Abstract 52: Results of DEFUSE 2: Imaging Endpoints
Authors: Albers Gregory W , Straka Matus , Kemp Stephanie , Mlynash Michael , Jovin Tudor G , Wechsler Lawrence R , Wilder Michael J , Lutsep Helmi J , Keogh Bart P , Bernstein Richard A , Chang Cherylee W , Warach Steven , Fazekas Franz , Thai Demi , Inoue Manabu , Tipirneni Aaryani , Hamilton Scott , Zaharchuk Greg , Marks Michael P , Bammer Roland , Lansberg Maarten G ,   The DEFUSE 2 Investigators
Published: July 2021

Background:
The aim of DEFUSE 2 is to determine if predefined MRI profiles predict clinical and imaging outcomes following endovascular reperfusion therapy.

Methods:
This prospective, NIH funded, multi-center study enrolled consecutive acute stroke patients in whom an MRI scan could be obtained immediately prior to intra-arterial therapy. A follow-up MRI was performed within 12 hrs of completion of the procedure and again at 5 days. PWI and DWI lesion volumes were determined using a fully automated software program (RAPID). Lesion growth (infarct volume on 5 day FLAIR - baseline DWI volume) was compared for patients with and without the Target mismatch profile based on whether early reperfusion occurred. The Target mismatch profile was defined as PWI(Tmax>6s) / DWI >1.8, DWI <70 mL and PWI(Tmax>10s) <100 mL. Early reperfusion was defined as a >50% reduction in PWI volume following the procedure. The incidence and extent of DWI reversal was assessed and the fate of PWI lesions that were not reperfused was determined. Favorable clinical response was defined as an improvement in NIHSS ≥8 or 0-1 at 30 days.

Results:
This abstract represents a preliminary analysis of 71 of 101 patients who were treated with endovascular therapy (final results to be presented). Among the 54 patients with Target mismatch, early reperfusion was achieved in 70% and was associated with less infarct growth (relative median growth 210% vs. 450%, p=0.01) and a higher rate of favorable clinical response (OR=5.4; 95%CI 1.5-19.2). In patients without the Target mismatch profile (N= 13) early reperfusion was not associated with a reduction in infarct growth (relative median growth was 220% in both reperfusers and non-reperfusers; p=0.94) or an increased rate of favorable clinical response (OR=0.1; 95%CI 0.004-2.2). 96% of all voxels that were DWI positive at baseline were incorporated into the final infarct (assessed on the co-registered 5 day FLAIR); only 3 of 71 patients had FLAIR volumes that were smaller than the baseline DWI lesion (mean difference 3 mL). 80% of the voxels that had a PWI lesion (Tmax>6s) on the post-procedure scan were incorporated into the final infarct. The correlation between the union of the baseline DWI + early follow-up PWI lesion and the 5 day FLAIR volume was high (r=0.84; p< 0.0001). In 82% of the patients, the day 5 FLAIR volume was as at least as large as the union of the baseline DWI + early follow-up PWI lesion.

Conclusion:
Patients with the Target mismatch profile who achieve early reperfusion following intra-arterial therapy have less infarct growth and more favorable clinical outcomes. In contrast, no benefit of reperfusion was evident for non-Target mismatch patients. Baseline DWI lesions are virtually always fully incorporated into the final infarct volume, regardless of reperfusion. Tissue that remains hypoperfused (Tmax >6s) following endovascular therapy reliably progresses to infarction.