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Brain Advance Access originally published online on January 29, 2008
Brain 2008 131(4):1123-1133; doi:10.1093/brain/awn004
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© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Myeloperoxidase-targeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis

John W. Chen1,2, Michael O. Breckwoldt2, Elena Aikawa2, Gloria Chiang2 and Ralph Weissleder1,2

1Center for Systems Biology and 2Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, 5404 Building 149, 13th Street, Charlestown, MA 02129, USA

Correspondence to: John W. Chen, 5404 Building 149, 13th Street, Charlestown, MA 02129, USA E-mail: chenjo{at}helix.mgh.harvard.edu

Inflammatory demyelinating plaques are the pathologic hallmark of active multiple sclerosis and often precede clinical manifestations. Non-invasive early detection of active plaques would thus be crucial in establishing pre-symptomatic diagnosis and could lead to early preventive treatment strategies. Using murine experimental autoimmune encephalomyelitis as a model of multiple sclerosis, we demonstrate that a prototype paramagnetic myeloperoxidase (MPO) sensor can detect and confirm more, smaller, and earlier active inflammatory lesions in living mice by in vivo MRI. We show that MPO expression corresponded with areas of inflammatory cell infiltration and demyelination, and higher MPO activity as detected by MPO imaging, biochemical assays, and histopathological analyses correlated with increased clinical disease severity. Our findings present a potential new translational approach for specific non-invasive inflammatory plaque imaging. This approach could be used in longitudinal studies to identify active demyelinating plaques as well as to more accurately track disease course following treatment in clinical trials.

Key Words: myeloperoxidase; neuroinflammation; demyelination; targeted imaging; MRI

Abbreviations: MPO, myeloperoxidase; DTPA(Gd), diethylenetriamine-pentaacetate gadolinium; 5-HT-DTPA(Gd), bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate gadolinium; EAE, experimental autoimmune encephalomyelitis; BBB, blood–brain barrier; ROI, region of interest; PLP, proteolipid protein; MS, multiple sclerosis; R1, longitudinal relaxivity; PBS, phosphate-buffered saline; FITC, fluorescein isothiocyanate; CNR, contrast-to-noise ratio; SD, standard deviation; SEM, standard error of measurement; PET, positron emission tomography; SPECT, single photon emission computed tomography

Received September 3, 2007. Revised January 4, 2008. Accepted January 7, 2008.


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