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.

Keywords: a structured report; amyotrophic lateral sclerosis; brain MR image analysis; imaging biomarkers; neurodegenerative disorders.

FIGURE 1

FLAIR MR images from an exemplary patient with ELA (left) and a control subject (right) evaluated in our center, showing bilateral hyperintensities of the corticospinal tract in subcortical white matter and posterior limb of capsula internal in the ELA patient.

FIGURE 2

Susceptibility Weighted MR images from 3 different exemplary ELA patients (upper row) and a control subject (lower row) for comparison, evaluated in our center. Note the iron-related hypointensities in the motor cortex at the lower limbs, upper limbs, and bulbar region (from left to right) in the patients with ELA.

FIGURE 3

Control subject (left) and exemplary ELA patient (right) 3D cortical thickness surface rendering maps, evaluated in our center, showing the decreased thickness in specific gray matter areas (colors represent different thickness as shown in the bar).

FIGURE 4

DTI tractography overlaid on coronal T1-weighted images of a control subject (left) and exemplary ELA patient (right) evaluated in our center. The Corticospinal Tract (CST) at 2 different levels allows comparing the differences in Fractional Anisotropy between control subjects and ELA patients. R_CST, right CST; L_CST, left CST; R_IC, right Posterior Limb of Internal Capsule (red line); L_IC, left Posterior Limb of Internal Capsule (brown line); R_LV, right Centrum Semiovale at top of the lateral ventricle (green line); and L_LV, left Centrum Semiovale at top of the lateral ventricle (yellow line).

FIGURE 5

MR pipeline followed in our center to highlight the iron deposits. Susceptibility Weighted (SW) images are registered to the T1 space. Then, skull stripping is obtained from 3D T1-weighted images. The segmentation process, based on atlas and threshold techniques, isolate the white matter (WM) and gray matter (GM). Surface extraction obtains the frontiers between WM-GM (red line) and WM-pia (green line). The 3D inflated pial surface reconstruction improves the sulci (light gray) and gyrus (dark gray) visualization. Finally, iron deposits from SW images are matched over the inflated surface.