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Background and purpose: This study sought to evaluate the relationship of progressive corticospinal tract (CST) degeneration with survival in patients with amyotrophic lateral sclerosis (ALS). Methods: Forty‐one ALS patients and 42 healthy controls were prospectively recruited from the Canadian ALS Neuroimaging Consortium. Magnetic resonance imaging scanning and clinical evaluations were performed on participants at three serial visits with 4‐month intervals. Texture analysis was performed on T1‐weighted magnetic resonance imaging scans and the texture feature 'autocorrelation' was quantified. Whole‐brain group‐level comparisons were performed between patient subgroups. Linear mixed models were used to evaluate longitudinal progression. Region‐of‐interest and 3D voxel‐wise Cox proportional‐hazards regression models were constructed for survival prediction. For all survival analyses, a second independent cohort was used for model validation. Results: Autocorrelation of the bilateral CST was increased at baseline and progressively increased over time at a faster rate in ALS short survivors. Cox proportional‐hazards regression analyses revealed autocorrelation of the CST as a significant predictor of survival at 5 years follow‐up (hazard ratio 1.28, p = 0.005). Similarly, voxel‐wise whole‐brain survival analyses revealed that increased autocorrelation of the CST was associated with shorter survival. ALS patients stratified by median autocorrelation in the CST had significantly different survival times using the Kaplan–Meier curve and log‐rank tests (χ2 = 7.402, p = 0.007). Conclusions: Severity of cerebral degeneration is associated with survival in ALS. CST degeneration progresses faster in subgroups of patients with shorter survival. Neuroimaging holds promise as a tool to improve patient management and facilitation of clinical trials. [ABSTRACT FROM AUTHOR]

Progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) remains poorly understood. Here, three‐dimensional (3D) texture analysis was used to study longitudinal gray and white matter cerebral degeneration in ALS from routine T1‐weighted magnetic resonance imaging (MRI). Participants were included from the Canadian ALS Neuroimaging Consortium (CALSNIC) who underwent up to three clinical assessments and MRI at four‐month intervals, up to 8 months after baseline (T0). Three‐dimensional maps of the texture feature autocorrelation were computed from T1‐weighted images. One hundred and nineteen controls and 137 ALS patients were included, with 81 controls and 84 ALS patients returning for at least one follow‐up. At baseline, texture changes in ALS patients were detected in the motor cortex, corticospinal tract, insular cortex, and bilateral frontal and temporal white matter compared to controls. Longitudinal comparison of texture maps between T0 and Tmax (last follow‐up visit) within ALS patients showed progressive texture alterations in the temporal white matter, insula, and internal capsule. Additionally, when compared to controls, ALS patients had greater texture changes in the frontal and temporal structures at Tmax than at T0. In subgroup analysis, slow progressing ALS patients had greater progressive texture change in the internal capsule than the fast progressing patients. Contrastingly, fast progressing patients had greater progressive texture changes in the precentral gyrus. These findings suggest that the characteristic longitudinal gray matter pathology in ALS is the progressive involvement of frontotemporal regions rather than a worsening pathology within the motor cortex, and that phenotypic variability is associated with distinct progressive spatial pathology. [ABSTRACT FROM AUTHOR]

