Non-Gaussian diffusion MRI of gray matter is associated with cognitive impairment in multiple sclerosis

Abstract

Background Non-Gaussian diffusion imaging by using diffusional kurtosis imaging (DKI) allows assessment of isotropic tissue as of gray matter (GM), an important limitation of diffusion tensor imaging (DTI). Objective In this study, we describe DKI and DTI metrics of GM in MS patients and their association with cognitive deficits. Methods Thirty-four patients with relapsing-remitting MS and 17 controls underwent MRI on a 3T scanner including a sequence for DKI with 30 diffusion directions and 3b values for each direction. Mean kurtosis (MK), mean diffusivity and fractional anisotropy (FA) of cortical and subcortical GM were measured using histogram analysis. Spearman rank correlations were used to characterize associations among imaging measures and clinical/neuropsychological scores. Results In cortical GM, a significant decrease of MK (0.68 vs. 0.73; p<0.001) and increase of FA (0.16 vs. 0.13; p<0.001) was found in patients compared to controls. Decreased cortical MK was correlated with poor performance on Delis-Kaplan Executive Function System test (r=0.66, p=0.01). Conclusion Mean kurtosis is sensitive to abnormality in GM of MS patients and can provide information that is complementary to that of conventional DTI-derived metrics. The association between MK and cognitive deficits suggests that DKI might serve as a clinically relevant biomarker for cortical injury.

Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination

“…As such, a decrease of MK is believed to be linked to a loss of microstructure. Furthermore, in line with our findings, a decrease of MK has been observed in the grey matter of the spinal cord of MS patients (Raz et al , 2013) and a very recent study by Bester et al who reported a decrease of MK in cortical grey matter of MS patients, which also correlated with cognitive deficits (Bester et al , 2014). …”

“…Hence DK metrics estimate the degree of diffusion restriction, which is related to tissue complexity in both white and grey matter (Hui et al, 2008; Jensen and Helpern, 2010; Jensen et al , 2005; Wu and Cheung, 2010). Sensitivity of DKI to detect microstructural alterations has been demonstrated in normal developing (Paydar et al , 2014) and aging humans (Coutu et al , 2014; Falangola et al , 2008) and patients suffering from several neurological disorders including MS and other demyelinating diseases (Bester et al , 2014; Kimura et al , 2014; Raz et al , 2013; Yoshida et al , 2013). …”

Pathology and MRI: exploring cognitive impairment in MS

“…6,90,[104][105][106][107] Cross-sectional studies suggest that brain volume loss may be a better predictor of cognitive impairment than focal white matter lesion burden. 50,108 A recent investigation in patients with RIS reported cognitive impairment in 28% of patients and an association of higher T1 lesion volumes and lower cortical volumes with worse cognitive performance.…”

Quantification of normal-appearing white matter tract integrity in multiple sclerosis: a diffusion kurtosis imaging study

“…The successful management of MS and monitoring of treatment response thus call for new markers with an increased sensitivity and specificity for the disease’s various pathological processes. Unlike conventional MRI, diffusion MRI techniques, including diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) [7], are sensitive to diffuse microscopic injury in the normal-appearing white matter (NAWM) and gray matter of MS patients [8–10]. Both DTI and DKI metrics, however, are empirical diffusion measures and lack microstructural and pathological specificity [7].…”