Role of DTI-MRI parameters in diagnosis of ALS: useful biomarkers for daily practice? Tertiary centre experience and literature review

Abstract

Introduction. Despite the rapid development of neuroimaging techniques, the diagnosis of amyotrophic lateral sclerosis (ALS) remains a significant challenge. Magnetic resonance imaging (MRI) is important for ruling out ALS mimickers, while Diffusion Tensor Imaging (DTI) is a useful tool for the identification of cortical tract damage. The aim of this study was to identify the optimal set of DTI parameters to support the diagnosis of ALS that could be applied to everyday MRI and be used as a disease biomarker in daily practice.Material and methods. Forty-seven ALS patients and 55 age-and gender-matched healthy individuals underwent MRI using a 1.5-Tesla scanner including a DTI sequence with 30 spatial directions and a b-value 0/1,000 s/mm2. Two independent researchers measured the DTI parameters: fractional anisotropy (FA), TRACE and apparent diffusion coefficient (ADC) using freehand regions of interest (ROIs) placed along both corticospinal tracts (CSTs), starting at the level of the internal capsule and ending at the medulla.Results. Statistical significance was only achieved for fractional anisotropy (FA) (ALS vs controls, p < 0.001). The highest sensitivity was found in the brainstem (cerebral peduncles, pons and pyramids) where it ranged from 72.3% to 80.9%, whereas the highest specificity was observed at the level of the internal capsule (94.6%). The combined highest sensitivity and specificity was obtained in the pons (72.3% and 72.7%, respectively). Classifier based positive predictive values for Youden index cut-off scores varied between 60.7% and 69.4%. Conclusions.Fractional anisotropy (FA) measured at the level of the brainstem was shown to be the single most relevant parameter in differentiating patients with ALS from healthy subjects. This has the potential to become an ALS-specific biomarker for patient identification in daily practice.

In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use

“…Brain magnetic resonance imaging (MRI) may show white matter T2 hyperintensity in corticospinal tracts but with low diagnostic accuracy [ 93 ]. Another group explored diffusion-tensor imaging (DTI) in ALS as a proxy to evaluate the integrity of white matter fibers, finding fractional anisotropy at the brainstem as a differential parameter in ALS compared to healthy controls, proposing DTI MRI as a clinical biomarker for ALS [ 94 ].…”

Open imaging protocols, amyotrophic lateral sclerosis and other neurodegenerative disorders

“…Manual identification of critical landmarks is feasible in small clinical datasets, but is more difficult when encompassing extensive population studies. Research presented in this issue has manually extracted anatomical landmarks and average values [1]. Achieving reproducibility of these measurements using automatic registration-based methods would represent a significant advance [7].…”

“…The source of the abnormal signal captured in the recent study by Maj et al came from an altered white matter tract signal, and possibly myelination [1]. Identifying and measuring demyelination of the cortico-spinal pathway has been attempted using various magnetic resonance imaging methods.…”

“…The evaluation of imaging biomarker efficiency is a complicated task when it is based on real-world data derived from a single centre [1]. Over the last decade, there have been more than 125 registered trials investigating treatment effects and monitoring disease progression in amyotrophic lateral sclerosis [2].…”

Machine learning classificatory as a tool in the diagnosis of amyotrophic lateral sclerosis using diffusion tensor imaging parameters collected with 1.5T MRI scanner: A case study

“…This method, in particular, allows measuring microstructural pathological abnormalities in the corticospinal tract (CST), which reflect the degree of brainstem and cerebral cortex atrophy characteristic of ALS [13]. The studies [14][15][16][17] demonstrate that diffusion-weighted MRI-based neuroimaging provides reliable measurements for assessing clinical severity and monitoring the progression of the disease and should be included in clinical evaluation protocols for patients with suspected ALS. DTI provides unique information about the microstructure of white matter in the central nervous system.…”