The WAKE-UP trial (Efficacy and Safety of MRI-based Thrombolysis in Wake-Up Stroke) randomized 503 patients with AIS who awoke with stroke or had unclear time of onset >4.5 hours from last known well and could be treated with IV alteplase within 4.5 hours of stroke symptom recognition. Eligibility required MRI mismatch between abnormal signal on DW-MRI and no visible signal change on FLAIR. DW-MRI lesions larger than one-third of the territory of the middle cerebral artery (MCA), NIHSS score >25, contraindication to treatment with alteplase, or planned thrombectomy were all exclusions. The trial was terminated early for lack of funding before the designated 800 patients were randomized. Ninety-four percent were wake-up strokes. Median NIHSS score was 6. Median time from last known well was slightly over 10 hours. At baseline, one-third of the patients had vessel occlusion on time-of-flight MRA, and three-quarters of the FLAIR lesions were <9 mL. The end point of an mRS score of 0 to 1 at 90 days was achieved in 53.3% of the IV alteplase group and in 41.8% of the placebo group (P=0.02).88 See Table XIX in online Data Supplement 2.2.3. Mechanical Thrombectomy Eligibility Vessel Imaging COR LOE New, Revised, or Unchanged For patients who otherwise meet criteria for mechanical thrombectomy, noninvasive vessel imaging of the intracranial arteries is recommended during the initial imaging evaluation. I A Recommendation reworded for clarity from 2015 Endovascular. COR and LOE unchanged. See Table XCV in online Data Supplement 1 for original wording. For patients with suspected LVO who have not had noninvasive vessel imaging as part of their initial imaging assessment for stroke, noninvasive vessel imaging should then be obtained as quickly as possible (eg, during alteplase infusion if feasible). I A Recommendation revised from 2015 Endovascular. COR and LOE unchanged. 