Longitudinal diffusion tensor imaging in amyotrophic lateral sclerosis

Carsten Keil, Tino Prell, Thomas Peschel, Viktor Hartung, Reinhard Dengler, Julian Grosskreutz, Carsten Keil, Tino Prell, Thomas Peschel, Viktor Hartung, Reinhard Dengler, Julian Grosskreutz

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, caused by progressive loss of motor neurons. Changes are widespread in the subcortical white matter in ALS. Diffusion tensor imaging (DTI) detects pathological changes in white matter fibres in vivo, based on alterations in the degree (diffusivity, ADC) and directedness (fractional anisotropy, FA) of proton movement.

Methods: 24 patients with ALS and 24 age-matched controls received 1.5T DTI. FA and ADC were analyzed using statistical parametric mapping. In 15 of the 24 ALS patients, a second DTI was obtained after 6 months.

Results: Decreased FA in the corticospinal tract (CST) and frontal areas confirm existing results. With a direct comparison of baseline and follow-up dataset, the progression of upper motor neuron degeneration, reflected in FA decrease, could be captured along the CST and in frontal areas. The involvement of cerebellum in the pathology of ALS, as suspected from functional MRI studies, could be confirmed by a reduced FA (culmen, declive). These structural changes correlated well with disease duration, ALSFRS-R, and physical and executive functions.

Conclusion: DTI detects changes that are regarded as prominent features of ALS and thus, shows promise in its function as a biomarker. Using the technique herein, we could demonstrate DTI changes at follow-up which correlated well with clinical progression.

Figures

Figure 1
Figure 1
Group comparisons of ALS patients versus controls. A results are superimposed on the mean of all subjects of spatially normalized anisotropy images. Voxels with a significant decrease in FA in the patients versus controls are found in the precentral gyrus, the CST and pons (p < 0,001 uncorrected). ADC results are superimposed on the mean of all subjects of spatially normalized anisotropy images. Voxels with a significant increase in ADC in the patients versus controls are found in the precentral gyrus, CST, pons, frontal ares and limbic system (p < 0,001 uncorrected).
Figure 2
Figure 2
Direct comparison between T0 and follow-up in ALS patients. Comparison of FA results between T0 and follow-up (n=15) with paired t-test superimposed on the mean of all subjects of spatially normalized anisotropy images. FA is significantly reduced in the follow-up in the precentral gyrus, CST (at the mesencephal level), in the cerebellum (culmen, declive), the temporal and parietal lobe (p < 0,001 uncorrected). Comparison of ADC results between T0 and follow-up (n=15) with paired t-test superimposed on the mean of all subjects of spatially normalized anisotropy images. Diffusivity is significantly enhanced after 6 months in the internal and external capsule (p < 0,001 uncorrected).

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