title: Optimizing image registration and infarct definition in stroke research.
abstract: OBJECTIVE
  Accurate representation of final infarct volume is essential for assessing the efficacy of stroke interventions in imaging-based studies. This study defines the impact of image registration methods used at different timepoints following stroke, and the implications for infarct definition in stroke research.
  
  
  METHODS
  Patients presenting with acute ischemic stroke were imaged serially using magnetic resonance imaging. Infarct volume was defined manually using four metrics: 24-h b1000 imaging; 1-week and 1-month T2-weighted FLAIR; and automatically using predefined thresholds of ADC at 24 h. Infarct overlap statistics and volumes were compared across timepoints following both rigid body and nonlinear image registration to the presenting MRI. The effect of nonlinear registration on a hypothetical trial sample size was calculated.
  
  
  RESULTS
  Thirty-seven patients were included. Nonlinear registration improved infarct overlap statistics and consistency of total infarct volumes across timepoints, and reduced infarct volumes by 4.0 mL (13.1%) and 7.1 mL (18.2%) at 24 h and 1 week, respectively, compared to rigid body registration. Infarct volume at 24 h, defined using a predetermined ADC threshold, was less sensitive to infarction than b1000 imaging. 1-week T2-weighted FLAIR imaging was the most accurate representation of final infarct volume. Nonlinear registration reduced hypothetical trial sample size, independent of infarct volume, by an average of 13%.
  
  
  CONCLUSIONS
  Nonlinear image registration may offer the opportunity of improving the accuracy of infarct definition in serial imaging studies compared to rigid body registration, helping to overcome the challenges of anatomical distortions at subacute timepoints, and reducing sample size for imaging-based clinical trials.
authors.affiliation: Acute Vascular Imaging Centre Radcliffe Department of Medicine University of Oxford Level 2, John Radcliffe Hospital Oxford OX3 9DU United Kingdom.
authors.forename: George W J
authors.initials: GW
authors.lastname: Harston
authors.affiliation: Department of Neuroradiology Oxford University Hospitals NHS Trust John Radcliffe Hospital Oxford OX3 9DU United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Minks
authors.affiliation: Department of Neuroradiology Oxford University Hospitals NHS Trust John Radcliffe Hospital Oxford OX3 9DU United Kingdom.
authors.forename: Fintan
authors.initials: F
authors.lastname: Sheerin
authors.affiliation: Department of Engineering Science Institute of Biomedical Engineering University of Oxford Old Road Campus Research Building Oxford OX3 7DQ United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Payne
authors.affiliation: Department of Engineering Science Institute of Biomedical Engineering University of Oxford Old Road Campus Research Building Oxford OX3 7DQ United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Chappell
authors.affiliation: Oxford Centre for Functional MRI of the Brain Nuffield Department of Clinical Neurosciences University of Oxford John Radcliffe Hospital Level 6, West Wing Oxford OX3 7DQ United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Jezzard
authors.affiliation: Oxford Centre for Functional MRI of the Brain Nuffield Department of Clinical Neurosciences University of Oxford John Radcliffe Hospital Level 6, West Wing Oxford OX3 7DQ United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkinson
authors.affiliation: Acute Vascular Imaging Centre Radcliffe Department of Medicine University of Oxford Level 2, John Radcliffe Hospital Oxford OX3 9DU United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Kennedy