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, B
1
+
‐corrected 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 T
1
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 T
1
maps were computed from two VFA acquisitions (4° and 20°). Mean R
1
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 T
1
and R
1
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 R
1
and ferumoxytol concentration (
R
= 0.975,
p
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 T
1
shortening, consistent with the expected iron accumulation. The dual‐echo capabilities of PETALUTE facilitated observation of elevated T
1
with preserved T
2
*‐weighted signal in one of the mammary tumors.
Conclusions
The proposed PETALUTE‐based T
1
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 T
1
mapping.