In Vivo MRI Visualization of Acute Myocardial Ischemia and Reperfusion in Ferrets by the Persistent Action of the Contrast Agent Gd(BME-DTTA)

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Abstract
Background Contrast agent–enhanced magnetic resonance imaging (MRI) has the potential to visualize myocardial ischemia. To date, however, no agent has been found that has a sustained effect that allows MRI detection for the entire duration of ischemia and reperfusion and thus is useful in conjunction with stress test MRI. In this article, we introduce the gadolinium complex of N 3 , N 6 -bis(2′-myristoyloxyethyl)-1,8-dioxo-triethylene-tetraamine- N , N , N ′, N ′-tetraacetic acid [Gd(BME-DTTA)], an agent potentially useful for such a purpose. Methods and Results Four protocols were carried out. ECG-triggered, partially T1-weighted, spin-echo MRI was used in protocols A through C. In protocol A, in nonischemic ferrets, 50 μmol/kg Gd(BME-DTTA) induced a 70±5% intensity enhancement lasting 3 hours. In protocol B, the left anterior descending coronary artery was occluded, and a 99m Tc-sestamibi–induced autoradiographic contrast verified ( r =.87, P <.01) a Gd(BME-DTTA)-induced (n=5) or Gd(DTPA)- induced (n=4) MRI contrast. In the Gd(BME-DTTA) group a sustained contrast and in the Gd(DTPA) group a short-lived contrast were observed. In protocol C (n=11), during ischemia, a 31±3.3% ( P <.02) contrast was evident between the ischemic and nonischemic myocardial regions. Upon reperfusion, a contrast of 19±3% ( P <.05) and 13±4.5% ( P <.05) persisted for 5 and 15 minutes, respectively. Beyond 15 minutes, the contrast continued to diminish gradually. Nonradioactive microspheres verified ( r =.87, P <.05) ischemia and reperfusion in this model. In protocol D (n=4), blood ΔR1 data showed that the blood pool retained Gd(BME-DTTA) for the entire time frame of the experiment at high enough concentration to provide an appropriate wash-in effect during the initial contrast enhancement and during reperfusion. Conclusions This study demonstrates that Gd(BME-DTTA) induces a sustained MRI contrast between regions of normal versus ischemic myocardium, showing the potential of this agent for the diagnosis of ischemic heart disease in conjunction with stress tests.