Introduction Late gadolinium enhanced MRI (LGE-MRI) can quantify infarct size after myocardial infarction (MI) but is non-specific and reflects the increased membrane rupture and extracellular space that develop post MI.1 Mn is a potent T1-contrast agent that enters myocytes through active calcium channels, thus reducing T1 in viable myocardium.2 This active process rapidly ceases under ischemia. Hence, we hypothesised that Mn-enhanced MRI (MEMRI) could quantify final infarct size earlier than LGE-MRI.
Methods Myocardial infarction was induced in 7 mice which then underwent MEMRI (n=4, 0.1 mmol/kg MnCl2) or LGE-MRI (n=3, 0.5 mmol/kg Gd-DTPA) at 1 hour post MI. All animals then underwent both MEMRI and LGEMRI at ∼24 hours post MI with a contrast washout period of at least 5 hours between scans. Imaging was performed using a 9.4T Agilent MRI system and a multi-slice inversion recovery sequence in the short-axis orientation covering the whole left ventricle TE/TR=3.04/1.11 ms, TI=∼600 ms for MEMRI and ∼350 ms for LGE-MRI, 900 excitation pulse, slice thickness=1.0 mm, FOV=25.6 × 25.6 mm, matrix size=128 × 128) as described.3
Results At 1 hour post MI, viable myocardium was enhanced in MEMRI, allowing early delineation of the occlusion zone as 41%±8% of the myocardium, whereas only subtle enhancement was seen on LGE-MRI, yielding a significantly lower value of 12%±2% (p=0.03. Figure 1). At ∼24 hours post MI, the MEMRI measure of infarct size remained constant (41%±5%) whilst LGE-MRI significantly increased to a level comparable with MEMRI (37%±3%). Figure 2 shows a direct comparison of MEMRI and LGE-MRI acquired in the same animal at 22 and 27 hours after MI, respectively, with matching histological TTC staining for infarct size.
Discussion Effected myocytes rapidly stop internalising Mn under ischemic conditions, allowing early delineation of the occlusion zone. The membrane rupture that underlies LGE-MRI occurs later, meaning LGE-MRI underestimates the occlusion zone during the first hours post MI.
Conclusions The present study shows MEMRI can quantify final infarct size earlier than LGE-MRI. This provides a sensitive approach which could be used as an early measure of cell death and myocardial viability when assessing the efficacy of new drugs which target acute MI.
. Doltra A, Amundsen BH, Gebker R, Fleck E, Kelle S. Emerging concepts for myocardial late gadolinium enhancement MRI. Current Cardiology Reviews2013;9:185.
. Waghorn B, Schumacher A, Liu J, Jacobs S, Baba A, Matsuda T, Hu TC-C. Indirectly probing Ca(2+) handling alterations following myocardial infarction in a murine model using T(1)-mapping manganese-enhanced magnetic resonance imaging. Magnetic Resonance in Medicine2011;65:239.
. Chow A, Stuckey DJ, Kidher E, Rocco M, Jabbour RJ, Mansfield CA, Darzi A, Harding SE, Stevens MM, Athanasiou T. Human induced pluripotent stem cell-derived cardiomyocyte encapsulating bioactive hydrogels improve rat heart function post myocardial infarction. Stem Cell Reports 2017;9:1415.
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