SU‐GG‐BRC‐01: Modeling Myocardial Mn2+ Efflux Rates Using Manganese‐Enhanced MRI T1 Mapping in a Murine Myocardial Infarction Model

Purpose: Alterations in myocyte [formula omitted] handling appear to be centrally involved in the dysfunctional characteristics of the failing heart. This study uses quantitative manganese‐enhanced MRI techniques to detect changes in the [formula omitted] efflux relative to [formula omitted] fluctuations in mice following inhibition of the sodium calcium exchanger (NCX) with SEA0400. Furthermore, the technique was applied to a mouse myocardial infarction (MI) model. Segmentation and modeling analyses were used to examine regional changes in [formula omitted] efflux rates, allowing for a study of the dynamics in the peri‐infarction zone. Methods and Materials: [formula omitted] was infused via the tail vein into C57Bl/6 mice (n=88). T₁‐maps were obtained both pre‐ and post‐infusion at multiple time points. Time dependent changes in the relaxation rate (ΔR₁) were calculated in the myocardium. For the MI mice various affected zones within the myocardium were identified and analyzed using segmentation software. The results from control and SEA0400 treated mice were applied to a pharmacokinetic model in order to estimate the [formula omitted] transfer rates. Results: The ΔR₁ efflux half‐life was doubled following treatment with 50 mg/kg SEA0400, with the two compartment model predicting a reduction in the myocardial efflux rate by more than a factor of two. In the MI group constant ΔR₁ values for viable and infarcted tissue were fit with radial analysis. A significant difference was observed between the efflux rates of the infarcted region to that of the viable region, with a continuous range of efflux rates in the peri‐infarcted region. Conclusions: Quantitative MEMRI with T₁‐mapping has demonstrated the sensitivity to observe changes in [formula omitted] efflux with the ability to model the relative efflux rates. The technique also provides enough sensitivity for identifying the potentially salvageable adjacent zone as well as examining regional alterations in [formula omitted] fluxes leading to relative [formula omitted] information, potentially applicable to monitoring disease progression.