Ultrasound enhanced thrombolysis in acute arterial ischemia

Research output: Contribution to journalReview article

47 Citations (Scopus)

Abstract

In vitro and animal studies have shown that thrombolysis with intravenous tissue plasminogen activator (tPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Moreover, intravenous gaseous microspheres with ultrasound have been shown to be a potential alternative to fibrinolytic agents to recanalize discrete peripheral thrombotic arterial occlusions or acute arteriovenous graft thromboses. Small phase I-II randomized and non-randomized clinical trials have shown promising results concerning the potential applications of ultrasound-enhanced thrombolysis in the setting of acute cerebral ischemia. CLOTBUST was an international four-center phase II trial, which demonstrated that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments tPA-induced arterial recanalization (sustained complete recanalization rates: 38% vs. 13%) with a non-significant trend toward an increased rate of clinical recovery from stroke, as compared with placebo. The rates of symptomatic intracerebral hemorrhage (sICH) were similar in the active and placebo group (4.8% vs. 4.8%). Smaller single-center clinical trials using transcranial color-coded sonography (TCCD) reported recanalization rates ranging from 27% to 64% and sICH rates of 0-18%. A separate clinical trial evaluating the safety and efficacy of therapeutic low-frequency ultrasound was discontinued because of a concerning sICH rate of 36% in the active group. To further enhance the ability of tPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Moreover, potential enhancement of intra-arterial tPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter) in ongoing phase II-III clinical trials. Intravenous platelet-targeted microbubbles with low-frequency ultrasound are currently investigated as a rapid noninvasive technique to identify thrombosed intracranial and peripheral vessels. Multi-national dose escalation studies of microspheres and the development of an operator independent ultrasound device are underway.

Original languageEnglish (US)
Pages (from-to)303-311
Number of pages9
JournalUltrasonics
Volume48
Issue number4
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

Fingerprint

ischemia
Tissue Plasminogen Activator
Cerebral Hemorrhage
Ischemia
Microspheres
hemorrhages
Phase II Clinical Trials
Thrombosis
perflutren
Stroke
Placebos
Clinical Trials
strokes
Intracranial Thrombosis
Microbubbles
Phase III Clinical Trials
Fibrinolytic Agents
Brain Ischemia
low frequencies
thrombosis

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Acoustics and Ultrasonics

Cite this

Ultrasound enhanced thrombolysis in acute arterial ischemia. / Tsivgoulis, Georgios; Culp, William C.; Alexandrov, Andrei.

In: Ultrasonics, Vol. 48, No. 4, 01.08.2008, p. 303-311.

Research output: Contribution to journalReview article

@article{fafa0f3df4744a09beb2f18d8cfa80e5,
title = "Ultrasound enhanced thrombolysis in acute arterial ischemia",
abstract = "In vitro and animal studies have shown that thrombolysis with intravenous tissue plasminogen activator (tPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Moreover, intravenous gaseous microspheres with ultrasound have been shown to be a potential alternative to fibrinolytic agents to recanalize discrete peripheral thrombotic arterial occlusions or acute arteriovenous graft thromboses. Small phase I-II randomized and non-randomized clinical trials have shown promising results concerning the potential applications of ultrasound-enhanced thrombolysis in the setting of acute cerebral ischemia. CLOTBUST was an international four-center phase II trial, which demonstrated that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments tPA-induced arterial recanalization (sustained complete recanalization rates: 38{\%} vs. 13{\%}) with a non-significant trend toward an increased rate of clinical recovery from stroke, as compared with placebo. The rates of symptomatic intracerebral hemorrhage (sICH) were similar in the active and placebo group (4.8{\%} vs. 4.8{\%}). Smaller single-center clinical trials using transcranial color-coded sonography (TCCD) reported recanalization rates ranging from 27{\%} to 64{\%} and sICH rates of 0-18{\%}. A separate clinical trial evaluating the safety and efficacy of therapeutic low-frequency ultrasound was discontinued because of a concerning sICH rate of 36{\%} in the active group. To further enhance the ability of tPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Moreover, potential enhancement of intra-arterial tPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter) in ongoing phase II-III clinical trials. Intravenous platelet-targeted microbubbles with low-frequency ultrasound are currently investigated as a rapid noninvasive technique to identify thrombosed intracranial and peripheral vessels. Multi-national dose escalation studies of microspheres and the development of an operator independent ultrasound device are underway.",
author = "Georgios Tsivgoulis and Culp, {William C.} and Andrei Alexandrov",
year = "2008",
month = "8",
day = "1",
doi = "10.1016/j.ultras.2007.11.008",
language = "English (US)",
volume = "48",
pages = "303--311",
journal = "Ultrasonics",
issn = "0041-624X",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Ultrasound enhanced thrombolysis in acute arterial ischemia

AU - Tsivgoulis, Georgios

AU - Culp, William C.

