Fast and Robust T1 Mapping Based on a 3D Dual-Echo UTE Sequence (PETALUTE) for SPION Biodistribution Assessment

TL;DR

This paper introduces PETALUTE, a fast, robust 3D dual-echo UTE MRI sequence for accurate T1 mapping of SPIONs, enabling improved biodistribution assessment with high spatial resolution and reduced scan time.

Contribution

The study develops a novel PETALUTE sequence that offers rapid, B1-corrected T1 mapping with positive contrast and better quantification of ferumoxytol distribution compared to traditional methods.

Findings

PETALUTE shows strong linear correlation between R1 and ferumoxytol concentration.

It provides high-resolution imaging in under 5 minutes.

It outperforms RARE-VTR in positive contrast and quantification accuracy.

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) such as ferumoxytol are promising theranostic agents detectable with MRI. Relaxation time mapping offers reproducible, quantitative biomarkers of SPION distribution, but conventional methods suffer from susceptibility artifacts, long echo times, and extended scan durations, limiting accurate quantification. This study developed a fast, B1-corrected T1-mapping protocol using PETALUTE, a 3D dual-echo ultrashort-echo MRI sequence with a rosette k-space trajectory and variable flip-angle acquisition for quantitative ferumoxytol imaging. Agarose phantoms containing 0-5000 ppm ferumoxytol were scanned at 7T with PETALUTE and vendor-supplied RARE-VTR. PETALUTE T1 maps were derived from two flip angles (4 deg and 20 deg), and mean R1 values were correlated with ferumoxytol concentration. For in vivo feasibility, mice bearing 4T1 mammary and flank tumors were scanned 24 h post-injection (ferumoxytol: n=2, 40 mg/kg; control: n=1). Regions of interest in muscle and tumors were analyzed to compare T1 and R1 values obtained with both methods. PETALUTE produced positive contrast for all phantom concentrations except 5000 ppm, whereas RARE-VTR did not. PETALUTE demonstrated a significant linear correlation between R1 and ferumoxytol concentration (R=0.975, p<0.01), in contrast to RARE-VTR (R=0.672, p=0.144). In vivo, PETALUTE enabled high-resolution, whole-abdominal imaging in 4 min 19 s. Ferumoxytol-injected mice showed T1 shortening in flank tumors, consistent with iron uptake, and PETALUTE revealed elevated T1 value with preserved T2*-weighted signal in one mammary tumor. PETALUTE-based T1 mapping provides fast, quantitative, positive-contrast ferumoxytol imaging with greater spatial coverage and a wider usable concentration range than conventional RARE-VTR.