期刊
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
卷 4, 期 9, 页码 663-679出版社
WILEY
DOI: 10.1002/acn3.445
关键词
-
资金
- UCL Grand Challenges scheme
- Horizon Framework Programme (H)-EU.3.1 CDS-QUAMRI grant [634541]
- Engineering and Physical Sciences Research Council (EPSRC) Platform Grant for medical image computing for next-generation healthcare technology [EP/M020533/1]
- UK Multiple Sclerosis Society [892/08]
- Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centres [BRC RD03/10/RAG0449]
- European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS)
- EPSRC [M507970, G007748, I027084, M020533, N018702]
- UK Multiple Sclerosis Society
- H-EU.3.1 [634541, 666992-2]
- Engineering and Physical Sciences Research Council [EP/G007748/1, EP/I027084/1, EP/L022680/1, EP/M020533/1, EP/N018702/1, EP/M00855X/1, EP/M029778/1] Funding Source: researchfish
- International Spinal Research Trust [IMG006] Funding Source: researchfish
- Medical Research Council [MR/L022656/1, MR/M009106/1] Funding Source: researchfish
- EPSRC [EP/M00855X/1, EP/G007748/1, EP/M029778/1, EP/N018702/1, EP/M020533/1, EP/I027084/1, EP/L022680/1] Funding Source: UKRI
- MRC [MR/M009106/1, MR/L022656/1] Funding Source: UKRI
Objective: Conventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging, NODDI), to demonstrate the strong potential of the new marker. Methods: We related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion. Results: We report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI-derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates. Interpretation: Neurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据