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Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients
- Source :
- Frontiers in Neurology, Vol 11 (2020), Frontiers in Neurology
- Publication Year :
- 2020
- Publisher :
- Frontiers Media SA, 2020.
-
Abstract
- Background: Oxidative stress and protein aggregation are key mechanisms in amyotrophic lateral sclerosis (ALS) disease. Reduced glutathione (GSH) is the most important intracellular antioxidant that protects neurons from reactive oxygen species. We hypothesized that levels of GSH measured by MR spectroscopic imaging (MRSI) in the motor cortex and corticospinal tract are linked to clinical trajectory of ALS patients.Objectives: Investigate the value of GSH imaging to probe clinical decline of ALS patients in combination with other neurochemical and structural parameters.Methods: Twenty-four ALS patients were imaged at 3 T with an advanced MR protocol. Mapping GSH levels in the brain is challenging, and for this purpose, we used an optimized spectral-edited 3D MRSI sequence with real-time motion and field correction to image glutathione and other brain metabolites. In addition, our imaging protocol included (i) an adiabatic T1ρ sequence to image macromolecular fraction of brain parenchyma, (ii) diffusion tensor imaging (DTI) for white matter tractography, and (iii) high-resolution anatomical imaging.Results: We found GSH in motor cortex (r = −0.431, p = 0.04) and corticospinal tract (r = −0.497, p = 0.016) inversely correlated with time between diagnosis and imaging. N-Acetyl-aspartate (NAA) in motor cortex inversely correlated (r = −0.416, p = 0.049), while mean water diffusivity (r = 0.437, p = 0.033) and T1ρ (r = 0.482, p = 0.019) positively correlated with disease progression measured by imputed change in revised ALS Functional Rating Scale. There is more decrease in the motor cortex than in the white matter for GSH compared to NAA, glutamate, and glutamine.Conclusions: Our study suggests that a panel of biochemical and structural imaging biomarkers defines a brain endophenotype, which can be used to time biological events and clinical progression in ALS patients. Such a quantitative brain endophenotype may stratify ALS patients into more homogeneous groups for therapeutic interventions compared to clinical criteria.
- Subjects :
- Pathology
medicine.medical_specialty
amyotrophic lateral sclerosis (ALS)
macromolecular fraction
neurochemistry
T1 relaxation in the rotating frame (T1rho)
diffusion tensor imaging (DTI)
lcsh:RC346-429
White matter
Neurochemical
medicine
Neurochemistry
magnetic resonance spectroscopic imaging (MRSI)
Amyotrophic lateral sclerosis
lcsh:Neurology. Diseases of the nervous system
Original Research
business.industry
Neurodegeneration
neurodegeneration
medicine.disease
glutathione (GSH)
medicine.anatomical_structure
Neurology
Corticospinal tract
Neurology (clinical)
business
Diffusion MRI
Motor cortex
Subjects
Details
- ISSN :
- 16642295
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Neurology
- Accession number :
- edsair.doi.dedup.....4c70ce4617a91e1df383c785a7326fa3
- Full Text :
- https://doi.org/10.3389/fneur.2020.590573