title: Diffusion basis spectrum imaging detects and distinguishes coexisting subclinical inflammation, demyelination and axonal injury in experimental autoimmune encephalomyelitis mice.
abstract: Clinicopathological paradox has hampered significantly the effective assessment of the efficacy of therapeutic intervention for multiple sclerosis. Neuroimaging biomarkers of tissue injury could guide 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 the complex pathologies seen in multiple sclerosis and its animal models. Recently, a novel technique of 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 T-cell 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. The therapeutic efficacy of Lenaldekar treatment was evaluated 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 axonal injury, 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.
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO, USA.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Cusick
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Jane E
authors.initials: JE
authors.lastname: Libbey
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trinkaus
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fujinami
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D003711:Demyelinating Diseases / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D056324:Diffusion Tensor Imaging; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006835:Hydrazones / Q000627:therapeutic use; D007211:Indoles / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D011804:Quinolines / Q000627:therapeutic use; D012008:Recurrence
chemical_list: C571887:1H-indole-3-carbaldehyde quinolin-8-yl-hydrazone; D015415:Biomarkers; D006835:Hydrazones; D007211:Indoles; D004676:Myelin Basic Protein; D011804:Quinolines; C007293:DAPI
keywords: Lenaldekar; axonal injury; demyelination; diffusion MRI; diffusion basis spectrum imaging (DBSI); experimental autoimmune encephalomyelitis (EAE); inflammation; multiple sclerosis