Free water determines diffusion alterations and clinical status in cerebral small vessel disease

Duering, Marco; Finsterwalder, Sofia; Baykara, Ebru; Tuladhar, Anil M.; Gesierich, Benno; Konieczny, M.; Malik, Rainer; Franzmeier, Nicolai; Ewers, Michael; Jouvent, Éric; Biessels, Geert Jan; Schmidt, Reinhold; Leeuw, Frank‐Erik de; Pasternak, Ofer; Dichgans, Martin

doi:10.1016/j.jalz.2017.12.007

Cited by 137 publications

(181 citation statements)

References 46 publications

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“…The tissue correlate of altered diffusion metrics in cSVD is still debated. A recent study suggests that increased extracellular water content is a major contributor [50] .…”

Section: Resultsmentioning

confidence: 99%

Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration

Smith

Biessels

Guio

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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104

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Introduction Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease. Methods Surveys, teleconferences, and an in-person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis. Results A framework for neuroimaging biomarker development was developed based on validating repeatability and reproducibility, biological principles, and feasibility of implementation. The status of current MRI biomarkers was reviewed. A website was created at www.harness-neuroimaging.org with acquisition protocols, a software database, rating scales and case report forms, and a deidentified MRI repository. Conclusions The HARNESS initiative provides resources to reduce variability in measurement in MRI studies of cerebral small vessel disease.

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“…The tissue correlate of altered diffusion metrics in cSVD is still debated. A recent study suggests that increased extracellular water content is a major contributor [50] .…”

Section: Resultsmentioning

confidence: 99%

Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration

Smith

Biessels

Guio

et al. 2019

Alz & Dem Diag Ass & Dis Mo

Self Cite

104

View full text Add to dashboard Cite

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“…This was done using tools from MRtrix3 (http://www.mrtrix.org/, dwidenoise, mrdegibbs) and the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL; version 5.0.9, eddy, topup) (Smith et al, ). After preprocessing, fractional anisotropy and FW were calculated as previously described (Duering et al, ). Briefly, diffusion tensors were estimated using linear least squares implemented in MATLAB.…”

Section: Methodsmentioning

confidence: 99%

Alterations and test–retest reliability of functional connectivity network measures in cerebral small vessel disease

Gesierich

Tuladhar

Telgte

et al. 2020

Human Brain Mapping

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While structural network analysis consolidated the hypothesis of cerebral small vessel disease (SVD) being a disconnection syndrome, little is known about functional changes on the level of brain networks. In patients with genetically defined SVD (CADASIL, n = 41) and sporadic SVD (n = 46), we independently tested the hypothesis that functional networks change with SVD burden and mediate the effect of disease burden on cognitive performance, in particular slowing of processing speed. We further determined test–retest reliability of functional network measures in sporadic SVD patients participating in a high‐frequency (monthly) serial imaging study (RUN DMC—InTENse, median: 8 MRIs per participant). Functional networks for the whole brain and major subsystems (i.e., default mode network, DMN; fronto‐parietal task control network, FPCN; visual network, VN; hand somatosensory‐motor network, HSMN) were constructed based on resting‐state multi‐band functional MRI. In CADASIL, global efficiency (a graph metric capturing network integration) of the DMN was lower in patients with high disease burden (standardized beta = −.44; p [corrected] = .035) and mediated the negative effect of disease burden on processing speed (indirect path: std. beta = −.20, p = .047; direct path: std. beta = −.19, p = .25; total effect: std. beta = −.39, p = .02). The corresponding analyses in sporadic SVD showed no effect. Intraclass correlations in the high‐frequency serial MRI dataset of the sporadic SVD patients revealed poor test–retest reliability and analysis of individual variability suggested an influence of age, but not disease burden, on global efficiency. In conclusion, our results suggest that changes in functional connectivity networks mediate the effect of SVD‐related brain damage on cognitive deficits. However, limited reliability of functional network measures, possibly due to age‐related comorbidities, impedes the analysis in elderly SVD patients.

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“…For each sample, we calculated 1501 conditional inference trees with unbiased variable selection and default parameters as previously described. 11 We calculated conditional variable importance together with a 95% confidence interval from 100 repetitions.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…10 As such, free water imaging might be able to disentangle the effects of AD and SVD. [11][12][13][14] Previous studies using DTI or free water imaging were limited by the lack of biomarker evidence of AD pathology or insufficient consideration of mixed pathology. Assessing the individual contributions of AD and SVD toward diffusion MRI alterations requires a systematic study covering the entire spectrum of "pure AD," mixed disease, and "pure SVD.…”

Section: Introductionmentioning

confidence: 99%

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

Finsterwalder

Vlegels

Gesierich

et al. 2020

Alzheimer's & Dementia

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* Data used in preparation of this article were obtained from the Dominantly Inherited Alzheimer Network (DIAN) database, the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) database, and the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within DIAN, DELCODE, and ADNI contributed to the design and implementation of the respective studies and/or provided data but did not participate in analysis or writing of this report. A complete listing of the DIAN consortium, the DELCODE study group, and ADNI investigators can be found in the Supplement (DIAN and DELCODE) and at http://adni.loni.usc.edu/wp-content/uploads/ how_to_apply/ADNI_Acknowledgement_List. pdf (ADNI). Sofia Finsterwalder and Naomi Vlegels both contributed equally to the study.

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Free water determines diffusion alterations and clinical status in cerebral small vessel disease

Abstract: Diffusion alterations and clinical status in SVD are largely determined by extracellular fluid increase rather than alterations of white matter fiber organization.

Cited by 137 publications

References 46 publications

Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration

Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration

Alterations and test–retest reliability of functional connectivity network measures in cerebral small vessel disease

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

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