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

Abstract

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. 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. 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. 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.