Influence of Myocardial Hemorrhage on Staging of Reperfused Myocardial Infarctions With T2 Cardiac Magnetic Resonance Imaging: Insights Into the Dependence on Infarction Type With Ex Vivo Validation

Abstract

Objectives: This study sought to determine whether T₂ cardiac magnetic resonance (CMR) can stage both hemorrhagic and nonhemorrhagic myocardial infarctions (MIs).

Background: CMR-based staging of MI with or without contrast agents relies on the resolution of T₂ elevations in the chronic phase, but whether this approach can be used to stage both hemorrhagic and nonhemorrhagic MIs is unclear.

Methods: Hemorrhagic (n = 15) and nonhemorrhagic (n = 9) MIs were created in dogs. Multiparametric noncontrast mapping (T₁, T₂, and T₂*) and late gadolinium enhancement (LGE) were performed at 1.5- and 3.0-T at 5 days (acute) and 8 weeks (chronic) post-MI. CMR relaxation values and LGE intensities of hemorrhagic, peri-hemorrhagic, nonhemorrhagic, and remote territories were measured. Histopathology was performed to elucidate CMR findings.

Results: T₂ of nonhemorrhagic MIs was significantly elevated in the acute phase relative to remote territories (1.5-T: 39.8 ± 12.8%; 3.0-T: 27.9 ± 16.5%; p < 0.0001 for both) but resolved to remote values by week 8 (1.5-T: -0.0 ± 3.2%; p = 0.678; 3.0-T: -0.5 ± 5.9%; p = 0.601). In hemorrhagic MI, T₂ of hemorrhage core was significantly elevated in the acute phase (1.5-T: 17.7 ± 10.0%; 3.0-T: 8.6 ± 8.2%; p < 0.0001 for both) but decreased below remote values by week 8 (1.5-T: -8.2 ± 3.9%; 3.0-T: -5.6 ± 6.0%; p < 0.0001 for both). In contrast, T₂ of the periphery of hemorrhage within the MI zone was significantly elevated in the acute phase relative to remote territories (1.5-T: 35.0 ± 16.1%; 3.0-T: 24.2 ± 10.4%; p < 0.0001 for both) and remained elevated at 8 weeks post-MI (1.5-T: 8.6 ± 5.1%; 3.0-T: 6.0 ± 3.3%; p < 0.0001 for both). The observed elevation of T₂ in the peri-hemorrhagic zone of MIs and the absence of T₂ elevation in nonhemorrhagic MIs were consistent with ongoing or absence of histological evidence of inflammation, respectively.

Conclusions: Hemorrhagic MIs are associated with persisting myocardial inflammation and edema, which can confound staging of hemorrhagic MIs when T₂ elevations alone are used to discriminate between acute and chronic MI. Moreover, given the poor prognosis in patients with hemorrhagic MI, CMR evidence for myocardial hemorrhage with persistent edema may evolve as a risk marker in patients after acute MI.

Keywords: acute myocardial infarction; cardiac magnetic resonance; hemorrhage; inflammation; iron; preclinical study.