Quantitative Susceptibility Mapping and R2 * of Ischemia–Reperfusion Injury Relates to Reactive Oxygen Species Activity

PURPOSE: Iron deposition following ischemia-reperfusion injury (IRI) plays a catalytic role in reactive oxygen species (ROS) production, contributing to myocardial injury and subsequent heart failure. There is a need for noninvasive imaging methods that quantify iron deposition and ROS activity post-IRI. We aimed to evaluate the relationship between myocardial iron content, measured by quantitative susceptibility mapping (QSM) and R2*, and ROS activity using PET. METHODS: IRI was induced in eight swine by percutaneous coronary artery occlusion. Three to seven days post-infarction, cardiac magnetic resonance imaging was performed to acquire multi-echo gradient echo images to reconstruct QSM and R2* maps. ROS activity was quantified using a ROS-activated radiotracer [18F]ROStrace and corrected for myocardial blood flow. RESULTS: Magnetic susceptibility and R2* were significantly elevated in hemorrhagic myocardial regions compared to remote myocardium (susceptibility: 0.07 ± 0.08 vs. -0.03 ± 0.05 ppm, p value = 0.02; R2*: 43.9 ± 5.0 vs. 23.6 ± 5.6 Hz, p value = 0.0003). Infarct ROS activity was significantly higher than in remote regions (0.15 ± 0.04 vs. 0.11 ± 0.04 mL/g, p value = 0.0009). A moderate and positive correlation was found across R2*, susceptibility and ROS activity, with the strongest association between R2* and ROS activity (bootstrapped ρ = 0.59, p value = 0.073; uncorrected ρ = 0.65, p value = 0.02). CONCLUSION: This study demonstrates a moderate association between iron-sensitive MRI biomarkers in the myocardium and ROS activity in IRI. These findings suggest a relationship between iron-related tissue changes and ROS and highlight R2* and QSM as important imaging biomarkers, potentially aiding in the evaluation of therapeutic targets for treatment of myocardial reperfusion injury.