Regional contrast agent quantification in a mouse model of myocardial infarction using 3D cardiac T₁mapping

Quantitative relaxation time measurements by cardiovascular magnetic resonance (CMR) are of paramount importance in contrast-enhanced studies of experimental myocardial infarction. First, compared to qualitative measurements based on signal intensity changes, they are less sensitive to specific parameter choices, thereby allowing for better comparison between different studies or during longitudinal studies. Secondly, T₁ measurements may allow for quantification of local contrast agent concentrations. In this study, a recently developed 3D T₁ mapping technique was applied in a mouse model of myocardial infarction to measure differences in myocardial T₁ before and after injection of a liposomal contrast agent. This was then used to assess the concentration of accumulated contrast agent.

Myocardial ischemia/reperfusion injury was induced in 8 mice by transient ligation of the LAD coronary artery. Baseline quantitative T₁ maps were made at day 1 after surgery, followed by injection of a Gd-based liposomal contrast agent. Five mice served as control group, which followed the same protocol without initial surgery. Twenty-four hours post-injection, a second T₁ measurement was performed. Local ΔR₁ values were compared with regional wall thickening determined by functional cine CMR and correlated to ex vivo Gd concentrations determined by ICP-MS.

Compared to control values, pre-contrast T₁ of infarcted myocardium was slightly elevated, whereas T₁ of remote myocardium did not significantly differ. Twenty-four hours post-contrast injection, high ΔR₁ values were found in regions with low wall thickening values. However, compared to remote tissue (wall thickening > 45%), ΔR₁ was only significantly higher in severe infarcted tissue (wall thickening < 15%). A substantial correlation (r = 0.81) was found between CMR-based ΔR₁ values and Gd concentrations from ex vivo ICP-MS measurements. Furthermore, regression analysis revealed that the effective relaxivity of the liposomal contrast agent was only about half the value determined in vitro.

3D cardiac T₁ mapping by CMR can be used to monitor the accumulation of contrast agents in contrast-enhanced studies of murine myocardial infarction. The contrast agent relaxivity was decreased under in vivo conditions compared to in vitro measurements, which needs consideration when quantifying local contrast agent concentrations.