====== Sonothrombolysis ======

{{ ::sonothrombolysis.jpg|}}
[[Ultrasound]] has been extensively investigated to promote [[clot lysis]] for the treatment of [[stroke]], [[myocardial infarction]], and acute peripheral arterial occlusions, with or without the use of [[tPA]] or [[contrast]] agents. In the age of modern [[minimally invasive]] [[technique]]s, magnetic resonance imaging-guided [[high intensity focused ultrasound]] is a new emerging modality that seems to promise therapeutic utilities for both ischemic and hemorrhagic stroke. High-intensity focused ultrasound causes thermal heating as the tissue absorbs the mechanical energy transmitted by the ultrasonic waves leading to tissue denaturation and coagulation. Several in-vitro and in-vivo studies have demonstrated the viability of this technology for [[sonothrombolysis]] in both types of stroke and have warranted clinical trials. Apart from safety and efficacy, initiation of trials would further enable answers regarding its practical application in a clinical setup. Though this technology has been under study for treatment of various brain diseases for some decades now, relatively very few neurologists and even neurosurgeons seem to be acquainted with it
((Zafar A, Quadri SA, Farooqui M, Ortega-Gutiérrez S, Hariri OR, Zulfiqar M,
Ikram A, Khan MA, Suriya SS, Nunez-Gonzalez JR, Posse S, Mortazavi MM, Yonas H.
MRI-Guided High-Intensity Focused Ultrasound as an Emerging Therapy for Stroke: A
Review. J Neuroimaging. 2018 Oct 8. doi: 10.1111/jon.12568. [Epub ahead of print]
Review. PubMed PMID: 30295987.
)).
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Recent studies have shown that inconsistent results of [[safety]] and [[efficacy]] between [[sonothrombolysis]] vs. non-sonothombolysis in [[acute ischemic stroke]] (AIS). 

Chen et al., implemented a [[meta-analysis]] to explore the value of sonothrombolysis in AIS treatment. The [[MEDLINE]], [[EMBASE]], and [[Cochrane Library]] [[database]]s were searched for [[randomized]] [[controlled trial]]s (RCTs) which had evaluated sonothrombolysis or [[ultrasound]] [[thrombolysis]] in AIS. One hundred five studies were retrieved and analyzed, among them, 7 RCTs were included in the current meta-analysis. In comparison with the non-sonothombolysis, sonothrombolysis significantly improved complete [[recanalization]] (RR 2.16, 95% CI 1.51 to 3.08, P < 0.001), complete or partial recanalization (RR 1.90, 95% CI 1.26 to 2.88, P = 0.002), there is also a tendency to improvement of ≥ 4 points in [[NIHSS]] score (RR 1.43, 95% CI 0.99 to 2.07, P = 0.057). However, sonothrombolysis and non-sonothrombolysis had insignificant differences in neurological [[recovery]] and adverse events. In subgroup analysis, they found that "With t-PA", "NIHSS > 15", "Treatment time ≤ 150min", and "Age ≤ 65 years" are potential favorable factors for [[efficacy]] [[outcome]]s of sonothombolysis. Sonothrombolysis can significantly increase the rate of recanalization in patients with AIS compared with non-sonothrombolysis, but there is no significant effect on improving neurological functional recovery and avoiding complications
((Chen Z, Xue T, Huang H, Xu J, Shankar S, Yu H, Wang Z. Efficacy and safety of 
sonothombolysis versus non-sonothombolysis in patients with acute ischemic
stroke: A meta-analysis of randomized controlled trials. PLoS One. 2019 Jan
9;14(1):e0210516. doi: 10.1371/journal.pone.0210516. eCollection 2019. PubMed
PMID: 30625224.
)).
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In a study the sonothrombolytic efficacy of a new nanoscaled ultrasound contrast agent (NUSCA) was investigated. This new contrast agent has a size of less than 100 nm and should thus be able to penetrate the thrombus and achieve a [[thrombolysis]] from inside out. In this study human whole [[blood clot]]s were exposed to US, US and NUSCA, US and [[recombinant tissue plasminogen activator]] (rt-Pa) or [[urokinase]] (UK), or a combination of US, NUSCA and thrombolytic drug in a closed-loop flow model. They sonicated with diagnostic US at a frequency of 2.85 MHz for 30 min. Clot mass loss of 50.6 ± 6.0% for the combination of US, NUSCA and rt-PA was found. Using UK as thrombolytic drug 57.7 ± 9.0% clot mass loss could be seen. Thus the weight loss exceeded the conventional values of up to 30%. Scanning electron microscopy (SEM) images revealed changes of the [[fibrin]] network on the [[thrombus]] surface. The NUSCA was able to loosen the network and induce large pores in the thrombus surface. The high rates of clot mass loss and the obvious changings of fibrin structure make our NUSCA a promising tool for sonothrombolytic therapy
((Brüßler J, Strehlow B, Becker A, Schubert R, Schümmelfeder J, Nimsky C,
Bakowsky U. Nanoscaled ultrasound contrast agents for enhanced sonothrombolysis. 
Colloids Surf B Biointerfaces. 2018 Dec 1;172:728-733. doi:
10.1016/j.colsurfb.2018.09.037. Epub 2018 Sep 17. PubMed PMID: 30245298.
)).