A Distinct MR Imaging Phenotype in Amyotrophic Lateral Sclerosis: Correlation between T1 Magnetization Transfer Contrast Hyperintensity along the Corticospinal Tract and Diffusion Tensor Imaging Analysis

Purpose-To determine if decline in corpus callosum (CC) white matter integrity in patients with amyotrophic lateral sclerosis (ALS) is localized to motor-related areas.Materials and Methods-Twenty-one ALS patients and 21 controls participated. Diffusion tensor images (DTI) were acquired using 3 Tesla (T) MRI. Tract-based spatial statistics were used to examine whole-brain white matter damage. A segmentation schema was used to define CC volumes-of-interest (VOI). Fractional anisotropy (FA) and radial-and axial-diffusivity (RD, AD) were extracted from VOIs and compared between groups. DTI measurements in motor-related Area III were tested for correlation with symptoms and disease duration.Results-Extracted FA values from CC VOIs were reduced in ALS patients (P≤0.0001), particularly in Areas II and III (P≤0.01). Reduced FA in Area III correlated with disease symptomology (P≤0.05) and duration (P≤0.02). Between-group whole-brain comparisons (P≤0.05, corrected) showed reduced FA and increased RD throughout white matter regions including the CC, corona radiata, and internal capsule. AD was increased in the left corona radiata and internal and external capsules.Conclusion-FA in motor-related regions of the CC is more affected than other CC areas in ALS patients. Microstructural pathology of transcallosal fiber tracts may represent a future component of an imaging biomarker for ALS. AMYOTROPHIC LATERAL SCLEROSIS (ALS) is a progressive neurodegenerative disease affecting both upper-and lower-motor neurons. There are active efforts in the field of neuroimaging to discover a biomarker to aid in earlier diagnosis, improve the understanding of motor-neuron degeneration, and perhaps serve as an outcome measure for disease-modifying therapies. Unfortunately, early diagnosis of ALS has proven elusive as clinical confirmation can only occur after both upper (UMN) and lower motor neuron (LMN) involvement are detected by neurologic examination, which often occurs at a time point of advanced pathology (1). While noninvasive neurophysiologic techniques exist to detect subclinical LMN dysfunction, there is no sensitive tool that can similarly distinguish UMN dysfunction to aid in early diagnosis (2). For these reasons, much attention has turned toward neuroimaging as a means of identifying UMN involvement (3). KeywordsParticular interest in the use of diffusion tensor imaging (DTI) to identify UMN involvement in ALS has been growing. DTI research to date has largely replicated findings from postmortem studies indicating widespread microstructure deterioration along the UMNs of the corticospinal tract and corpus callosum (CC), validating this method as a valuable in vivo marker of the disease process (4-7). The CC in patients with ALS has consistently shown DTI changes, with decreased fractional anisotropy (FA) and increased radial and axial diffusivity (RD, AD) compared with control subjects (8). These changes may correspond to degeneration of transcallosal fibers passing between primary motor cortices observed at 1.5T (9). H...

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“…See Figure 1 for FA, RD, and AD results. These results are in line with previous findings in the literature (26)(27)(28).…”

Section: Tbss Dti: Decreased Fa and Increased Ad And Rd In Als Patientssupporting

confidence: 83%

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

Chapman¹,

Jelsone‐swain²,

Johnson³

et al. 2014

Magnetic Resonance Imaging

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“…The posterior limb of the internal capsule is the place where the most pronounced decrease in FA and increase in MD have been demonstrated 15,38 . Decreased FA in patients with ALS has been found to correlate with disease severity 11,42,43 , rate of disease progression 44 , and clinical 38,45 and electrophysiological 46 measures of UMN involvement. The analysis of FA and MD support the view that ALS is a multisystem degenerative disease in which abnormalities of extra-motor areas play an important role in its pathophysiology, given that it has been possible to demonstrate that the abnormalities are not restricted to the motor tract (Fig 3) but also extend to extra-motor regions, including the corpus callosum, frontal and parietal WM, insula, and hippocampal formation 14,38 .…”

Section: Non-conventional Mrimentioning

confidence: 99%

“…Previous reports have supported that MRI should be included in the workup of any patient with weakness and pyramidal signs [9][10][11] . Furthermore, some authors have suggested new MR techniques for the list of potential ALS biomarkers 4,[12][13][14] .…”

mentioning

confidence: 99%

Is magnetic resonance imaging a plausible biomarker for upper motor neuron degeneration in amyotrophic lateral sclerosis/primary lateral sclerosis or merely a useful paraclinical tool to exclude mimic syndromes? A critical review of imaging applicability in clinical routine

Rocha

Júnior

2012

Arq. Neuro-Psiquiatr.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons in the cerebral cortex, brainstem, and spinal cord, brain regions in which conventional magnetic resonance imaging is often uninformative. Although the mean time from symptom onset to diagnosis is estimated to be about one year, the current criteria only prescribe magnetic resonance imaging to exclude "ALS mimic syndromes". Extensive application of non-conventional magnetic resonance imaging (MRI) to the study of ALS has improved our understanding of the in vivo pathological mechanisms involved in the disease. These modern imaging techniques have recently been added to the list of potential ALS biomarkers to aid in both diagnosis and monitoring of disease progression. This article provides a comprehensive review of the clinical applicability of the neuroimaging progress that has been made over the past two decades towards establishing suitable diagnostic tools for upper motor neuron (UMN) degeneration in ALS.

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“…Most DTI studies of ALS have been cross-sectional studies at a single time-point, which have focused on abnormalities in the white matter (WM) of the motor system (Carrara, Carapelli et al 2012, Kwan, Meoded et al 2013, Müller, Turner et al 2016 (Sood, Gupta et al 2010) and NAA/creatine , along CST.…”

Section: Serial Mri Studiesmentioning

confidence: 99%

“…MD is used clinically to identify damage in white matter that appears normal on structural imaging (Werring, Clark et al 1999, Bammer, Augustin et al 2000. Most DTI studies of ALS have been cross-sectional studies at a single time-point and have focused on abnormalities in the white matter (WM) of the motor system (Carrara, Carapelli et al 2012, Kwan, Meoded et al 2013, Müller, Turner et al 2016. However, some studies have reported the involvement of association tracts and subcortical structures (Pettit, Bastin et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Measuring the progression of upper motor neuron disease using diffusion MRI and its correlation with Clinical phenotype

Alruwaili¹

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A Distinct MR Imaging Phenotype in Amyotrophic Lateral Sclerosis: Correlation between T1 Magnetization Transfer Contrast Hyperintensity along the Corticospinal Tract and Diffusion Tensor Imaging Analysis

Cited by 24 publications

References 52 publications

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

Is magnetic resonance imaging a plausible biomarker for upper motor neuron degeneration in amyotrophic lateral sclerosis/primary lateral sclerosis or merely a useful paraclinical tool to exclude mimic syndromes? A critical review of imaging applicability in clinical routine

Measuring the progression of upper motor neuron disease using diffusion MRI and its correlation with Clinical phenotype

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