Dataset Information

Cerebral degeneration in amyotrophic lateral sclerosis: A prospective multicenter magnetic resonance spectroscopy study.

ABSTRACT: Background:We investigated cerebral degeneration and neurochemistry in patients with amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS). Methods:We 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. Results:In 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. Conclusions:This 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.

SUBMITTER: Srivastava O

PROVIDER: S-EPMC6814429 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cerebral degeneration in amyotrophic lateral sclerosis: A prospective multicenter magnetic resonance spectroscopy study.

Srivastava Ojas O Hanstock Chris C Chenji Sneha S Mah Dennell D Eurich Dean D Ta Daniel D Seres Peter P Luk Collin C Zinman Lorne L Abrahao Agessandro A Graham Simon J SJ Genge Angela A Korngut Lawrence L Frayne Richard R Kalra Sanjay S

Neurology. Clinical practice 20191001 5

<h4>Background</h4>We investigated cerebral degeneration and neurochemistry in patients with amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS).<h4>Methods</h4>We 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 ...[more]

PMID: 31750025

Similar Datasets

Project description:The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA + NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P = 0.005, respectively) indicating neuronal injury and/or loss in the precentral gyrus. tNA correlated with disease progression as measured by forced vital capacity (FVC) (P = 0.014; Rρ = 0.66) and tNA/tCr correlated with overall functional decline as measured by worsening of the ALS Functional Rating Scale-Revised (ALSFRS-R) (P = 0.004; Rρ = -0.74). These findings underscore the importance of NAA as a reliable biomarker for neuronal injury and disease progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC (P = 0.013; Rρ = 0.66), a clinical marker of disease progression. The decrease in Glu is most likely driven by intracellular Glu loss due to neuronal loss and degeneration. Neither choline containing components (Cho), a marker for cell membrane turnover, nor myo-Inositol (mI), a suspected marker for neuroinflammation, showed significant differences between the two groups. However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rρ = 0.74), which may reflect a relative increase of activated microglia around motor neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to study molecular changes related to neuronal injury and/or loss in people with ALS.

Project description:(1) Background: This work characterizes the sensitivity of magnetic resonance-based Relaxivity Contrast Imaging (RCI) to Amyotrophic Lateral Sclerosis (ALS)-induced changes in myofiber microstructure. Transverse Relaxivity at Tracer Equilibrium (TRATE), an RCI-based parameter, was evaluated in the lower extremities of ALS patients and healthy subjects. (2) Methods: In this IRB-approved study, 23 subjects (12 ALS patients and 11 healthy controls) were scanned at 3T (Philips, The Netherlands). RCI data were obtained during injection of a gadolinium-based contrast agent. TRATE, fat fraction and T2 measures, were compared in five muscle groups of the calf muscle, between ALS and control populations. TRATE was also evaluated longitudinally (baseline and 6 months) and was compared to clinical measures, namely ALS Functional Rating Scale (ALSFRS-R) and Hand-Held Dynamometry (HHD), in a subset of the ALS population. (3) Results: TRATE was significantly lower (p < 0.001) in ALS-affected muscle than in healthy muscle in all muscle groups. Fat fraction differences between ALS and healthy muscle were statistically significant for the tibialis anterior (p = 0.01), tibialis posterior (p = 0.004), and peroneus longus (p = 0.02) muscle groups but were not statistically significant for the medial (p = 0.07) and lateral gastrocnemius (p = 0.06) muscles. T2 differences between ALS and healthy muscle were statistically significant for the tibialis anterior (p = 0.004), peroneus longus (p = 0.004) and lateral gastrocnemius (p = 0.03) muscle groups but were not statistically significant for the tibialis posterior (p = 0.06) and medial gastrocnemius (p = 0.07) muscles. Longitudinally, TRATE, averaged over all patients, decreased by 28 ± 16% in the tibialis anterior, 47 ± 18% in the peroneus longus, 25 ± 19% in the tibialis posterior, 29 ± 14% in the medial gastrocnemius and 35 ± 18% in the lateral gastrocnemius muscles between two timepoints. ALSFRS-R scores were stable in two of four ALS patients. HHD scores decreased in three of four ALS patients. (4) Conclusion: RCI-based TRATE was shown to consistently differentiate ALS-affected muscle from healthy muscle and also provide a quantitative measure of longitudinal muscle degeneration.

Dataset Information

Cerebral degeneration in amyotrophic lateral sclerosis: A prospective multicenter magnetic resonance spectroscopy study.

Publications

Cerebral degeneration in amyotrophic lateral sclerosis: A prospective multicenter magnetic resonance spectroscopy study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets