scholarly journals Magnetic Resonance Imaging Indexes of Therapeutic Efficacy of Recombinant Tissue Plasminogen Activator Treatment of Rat at 1 and 4 Hours after Embolic Stroke

2000 ◽  
Vol 20 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Quan Jiang ◽  
Rui Lan Zhang ◽  
Zheng Gang Zhang ◽  
James R. Ewing ◽  
Ping Jiang ◽  
...  

With use of magnetic resonance imaging (MRI), the effects of early and delayed treatment of embolic stroke in rat with recombinant tissue plasminogen activator (rt-PA) were investigated. Rats with embolic stroke were treated with rt-PA at 1 (n = 9) or 4 (n = 7) hours after stroke onset or were untreated (n = 15). Diffusion-weighted imaging, perfusion-weighted imaging, and T2-weighted imaging were performed before and after embolization from 1 hour to 7 days. No significant differences were detected in the relative areas with low cerebral blood flow (CBF), apparent diffusion coefficient of water (ADCw), and T2 between the 4-hour treated group and the untreated group. Significant decreases in the average relative areas with low CBF were detected in the 1-hour treated group from 4 to 48 hours after embolization as compared with the untreated group. The increase in T2 in the 1-hour treated group was significantly lower than in the untreated and 4-hour treated groups. A significant increase in ADCw was detected in the 1-hour treated group at 3 and 24 hours after embolization as compared with the untreated and 4-hour treated groups. Secondary embolization was detected by both MRI and laser scanning confocal microscopy. The data suggest that MRI can detect the efficacy of rt-PA treatment and secondary ischemic damage.

1998 ◽  
Vol 18 (7) ◽  
pp. 758-767 ◽  
Author(s):  
Quan Jiang ◽  
Rui Lan Zhang ◽  
Zheng Gang Zhang ◽  
James R. Ewing ◽  
George W. Divine ◽  
...  

Thrombolysis of embolic stroke in the rat was measured using diffusion (DWI)-, T2 (T2WI)-, and perfusion (PWI)-weighted magnetic resonance imaging (MRI). An embolus was placed at the origin of the middle cerebral artery (MCA) by injection of an autologous single blood clot via an intraluminal catheter placed in the intracranial segment of internal carotid artery. Rats were treated with a recombinant tissue plasminogen activator (rt-PA) 1 hour after embolization (n = 9) or were not treated (n = 15). Diffusion-weighted imaging, T2WI, and PWI were performed before, during, and after embolization from 1 hour to 7 days. After embolization in both rt-PA-treated and control animals, the apparent diffusion coefficient of water (ADCw) and cerebral blood flow (CBF) in the ischemic region significantly declined from the preischemic control values ( P < 0.001). However, mean CBF and ADCw in the rt-PA—treated group was elevated early after administration of rt-PA compared with the untreated control group, and significant differences between the two groups were detected in CBF (24 hours after embolization, P < 0.05) and ADCw (3, 4, and 24 hours after embolization, P < 0.05). T2 values maximized at 24 (control group, P < 0.001) or 48 hours (treated group, P < 0.01) after embolization. The increase in T2 in the control group was significantly higher at 24 hours and 168 hours than in the rt-PA—treated group ( P < 0.05). Significant correlations ( r ≥ 0.80, P < 0.05) were found between lesion volume measured 1 week after embolization and CBF and ADCw obtained 1 hour after injection of rt-PA. Within a coronal section of brain, MRI cluster analysis, which combines ADCw and T2 data maps, indicated a significant reduction ( P < 0.05) in the lesion 24 hours after thrombolysis compared with nontreated animals. These data demonstrate that the values for CBF and ADCw obtained 1 hour after injection of rt-PA correlate with histologic outcome in the tissue, and that the beneficial effect of thrombolysis of an intracranial embolus by means of rt-PA is reflected in an increase of CBF and ADCw, a reduction in the increase of T2, and a reduction of the ischemic lesion size measured using MRI cluster analysis.


Neurosurgery ◽  
2002 ◽  
Vol 50 (2) ◽  
pp. 251-260 ◽  
Author(s):  
Jose I. Suarez ◽  
Osama O. Zaidat ◽  
Jeffrey L. Sunshine ◽  
Robert Tarr ◽  
Warren R. Selman ◽  
...  

