title: Diffusion MRI quantifies early axonal loss in the presence of nerve swelling.
abstract: Magnetic resonance imaging markers have been widely used to detect and quantify white matter pathologies in multiple sclerosis. We have recently developed a diffusion basis spectrum imaging (DBSI) to distinguish and quantify co-existing axonal injury, demyelination, and inflammation in multiple sclerosis patients and animal models. It could serve as a longitudinal marker for axonal loss, a primary cause of permanent neurological impairments and disease progression.
  
  
  
  Eight 10-week-old female C57BL/6 mice underwent optic nerve DBSI, followed by a week-long recuperation prior to active immunization for experimental autoimmune encephalomyelitis (EAE). Visual acuity of all mice was assessed daily. Longitudinal DBSI was performed in mouse optic nerves at baseline (naïve, before immunization), before, during, and after the onset of optic neuritis. Tissues were perfusion fixed after final in vivo scans. The correlation between DBSI detected pathologies and corresponding immunohistochemistry markers was quantitatively assessed.
  
  
  
  In this cohort of EAE mice, monocular vision impairment occurred in all animals. In vivo DBSI detected, differentiated, and quantified optic nerve inflammation, demyelination, and axonal injury/loss, correlating nerve pathologies with visual acuity at different time points of acute optic neuritis. DBSI quantified, in the presence of optic nerve swelling, ~15% axonal loss at the onset of optic neuritis in EAE mice.
  
  
  
  Our findings support the notion that axonal loss could occur early in EAE mice. DBSI detected pathologies in the posterior visual pathway unreachable by optical coherence tomography and without confounding inflammation induced optic nerve swelling. DBSI could thus decipher the interrelationship among various pathological components and the role each plays in disease progression. Quantification of the rate of axonal loss could potentially serve as the biomarker to predict treatment outcome and to determine when progressive disease starts.
authors.affiliation: Radiology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Tsen-Hsuan
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Radiology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA.|Current Address: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institute, 35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Chiang
authors.affiliation: Radiology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA.|Current Address: School of Health Sciences, Purdue University, 550 W Stadium Ave, West Lafayette, IN, 47907, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Perez-Torres
authors.affiliation: Radiology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Biostatistics, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wallendorf
authors.affiliation: Pathology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Neurology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA.|Hope Center for Neurological Disorders, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.affiliation: Radiology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA. ssong@wustl.edu.|Hope Center for Neurological Disorders, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, USA. ssong@wustl.edu.|Biomedical Engineering, Washington University, 1 Brookings Dr, St. Louis, MO, 63130, USA. ssong@wustl.edu.|Biomedical MR Laboratory, Washington University School of Medicine, Campus Box 8227, Room 2313, 4525 Scott Ave, St Louis, MO, 63110, USA. ssong@wustl.edu.
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000639:trends*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009900:Optic Nerve / Q000000981:diagnostic imaging* / Q000473:pathology; D009902:Optic Neuritis / Q000000981:diagnostic imaging* / Q000473:pathology
keywords: Axonal loss; DBSI; Diffusion MRI; Multiple sclerosis; Optic neuritis