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

63 Citations (Scopus)

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

Fingerprint

Ferrosoferric Oxide
Intracranial Aneurysm
Aneurysm
Macrophages
Rupture
Iron

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hasan, D. M., Mahaney, K. B., Magnotta, V. A., Kung, D. K., Lawton, M. T., Hashimoto, T., ... 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

Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI : A pilot study. / Hasan, David M.; Mahaney, Kelly B.; Magnotta, Vincent A.; Kung, David K.; Lawton, Michael T.; Hashimoto, Tomoki; Winn, H. Richard; Saloner, David; Martin, Alastair; Gahramanov, Seymur; Dósa, Edit; Neuwelt, Edward; Young, William L.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 32, No. 4, 04.2012, p. 1032-1038.

Research output: Contribution to journalArticle

Hasan, DM, Mahaney, KB, Magnotta, VA, Kung, DK, Lawton, MT, Hashimoto, T, Winn, HR, Saloner, D, Martin, A, Gahramanov, S, Dósa, E, Neuwelt, E & Young, WL 2012, 'Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: A pilot study', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 4, pp. 1032-1038. https://doi.org/10.1161/ATVBAHA.111.239871
Hasan, David M. ; Mahaney, Kelly B. ; Magnotta, Vincent A. ; Kung, David K. ; Lawton, Michael T. ; Hashimoto, Tomoki ; Winn, H. Richard ; Saloner, David ; Martin, Alastair ; Gahramanov, Seymur ; Dósa, Edit ; Neuwelt, Edward ; Young, William L. / Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI : A pilot study. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2012 ; Vol. 32, No. 4. pp. 1032-1038.
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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.",
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AU - Kung, David K.

AU - Lawton, Michael T.

AU - Hashimoto, Tomoki

AU - Winn, H. Richard

AU - Saloner, David

AU - Martin, Alastair

AU - Gahramanov, Seymur

AU - Dósa, Edit

AU - Neuwelt, Edward

AU - Young, William L.

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N2 - 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.

AB - 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.

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KW - magnetic resonance imaging

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