Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: A pilot study

David M. Hasan, Kelly B. Mahaney, Vincent A. Magnotta, David K. Kung, Michael T. Lawton, Tomoki Hashimoto, H. Richard Winn, David Saloner, Alastair Martin, Seymur Gahramanov, Edit Dósa, Edward Neuwelt, William L. Young

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Objective-Macrophages play a critical role in cerebral aneurysm formation and rupture. The purpose of this study is to demonstrate the feasibility and optimal parameters of imaging macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI. Methods and Results-Nineteen unruptured aneurysms in 11 patients were imaged using T2*-GE-MRI sequence. Two protocols were used. Protocol A was an infusion of 2.5 mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B was an infusion of 5 mg/kg of ferumoxytol and imaging at day 0 and 3. All images were reviewed independently by 2 neuroradiologists to assess for ferumoxytol-associated loss of MRI signal intensity within aneurysm wall. Aneurysm tissue was harvested for histological analysis. Fifty percent (5/10) of aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls compared to 78% (7/9) of aneurysms in protocol B. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+, demonstrating macrophage infiltration, and Prussian blue, demonstrating uptake of iron particles. Tissue harvested from controls stained positive for CD68 but not Prussian blue. Conclusion-Imaging with T2*-GE-MRI at 72 hours postinfusion of 5 mg/kg of ferumoxytol establishes a valid and useful approximation of optimal dose and timing parameters for macrophages imaging within aneurysm wall. Further studies are needed to correlate these imaging findings with risk of intracranial aneurysm rupture.

Original languageEnglish (US)
Pages (from-to)1032-1038
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • aneurysms
  • ferumoxytol
  • inflammation
  • macrophages
  • magnetic resonance imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Hasan, D. M., Mahaney, K. B., Magnotta, V. A., Kung, D. K., Lawton, M. T., Hashimoto, T., Winn, H. R., Saloner, D., Martin, A., Gahramanov, S., Dósa, E., Neuwelt, E., & Young, W. L. (2012). Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: A pilot study. Arteriosclerosis, thrombosis, and vascular biology, 32(4), 1032-1038. https://doi.org/10.1161/ATVBAHA.111.239871