Utility Decay Rates of T1-Weighted Magnetic Resonance Imaging Contrast Based on Redox-Sensitive Paramagnetic Nitroxyl Contrast Agents

The availability and applicability of the combination of paramagnetic nitroxyl contrast agent and T-1-weighted gradient echo (GE)-based dynamic magnetic resonance imaging (MRI) measurement for redox imaging are described. The time courses of T-1-weighted GE MRI signal intensities according to first-order paramagnetic loss of a nitroxyl contrast agent were simulated for several experimental conditions. The apparent decay rate calculated based on decreasing T-1-weighted MRI contrast (k(MRI))can show an approximate value of the original decay rate (k(true)) discretionarily given for simulation with suitable experimental parameters. The difference between k(MRI) and k(true) can be sufficiently small under T-1-weighted spoiled gradient echo (SPGR) scan conditions (repetition time=75 ms, echo time=3 ms, and flip angle=45 degrees), with a conventional redox-sensitive nitroxyl contrast agent, such as 4-hydroxy-2,2,6,6,-tetramethylpiperidine-N-oxyl (TEMPOL) and/or 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (carbamoyl-PROXYL), and with i.v. doses of below 1.5 mu mol/g b.w. for mice. The results of this simulation suggest that the k(MRI) of nitroxyl contrast agents can be the primary index of redox status under biological conditions.