High-resolution post-mortem CMR imaging clearly reveals intramyocardial haemorrhage in a rat model of acute myocardial infarction

Abstract Background Following an acute myocardial infarction (AMI), reperfusion therapy can induce additional cellular damage to the myocardium, a phenomenon known as ischemia-reperfusion (IR) injury. The severity of IR injury correlates with increased morbidity and mortality, with intramyocardial haemorrhage (IMH) being a key manifestation. Cardiac Magnetic Resonance (CMR), particularly T2* mapping, offers a non-invasive means of detecting IMH. In preclinical studies, CMR-based detection of IMH can be validated histologically, supporting its accuracy and reliability. By retrieving T2* maps from animal models and validating these findings through histology, we can bridge the gap between experimental research and clinical scenarios. Purpose To establish a robust and reproducible diagnostic approach for detecting IMH in a preclinical AMI model, thereby facilitating translation to clinical practice. Methods Rats (n=9) underwent 45 minutes of myocardial ischemia via occlusion of the left anterior descending coronary artery. CMR was performed after 2-3 hours of reperfusion using a 7T Bruker ClinScan horizontal bore MR system. To assess IMH, ECG-triggered multi-gradient-echo images were acquired to calculate T2* maps on mid ventricular short axis slices. Late gadolinium enhancement (LGE) imaging was performed to delineate infarcted myocardium. Three hours after reperfusion, isolated rat hearts were retrogradely perfused at 70 mmHg with oxygenated Krebs-Henseleit buffer, followed by Fluorinert, a proton-free fluid used to minimize susceptibility artifacts. Subsequently, the hearts were scanned in an 11.7T Biospec Avance III small animal MR system equipped with a cryoprobe to acquire T2* maps. IMH was identified as regions with low T2* values within the infarcted myocardium. Thioflavin-S, Evans Blue and TTC staining were performed to assess the no-reflow (NR) area, area at risk (AAR) and infarct area (IS), respectively. Results LGE CMR imaging confirmed myocardial infarction in all rats following 3 hours of reperfusion (Figure 1A). In vivo T2* maps failed to visualize IMH due to susceptibility and motion artifacts (Figure 1B). In contrast, high-resolution T2* maps of the post-mortem rat hearts enabled detailed visualization of IMH, defined by markedly reduced T2* values in the infarct core (Figure 1C). Corresponding macroscopic images revealed red discoloration indicative of haemorrhage (Figure 1D), which spatially aligned with regions of IMH seen on T2* imaging. IMH on T2* imaging was confined to infarcted tissue and closely matched NR areas identified using Thioflavin-S (Figure 1D). Conclusion These findings highlight the value of high-resolution post-mortem CMR in providing a comprehensive assessment of IMH in small animal AMI models. In addition, caution is advised when interpreting IMH using T2* imaging in vivo, as this technique is susceptible to confounding factors such as motion and susceptibility artifacts.For image description, please refer to the figure legend and surrounding text.