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Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients.
Andronesi, Ovidiu C; Nicholson, Katharine; Jafari-Khouzani, Kourosh; Bogner, Wolfgang; Wang, Jing; Chan, James; Macklin, Eric A; Levine-Weinberg, Mark; Breen, Christopher; Schwarzschild, Michael A; Cudkowicz, Merit; Rosen, Bruce R; Paganoni, Sabrina; Ratai, Eva-Maria.
Afiliação
  • Andronesi OC; Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.
  • Nicholson K; Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United States.
  • Jafari-Khouzani K; Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.
  • Bogner W; High Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
  • Wang J; Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.
  • Chan J; Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Macklin EA; Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States.
  • Levine-Weinberg M; Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States.
  • Breen C; Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United States.
  • Schwarzschild MA; Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United States.
  • Cudkowicz M; MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, United States.
  • Rosen BR; Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United States.
  • Paganoni S; Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.
  • Ratai EM; Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United States.
Front Neurol ; 11: 590573, 2020.
Article em En | MEDLINE | ID: mdl-33343494
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Guideline Idioma: En Revista: Front Neurol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Guideline Idioma: En Revista: Front Neurol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos