Iron Sucrose as MRI Contrast Agent in Ischemic Stroke Model

Background Despite the growing concern about the safety of gadolinium-based contrast agents (GBCAs), they are still the most commonly used. Ferumoxytol, as an off-label alternative MRI contrast agent, cannot be administered by a rapid bolus for dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI). Purpose To assess the feasibility of iron sucrose (IS) as a contrast agent for MR angiography (MRA) and DSC-PWI. Study Type Prospective animal model. Animal Model Thirty-six normal rats (16 for MRA, 20 for biocompability tests) and 36 occlusion of the middle cerebral artery (MCAO) model rats. Field Strength/Sequence 3.0T; head and neck angiography, using a fast spoiled gradient-recalled-echo (FSPGR) sequence and DSC-MRI using echo planar imaging(EPI) sequence. Assessment MRA was performed on normal rats to examine the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of different doses of IS. DSC-PWI was performed on MCAO rats at 0, 24, 48, and 72 hours postreperfusion to investigate the lesion detectability of IS. Arterial spin labeling (ASL) and DSC-PWI enhanced by GBCAs were conducted on MCAO rats as controls. Statistical Tests Kruskal-Wallis test was used to compare qualitative assessment. One-way analysis of variance (ANOVA) was used to compare the parametric data. Pearson's r values were evaluated between relative cerebral blood flow(rCBF)-ASL, rCBF-DSCIS, and rCBF obtained from DSC-PWI enhanced by GBCA. Results The mean SNR and CNR of the common carotid artery at doses of 10 mg Fe/kg of IS were comparable with the standard dose of GBCAs (SNR: 68.04 +/- 12.55 vs. 67.72 +/- 14.66; CNR: 23.78 +/- 7.21vs. 21.63 +/- 6.83). In MCAO rat models, rCBF and relative cerebral blood volume (rCBV) of ipsilateral striatum declined (0.72 +/- 0.14, 0.86 +/- 0.11) with prolonged relative mean transit time (rMTT) and relative time-to-peak (rTTP) (1.27 +/- 0.24, 1.07 +/- 0.03) following occlusion. Hyperperfusion was observed in all rats at 48 and 72 hours postreperfusion, in 4/6 rats at 24 hours postreperfusion for IS-mediated DSC-PWI. Data Conclusion IS may be an effective contrast agent for both MRA and DSC-PWI in ischemic stroke models. Level of Evidence 1 Technical Efficacy Stage 1