• Primary Hypothesis - lesion growth
• In patients with penumbra, there will be attenuation of lesion growth (outcome T2 lesion volume - acute DWI volume ) with tPA.

• Secondary Hypotheses
• In the non-penumbral group, lesion growth will be lower and will not be attenuated by tPA.
• Favourable functional outcome (mRS 0-2) will be more likely in patients with penumbra receiving tPA.
• That the proportion of patients achieving good neurological outcome (an 8 point improvement in NIH-SS or outcome NIH-SS of 0, 1) will be greater in those patients with a penumbra receiving tPA.
• Symptomatic hemorrhagic transformation (sICH) will be predicted by the size of the baseline DWI volume in those patients receiving tPA.
• Reperfusion (greater than 90% PWI lesion reduction, or recanalisation on MRA, between the acute and sub-acute interval), will be increased (in patients with penumbra) receiving tPA.
• In patients with malignant mismatch (Definition DWI 100ml or more and / or PWI 100ml or more) there will be unfavourable clinical outcome (even if there is attenuation of growth).

• - Reperfusion defined as change between acute PWI volume(3-6 hours) and subacute PWI volume (3-5 days);
• - symptomatic hemorrhagic transformation at day 3, as assessed by MRI;
• - infarct volume, as measured with T2-weighted MRI;
• - degree of recanalization of the MCA;
• - proportion of patients making an 11-point improvement in their NIHSS score;
• - percentage of patients reaching an MRS score of 0 - 2 or
• - Barthel Index (BI) score >= 85.

To determine whether the extent of the ischemic penumbra apparent on perfusion-diffusion MRI can be used to identify patients who would respond positively and safely to tissue plasminogen activator (tPA) beyond 3 hours post-stroke.

Inclusion Criteria:

• Patients who present:
• with acute hemispheric stroke within 3-6 hours of onset,
• have at least moderate limb weakness,
• a National Institute of Health Stroke Scale (NIHSS) score > 4,
• had a pre-stroke modified Rankin Scale (MRS) score of 0 - 2
• and who are able to undergo CT and MRI, are eligible for this study.

Exclusion Criteria:

• Females who are pregnant or breast-feeding,
• persons who have CT-verified hemorrhagic stroke, major ischemia ( > 33% of the middle cerebral artery (MCA) territory infarcted), subarachnoid hemorrhage, arteriovenous malformation, aneurysm, intracranial neoplasm that is terminal or poses a risk of hemorrhage ,
• are comatose or severely obtunded with fixed eye deviation and complete hemiplegia,
• have had another stroke within the past 6 weeks,
• have had a seizure prior to the administration of the study drug,
• have active peptic ulceration, bleeding diatheses, previous intracerebral hemorrhage,
• blood pressure > 185/110,
• major surgery or trauma within the past 30 days, or any other contraindications to tPA
• have a presumed septic embolus or a myocardial infarction within the past 30 days
• blood glucose values are < 2.8 or > 22.0 mmol/L,
• pacemakers, aneurysm clips, implanted devices, claustrophobia, or any other contraindications to MRI,
• decreased consciousness,
• rapid clinical improvement,
• confounding neurological condition (e.g. dementia),
• any other life-threatening illness, or who are participating in another clinical trial, will be excluded from this study.