(Circulation. 1995;92:3549-3559.)
© 1995 American Heart Association, Inc.
Articles |
In Vivo MRI Visualization of Acute Myocardial Ischemia and Reperfusion in Ferrets by the Persistent Action of the Contrast Agent Gd(BME-DTTA)
Presented in part at the 11th Annual Meeting of the Society of Magnetic Resonance in Medicine, Berlin, Germany, August 8-14, 1992, and at the second Annual Meeting of the Society of Magnetic Resonance, San Francisco, Calif, August 8-12, 1994.
From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham.
Correspondence to Gabriel A. Elgavish, PhD, University of Alabama at Birmingham, Division of Cardiovascular Disease, Department of Medicine, Room 336 Tinsley Harrison Tower, Birmingham, AL 35294-0006. E-mail bch0054@uabdpo.dpo.uab.edu.
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 N3,N6-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
99mTc-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 
R1 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.
Key Words: magnetic resonance imaging • perfusion • ischemia • contrast media • gadolinium • 99mTc-sestamibi
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