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J Cereb Blood Flow Metab. 2019 Dec;39(12):2521-2535. doi: 10.1177/0271678X18802119. Epub 2018 Sep 21.

Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage.

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Department of Translational Medicine and Cell Technology, Fraunhofer Research Institution for Marine Biotechnology and Cell Technology, Lübeck, Germany.
Institute for Medical and Marine Biotechnology, University of Lübeck, Lübeck, Germany.
Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Cell Biology and Genetics Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
Department of Cellular Pathology, St George's University Hospitals NHS Foundation Trust, London, UK.
Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
Department of Neuroradiology, University Hospital of Leipzig, Leipzig, Germany.
Clinic for Nuclear Medicine, University of Leipzig, Leipzig, Germany.
OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum.
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, and Hunter Medical Research Institute, The University of Newcastle, Callaghan, Australia.
Institute of Biomedical Engineering, Faculty of Electrical and Computer Engineering, Technical University of Dresden, Dresden, Germany.
Department for Cell Therapies, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
Department of Pharmacology and Personalised Medicine, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.


Intracerebral hemorrhage (ICH) is an important stroke subtype, but preclinical research is limited by a lack of translational animal models. Large animal models are useful to comparatively investigate key pathophysiological parameters in human ICH. To (i) establish an acute model of moderate ICH in adult sheep and (ii) an advanced neuroimage processing pipeline for automatic brain tissue and hemorrhagic lesion determination; 14 adult sheep were assigned for stereotactically induced ICH into cerebral white matter under physiological monitoring. Six hours after ICH neuroimaging using 1.5T MRI including structural as well as perfusion and diffusion, weighted imaging was performed before scarification and subsequent neuropathological investigation including immunohistological staining. Controlled, stereotactic application of autologous blood caused a space-occupying intracerebral hematoma of moderate severity, predominantly affecting white matter at 5 h post-injection. Neuroimage post-processing including lesion probability maps enabled automatic quantification of structural alterations including perilesional diffusion and perfusion restrictions. Neuropathological and immunohistological investigation confirmed perilesional vacuolation, axonal damage, and perivascular blood as seen after human ICH. The model and imaging platform reflects key aspects of human ICH and enables future translational research on hematoma expansion/evacuation, white matter changes, hematoma evacuation, and other aspects.


Brain; hemorrhage; large animal; perfusion; segmentation

[Available on 2020-12-01]

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