A Novel Imaging Marker for Small Vessel Disease Based on Skeletonization of White Matter Tracts and Diffusion Histograms

被引:292
作者
Baykara, Ebru [1 ]
Gesierich, Benno [1 ]
Adam, Ruth [1 ]
Tuladhar, Anil Man [2 ]
Biesbroek, J. Matthijs [3 ]
Koek, Huiberdina L. [4 ]
Ropele, Stefan [5 ]
Jouvent, Eric [6 ,7 ,8 ]
Chabriat, Hugues [6 ,7 ,8 ]
Ertl-Wagner, Birgit [9 ]
Ewers, Michael [1 ]
Schmidt, Reinhold [5 ]
de Leeuw, Frank-Erik [2 ]
Biessels, Geert Jan [3 ]
Dichgans, Martin [1 ,10 ,11 ]
Duering, Marco [1 ]
机构
[1] LMU, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany
[2] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands
[3] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, Utrecht, Netherlands
[4] Univ Med Ctr Utrecht, Dept Geriatr, Utrecht, Netherlands
[5] Med Univ Graz, Dept Neurol, Graz, Austria
[6] Univ Paris Diderot, UMR S 1161, Sorbonne Paris Cite, Natl Inst Hlth & Med Res INSERM, Paris, France
[7] Sorbonne Paris Cite, Dept Hosp Univ NeuroVasc, Paris, France
[8] Lariboisiere Hosp, AP HP, Dept Neurol, Paris, France
[9] LMU, Klinikum Univ Munchen, Inst Clin Radiol, Munich, Germany
[10] Munich Cluster Syst Neurol SyNergy, Munich, Germany
[11] German Ctr Neurodegenerat Dis DZNE, Munich, Germany
关键词
COGNITIVE IMPAIRMENT; BRAIN; PROGRESSION; CADASIL; MRI;
D O I
10.1002/ana.24758
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To establish a fully automated, robust imaging marker for cerebral small vessel disease (SVD) and related cognitive impairment that is easy to implement, reflects disease burden, and is strongly associated with processing speed, the predominantly affected cognitive domain in SVD. Methods: We developed a novel magnetic resonance imaging marker based on diffusion tensor imaging, skeletonization of white matter tracts, and histogram analysis. The marker (peak width of skeletonized mean diffusivity [PSMD]) was assessed along with conventional SVD imaging markers. We first evaluated associations with processing speed in patients with genetically defined SVD (n=113). Next, we validated our findings in independent samples of inherited SVD (n=57), sporadic SVD (n 5 444), and memory clinic patients with SVD (n=105). The new marker was further applied to healthy controls (n=241) and to patients with Alzheimer's disease (n = 153). We further conducted a longitudinal analysis and interscanner reproducibility study. Results: PSMD was associated with processing speed in all study samples with SVD (p-values between 2.8 x 10(-3) and 1.8 x 10(-10)). PSMD explained most of the variance in processing speed (R-2 ranging from 8.8% to 46%) and consistently outperformed conventional imaging markers (white matter hyperintensity volume, lacune volume, and brain volume) in multiple regression analyses. Increases in PSMD were linked to vascular but not to neurodegenerative disease. In longitudinal analysis, PSMD captured SVD progression better than other imaging markers. Interpretation: PSMD is a new, fully automated, and robust imaging marker for SVD. PSMD can easily be applied to large samples and may be of great utility for both research studies and clinical use.
引用
收藏
页码:581 / 592
页数:12
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