Fast and robust T1 mapping based on a 3D dual‐echo UTE sequence (PETALUTE) for superparamagnetic iron oxide nanoparticle (SPION) biodistribution assessment

Abstract

Abstract Background 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. Purpose To address the limitations of conventional approaches, this study aimed to develop a fast, B1 +‐corrected T1 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. Methods 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. Results 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. Conclusions 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.