MRI-Based Mapping of Cerebral Propagation in Amyotrophic Lateral Sclerosis

Müller, Hans‐Peter; Kassubek, Jan

doi:10.3389/fnins.2018.00655

Cited by 14 publications

(12 citation statements)

References 44 publications

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“…This system plays an important role in movement regulation and modulates higher cognitive functions ( Palesi et al, 2017 ; Wagner and Luo, 2020 ). Based on a multicenter DTI study, corticopontine tract (CPT) FA decreases have been related to stage 2 of a lately suggested pathological staging system ( Kassubek et al, 2014 ; Müller and Kassubek, 2018 ). Moreover, a DTI study has shown that disruption of white matter integrity of the cortico-ponto-cerebellar system in ALS patients was associated with the pseudobulbar syndrome, ( Floeter et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

Zhang

Jin

et al. 2021

Front. Neurosci.

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IntroductionThe brainstem is an important component in the pathology of amyotrophic lateral sclerosis (ALS). Although neuroimaging studies have shown multiple structural changes in ALS patients, few studies have investigated structural alterations in the brainstem. Herein, we compared the brainstem structure between patients with ALS and healthy controls.MethodsA total of 33 patients with ALS and 33 healthy controls were recruited in this study. T1-weighted and diffusion tensor imaging (DTI) were acquired on a 3 Tesla magnetic resonance imaging (3T MRI) scanner. Volumetric and vertex-wised approaches were implemented to assess the differences in the brainstem’s morphological features between the two groups. An atlas-based region of interest (ROI) analysis was performed to compare the white matter integrity of the brainstem between the two groups. Additionally, a correlation analysis was used to evaluate the relationship between ALS clinical characteristics and structural features.ResultsVolumetric analyses showed no significant difference in the subregion volume of the brainstem between ALS patients and healthy controls. In the shape analyses, ALS patients had a local abnormal surface contraction in the ventral medulla oblongata and ventral pons. Compared with healthy controls, ALS patients showed significantly lower fractional anisotropy (FA) in the left corticospinal tract (CST) and bilateral frontopontine tracts (FPT) at the brainstem level, and higher radial diffusivity (RD) in bilateral CST and left FPT at the brainstem level by ROI analysis in DTI. Correlation analysis showed that disease severity was positively associated with FA in left CST and left FPT.ConclusionThese findings suggest that the brainstem in ALS suffers atrophy, and degenerative processes in the brainstem may reflect disease severity in ALS. These findings may be helpful for further understanding of potential neural mechanisms in ALS.

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Section: Discussionmentioning

confidence: 99%

Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

Zhang

Jin

et al. 2021

Front. Neurosci.

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“…DTI metrics maps (FA, axial diffusivity—AxD, radial diffusivity—RD, mean diffusivity—MD) are calculated from these stereotaxically normalized data sets and are in a following step smoothed with a Gaussian filter with a size of about two to three times the recording voxel size, that way providing a good balance between sensitivity and specificity. The axonal damage and myelin degradation is mirrored by DTI metrics; differences at the group level to assess microstructural alterations by statistical analysis of DTI metrics can be performed by various approaches (Müller and Kassubek, 2018 ): (1) unbiased voxelwise comparison by whole brain-based spatial statistics (WBSS) (Müller et al, 2012b ) or tractwise comparison by tract-based spatial statistics (TBSS) (Smith et al, 2006 ) or (2) hypothesis-guided tract-based quantification by analyzing DTI metrics in tract systems by TOI-based tractwise FA statistics (TFAS) (Müller et al, 2007 ) ( Figure 4 ).…”

Section: Methodsmentioning

confidence: 99%

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

et al. 2020

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The understanding of human and non-human microstructural brain alterations in the course of neurodegenerative diseases has substantially improved by the non-invasive magnetic resonance imaging (MRI) technique of diffusion tensor imaging (DTI). Animal models (including disease or knockout models) allow for a variety of experimental manipulations, which are not applicable to humans. Thus, the DTI approach provides a promising tool for cross-species cross-sectional and longitudinal investigations of the neurobiological targets and mechanisms of neurodegeneration. This overview with a systematic review focuses on the principles of DTI analysis as used in studies at the group level in living preclinical models of neurodegeneration. The translational aspect from in-vivo animal models toward (clinical) applications in humans is covered as well as the DTI-based research of the non-human brains' microstructure, the methodological aspects in data processing and analysis, and data interpretation at different abstraction levels. The aim of integrating DTI in multiparametric or multimodal imaging protocols will allow the interrogation of DTI data in terms of directional flow of information and may identify the microstructural underpinnings of neurodegeneration-related patterns.

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“…Importantly, FTD patients occasionally develop motor neuron disease, and for this reason, ALS and FTD have been suggested to be at the edges of the same disease spectrum (Couratier et al, 2017). These observations have been possible thanks to the combination of clues derived from human post‐mortem material (Braak & Braak, 1991; Strong et al, 2005; Kalaitzakis et al, 2008), longitudinal neuroimaging of living patients (Ewers et al, 2008; Seeley et al, 2009; Brettschneider et al, 2015; Müller & Kassubek, 2018; Young et al, 2020), and clinical monitoring (Perlmutter, 2009; Turner et al, 2010; Agüera‐Ortiz et al, 2010; Fang et al, 2017). Additionally, the development of in vitro and in vivo disease models has helped to elucidate, at least in part, the molecular basis of disease pathogenesis (Luk et al, 2012; Ruiz‐Riquelme et al, 2018; Kim et al, 2019; McAlary et al, 2019).…”

Section: The Progressive Nature Of Neurodegenerative Diseasesmentioning

confidence: 99%

Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis

et al. 2021

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder whose exact causative mechanisms are still under intense investigation. Several lines of evidence suggest that the anatomical and temporal propagation of pathological protein species along the neural axis could be among the main driving mechanisms for the fast and irreversible progression of ALS pathology. Many ALS‐associated proteins form intracellular aggregates as a result of their intrinsic prion‐like properties and/or following impairment of the protein quality control systems. During the disease course, these mutated proteins and aberrant peptides are released in the extracellular milieu as soluble or aggregated forms through a variety of mechanisms. Internalization by recipient cells may seed further aggregation and amplify existing proteostatic imbalances, thus triggering a vicious cycle that propagates pathology in vulnerable cells, such as motor neurons and other susceptible neuronal subtypes. Here, we provide an in‐depth review of ALS pathology with a particular focus on the disease mechanisms of seeding and transmission of the most common ALS‐associated proteins, including SOD1, FUS, TDP‐43, and C9orf72‐linked dipeptide repeats. For each of these proteins, we report historical, biochemical, and pathological evidence of their behaviors in ALS. We further discuss the possibility to harness pathological proteins as biomarkers and reflect on the implications of these findings for future research.

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MRI-Based Mapping of Cerebral Propagation in Amyotrophic Lateral Sclerosis

Cited by 14 publications

References 44 publications

Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis

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