Barthel, H.H.BarthelBoltze, J.J.BoltzeGrossmann, U.U.GrossmannSchildan, A.A.SchildanFörschler, A.A.FörschlerGille, U.U.GillePatt, M.M.PattSeese, A.A.SeeseEmmrich, F.F.EmmrichSabri, O.O.Sabri2022-03-042022-03-042007https://publica.fraunhofer.de/handle/publica/215146In stroke, stem cell (SC) treatment is currently in the stage of translation from preclinical to clinical testing as a new therapy option. It is estimated to have the potential to overcome the therapeutic nihilism which exists in stroke apart from the 3-hours time window in which thrombolysis is effective. We have developed a new large-animal stroke model with the aim to apply this model for evaluation of the effect of autologous SCs cells on stroke outcome. This present study was initiated to test whether it is feasible to quantify sheep brain perfusion and glucose consumption (as a surrogate parameter of brain viability) after stroke by employing a clinical PET scanner. In adult male Merino sheep, stroke was induced by complete left middle cerebral artery occlusion (MCAO) using high-frequency bipolar forceps. 24h after MCAO, 4.0mio kg-1 autologous mononuclear bone-marrow cells (containing 1.5-2.0% stromal and hematopoietic SCs) were given i.v. Brain PET was carried ou t immediately before SC application, 2wks and 6wks after MCAO. For that purpose, the sheep were anesthetized, i.v. injected with 1000 and 370 MBq [15O]H2O and [18F]FDG, respectively, and dynamically scanned on a clinical high-resolution ECAT EXACT HR+ scanner. The PET imaging was paralleled by neurological investigations using an established clinical score as well as by MRI (1.5T Gyroscan Integra; T1, T2, T2*, diffusion-weighted sequences, MRA). The PET image data were co-registered with the individual MRI data employing the MultiModality software. The animals were sacrificed 7wks after MCAO and brain histology was obtained. So far, 13 PET investigations have been carried out in the animals. Radiotracer input function which is required for PET data modeling was no obtainable from arterial blood samples. This was due to the follow-up design of this study and the complex anatomy of the sheep vasculature. As an alternative it was verified that it is possible to derive the input function internally fromen610616journal article