Monitoring dynamic calcium homeostasis alterations by T₁-weighted and T₁-mapping cardiac manganese enhanced MRI (MEMRI) in a murine myocardial infarction model
Waghorn, Benjamin J.
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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 calcium channels, manganese-enhanced MRI (MEMRI) is sensitive to the viability and the inotropic state of the heart. In spite of the established importance of calcium regulation in the heart both prior to, and following, myocardial injury, monitoring strategies to assess calcium 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. In order to optimize the current manganese infusion protocols, both dose dependent and temporal washout studies were performed. A non-linear relationship between infused MnCl₂ solution dose and increase in left ventricular free wall relaxation rate (∆R₁) was observed. Control mice also exhibited significant manganese clearance over time, with approximately 50% decrease of ∆R₁ occurring in just 2.5 hours. The complicated efflux time dependence possibly suggests multiple efflux mechanisms. Using the measured relationship between infused MnCl₂ and ∆R₁, absolute Mn concentration ICP-MS data analysis provided a means to estimate the absolute heart Mn concentration in vivo. We have shown that this technique has the sensitivity to observe or monitor potential Ca²+ handling alterations in vivo due to the physiological remodeling following myocardial infarction. Left ventricular free wall ∆R₁ values were significantly lower (P = 0.005) in the adjacent zone, surrounding the injured myocardial tissue, than healthy left ventricular free wall tissue. This inferred reduction in Mn concentration can be used to estimate potentially salvageable myocardium in vivo for future therapeutic treatment or evaluation of disease progression.