Background: Texture analysis (TA) is an image-analysis technique that detects complex intervoxel statistical patterns. 3D TA has shown potential in detecting cerebral degeneration not perceptible to the human eye in many neurological disorders. The reliability of this method's application in a multicenter study is unknown.Purpose: To assess the intrasite and intersite reliability of a novel 3D TA method from data acquired systematically from the Canadian ALS Neuroimaging Consortium (CALSNIC).Study Type: Prospective multicenter data with harmonized MR sequence parameters acquired from five sites.Population: Six healthy subjects.Field Strength: 3T 3D-MPRAGE and 3D-SPGR T1 -weighted MRI of the brain.Assessment: Voxel-based 3D TA was performed on the whole brain to produce texture maps.Statistical Tests: Intra- and intersite reliability of texture features was assessed using a two-way mixed-effects model for intraclass correlation coefficients (ICC). ICCs were calculated in a region-of-interest (ROI) analysis of predetermined anatomically relevant areas. A voxelwise approach was used to assess the whole brain.Results: In the ROI analyses, intrasite reliability was excellent (ICC > 0.75) across most regions and texture features (autocorrelation [autoc], contrast [contr], energy [energ]). Intersite reliability was excellent for most regions with autoc, ranging from fair to excellent for contr, and ICCs ranging from poor to good (<0.40-0.75) for energ. Voxelwise analyses revealed a large range in ICC across the brain for both intrasite and intersite ICCs (0.0-0.90), with higher reliability in the cortical gray matter compared with deeper subcortical structures.Data Conclusion: Overall, the reliability of 3D TA was highly dependent on texture feature, region studied, and method of analysis (ROI or voxelwise). Intrasite reproducibility was good to excellent, and better than intersite. ROI-based analyses present higher reliability in comparison with voxelwise analyses. Autoc has overall excellent reliability. These factors might be considered when designing future 3D TA studies.Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1200-1209. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether textures computed from T1‐weighted (T1W) images of the corticospinal tract (CST) in amyotrophic lateral sclerosis (ALS) are associated with degenerative changes evaluated by diffusion tensor imaging (DTI). Nineteen patients with ALS and 14 controls were prospectively recruited and underwent T1W and diffusion‐weighted magnetic resonance imaging. Three‐dimensional texture maps were computed from T1W images and correlated with the DTI metrics within the CST. Significantly correlated textures were selected and compared within the CST for group differences between patients and controls using voxel‐wise analysis. Textures were correlated with the patients' clinical upper motor neuron (UMN) signs and their diagnostic accuracy was evaluated. Voxel‐wise analysis of textures and their diagnostic performance were then assessed in an independent cohort with 26 patients and 13 controls. Results showed that textures autocorrelation, energy, and inverse difference normalized significantly correlated with DTI metrics (p < .05) and these textures were selected for further analyses. The textures demonstrated significant voxel‐wise differences between patients and controls in the centrum semiovale and the posterior limb of the internal capsule bilaterally (p < .05). Autocorrelation and energy significantly correlated with UMN burden in patients (p < .05) and classified patients and controls with 97% accuracy (100% sensitivity, 92.9% specificity). In the independent cohort, the selected textures demonstrated similar regional differences between patients and controls and classified participants with 94.9% accuracy. These results provide evidence that T1‐based textures are associated with degenerative changes in the CST. [ABSTRACT FROM AUTHOR]

Objective: To evaluate cerebral degenerative changes in ALS and their correlates with survival using 3D texture analysis. Methods: A total of 157 participants were included in this analysis from four neuroimaging studies. Voxel‐wise texture analysis on T1‐weighted brain magnetic resonance images (MRIs) was conducted between patients and controls. Patients were divided into long‐ and short‐survivors using the median survival of the cohort. Neuroanatomical differences between the two survival groups were also investigated. Results: Whole‐brain analysis revealed significant changes in image texture (FDR P < 0.05) bilaterally in the motor cortex, corticospinal tract (CST), insula, basal ganglia, hippocampus, and frontal regions including subcortical white matter. The texture of the CST correlated (P < 0.05) with finger‐ and foot‐tapping rate, measures of upper motor neuron function. Patients with a survival below the media of 19.5 months demonstrated texture change (FDR P < 0.05) in the motor cortex, CST, basal ganglia, and the hippocampus, a distribution which corresponds to stage 4 of the distribution TDP‐43 pathology in ALS. Patients with longer survival exhibited texture changes restricted to motor regions, including the motor cortex and the CST. Interpretation: Widespread gray and white matter pathology is evident in ALS, as revealed by texture analysis of conventional T1‐weighted MRI. Length of survival in patients with ALS is associated with the spatial extent of cerebral degeneration. [ABSTRACT FROM AUTHOR]