Iron Oxide Nanoparticle MRI for Human Brain Tumors: A Systematic Review and Protocol Level Meta analysis of Administered Doses Across Ferumoxtran 10, Ferumoxytol, and Ferumoxides

BackgroundGadolinium-based contrast agents (GBCAs) have recognized limitations for accurate delineation of brain tumor margins and perfusion assessment in neuro-oncology. Nanoparticle contrast agents (NP-CAs), particularly ultrasmall superparamagnetic iron oxides (USPIOs), may overcome these limitations by providing delayed uptake and tissue characterization. MethodsWe systematically searched PubMed, Embase, Scopus, Web of Science, and trial registries on July 2025 for human neuro-oncology studies using NP-CAs. The primary outcome was the change in relative cerebral blood volume ({Delta}rCBV) compared with that of GBCA imaging at prespecified time points. The secondary outcomes were the contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), reader-rated margin delineation, and safety. Two reviewers independently extracted the data and assessed the risk of bias via tools from the Joanna Briggs Institute. Random effects meta-analysis was performed when [≥]3 comparable datasets were available; otherwise, the results were synthesized narratively. ResultsSix studies met the inclusion criteria. Agents included ferumoxtran-10, ferumoxytol, and ferumoxides, with intravenous doses ranging from 0.56-7.00 mg Fe/kg. The pooled common-effect mean dose was 4.65 mg/kg. Across heterogeneous designs, NP-CAs consistently enhanced margin delineation and perfusion metrics: ferumoxtran-10 produced sharp, persistent T2/T2* rims beyond T1-GBCA enhancement, and ferumoxytol-based DSC (Dynamic Susceptibility Contrast) yielded a higher rCBV with reduced leakage effects. No serious adverse events were reported; infusion reactions were rare and inconsistently defined. ConclusionsCompared with GBCA, NP-CAs, particularly USPIOs, improve brain tumor margin visualization and perfusion assessment. However, methodological heterogeneity and small sample sizes limit certainty. Standardized protocols for dosing, acquisition, and safety monitoring, alongside biopsy-validated prospective trials, are needed before clinical adoption.