Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis

Mult Scler. 2019 Oct;25(12):1580-1592. doi: 10.1177/1352458518799583. Epub 2018 Sep 19.


Background: Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T1- and T2-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM.

Objective: To study cortical GM pathology related to CI in MS using glutamate-sensitive chemical exchange saturation transfer (GluCEST) MRI at 7.0 Tesla (7T).

Methods: A total of 20 patients with relapsing-remitting MS and 20 healthy controls underwent cognitive testing, anatomical imaging, and GluCEST imaging. Glutamate-sensitive image contrast was quantified for cortical GM, compared between cohorts, and correlated with clinical measures of CI.

Results and conclusion: Glutamate-sensitive contrast was significantly increased in the prefrontal cortex of MS patients with accumulated disability (p < 0.05). In addition, glutamate-sensitive contrast in the prefrontal cortex was significantly correlated with symbol digit modality test (rS = -0.814) and choice reaction time (rS = 0.772) scores in patients (p < 0.05), suggesting that GluCEST MRI may have utility as a marker for GM pathology and CI.

Keywords: Multiple sclerosis; cognitive dysfunction; glutamate; gray matter; magnetic resonance imaging; prefrontal cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / physiopathology*
  • Female
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacology
  • Gray Matter / pathology
  • Gray Matter / physiopathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / physiopathology*
  • White Matter / pathology
  • White Matter / physiopathology


  • Glutamic Acid