Monitoring dynamic alterations in calcium homeostasis by T1-weighted and T1-mapping cardiac manganese-enhanced MRI in a murine myocardial infarction model

Ben Waghorn, Tiffany Edwards, Yuhui Yang, Kai Hsiang Chuang, Nathan Yanasak, Tom C.C. Hu

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Manganese has been used as a T1-weighted MRI contrast agent in a variety of applications. Because manganese ions (Mn2+) enter viable myocardial cells via voltage-gated Ca2+ channels, manganese-enhanced MRI is sensitive to the viability and inotropic state of the heart. In spite of the established importance of Ca2+ regulation in the heart both before and after myocardial injury, monitoring strategies to assess Ca2+ homeostasis in affected cardiac tissues are limited. This study implements a T1-mapping method to obtain quantitative information both dynamically and over a range of MnCl2 infusion doses. To optimize the current Mn2+ infusion protocols, we performed both dose-dependent and temporal washout studies. A non-linear relationship between infused MnCl2 solution dose and increase in left ventricular wall relaxation rate (DR1) was observed. Control mice also exhibited significant Mn2+ clearance over time, with a decrease in DR1 of ~50% occurring in just 2.5 h. The complicated efflux time dependence possibly suggests multiple efflux mechanisms. With the use of the measured relationship between infused Mn2+ dose, DR1, and inductively coupled plasma mass spectrometry data analysis provided a means of estimating the absolute heart Mn concentration in vivo. We show that this technique has the sensitivity to observe or monitor potential alterations in Ca2+ handling in vivo because of the physiological remodeling after myocardial infarction. Left ventricular free wall DR1 values were significantly lower (P = 0.005) in the adjacent zone, surrounding the injured myocardial tissue, than in healthy tissue. This inferred reduction in Mn concentration can be used to estimate potentially salvageable myocardium in vivo for future treatment or evaluation of disease progression.

Original languageEnglish (US)
Pages (from-to)1102-1111
Number of pages10
JournalNMR in Biomedicine
Volume21
Issue number10
DOIs
Publication statusPublished - Dec 1 2008

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Keywords

  • Calcium
  • Cardiac MRI
  • Heart
  • Manganese
  • Mouse
  • Myocardial infarction
  • T mapping

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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