At one to three months post-stroke, participants undergo 3 T MRI to measure BBB integrity, CVR, cerebral blood flow (CBF) and intracranial vascular and CSF pulsatility (protocol in online Supplementary Appendix 2). We assess BBB integrity using dynamic contrast-enhanced (DCE)-MRI and gadolinium-based contrast agent (gadobutrol) injection,11 ,43 (link) unless eGFR <30 ml/min. We assess CVR using a blood oxygenation level dependent (BOLD) MRI sequence, during which participants inhale air with intermittent-added CO2 (12-min paradigm alternating 2 min air and 3 min 6% CO2) through a tight-fitting facemask, described previously.13 ,44 (link) Arterial, venous and CSF pulsatility are measured using phase contrast MRI sequences.14 (link),44 (link) We measure CBF using major arterial phase contrast flow measures obtained during pulsatility measurements (and arterial spin labelling where feasible).
We process MRI computationally using well-validated methods to assess intracranial volume, CSF, normal-appearing white and grey matter, WMH volumes, index and prior stroke lesion volumes, lacunes, microbleeds and perivascular space metrics.45 ,46 (link) We visually quantify index and prior stroke lesions (location, type), WMH (baseline, change), lacunes (number, location), perivascular spaces, microbleeds, siderosis, superficial and deep brain volume loss, according to STRIVE criteria using validated scales.2 (link),47 (link)