In vivo R1-enhancement mapping of canine myocardium using ceMRI with Gd(ABE-DTTA) in an acute ischemia-reperfusion model.

PURPOSE: To demonstrate the usefulness of normalized DeltaR1 (DeltaR1(n)) mapping in myocardial tissue following the administration of the contrast agent (CA) Gd(ABE-DTTA). MATERIALS AND METHODS: Ischemia-reperfusion experiments were carried out in 11 dogs. The method exploited the relatively long tissue lifetime of Gd(ABE-DTTA), and thus no fast R1 measurement technique was needed. Myocardial perfusion was determined with colored microspheres (MP). RESULTS: With varying extent of ischemia, impaired wall motion (WM) and lower DeltaR1(n) values were detected in the ischemic sectors, as opposed to the nonischemic sectors where normal WM and higher DeltaR1(n) were observed. Based on the DeltaR1(n), data from the myocardial perfusion assay and the DeltaR1(n) maps were compared in the ischemic sectors. A correlation analysis of these two parameters demonstrated a significant correlation (R = 0.694, P < 0.005), validating the DeltaR1(n)-mapping method for the quantitation of ischemia. Similarly, pairwise correlations were found for the MP, DeltaR1(n), and wall thickening (WT) values in the same areas. Based on the correlation between DeltaR1(n) and MP, DeltaR1(n) maps calculated with a pixel-by-pixel resolution can be converted to similarly high-resolution myocardial perfusion maps. CONCLUSION: These results suggest that the extent of the severity of ischemia can be quantitatively represented by DeltaR1(n) maps obtained in the presence of our CA.

Synthesis and in vivo evaluation of new contrast agents for cardiac MRI.

Analogues 2-6 of N(3),N(6)-bis(2'-myristoyloxyethyl)-1, 8-dioxotriethylenetetraamine-N,N,N',N'-tetraacetic acid (BME-DTTA) (1), which like 1 are also based on the DTTA structure but contain shorter fatty acyl chains, were synthesized to improve the water solubility of the corresponding gadolinium complexes. The gadolinium complexes of 1 and 3-5 have very low solubility in water. Thus liposomal preparations are necessary for their in vivo MRI application. These liposomal preparations retain high in vitro relaxivities (27.1, 21.57, 20.32, 23.1 s(-1) mM(-1), respectively) and induce sustained MRI signal intensity enhancements (67.2, 38.4, 52.1, 41.7 in arbitrary units, respectively). The gadolinium complex of 2 is quite soluble in water. Its lifetime in the blood stream, however, is short. The gadolinium complex of analogue 6, N-(2-butyryloxyethyl)-N'-(2-ethyloxyethyl)-N,N'-bis[N' ',N' '-bis(carboxymethyl)acetamido]-1,2-ethanediamine (ABE-DTTA), has demonstrated its potential as a water-soluble, cardiac-specific, MRI contrast agent. It is completely soluble in water at a 25 mM concentration, allowing the preparation of an injectable dose. The in vitro relaxivity of the complex is 16.24 s(-1) mM(-1). The agent shows a specific accumulation in the heart tissue reaching its maximum within 15 min after administration, inducing a sustained MRI signal intensity enhancement of 43.6%. This enhancement lasts for at least 3 h, thus indicating a reasonably long lifetime of this contrast agent in the myocardium without deleterious effects on heart function parameters.