Journal
BRAIN
Volume 131, Issue -, Pages 1123-1133Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awn004
Keywords
myeloperoxidase; neuroinflammation; demyelination; targeted imaging; MRI
Categories
Funding
- NCI NIH HHS [R24-CA92782, R24 CA092782-05, R24 CA092782] Funding Source: Medline
- NHLBI NIH HHS [R01 HL078641-03, R01-HL078641, R01 HL078641] Funding Source: Medline
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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.
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