Diffusion basis spectrum imaging detects and distinguishes coexisting subclinical inflammation, demyelination and axonal injury in experimental autoimmune encephalomyelitis mice

Xiaojie Wang, Matthew F. Cusick, Yong Wang, Peng Sun, Jane E. Libbey, Kathryn Trinkaus, Robert S. Fujinami, Sheng-Kwei Song
2014 NMR in Biomedicine  
Clinicopathological paradox has significantly hampered the effective assessment of the efficacy of therapeutic intervention of multiple sclerosis. The neuroimaging biomarkers of tissue injury could guide a more effective treatment by accurately reflecting the underlying subclinical pathologies. Diffusion tensor imaging-derived directional diffusivity and anisotropy indices have been applied to characterize white matter disorders. However, these biomarkers are sometimes confounded by complex
more » ... ologies seen in multiple sclerosis and its animal models. Recently, a novel diffusion basis spectrum imaging has been developed to quantitatively assess axonal injury, demyelination, and inflammation in a mouse model of inflammatory demyelination. Lenaldekar, which inhibits Tcell expansion in a non-cytolytic manner, has been shown to suppress relapses and preserve white matter integrity in mice with experimental autoimmune encephalomyelitis. In this study, relapsing-remitting experimental autoimmune encephalomyelitis was induced through active immunization of SJL/J mice with a myelin proteolipid protein peptide. We evaluated the therapeutic efficacy of Lenaldekar treatment via daily clinical score, cross-sectional ex vivo diffusion basis spectrum imaging examination, and histological analysis. Lenaldekar greatly reduced relapse severity and protected white matter integrity in these experimental autoimmune encephalomyelitis mice. Diffusion basis spectrum imaging-derived axial diffusivity, radial diffusivity and restricted diffusion tensor fraction accurately reflected axon, myelin integrity and inflammation associated cellularity change, respectively. These results support the potential use of diffusion basis spectrum imaging as an effective outcome measure for preclinical drug evaluation.
doi:10.1002/nbm.3129 pmid:24816651 pmcid:PMC4071074 fatcat:5tslqbdv3bdc5ki3skybjypmr4