Association Between Enlarged Perivascular Spaces and White Matter Microstructure

HomeStrokeVol. 52, No. 11Association Between Enlarged Perivascular Spaces and White Matter Microstructure Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toSupplementary MaterialsFree AccessLetterPDF/EPUBAssociation Between Enlarged Perivascular Spaces and White Matter Microstructure Zi-Yue Liu, MD, Si-Yu Chen, MD, Mei-Jun Shu, MD, Fei-Fei Zhai, MD, Fei Han, MD, Li-Xin Zhou, MD, Jun Ni, MD, PhD, Ming Yao, MD, Shu-Yang Zhang, MD, PhD, Zheng-Yu Jin, MD, Li-Ying Cui, MD, PhD and Yi-Cheng Zhu, MD, PhD Zi-Yue LiuZi-Yue Liu https://orcid.org/0000-0002-3246-2301 Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Si-Yu ChenSi-Yu Chen Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, China (S.-Y.C.). Search for more papers by this author , Mei-Jun ShuMei-Jun Shu https://orcid.org/0000-0001-7584-5508 Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Fei-Fei ZhaiFei-Fei Zhai Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Fei HanFei Han Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Li-Xin ZhouLi-Xin Zhou Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Jun NiJun Ni Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Ming YaoMing Yao Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Shu-Yang ZhangShu-Yang Zhang Department of Cardiology (S.-Y.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Zheng-Yu JinZheng-Yu Jin https://orcid.org/0000-0002-6179-9632 Department of Radiology (Z.-Y.J.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author , Li-Ying CuiLi-Ying Cui Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author and Yi-Cheng ZhuYi-Cheng Zhu Correspondence to: Yi-Cheng Zhu, MD, PhD, No. 1 Shuaifuyuan, Wangfujing, Beijing 100730, China. Email E-mail Address: [email protected] https://orcid.org/0000-0002-8966-1379 Department of Neurology (Z.-Y.L., M.-J.S., F.-F.Z., F.H., L.-X.Z., J.N., M.Y., L.-Y.C., Y.-C.Z.), State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Search for more papers by this author Originally published30 Sep 2021https://doi.org/10.1161/STROKEAHA.121.036077Stroke. 2021;52:e744–e745Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 30, 2021: Ahead of Print Enlarged perivascular spaces (EPVSs) are found to play a potential role in interstitial fluid drainage,1,2 and their microstructural relations are not fully understood. In a large sample of community-based population, we investigated how are EPVS associated with white matter (WM) microstructural integrity via diffusion tensor images technique and free water (FW) elimination mode. We hypothesis that severe EPVS is related to WM microstructural damage.MethodsAnonymized data will be shared by request from the qualified investigator after ethics clearance and approval by all members of the project group.This was a cross-sectional study on baseline data of the Shunyi cohort study (Figure I in the Data Supplement). The burden of EPVS in basal ganglia and WM were visually rated3 and trichotomized into mild, moderate, and severe (weighted κ coefficient, 0.75 and 0.67, in basal ganglia and WM separately).Based on single-shell diffusion tensor images, diffusion metrics maps were accessed using PANDA (https://www.nitrc.org/projects/panda/), while FW diffusion mode maps were created using DIPY (http://nipy.org/dipy/index.html).4 Tract-based spatial statistics (FMRIB Center, Oxford, United Kingdom) were applied for voxel-wise analyses.An informed consent form was signed by each participant, and this study was approved by the Medical Review Ethics Committee of Peking Union Medical College Hospital (Reference number: B-160).ResultsWe included 1025 participants: the mean age was 55.5 years (range, 35–80 years) and 362 (35.3%) of the participants were female.Voxel-wise diffusion tensor image analysis results (Figure): In both basal ganglia and WM, participants with severe EPVS had significantly lower fractional