Thrombolytic effects of a combined therapy with targeted microbubbles and ultrasound in a 6 h cerebral thrombosis rabbit model

Ren, Shuting; Long, Lihui; Wang, Mei; Li, Yiping; Qin, Hao; Hui, Zhang; Jing, Bo-Bin; Li, Yingxue; Zang, Wei-Jin; Wang, Bing; Shen, Xin-Liang

doi:10.1007/s11239-011-0644-z

Cited by 12 publications

(10 citation statements)

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“…The acoustic pressure range for safe insonification of brain tissue for frequencies in the sub-megahertz range can be determined in animal models and is under investigation (Nedelmann et al, 2008; Schneider et al, 2006; Shimizu et al, 2012). Similarly, the pressure range for efficient thrombolysis enhancement depends on the conditions of the treatment (frequency, presence of a contrast agent) and can be assessed in vitro (Datta et al, 2008, 2006; Hitchcock et al, 2011; Wang Z. et al, 2008) or in animal models (Ren et al, 2011; Saguchi et al, 2008; Wang B. et al, 2008). Considering experimentally established pressure ranges for safe and efficient ultrasound-enhanced thrombolysis, the clinical applicability of a treatment can be assessed using the results of the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The efficiency of UET in the sub-megahertz range have been demonstrated in vitro and in vivo (Behrens et al, 2001; Datta et al, 2006; Hitchcock et al, 2011; Ren et al, 2011; Saguchi et al, 2008; Wang Z. et al, 2008). However, the clinical applicability of low-frequency UET remains to be demonstrated.…”

Section: Introductionmentioning

confidence: 99%

“…A high pressure amplitude combined with constructive interference due to reflections from the contralateral bone likely caused strong local inertial cavitation that induced negative bioeffects (Baron et al, 2009; Wang Z. et al, 2008). Nevertheless, safe and efficient UET has been shown in small animal models (Ren et al, 2011; Saguchi et al, 2008). Ultrasound at 500 kHz with an amplitude that induced thrombolysis enhancement in small animals was also applied transcranially to primates without causing adverse effects (Shimizu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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In silico Study of Low-Frequency Transcranial Ultrasound Fields in Acute Ischemic Stroke Patients

Bouchoux

Shivashankar

Abruzzo

et al. 2014

Ultrasound in Medicine & Biology

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Ultrasound in the sub-megahertz range enhances thrombolysis and may be applied transcranially to ischemic stroke patients. The consistency of transcranial insonification needs to be evaluated. Acoustic and thermal simulations based on computed-tomography (CT) scans of 20 patients were performed. An unfocused 120-kHz transducer allowed homogeneous insonification of the thrombus, and positioning based on external landmarks performed similarly to an optimized placement based on CT data. With a weakly focused 500-kHz transducer, the landmark-based positioning underperformed. The predicted inter-patient variation of in situ acoustic pressure was similar with both transducers for the optimized placement (18.0–26.4% relative standard deviation). The simulated maximum acoustic pressure in intervening tissues was 2.6±0.6 and 2.0±0.7 times the pressure in the thrombus for the 120-kHz and 500-kHz transducers, respectively. A 1 W/cm2 insonification of the thrombus caused a 3.8±2.2°C temperature increase in the bone for the 120-kHz transducer, and a 13.4±3.3°C increase for the 500-kHz transducer. Contralateral local maxima up to 1.1 times the pressure amplitude in the targeted zone were predicted for the 120-kHz transducer. We established two transducer placement approaches, one based on analysis of a head CT and the other using simple external, visible landmarks. Both approaches allowed consistent insonification of the thrombus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In silico Study of Low-Frequency Transcranial Ultrasound Fields in Acute Ischemic Stroke Patients

Bouchoux

Shivashankar

Abruzzo

et al. 2014

Ultrasound in Medicine & Biology

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“…Nedelmann et al [ 32 ] used MRI T2 relaxation time as indicator of edema formation. Cerebral infarct volume was assessed by eight studies as a treatment outcome [ 21 – 25 , 28 , 31 , 32 ]. Nedelmann et al and Schleicher et al [ 32 , 33 ] evaluated vascular volumes with microcomputed tomography.…”

Section: Resultsmentioning

confidence: 99%

“…Nine studies used histological analysis to assess intracranial hemorrhage (ICH) [ 20 – 25 , 28 , 32 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

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

Auboire¹,

Sennoga²,

Hyvelin³

et al. 2018

PLoS ONE

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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/

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Effects of air embolism size and location on porcine hepatic microcirculation in machine perfusion

et al. 2014

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The handling of donor organs frequently introduces air into the microvasculature, but little is known about the extent of the damage caused as a function of the embolism size and distribution. Here we introduced embolisms of different sizes into the portal vein, the hepatic artery, or both during the flushing stage of porcine liver procurement. The outcomes were evaluated during 3 hours of machine perfusion and were compared to the outcomes of livers with no embolisms. Dynamic contrast-enhanced ultrasound (DCEUS) was used to assess the perfusion quality, and it demonstrated that embolisms tended to flow mostly into the left lobe, occasionally into the right lobe, and rarely into the caudate lobe. Major embolisms could disrupt the flow entirely, whereas minor embolisms resulted in reduced or heterogeneous flow. Embolisms occasionally migrated to different regions of the same lobe and, regardless of their size, caused a general deterioration in the flow over time. Histological damage resulted primarily when both vessels of the liver were compromised, whereas bile production was diminished in livers that had arterial embolisms. Air embolisms produced a dose-dependent increase in vascular resistance and a decline in oxygen consumption. This is the first article to quantify the impact of air embolisms on microcirculation in an experimental model, and it demonstrates that air embolisms have the capacity to degrade the integrity of donor organs. The extent of organ damage is strongly dependent on the size and distribution of air embolisms. The diagnosis of embolism severity can be safely and easily made with DCEUS. Liver Transpl 20:601-611, 2014. V C 2014 AASLD.Received October 12, 2013; accepted January 5, 2014.Air embolisms in donor organs are a well-known occurrence. Wolf et al. 1 demonstrated that before transplantation, one-third of donor livers contain intrahepatic air, whereas Liu et al. 2 showed that embolisms occur largely as a result of the routine handling of donor organs. Air can be actively perfused into the donor organ's vasculature during the delivery of the cold flush at the time of procurement, 3,4 during a venovenous bypass, 5-7 and, as machine perfusion (MP) gains popularity, at the time of the connection and during dynamic donor organ preservation. 8 The passive introduction of air can occur when subatmospheric pressures are generated in the vasculature, such as when the organ is suspended above the fluid line and drained, the vasculature is perforated, or air is encapsulated during an anastomosis.2,4,9 Air embolisms are Abbreviations: ALT, alanine aminotransferase; CL, caudate lobe; DCEUS, dynamic contrast-enhanced ultrasound; HA, hepatic artery; LLL, left lateral lobe; LML, left medial lobe; MP, machine perfusion; PV, portal vein.

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Thrombolytic effects of a combined therapy with targeted microbubbles and ultrasound in a 6 h cerebral thrombosis rabbit model

Cited by 12 publications

References 29 publications

In silico Study of Low-Frequency Transcranial Ultrasound Fields in Acute Ischemic Stroke Patients

In silico Study of Low-Frequency Transcranial Ultrasound Fields in Acute Ischemic Stroke Patients

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

Effects of air embolism size and location on porcine hepatic microcirculation in machine perfusion

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