Diffusion tensor imaging biomarkers and clinical assessments in amyotrophic lateral sclerosis (ALS) patients: an exploratory study

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Biomarkers are needed to improve diagnosis, gauge progression, and evaluate treatment. Diffusion tensor imaging (DTI) is a promising biomarker for detecting microstructural alterations in the white matter tracts. This study aimed to assess DTI metrics as biomarkers and to examine their relationship with clinical assessments in patients with ALS. Eleven patients with ALS and 21 healthy controls (HCs) underwent 3T MRI with DTI. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were compared between key motor and extra-motor tract groups. Group comparisons and correlations between DTI metrics also correlated with clinical scores of disability (ALSFRS-R), muscle strength (dynamometry), and motor unit loss (MUNIX). Widespread differences were found between patients with ALS and HCs in DTI metrics, including decreased FA and increased diffusivity metrics. However, MD and RD are more sensitive metrics for detecting white matter changes in patients with ALS. Significant interhemispheric correlations between the tract DTI metrics were also observed. DTI metrics showed symmetry between the hemispheres and correlated with the clinical assessments. MD, RD, and AD increases significantly correlated with lower ALSFRS-R and MUNIX scores and weaker dynamometry results. DTI reveals microstructural damage along the motor and extra-motor regions in ALS patients. DTI metrics can serve as quantitative neuroimaging biomarkers for diagnosis, prognosis, monitoring of progression, and treatment. Combined analysis of imaging, electrodiagnostic, and functional biomarkers shows potential for characterizing disease pathophysiology and progression.

Keywords: amyotrophic lateral sclerosis; biomarkers; diffusion tensor imaging; motor neuron disease; neuroimaging; prognosis.

Figure 1

Most of the significant differences in (A) FA, (B) MD, (C) RD, and (D) AD metrics (A P value of less than 0.05 is shown with a single star (*). A P value less than 0.01, denoted by two stars (**). A P value of less than 0.001 is denoted by three stars (***)). AD, axial diffusivity; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity.

Figure 2

Some significant correlations of diffusion tensor imaging metrics between tracts (the alteration in these tracts between the two groups is significant; refer to Table 3). AD, axial diffusivity; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity.

Figure 3

Significant correlations between disease duration and diffusion tensor imaging metrics of left corticospinal tract. AD, axial diffusivity; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity.

Figure 4

Significant correlations between the right MUSIX median and diffusion tensor imaging metrics of the middle cerebellar peduncle. AD, axial diffusivity; FA, fractional anisotropy; MD, mean diffusivity; MUSIX, motor unit size index; RD, radial diffusivity.

Figure 5

Significant correlations between right MUSIX ulnar and left diffusion tensor imaging metrics of superior cerebellar peduncle. AD, axial diffusivity; FA, fractional anisotropy; MD, mean diffusivity; MUSIX, motor unit size index; RD, radial diffusivity.