This is an open label multicentre trial, evaluating the utility of MRI-guided thrombolysis for stroke beyond time window by Tenecteplase (TNK-tPA). This exploratory study was to describe the feasibility and outcome of thrombolytic therapy with TNK-tPA in 4.5-24 hours after stroke guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia.

In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome at 90 days. This trial will enroll acute ischemic stroke patients within 4.5 to 24 hours of onset. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had a ischemic penumbra. Randomization will be 1:1 to TNK-tPA (experimental) or standard treatment (control), in compliance with guidelines for acute stroke. Clinical outcome was assessed by disability on the basis of the modified Rankin scale at 90 days follow-up, which will be performed by a blinded assessor.

Inclusion Criteria:

1. Patient age 18-80 years;
2. The time from onset to treatment: 4.5-24 hours;
3. Acute Ischemic stroke confirmed by MRI;
4. NIHSS score ：6-25, or NIHSS score≤ 5 but culprit vessel occlusion or severe stenosis ( ICA, MCA-M1/M2, ACA) on CTA/MRA;
5. Imaging requirements: (1) DWI infarct region: no more than 1/3 of middle cerebral artery territory or 1/2 of the anterior cerebral artery territory or 1/2 of the posterior cerebral artery territory; (2) DWI infarct volume <70 ml; (2) presence of DWI/Flair mismatch: DWI high signal and Flair visually normal;
6. the first onset of ischemic stroke or previous stroke with no obvious sequelae (mRS≤1);
7. Signed informed consent

Exclusion Criteria:

1. Planned endovascular treatment;
2. Serious neurological deficits before onset ( mRS ≥ 2);
3. Obvious head injuries or strokes within 3 months;
4. Subarachnoid hemorrhage;
5. History of intracranial hemorrhage;
6. Intracranial tumor, arteriovenous malformation or aneurysm;
7. Intracranial or spinal cord surgery within 3 months;
8. Arterial puncture at a noncompressible site within the previous seven days;
9. Active internal hemorrhage;
10. coagulation abnormalities: platelet count of <100000/mm3 ；
11. Aortic arch dissection；
12. Heparin therapy within 24 hours;
13. Infective endocarditis；
14. Oral warfarin is being taken and INR>1.6 or APTT abnormal；
15. oral anticoagulation therapy；
16. Systolic pressure ≥185 mmHg or diastolic pressure ≥110 mmHg；
17. Blood glucose < 50 mg/dl (2.7mmol/L)；
18. Pregnancy;
19. Neurological deficit after epileptic seizures;
20. Major surgery within 1 month;
21. Gastrointestinal or urinary tract hemorrhage within the previous 30 days;
22. Myocardial infarction within 3 months;
23. allergy to study drugs;
24. Contradictory to MRI examination；
25. MRI image not qualified for evaluation；
26. Other serious illness；
27. Participating in other clinical trials within 3 months;
28. patients not suitable for this clinical studies considered by researcher.

The Outcomes will be performed by a blinded assessor.