Abstract

Conventional magnetic resonance imaging (cMRI) is poorly sensitive to pathological changes related to multiple sclerosis (MS) in normal-appearing white matter (NAWM) and gray matter (GM), with the added difficulty of not being very reproducible. Quantitative MRI (qMRI), on the other hand, attempts to represent the physical properties of tissues, making it an ideal candidate for quantitative medical image analysis or radiomics. We therefore hypothesized that qMRI-based radiomic features have added diagnostic value in MS compared to cMRI. This study investigated the ability of cMRI (T1w) and qMRI features extracted from white matter (WM), NAWM, and GM to distinguish between MS patients (MSP) and healthy control subjects (HCS). We developed exploratory radiomic classification models on a dataset comprising 36 MSP and 36 HCS recruited in CHU Liege, Belgium, acquired with cMRI and qMRI. For each image type and region of interest, qMRI radiomic models for MS diagnosis were developed on a training subset and validated on a testing subset. Radiomic models based on cMRI were developed on the entire training dataset and externally validated on open-source datasets with 167 HCS and 10 MSP. Ranked by region of interest, the best diagnostic performance was achieved in the whole WM. Here the model based on magnetization transfer imaging (a type of qMRI) features yielded a median area under the receiver operating characteristic curve (AUC) of 1.00 in the testing sub-cohort. Ranked by image type, the best performance was achieved by the magnetization transfer models, with median AUCs of 0.79 (0.69–0.90, 90% CI) in NAWM and 0.81 (0.71–0.90) in GM. The external validation of the T1w models yielded an AUC of 0.78 (0.47–1.00) in the whole WM, demonstrating a large 95% CI and a low sensitivity of 0.30 (0.10–0.70). This exploratory study indicates that qMRI radiomics could provide efficient diagnostic information using NAWM and GM analysis in MSP. T1w radiomics could be useful for a fast and automated check of conventional MRI for WM abnormalities once acquisition and reconstruction heterogeneities have been overcome. Further prospective validation is needed, involving more data for better interpretation and generalization of the results.

Highlights

  • Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system, responsible for focal and diffuse damages, including both demyelination and neurodegeneration, and often leading to physical and mental disability (Lassmann, 2018; Chen et al, 2019)

  • The objective of the study was to investigate the ability of radiomic features found in white matter (WM), normal appearing white matter (NAWM), and gray matter (GM), extracted from conventional magnetic resonance imaging (cMRI) and Quantitative MRI (qMRI) maps, to distinguish between healthy control subjects (HCS) and MS patients (MSP)

  • This study was performed on three datasets: dataset 1 (DS1) contains both cMRI (T1w and FLAIR) and four types of qMRI maps (PD, magnetization transfer (MT), R1, and R2∗) of both MSP and HCS, dataset 2 (DS2) contains cMRI (T1W) of HCS, and dataset 3 (DS3) contains the cMRI of MSP (T1w and FLAIR)

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Summary

Introduction

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system, responsible for focal and diffuse damages, including both demyelination and neurodegeneration, and often leading to physical and mental disability (Lassmann, 2018; Chen et al, 2019). It is not sensitive to detect and track diffuse pathological changes occurring both in the normal appearing white matter (NAWM) and gray matter (GM) These changes appear in the early stages of the disease and better correlate with clinical outcomes than only the WM focal lesion load (Griffin et al, 2002; Bonnier et al, 2014; Yoo et al, 2018; Davda et al, 2019; Treaba et al, 2019). Routine cMRI voxel intensities are expressed in arbitrary units, which vary based on a large number of factors, including the patient being examined, equipment, and protocol being used This makes MRI analysis strongly dependent on the expertise of the medical specialist and hinders data reproducibility and comparison in follow-up and crosssectional studies. There is an unmet clinical need for the development and automated detection of quantitative and objective early MS biomarkers

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