title: Decoding diffusivity in multiple sclerosis: analysis of optic radiation lesional and non-lesional white matter.
abstract: OBJECTIVE
  Diffusion tensor imaging (DTI) has been suggested as a new promising tool in MS that may provide greater pathological specificity than conventional MRI, helping, therefore, to elucidate disease pathogenesis and monitor therapeutic efficacy. However, the pathological substrates that underpin alterations in brain tissue diffusivity are not yet fully delineated. Tract-specific DTI analysis has previously been proposed in an attempt to alleviate this problem. Here, we extended this approach by segmenting a single tract into areas bound by seemingly similar pathological processes, which may better delineate the potential association between DTI metrics and underlying tissue damage.
  
  
  METHODS
  Several compartments were segmented in optic radiation (OR) of 50 relapsing-remitting MS patients including T2 lesions, proximal and distal parts of fibers transected by lesion and fibers with no discernable pathology throughout the entire length of the OR.
  
  
  RESULTS
  Asymmetry analysis between lesional and non-lesional fibers demonstrated a marked increase in Radial Diffusivity (RD), which was topographically limited to focal T2 lesions and potentially relates to the lesional myelin loss. A relative elevation of Axial Diffusivity (AD) in the distal part of the lesional fibers was observed in a distribution consistent with Wallerian degeneration, while diffusivity in the proximal portion of transected axons remained normal. A moderate, but significant elevation of RD in OR non-lesional fibers was strongly associated with the global (but not local) T2 lesion burden and is probably related to microscopic demyelination undetected by conventional MRI.
  
  
  CONCLUSIONS
  This study highlights the utility of the compartmentalization approach in elucidating the pathological substrates of diffusivity and demonstrates the presence of tissue-specific patterns of altered diffusivity in MS, providing further evidence that DTI is a sensitive marker of tissue damage in both lesions and NAWM. Our results suggest that, at least within the OR, parallel and perpendicular diffusivities are affected by tissue restructuring related to distinct pathological processes.
authors: Department of Ophthalmology, Save Sight Institute, University of Sydney, Sydney, Australia; Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
authors: Alexander
authors: A
authors: Klistorner
authors: Westmead Hospital, Sydney, NSW, Australia.
authors: Nikitha
authors: N
authors: Vootakuru
authors: Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
authors: Chenyu
authors: C
authors: Wang
authors: North Shore Hospital, Sydney, NSW, Australia.
authors: Con
authors: C
authors: Yiannikas
authors: Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
authors: Stuart L
authors: SL
authors: Graham
authors: North Shore Hospital, Sydney, NSW, Australia.
authors: John
authors: J
authors: Parratt
authors: St. Vincent Hospital, Sydney, NSW, Australia.
authors: Raymond
authors: R
authors: Garrick
authors: Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Netta
authors: N
authors: Levin
authors: Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
authors: Lynette
authors: L
authors: Masters
authors: Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
authors: Jim
authors: J
authors: Lagopoulos
authors: Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
authors: Michael H
authors: MH
authors: Barnett
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009902:Optic Neuritis / Q000209:etiology / Q000473:pathology; D011859:Radiography; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*