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Ferumoxytol-enhanced MRI differentiation of meningioma from dural metastases: a pilot study with immunohistochemical observations

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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.

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Acknowledgments

This work was supported by a Veterans Administration merit review Grant and by National Institute of Health Grants NS44687, and CA137488, and by the Walter S. and Lucienne Driskill Foundation to EAN. The authors thank Samantha Rolph and Emily Hochhalter Youngers for their help with manuscript preparation.

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Authors and Affiliations

  1. Department of Neuroradiology, Oregon Health & Science University, Portland, OR, USA

    Bronwyn E. Hamilton, Joao Prola-Netto & Gary M. Nesbit

  2. Department of Pathology, Oregon Health & Science University, Portland, OR, USA

    Randall L. Woltjer & Thao Pham

  3. Dotter Interventional Institute, Oregon Health & Science University, Portland, OR, USA

    Gary M. Nesbit

  4. Department of Neurosurgery, University of New Mexico, Albuquerque, NM, USA

    Seymur Gahramanov

  5. Miami Cardiac and Vascular Institute, Miami, FL, USA

    Jaime Wagner

  6. Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L603, Portland, OR, 97239-3098, USA

    Edward A. Neuwelt

  7. Department of Neurosurgery, Oregon Health & Science University, Portland, OR, USA

    Edward A. Neuwelt

  8. Portland Veterans Affairs Medical Center, Portland, OR, USA

    Edward A. Neuwelt

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  1. Bronwyn E. Hamilton
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  2. Randall L. Woltjer
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  3. Joao Prola-Netto
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  4. Gary M. Nesbit
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  5. Seymur Gahramanov
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  6. Thao Pham
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  7. Jaime Wagner
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  8. Edward A. Neuwelt
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Corresponding author

Correspondence to Edward A. Neuwelt.

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The authors have no conflicts of interest.

Disclosures

Dr. Neuwelt’s studies involving ferumoxytol were entirely funded by the Veterans Administration and NIH research Grants, and the Walter S. and Lucienne Driskill Foundation. None of the authors have financial interests in ferumoxytol, or in its developer AMAG.

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Hamilton, B.E., Woltjer, R.L., Prola-Netto, J. et al. Ferumoxytol-enhanced MRI differentiation of meningioma from dural metastases: a pilot study with immunohistochemical observations. J Neurooncol 129, 301–309 (2016). https://doi.org/10.1007/s11060-016-2175-0

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  • DOI: https://doi.org/10.1007/s11060-016-2175-0

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