Diffusion Tensor Imaging Abnormalities in Cognitively Impaired Multiple Sclerosis Patients

Background:Cognitive impairment can add to the burden of disease in patients with multiple sclerosis (MS). The aim of this study was to assess the relative importance of diffusion tensor imaging (DTI) indices derived from normal appearing white matter (NAWM) and grey matter (NAGM) in determining cognitive dysfunction in MS patients.Methods:Sixty two MS patients [51 female, mean age= 41 (sd=9.6) years, median expanded disability status scale (EDSS)=2.5] meeting modified McDonald criteria for MS underwent neuropsychological testing using the Neuropsychological Screening Battery for MS (NSBMS) and magnetic resonance imaging (MRI, 1.5T GE) that included DTI sequences. Total T1 hypointense and T2 hyperintense lesion volumes were obtained using semi-automated software. Lesion volumes were subtracted from whole-brain parenchyma to obtain measures of NAWM and NAGM. Fractional anisotropy (FA) of NAWM and mean diffusivity (MD) of NAGM were obtained.Results:Cognitive impairment was present in 11 patients (18%). These patients had higher EDSS scores, were less educated, and were more likely to have secondary progressive MS. They also had higher hypointense (p=0.001) and hyperintense (p=0.004) lesion volumes, greater NAWM atrophy (p=0.007), lower FA of total NAWM (p=0.003), and higher MD of total NAGM (p=0.015). Using a logistic regression analysis, and after controlling for demographic and disease-related differences between groups, FA of NAWM emerged as a significant predictor of cognitive impairment adding to the variance derived from lesion and atrophy data.Conclusion:This study underlies the important role of normal-appearing brain tissue in the pathogenesis of MS-related cognitive impairment.

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Diffusion tensor imaging abnormalities in depressed multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458509355461 ◽

2009 ◽

Vol 16 (2) ◽

pp. 189-196 ◽

Cited By ~ 61

Author(s):

A. Feinstein ◽

P. O'Connor ◽

N. Akbar ◽

L. Moradzadeh ◽

CJM Scott ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Grey Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Resonance Imaging ◽

Normal Appearing White Matter

Depression is common in patients with multiple sclerosis, but to date no studies have explored diffusion tensor imaging indices associated with mood change. This study aimed to determine cerebral correlates of depression in multiple sclerosis patients using diffusion tensor imaging. Sixty-two subjects with multiple sclerosis were assessed for depression with the Beck Depression Inventory (BDI-II). All subjects underwent magnetic resonance imaging. Whole brain and regional volumes were calculated for lesions (hyper/hypointense) and normal-appearing white and grey matter. Fractional anisotropy and mean diffusivity were calculated for each brain region. Magnetic resonance imaging comparisons were undertaken between depressed (Beck Depression Inventory ≥19) and non-depressed subjects. Depressed subjects (n = 30) had a higher hypointense lesion volume in the right medial inferior frontal region, a smaller normal-appearing white matter volume in the left superior frontal region, and lower fractional anisotropy and higher mean diffusivity in the left anterior temporal normal-appearing white matter and normal-appearing grey matter regions, respectively. Depressed subjects also had higher mean diffusivity in right inferior frontal hyperintense lesions. Magnetic resonance imaging variables contributed to 43% of the depression variance. We conclude that the presence of more marked diffusion tensor imaging abnormalities in the normal-appearing white matter and normal-appearing grey matter of depressed subjects highlights the importance of more subtle measures of structural brain change in the pathogenesis of depression.

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Relationship between timed 25-foot walk and diffusion tensor imaging in multiple sclerosis

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217316655365 ◽

2016 ◽

Vol 2 ◽

pp. 205521731665536 ◽

Cited By ~ 2

Author(s):

Sylvia Klineova ◽

Rebecca Farber ◽

Catarina Saiote ◽

Colleen Farrell ◽

Bradley N Delman ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Diffusion Tensor Imaging ◽

Magnetic Resonance ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Resonance Imaging ◽

Corticospinal Tracts ◽

Multiple Sclerosis Patients ◽

And Diffusion

Objective/Background The majority of multiple sclerosis patients experience impaired walking ability, which impacts quality of life. Timed 25-foot walk is commonly used to gauge gait impairment but results can be broadly variable. Objective biological markers that correlate closely with patients’ disability are needed. Diffusion tensor imaging, quantifying fiber tract integrity, might provide such information. In this project we analyzed relationships between timed 25-foot walk, conventional and diffusion tensor imaging magnetic resonance imaging markers. Design/Methods A cohort of gait impaired multiple sclerosis patients underwent brain and cervical spinal cord magnetic resonance imaging. Diffusion tensor imaging mean diffusivity and fractional anisotropy were measured on the brain corticospinal tracts and spinal restricted field of vision at C2/3. We analyzed relationships between baseline timed 25-foot walk, conventional and diffusion tensor imaging magnetic resonance imaging markers. Results Multivariate linear regression analysis showed a statistically significant association between several magnetic resonance imaging and diffusion tensor imaging metrics and timed 25-foot walk: brain mean diffusivity corticospinal tracts (p = 0.004), brain corticospinal tracts axial and radial diffusivity (P = 0.004 and 0.02), grey matter volume (p = 0.05), white matter volume (p = 0.03) and normalized brain volume (P = 0.01). The linear regression model containing mean diffusivity corticospinal tracts and controlled for gait assistance was the best fit model (p = 0.004). Conclusions Our results suggest an association between diffusion tensor imaging metrics and gait impairment, evidenced by brain mean diffusivity corticospinal tracts and timed 25-foot walk.

