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Abstract
Restoration of coronary blood flow after a heart attack can cause reperfusion injury potentially leading to impaired cardiac function, adverse tissue remodeling and heart failure. Iron is an essential biometal that may have a pathologic role in this process. There is a clinical need for a precise noninvasive method to detect iron for risk stratification of patients and therapy evaluation. Here, we report that magnetic susceptibility imaging in a large animal model shows an infarct paramagnetic shift associated with duration of coronary artery occlusion and the presence of iron. Iron validation techniques used include histology, immunohistochemistry, spectrometry and spectroscopy. Further mRNA analysis shows upregulation of ferritin and heme oxygenase. While conventional imaging corroborates the findings of iron deposition, magnetic susceptibility imaging has improved sensitivity to iron and mitigates confounding factors such as edema and fibrosis. Myocardial infarction patients receiving reperfusion therapy show magnetic susceptibility changes associated with hypokinetic myocardial wall motion and microvascular obstruction, demonstrating potential for clinical translation.
Restoration of coronary blood flow after a heart attack may lead to reperfusion injury and pathologic iron deposition. Here, the authors perform magnetic susceptibility imaging showing its association with iron in a large animal model of myocardial infarction during wound healing, and showing feasibility in acute myocardial infarction patients undergoing percutaneous coronary intervention.
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1 University of Pennsylvania, Department of Bioengineering, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
2 University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
3 University of Pennsylvania, Department of Biophysics, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
4 University of Pennsylvania, Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
5 University of Pennsylvania, Department of Surgery, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
6 University of Pennsylvania, Department of Medicine, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
7 University of Pennsylvania, Department of Surgery, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); Children’s Hospital of Philadelphia, Department of Pediatrics, Philadelphia, USA (GRID:grid.239552.a) (ISNI:0000 0001 0680 8770)
8 Columbia University Irving Medical Center, Department of Surgery, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729)
9 Columbia University, Department of Chemistry, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729)
10 University of Pennsylvania, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
11 University of Pennsylvania, Department of Medicine, Penn Presbyterian Medical Center, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
12 University of Pennsylvania, Department of Bioengineering, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); University of Pennsylvania, Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)