Ferumoxytol-Enhanced Cardiac Magnetic Resonance for Delineation of Hyperacute Intramyocardial Hemorrhage With Ex Vivo Validation.

OBJECTIVES

Intramyocardial hemorrhage (IMH) is the most severe form of injury associated with reperfusion therapy during acute myocardial infarction (AMI). Although T 2 *-weighted cardiac MRI is regarded as the reference standard for IMH detection, its application is limited in the hyperacute phase. Ferumoxytol, an iron-based contrast agent characterized by potent T 1 -shortening and a long intravascular half-life, may enable earlier detection. This study assessed a T 1 -weighted approach using ferumoxytol-enhanced MRI (FE-MRI) for early detection of IMH after ischemia-reperfusion injury in a swine model.

MATERIALS AND

METHODS

IMH was induced in 22 Yorkshire swine using a closed-chest ischemia-reperfusion model with intracoronary collagenase administration. FE-MRI was performed immediately after reperfusion using T 1 -weighted cine imaging and serial T 1 mapping with a modified Look-Locker inversion recovery (MOLLI) pulse sequence. Imaging findings were compared among IMH-positive (IMH+), IMH-negative (IMH-), and control animals. Results were validated through gross pathology, histology, and electron microscopy.

RESULTS

Nine animals completed imaging, of which 5 were IMH+ and 4 IMH- based on histopathology and FE-MRI. In IMH+ animals, the T 1 within hemorrhagic reperfused myocardium was significantly lower than remote myocardium [420.8 ms (380.5, 656.3) vs. 806.0 ms (781.0, 818.8); P <0.001], and lower than healthy myocardium in the control animal [808.2 ms (796.3, 811.0)]. IMH- animals exhibited significantly higher myocardial T 1 than IMH+ animals in both non-hemorrhagic reperfused [807.8 ms (786.1, 830.3); P <0.001] and remote myocardium [805.6 ms (786.1, 825.5); P <0.001]. A mixed-effects model confirmed significant cohort-specific T 1 decrease within hemorrhagic reperfused tissue of IMH+ animals (estimate= -0.49±0.15; P =0.001), with a significant time-dependent effect (β= -0.125±0.03; P <0.001). Remote myocardial and left ventricular blood pool T 1 did not differ between groups (both P >0.05). Gross and microscopic findings confirmed extravasated erythrocytes and disrupted myocardial architecture, consistent with hemorrhagic injury.

CONCLUSIONS

This proof-of-concept study demonstrates the feasibility and potential of T 1 -weighted FE-MRI as a unique approach for detecting IMH immediately after ischemia-reperfusion injury. Early identification of IMH by FE-MRI may facilitate translational efforts to develop and evaluate targeted therapies that reduce IMH burden and improve post-AMI outcomes.