Myeloperoxidase-targeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis.
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.
Chen
John W
JW
Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, 5404 Building 149, 13th Street, Charlestown, MA 02129, USA. chenjo@helix.mgh.harvard.edu
Breckwoldt
Michael O
MO
Aikawa
Elena
E
Chiang
Gloria
G
Weissleder
Ralph
R
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology / Q000473:pathology; D004796:Clinical Enzyme Tests / Q000379:methods; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D008264:Macrophages / Q000201:enzymology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000201:enzymology; D018613:Microscopy, Confocal; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D015415:Biomarkers; D009195:Peroxidase