title: Moving beyond a single perfusion threshold to define penumbra: a novel probabilistic mismatch definition.
abstract: OBJECTIVE
  The mismatch lesion volumes defined by perfusion-weighted imaging exceeding diffusion-weighted imaging have been used as a marker of ischemic penumbral tissue. Defining the perfusion lesion by thresholding has shown promise as a practical tool; several positron emission tomography studies have indicated a more probabilistic relationship between perfusion and infarction. Here, we used a randomized controlled trial dataset of tissue-type plasminogen activator 3 to 6 hours after stroke to: (1) quantify the relationship between severity of hypoperfusion (measured by Tmax) and risk of infarction; (2) exploit this relationship to present a novel definition of mismatch based on infarct probabilities rather than dichotomies; and (3) examine the treatment response in the subgroup of patients with mismatch by the new definition.
  
  
  METHODS
  Patients from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) were included. Baseline perfusion-weighted imaging and 90-day T2-weighted imaging were coregistered. Perfusion-weighted imaging lesion volumes were divided into 10 Tmax delay strata, and infarct risk was defined as the fraction of the tissue at a given Tmax strata that progressed to infarction by day 90.
  
  
  RESULTS
  Sixty-two patients were studied. Infarct risk was an increasing function of Tmax for all subgroups, including the whole cohort. The probabilistic approach outperformed all Tmax thresholds, with exception of the Tmax ≥ 10 threshold, for which it was only favored by a trend.
  
  
  CONCLUSIONS
  Infarct risk and treatment effect increased with severity of perfusion abnormalities. This suggests that a severity-weighted mismatch definition may define penumbral tissue more accurately.
authors.affiliation: National Stroke Research Institute, Florey Neuroscience Institutes, Austin Health, University of Melbourne, Victoria 3053, Australia. gdonnan@unimelb.edu.au
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Nagakane
authors.forename: Soren
authors.initials: S
authors.lastname: Christensen
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Ogata
authors.forename: Leonid
authors.initials: L
authors.lastname: Churilov
authors.forename: Henry
authors.initials: H
authors.lastname: Ma
authors.forename: Mark W
authors.initials: MW
authors.lastname: Parsons
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Desmond
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Levi
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Butcher
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002544:Cerebral Infarction / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator