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

• Published in: Brain (London, England : 1878) Vol. 131; no. 4; pp. 1123 - 1133
• Main Authors: Chen, John W., Breckwoldt, Michael O., Aikawa, Elena, Chiang, Gloria, Weissleder, Ralph
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2008; Oxford Publishing Limited (England)
• Subjects: Animals; Biological and medical sciences; Biomarkers - metabolism; Cerebellum - enzymology; Cerebellum - pathology; Clinical Enzyme Tests - methods; demyelination; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - diagnosis; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; Macrophages - enzymology; Magnetic Resonance Imaging - methods; Medical sciences; Mice; Mice, Inbred C57BL; Microglia - enzymology; Microscopy, Confocal; MRI; Multiple Sclerosis - diagnosis; Multiple Sclerosis - pathology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; myeloperoxidase; neuroinflammation; Neurology; Peroxidase - metabolism; Sensitivity and Specificity; Severity of Illness Index; targeted imaging; myeloperoxidase; neuroinflammation; MRI; demyelination; targeted imaging; Autoimmunity; Immunopathology; Nervous system diseases; Multiple sclerosis; Enzyme; Autoimmune disease; Murine encephalomyelitis; Nuclear magnetic resonance imaging; Inflammatory disease; Infection; Peroxidases; Demyelination; Viral disease; Central nervous system disease; Peroxidase; Oxidoreductases
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awn004

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.