The relationship between white matter fiber damage and gray matter perfusion in large-scale functionally defined networks in multiple sclerosis.
BACKGROUND
Recent studies utilizing perfusion as a surrogate of cortical integrity show promise for overall cognition, but the association between white matter (WM) damage and gray matter (GM) integrity in specific functional networks is not previously studied.


OBJECTIVE
To investigate the relationship between WM fiber integrity and GM node perfusion within six functional networks of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients.


METHODS
Magnetic resonance imaging (MRI) and neurocognitive testing were performed on 19 healthy controls (HC), 39 RRMS, and 45 SPMS patients. WM damage extent and severity were quantified with T2-hyper/T1-hypointense (T2h/T1h) lesion volume and degree of perfusion reduction in lesional and normal-appearing white matter (NAWM), respectively. A two-step linear regression corrected for confounders was employed.


RESULTS
Cognitive impairment was present in 20/39 (51%) RRMS and 25/45 (53%) SPMS patients. GM node perfusion was associated with WM fiber damage severity (WM hypoperfusion) within each network-including both NAWM ( R2= 0.67-0.89, p < 0.0001) and T2h ( R2= 0.39-0.62, p < 0.0001) WM regions-but was not significantly associated ( p > 0.01) with WM fiber damage extent (i.e. T2h/T1h lesion volumes).


CONCLUSIONS
Overall, GM node perfusion was associated with severity rather than extent of WM network damage, supporting a primary etiology of GM hypoperfusion.
Department of Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
Ashley Y
AY
Ma
Department of Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
Rita C
RC
Vitorino
Department of Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
Seyed-Parsa
SP
Hojjat
Department of Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
Alannah D
AD
Mulholland
Department of Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada.
Liying
L
Zhang
Department of Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Liesly
L
Lee
Department of Biomedical Engineering and Radiology, Northwestern University, Chicago, IL, USA.
Timothy J
TJ
Carroll
Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA.
Charles G
CG
Cantrell
Department of Radiology, University of Manitoba, Winnipeg, MB, Canada/Neuroscience Research Program and Division of Diagnostic Imaging, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, MB, Canada.
Chase R
CR
Figley
Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada/Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
Richard I
RI
Aviv
D000328:Adult; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications / Q000000981:diagnostic imaging*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000000981:diagnostic imaging*; D009415:Nerve Net / Q000000981:diagnostic imaging*; D055420:Perfusion Imaging; D012720:Severity of Illness Index; D066127:White Matter / Q000000981:diagnostic imaging*
Multiple sclerosis; cognition; functional network; magnetic resonance imaging; node; perfusion