title: Selection of thrombolytic therapy beyond 3 h using magnetic resonance imaging.
abstract: OBJECTIVE
  Use of intravenous thrombolytic therapy in ischaemic stroke is restricted to a 3-h time window because of the proof of this time window in pivotal clinical trials. Thrombolysis is aimed at recanalization of occluded arteries and reperfusion of the ischaemic penumbra, a region of critically hypoperfused, functionally impaired, but potentially viable brain. There are a number of current prospective trials that are testing the hypothesis that the presence of the penumbra will predict thrombolytic responders beyond 3 h.
  
  
  RESULTS
  Using magnetic resonance imaging, a mismatch between a larger perfusion-weighted imaging lesion and smaller diffusion-weighted imaging lesion is considered to represent the ischaemic penumbra. Perfusion-weighted imaging provides semiquantitative cerebral blood flow imaging and diffusion-weighted imaging is an index of the largely irreversible ischaemic core. This definition has been modified with the recognition that the perfusion-weighted imaging lesion includes benign oligaemia and that a portion of the diffusion-weighted imaging core is potentially salvageable with rapid reperfusion. Most acute stroke patients have a magnetic resonance imaging-penumbral signature within 6 h of stroke onset. The penumbra is commonly, but not invariably, associated with proximal arterial occlusion and is time-dependent. Preliminary studies have shown benefit from thrombolytic therapy beyond the established 3-h window.
  
  
  CONCLUSIONS
  Penumbral imaging using magnetic resonance imaging with perfusion over diffusion weighted imaging mismatch can provide a physiological 'tissue clock' in individual patients. Based on this hypothesis, a number of prospective trials are being performed. These include EPITHET, DEFUSE, DIAS, MR RESCUE and ROSIE.
authors.affiliation: Department of Neurology, Royal Melbourne Hospital/University of Melbourne, Australia. Stephen.Davis@mh.org.au
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Butcher
authors.forename: Mark
authors.initials: M
authors.lastname: Parsons
mesh_terms: D001921:Brain / Q000473:pathology; D002560:Cerebrovascular Circulation; D002986:Clinical Trials as Topic; D005069:Evaluation Studies as Topic; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology*; D013997:Time Factors
chemical_list: D005343:Fibrinolytic Agents