title: Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging.
abstract: The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke.
authors.affiliation: 1 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, UK.
authors.forename: George W J
authors.initials: GW
authors.lastname: Harston
authors.affiliation: 2 Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK 3 Department of Mechatronics and Biomedical Engineering, Lee Kong Chian Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Malaysia.
authors.forename: Yee Kai
authors.initials: YK
authors.lastname: Tee
authors.affiliation: 4 Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Blockley
authors.affiliation: 4 Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, UK.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Okell
authors.affiliation: 1 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, UK.
authors.forename: Sivarajan
authors.initials: S
authors.lastname: Thandeswaran
authors.affiliation: 1 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, UK.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Shaya
authors.affiliation: 5 Department of Neuroradiology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Fintan
authors.initials: F
authors.lastname: Sheerin
authors.affiliation: 5 Department of Neuroradiology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Martino
authors.initials: M
authors.lastname: Cellerini
authors.affiliation: 2 Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Payne
authors.affiliation: 4 Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Jezzard
authors.affiliation: 2 Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Chappell
authors.affiliation: 1 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, UK james.kennedy@rdm.ox.ac.uk.
authors.forename: James
authors.initials: J
authors.lastname: Kennedy
mesh_terms: D000369:Aged, 80 and over; D000704:Analysis of Variance; D020520:Brain Infarction / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000175:diagnosis* / Q000209:etiology*
keywords: acidosis; chemical exchange saturation transfer; ischaemic stroke; magnetic resonance imaging; pH-weighted imaging