Reversible Edema in the Penumbra Correlates With Severity of Hypoperfusion.

Scheldeman, Lauranne; Wouters, Anke; Dupont, Patrick; Christensen, Soren; Boutitie, Florent; Cheng, Bastian; Ebinger, Martin; Endres, Matthias; Fiebach, Jochen B; Gerloff, Christian; Muir, Keith W; Nighoghossian, Norbert; Pedraza, Salvador; Simonsen, Claus Z; Ringelstein, Erich B; Chamorro, Angel; Grond, Martin; Laage, Rico; Schneider, Armin; Thomalla, Götz; Thijs, Vincent; Lemmens, Robin

BACKGROUND AND PURPOSE We aimed to investigate fluid-attenuated inversion recovery changes in the penumbra. METHODS We determined core and perfusion lesions in subjects from the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) and AXIS 2 trial (Granulocyte Colony-Stimulating Factor in Patients With Acute Ischemic Stroke) with perfusion- and diffusion-weighted imaging at baseline. Only subjects with a mismatch volume >15 mL and ratio >1.2 were included. We created voxel-based relative fluid-attenuated inversion recovery signal intensity (rFLAIR SI) maps at baseline and follow-up. We studied rFLAIR SI in 2 regions of interest: baseline penumbra (baseline perfusion lesion-[core lesion+voxels with apparent diffusion coefficient <620 10-6 mm2/s]) and noninfarcted penumbra (baseline perfusion lesion-follow-up fluid-attenuated inversion recovery lesion) at 24 hours (WAKE-UP) or 30 days (AXIS 2). We analyzed the association between rFLAIR SI and severity of hypoperfusion, defined as time to maximum of the residue function. RESULTS In the baseline penumbra, rFLAIR SI was elevated (ratio, 1.04; P=1.7×10-13; n=126) and correlated with severity of hypoperfusion (Pearson r, 0.03; P<1.0×10-4; n=126). In WAKE-UP, imaging at 24 hours revealed a further increase of rFLAIR SI in the noninfarcted penumbra (ratio, 1.05 at 24 hours versus 1.03 at baseline; P=7.1×10-3; n=43). In AXIS 2, imaging at 30 days identified reversibility of the rFLAIR SI (ratio, 1.02 at 30 days versus 1.04 at baseline; P=1.5×10-3; n=26) since it was no longer different from 1 (ratio, 1.01 at 30 days; P=0.099; n=26). CONCLUSIONS Penumbral rFLAIR SI increases appear early after stroke onset, correlate with severity of hypoperfusion, further increase at 24 hours, and are reversible by 30 days. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT01525290. URL: https://clinicaltrials.gov; Unique identifier: NCT00927836.