Ultrasound Identification and Lysis of Clots (original) (raw)
Related papers
Ultrasound-Enhanced Thrombolysis for Acute Ischemic Stroke: Phase I. Findings of the CLOTBUST Trial
Journal of Neuroimaging, 2004
Background. Tissue plasminogen activator (TPA) activity may be enhanced with ultrasound, potentially 2 MHz transcranial Doppler (TCD). The authors present Phase I data of the CLOTBUST (Combined Lysis of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic TPA). Subjects and Methods. Nonrandomized stroke patients with proximal arterial occlusion on a prebolus TCD receiving intravenous 0.9 mg/kg TPA within 3 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5. Results. 55 patients (mean age 69 ± 15 years, median baseline NIH Stroke Scale [NIHSS] 18, range 4-29, 90% with ³ 9 points) were treated at 125 ± 36 minutes from symptom onset. TCD monitoring began at 117 ± 39 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 20 patients (36%). Dramatic recovery (NIHSS score ≤ 3) occurred in 20% at 2 hours and in 24% at 24 hours. Overall improvement by ≥ 4 NIHSS points was found in 49% at 24 hours. Improvement was associated with recanalization during or shortly after TPA infusion (Φ r 2 = .5, P = .03); however, in 6/20 patients with complete recanalization (30%), no immediate clinical change was noticed within 2 hours. Overall symptomatic hemorrhage rate was 5.5%. Conclusions. Continuous TCD insonation for up to 2 hours at maximum intensities allowed by current bio-safety guidelines is safe. Dramatic recovery and complete recanalization shortly after TPA bolus are feasible goals for thrombolysis given with TCD monitoring.
Stroke, 2006
Background and Purpose-We sought to evaluate the effects of administration of microbubbles (MBs) on the beginning, speed, and degree of middle cerebral artery (MCA) recanalization during systemic thrombolysis and continuous 2-MHz pulsed-wave transcranial Doppler (TCD) monitoring. Methods-We evaluated 111 patients with acute stroke attributable to MCA occlusion treated with intravenous tissue plasminogen activator (tPA). Thirty-eight patients were treated with tPA plus continuous 2-hour TCD monitoring plus 3 doses of 2.5 g (400 mg/mL) of galactose-based MBs given at 2, 20, and 40 minutes after tPA bolus (MB group). These patients were compared with 73 patients who were allocated to receive tPA plus continuous 2-hour TCD ultrasound (US) monitoring (tPA/US group) or tPA plus placebo monitoring (tPA group), most of whom were enrolled in a previous study of US-enhanced thrombolysis. The beginning, degree, and time to maximum completeness of recanalization during the first 2 hours of tPA bolus were recorded. Results-Median prebolus National Institutes of Health Stroke Scale (NIHSS) score was 18. Eighty patients (72%) had a proximal and 31 (28%) a distal MCA occlusion on TCD. Thirty-seven patients (33%) received tPA/US, 38 (34%) received tPA/US/MB, and 36 (32%) were treated with tPA alone. Stroke severity, time to treatment, location of MCA occlusion, and presence of carotid artery disease were similar among groups. Two-hour recanalization was seen in 14 (39%), 25 (68%), and 27 patients (71%) in the tPA, tPA/US, and tPA/US/MB groups, respectively (Pϭ0.004). Two-hour complete recanalization rate was significantly (Pϭ0.038) higher in the tPA/US/MB group (54.5%) compared with tPA/US (40.8%) and tPA (23.9%) groups. The time to beginning of recanalization after tPA bolus was 26Ϯ18 minutes in the tPA/US group and 19Ϯ12 minutes in the tPA/US/MB group (Pϭ0.12). Four patients (3.6%) experienced symptomatic intracranial hemorrhage: 2 (5.5%), 1 (2.7%), and 1 patient (2.6%) who received tPA only, tPA/US, and tPA/US/MB, respectively, experienced symptomatic intracranial hemorrhage. At 24 hours, 31%, 41%, and 55% of tPA, tPA/US, and tPA/US/MB improved Ͼ4 points in the NIHSS score. Conclusions-Administration of MBs induces further acceleration of US-enhanced thrombolysis in acute stroke, leading to a more complete recanalization and to a trend toward better short-and long-term outcome. (Stroke. 2006;37:425-429.)
Ultrasound enhanced thrombolysis: applications in acute cerebral ischemia
Journal of clinical neurology (Seoul, Korea), 2007
Intravenous tissue plasminogen activator (TPA) improves patient chances to recover from stroke by inducing mostly partial recanalization of large intracranial thrombi. TPA activity can be enhanced with ultrasound including 2 MHz transcranial Doppler (TCD). TCD identifies residual blood flow signals around thrombi, and, by delivering mechanical pressure waves, exposes more thrombus surface to circulating TPA. The international multi-center CLOTBUST trial showed that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming multi-disciplinary experimental research conducted worldwide for the past 30 years.In the CLOTBUST trial, the dramatic clinical recovery from stroke coupled with complete recanalization within 2 hours after TPA bolus occurred in 25% of patients treated with TPA+TCD compared to 8% who received TPA alone (p=0.02). Complete clearance of a thrombus and dramatic recovery of brain functions during treatment are feasible goals for ultrasound-enhance...
2010
Background-The duration of cerebral blood flow impairment correlates with irreversibility of brain damage in animal models of cerebral ischemia. Our aim was to correlate clinical recovery from stroke with the timing of arterial recanalization after therapy with intravenous tissue plasminogen activator (tPA). Methods-Patients with symptoms of cerebral ischemia were treated with 0.9 mg/kg tPA IV within 3 hours after stroke onset (standard protocol) or with 0.6 mg/kg at 3 to 6 hours (an experimental institutional review board-approved protocol). National Institutes of Health Stroke Scale (NIHSS) scores were obtained before treatment, at the end of tPA infusion, and at 24 hours; Rankin Scores were obtained at long-term follow-up. Transcranial Doppler (TCD) was used to locate arterial occlusion before tPA and to monitor recanalization (Marc head frame, Spencer Technologies; Multigon 500M, DWL MultiDop-T). Recanalization on TCD was determined according to previously developed criteria. Results-Forty patients were studied (age 70Ϯ16 years, baseline NIHSS score 18.6Ϯ6.2). A tPA bolus was administered at 132Ϯ54 minutes from symptom onset. Recanalization on TCD was found at the mean time of 251Ϯ171 minutes after stroke onset: complete recanalization occurred in 12 (30%) patients and partial recanalization occurred in 16 (40%) patients (maximum observation time 360 minutes). Recanalization occurred within 60 minutes of tPA bolus in 75% of patients who recanalized. The timing of recanalization inversely correlated with early improvement in the NIHSS scores within the next hour (polynomial curve, third order r 2 ϭ0.429, PϽ0.01) as well as at 24 hours. Complete recanalization was common in patients who had follow-up Rankin Scores if 0 to 1 (Pϭ0.006). No patients had early complete recovery if an occlusion persisted for Ͼ300 minutes. Conclusions-The timing of arterial recanalization after tPA therapy as determined with TCD correlates with clinical recovery from stroke and demonstrates a 300-minute window to achieve early complete recovery. These data parallel findings in animal models of cerebral ischemia and confirm the relevance of these models in the prediction of response to reperfusion therapy. (Stroke. 2000;31:1812-1816.)