Abstract
BackgroundThe peak width of skeletonized mean diffusivity (PSMD) has been proposed as a fully automated imaging marker of relevance to cerebral small vessel disease (SVD). We assessed PSMD in relation to conventional SVD markers, global measures of neurodegeneration, and cognition.Methods145 participants underwent 3T brain MRI and cognitive assessment. 112 were patients with mild cognitive impairment, Alzheimer’s disease, progressive supranuclear palsy, dementia with Lewy bodies, or frontotemporal dementia. PSMD, SVD burden [white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), microbleeds, lacunes], average mean diffusivity (MD), gray matter (GM), white matter (WM), and total intracranial volume were quantified. Robust linear regression was conducted to examine associations between variables. Dominance analysis assessed the relative importance of markers in predicting various outcomes. Regional analyses examined spatial overlap between PSMD and WMH.ResultsPSMD was associated with global and regional SVD measures, especially WMH and microbleeds. Dominance analysis demonstrated that among SVD markers, WMH was the strongest predictor of PSMD. Furthermore, PSMD was more closely associated to WMH than with GM and WM volumes. PSMD was associated with WMH across all regions, and correlations were not significantly stronger in corresponding regions (e.g., frontal PSMD and frontal WMH) compared to non-corresponding regions. PSMD outperformed all four conventional SVD markers and MD in predicting cognition, but was comparable to GM and WM volumes.DiscussionPSMD was robustly associated with established SVD markers. This new measure appears to be a marker of diffuse brain injury, largely due to vascular pathology, and may be a useful and convenient metric of overall cerebrovascular burden.
Highlights
The clinical significance of cerebral small vessel disease (SVD) in cognitive impairment, dementia, and stroke creates an urgent need to identify and develop valid markers of relevance to SVD (Pantoni, 2010)
In terms of cerebrovascular burden, 37% had significant white matter hyperintensities (WMHs), defined as PVH extending into the deep white matter (WM) (Fazekas 3) and/or confluent or early confluent deep WMH (DWMH) (Fazekas 2–3). 45% displayed moderate to severe enlarged perivascular spaces (EPVS) in the basal ganglia (BG), 35% possessed one or more lacune, and 35% had at least one microbleed
Expanding on existing research, which has mostly examined peak width of skeletonized mean diffusivity (PSMD) in relation to WMH (Baykara et al, 2016; Deary et al, 2019), this present study demonstrated that associations with PSMD were not confined to WMH, but extended to other key SVD markers of EPVS, lacunes, and microbleeds, and total SVD burden
Summary
The clinical significance of cerebral small vessel disease (SVD) in cognitive impairment, dementia, and stroke creates an urgent need to identify and develop valid markers of relevance to SVD (Pantoni, 2010). A new fully automated measure, known as the peak width of skeletonized mean diffusivity (PSMD), has been proposed as a marker of SVD (Baykara et al, 2016). PSMD outperformed established MD parameters in terms of association with processing speed, including mean, median, peak height, full width at half maximum (Baykara et al, 2016). The peak width of skeletonized mean diffusivity (PSMD) has been proposed as a fully automated imaging marker of relevance to cerebral small vessel disease (SVD). We assessed PSMD in relation to conventional SVD markers, global measures of neurodegeneration, and cognition
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