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Detection of Monocyte/Macrophage and Microglia Activation in the TMEV Model of Chronic Demyelination Using USPIO‐Enhanced Ultrahigh‐Field Imaging
Author(s) -
Zivadinov Robert,
Schweser Ferdinand,
Dwyer Michael G.,
Pol Suyog
Publication year - 2020
Publication title -
journal of neuroimaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.822
H-Index - 64
eISSN - 1552-6569
pISSN - 1051-2284
DOI - 10.1111/jon.12768
Subject(s) - medicine , microglia , pathology , atrophy , biomarker , imaging biomarker , magnetic resonance imaging , inflammation , multiple sclerosis , histopathology , ferumoxytol , cd68 , immunohistochemistry , immunology , radiology , biology , biochemistry
BACKGROUND AND PURPOSE Blood‐derived monocytes/macrophages can be labeled with ultrasmall superparamagnetic iron oxides (USPIO) at periphery and subsequently migrate into areas of inflammation in the brain. We investigated temporal pattern of migration of peripheral immune cells in Theiler's murine encephalomyelitis virus (TMEV) model of chronic demyelination by USPIO‐enhanced imaging. METHODS Fifteen SJL mice (Envigo, Indianapolis, IN) were injected with TMEV ( n = 12) or saline ( n = 3) at 7 weeks of age. Brain MRI of 9.4 T was performed at 3 months postinfection (mpi) (the peak of inflammatory phase), at 4, 5, and 7 mpi (throughout neurodegenerative phase) using T2*‐weighted gradient echo MRI, and performed 24 hours after USPIO injection. Contrast enhancing lesion (CEL) number and volume were measured and development of brain atrophy was assessed across serial time points. Clinical disability scale and rotarod score assessed disease progression. RESULTS CEL was detected in a total of eight (66.7%) TMEV‐infected animals and none of the Controls. The CEL was present in four (33.3%) TMEV‐infected animals at 3 mpi, two (16.7%) at 4 mpi, six (54.5%) at 5 mpi, and four (44.4%) at 7 mpi, respectively. In TMEV‐infected animals, the CEL number and volume increased significantly from 3 to 7 mpi ( P < .01 for both). The correlation between total CEL number and volume with clinical and MRI outcomes was trending ( P < .05). On histopathology analysis, CEL showed increased density of Iba1 staining for microglia activity. CONCLUSIONS Serial USPIO imaging is a promising biomarker for investigating the effect of therapeutic interventions on monocytes/macrophages and microglia activation and neurodegeneration in TMEV‐infected animals.