title: Investigating potentially salvageable penumbra tissue in an in vivo model of transient ischemic stroke using sodium, diffusion, and perfusion magnetic resonance imaging.
abstract: Diffusion magnetic resonance imaging (MRI) is the current-state-of-the-art technique to clinically investigate acute (0-24 h) ischemic stroke tissue. However, reduced apparent diffusion coefficient (ADC)-considered a marker of tissue damage-was observed to reverse spontaneously during the subacute stroke phase (24-72 h) which means that low ADC cannot be used to reflect the damaged tissue after 24 h in experimental and clinical studies. One reason for the change in ADC is that ADC values drop with cytotoxic edema (acute phase) and rise when vasogenic edema begins (subacute phase). Recently, combined1H- and23Na-MRI was proposed as a more accurate approach to improve delineation between reversible (penumbra) and irreversible ischemic injury (core). The aim of this study was to investigate the effects of reperfusion on the ADC and the sodium MRI signal after experimental ischemic stroke in rats in well-defined areas of different viability levels of the cerebral lesion, i.e. core and penumbra as defined via perfusion and histology. Transient middle cerebral artery occlusion was induced in male rats by using the intraluminal filament technique. MRI sodium, perfusion and diffusion measurement was recorded before reperfusion, shortly after reperfusion and 24 h after reperfusion. The animals were reperfused after 90 min of ischemia.
  
  
  
  Sodium signal in core did not change before reperfusion, increased after reperfusion while sodium signal in penumbra was significantly reduced before reperfusion, but showed no changes after reperfusion compared to control. The ADC was significantly decreased in core tissue at all three time points compared to contralateral side. This decrease recovered above commonly applied viability thresholds in the core after 24 h.
  
  
  
  Reduced sodium-MRI signal in conjunction with reduced ADC can serve as a viability marker for penumbra detection and complement hydrogen diffusion- and perfusion-MRI in order to facilitate time-independent assessment of tissue fate and cellular bioenergetics failure in stroke patients.
authors.affiliation: Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany.|Trinity Institute of Neuroscience, University of Dublin, Dublin, Ireland.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Wetterling
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Chatzikonstantinou
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, Mannheim, Germany.|CESP, INSERM UMRS1178, Faculté de Pharmacie, University Paris-Sud, Université Paris-Saclay, 92296, Chatenay-Malabry, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Tritschler
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Meairs
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Fatar
authors.affiliation: Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany.
authors.forename: Lothar R
authors.initials: LR
authors.lastname: Schad
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, Mannheim, Germany. Saema.Ansar@med.lu.se.|Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Sölvegatan 17, BMC A13, 22184, Lund, Sweden. Saema.Ansar@med.lu.se.
authors.forename: Saema
authors.initials: S
authors.lastname: Ansar
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging* / Q000503:physiopathology; D018810:Magnetic Resonance Angiography; D008297:Male; D011522:Protons; D017208:Rats, Wistar; D012975:Sodium Isotopes; D020521:Stroke / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D011522:Protons; D012975:Sodium Isotopes
keywords: Diffusion; Magnetic resonance imaging; Perfusion; Sodium; Stroke