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July 16, 2013; 81 (3) Article

Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL

Brian T. Farrell, Bronwyn E. Hamilton, Edit Dósa, Endre Rimely, Morad Nasseri, Seymur Gahramanov, Cynthia A. Lacy, Eugene P. Frenkel, Nancy D. Doolittle, Paula M. Jacobs, Edward A. Neuwelt
First published June 14, 2013, DOI: https://doi.org/10.1212/WNL.0b013e31829bfd8f
Brian T. Farrell
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
MD, PhD
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Bronwyn E. Hamilton
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
MD
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Edit Dósa
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
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Endre Rimely
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
MD
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Morad Nasseri
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
MD
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Seymur Gahramanov
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
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Cynthia A. Lacy
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
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Eugene P. Frenkel
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
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Nancy D. Doolittle
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
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Paula M. Jacobs
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
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Edward A. Neuwelt
From the Departments of Neurosurgery (B.T.F., E.A.N.), Radiology (B.E.H.), and Neurology (E.D., E.R., M.N., S.G., C.A.L., N.D.D., E.A.N.), Oregon Health & Science University, Portland, OR; Hematology Oncology (E.P.F.), Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Cancer Imaging Program (P.M.J.), National Cancer Institute, Rockville, MD; and Department of Veterans Affairs Medical Center (E.A.N.), Portland, OR.
MD
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Full PDF
Citation
Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL
Brian T. Farrell, Bronwyn E. Hamilton, Edit Dósa, Endre Rimely, Morad Nasseri, Seymur Gahramanov, Cynthia A. Lacy, Eugene P. Frenkel, Nancy D. Doolittle, Paula M. Jacobs, Edward A. Neuwelt
Neurology Jul 2013, 81 (3) 256-263; DOI: 10.1212/WNL.0b013e31829bfd8f

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Abstract

Objective: The study goal was to assess the benefits and potential limitations in the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in the MRI diagnosis of CNS inflammatory diseases and primary CNS lymphoma.

Methods: Twenty patients with presumptive or known CNS lesions underwent MRI study. Eighteen patients received both gadolinium-based contrast agents (GBCAs) and 1 of 2 USPIO contrast agents (ferumoxytol and ferumoxtran-10) 24 hours apart, which allowed direct comparative analysis. The remaining 2 patients had only USPIO-enhanced MRI because of a renal contraindication to GBCA. Conventional T1- and T2-weighted MRI were acquired before and after contrast administration in all patients, and perfusion MRI for relative cerebral blood volume (rCBV) assessment was obtained in all 9 patients receiving ferumoxytol.

Results: USPIO-enhanced MRI showed an equal number of enhancing brain lesions in 9 of 18 patients (50%), more enhancing lesions in 2 of 18 patients (11%), and fewer enhancing lesions in 3 of 18 patients (17%) compared with GBCA-enhanced MRI. Four of 18 patients (22%) showed no MRI enhancement. Dynamic susceptibility-weighted contrast-enhanced perfusion MRI using ferumoxytol showed low rCBV (ratio <1.0) in 3 cases of demyelination or inflammation, modestly elevated rCBV in 5 cases of CNS lymphoma or lymphoproliferative disorder (range: 1.3–4.1), and no measurable disease in one case.

Conclusions: This study showed that USPIO-enhanced brain MRI can be useful in the diagnosis of CNS inflammatory disorders and lymphoma, and is also useful for patients with renal compromise at risk of nephrogenic systemic fibrosis who are unable to receive GBCA.

GLOSSARY

CNSL=
CNS lymphoma;
DSC=
dynamic susceptibility-weighted contrast-enhanced;
GBCA=
gadolinium-based contrast agent;
NSF=
nephrogenic systemic fibrosis;
PCNSL=
primary CNS lymphoma;
PTLD=
posttransplant lymphoproliferative disorder;
PWI=
perfusion-weighted imaging;
rCBV=
relative cerebral blood volume;
USPIO=
ultrasmall superparamagnetic iron oxide

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received August 30, 2012.
  • Accepted in final form April 2, 2013.
  • © 2013 American Academy of Neurology
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