期刊
NEUROIMAGE-CLINICAL
卷 22, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2019.101699
关键词
Multiple sclerosis; Multi-shell diffusion MRI; Axonal pathology; Normal-appearing white matter
类别
资金
- National Institute of Health [NIH R01NS07832201 A1]
- Human Connectome Project, MGH-USC Consortium [NIH U01MH093765]
- NARSAD Young Investigator Grant [25104]
- European Research Council through a Marie Sklodowska-Curie Individual Fellowship [749506]
- Stockholm City Council (ALF grants) [20120213, 20150166]
- Karolinska Institutet (ALF grants) [20120213, 20150166]
- Swedish Society for Medical Research
- National Multiple Sclerosis Society [FG-1507-05459]
- [NIHP41EB015896]
- [10RR023043]
- [1S10RR023401]
- [1S10RR019307]
- Marie Curie Actions (MSCA) [749506] Funding Source: Marie Curie Actions (MSCA)
Irreversible white matter (WM) damage, including severe demyelination and axonal loss, is a main determinant of long-term disability in multiple sclerosis (MS). Non-invasive detection of changes in microstructural WM integrity in the disease is challenging since commonly used imaging metrics lack the necessary sensitivity, especially in the early phase of the disease. This study aims at assessing microstructural WM abnormalities in early-stage MS by using ultra-high gradient strength multi-shell diffusion MRI and the restricted signal fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED), a metric sensitive to the volume fraction of axons. In 22 early MS subjects (disease duration <= 5 years) and 15 age-matched healthy controls, restricted fraction estimates were obtained through the CHARMED model along with conventional Diffusion Tensor Imaging (DTI) metrics. All imaging parameters were compared cross-sectionally between the MS subjects and controls both in WM lesions and normal-appearing white matter (NAWM). We found a significant reduction in FR focally in WM lesions and widespread in the NAWM in MS patients relative to controls (corrected p < .05). Signal fraction changes in NAWM were not driven by perilesional tissue, nor were they influenced by proximity to the ventricles, challenging the hypothesis of an outside-in pathological process driven by CSF-mediated immune cytotoxic factors. No significant differences were found in conventional DTI parameters. In a cross-validated classification task, FR showed the largest effect size and outperformed all other diffusion imaging metrics in discerning lesions from contralateral NAWM. Taken together, our data provide evidence for the presence of widespread microstructural changes in the NAWM in early MS stages that are, at least in part, unrelated to focal demyelinating lesions. Interestingly, these pathological changes were not yet detectable by conventional diffusion imaging at this early disease stage, highlighting the sensitivity and value of multi-shell diffusion imaging for better characterizing axonal microstructure in MS.
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