ABSTRACT OBJECTIVE To determine the feasibility of combined intravenous and intra-arterial thrombolytic therapy for acute ischemic strokes and to evaluate its associated risks, using magnetic resonance imaging as a triage tool. Intravenous treatment followed by intra-arterial infusion may increase the rate of recanalization and lead to better clinical results, with reduced frequency of intracranial hemorrhage. METHODS Our Brain Attack Team evaluated patients who presented within 3 hours after symptom onset. Patients who did not demonstrate improvement and exhibited no evidence of intracranial hemorrhage on head computed tomographic scans were treated with intravenously administered recombinant tissue plasminogen activator (0.6 mg/kg) and underwent emergency magnetic resonance imaging of the head. T2-weighted turbo-gradient and spin echo and echo-planar diffusion- and perfusion-weighted imaging scans were obtained. Patients with evidence of imaging abnormalities indicating acute cortical infarction underwent cerebral angiography. After determination of vessel occlusion, intra-arterially administered urokinase (up to 750,000 units) or intra-arterially administered recombinant tissue plasminogen activator (maximal dose, 0.3 mg/kg) was used to achieve recanalization. RESULTS We treated 45 patients with this protocol. The mean age was 67 ± 13 years, and 58% of the patients were women. There was a significant improvement in National Institutes of Health Stroke Scale scores after treatment. There was good correlation between abnormal perfusion-weighted imaging findings and cerebral angiographic findings (complete vessel occlusion). The incidence of symptomatic intracranial hemorrhage was 4.4% in this cohort. Seven patients died in the hospital, and the majority of survivors (77%) experienced good outcomes (Barthel index of ≥95) 3 months after treatment. CONCLUSION Our data demonstrate that this protocol is feasible and that combined intravenous and intra-arterial thrombolysis to treat acute ischemic strokes is sufficiently safe to warrant further evaluation.


2002 ◽  
Vol 97 (4) ◽  
pp. 954-962 ◽  
Author(s):  
Veit Rohde ◽  
Ina Rohde ◽  
Ruth Thiex ◽  
Azize Ince ◽  
Axel Jung ◽  
...  

Object. Fibrinolysis therapy accomplished using tissue plasminogen activator (tPA) and aspiration is considered to be a viable alternative to microsurgery and medical therapy for the treatment of deep-seated spontaneous intracerebral hematomas (SICHs). Tissue plasminogen activator is a mediator of thrombin- and ischemia-related delayed edema. Because both thrombin release and ischemia occur after SICH, the authors planned to investigate the effect of fibrinolytic therapy on hematoma and delayed edema volume. Methods. A spherical hematoma was created in the frontal white matter of 18 pigs. In the tPA-treated group (nine pigs), a mean of 1.55 ml tPA was injected into the clot and the resulting liquefied blood was aspirated. Magnetic resonance (MR) imaging was performed on Days 0 (after surgery), 4, and 10, and the volumes of hematoma and edema were determined. In the animals not treated with tPA (untreated group; nine pigs), the volume of hematoma dropped from 1.43 ± 0.42 ml on Day 0 to 0.85 ± 0.28 ml on Day 10. In the tPA-treated group, the volume of hematoma was reduced from 1.51 ± 0.28 ml on Day 0 to 0.52 ± 0.39 ml on Day 10. In comparison with the untreated group, the reduction in hematoma volume was significantly accelerated (p = 0.02). In the untreated group, perihematomal edema increased from 0.32 ± 0.61 ml to 1.73 ± 0.73 ml on Day 4, before dropping to 1.17 ± 0.92 ml on Day 10. In the tPA-treated group, the volume of the edema increased from 0.09 ± 0.21 ml on Day 0 to 1.93 ± 0.79 ml on Day 4, and further to 3.34 ± 3.21 ml on Day 10. The increase in edema volume was significantly more pronounced in the tPA-treated group (p = 0.04). Conclusions. Despite a significantly accelerated reduction in hematoma volume, the development of delayed perifocal edema was intensified by fibrinolytic therapy, which is probably related to the function of tPA as a mediator of edema formation after thrombin release and ischemia. Further experimental and clinical investigations are required to establish the future role of fibrinolysis in the management of SICH.


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