Ferumoxytol-Enhanced MRI to Image Inflammation Within Human Brain Arteriovenous Malformations: a Pilot Investigation

Inflammation cell infiltration and cytokine expression are seen in the vascular walls and intervening stroma of resected brain arteriovenous malformation (bAVM) specimens, even in unruptured and previously untreated lesions. Macrophages may play a critical role in bAVM progression to rupture and could serve as a marker for rupture risk. We assessed feasibility of imaging macrophages within the bAVM nidus using ferumoxytol-enhanced magnetic resonance imaging (MRI) in four patients with already diagnosed bAVMs using iron-sensitive imaging (ISI; T2* GE MRI sequence). Patients were imaged at baseline and at either 1 day (n = 2) or 5 days (n = 2) after infusion of 5 mg/kg of ferumoxytol. Residual intravascular ferumoxytol obscured evaluation for uptake in bAVM vascular walls and stroma at the 1-day time point. The two cases imaged at 5 days showed less intravascular tracer but had signal loss in the nidal region consistent with ferumoxytol localization. One case underwent surgical resection; there was prominent vascular wall CD68 staining. Ferumoxytol-enhanced MRI for assessing bAVM inflammatory cell burden appears feasible and has the potential to be developed as a biomarker to study lesional inflammatory events.