Spinal cord multi‐parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis

Abstract

To cite this version:G. Querin, M. M. El Mendili, T. Lenglet, S. Delphine, V. Marchand-Pauvert, et AbstractBackground: Assessing survival is a critical issue in patients with Amyotrophic Lateral Sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by MRI and disease progression. Aim of the study was than to determine the predictive added value of multimodal SC MRI on survival. Methods: 49 ALS patients were recruited and clinical data collected. Patients were scored on ALSFRS-R and manual muscle testing. They were followed longitudinally to assess survival. Cervical spinal cord was imaged using 3T MRI system. Cord volume and cross-sectional area (CSA) at each vertebral level were computed. DTI metrics were measured. Imaging metrics and clinical variables were used as inputs for a multivariate Cox regression survival model. Results: When building a multivariate Cox regression model with clinical and MRI parameters, FA, MTR, and CSA at C2-C3, C4-C5, C5-C6 and C6-C7 vertebral levels were significant. Moreover, hazard ratio (HR) calculated for CSA at C3-C4 and C5-C6 levels indicated an increased risk for patients with SC atrophy (respectively 0.66 and 0.68). In our cohort, MRI parameters seem to be more predictive than clinical variables, which had HR very close to 1. Conclusions:We suggest that multimodal SC MRI could be a useful tool in survival prediction especially if used at the beginning of the disease and when combined with clinical variables. To validate it as a biomarker, results confirmation in independent bigger cohorts of patients is warranted.

Presymptomatic spinal cord pathology in c9orf72 mutation carriers: A longitudinal neuroimaging study

“…35 The precise molecular mechanisms underlying C9orf72-associated degeneration remains largely unknown, even if putative cell-to-cell propagation of the DPRs and TDP-43 inclusions has been proposed. 36 Despite the detection sensitivity of novel spinal imaging techniques in ALS, [24][25][26][37][38][39] the lack of imaging findings in younger mutation carriers may be due to technological limitations and does not necessarily represent lack of pathology. Presymptomatic imaging in C9orf72 has dual academic and clinical relevance.…”

“…19 The frontotemporal, insular, hippocampal, and thalamic changes identified in asymptomatic cohorts are consistent with the genotype-associated signature of symptomatic cohorts. [24][25][26][27] The primary objective of this study is the comprehensive characterization of cervical SC GM and WM integrity in asymptomatic C9orf72 hexanucleotide carriers. 21 SC pathology in C9orf72 mutations carriers, however, has not been studied in vivo to date.…”

“…In recent years, spinal imaging has seen momentous developments, and the combination of novel biomarkers 22 and analysis pipelines 23 allows the quantitative characterization of disease-associated gray and WM profiles, captures progressive changes, and may have a role in diagnostic applications. [24][25][26][27] The primary objective of this study is the comprehensive characterization of cervical SC GM and WM integrity in asymptomatic C9orf72 hexanucleotide carriers. The secondary aim is to appraise longitudinal changes and discuss associations with brain pathology.…”

Region‐specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer)

“…However, changes in DTI metrics could reflect various pathological mechanisms, such as inflammation, edema, demyelination or axonal degeneration, hence limiting the specificity of the technique . In the same way, MT has also been used extensively and the derived MT metric (MT ratio or MTR) has proven to be highly sensitive to microstructural tissue changes, especially to myelin alterations . However, MT has been reported to have specificity limitation towards myelin, being sensitive to the whole macromolecular pool and not only to myelinated structures.…”

Changes of cerebrospinal fluid in the upper neck area with age using diffusion weighted MR imaging

“…[2] Moreover, neuroradiology suggest a strong relationship between amyotrophic lateral sclerosis progression and spinal cord atrophy by MR imaging. [3] Diffusion weighted MR imaging (DWI) is a fast sequence constructed from fast advanced spin echo and echo-planar imaging (EPI). [4] DWI allows a quantitative index of water diffusivity for each voxel that provides visualization of the microscopic motion of water molecules within tissues.…”