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Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction - PubMed

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Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction

Nur Hayati Jasmin et al. Adv Sci (Weinh). 2021 Jun.

Abstract

Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but are challenging to obtain. Here, manganese, a calcium analogue and clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an imaging biomarker of myocardial viability in the first hours after experimental MI. Safe Mn2+ dosing is confirmed by measuring in vitro beating rates, calcium transients, and action potentials in cardiomyocytes, and in vivo heart rates and cardiac contractility in mice. Quantitative T1 mapping-manganese-enhanced MRI (MEMRI) reveals elevated and increasing Mn2+ uptake in viable myocardium remote from the infarct, suggesting MEMRI offers a quantitative biomarker of cardiac inotropy. MEMRI evaluation of infarct size at 1 h, 1 and 14 days after MI quantifies myocardial viability earlier than the current gold-standard technique, late-gadolinium-enhanced MRI. These data, coupled with the re-emergence of clinical Mn2+ -based contrast agents open the possibility of using MEMRI for direct evaluation of myocardial viability early after ischemic onset in patients.

Keywords: MRI; imaging; manganese; myocardial infarction; viability.

© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Effects of manganese on cardiac electrophysiology and function: a) Upper panel: Representative optical action potential and Ca2+ transient traces from HL‐1 cardiomyocytes at baseline and at 2 and 5 min after superfusion with 0.1 mM MnCl2 with/out CaG supplement. Lower panel: APD50 and APD80 were not affected by 0.1 mM MnCl2 (n = 5), but Ca2+ transient amplitude was reduced by 0.1 mM MnCl2 and partially restored by supplement with 0.1 mM CaG (n = 4). Data were analyzed by paired two‐tailed Student's t‐test to compare with baseline **p = 0.0011 ****p < 0.0001 and unpaired two‐tailed Student's t‐test to compare MnCl2 to MnCl2+CaG‐ ## p = 0.0011 ### p = 0.0003). b) Representative optical action potential traces from human iPSC derived cardiomyocytes at baseline and at 2 and 5 min after superfusion with 0.1 mM MnCl2. APD50 and APD80 were not affected by 0.1 mM MnCl2 (n = 6). c) Representative end systolic ultrasound images acquired before and after injection of the compounds indicated. d) Time course of myocardial contractility quantified as fractional shortening showed immediate reduction in myocardial contractility after i.v. infusion of 0.1 mM MnCl2 (n = 6) which can be reversed when Mn2+ was supplemented with CaG (MnCaG) at either 1:1 or 2:1 MnCl2 to CaG ratio (n = 6). Mean value ± standard error mean (SEM). Data were compared between groups at each time point by one‐way ANOVA (****p < 0.0001 at 1 s to 1 min post injection) and compared to baseline in each group using two‐way repeated measures ANOVA followed by Dunnett's post hoc test (Table S1, Supporting Information). Raw data are presented in Table S1 in the Supporting Information.

Figure 2
Figure 2

Time course of manganese uptake in control mice. a) R1 values (mean ± SEM) in myocardium, liver, muscle, and blood at baseline, 10, 30, 60 min and 24 h post injection of 1) 0.02 mM MnCl2 i.v. (n = 6); 2) 0.1 mM MnCl2 + 0.1 mM CaG i.v. [MnCaG1:1] (n = 5); 3) 0.1 mM MnCl2 + 0.05 mM CaG i.v. [mnCaG2:1] (n = 5); or 4) 0.1 mM MnCl2 i.p. (n = 5). Data were analyzed by one‐way ANOVA. Myocardium 10, 30, and 60 min (****p < 0.0001); liver 10, 30 (****p < 0.0001), and 60 min (***p = 0.0002); muscle 60 min (**p < 0.0033); and blood 10 min (***p = 0.0008), 30 min (***p = 0.0005), and 60 min (****p < 0.0001). b) Representative images for each group at baseline, 10, 30, and 60 min and 24 h post injection.

Figure 3
Figure 3

T1 mapping of manganese uptake acutely after MI. a) Time course of changes in R1 over the first 3 h of MI from the area‐at‐risk segments (AAR‐MI, n = 8) and viable segments remote from the AAR (Remote‐MI, n = 8) of infarcted hearts; and naïve mice with the same Mn2+ infusion times (Viable‐Naïve, n = 5). Mice received i.p. injections of 0.1 mM MnCl2 40 min before permanent coronary occlusion. Measurements were repeated at 2 days (n = 5) after MI (60 min after re‐administration of 0.1 mM MnCl2). Statistical significance were calculated using one‐way ANOVA followed by Tukey's post hoc test to compare between groups at 1 h (***p = 0.0004), 2 h (***p = 0.0007), 3 h (***p = 0.0004), and 48 h and using two‐way repeated measures ANOVA followed by Tukey's post hoc test (Viable‐MI group, 1 h versus 3 h, # p = 0.0481). b) Representative T1 maps of infarcted and healthy mice. Blue arrow = Remote‐MI, Yellow arrow = AAR‐MI, Green arrow = Viable‐Naïve.

Figure 4
Figure 4

Direct comparison of MEMRI with LGE‐MRI in AMI. a) Representative MEMRI and LGE‐MRI images acquired in mice at 1 h, 1 and 14 days after MI and compared with 14 days histological TTC staining for delineation of infarct area. b) Mean of infarct size measured by MEMRI and LGE‐MRI at 1 h (n = 7), 1 day (n = 14), and 14 days (n = 10) after MI and compared with histological TTC staining. Data were analyzed using unpaired (MEMRI vs LGE‐MRI at 1 h, **p = 0.0015) and paired (MEMRI vs LGE‐MRI at 1 day and 14 days) two‐tailed t‐tests and one‐way ANOVA followed by Tukey's post hoc test (LGE‐MRI, 1 h vs 1 day, ## p = 0.0083 and 1 h vs 14 days, # p = 0.024). c) Correlation between 1 h versus 1 day MEMRI (p = 0.0003) and LGE‐MRI (ns) measurements of infarct size. d) Correlation between MEMRI versus LGE‐MRI measurements of infarct size at 1 (p = 0.0002) and 14 days post‐MI (p = 0.0001). Correlations were calculated using Pearson correlation.

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References

    1. Neumann F. J., Sousa‐Uva M., Ahlsson A., Alfonso F., Banning A. P., Benedetto U., Byrne R. A., Collet J. P., Falk V., Head S. J., Juni P., Kastrati A., Koller A., Kristensen S. D., Niebauer J., Richter D. J., Seferovic P. M., Sibbing D., Stefanini G. G., Windecker S., Yadav R., Zembala M. O., Group ESCSD , Eur. Heart J. 2019, 40, 87. - PubMed
    1. Bulluck H., Dharmakumar R., Arai A. E., Berry C., Hausenloy D. J., Circulation 2018, 137, 1949. - PMC - PubMed
    1. Stuckey D. J., McSweeney S. J., Thin M. Z., Habib J., Price A. N., Fiedler L. R., Gsell W., SK P., Schneider M. D., Circ.: Cardiovasc. Imaging 2014, 7, 240. - PubMed
    1. Rider O. J., Apps A., Miller J., Lau J. Y. C., Lewis A. J. M., Peterzan M. A., Dodd M. S., Lau A. Z., Trumper C., Gallagher F. A., Grist J. T., Brindle K. M., Neubauer S., Tyler D. J., Circ. Res. 2020, 126, 725. - PMC - PubMed
    1. Spath N. B., Thompson G., Baker A. H., Dweck M. R., Newby D. E., Semple S. I. K., Heart 2019, 105, 1695. - PMC - PubMed

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