title: In vivo detection of connectivity between cortical and white matter lesions in early MS.
abstract: BACKGROUND
  The relationship between cortical lesions (CLs) and white matter lesions (WMLs) in multiple sclerosis (MS) is poorly understood. Pathological studies support a topographical association between CLs and underlying subcortical WMLs and suggest CLs may play a role in both disease initiation and progression. We hypothesized that cortical MS lesions are physically connected to white matter MS lesions via axonal connections.
  
  
  OBJECTIVE
  To assess the presence of CL-WML connectivity utilizing novel magnetic resonance imaging (MRI) methodology.
  
  
  METHODS
  In all, 28 relapsing-remitting MS patients and 25 controls received 3 T MRI scans, including double inversion recovery (DIR) for CL detection coupled with diffusion tensor imaging (DTI). CL and WML maps were created, and DTI was used to calculate inter-lesional connectivity and volumetric connectivity indices.
  
  
  RESULTS
  All patients showed inter-lesional WML connectivity (median 76% of WMLs connected to another WML; interquartile range (IQR), 58%-88%). On average, 52% of detected CLs per patient were connected to at least one WML (IQR, 42%-71%). Volumetric connectivity analysis showed significantly elevated cortical lesion ratios in MS patients (median, 2.3; IQR, 1.6-3.3) compared to null MS and healthy control datasets ( p < 0.001).
  
  
  CONCLUSIONS
  These findings provide strong evidence of inter-lesional connectivity between CLs and WMLs, supporting our hypothesis of intrinsic CL-WML connectivity.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jan-Mendelt
authors.initials: JM
authors.lastname: Tillema
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Mandrekar
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Istvan
authors.initials: I
authors.lastname: Pirko
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Port
mesh_terms: D000328:Adult; D001369:Axons; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D011237:Predictive Value of Tests; D066127:White Matter / Q000000981:diagnostic imaging* / Q000503:physiopathology
keywords: Magnetic resonance imaging; multiple sclerosis