Super High Contrast USPIO-Enhanced Cerebrovascular Angiography Using Ultrashort Time-to-Echo MRI

Abstract

Background. Ferumoxytol (Ferahame, AMAG Pharmaceuticals, Waltham, MA) is increasingly used off-label as an MR contrast agent due to its relaxivity and safety profiles. However, its potent T2${}^{\ast }$ relaxivity limits achievable T1-weighted positive contrast and leads to artifacts in standard MRI protocols. Optimization of protocols for ferumoxytol deployment is necessary to realize its potential. Methods. We present first-in-human clinical results of the Quantitative Ultrashort Time-to-Echo Contrast Enhanced (QUTE-CE) MRA technique using the superparamagnetic iron oxide nanoparticle agent ferumoxytol for vascular imaging of the head/brain in 15 subjects at 3.0T. The QUTE-CE MRA method was implemented on a 3T scanner using a stack-of-spirals 3D Ultrashort Time-to-Echo sequence. Time-of-flight MRA and standard TE T1-weighted (T1w) images were also collected. For comparison, gadolinium-enhanced blood pool phase images were obtained retrospectively from clinical practice. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and intraluminal signal heterogeneity (ISH) were assessed and compared across approaches with Welch’s two-sided $t$-test. Results. Fifteen volunteers ($54\pm 17$ years old, 9 women) participated. QUTE-CE MRA provided high-contrast snapshots of the arterial and venous networks with lower intraluminal heterogeneity. QUTE-CE demonstrated significantly higher SNR ($1707\pm 226$), blood-tissue CNR ($1447\pm 189$), and lower ISH ($0.091\pm 0.031$) compared to ferumoxytol T1-weighted ($551\pm 171$; $319\pm 144$; $0.186\pm 0.066$, respectively) and time-of-flight ($343\pm 104$; $269\pm 82$; $0.190\pm 0.016$, respectively), with $p<0.001$ in each comparison. The high CNR increased the depth of vessel visualization. Vessel lumina were captured with lower heterogeneity. Conclusion. Quantitative Ultrashort Time-to-Echo Contrast-Enhanced MR angiography provides approximately 5-fold superior contrast with fewer artifacts compared to other contrast-enhanced vascular imaging techniques using ferumoxytol or gadolinium, and to noncontrast time-of-flight MR angiography, for clinical vascular imaging. This trial is registered with NCT03266848.