Diffusion tensor MRI as a diagnostic tool of upper motor neuron involvement in amyotrophic lateral sclerosis

doi:10.1016/j.jns.2004.08.014

Journal of the Neurological Sciences

Volume 227, Issue 1, 15 December 2004, Pages 73-78

https://doi.org/10.1016/j.jns.2004.08.014 Get rights and content

Abstract

Background

Clinical identification of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS) is often difficult, particularly early in the course of the disease, or when lower motor neuron (LMN) dysfunction is prominent. Diffusion tensor MR imaging (DTI) can provide unique information on axonal organization by measuring diffusion anisotropy and the directionally independent diffusion.

Objective

The purpose of this study was to assess water diffusion changes along pyramidal tracts of the brainstem in patients with ALS and to investigate possible correlations between changes of diffusion properties and various clinical parameters.

Methods

We studied 16 patients (M:F=9:7, 50.5±12.4 years) with ALS as defined by clinical and electrophysiological examinations. These patients were compared with 11 healthy, age and sex-matched controls (M:F=5:6, 54.5±9.9 years). DTI was performed using a single shot SE-EPI with 25 noncollinear diffusion gradient directions (b=1000 s/mm²) and with no diffusion gradient on a 3.0-T MR system.

Results

By multifactorial ANOVA, the effects of group (patient versus control) and anatomical level on fractional anisotropy (FA) and mean diffusivity (MD) were significant (p<0.001 for both parameters), whereas the effect of side (left versus right) and interactions between factors (group by side and group by anatomical level) were not (p>0.05). In all subjects, FA and MD varied greatly depending on the anatomical level, and FA was highly variable even between contiguous slices in the pons and medulla, whereas relatively constant FA values were noted at the level of the midbrain. Cerebral peduncle was the only area that showed significant differences of diffusion properties between patients and controls (p<0.001 for FA, p=0.001 for MD). Correlation analysis revealed a significant inverse relationship between the FA value and the extent of UMN signs (r=−0.81, p<0.001).

Conclusions

Alteration of diffusion properties in the cerebral peduncle in ALS may reflect pathological changes in structures rather than regional architectural variations of the corticospinal tracts or experimental artifacts.

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily involving motor neurons in the cerebral cortex, brainstem and spinal cord [1]. A diagnosis of ALS requires a history of progressive weakness with evidence of both upper motor neuron (UMN) and lower motor neuron (LMN) dysfunction. However, whereas the presence of clinical and subclinical LMN signs can be demonstrated by electromyography, there is no widely accepted objective marker for UMN involvement in ALS. Moreover, the clinical evaluation of UMN dysfunction in ALS is often difficult, particularly early in the course of the disease or when LMN dysfunction is very prominent. For these reasons, the availability of a sensitive diagnostic procedure to objectively document the presence of UMN degeneration would be useful in clinical practice and for therapeutic trials.

Diffusion-weighted MRI (DWI) is increasingly being used to investigate the diffusion properties of tissue water in vivo [2]. By acquiring images with diffusion gradients oriented in multiple or at least six noncollinear directions, diffusion tensor MR imaging (DTI) can provide unique information on axonal organization by measuring diffusion anisotropy and directionally independent diffusion [3], [4]. This technique is of particular interest to those wishing to study the integrity of white matter fiber tracts [5], and it could be a useful modality for documenting and monitoring pyramidal tract pathology in ALS. In the first study of DTI in ALS, Ellis et al. [6] demonstrated that diffusion anisotropy was reduced along the corticospinal tracts, and that mean diffusivity (MD) was increased in ALS patients versus normal controls. However, they measured diffusion properties only in the supratentorial corticospinal tracts, incorporating the posterior limb of the internal capsule. In addition, recently, diffusion anisotropy has been reported to be highly variable and to depend on local architectural features of the tissues under investigations even within pyramidal tracts [7], [8]. These facts, however, have not been adequately addressed, which might result in erroneous interpretations of DTI results.

The purpose of this study was to assess water diffusion changes along the pyramidal tracts of the brainstem in ALS patients. We employed quantitative measurements of mean diffusivity (MD) and fractional anisotropy (FA) from the diffusion tensor MR images. We also investigated the possibility of correlations between changes in diffusion properties and various clinical parameters, including onset region, the level of diagnostic certainty, symptom severity, disease duration and the clinical extent of UMN signs.

Section snippets

Subjects

We investigated 16 ALS patients; their diagnoses were established according to the criteria of El Escorial in the revised form of Airlie House [9]. At the time of the investigation, four patients had definite ALS, six probable ALS and six probable ALS laboratory supported. For statistical evaluation, we scored “definite” as “3,” “probable” as “2” and “probable-laboratory supported” as “1.” Patients with hypertension, diabetes mellitus, a history of cerebrovascular disease or other neurological

FA and MD along the pyramidal tract in the brainstem

Mean FA values and standard deviations (S.D.) for the patient and control groups are shown in Fig. 2A, and mean MD and its S.D. in Fig. 2B. These values were obtained by averaging all voxels within each ROI. By multifactorial ANOVA, the effects of subject group and anatomical level on the diffusion parameters were significant (p<0.001 for both FA and MD), whereas the effect of sidedness and interactions between factors (group by side and group by anatomical level) were not (p>0.05). The FA

Discussion

We investigated water diffusion changes in ALS, and multifactorial ANOVA revealed that overall diffusivity and diffusion anisotropy are significantly altered in the pyramidal tracts in ALS patients versus normal controls. Ellis et al. [6] showed the similar changes of the diffusion properties in the supratentorial corticospinal tracts, and we confirmed this finding in the brainstem.

The interpretation of the DTI results, however, is not simple. Subsequent analysis at each anatomical level

Acknowledgements

This study was supported by a grant for “Development of New Medical Imaging Techniques in Radiation and Radioisotope” from the Mid and Long Term Nuclear R/D Program of the Korean Ministry of Science and Technology.

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¹: Drs. Hong and Lee have equally contributed to this study.

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Diffusion tensor MRI as a diagnostic tool of upper motor neuron involvement in amyotrophic lateral sclerosis

Abstract

Background

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Subjects

FA and MD along the pyramidal tract in the brainstem

Discussion

Acknowledgements

J. Magn. Reson.

Magn. Reson. Imaging

NeuroImage

J. Magn. Reson., Ser. B

Clinical features and diagnosis of amyotrophic lateral sclerosis

Looking into the functional architecture of the brain with diffusion MRI

Nat. Rev., Neurosci.

Diffusion tensor echo-planar imaging of human brain