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Brain white matter diffusion tensor metrics from clinical 1.5T MRI distinguish between ALS phenotypes

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Abstract

Patients with amyotrophic lateral sclerosis (ALS) can present with varying degrees of upper motor neuron (UMN) and lower motor neuron dysfunction. Previous diffusion tensor imaging (DTI) studies, in which ALS patients were not separated by the degree of UMN dysfunction, have resulted in conflicting or inconclusive results. We hypothesized that (1) categorizing ALS patients by their clinical phenotype can reveal differences in DTI abnormalities along the corticospinal tract (CST), and (2) data obtained from routine clinical DTI scans can provide this type of information. Clinical DTI scans were obtained at 1.5T in 87 ALS patients (categorized into four subgroups based on clinical phenotype) and in 12 neurologic controls. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity values from the CST were compared between ALS subgroups and controls. Significantly reduced FA and elevated MD values were observed in ALS patients compared to controls at the subcortical motor cortex level. Significant differences in AD values were not only seen between control and ALS patients but also between the ALS subgroups, suggesting divergent pathologies in these ALS patients. Classifying ALS patients by phenotype reveals differences in CST abnormalities between subgroups and may provide novel insights into disease mechanisms. The close similarity of our results from routine clinical scans with published research studies suggests wider accessibility to useful DTI metrics.

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Abbreviations

AD:

Axial diffusivity

ALS:

Amyotrophic lateral sclerosis

ANOVA:

Analysis of variance

CP:

Cerebral peduncle

CNS:

Central nervous system

CSoLV:

Centrum semiovale at top of lateral ventricle

CST:

Corticospinal tract

DTI:

Diffusion tensor imaging

DW:

Diffusion weighted

EMG:

Electromyography

EPI:

Echo planar imaging

FA:

Fractional anisotropy

FTD:

Frontotemporal dementia

FLAIR:

Fluid attenuated inversion recovery

FWE:

Family wise error

FDR:

False discovery rate

IC:

Posterior limb of internal capsule

LMN:

Lower motor neuron

MD:

Mean diffusivity

MoCA:

Montreal cognitive assessment

MRI:

Magnetic resonance imaging

MR:

Magnetic resonance

RD:

Radial diffusivity

ROI:

Region of interest

SS-EPI:

Single shot echo planar imaging

SubPMC:

Subjacent to primary motor cortex

TE:

Echo time

TR:

Repetition time

UMN:

Upper motor neuron

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Acknowledgments

The authors thank all the patients who participated in this study, Dr. Didier Allexandre for helpful discussions on statistics, and Dr. Ken Sakaie for helpful discussions on DTI image processing. Funding was provided by the Bright Side of the Road Foundation and the Fight ALS Fund.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Lerner Research Institute, Cleveland, USA

    Venkateswaran Rajagopalan

  2. Human Performance and Engineering Laboratory, Kessler Foundation Research Center, 300 Executive Drive, Suite 70, West Orange, NJ, 07052, USA

    Venkateswaran Rajagopalan & Guang H. Yue

  3. Neuromuscular Center, Department of Neurology, S90, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Erik P. Pioro

  4. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA

    Erik P. Pioro

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  1. Venkateswaran Rajagopalan
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Correspondence to Erik P. Pioro.

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Rajagopalan, V., Yue, G.H. & Pioro, E.P. Brain white matter diffusion tensor metrics from clinical 1.5T MRI distinguish between ALS phenotypes. J Neurol 260, 2532–2540 (2013). https://doi.org/10.1007/s00415-013-7012-1

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  • DOI: https://doi.org/10.1007/s00415-013-7012-1

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