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Clinical significance of atrophy and white matter mean diffusivity within the thalamus of multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458513478675 ◽

2013 ◽

Vol 19 (11) ◽

pp. 1478-1484 ◽

Cited By ~ 64

Author(s):

Ralph HB Benedict ◽

Hanneke E Hulst ◽

Niels Bergsland ◽

Menno M Schoonheim ◽

Michael G Dwyer ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

White Matter ◽

Cognitive Processing ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Brain Magnetic Resonance Imaging ◽

Cognitive Tests ◽

Explained Variance ◽

Multiple Sclerosis Patients

Background: Gray-matter (GM) atrophy is strongly predictive of cognitive impairment in multiple sclerosis (MS) patients. The thalamus is the region where the atrophy/cognition correlation is most robust. However, few studies have assessed diffusion tensor imaging (DTI) metrics within the thalamus. Objective: This study was designed to determine if thalamus white matter DTI predicts cognitive impairment after accounting for the effects of volume loss. Methods: We enrolled 75 MS patients and 18 healthy controls undergoing 3T brain magnetic resonance imaging (MRI). Thalamus volumes were calculated on 3D T1 images. Voxelwise analyses of DTI metrics were performed within the thalamic white matter tracts. Neuropsychological (NP) testing, acquired using consensus standard methods, contributed measures of memory, cognitive processing speed and executive function. Results: All cognitive tests were significantly predicted ( R2 =0.31, p<0.001) by thalamus volume after accounting for influence of demographics. Mean diffusivity was retained in regression models predicting all cognitive tests, adding from 7–13% of additional explained variance ( p<0.02) after accounting for thalamus volume. Conclusions: We confirm the significant role of thalamus atrophy in MS-associated cognitive disorder, and further report that subtle thalamus pathology as detected by DTI adds incremental explained variance in predicting cognitive impairment.

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Characterization of normal-appearing white matter in multiple sclerosis using quantitative susceptibility mapping in conjunction with diffusion tensor imaging

Neuroradiology ◽

10.1007/s00234-018-2137-7 ◽

2018 ◽

Vol 61 (1) ◽

pp. 71-79 ◽

Cited By ~ 4

Author(s):

Fang F. Yu ◽

Florence L. Chiang ◽

Nicholas Stephens ◽

Susie Y. Huang ◽

Berkin Bilgic ◽

...

Keyword(s):

Multiple Sclerosis ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Susceptibility Mapping ◽

Quantitative Susceptibility Mapping ◽

Normal Appearing White Matter

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Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter

Multiple Sclerosis Journal ◽

10.1191/1352458504ms997oa ◽

2004 ◽

Vol 10 (2) ◽

pp. 188-196 ◽

Cited By ~ 57

Author(s):

Emmanuelle Cassol ◽

Jean-Philippe Ranjeva ◽

Danielle Ibarrola ◽

Claude Mékies ◽

Claude Manelfe ◽

...

Keyword(s):

Multiple Sclerosis ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Lesion Load ◽

Normal Appearing White Matter ◽

Relapsing Remitting ◽

One Year ◽

Diffusion Tensor Imaging Dti

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-mo nthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P B-0.0001). O ver the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. A lthough this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.

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Diffusion Tensor Imaging of Normal Appearing White Matter and Its Correlation with Cognitive Functioning in Mild Cognitive Impairment and Alzheimer's Disease

Annals of the New York Academy of Sciences ◽

10.1196/annals.1379.021 ◽

2007 ◽

Vol 1097 (1) ◽

pp. 259-264 ◽

Cited By ~ 59

Author(s):

J. HUANG ◽

A. P AUCHUS

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Diffusion Tensor Imaging ◽

Mild Cognitive Impairment ◽

White Matter ◽

Cognitive Functioning ◽

Diffusion Tensor ◽

Normal Appearing White Matter

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A 24-month advanced magnetic resonance imaging study of multiple sclerosis patients treated with alemtuzumab

Multiple Sclerosis Journal ◽

10.1177/1352458518770085 ◽

2018 ◽

Vol 25 (6) ◽

pp. 811-818 ◽

Cited By ~ 8

Author(s):

Irene M Vavasour ◽

Roger Tam ◽

David KB Li ◽

Cornelia Laule ◽

Carolyn Taylor ◽

...

Keyword(s):

Multiple Sclerosis ◽

Magnetic Resonance ◽

Cortical Thickness ◽

Diffusion Tensor ◽

Imaging Study ◽

Water Fraction ◽

Normal Appearing White Matter ◽

Brain Parenchymal Fraction ◽

Brain Parenchymal ◽

Multiple Sclerosis Patients

Background: Tissue damage in both multiple sclerosis (MS) lesions and normal-appearing white matter (NAWM) are important contributors to disability and progression. Specific aspects of MS pathology can be measured using advanced imaging. Alemtuzumab is a humanised monoclonal antibody targeting CD52 developed for MS treatment. Objective: To investigate changes over 2 years of advanced magnetic resonance (MR) metrics in lesions and NAWM of MS patients treated with alemtuzumab. Methods: A total of 42 relapsing–remitting alemtuzumab-treated MS subjects were scanned for 2 years at 3 T. T1 relaxation, T2 relaxation, diffusion tensor, MR spectroscopy and volumetric sequences were performed. Mean T1 and myelin water fraction (MWF) were determined for stable lesions, new lesions and NAWM. Fractional anisotropy was calculated for the corpus callosum (CC) and N-acetylaspartate (NAA) concentration was determined from a large NAWM voxel. Brain parenchymal fraction (BPF), cortical thickness and CC area were also calculated. Results: No change in any MR measurement was found in lesions or NAWM over 24 months. BPF, cortical thickness and CC area all showed decreases in the first year followed by stability in the second year. Conclusion: Advanced MR biomarkers of myelin (MWF) and neuron/axons (NAA) show no change in NAWM over 24 months in alemtuzumab-treated MS participants.

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