Abstract
Objectives: White matter (WM) impairments involving both motor and extra-motor areas have been well-documented in amyotrophic lateral sclerosis (ALS). This study tested the potential of diffusion measurements in WM for identifying ALS based on support vector machine (SVM).Methods: Voxel-wise fractional anisotropy (FA) values of diffusion tensor images (DTI) were extracted from 22 ALS patients and 26 healthy controls and served as discrimination features. The revised ALS Functional Rating Scale (ALSFRS-R) was employed to assess ALS severity. Feature ranking and selection were based on Fisher scores. A linear kernel SVM algorithm was applied to build the classification model, from which the classification performance was evaluated. To promote classifier generalization ability, a leave-one-out cross-validation (LOOCV) method was adopted.Results: By using the 2,400~3,400 ranked features as optimal features, the highest classification accuracy of 83.33% (sensitivity = 77.27% and specificity = 88.46%, P = 0.0001) was achieved, with an area under receiver operating characteristic curve of 0.862. The predicted function value was positively correlated with patient ALSFRS-R scores (r = 0.493, P = 0.020). In the optimized SVM model, FA values from several regions mostly contributed to classification, primarily involving the corticospinal tract pathway, postcentral gyrus, and frontal and parietal areas.Conclusions: Our results suggest the feasibility of ALS diagnosis based on SVM analysis and diffusion measurements of WM. Additional investigations using a larger cohort is recommended in order to validate the results of this study.
Highlights
Amyotrophic lateral sclerosis (ALS) is a cryptogenetic and fatal neurodegenerative disorder that occurs in adults, involving the upper motor neurons as well as lower motor neurons
Taking the generalization accuracy as the statistical variable, the estimated permutation distribution is shown in Figure 3, which shows that the probability is very low (P = 0.0001), indicating that our results are highly reliable
The white matter (WM) regions with relatively increased fractional anisotropy (FA) in the healthy controls (HC) group were located in several areas, such as bilateral corona radiate and precentral gyrus, right postcentral gyrus, right posterior limb of internal capsule, left superior frontal gyrus, left angular gyrus, left middle temporal gyrus, left middle occipital gyrus, bilateral midbrain, and bilateral pons and medulla, whereas the WM regions with relatively increased FA in the patient group were located in the left frontal lobe, left inferior parietal lobule, and right superior parietal lobule
Summary
Amyotrophic lateral sclerosis (ALS) is a cryptogenetic and fatal neurodegenerative disorder that occurs in adults, involving the upper motor neurons as well as lower motor neurons. ALS is a heterogeneous disease and is generally difficult to diagnosis during the early stages. Most ALS patients die of respiratory failure. The median survival time of ALS is 3–5 years [1]. Riluzole can only prolong survival time by 2–3 months [2].
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