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Monitoring dynamic alterations in calcium homeostasis by T 1 ‐weighted and T 1 ‐mapping cardiac manganese‐enhanced MRI in a murine myocardial infarction model
Author(s) -
Waghorn Ben,
Edwards Tiffany,
Yang Yuhui,
Chuang KaiHsiang,
Yanasak Nathan,
Hu Tom C.C.
Publication year - 2008
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1287
Subject(s) - in vivo , homeostasis , washout , chemistry , myocardial infarction , inotrope , manganese , medicine , calcium , cardiology , biology , microbiology and biotechnology , organic chemistry
Manganese has been used as a T 1 ‐weighted MRI contrast agent in a variety of applications. Because manganese ions (Mn 2+ ) enter viable myocardial cells via voltage‐gated Ca 2+ channels, manganese‐enhanced MRI is sensitive to the viability and inotropic state of the heart. In spite of the established importance of Ca 2+ regulation in the heart both before and after myocardial injury, monitoring strategies to assess Ca 2+ homeostasis in affected cardiac tissues are limited. This study implements a T 1 ‐mapping method to obtain quantitative information both dynamically and over a range of MnCl 2 infusion doses. To optimize the current Mn 2+ infusion protocols, we performed both dose‐dependent and temporal washout studies. A non‐linear relationship between infused MnCl 2 solution dose and increase in left ventricular wall relaxation rate (Δ R 1 ) was observed. Control mice also exhibited significant Mn 2+ clearance over time, with a decrease in Δ R 1 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 Mn 2+ dose, Δ R 1 , 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 Ca 2+ handling in vivo because of the physiological remodeling after myocardial infarction. Left ventricular free wall Δ R 1 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. Copyright © 2008 John Wiley & Sons, Ltd.