title: Thromboembolic stroke in C57BL/6 mice monitored by 9.4 T MRI using a 1H cryo probe.
abstract: BACKGROUND
  A new thromboembolic animal model showed beneficial effects of t-PA with an infarct volume reduction of 36.8% in swiss mice. Because knock-out animal experiments for stroke frequently used C57BL76 mice we evaluated t-PA effects in this mouse strain and measured infarct volume and vascular recanalisation in-vivo by using high-field 9.4 T MRI and a 1H surface cryo coil.
  
  
  METHODS
  Clot formation was triggered by microinjection of murine thrombin into the right middle cerebral artery (MCA). Animals (n = 28) were treated with 10 mg/kg, 5 mg/kg or no tissue plasminogen activator (t-PA) 40 min after MCA occlusion. For MR-imaging a Bruker 9.4 T animal system with a 1H surface cryo probe was used and a T2-weighted RARE sequence, a diffusion weighted multishot EPI sequence and a 3D flow-compensated gradient echo TOF angiography were performed.
  
  
  RESULTS
  The infarct volume in animals treated with t-PA was significantly reduced (0.67 ± 1.38 mm3 for 10 mg/kg and 10.9 ± 8.79 mm3 for 5 mg/kg vs. 19.76 ± 2.72 mm3 ; p < 0.001) compared to untreated mice. An additional group was reperfused with t-PA inside the MRI. Already ten minutes after beginning of t-PA treatment, reperfusion flow was re-established in the right MCA. However, signal intensity was lower than in the contralateral MCA. This reduction in cerebral blood flow was attenuated during the first 60 minutes after reperfusion. 24 h after MCA occlusion and reperfusion, no difference in signal intensity of the contralateral and ipsilateral MCAs was observed.
  
  
  CONCLUSIONS
  We confirm a t-Pa effect using this stroke model in the C57BL76 mouse strain and demonstrate a chronological sequence MRI imaging after t-PA using a 1H surface cryo coil in a 9.4 T MRI. This setting will allow testing of new thrombolytic strategies for stroke treatment in-vivo in C57BL76 knock-out mice.
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. fatar@neuro.ma.uni-heidelberg.de.
authors.forename: Friederike L
authors.initials: FL
authors.lastname: Langhauser
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Heiler
authors.forename: Saskia
authors.initials: S
authors.lastname: Grudzenski
authors.forename: Andreas
authors.initials: A
authors.lastname: Lemke
authors.forename: Angelika
authors.initials: A
authors.lastname: Alonso
authors.forename: Lothar R
authors.initials: LR
authors.lastname: Schad
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hennerici
authors.forename: Stephen
authors.initials: S
authors.lastname: Meairs
authors.forename: Marc
authors.initials: M
authors.lastname: Fatar