Advanced MRI Methods for Diagnosis and Monitoring of Multiple Sclerosis (MS)

ABSTRACT Multiple sclerosis (MS) is an autoimmune neuroinflammatory disorder affecting the central nervous system (CNS). It is primarily driven by an immune‐mediated inflammatory response, leading to the demyelination of neurons. Neuroimaging, particularly magnetic resonance imaging (MRI), plays a crucial role in diagnosing, monitoring, and predicting the progression of MS. Conventional MRI sequences, including T1‐weighted (T1w), T2‐weighted (T2w), fluid‐attenuated inversion recovery (FLAIR), and post‐contrast T1 (T1ce) imaging, are commonly employed to visualize MS lesions. However, these standard MRI methods have limitations in clinical practice, such as reliance on the radiologist's expertise, difficulty in detecting heterogeneous patterns of demyelination in normal‐appearing white and gray matter, and lack of specificity in differentiating between various clinical subtypes of MS. In recent years, advanced MRI methods have shown promise in overcoming these limitations, offering improved diagnostic accuracy and monitoring capabilities for MS. These methods include magnetic resonance spectroscopy (MRS), magnetization transfer (MT), diffusion tensor imaging (DTI), quantitative susceptibility mapping (QSM), sodium (23Na) MRI, double inversion recovery (DIR), phase‐sensitive inversion‐recovery (PSIR), M2PRAGE, resting‐state functional MRI (Rs‐fMRI), diffusion‐weighted imaging (DWI), susceptibility‐weighted imaging (SWI), myelin water imaging (MWI), magnetic resonance fingerprinting (MRF), chemical exchange saturation transfer (CEST) MRI, and ultrasmall superparamagnetic iron oxide (USPIO). These methods have been extensively studied for their ability to provide novel biomarkers for demyelination, track lesion progression in white and gray matter, and assess neurodegeneration in MS. This review aims to explore the methods, current knowledge, weaknesses, and future prospects of advanced MRI methods, with a particular focus on their capacity to introduce novel diagnostic biomarkers based on the underlying pathophysiology of MS. For a better understanding, we also provide original clinical images from our tertiary MS care center. Additionally, we will discuss how these methods may be used to monitor disease progression across different stages of MS. Finally, we introduce our proposed protocol for imaging MS based on advanced MRI methods. Evidence Level 3. Technical Efficacy Stage 2.