title: Detection of ischemic penumbra using combined perfusion and T2* oxygen challenge imaging.
abstract: BACKGROUND
  Acute ischemic stroke is common and disabling, but there remains a paucity of acute treatment options and available treatment (thrombolysis) is underutilized. Advanced brain imaging, designed to identify viable hypoperfused tissue (penumbra), could target treatment to a wider population. Existing magnetic resonance imaging and computed tomography-based technologies are not widely used pending validation in ongoing clinical trials. T2* oxygen challenge magnetic resonance imaging, by providing a more direct readout of tissue viability, has the potential to identify more patients likely to benefit from thrombolysis - irrespective of time from stroke onset - and patients within and beyond the 4·5 h thrombolysis treatment window who are unlikely to benefit and are at an increased risk of hemorrhage.
  
  
  OBJECTIVE
  This study employs serial multimodal imaging and voxel-based analysis to develop optimal data processing for T2* oxygen challenge penumbra assessment. Tissue in the ischemic hemisphere is compartmentalized into penumbra, ischemic core, or normal using T2* oxygen challenge (single threshold) or T2* oxygen challenge plus cerebral blood flow (dual threshold) data. Penumbra defined by perfusion imaging/apparent diffusion coefficient mismatch (dual threshold) is included for comparison.
  
  
  METHODS
  Permanent middle cerebral artery occlusion was induced in male Sprague-Dawley rats (n = 6) prior to serial multimodal imaging: T2* oxygen challenge, diffusion-weighted and perfusion imaging (cerebral blood flow using arterial spin labeling).
  
  
  RESULTS
  Across the different methods evaluated, T2* oxygen challenge combined with perfusion imaging most closely predicted 24 h infarct volume. Penumbra volume declined from one to four-hours post-stroke: mean ± SD, 77 ± 44 to 49 ± 37 mm(3) (single T2* oxygen challenge-based threshold); 55 ± 41 to 37 ± 12 mm(3) (dual T2* oxygen challenge/cerebral blood flow); 84 ± 64 to 42 ± 18 mm(3) (dual cerebral blood flow/apparent diffusion coefficient), as ischemic core grew: 155 ± 37 to 211 ± 36 mm(3) (single apparent diffusion coefficient threshold); 178 ± 56 to 205 ± 33 mm(3) (dual T2* oxygen challenge/cerebral blood flow); 139 ± 30 to 168 ± 38 mm(3) (dual cerebral blood flow/apparent diffusion coefficient). There was evidence of further lesion growth beyond four-hours (T2-defined edema-corrected infarct, 231 ± 19 mm(3) ).
  
  
  CONCLUSIONS
  In conclusion, T2* oxygen challenge combined with perfusion imaging has advantages over alternative magnetic resonance imaging techniques for penumbra detection by providing serial assessment of available penumbra based on tissue viability.
authors.affiliation: Centre for Stroke and Brain Imaging Research, Institute of Neuroscience and Psychology, College of Medicine, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Robertson
authors.forename: Christopher
authors.initials: C
authors.lastname: McCabe
authors.forename: M Rosario
authors.initials: MR
authors.lastname: Lopez-Gonzalez
authors.forename: Graeme A
authors.initials: GA
authors.lastname: Deuchar
authors.forename: Krishna
authors.initials: K
authors.lastname: Dani
authors.forename: William M
authors.initials: WM
authors.lastname: Holmes
authors.forename: Keith W
authors.initials: KW
authors.lastname: Muir
authors.forename: Celestine
authors.initials: C
authors.lastname: Santosh
authors.forename: I Mhairi
authors.initials: IM
authors.lastname: Macrae
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: T2* MRI; ischemic penumbra; neuroimaging; oxygen challenge