AU - Alexandrov, Andrei

PY - 2008/8/1

Y1 - 2008/8/1

N2 - In vitro and animal studies have shown that thrombolysis with intravenous tissue plasminogen activator (tPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Moreover, intravenous gaseous microspheres with ultrasound have been shown to be a potential alternative to fibrinolytic agents to recanalize discrete peripheral thrombotic arterial occlusions or acute arteriovenous graft thromboses. Small phase I-II randomized and non-randomized clinical trials have shown promising results concerning the potential applications of ultrasound-enhanced thrombolysis in the setting of acute cerebral ischemia. CLOTBUST was an international four-center phase II trial, which demonstrated that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments tPA-induced arterial recanalization (sustained complete recanalization rates: 38% vs. 13%) with a non-significant trend toward an increased rate of clinical recovery from stroke, as compared with placebo. The rates of symptomatic intracerebral hemorrhage (sICH) were similar in the active and placebo group (4.8% vs. 4.8%). Smaller single-center clinical trials using transcranial color-coded sonography (TCCD) reported recanalization rates ranging from 27% to 64% and sICH rates of 0-18%. A separate clinical trial evaluating the safety and efficacy of therapeutic low-frequency ultrasound was discontinued because of a concerning sICH rate of 36% in the active group. To further enhance the ability of tPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Moreover, potential enhancement of intra-arterial tPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter) in ongoing phase II-III clinical trials. Intravenous platelet-targeted microbubbles with low-frequency ultrasound are currently investigated as a rapid noninvasive technique to identify thrombosed intracranial and peripheral vessels. Multi-national dose escalation studies of microspheres and the development of an operator independent ultrasound device are underway.

AB - In vitro and animal studies have shown that thrombolysis with intravenous tissue plasminogen activator (tPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Moreover, intravenous gaseous microspheres with ultrasound have been shown to be a potential alternative to fibrinolytic agents to recanalize discrete peripheral thrombotic arterial occlusions or acute arteriovenous graft thromboses. Small phase I-II randomized and non-randomized clinical trials have shown promising results concerning the potential applications of ultrasound-enhanced thrombolysis in the setting of acute cerebral ischemia. CLOTBUST was an international four-center phase II trial, which demonstrated that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments tPA-induced arterial recanalization (sustained complete recanalization rates: 38% vs. 13%) with a non-significant trend toward an increased rate of clinical recovery from stroke, as compared with placebo. The rates of symptomatic intracerebral hemorrhage (sICH) were similar in the active and placebo group (4.8% vs. 4.8%). Smaller single-center clinical trials using transcranial color-coded sonography (TCCD) reported recanalization rates ranging from 27% to 64% and sICH rates of 0-18%. A separate clinical trial evaluating the safety and efficacy of therapeutic low-frequency ultrasound was discontinued because of a concerning sICH rate of 36% in the active group. To further enhance the ability of tPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Moreover, potential enhancement of intra-arterial tPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter) in ongoing phase II-III clinical trials. Intravenous platelet-targeted microbubbles with low-frequency ultrasound are currently investigated as a rapid noninvasive technique to identify thrombosed intracranial and peripheral vessels. Multi-national dose escalation studies of microspheres and the development of an operator independent ultrasound device are underway.

UR - http://www.scopus.com/inward/record.url?scp=48149110814&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48149110814&partnerID=8YFLogxK

U2 - 10.1016/j.ultras.2007.11.008

DO - 10.1016/j.ultras.2007.11.008

M3 - Review article

VL - 48

SP - 303

EP - 311

JO - Ultrasonics

JF - Ultrasonics

SN - 0041-624X

IS - 4

ER -