Assessment of stunned and viable myocardium using manganese-enhanced MRI

Abstract

Objective: In a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling.

Methods: Healthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model.

Results: After manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p<0.0001) with intermediate T1 values (1007±31 ms) in peri-infarct regions. Compared with LGE, MEMRI was more sensitive in detecting dysfunctional myocardium (dysfunctional fraction 40.5±11.9 vs 34.9%±13.9%; p=0.02) and tracked more closely with abnormal wall motion (r²=0.72 vs 0.55; p<0.0001). Kinetic modelling showed reduced myocardial manganese influx between remote, peri-infarct and infarct regions, enabling absolute discrimination of infarcted myocardium. After 3 months, manganese uptake increased in peri-infarct regions (16.5±3.5 vs 22.8±3.5 mL/100 g/min, p<0.0001), but not the remote (23.3±2.8 vs 23.0±3.2 mL/100 g/min, p=0.8) or infarcted (11.5±3.7 vs 14.0±1.2 mL/100 g/min, p>0.1) myocardium.

Conclusions: Through visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases.

Trial registration numbers: NCT03607669; EudraCT number 2016-003782-25.

Keywords: heart failure; magnetic resonance imaging; myocardial infarction.

Figure 1

Manganese-enhanced MRI in healthy volunteers. Representative T1 colour maps (A) and T1 over time (B, n=20) following manganese dipyridoxyl diphosphate (MnDPDP). Dashed line represents mean end of infusion, SD of the mean.

Figure 2

Manganese-enhanced MRI (MEMRI) in patients with myocardial infarction. Representative late gadolinium enhancement (LGE), native and MEMRI T1 mapping (A) and T1 profiles of myocardial regions of interest over time following manganese dipyridoxyl diphosphate (MnDPDP) (C) in a patient with extensive anterior myocardial infarction, compared with healthy control myocardium (n=20). Comparative representative LGE, native and MEMRI T1 mapping (B) and T1 profiles of myocardial regions of interest over time following MnDPDP (D) in a patient with subendocardial myocardial infarction, compared with healthy control myocardium (n=20). Dashed line represents end of infusion, error bars are SD of the mean.

Figure 3

Manganese-enhanced MRI (MEMRI) in myocardial regions of interest. MEMRI T1 values in patients with myocardial infarction (A) and influx constant (Ki), (B) in patients with myocardial infarction; infarct core, peri-infarct and remote myocardial regions of interest, compared with healthy control myocardium. ANOVA, analysis of variance.

Figure 4

Wall motion, late gadolinium enhancement (LGE) and manganese-enhanced MRI (MEMRI) T1 mapping colour maps at the core infarct slice in five patients, represented as 100-chord plots (anterior right ventricle insertion as reference point). Values demonstrate stronger correlation between MEMRI T1 than LGE with reduced wall motion in every patient.

Figure 5

Differential manganese uptake over time. Kinetic modelling of manganese uptake (Ki, influx constant) in patients with myocardial infarction; infarct core, peri-infarct and remote myocardial regions of interest, at acute (n=20) and 3-month (n=14) imaging time points.

Figure 6

Differential manganese uptake after myocardial infarction. Representative late gadolinium enhancement (LGE) and manganese-enhanced MRI (MEMRI) T1 mapping images (A) and Patlak plots (B) in a patient with myocardial infarction, demonstrating differential Ki (influx constant) between myocardial regions of interest over time. Grouped comparison T1 profiles for all patients and healthy control subjects (C). Dashed line represents end of infusion, error bars are SD of the mean. MnDPDP, manganese dipyridoxyl diphosphate.