Esther M C van Leijsen1, Mayra I Bergkamp1, Ingeborg W M van Uden1, Mohsen Ghafoorian2,3, Helena M van der Holst4, David G Norris5,6, Bram Platel2, Anil M Tuladhar1, Frank-Erik de Leeuw7. 1. From the Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Donders Center for Medical Neuroscience (E.M.C.v.L., M.I.B., I.W.M.v.U., A.M.T., F.-E.d.L.). 2. Department of Radiology and Nuclear Medicine, Diagnostic Image Analysis Group (M.G., B.P.), Radboud University Medical Center, Nijmegen, the Netherlands. 3. Institute for Computing and Information Sciences (M.G.). 4. Department of Neurology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, the Netherlands (H.M.v.d.H.). 5. Donders Institute for Brain, Cognition, and Behaviour, Centre for Cognitive Neuroimaging (D.G.N.), Radboud University, Nijmegen, the Netherlands. 6. Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Germany (D.G.N.). 7. From the Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Donders Center for Medical Neuroscience (E.M.C.v.L., M.I.B., I.W.M.v.U., A.M.T., F.-E.d.L.) frankerik.deleeuw@radboudumc.nl.
Abstract
BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normal-appearing white matter (NAWM) into WMH remains unknown. We examined whether and when progression of WMH was preceded by changes in fluid-attenuated inversion recovery and diffusion tensor imaging values, thereby taking into account differences between participants with mild versus severe baseline WMH. METHODS: From 266 participants of the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort), we semiautomatically segmented WMH at 3 time points for 9 years. Images were registered to standard space through a subject template. We analyzed differences in baseline fluid-attenuated inversion recovery, fractional anisotropy, and mean diffusivity (MD) values and changes in MD values over time between 4 regions: (1) remaining NAWM, (2) NAWM converting into WMH in the second follow-up period, (3) NAWM converting into WMH in the first follow-up period, and (4) WMH. RESULTS: NAWM converting into WMH in the first or second time interval showed higher fluid-attenuated inversion recovery and MD values than remaining NAWM. MD values in NAWM converting into WMH in the first time interval were similar to MD values in WMH. When stratified by baseline WMH severity, participants with severe WMH had higher fluid-attenuated inversion recovery and MD and lower fractional anisotropy values than participants with mild WMH, in all areas including the NAWM. MD values in WMH and in NAWM that converted into WMH continuously increased over time. CONCLUSIONS: Impaired microstructural integrity preceded conversion into WMH and continuously declined over time, suggesting a continuous disease process of white matter integrity loss that can be detected using diffusion tensor imaging even years before WMH become visible on conventional neuroimaging. Differences in microstructural integrity between participants with mild versus severe WMH suggest heterogeneity of both NAWM and WMH, which might explain the clinical variability observed in patients with similar small vessel disease severity.
BACKGROUND AND PURPOSE:White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normal-appearing white matter (NAWM) into WMH remains unknown. We examined whether and when progression of WMH was preceded by changes in fluid-attenuated inversion recovery and diffusion tensor imaging values, thereby taking into account differences between participants with mild versus severe baseline WMH. METHODS: From 266 participants of the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort), we semiautomatically segmented WMH at 3 time points for 9 years. Images were registered to standard space through a subject template. We analyzed differences in baseline fluid-attenuated inversion recovery, fractional anisotropy, and mean diffusivity (MD) values and changes in MD values over time between 4 regions: (1) remaining NAWM, (2) NAWM converting into WMH in the second follow-up period, (3) NAWM converting into WMH in the first follow-up period, and (4) WMH. RESULTS:NAWM converting into WMH in the first or second time interval showed higher fluid-attenuated inversion recovery and MD values than remaining NAWM. MD values in NAWM converting into WMH in the first time interval were similar to MD values in WMH. When stratified by baseline WMH severity, participants with severe WMH had higher fluid-attenuated inversion recovery and MD and lower fractional anisotropy values than participants with mild WMH, in all areas including the NAWM. MD values in WMH and in NAWM that converted into WMH continuously increased over time. CONCLUSIONS: Impaired microstructural integrity preceded conversion into WMH and continuously declined over time, suggesting a continuous disease process of white matter integrity loss that can be detected using diffusion tensor imaging even years before WMH become visible on conventional neuroimaging. Differences in microstructural integrity between participants with mild versus severe WMH suggest heterogeneity of both NAWM and WMH, which might explain the clinical variability observed in patients with similar small vessel disease severity.
Authors: Patrick J Lao; Robert S Vorburger; Atul Narkhede; Yunglin Gazes; Kay C Igwe; Juliet Colón; Erica Amarante; Vanessa A Guzman; Briana S Last; Christian Habeck; Yaakov Stern; Adam M Brickman Journal: Front Aging Neurosci Date: 2019-12-10 Impact factor: 5.750
Authors: Hyun Jeong Han; Byeong C Kim; Young Chul Youn; Jee Hyang Jeong; Jong Hun Kim; Jae-Hong Lee; Kee Hyung Park; Kyung Won Park; Eun-Joo Kim; Mi Sun Oh; Yong S Shim; Hyun Young Park; Bora Yoon; Soo Jin Yoon; Soo-Jin Cho; Key Chung Park; Duk L Na; Sun Ah Park; Jong-Min Lee; Seong Hye Choi Journal: Dement Neurocogn Disord Date: 2019-12-13