Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging
Abstract Background White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypoth...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-021-00264-1 |
| _version_ | 1818907570758221824 |
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| author | Xinfeng Yu Xinzhen Yin Hui Hong Shuyue Wang Yeerfan Jiaerken Fan Zhang Ofer Pasternak Ruiting Zhang Linglin Yang Min Lou Minming Zhang Peiyu Huang |
| author_facet | Xinfeng Yu Xinzhen Yin Hui Hong Shuyue Wang Yeerfan Jiaerken Fan Zhang Ofer Pasternak Ruiting Zhang Linglin Yang Min Lou Minming Zhang Peiyu Huang |
| author_sort | Xinfeng Yu |
| collection | DOAJ |
| description | Abstract Background White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs. Methods Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds. Results We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds. Conclusions Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future. |
| first_indexed | 2024-12-19T21:57:14Z |
| format | Article |
| id | doaj.art-ee558ff922ea4951b1379accfdd4f931 |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-12-19T21:57:14Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-ee558ff922ea4951b1379accfdd4f9312022-12-21T20:04:15ZengBMCFluids and Barriers of the CNS2045-81182021-06-0118111310.1186/s12987-021-00264-1Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imagingXinfeng Yu0Xinzhen Yin1Hui Hong2Shuyue Wang3Yeerfan Jiaerken4Fan Zhang5Ofer Pasternak6Ruiting Zhang7Linglin Yang8Min Lou9Minming Zhang10Peiyu Huang11Department of Radiology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Radiology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Radiology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Radiology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Radiology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Radiology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Radiology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Psychiatry, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Radiology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineDepartment of Radiology, The 2nd Affiliated Hospital, Zhejiang University School of MedicineAbstract Background White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs. Methods Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds. Results We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds. Conclusions Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future.https://doi.org/10.1186/s12987-021-00264-1White matterExtracellular fluidCerebral small vessel diseasesCADASILMRIDiffusion-weighted imaging |
| spellingShingle | Xinfeng Yu Xinzhen Yin Hui Hong Shuyue Wang Yeerfan Jiaerken Fan Zhang Ofer Pasternak Ruiting Zhang Linglin Yang Min Lou Minming Zhang Peiyu Huang Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging Fluids and Barriers of the CNS White matter Extracellular fluid Cerebral small vessel diseases CADASIL MRI Diffusion-weighted imaging |
| title | Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging |
| title_full | Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging |
| title_fullStr | Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging |
| title_full_unstemmed | Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging |
| title_short | Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging |
| title_sort | increased extracellular fluid is associated with white matter fiber degeneration in cadasil in vivo evidence from diffusion magnetic resonance imaging |
| topic | White matter Extracellular fluid Cerebral small vessel diseases CADASIL MRI Diffusion-weighted imaging |
| url | https://doi.org/10.1186/s12987-021-00264-1 |
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