TY - JOUR
T1 - Quantifying blood-brain barrier leakage in small vessel disease
T2 - Review and consensus recommendations
AU - Thrippleton, Michael J.
AU - Backes, Walter H.
AU - Sourbron, Steven
AU - Ingrisch, Michael
AU - van Osch, Matthias J. P.
AU - Dichgans, Martin
AU - Fazekas, Franz
AU - Ropele, Stefan
AU - Frayne, Richard
AU - van Oostenbrugge, Robert J.
AU - Smith, Eric E.
AU - Wardlaw, Joanna M.
N1 - Funding Information:
The HARNESS initiative (www.harness-neuroimaging.org) was funded by the European Union Joint Programme–Neurodegenerative Disease Research Working Groups for Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration. The project has also received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 666881, SVDs@Target, The Fondation Leducq (16 CVD 05) and the Medical Research Council-funded Dementia Research Institute. M.J.T. acknowledges financial support from the NHS Lothian Research and Development Office. W.H.B. thanks the “Alzheimer Nederland,” “Stichting De Weijerhorst,” “Academisch Fonds,” “Nederlands Wetenschappelijk Onderzoek,” and the “Hersenstichting” organization for financial support. R.F. thanks the Canadian Institutes for Health Research (CIHR) and the Hopewell Professorship in Brain Imaging. The authors acknowledge Dr. Gordon Blair and the SVDs@TARGET study team for the data shown in Figs. 2 and 4.
Funding Information:
The HARNESS initiative ( www.harness-neuroimaging.org ) was funded by the European Union Joint Programme–Neurodegenerative Disease Research Working Groups for Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration. The project has also received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 666881 , SVDs@Target, The Fondation Leducq (16 CVD 05) and the Medical Research Council-funded Dementia Research Institute . M.J.T. acknowledges financial support from the NHS Lothian Research and Development Office. W.H.B. thanks the “Alzheimer Nederland,” “Stichting De Weijerhorst,” “Academisch Fonds,” “Nederlands Wetenschappelijk Onderzoek,” and the “Hersenstichting” organization for financial support. R.F. thanks the Canadian Institutes for Health Research (CIHR) and the Hopewell Professorship in Brain Imaging. The authors acknowledge Dr. Gordon Blair and the SVDs@TARGET study team for the data shown in Figs. 2 and 4 .
Publisher Copyright:
© 2019 The Authors
PY - 2019/6
Y1 - 2019/6
N2 - Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance. It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology. Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature. Although dynamic contrast-enhanced magnetic resonance imaging is well established, challenges emerge in cSVD because of the subtle nature of BBB impairment. The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified. We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
AB - Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance. It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology. Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature. Although dynamic contrast-enhanced magnetic resonance imaging is well established, challenges emerge in cSVD because of the subtle nature of BBB impairment. The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified. We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
KW - ALZHEIMERS-DISEASE
KW - ARTERIAL INPUT FUNCTION
KW - Blood-brain barrier
KW - Cerebral small vessel disease
KW - DCE-MRI
KW - Dementia
KW - ENHANCED T-1-WEIGHTED MRI
KW - Endothelial dysfunction
KW - GA-68 EDTA
KW - IN-VIVO
KW - MRI
KW - MULTIPLE-SCLEROSIS
KW - PERMEABILITY CHANGES
KW - Permeability
KW - WATER EXCHANGE
KW - WHITE-MATTER LESIONS
U2 - 10.1016/j.jalz.2019.01.013
DO - 10.1016/j.jalz.2019.01.013
M3 - (Systematic) Review article
C2 - 31031101
SN - 1552-5260
VL - 15
SP - 840
EP - 858
JO - Alzheimer's & Dementia
JF - Alzheimer's & Dementia
IS - 6
ER -