MRI of experimental focal cerebral ischemia in sheep

Purpose: With respect to the specific characteristic of rete mirabile epidurale rostrale in sheep, the aim of this study was to investigate the use of time of flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and to validate MCA occlusion in a new model of experimental focal cerebral ischemia by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study stroke therapy using autologous stem cells from umbilical cord blood). Furthermore, we wanted to assess the extent and natural time course of ischemic focal brain injury in sheep using functional and morphological magnetic resonance imaging (MRI). Materials and Method: 13 Merino sheep were examined. In 4 of the animals all, in 5 sheep I or 2 MCA branches were occluded and in 1 one case touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI sessions were performed in 10 sheep. These sessions included T1, T2, T2* sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2-46 days after the onset of stroke using a 1.5T clinical MR scanner. Corrosion casts of the cerebral arteries of 3 sheep were prepared and compared to MRA. Results: The MRA visualized the vessel anatomy or occlusion distal to the rete mirabile. Anatomical variants concerning the variant origin of the MCA and inconstant arteria choroidea rostralis and communicans rostralis were revealed. Sheep with occluded left MCA showed space occupying lesions with a drop in ADC values. Depending on the number of preserved MCA branches (0; 1; 2), highly significant (p < 0.001) differences in lesion size (21 +/- 5.7; 13; 1.7 +/- 1.3 ml) could be found. No indication of ischemia but minimal contusion damage was observed in the sham operated animal. Conclusions: In our study focal cerebral ischemia was generated in sheep and examined using MRI for the first time. Depending on the occlusion type, the model produced a reproducible lesion size. TOF-MRA proved to be able to clearly depict the anatomy, variants and occlusion type of cerebral arteries in sheep in a manner comparable to that of corrosion casts despite the upstream rete mirabile. MRI with MRA is a useful tool for assessing the extent of brain injury and the type of MCA occlusion and is therefore suitable for non-invasive monitoring of lesion development upon stroke.