Fast and robust T1 mapping based on a 3D dual-echo UTE sequence (PETALUTE) for superparamagnetic iron oxide...

Superparamagnetic iron oxide nanoparticles (SPIONs), such as ferumoxytol, are promising theranostic agents that can be assessed with MRI. Relaxation time mapping can provide reproducible and quantitative biomarkers of SPION distribution, suitable for longitudinal and cross-individual studies. However, conventional approaches suffer from strong susceptibility artifacts, long echo times (TE), and prolonged scan times, which limit the accurate quantification of SPION biodistribution.

To address the limitations of conventional approaches, this study aimed to develop a fast, B₁ ⁺-corrected $T_1$ mapping protocol based on PETALUTE (a 3D dual-echo ultrashort echo time MRI sequence with a petal-like rosette k-space trajectory) using a variable flip-angle (VFA) acquisition for T₁ mapping to assess ferumoxytol distribution.

Agarose phantoms containing 0-5000 µg/mL ferumoxytol were scanned on a preclinical 7T MRI system using PETALUTE and RARE-VTR (rapid acquisition with relaxation enhancement and variable repetition time). PETALUTE T₁ maps were computed from two VFA acquisitions (4° and 20°). Mean R₁ values were correlated with ferumoxytol concentration to assess the method's reliability. For in vivo feasibility testing, mice bearing 4T1 mammary tumors and flank tumors were assigned to the control (n = 1) or ferumoxytol-injected group (n = 2; 40 mg/kg i.v.). Abdominal MRI scans were performed 24 h post-injection with both PETALUTE and RARE-VTR. Regions of interest in the thigh muscle, mammary tumors, and flank tumors were analyzed to compare the estimated T₁ and R₁ values obtained with both methods.

In the phantom study, PETALUTE preserved positive contrast for ferumoxytol at all concentrations, whereas the conventional RARE-VTR sequence exhibited signal loss and hypointensity. For PETALUTE, there was a significant linear correlation between R₁ and ferumoxytol concentration (R = 0.975, p < 0.01), while RARE-VTR showed no significant correlation (R = 0.672, p = 0.144). In vivo, PETALUTE provided high-resolution, non-gated, whole-abdominal images with short acquisition times (4 min 19 s). In ferumoxytol-injected mice, flank tumors exhibited T₁ shortening, consistent with the expected iron accumulation. The dual-echo capabilities of PETALUTE facilitated observation of elevated T₁ with preserved T₂*-weighted signal in one of the mammary tumors.

The proposed PETALUTE-based T₁ mapping enables fast and positive-contrast ferumoxytol imaging with higher spatial coverage and more stable measurements across a wider concentration range than conventional RARE-VTR T₁ mapping.