Quantitative susceptibility mapping of the motor cortex: a comparison of susceptibility among patients with amyotrophic lateral sclerosis, cerebrovascular disease, and healthy controls

BackgroundWe investigated cerebral degeneration and neurochemistry in patients with amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS).MethodsWe prospectively studied 65 patients and 43 age-matched healthy controls. Participants were recruited from 4 centers as part of a study in the Canadian ALS Neuroimaging Consortium. All participants underwent single-voxel proton MRS using a protocol standardized across all sites. Metabolites reflecting neuronal integrity (total N-acetyl aspartyl moieties [tNAA]) and gliosis (myo-inositol [Ino]), as well as creatine (Cr) and choline (Cho), were quantified in the midline motor cortex and midline prefrontal cortex. Comparisons were made between patients with ALS and healthy controls. Metabolites were correlated with clinical measures of upper motor neuron dysfunction, disease progression rate, and cognitive performance.ResultsIn the motor cortex, tNAA/Cr, tNAA/Cho, and tNAA/Ino ratios were reduced in the ALS group compared with controls. Group differences in tNAA/Cr and tNAA/Cho in the prefrontal cortex displayed reduced ratios in ALS patients; however, these were not statistically significant. Reduced motor cortex ratios were associated with slower foot tapping rate, whereas only motor tNAA/Ino was associated with finger tapping rate. Disease progression rate was associated with motor tNAA/Cho. Verbal fluency, semantic fluency, and digit span forwards and backwards were associated with prefrontal tNAA/Cr.ConclusionsThis study demonstrates that cerebral degeneration in ALS is more pronounced in the motor than prefrontal cortex, that multicenter MRS studies are feasible, and that motor tNAA/Ino shows promise as a potential biomarker.

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Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases

Frontiers in Neuroscience ◽

10.3389/fnins.2021.618435 ◽

2021 ◽

Vol 15 ◽

Author(s):

Parsa Ravanfar ◽

Samantha M. Loi ◽

Warda T. Syeda ◽

Tamsyn E. Van Rheenen ◽

Ashley I. Bush ◽

...

Keyword(s):

Systematic Review ◽

Amyotrophic Lateral Sclerosis ◽

Magnetic Susceptibility ◽

Neurodegenerative Diseases ◽

Huntington's Disease ◽

Friedreich’S Ataxia ◽

Susceptibility Mapping ◽

Quantitative Susceptibility Mapping ◽

The Brain ◽

Lateral Sclerosis

Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.

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Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis

NeuroImage Clinical ◽

10.1016/j.nicl.2019.101953 ◽

2019 ◽

Vol 24 ◽

pp. 101953 ◽

Cited By ~ 7

Author(s):

Thomas Welton ◽

Jerome J. Maller ◽

R. Marc Lebel ◽

Ek T. Tan ◽

Dominic B. Rowe ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Susceptibility Mapping ◽

Quantitative Susceptibility Mapping ◽

Structural Abnormalities ◽

Diffusion Kurtosis ◽

Lateral Sclerosis

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Serial assessment of iron in the motor cortex in limb-onset Amyotrophic Lateral Sclerosis using Quantitative Susceptibility Mapping

10.1101/865709 ◽

2019 ◽

Author(s):

Anjan Bhattarai ◽

Zhaolin Chen ◽

Phillip G. D. Ward ◽

Paul Talman ◽

Susan Mathers ◽

...

