Imaging Biomarkers for the Diagnosis and Prognosis of Neurodegenerative Diseases. The Example of Amyotrophic Lateral Sclerosis

Abstract

The term amyotrophic lateral sclerosis (ALS) comprises a heterogeneous group of fatal neurodegenerative disorders of largely unknown etiology characterized by the upper motor neurons (UMN) and/or lower motor neurons (LMN) degeneration. The development of brain imaging biomarkers is essential to advance in the diagnosis, stratification and monitoring of ALS, both in the clinical practice and clinical trials. In this review, the characteristics of an optimal imaging biomarker and common pitfalls in biomarkers evaluation will be discussed. Moreover, the development and application of the most promising brain magnetic resonance (MR) imaging biomarkers will be reviewed. Finally, the integration of both qualitative and quantitative multimodal brain MR biomarkers in a structured report will be proposed as a support tool for ALS diagnosis and stratification.

Diagnostic and Prognostic Value of Conventional Brain MRI in the Clinical Work-Up of Patients with Amyotrophic Lateral Sclerosis

“…In this study, we retrospectively evaluated the 3T-MRI data of a large group of ALS patients in order to identify specific changes in CST T2/FLAIR hyperintensity, MC T2*/SWI hypointensity, and selective motor cortex atrophy, which are related to UMN involvement. We found that all of these MRI features occurred more frequently in ALS patients than in controls, in line with previous results [4,5]. We obtained good diagnostic accuracy, particularly when considering CST FLAIR hyperintensity (accuracy: 72%) and motor cortex SWI hypointensity (accuracy: 71%).…”

“…Conventional Magnetic Resonance Imaging (MRI) of the brain is routinely performed in the diagnostic workup for ALS in order to rule out other pathologies that present involvement of UMNs. However, over the last few decades, numerous studies using both qualitative and quantitative evaluation have reported abnormal MRI findings at the level of the pyramidal pathway in patients with ALS [4,5]. The most interesting results were obtained in studies using advanced MR techniques that are able to detect subtle changes in the motor cortex or the corticospinal tract (CST).…”

“…The qualitative evaluation of MRI images remains the most-used approach in the diagnostic procedure that is applied to these patients, and many studies report variations in definite radiological features. In patients with ALS, conventional MRI (i.e., T2-weighted, proton density (PD)-weighted, and fluid attenuated inversion recovery (FLAIR) sequence) can be used to detect changes in signal intensity along the CST [4,5]. A low-signal-intensity rim, probably related to iron deposition, can be found in T2-weighted images and, even more prominently, in T2*-weighted and susceptibility-weighted images (SWI) of the precentral cortex of ALS patients [4].…”

“…In patients with ALS, conventional MRI (i.e., T2-weighted, proton density (PD)-weighted, and fluid attenuated inversion recovery (FLAIR) sequence) can be used to detect changes in signal intensity along the CST [4,5]. A low-signal-intensity rim, probably related to iron deposition, can be found in T2-weighted images and, even more prominently, in T2*-weighted and susceptibility-weighted images (SWI) of the precentral cortex of ALS patients [4]. Furthermore, the motor cortex can be visibly atrophic [4,5].…”

“…A low-signal-intensity rim, probably related to iron deposition, can be found in T2-weighted images and, even more prominently, in T2*-weighted and susceptibility-weighted images (SWI) of the precentral cortex of ALS patients [4]. Furthermore, the motor cortex can be visibly atrophic [4,5]. Such features seem to be more easily detectable using high-field scanners.…”