Impact of field strength and iron oxide nanoparticle concentration on the linearity and diagnostic accuracy of off‐resonance imaging

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Abstract
Off‐resonance imaging (ORI) techniques are being increasingly used to image iron oxide imaging agents such as monocrystalline iron oxide nanoparticles (MION). However, the diagnostic accuracy, linearity, and field dependence of ORI have not been fully characterized. In this study, the sensitivity, specificity, and linearity of ORI were thus examined as a function of both MION concentration and magnetic field strength (4.7 and 14 T). MION phantoms with and without an air interface as well as MION uptake in a mouse model of healing myocardial infarction were imaged. MION‐induced resonance shifts were shown to increase linearly with MION concentration. In contrast, the ORI signal/sensitivity was highly non‐linear, initially increasing with MION concentration until T2 became comparable to the TE and decreasing thereafter. The specificity of ORI to distinguish MION‐induced resonance shifts from on‐resonance water was found to decrease with increasing field because of the increased on‐resonance water linewidths (15 Hz at 4.7 T versus 45 Hz at 14 T). Large resonance shifts (∼300 Hz) were observed at air interfaces at 4.7 T, both in vitro and in vivo, and led to poor ORI specificity for MION concentrations less than 150 µg Fe/mL. The in vivo ORI sensitivity was sufficient to detect the accumulation of MION in macrophages infiltrating healing myocardial infarcts, but the specificity was limited by non‐specific areas of positive contrast at the air/tissue interfaces of the thoracic wall and the descending aorta. Improved specificity and linearity can, however, be expected at lower fields where decreased on‐resonance water linewidths, reduced air‐induced resonance shifts, and longer T2 relaxation times are observed. The optimal performance of ORI will thus likely be seen at low fields, with moderate MION concentrations and with sequences containing very short TEs. Copyright © 2007 John Wiley & Sons, Ltd.