on day 0. Cardiac tissue was harvested and CD68 and Elastica van Gieson staining were performed.

ELISA assays and human anti-VCAM-1 immunohistochemistry confirmed VCAM-1 targeting in cardiac inflammation (Figure 1). After MPIO@αVCAM-1 injection, hypointensities were detected in the myocardial wall of rats injected with myosin, significantly higher than in SHAM rats (*P<0.05), indicating VCAM-1 binding (Figure 2). No significant hyposignal was observed in rats injected with non-targeted MPIO@IgG, confirming specificity of the probe for VCAM-1(*P<0.05) (Figure 3). In myosin-treated animals, macrophage infiltration and early fibrosis were observed, highlighting the potential of this imaging approach to avoid the need for biopsies (Figure 4). The MPIO@αVCAM-1 signal allowed early inflammation detection (at 14 days) (Figure 5) and differentiation between treated and untreated rats compared to LGE.

Cardiac immuno-MRI of VCAM-1 provides sensitive tracking of myocardial inflammation, enhancing diagnostic specificity. Implementation of this novel technology in hospital could significantly refine the management of myocarditis patient.