Abstract

Purpose: The purpose of this study is classifying multiple sclerosis (MS) patients in the four clinical forms as defined by the McDonald criteria using machine learning algorithms trained on clinical data combined with lesion loads and magnetic resonance metabolic features.Materials and Methods: Eighty-seven MS patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17 Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy controls were included in this study. Longitudinal data available for each MS patient included clinical (e.g., age, disease duration, Expanded Disability Status Scale), conventional magnetic resonance imaging and spectroscopic imaging. We extract N-acetyl-aspartate (NAA), Choline (Cho), and Creatine (Cre) concentrations, and we compute three features for each spectroscopic grid by averaging metabolite ratios (NAA/Cho, NAA/Cre, Cho/Cre) over good quality voxels. We built linear mixed-effects models to test for statistically significant differences between MS forms. We test nine binary classification tasks on clinical data, lesion loads, and metabolic features, using a leave-one-patient-out cross-validation method based on 100 random patient-based bootstrap selections. We compute F1-scores and BAR values after tuning Linear Discriminant Analysis (LDA), Support Vector Machines with gaussian kernel (SVM-rbf), and Random Forests.Results: Statistically significant differences were found between the disease starting points of each MS form using four different response variables: Lesion Load, NAA/Cre, NAA/Cho, and Cho/Cre ratios. Training SVM-rbf on clinical and lesion loads yields F1-scores of 71–72% for CIS vs. RR and CIS vs. RR+SP, respectively. For RR vs. PP we obtained good classification results (maximum F1-score of 85%) after training LDA on clinical and metabolic features, while for RR vs. SP we obtained slightly higher classification results (maximum F1-score of 87%) after training LDA and SVM-rbf on clinical, lesion loads and metabolic features.Conclusions: Our results suggest that metabolic features are better at differentiating between relapsing-remitting and primary progressive forms, while lesion loads are better at differentiating between relapsing-remitting and secondary progressive forms. Therefore, combining clinical data with magnetic resonance lesion loads and metabolic features can improve the discrimination between relapsing-remitting and progressive forms.

Highlights

  • Multiple sclerosis (MS) is an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons (Compston and Coles, 2008)

  • Using the previously described (Section 2.6) linear mixedeffects models we found that the fixed effect MS course is statistically significant in the evolution of NAA/Cho, NAA/Cre, Cho/Cre, and lesion load (LL), with corresponding p-values of: 3.4 × 10−6, 2 × 10−4, 2.3 × 10−2, and 2.6 × 10−4

  • We performed nine binary classification tasks and report F1-scores and balanced accuracy rate (BAR) values after learning linear and non-linear classifiers on combinations of clinical data, lesion loads, and metabolic features

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Summary

Introduction

Multiple sclerosis (MS) is an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons (Compston and Coles, 2008). Two thirds of the RR patients will develop a secondary progressive (SP) form, while the other third will follow a benign course (Scalfari et al, 2010). The rest of MS patients (15%) will start directly with a primary progressive (PP) form. The criteria to diagnose MS forms was originally formulated by McDonald et al (2001) and revised by Polman et al (2005, 2011). They all rely on using conventional magnetic resonance imaging techniques (MRI) such as T1-weighted, gadoliniumenhanced T1-weighted MRI, as well as T2-weighted and FLAIR, due to a high sensitivity for visualizing MS lesions. Conventional MRI is used for quantifying lesion load (LL), a marker of inflammation process but only a moderate predictor of MS evolution (Filippi et al, 1994)

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