anisotropy and higher mean diffusivity in diffusely scattered regions on the WM skeleton. In the FW diffusion mode, higher FW-corrected mean diffusivity values associated with severe EPVS were also observed across widespread regions in all models.Download figureDownload PowerPointFigure. Tract-based spatial statistics analysis of the diffusion metrics in severe vs mild enlarged perivascular space groups.A and B show comparisons of diffusion metrics of severe vs mild groups in basal ganglia and white matter, respectively; red or blue colormaps indicate threshold-free cluster enhancement corrected P<0.05. Model 1: adjusted for age and sex; model 2: additionally adjusted for the presence of lacunes, cerebral microbleeds, and white matter hyperintensity volume. FA indicates fractional anisotropy; MD, mean diffusivity; t-FA, tissue compartment of FA; and t-MD, tissue compartment of MD.DiscussionIn a large community population, we observed severe EPVS associated with widespread WM microstructural damage presented by diffusion tensor image metrics. This is consistent with Audrey et al’s findings.2 Further, by cutting down FW contamination from EPVSs, we revealed close-to-truth WM structural damage related to EPVS burden. Limited by the accuracy of the single-shell FW model, future research using advanced multi-shell acquisitions is expected to better illustrate the structural relations of EPVS.Sources of FundingThis study was funded by National Key Research and Development Program of China (No. 2016YFC0901004), National Natural Science Foundation of China (No. 81971138), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS No. 2017-I2M-3-008), and the Strategic Priority Research Program “Biological basis of aging and therapeutic strategies” of the Chinese Academy of Sciences (grant XDB39040300).Supplemental MaterialsExpanded Methods and ResultsOnline FigureOnline Tables I and IIDisclosures None.FootnotesThis manuscript was sent to Liping Liu, Guest Editor, for review by expert referees, editorial decision, and final disposition.The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.121.036077.For Sources of Funding and Disclosures, see page e744–e745.Correspondence to: Yi-Cheng Zhu, MD, PhD, No. 1 Shuaifuyuan, Wangfujing, Beijing 100730, China. Email [email protected]comcnReferences1. Wardlaw JM, Benveniste H, Nedergaard M, Zlokovic BV, Mestre H, Lee H, Doubal FN, Brown R, Ramirez J, MacIntosh BJ, et al.; colleagues from the Fondation Leducq Transatlantic Network of Excellence on the Role of the Perivascular Space in Cerebral Small Vessel Disease. Perivascular spaces in the brain: anatomy, physiology and pathology.Nat Rev Neurol. 2020; 16:137–153. doi: 10.1038/s41582-020-0312-zGoogle Scholar2. Low A, Mak E, Stefaniak JD, Malpetti M, Nicastro N, Savulich G, Chouliaras L, Markus HS, Rowe JB, O’Brien JT. Peak width of skeletonized mean diffusivity as a marker of diffuse cerebrovascular damage.Front Neurosci. 2020; 14:238. doi: 10.3389/fnins.2020.00238CrossrefMedlineGoogle Scholar3. Zhu YC, Dufouil C, Mazoyer B, Soumaré A, Ricolfi F, Tzourio C, Chabriat H. Frequency and location of dilated Virchow-Robin spaces in elderly people: a population-based 3D MR imaging study.AJNR Am J Neuroradiol. 2011; 32:709–713. doi: 10.3174/ajnr.A2366CrossrefMedlineGoogle Scholar4. Garyfallidis E, Brett M, Amirbekian B, Rokem A, van der Walt S, Descoteaux M, Nimmo-Smith I; Dipy Contributors. Dipy, a library for the analysis of diffusion MRI data.Front Neuroinform. 2014; 8:8. doi: 10.3389/fninf.2014.00008Google Scholar Previous Back to top Next FiguresReferencesRelatedDetails November 2021Vol 52, Issue 11Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.121.036077PMID: 34587792 Originally publishedSeptember 30, 2021 Keywordscross-sectional studieswhite mattercohort studiesneuroimagingcerebral small vessel diseasesPDF download Advertisement SubjectsImagingMagnetic Resonance Imaging (MRI)Vascular Disease