Data fusion detects consistent relations between non-lesional white matter myelin, executive function, and clinical characteristics in multiple sclerosis

Abstract

We examined the influence of dysfunctional, non-lesional white matter on cognitive performance in multiple sclerosis (MS). Forty-six MS subjects were assessed using MRI-based myelin water imaging (MWI), and average myelin water fraction (MWF) values across 20 white matter regions of interest (ROIs) were determined. A data-fusion method, multiset canonical correlation analysis (MCCA), was used to investigate the multivariate, deterministic joint relations between MWF, executive function, and demographic and clinical characteristics. MCCA revealed one significant component (p = 0.009) which consisted of three linked profiles, with a pairwise correlation between the MWF and cognitive profiles of r = 0.37, a correlation between MWF and demographics profiles of r = 0.31, and between cognitive and demographics profiles r = 0.64. White matter ROIs representing long-range intra-hemispheric tracts and ROIs connecting the two hemispheres were positively related through their individual profiles to overall cognitive performance, education and female gender, while age, EDSS, and disease duration were related negatively. Surprisingly, lesions within the ROIs had a negligible effect on overall relations between imaging, cognitive, and demographic variables. These findings indicate that there is a strong association between a pattern of MWF values and cognitive performance in MS, which is modulated by age, education, and disease severity. Moreover, this consistent relation involves multiple white matter regions and is separate from the influence of lesions.

Connection between microstructural alterations detected by diffusion MRI and cognitive dysfunction in MS: A model-free analysis approach

“…EDSS includes a summarized assessment of cognitive function, but it does not measure different aspects of it in detail, even though cognitive impairment is similarly, if not more important than physical disability in the progression of MS (Fricska-Nagy et al, 2016). Impaired cognitive performance in various domains such as verbal fluency (Blecher et al, 2019), information processing speed (Abel et al, 2019;Johnen et al, 2019) or multiple cognitive tests (Baumeister et al, 2019) was also associated with white matter pathology, although these studies mostly used ROI based approaches.…”

Using myelin water imaging to link underlying pathology to clinical function in multiple sclerosis: A scoping review

“…This sample encompassed 245 females and 122 males, though one study did not report sex (Oh et al, 2007), with an average age of 45.6(5.7) years, and an average EDSS score of 3.5 (1.5) with a range of 2.0-8.5. These studies encompass data collected in the United States (Oh, 2007;King et al, 2018), Canada (Kitzler et al, 2012;Manogaran, 2016;Vavasour, 2018;Baumeister, 2019;Abel, 2019;Zhao, 2019;Abel et al, 2020b), the United Kingdom (Kolind, 2012;Kolind, 2015), and Sweden (Ouellette et al, 2020). Notably, six studies collected data at the University of British Columbia (UBC) MS Clinic (Abel, 2019;Abel, 2020;Baumeister, 2019;Manogaran, 2016;Vavasour, 2018;Zhao, 2019).…”

“…These studies encompass data collected in the United States (Oh, 2007;King et al, 2018), Canada (Kitzler et al, 2012;Manogaran, 2016;Vavasour, 2018;Baumeister, 2019;Abel, 2019;Zhao, 2019;Abel et al, 2020b), the United Kingdom (Kolind, 2012;Kolind, 2015), and Sweden (Ouellette et al, 2020). Notably, six studies collected data at the University of British Columbia (UBC) MS Clinic (Abel, 2019;Abel, 2020;Baumeister, 2019;Manogaran, 2016;Vavasour, 2018;Zhao, 2019). One study was a multicenter trial that recruited persons with RRMS across four sites: UBC, The University of Chicago, Dartmouth-Hitchcock Medical Center and University of Michigan , in which 8 participants from this study were a part of the CARE-MS II phase III clinical trial (Coles et al, 2012) and the remaining 35 were from an open-label investigator-sponsored study (ISS).…”

“…Two studies performed MWI using a 3D 48-echo GRASE T2 relaxation sequence at 3T (Abel, 2019;Abel, 2020), four studies used a 3D 32echo GRASE T2 relaxation sequence at 3T (Baumeister, 2019;King et al, 2018;Manogaran, 2016;Zhao, 2019), three studies used a mcDESPOT protocol comprised of a series of sagittally-oriented spoiled gradient recalled echo and balanced steady state free procession acquisitions across a range of flip angles at 1.5T (Kitlzer, 2012;Kolind, 2012;Kolind, 2015), two studies used a seven slice 32-echo spin-echo sequence at 3T Vavasour, 2018), one study used a multi-slice 12-echo T2 prep spiral sequence at 3T (Oh, 2007), and one study used a multi-echo T 2 QRAPMASTER approach at 3T (Ouellette, 2020) adopted from previous methods by Warntjes, et al (Warntjes et al, 2008). Only four of 13 studies reported their MWI acquisition time (Kitzler et al, 2012;Kolind, 2012;Kolind, 2015;Oh, 2007), in which all were under 14 min and suggests the feasibility of MWI in a time-sensitive clinical setting.…”

“…(Table 2). However, six of 13 studies extracted MWF values from explicit brain ROIs (Abel, 2019;Abel, 2020, Baumeister, 2019Kolind, 2015;Manogaran, 2016;Zhao et al, 2019) that were selected a priori according to their common disruption and known involvement in MS-related pathology and subsequent motor and cognitive impairment. First, the corpus callosum (CC) was the most examined ROI; five studies extracted MWF values from the entire CC (Abel, 2020;Abel, 2019;Kolind, 2015) or specific CC segments including the genu, body and splenium (Zhao, 2019;Baumeister, 2019).…”