Abstract 107: Early Change in Ferumoxytol-Enhanced Magnetic Resonance Imaging Signal Suggests Unstable Human Cerebral Aneurysm. A Pilot Study

Background: Imaging with magnetic resonance imaging (MRI) 72 hours after infusion of ferumoxytol demonstrated maximal uptake by macrophages in the wall of human cerebral aneurysms. The clinical significance of early (i.e. within the first 24 hours) uptake of ferumoxytol by macrophages in the wall of human cerebral aneurysms is not clear. The purpose of this study was to determine whether early uptake of ferumoxytol which may indicate inflammation, suggests unstable cerebral aneurysm. Methods: 30 unruptured aneurysms in 22 patients were imaged with MRI 24 hours after infusion of ferumoxytol. Eighteen aneurysms were also imaged 72 hours after infusion of ferumoxytol. Aneurysm dome tissue was collected from four patients with early MRI signal changes, five patients with late signal changes, and five other patients with ruptured aneurysms. The tissue was immunostained for expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal-prostaglandin-E2 synthase-1 (mPGES-1) and macrophages. Findings: In 23% (7/30) of aneurysms, there was pronounced early uptake of ferumoxytol. Four aneurysms were clipped. The remaining three aneurysms which were managed conservatively with observation, all ruptured within six months. In 89% (16/18) of aneurysms, there was pronounced uptake of ferumoxytol at 72 hours. Nine aneurysms were surgically clipped and nine were managed conservatively; none ruptured or increased in size in six months. With immunostaining, expression of COX-2, mPGES-1, and macrophages was similar in unruptured aneurysms with early uptake of ferumoxytol and ruptured aneurysms. Expression of these inflammatory molecules was significantly higher in aneurysms with early uptake of ferumoxytol than in aneurysms with late uptake. Interpretation: Uptake of ferumoxytol in aneurysm walls within the first 24 hours strongly suggests aneurysm instability and probability of rupture within six months, and may warrant intervention. Larger clinical studies are indicated to validate this preliminary observation.