Intracellular manganese ions provide strong T1 relaxation in rat myocardium

The efficacy of manganese ions (Mn2+) as intracellular (ic) contrast agents was assessed in rat myocardium. T-1 and T-2 and Mn content were measured in ventricular tissue excised from isolated perfused hearts in which a 5-min wash-in with 0, 30, 100, 300, or 1000 muM of Mn dipyridoxyl diphosphate (MnDPDP) was followed by a 15-min wash-out to remove extracellular (ec) Mn2+. An inversion recovery (IR) analysis at 20 MHz revealed two T-1 components: an is and short T1-1 (650-251 ms), and an ec and longer T1-2 (2712-1042 ms). Intensities were about 68% and 32%, respectively. Tissue Mn content correlated particularly well with is R1-1 A two-site water-exchange analysis of T-1 data documented slow water exchange with is and ec lifetimes of 11.3 s and 7.5 s, respectively, and no differences between apparent and intrinsic relaxation parameters. Ic relaxivity induced by Mn2+ ions in is water was as high as 56 (s mM)(-1), about 8 times and 36 times higher than with Mn2+ aqua ions and MnDPDP, respectively, in vitro. This value is as high as any reported to date for any synthetic protein-bound metal chelate. The increased rotational correlation time (tau(R)) between proton and electron (Mn2+) spins, and maintained inner-sphere water access, might make is Mn2+ ions and Mn2+-ion-releasing contrast media surprisingly effective for T-1-weighted imaging. (C) 2004 Wiley-Liss, Inc.