Multi orientation Quantitative Susceptibility Mapping for Accurate Quantification of Iron in Hemorrhagic Myocardial Infarction

Congestive heart failure(CHF) following Acute Myocardial Infarction (AMI) has emerged as a critical contributor to the rising incidence of heart failure. Today, post-MI CHF affects 2.1 million Americans and causes a concerning 300,000 fatalities every year. Recent studies have established that hemorrhagic myocardial infarction(hMI)-induced intramyocardial iron deposition can cause augmented reperfusion injuries, prolonged myocardial inflammation, and adverse ventricular remodeling that leads to CHF. More importantly, studies have shown that iron depletion therapies can deter these adverse effects and facilitate positive post-MI recovery. This underscores the urgent need for reliable, noninvasive quantification of intramyocardial iron content that can monitor the longitudinal progression of cytotoxic iron, guide the development of novel iron-targeted therapies, and facilitate individualized hMI treatment plans for improving its long-term outcome. However, due to technical limitations, the current standard method for cardiac iron imaging (R2* cardiac MRI) has limited accuracy for iron quantification in hMI hearts. Quantitative Susceptibility Mapping (QSM) MRI has recently been developed as a powerful tool to quantify iron. QSM can directly measure tissue iron content through its underlying magnetic susceptibility, which is resistant to confounders in the conventional R2* measurements, making it the clinical standard for iron assessment in the brain. Despite its benefits, QSM faces significant technical challenges when translating to infarcted hearts. These challenges include vulnerability to unstable vital motion, elevated water content from myocardial edema, compromised by the strong off-resonance artifacts at heart-lung interfaces, and deconvolution errors in hemorrhagic lesions. Here, we propose to develop and validate a fast, free-running, motion-robust, confounder-resistant cardiac QSM technique to provide reliable and consistent iron quantification in infarcted hearts. We will test its precision under animal models with controlled myocardial iron overload and establish its accuracy against high-resolution mass spectrometry imaging in hMI animals. Culminating this research would transform the clinical care for MI patients by (1) establishing a fast, non-invasive, quantitative mean for assessing intramyocardial hemorrhage, (2) facilitating the ongoing development of novel iron-targeted therapies, and (3) enabling individualized management planning, and ultimately improving its long-term outcome. Project Number: 1R01HL181091-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Hsin-Jung Yang (+1 co-PI) | Institution: CEDARS-SINAI MEDICAL CENTER, LOS ANGELES, CA | Award Amount: $757,555 | Activity Code: R01 | Study Section: Emerging Imaging Technologies and Applications Study Section[EITA] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HL18109101