In vivo characterization of white matter pathology in premanifest huntington's disease
Open accessAbstract
Objective: Huntington's disease (HD) is a monogenic, fully penetrant neurodegenerative disorder, providing an ideal model for understanding brain changes occurring in the years prior to disease onset. Diffusion tensor imaging (DTI) studies show widespread white matter disorganization in the early premanifest stages (pre‐HD). However, although DTI has proved informative, it provides only limited information about underlying changes in tissue properties. Neurite orientation dispersion and density imaging (NODDI) is a novel magnetic resonance imaging (MRI) technique for characterizing axonal pathology more specifically, providing metrics that separately quantify axonal density and axonal organization. Here, we provide the first in vivo characterization of white matter pathology in pre‐HD using NODDI. Methods: Diffusion‐weighted MRI data that support DTI and NODDI were acquired from 38 pre‐HD and 45 control participants. Using whole‐brain and region‐of‐interest analyses, NODDI metrics were compared between groups and correlated with clinical scores of disease progression. Whole‐brain changes in DTI metrics were also examined. Results: The pre‐HD group displayed widespread reductions in axonal density compared with control participants; this correlated with measures of clinical disease progression in the body and genu of the corpus callosum. There was also evidence in the pre‐HD group of increased coherence of axonal packing in the white matter surrounding the basal ganglia. Interpretation: Our findings suggest that reduced axonal density is one of the major factors underlying white matter pathology in pre‐HD, coupled with altered local organization in areas surrounding the basal ganglia. NODDI metrics show promise in providing more specific information about the biological processes underlying HD and neurodegeneration per se. Ann Neurol 2018;84:497–504
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- Authors
- Zhang, J., Gregory, S., Scahill, R. I., Durr, A., Thomas, D. L., Lehericy, S., Rees, G., Tabrizi, S. J., Zhang, H., & the TrackOn‐HD investigators
- Affiliations
- University College London (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- UCL Queen Square Institute of Neurology (GB)
- ICM – Institut du Cerveau et de la Moelle Epinière, INSERM U1127, CNRS UMR7225, Sorbonne Universités – UPMC Université Paris VI UMR_S1127 and APHP, Genetic department Pitié–Salpêtrière University Hospital Paris France
- Neuroimaging Research Center, Brain and Spinal Cord Institute Pierre and Marie Curie University, Inserm UMR1127, CNRS 7225 Paris France
- Corresponding author
- Zhang, Jiaying
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2018-09-15
- Volume
- 84
- Issue
- 4
- Pages
- 497-504
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC6221120
- OpenAlex
- W2887241590
- Cited by
- 80
- References
- 32
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 9 · 2023: 6 · 2022: 12 · 2021: 14 · 2020: 8 · 2019: 11 · 2018: 4
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- CHDI Foundation
- China Scholarship Council
- Engineering and Physical Sciences Research Council (EP/L022680/1)
- Wellcome Trust (200181/Z/15/Z)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- premanifest Huntington's disease, white matter pathology, NODDI, axon density, corpus callosum, basal ganglia, neurodegeneration, disease progression, diffusion MRI
- MeSH terms
- Adult, Aged, Brain, Female, Humans, Huntington Disease, Male, Middle Aged, Diffusion Tensor Imaging, Prodromal Symptoms, White Matter
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