MRI measurement of the delayed secondary ischaemic injury following endovascular thrombectomy: results from the REPERFUSE-NA1 study

Background: Brain injury due to stroke is an important determinant of long-term disability. The acute lesion visible on MRI with DWI underestimates the total burden of the ischaemic injury. The objectives of this study are: (1) quantify the delayed secondary ischaemic injury volume by calculating the whole and regional brain volume loss at 90-days post-stroke and (2) determine whether brain volume loss independently predicted functional outcome at 90 days. Methods: REPERFUSE-NA1 is a prospective, multisite MRI sub-study of the ESCAPE–NA1 trial (ClinicalTrialGov #NCT02930018), which randomised participants receiving endovascular therapy (EVT) to nerinetide versus placebo. MRI was acquired immediately after therapy (day 1, <5 hours post-EVT) and at 90-days. The primary outcome was change in whole-brain volume between day 1 and 90. Serial MR metrics were used to generate sample size calculations for future neuroprotectant trials. Results: A total of 43 patients of mean age 65.1 years (SD = 14.9, 51.2% female, median NIHSS 15 [Q1–Q3 = 11–20]) were included. In the entire cohort, there was significant whole-brain volume loss (P < .001), ventricular enlargement (P < .001), and cortical grey matter (P = .001), subcortical white matter (P < .001), thalamic (P < .001), and hippocampal (P < .001) volume loss in the ipsilateral hemisphere. Baseline DWI volume and ipsilateral hemispheric brain atrophy were significant predictors of functional independence, with P-values of < .001. There was no significant association between nerinetide treatment and volume changes at 90-days. For a prospective 90-day neuroprotectant trial to demonstrate 50% reduction, 41 patients per group would be needed using ventricular volume change. Conclusion: This study indicates that whole-brain volume loss is a feasible measurement of delayed secondary ischaemic injury. Future neuroprotectant clinical trials could utilise MR-based markers of delayed ischaemic injury.