Combined Iron Oxide Nanoparticle Ferumoxytol and Gadolinium Contrast Enhanced MRI Defines Glioblastoma Pseudo-progression

Abstract

Background

Noninvasively differentiating therapy-induced pseudo-progression from recurrent disease in patients with glioblastoma is prospectively difficult due to the current lack of a biologically specific imaging metric. Ferumoxytol iron oxide nanoparticle MRI contrast characterizes innate immunity mediated neuroinflammation; therefore, we hypothesized that combined ferumoxytol and gadolinium enhanced MRI could serve as a biomarker of glioblastoma pseudo-progression.

Methods

In this institutional review board approved, retrospective study, we analyzed ferumoxytol and gadolinium contrast enhanced T₁-weighted 3T MRI in 45 patients with glioblastoma over multiple clinical time points. IDH-1 mutational status was characterized by exome sequencing. Sum of products diameter measurements were calculated according to RANO criteria from both gadolinium and ferumoxytol enhanced sequences. Enhancement mismatch was calculated as the natural log of the ferumoxytol to gadolinium sum of products diameter ratio. Analysis of variance and Students t-test assessed differences in mismatch ratios. P-value < 0.05 indicated statistical significance.

Results

With the development of pseudo-progression we observed a significantly elevated mismatch ratio when compared to disease recurrence (P< 0.01) within IDH-1 wild type patients. Patients with IDH-1 mutation demonstrated significantly reduced mismatch ratio with the development of pseudo-progression when compared to disease recurrence (P< 0.01). Receiver operator curve analysis demonstrated 100% sensitivity and specificity for the use of mismatch ratios as a diagnostic biomarker of pseudo-progression.

Conclusion

Our study suggests that ferumoxytol to gadolinium contrast mismatch ratios are a MRI biomarker for the diagnosis of pseudo-progression in patients with glioblastoma. This may be due to the unique characterization of therapy-induced neuroinflammation.