title: The physiological significance of the time-to-maximum (Tmax) parameter in perfusion MRI.
abstract: OBJECTIVE
  Many perfusion-related MRI parameters are used to investigate the penumbra in stroke. Although time-to-maximum (Tmax) of the residue function has been suggested as a very promising parameter, its physiological meaning and sensitivity to experimental conditions are not well-understood.
  
  
  METHODS
  We used simulations to further our understanding of the practical meaning of Tmax and to provide recommendations for its use in clinical investigations. We interpret in vivo examples guided by the simulation findings.
  
  
  RESULTS
  Whereas Tmax has several attractive properties for clinical use, it is shown that its physiological interpretation is complex and affected by experimental conditions. Tmax is found to reflect a combination of delay, dispersion, and, to a lesser degree, mean transit time. It should therefore mainly be considered a measure of macrovascular characteristics. Furthermore, based on the simulations, use of temporal-interpolation is highly recommended, as is correction for slice-acquisition timing differences.
  
  
  CONCLUSIONS
  Special care should be taken when setting-up Tmax thresholds for data acquired with different protocols (eg, multicenter studies) because various factors can influence the measured Tmax. Because of its complementary information, used in conjunction with delay-insensitive cerebral blood-flow, cerebral blood volume, and mean transit time maps, Tmax should provide important additional information on brain hemodynamic status.
authors.affiliation: Brain Research Institute, Neurosciences Building, Austin Health, Banksia Street, Heidelberg West, Victoria 3081, Australia. fercala@brain.org.au
authors.forename: Fernando
authors.initials: F
authors.lastname: Calamante
authors.forename: Søren
authors.initials: S
authors.lastname: Christensen
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Desmond
authors.forename: Leif
authors.initials: L
authors.lastname: Ostergaard
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.forename: Alan
authors.initials: A
authors.lastname: Connelly
mesh_terms: D001810:Blood Volume / Q000502:physiology; D001921:Brain / Q000098:blood supply* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008955:Models, Cardiovascular