Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients
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 spec...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2020.590573/full |
| _version_ | 1818431468158844928 |
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| author | Ovidiu C. Andronesi Katharine Nicholson Kourosh Jafari-Khouzani Wolfgang Bogner Jing Wang Jing Wang James Chan Eric A. Macklin Mark Levine-Weinberg Christopher Breen Michael A. Schwarzschild Merit Cudkowicz Bruce R. Rosen Sabrina Paganoni Sabrina Paganoni Eva-Maria Ratai |
| author_facet | Ovidiu C. Andronesi Katharine Nicholson Kourosh Jafari-Khouzani Wolfgang Bogner Jing Wang Jing Wang James Chan Eric A. Macklin Mark Levine-Weinberg Christopher Breen Michael A. Schwarzschild Merit Cudkowicz Bruce R. Rosen Sabrina Paganoni Sabrina Paganoni Eva-Maria Ratai |
| author_sort | Ovidiu C. Andronesi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T15:49:47Z |
| format | Article |
| id | doaj.art-95731cf9e77c4393b38ac41422e028cd |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-14T15:49:47Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-95731cf9e77c4393b38ac41422e028cd2022-12-21T22:55:24ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-12-011110.3389/fneur.2020.590573590573Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in PatientsOvidiu C. Andronesi0Katharine Nicholson1Kourosh Jafari-Khouzani2Wolfgang Bogner3Jing Wang4Jing Wang5James Chan6Eric A. Macklin7Mark Levine-Weinberg8Christopher Breen9Michael A. Schwarzschild10Merit Cudkowicz11Bruce R. Rosen12Sabrina Paganoni13Sabrina Paganoni14Eva-Maria Ratai15Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United StatesNeurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United StatesDepartment of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United StatesHigh Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, AustriaDepartment of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBiostatistics Center, Massachusetts General Hospital, Boston, MA, United StatesBiostatistics Center, Massachusetts General Hospital, Boston, MA, United StatesNeurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United StatesNeurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United StatesMassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, United StatesNeurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United StatesDepartment of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United StatesNeurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, United StatesSpaulding Rehabilitation Hospital, Boston, MA, United StatesDepartment of Radiology, A. A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United StatesBackground: 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.https://www.frontiersin.org/articles/10.3389/fneur.2020.590573/fullmagnetic resonance spectroscopic imaging (MRSI)neurochemistryglutathione (GSH)neurodegenerationT1 relaxation in the rotating frame (T1rho)macromolecular fraction |
| spellingShingle | Ovidiu C. Andronesi Katharine Nicholson Kourosh Jafari-Khouzani Wolfgang Bogner Jing Wang Jing Wang James Chan Eric A. Macklin Mark Levine-Weinberg Christopher Breen Michael A. Schwarzschild Merit Cudkowicz Bruce R. Rosen Sabrina Paganoni Sabrina Paganoni Eva-Maria Ratai Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients Frontiers in Neurology magnetic resonance spectroscopic imaging (MRSI) neurochemistry glutathione (GSH) neurodegeneration T1 relaxation in the rotating frame (T1rho) macromolecular fraction |
| title | Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients |
| title_full | Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients |
| title_fullStr | Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients |
| title_full_unstemmed | Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients |
| title_short | Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients |
| title_sort | imaging neurochemistry and brain structure tracks clinical decline and mechanisms of als in patients |
| topic | magnetic resonance spectroscopic imaging (MRSI) neurochemistry glutathione (GSH) neurodegeneration T1 relaxation in the rotating frame (T1rho) macromolecular fraction |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2020.590573/full |
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