Prediction of hemorrhagic transformation after thrombolytic therapy of clot embolism: an MRI investigation in rat brain.
OBJECTIVE
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 perfusion 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 perfusion 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.
Neumann-Haefelin
C
C
Department of Experimental Neurology, Max-Planck Institute for Neurological Research, Cologne, Germany.
Brinker
G
G
Uhlenküken
U
U
Pillekamp
F
F
Hossmann
K-A
KA
Hoehn
M
M
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D004058:Diffusion / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D019786:Gadolinium DTPA; D015994:Incidence; D007261:Infusions, Intra-Arterial; D020766:Intracranial Embolism / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D011237:Predictive Value of Tests; D051381:Rats; D011918:Rats, Inbred SHR; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*
D011994:Recombinant Proteins; C103761:gadolinium-DTPA bis-glucosamide; D010959:Tissue Plasminogen Activator; D019786:Gadolinium DTPA