Keyword(s):

Motor Cortex ◽

Iron Concentration ◽

Motor Area ◽

Healthy Controls ◽

Quantitative Susceptibility Mapping ◽

Iron Dysregulation ◽

Als Patients ◽

Lateral Sclerosis ◽

Limb Onset

ABSTRACTObjectiveDysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with Amyotrophic Lateral Sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based Quantitative Susceptibility Mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a six-month period.MethodsIron concentration was investigated using magnetic resonance based -QSM in the primary motor cortex and the pre-motor area in thirteen limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and eleven age and sex-matched healthy controls. Nine ALS patients underwent follow-up scans at six months.ResultsSignificantly increased QSM was observed in the left posterior primary motor area (p = 0.02, Cohen’s d = 0.9) and right anterior primary motor area (p = 0.02, Cohen’s d = 0.92) in all individuals with limb-onset ALS compared to healthy controls. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to healthy controls. No significant change in QSM was observed at the six-month follow-up scans in the ALS patients.ConclusionsThe findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a radiological indicator in disease diagnosis, and in clinical trials in limb-onset ALS and its subtypes.HighlightsSerial measurement of QSM in the motor cortex in limb-onset ALS was performedQSM changes in the motor cortex in ALS sub-groups were investigatedHigher QSM was observed in the motor cortex in Lumbar ALS relative to controlsQSM is sensitive to iron dysregulation in the motor cortex in limb-onset ALS

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A specific biomarker for amyotrophic lateral sclerosis: Quantitative susceptibility mapping

Clinical Imaging ◽

10.1016/j.clinimag.2020.12.018 ◽

2021 ◽

Author(s):

Kathryn Dean ◽

Beiyi Shen ◽

Gulce Askin ◽

Andrew D. Schweitzer ◽

Mona Shahbazi ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Susceptibility Mapping ◽

Quantitative Susceptibility Mapping ◽

Lateral Sclerosis

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Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

Journal of Speech Language and Hearing Research ◽

10.1044/2019_jslhr-19-00178 ◽

2020 ◽

Vol 63 (1) ◽

pp. 59-73 ◽

Cited By ~ 3

Author(s):

Panying Rong

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Acoustic Analysis ◽

Speaking Rate ◽

Disease Stage ◽

Healthy Controls ◽

Tongue Movement ◽

Major Barrier ◽

Syllable Repetition ◽

Oral Diadochokinesis ◽

Lateral Sclerosis

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

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Lingual–Alveolar Contact Pressure During Speech in Amyotrophic Lateral Sclerosis: Preliminary Findings

Journal of Speech Language and Hearing Research ◽

10.1044/2016_jslhr-s-16-0107 ◽

2017 ◽

Vol 60 (4) ◽

pp. 810-825 ◽

Cited By ~ 5

Author(s):

Jeff Searl ◽

Stephanie Knollhoff ◽

Richard J. Barohn

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Healthy Volunteers ◽

Contact Pressure ◽

Statistical Difference ◽

Healthy Controls ◽

Perceptual Judgments ◽

Before And After ◽

Preliminary Study ◽

Contact Pressures ◽

Lateral Sclerosis

Purpose This preliminary study on lingual–alveolar contact pressures (LACP) in people with amyotrophic lateral sclerosis (ALS) had several aims: (a) to evaluate whether the protocol induced fatigue, (b) to compare LACP during speech (LACP-Sp) and during maximum isometric pressing (LACP-Max) in people with ALS (PALS) versus healthy controls, (c) to compare the percentage of LACP-Max utilized during speech (%Max) for PALS versus controls, and (d) to evaluate relationships between LACP-Sp and LACP-Max with word intelligibility. Method Thirteen PALS and 12 healthy volunteers produced /t, d, s, z, l, n/ sounds while LACP-Sp was recorded. LACP-Max was obtained before and after the speech protocol. Word intelligibility was obtained from auditory–perceptual judgments. Results LACP-Max values measured before and after completion of the speech protocol did not differ. LACP-Sp and LACP-Max were statistically lower in the ALS bulbar group compared with controls and PALS with only spinal symptoms. There was no statistical difference between groups for %Max. LACP-Sp and LACP-Max were correlated with word intelligibility. Conclusions It was feasible to obtain LACP-Sp measures without inducing fatigue. Reductions in LACP-Sp and LACP-Max for bulbar speakers might reflect tongue weakness. Although confirmation of results is needed, the data indicate that individuals with high word intelligibility maintained LACP-Sp at or above 2 kPa and LACP-Max at or above 50 kPa.

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