Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences

Abstract

Purpose Conventional MRI using contrast agents is semiquantitative because it is inherently sensitive to extravoxular susceptibility artifacts, field inhomogeneity, partial voluming, perivascular effects, and motion/flow artifacts. Herein we demonstrate a quantitative contrast-enhanced MRI technique using ultrashort time-to-echo pulse sequences for measuring clinically relevant concentrations of ferumoxytol, a superparamagnetic iron oxide nanoparticle contrast agent with high sensitivity and precision in vitro and in vivo. Methods The method achieves robust, reproducible results by using rapid signal acquisition at ultrashort time-to-echo (UTE) to produce positive contrast images with pure T1 weighting and little T2∗ decay. The spoiled gradient echo equation is used to transform UTE intensities directly into concentration using experimentally determined relaxivity constants and image acquisition parameters. Results A multiparametric optimization of acquisition parameters revealed an optimal zone capable of producing high-fidelity measurements. Clinically relevant intravascular concentrations of ferumoxytol were measured longitudinally in mice with high sensitivity and precision (∼7.1% error). MRI measurements were independently validated by elemental iron analysis of sequential blood draws. Automated segmentation of ferumoxytol concentration yielded high quality three-dimensional images for visualization of perfusion. Conclusions This ability to longitudinally quantify blood pool CA concentration is unique to quantitative UTE contrast-enhanced (QUTE-CE) MRI and makes QUTE-CE MRI competitive with nuclear imaging. Magn Reson Med 74:431-441, 2015.