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Lookup NU author(s): Professor James WasonORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2022 The Authors. Background: DTI is sensitive to white matter (WM) microstructural damage and has been suggested as a surrogate marker for phase 2 clinical trials in cerebral small vessel disease (SVD). The study's objective is to establish the best way to analyse the diffusion-weighted imaging data in SVD for this purpose. The ideal method would be sensitive to change and predict dementia conversion, but also straightforward to implement and ideally automated. As part of the OPTIMAL collaboration, we evaluated five different DTI analysis strategies across six different cohorts with differing SVD severity. Methods: Those 5 strategies were: (1) conventional mean diffusivity WM histogram measure (MD median), (2) a principal component-derived measure based on conventional WM histogram measures (PC1), (3) peak width skeletonized mean diffusivity (PSMD), (4) diffusion tensor image segmentation θ (DSEG θ) and (5) a WM measure of global network efficiency (Geff). The association between each measure and cognitive function was tested using a linear regression model adjusted by clinical markers. Changes in the imaging measures over time were determined. In three cohort studies, repeated imaging data together with data on incident dementia were available. The association between the baseline measure, change measure and incident dementia conversion was examined using Cox proportional-hazard regression or logistic regression models. Sample size estimates for a hypothetical clinical trial were furthermore computed for each DTI analysis strategy. Results: There was a consistent cross-sectional association between the imaging measures and impaired cognitive function across all cohorts. All baseline measures predicted dementia conversion in severe SVD. In mild SVD, PC1, PSMD and Geff predicted dementia conversion. In MCI, all markers except Geff predicted dementia conversion. Baseline DTI was significantly different in patients converting to vascular dementia than to Alzheimer’ s disease. Significant change in all measures was associated with dementia conversion in severe but not in mild SVD. The automatic and semi-automatic measures PSMD and DSEG θ required the lowest minimum sample sizes for a hypothetical clinical trial in single-centre sporadic SVD cohorts. Conclusion: DTI parameters obtained from all analysis methods predicted dementia, and there was no clear winner amongst the different analysis strategies. The fully automated analysis provided by PSMD offers advantages particularly for large datasets.
Author(s): Egle M, Hilal S, Tuladhar AM, Pirpamer L, Bell S, Hofer E, Duering M, Wason J, Morris RG, Dichgans M, Schmidt R, Tozer DJ, Barrick TR, Chen C, de Leeuw F-E, Markus HS
Publication type: Article
Publication status: Published
Journal: NeuroImage: Clinical
Year: 2022
Volume: 35
Online publication date: 13/07/2022
Acceptance date: 10/07/2022
Date deposited: 10/08/2022
ISSN (electronic): 2213-1582
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.nicl.2022.103114
DOI: 10.1016/j.nicl.2022.103114
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