A landmark NINDS IV tPA trial showed that treatment with tPA within 3 hours of symptom onset improved neurologic impairment and functional outcome. Recently novel, semiquantitative PET measurements have been proposed to study the penumbra in humans that partially overcome the complexity of quantitative PET measurements. A perfusion-weighted imaging technique (PWI) is an evolving MR technology to study cerebral hemodynamics. The goal of hemodynamic imaging is to rapidly and accurately identify the area of hypoperfusion. Animal ischemia experiments have demonstrated that the lesion identified on diffusion-weighted imaging is larger than the area where ATP depletion has occurred; indicating that only part of the DWI lesion represents the ischemic core. The rationale of thrombolysis in acute stroke is to open occluded vessels and provide beneficial reperfusion. In animal stroke models, primary evidence of the efficacy of therapeutic intervention is established by a reduction in ischemic lesion volume compared to non-treated animals.