TY - JOUR
T1 - In vivo detection of connectivity between cortical and white matter lesions in early MS
AU - Tillema, Jan Mendelt
AU - Weigand, Stephen D.
AU - Mandrekar, Jay
AU - Shu, Yunhong
AU - Lucchinetti, Claudia F.
AU - Pirko, Istvan
AU - Port, John D.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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). Conclusion: These findings provide strong evidence of inter-lesional connectivity between CLs and WMLs, supporting our hypothesis of intrinsic CL-WML connectivity.
AB - 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). Conclusion: These findings provide strong evidence of inter-lesional connectivity between CLs and WMLs, supporting our hypothesis of intrinsic CL-WML connectivity.
KW - Magnetic resonance imaging
KW - multiple sclerosis
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U2 - 10.1177/1352458516671027
DO - 10.1177/1352458516671027
M3 - Article
C2 - 27698248
AN - SCOPUS:85020195971
VL - 23
SP - 973
EP - 981
JO - Multiple Sclerosis
JF - Multiple Sclerosis
SN - 1352-4585
IS - 7
ER -