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Prediction of hemorrhagic transformation after thrombolytic therapy of clot embolism - An MRI investigation in rat brain

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Neumann-Haefelin,  C.
Konstantin-Alexander Hossmann, Emeriti, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society;

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Brinker,  Gerrit
Konstantin-Alexander Hossmann, Emeriti, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society;

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Uhlenküken,  Ulla
In-vivo-NMR, Research Groups, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society;

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Pillekamp,  Frank
Konstantin-Alexander Hossmann, Emeriti, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society;

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Hossmann,  Konstantin-Alexander
Konstantin-Alexander Hossmann, Emeriti, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society;

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Hoehn,  Mathias
In-vivo-NMR, Research Groups, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society;

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Citation

Neumann-Haefelin, C., Brinker, G., Uhlenküken, U., Pillekamp, F., Hossmann, K.-A., & Hoehn, M. (2002). Prediction of hemorrhagic transformation after thrombolytic therapy of clot embolism - An MRI investigation in rat brain. Stroke, 33(5), 1392-1398.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0026-D85D-8
Abstract
Copyright 2002 American Heart Association, Inc.
Background and Purpose-Thrombolytic treatment of stroke carries the risk of hemorrhagic transformation. Therefore, the potential of MRI for prediction of recombinant tissue plasminogen activator (rtPA)-induced bleeding is explored to identify patients in whom rtPA treatment may provoke such complications. Methods-Spontaneously hypertensive rats (SHR) (n=9) were submitted to middle cerebral artery (MCA) clot embolism, followed 3 hours later by intra-arterial infusion of 10 mg/kg rtPA. Untreated SHR (n=9) were infused with saline. MRI imaging was performed before treatment and included apparent diffusion coefficient (ADC), T2, and per-fusion mapping and contrast enhancement with gadolinium-DTPA. The distribution of intracerebral hemorrhages was studied 3 days later by histological staining. Results-Clot embolism led to the rapid decline of ADC in the territory of the occluded artery. Tissue lesion volume derived from ADC imaging increased by 155 +/- 69% in the untreated animals and by 168 +/- 87% in the treated animals (P=NS), determined on the histological sections after 3 days. This same lesion growth in both groups indicated absence of therapeutic effect after 3-hour treatment delay. Hemorrhagic transformations were significantly more frequent in treated SHR (P<0.05). In untreated rats, hemorrhages were found in the border zone of the ischemic territory in treated animals, hemorrhagic transformations occurred in the ischemic core region. rtPA-induced hemorrhages were predicted by a disturbance of the blood-brain barrier in 3 of 4 animals before treatment by Gd-DTPA contrast enhancement but not by ADC, T2, or per-fusion imaging. The region of contrast enhancement colocalized with subsequent bleeding in these animals. Conclusions-The disturbance of blood-brain barrier but not of other MR parameters allows risk assessment for hemorrhagic transformation induced by subsequent thrombolytic treatment.