Microbubbles combined with ultrasound therapy in ischemic stroke: A systematic review of in-vivo preclinical studies

Abstract

BackgroundMicrobubbles (MBs) combined with ultrasound sonothrombolysis (STL) appears to be an alternative therapeutic strategy for acute ischemic stroke (IS), but clinical results remain controversial.ObjectiveThe aim of this systematic review is to identify the parameters tested; to assess evidence on the safety and efficacy on preclinical data on STL; and to assess the validity and publication bias.MethodsPubmed® and Web of ScienceTM databases were systematically searched from January 1995 to April 2017 in French and English. We included studies evaluating STL on animal stroke model. This systematic review was conducted in accordance with the PRISMA guidelines. Data were extracted following a pre-defined schedule by two of the authors. The CAMARADES criteria were used for quality assessment. A narrative synthesis was conducted.ResultsSixteen studies met the inclusion criteria. The result showed that ultrasound parameters and types of MBs were heterogeneous among studies. Numerous positive outcomes on efficacy were found, but only four studies demonstrated superiority of STL versus recombinant tissue-type plasminogen activator on clinical criteria. Data available on safety are limited.LimitationsQuality assessment of the studies reviewed revealed a number of biases.ConclusionFurther in vivo studies are needed to demonstrate a better efficacy and safety of STL compared to currently approved therapeutic options.Systematic review registrationhttp://syrf.org.uk/protocols/

Efficacy and safety of sonothombolysis versus non-sonothombolysis in patients with acute ischemic stroke: A meta-analysis of randomized controlled trials

“…Hence, the ultrasound-induced blast of microbubbles may speed up the dissolution of thrombus. Microbubbles combined with TCD/TCCS were also applied to some other clinical trials, which might be able to get better clinical outcomes [12].…”

Advances in Sonothrombolysis Techniques Using Piezoelectric Transducers

“…Given the culmination of transcranial Doppler, microbubble mediated, and intravascular sonothrombolysis research to clinical trials, it is still necessary to improve these technologies to address the observed clinical outcomes and limitations. There have been several extensive reviews on the benefits of thrombolytic mediated sonothrombolysis, microbubble mediated sonothrombolysis, and intravascular sonothrombolysis [60,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81]. However, there still exists a clinical need for thrombolysis techniques which can decrease the risk of hemhorrage, vessel damage, and pulmonary embolism while also reducing the dose of thrombolytic agents and treatment times for patients.…”

“…The use of standard lipid shelled microbubbles such as Sonovue and Definity either alone or in combination with thrombolytic agents such as tPA have been studied and reviewed in great detail [67,75]. Microbubbles both alone and when used in combination with a thrombolytic agent for sonothrombolysis treatment uniformly outperform traditional thrombolytic treatments.…”

Progress in the Treatment of Acute Ischemic Stroke, Current Challenges and the Establishment of Clinical Decision-Making System

“…Thrombolysis combined with ultrasound refers to the use of ultrasonic pulse to fracture emboli during thrombolysis. It increases the contact area of emboli and drug, promotes the dissolution of thrombus and makes good blood vessel dredging, which has become a hot spot of current research [32,33].…”