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


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.


CONCLUSIONS
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.
Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, USA. david-hasan@uiowa.edu
David M
DM
Hasan
Kelly B
KB
Mahaney
Vincent A
VA
Magnotta
David K
DK
Kung
Michael T
MT
Lawton
Tomoki
T
Hashimoto
H Richard
HR
Winn
David
D
Saloner
Alastair
A
Martin
Seymur
S
Gahramanov
Edit
E
Dósa
Edward
E
Neuwelt
William L
WL
Young
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004396:Coloring Agents; D003287:Contrast Media; D005240:Feasibility Studies; D005260:Female; D005295:Ferrocyanides; D052203:Ferrosoferric Oxide; D006801:Humans; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000276:immunology / Q000473:pathology*; D007484:Iowa; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D004396:Coloring Agents; D003287:Contrast Media; D005295:Ferrocyanides; D052203:Ferrosoferric Oxide; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C000170:ferric ferrocyanide