Relaxometry and magnetometry of the MR contrast agent MION-46L.

MION-46L is an ultrasmall monocrystalline superparamagnetic (SPM) iron oxide that is of current interest as an MR contrast agent. It is believed to consist primarily of small maghemite or magnetite crystals that possess a SPM moment, but the exact magnetic properties and related mechanisms of T1 and T2 proton relaxation enhancement are not well understood. We have obtained a comprehensive data set consisting of magnetization curves, EPR spectra, and 1/T1 and 1/T2 nuclear magnetic relaxation dispersion (NMRD) profiles for this contrast agent. The magnetization curves show a primary curvature consistent with a SPM moment of 10,300 Bohr magnetons (BM) per particle. In addition, there is a secondary high-field curvature that is consistent with a smaller SPM moment of 1600 BM, which may be responsible for the observed high-field increase in 1/T2. Finally, there appear to be a considerable number of paramagnetic ions present that are needed to account for the high-field increase in magnetization, and that can provide an alternative explanation for the magnitude of the low-field T1 plateau. This ‘‘three-phase model’’ appears to be successful in explaining in a self-consistent and quantitative manner the combined results of the magnetometry, relaxometry, and EPR studies. Magn Reson Med 42:379‐384, 1999. Published 1999 Wiley-Liss, Inc.† Superparamagnetic (SPM) nanoparticles are currently under investigation as potential contrast agents for both standard and functional MR imaging. These small ferrimagnetic particles have magnetic moments that, because of the small crystal size, are unhindered by lattice orientation and therefore do not exhibit hysteresis, hence the term ‘‘superparamagnetic.’’ In an applied magnetic field, the moments are therefore free to align themselves along the field, thereby creating microscopic field gradients that dephase nearby protons. This, in turn, shortens the NMR relaxation time T2, over and beyond the usual dipole-dipole relaxation mechanism that affects both T1 and T2. The first attempt to explain T2-shortening by SPM particles by the standard quantum mechanical theory of relaxation failed to take into account the induced magnetization (1). This serious oversight was later remedied (2,3), and the resulting theory was found to be in good agreement with T1 data for AMI-25 iron oxide particles. However, it was not able to explain the elevated ‘‘plateau’’ shown by MION-46L at low fields, i.e., the increase in relaxation rate that appears below about 0.01 T. Later, a low-field term was added (or restored) to the theory (4), but this resulted in an overestimation of the plateau. The magnitude of the plateau has now been successfully explained by invoking a reduced effect of the crystalline anisotropy (5). Although the T2-shortening of MION-46L is significantly greater than T1-shortening at high fields, there have been few T2 measurements because of the difficulty of measuring T2 at different field strengths. Yet MION-46L (6,7) is a good candidate for theoretical comparison because of its monocrystallinity and low tendency to agglomerate. We report herein on measurements of T1 and T2 of MION-46L over the field range 0.025‐1.5 T, using a variablefield relaxometer, as well as magnetometry and electron spin resonance (ESR) studies. Both the magnetometry and relaxometry data suggest that there is a second, smaller SPM component present, with magnetic moments about one-sixth that of the core. This would explain the secondary curvature seen in the magnetization curves, and also the increase in 1/T2, at high fields. In addition, the magnetometry results suggest the presence of paramagnetic (PM) ions. We show that such PM atoms may provide an alternative explanation for the magnitude of the lowfield T1/T2 plateau, that may possibly supplement the crystalline anistropy explanation given earlier (5).