Gordon W Blair1, Michael J Thrippleton1, Yulu Shi1, Iona Hamilton1, Michael Stringer1, Francesca Chappell1, David Alexander Dickie1, Peter Andrews1, Ian Marshall1, Fergus N Doubal1, Joanna M Wardlaw2. 1. From the Brain Research Imaging Centre (G.W.B., M.J.T., Y.S., I.H., M.S., F.C., P.A., I.M., F.N.D., J.M.W.), Centre for Clinical Brain Sciences, University of Edinburgh, United Kingdom; UK Dementia Research Institute at The University of Edinburgh (G.W.B., M.J.T., Y.S., I.H., M.S., F.N.D., J.M.W.), Edinburgh Medical School, United Kingdom; Beijing Tiantan Hospital Affiliated to Capital Medical University (Y.S.), China; Institute of Cardiovascular and Medical Sciences (D.A.D.), University of Glasgow, United Kingdom; and Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.W.), University of Edinburgh, United Kingdom. 2. From the Brain Research Imaging Centre (G.W.B., M.J.T., Y.S., I.H., M.S., F.C., P.A., I.M., F.N.D., J.M.W.), Centre for Clinical Brain Sciences, University of Edinburgh, United Kingdom; UK Dementia Research Institute at The University of Edinburgh (G.W.B., M.J.T., Y.S., I.H., M.S., F.N.D., J.M.W.), Edinburgh Medical School, United Kingdom; Beijing Tiantan Hospital Affiliated to Capital Medical University (Y.S.), China; Institute of Cardiovascular and Medical Sciences (D.A.D.), University of Glasgow, United Kingdom; and Centre for Cognitive Ageing and Cognitive Epidemiology (J.M.W.), University of Edinburgh, United Kingdom. Joanna.wardlaw@ed.ac.uk.
Abstract
OBJECTIVE: To investigate cerebrovascular reactivity (CVR), blood flow, vascular and CSF pulsatility, and their independent relationship with cerebral small vessel disease (SVD) features in patients with minor ischemic stroke and MRI evidence of SVD. METHODS: We recruited patients with minor ischemic stroke and assessed CVR using blood oxygen level-dependent MRI during a hypercapnic challenge, cerebral blood flow (CBF), vascular and CSF pulsatility using phase-contrast MRI, and structural magnetic resonance brain imaging to quantify white matter hyperintensities (WMHs) and perivascular spaces (PVSs). We used multiple regression to identify parameters associated with SVD features, controlling for patient characteristics. RESULTS: Fifty-three of 60 patients completed the study with a full data set (age 68.0% ± 8.8 years, 74% male, 75% hypertensive). After controlling for age, sex, and systolic blood pressure, lower white matter CVR was associated with higher WMH volume (-0.01%/mm Hg per log10 increase in WMH volume, p = 0.02), basal ganglia PVS (-0.01%/mm Hg per point increase in the PVS score, p = 0.02), and higher venous pulsatility (superior sagittal sinus -0.03%/mm Hg, p = 0.02, per unit increase in the pulsatility index) but not with CBF (p = 0.58). Lower foramen magnum CSF stroke volume was associated with worse white matter CVR (0.04%/mm Hg per mL increase in stroke volume, p = 0.04) and more severe basal ganglia PVS (p = 0.09). CONCLUSIONS: Lower CVR, higher venous pulsatility, and lower foramen magnum CSF stroke volume indicate that dynamic vascular dysfunctions underpin PVS dysfunction and WMH development. Further exploration of microvascular dysfunction and CSF dynamics may uncover new mechanisms and intervention targets to reduce SVD lesion development, cognitive decline, and stroke.
OBJECTIVE: To investigate cerebrovascular reactivity (CVR), blood flow, vascular and CSF pulsatility, and their independent relationship with cerebral small vessel disease (SVD) features in patients with minor ischemic stroke and MRI evidence of SVD. METHODS: We recruited patients with minor ischemic stroke and assessed CVR using blood oxygen level-dependent MRI during a hypercapnic challenge, cerebral blood flow (CBF), vascular and CSF pulsatility using phase-contrast MRI, and structural magnetic resonance brain imaging to quantify white matter hyperintensities (WMHs) and perivascular spaces (PVSs). We used multiple regression to identify parameters associated with SVD features, controlling for patient characteristics. RESULTS: Fifty-three of 60 patients completed the study with a full data set (age 68.0% ± 8.8 years, 74% male, 75% hypertensive). After controlling for age, sex, and systolic blood pressure, lower white matter CVR was associated with higher WMH volume (-0.01%/mm Hg per log10 increase in WMH volume, p = 0.02), basal ganglia PVS (-0.01%/mm Hg per point increase in the PVS score, p = 0.02), and higher venous pulsatility (superior sagittal sinus -0.03%/mm Hg, p = 0.02, per unit increase in the pulsatility index) but not with CBF (p = 0.58). Lower foramen magnum CSF stroke volume was associated with worse white matter CVR (0.04%/mm Hg per mL increase in stroke volume, p = 0.04) and more severe basal ganglia PVS (p = 0.09). CONCLUSIONS: Lower CVR, higher venous pulsatility, and lower foramen magnum CSF stroke volume indicate that dynamic vascular dysfunctions underpin PVS dysfunction and WMH development. Further exploration of microvascular dysfunction and CSF dynamics may uncover new mechanisms and intervention targets to reduce SVD lesion development, cognitive decline, and stroke.
Authors: A Mahammedi; L L Wang; B J Williamson; P Khatri; B Kissela; R P Sawyer; R Shatz; V Khandwala; A Vagal Journal: AJNR Am J Neuroradiol Date: 2021-10-07 Impact factor: 3.825
Authors: Una Clancy; Daniela Jaime Garcia; Michael S Stringer; Michael J Thrippleton; Maria C Valdés-Hernández; Stewart Wiseman; Olivia Kl Hamilton; Francesca M Chappell; Rosalind Brown; Gordon W Blair; Will Hewins; Emilie Sleight; Lucia Ballerini; Mark E Bastin; Susana Munoz Maniega; Tom MacGillivray; Kirstie Hetherington; Charlene Hamid; Carmen Arteaga; Alasdair G Morgan; Cameron Manning; Ellen Backhouse; Iona Hamilton; Dominic Job; Ian Marshall; Fergus N Doubal; Joanna M Wardlaw Journal: Eur Stroke J Date: 2020-06-05
Authors: Emilie Sleight; Michael S Stringer; Ian Marshall; Joanna M Wardlaw; Michael J Thrippleton Journal: Front Physiol Date: 2021-02-25 Impact factor: 4.566
Authors: Gordon W Blair; Esther Janssen; Michael S Stringer; Michael J Thrippleton; Francesca Chappell; Yulu Shi; Iona Hamilton; Katie Flaherty; Jason P Appleton; Fergus N Doubal; Philip M Bath; Joanna M Wardlaw Journal: Stroke Date: 2021-12-01 Impact factor: 7.914
Authors: Michael S Stringer; Gordon W Blair; Yulu Shi; Iona Hamilton; David A Dickie; Fergus N Doubal; Ian M Marshall; Michael J Thrippleton; Joanna M Wardlaw Journal: Front Physiol Date: 2021-06-02 Impact factor: 4.755