title: Ferumoxytol-enhanced MRI differentiation of meningioma from dural metastases: a pilot study with immunohistochemical observations.
abstract: Malignant dural neoplasms are not reliably distinguished from benign dural neoplasms with contrast-enhanced magnetic resonance imaging (MRI). MRI enhancement in central nervous system (CNS) diseases imaged with ferumoxytol has been attributed to intracellular uptake in macrophages rather than vascular leakage. We compared imaging to histopathology and immunohistochemistry in meningiomas and dural metastases having ferumoxytol-enhanced MRI (FeMRI) and gadolinium-enhanced MRI (GdMRI) in order to correlate enhancement patterns to macrophage presence and vascular state. All patients having extraaxial CNS tumors were retrospectively selected from one of two ongoing FeMRI studies. Enhancement was compared between GdMRI and FeMRI. Diagnoses were confirmed histologically and/or by characteristic imaging. Tumor and vascular histology was reviewed. Immunohistochemical staining for CD68 (a macrophage marker), Connexin-43 (Cx43) (a marker of normal gap junctions), and smooth muscle actin (SMA) as a marker of vascularity, was performed in seven study cases with available tissue. Immunohistochemistry was performed on archival material from 33 subjects outside of the current study as controls: 20 WHO grade I cases of meningioma and 13 metastatic tumors. Metastases displayed marked delayed enhancement on FeMRI, similar to GdMRI. Four patients with dural metastases and one patient with meningioma showed similar enhancement on FeMRI and GdMRI. Five meningiomas with typical enhancement on GdMRI lacked enhancement on FeMRI. Enhancement on FeMRI was better associated with decreased Cx43 expression than intralesional macrophages. These pilot data suggest that FeMRI may better differentiate metastatic disease from meningiomas than GdMRI, and that differences in tumor vasculature rather than macrophage presence could underlie differences in contrast enhancement.
authors.affiliation: Department of Neuroradiology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Bronwyn E
authors.initials: BE
authors.lastname: Hamilton
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Woltjer
authors.affiliation: Department of Neuroradiology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Joao
authors.initials: J
authors.lastname: Prola-Netto
authors.affiliation: Department of Neuroradiology, Oregon Health & Science University, Portland, OR, USA.|Dotter Interventional Institute, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Nesbit
authors.affiliation: Department of Neurosurgery, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Seymur
authors.initials: S
authors.lastname: Gahramanov
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Thao
authors.initials: T
authors.lastname: Pham
authors.affiliation: Miami Cardiac and Vascular Institute, Miami, FL, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L603, Portland, OR, 97239-3098, USA. neuwelte@ohsu.edu.|Department of Neurosurgery, Oregon Health & Science University, Portland, OR, USA. neuwelte@ohsu.edu.|Portland Veterans Affairs Medical Center, Portland, OR, USA. neuwelte@ohsu.edu.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D005260:Female; D052203:Ferrosoferric Oxide / Q000493:pharmacokinetics*; D005682:Gadolinium / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008577:Meningeal Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary; D008579:Meningioma / Q000000981:diagnostic imaging* / Q000556:secondary; D008875:Middle Aged; D010865:Pilot Projects; D012189:Retrospective Studies; D055815:Young Adult; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018031:Connexin 43; D052203:Ferrosoferric Oxide; D005682:Gadolinium; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Blood–brain barrier; Contrast agents; Extraaxial masses; Ferumoxytol; Immunohistochemistry; MRI