Reversible Relative FLAIR Signal Intensity Changes in the Penumbra Correlate With Severity of Hypoperfusion.

In ischemic stroke, the study of edema, measurable as fluid attenuated inversion recovery (FLAIR) signal increase, has mainly focused on the ischemic core and less on the surrounding penumbra. To the naked eye, no FLAIR changes are present in the penumbra. However, changes in perfusion status could induce physiological changes resulting in subtle penumbral FLAIR signal alterations. To investigate penumbral FLAIR changes, we included subjects from the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) and Granulocyte Colony-Stimulating Factor in Patients With Acute Ischemic Stroke (AXIS 2) trial with perfusion- and diffusion-weighted imaging (PWI, DWI) and FLAIR at baseline. We used RAPID software to calculate the core and perfusion lesion on DWI and PWI and selected subjects with a minimal mismatch volume (15 ml) and ratio (1.2). We created voxel-based relative FLAIR signal intensity (rFLAIR SI) maps at baseline and follow up (FU) by calculating the ratio of the FLAIR intensity in one voxel and the median FLAIR intensity in a sphere with 15 mm radius around a contralateral homologues voxel. We studied rFLAIR SI in two regions of interest: the baseline penumbra (baseline perfusion lesion - [core lesion + voxels with apparent diffusion coefficient <620 10 -6 mm 2 /s]) and the non-infarcted penumbra (baseline perfusion lesion - FU FLAIR lesion) at 24 hours (WAKE-UP) or 30 days (AXIS 2). Severity of hypoperfusion was defined as the time to maximum of the residue function. 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’s r 0.03, p<1.0*10 -4 , n=126). At 24 hours in a subgroup from WAKE-UP, rFLAIR SI in the non-infarcted penumbra further increased (ratio=1.05 at 24h vs 1.03 at baseline, p=7.1*10 -3 , n=43). In a different subgroup from AXIS 2, this increase in rFLAIR SI was reversible (ratio=1.02 at 30d vs 1.04 at baseline, p=1.5*10 -3 n=26) since it wa