TY - JOUR
T1 - Peak Width of Skeletonized Mean Diffusivity as a Marker of Diffuse Cerebrovascular Damage
AU - Low, Audrey
AU - Mak, Elijah
AU - Stefaniak, James D
AU - Malpetti, Maura
AU - Nicastro, Nicolas
AU - Savulich, George
AU - Chouliaras, Leonidas
AU - Markus, Hugh S
AU - Rowe, James B
AU - O'Brien, John T
N1 - Funding Information:
We thank our participant volunteers for their participation in the Neuroinflammation in Memory and Related Other Disorders (NIMROD) study, the radiographers at the Wolfson Brain Imaging Centre (WBIC) for their technical expertise and support in data acquisition, and the NIHR Dementias and Neurodegenerative Diseases Research Network (DeNDRoN) for their help in subject recruitment. Funding. This study was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) Dementia and Neurodegeneration Theme (Grant Reference Number 146281). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. AL was supported by the Lee Kuan Yew Fitzwilliam Scholarship and the Tan Kah Kee Postgraduate Scholarship. JS was a Wellcome Clinical Ph.D. Fellow funded on grant 203914/Z/16/Z to the Universities of Manchester, Leeds, Newcastle, and Sheffield. JR was supported by the Wellcome Trust (103838). HM and JO?B were each supported by the NIHR Senior Investigator awards.
Publisher Copyright:
© Copyright © 2020 Low, Mak, Stefaniak, Malpetti, Nicastro, Savulich, Chouliaras, Markus, Rowe and O’Brien.
PY - 2020/3/19
Y1 - 2020/3/19
N2 - Background: 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.Methods: 145 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.Results: PSMD 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.Discussion: PSMD 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.
AB - Background: 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.Methods: 145 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.Results: PSMD 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.Discussion: PSMD 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.
KW - cognition
KW - dementia
KW - diffusion tensor imaging
KW - magnetic resonance imaging
KW - small vessel disease
KW - white matter hyperintensities
UR - http://www.scopus.com/inward/record.url?scp=85083069132&partnerID=8YFLogxK
U2 - 10.3389/fnins.2020.00238
DO - 10.3389/fnins.2020.00238
M3 - Article
C2 - 32265640
SN - 1662-4548
VL - 14
SP - 238
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 238
ER -