Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s disease
Introduction: Strong evidence suggests a significant role for iron accumulation in the brain in addition to the well-documented neurodegenerative aspects of Huntington’s disease (HD). The putative mechanisms by which iron is linked to the HD pathogenesis are multiple, including oxidative stress, fer...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | NeuroImage: Clinical |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158223001390 |
| _version_ | 1797802865360633856 |
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| author | Nadine Anniek van de Zande Marjolein Bulk Chloé Najac Louise van der Weerd Jeroen de Bresser Jan Lewerenz Itamar Ronen Susanne Tamara de Bot |
| author_facet | Nadine Anniek van de Zande Marjolein Bulk Chloé Najac Louise van der Weerd Jeroen de Bresser Jan Lewerenz Itamar Ronen Susanne Tamara de Bot |
| author_sort | Nadine Anniek van de Zande |
| collection | DOAJ |
| description | Introduction: Strong evidence suggests a significant role for iron accumulation in the brain in addition to the well-documented neurodegenerative aspects of Huntington’s disease (HD). The putative mechanisms by which iron is linked to the HD pathogenesis are multiple, including oxidative stress, ferroptosis and neuroinflammation. However, no previous study in a neurodegenerative disease has linked the observed increase of brain iron accumulation as measured by MRI with well-established cerebrospinal fluid (CSF) and blood biomarkers for iron accumulation, or with associated processes such as neuroinflammation. This study is designed to link quantitative data from iron levels and neuroinflammation metabolites obtained from 7T MRI of HD patients, with specific and well-known clinical biofluid markers for iron accumulation, neurodegeneration and neuroinflammation. Biofluid markers will provide quantitative measures of overall iron accumulation, neurodegeneration and neuroinflammation, while MRI measurements on the other hand will provide quantitative spatial information on brain pathology, neuroinflammation and brain iron accumulation, which will be linked to clinical outcome measures. Methods: This is an observational cross-sectional study, IMAGINE-HD, in HD gene expansion carriers and healthy controls. We include premanifest HD gene expansion carriers and patients with manifest HD in an early or moderate stage. The study includes a 7T MRI scan of the brain, clinical evaluation, motor, functional, and neuropsychological assessments, and sampling of CSF and blood for the detection of iron, neurodegenerative and inflammatory markers. Quantitative Susceptibility Maps will be reconstructed using T2* weighted images to quantify brain iron levels and Magnetic Resonance Spectroscopy will be used to obtain information about neuroinflammation by measuring cell-specific intracellular metabolites’ level and diffusion. Age and sex matched healthy subjects are included as a control group. Discussion: Results from this study will provide an important basis for the evaluation of brain iron levels and neuroinflammation metabolites as an imaging biomarker for disease stage in HD and their relationship with the salient pathomechanisms of the disease on the one hand, and with clinical outcome on the other. |
| first_indexed | 2024-03-13T05:12:13Z |
| format | Article |
| id | doaj.art-9b3db2c2e5004b92ac3389c1fe28e6ac |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-03-13T05:12:13Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-9b3db2c2e5004b92ac3389c1fe28e6ac2023-06-16T05:09:41ZengElsevierNeuroImage: Clinical2213-15822023-01-0139103450Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s diseaseNadine Anniek van de Zande0Marjolein Bulk1Chloé Najac2Louise van der Weerd3Jeroen de Bresser4Jan Lewerenz5Itamar Ronen6Susanne Tamara de Bot7Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands; Corresponding author.C.J. Gorter MRI Center, Department of Radiology, Leiden University Medical Centre, Leiden, The NetherlandsC.J. Gorter MRI Center, Department of Radiology, Leiden University Medical Centre, Leiden, The NetherlandsDepartment of Radiology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Centre, Leiden, The NetherlandsDepartment of Radiology, Leiden University Medical Centre, Leiden, The NetherlandsDepartment of Neurology, University of Ulm, Ulm, Baden-Württemberg, GermanyClinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, United KingdomDepartment of Neurology, Leiden University Medical Centre, Leiden, The NetherlandsIntroduction: Strong evidence suggests a significant role for iron accumulation in the brain in addition to the well-documented neurodegenerative aspects of Huntington’s disease (HD). The putative mechanisms by which iron is linked to the HD pathogenesis are multiple, including oxidative stress, ferroptosis and neuroinflammation. However, no previous study in a neurodegenerative disease has linked the observed increase of brain iron accumulation as measured by MRI with well-established cerebrospinal fluid (CSF) and blood biomarkers for iron accumulation, or with associated processes such as neuroinflammation. This study is designed to link quantitative data from iron levels and neuroinflammation metabolites obtained from 7T MRI of HD patients, with specific and well-known clinical biofluid markers for iron accumulation, neurodegeneration and neuroinflammation. Biofluid markers will provide quantitative measures of overall iron accumulation, neurodegeneration and neuroinflammation, while MRI measurements on the other hand will provide quantitative spatial information on brain pathology, neuroinflammation and brain iron accumulation, which will be linked to clinical outcome measures. Methods: This is an observational cross-sectional study, IMAGINE-HD, in HD gene expansion carriers and healthy controls. We include premanifest HD gene expansion carriers and patients with manifest HD in an early or moderate stage. The study includes a 7T MRI scan of the brain, clinical evaluation, motor, functional, and neuropsychological assessments, and sampling of CSF and blood for the detection of iron, neurodegenerative and inflammatory markers. Quantitative Susceptibility Maps will be reconstructed using T2* weighted images to quantify brain iron levels and Magnetic Resonance Spectroscopy will be used to obtain information about neuroinflammation by measuring cell-specific intracellular metabolites’ level and diffusion. Age and sex matched healthy subjects are included as a control group. Discussion: Results from this study will provide an important basis for the evaluation of brain iron levels and neuroinflammation metabolites as an imaging biomarker for disease stage in HD and their relationship with the salient pathomechanisms of the disease on the one hand, and with clinical outcome on the other.http://www.sciencedirect.com/science/article/pii/S2213158223001390Huntington’s diseaseBiomarkersIron accumulationNeuroinflammationMRICSF |
| spellingShingle | Nadine Anniek van de Zande Marjolein Bulk Chloé Najac Louise van der Weerd Jeroen de Bresser Jan Lewerenz Itamar Ronen Susanne Tamara de Bot Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s disease NeuroImage: Clinical Huntington’s disease Biomarkers Iron accumulation Neuroinflammation MRI CSF |
| title | Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s disease |
| title_full | Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s disease |
| title_fullStr | Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s disease |
| title_full_unstemmed | Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s disease |
| title_short | Study protocol of IMAGINE-HD: Imaging iron accumulation and neuroinflammation with 7T-MRI + CSF in Huntington’s disease |
| title_sort | study protocol of imagine hd imaging iron accumulation and neuroinflammation with 7t mri csf in huntington s disease |
| topic | Huntington’s disease Biomarkers Iron accumulation Neuroinflammation MRI CSF |
| url | http://www.sciencedirect.com/science/article/pii/S2213158223001390 |
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