ArticleAnnals of clinical and translational neurology2019
White matter mean diffusivity correlates with myelination in tuberous sclerosis complex.
Article in Annals of clinical and translational neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology.NeuroImage · 2021Pooled it
- Pooled it
- Autism and Epilepsy in Patients With Tuberous Sclerosis Complex.Frontiers in neurology · 2020Pooled it
- Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?Annals of clinical and translational neurology · 2020Trial
- Colocalized White Matter Plasticity and Increased Cerebral Blood Flow Mediate the Beneficial Effect of Cardiovascular Exercise on Long-Term Motor Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Trial
- ENT1 inhibitor J4 restores cognitive function and white-matter integrity in a mouse model of tuberous sclerosis complex.Journal of biomedical science · 2026Article
- The Mechanism Underlying the Abnormal Expression of α-Synuclein in the Cortical Lesions of Patients With FCD Type IIb and TSC.CNS neuroscience & therapeutics · 2026Article
- Development of the arcuate fasciculus is linked to learning gains in reading.Imaging neuroscience (Cambridge, Mass.) · 2025Article
- The role of TSC1 and TSC2 proteins in neuronal axons.Molecular psychiatry · 2024Review
- Amelioration of the brain structural connectivity is accompanied with changes of gut microbiota in a tuberous sclerosis complex mouse model.Translational psychiatry · 2024Article
- The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer's disease.Brain : a journal of neurology · 2024Review
- White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer's disease continuum.Alzheimer's research & therapy · 2023Article
- Non-invasive assessment of normal and impaired iron homeostasis in the brain.Nature communications · 2023Article
- An automated pipeline for extracting histological stain area fraction for voxelwise quantitative MRI-histology comparisons.NeuroImage · 2022Article
- Synthetic MRI in children with tuberous sclerosis complex.Insights into imaging · 2022Article
- Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders.Frontiers in neurology · 2022Article
- Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP.Molecular autism · 2020Article
- Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveDiffusion tensor imaging (DTI) of the white matter is a biomarker for neurological disease burden in tuberous sclerosis complex (TSC). To clarify the basis of abnormal diffusion in TSC, we correlated ex vivo high-resolution diffusion imaging with histopathology in four tissue types: cortex, tuber, perituber, and white matter.
methodsSurgical specimens of three children with TSC were scanned in a 3T or 7T MRI with a structural image isotropic resolution of 137-300 micron, and diffusion image isotropic resolution of 270-1,000 micron. We stained for myelin (luxol fast blue, LFB), gliosis (glial fibrillary acidic protein, GFAP), and neurons (NeuN) and registered the digitized histopathology slides (0.686 micron resolution) to MRI for visual comparison. We then performed colocalization analysis in four tissue types in each specimen. Finally, we applied a linear mixed model (LMM) for pooled analysis across the three specimens.
resultsIn white matter and perituber regions, LFB optical density measures correlated with fractional anisotropy (FA) and inversely with mean diffusivity (MD). In white matter only, GFAP correlated with MD, and inversely with FA. In tubers and in the cortex, there was little variation in mean LFB and GFAP signal intensity, and no correlation with MRI metrics. Neuronal density correlated with MD. In the analysis of the combined specimens, the most robust correlation was between white matter MD and LFB metrics.
interpretationIn TSC, diffusion imaging abnormalities in microscopic tissue types correspond to specific histopathological markers. Across all specimens, white matter diffusivity correlates with myelination.
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Registered trials
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