Macrophage Imaging within Human Cerebral Aneurysm Wall Using Ferumoxytol-Enhanced MRI: Pilot Study

David M. Hasan, MD1

1Philadelphia, PA United States

Keywords: aneurysm, biomarker, magnetic resonance imaging, vascular, neuropathology

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     Macrophages play a critical role in cerebral aneurysm formation and progression to rupture.
     The purpose of this study is to determine the optimal parameters to image macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI.
     18 unruptured aneurysms in 12 patients were imaged using T2* GE MRI sequence.
     Two protocols were utilized. Protocol A: infusion of 2.5 mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B: infusion of 5 mg/kg of ferumoxytol and imaging at day 0, 1, 3 and 5. All images were reviewed independently by two neuroradiologists to assess for ferumoxtyol-associated loss of signal intensity. Aneurysm dome tissue was harvested from patients infused with ferumoxytol and controls (no ferumoxytol) and stained with CD68 to detect macrophages and Prussian Blue to detect iron oxidize nanoparticles.
     Five out of 10 (50%) aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls. Eight out of 8 (100%) aneurysms in protocol B showed clear ferumoxytol-associated MRI signal changes in the aneurysm wall at 72 hours post infusion. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+ and Prussian Blue. Tissue harvested from control aneurysms stained positive for CD68+ but not Prussian Blue.
     This study evaluated a small sample of aneurysms.
     Infusion dosing of 5mg/kg of ferumoxytol and imaging at 72 hours post injection using T2* GE MRI demonstrated maximal uptake of ferumoxytol in aneurysm wall, corresponding to regions of macrophages infiltrate.
     Further studies are needed to correlate the use of this technique and risk-stratification of unruptured intracranial aneurysms.


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