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 T2*-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 T1-shortening and a long intravascular half-life, may enable earlier detection. This study assessed a T1-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 T1-weighted cine imaging and serial T1 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 T1 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 T1 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 T1 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 T1 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 T1-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.