Low-Frequency Therapeutic Ultrasound with Varied Duty Cycle: Effects on the Ischemic Brain and the Inner Ear

Reuter, P.; Masomi, Julia; Kuntze, Holger; Fischer, I.; Helling, Kai; Sommer, Clemens; Alessandri, Beat; Heimann, Axel; Gerriets, Tibo; Marx, Jürgen; Kempski, Oliver; Nedelmann, Max

doi:10.1016/j.ultrasmedbio.2010.04.013

Cited by 8 publications

(5 citation statements)

References 22 publications

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“…The transducers used in the TRUMBI trial [14] had a total area of about 2,830 mm 2 , which is about 18-fold of that (≈150 mm 2 ) of a conventional clinical transcranial Doppler ultrasound transducer. In addition, the transducers used in the animal experiments by Schneider et al [15] and by Reuter et al [18] were also relatively large (350 mm 2 , about 17.5-fold higher than the LFTUS in the present study). These large transducers result in delivery of much more acoustic energy into the intracranial cavity and increase the formation of dangerous standing waves near the opposite cranium [10,30].…”

Section: Discussionmentioning

confidence: 47%

“…However, the TRUMBI trial demonstrated that low-frequency transcranial ultrasound (LFTUS) is associated with a very high rate of symptomatic intracranial hemorrhages in patients with AIS [14]. Studies performed to investigate the reasons for these complications [15,16,17,18] suggest that hemorrhage may be related to a variety of factors, including intensity-dependent effects in the brain [15] and disruption of the blood-brain barrier [16]. …”

Section: Introductionmentioning

confidence: 99%

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Safety of Low-Frequency Transcranial Ultrasound in Permanent Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats

Wang

Fukuda²,

Azuma³

et al. 2011

Cerebrovasc Dis

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Background: Some studies suggest that low-frequency transcranial ultrasound (LFTUS) can enhance thrombolysis, but other studies suggest that it may have adverse effects on intracranial tissues. We previously reported that LFTUS with appropriate parameters was effective and safe in a normotensive rat model of thromboembolic middle cerebral artery occlusion (MCAO) stroke. The goal of this study was to test the safety of this strategy in a spontaneously hypertensive rat (SHR) model of permanent MCAO. Methods: Right MCAO was achieved in male SHRs using intraluminal nylon sutures. Rats exhibiting left hemiparesis were randomly assigned to one of four different groups: (1) normal saline (NS) group (n = 8), intravenous administration of NS as placebo at 3 h after MCAO; (2) NS+LFTUS group (n = 10), NS administration with simultaneous application of LFTUS (480.4 kHz, continuous wave, at an intensity of 0.3 W/cm²) for 1 h; (3) tissue plasminogen activator (tPA) group (n = 11), intravenous administration of alteplase (10 mg/kg body weight) over 1 h instead of NS; or (4) tPA+LFTUS group (n = 11), tPA administration and application of LFTUS. Twenty-four hours after treatment, neurological change was evaluated, and brains were removed and examined histologically. Results: There was no significant difference (p > 0.09) when comparing changes in neurologic status and body weight, infarct ratio, edema ratio, or hemorrhagic transformation among the four groups. Conclusions: Our findings suggest that sonothrombolytic treatment with LFTUS with appropriate parameters is safe when used for the treatment of ischemic stroke in hypertensive rats under the undesired permanent MCAO condition.

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Section: Discussionmentioning

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Safety of Low-Frequency Transcranial Ultrasound in Permanent Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats

Wang

Fukuda²,

Azuma³

et al. 2011

Cerebrovasc Dis

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“…Numerous studies have been conducted to investigate the targeted treatment using low-frequency ultrasound to date (Wu and Nyborg, 2008;Pitt et al, 2011;Reuter et al, 2010). The application of therapeutic ultrasound in combination with contrast agent is a new concept and has elicited interest in various medical fields (Postema and Gilja, 2011; Burke and Price, 2010).…”

Section: Discussionmentioning

confidence: 99%

Low-frequency low-intensity ultrasound with contrast agent for the treatment of subcutaneous tumors in mice

Shen¹

2011

Sci. Res. Essays

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To determine the effects of ultrasound exposure in the presence of microbubble contrast agent (SonoVue) on the subcutaneous tumor of nude mice. Nude mice bearing subcutaneous tumor were prepared and treated with ultrasound. These animals were divided into three groups: control group (without treatment), low-frequency ultrasound group (US) and low-frequency ultrasound  contrast agent group (US+UCA). UCA was microbubble contrast agent (SonoVue). The tumors were exposed to pulsed ultrasound with a 40% duty cycle and an intensity of 26 MW/cm 2 at a frequency of 20 kHz for 3 minutes using a digital sonifier once every other day for two weeks. The damage to vascular endothelial cells was assessed via transmission electron microscopy (TEM). The protein expressions of VEGF and COX-2 of vessels were detected by Western blot assay. The percentage of tumor shrinkage in US UCA group was higher than US group and down-regulation of VEGF and COX-2 were detected in US  UCA group. After treatment, degeneration of endothelial cells, mitochondrial vacuolation and lumen occlusion were observed in the tumor of US  UCA group. These changes were seldom observed in the US group. Low-frequency ultrasound in the presence of contrast agent may exert therapeutic effect on subcutaneous tumor through destruct of the blood vessels in the tumor.

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“…Researchers have utilized different animal species, including mice, rats, rabbits, pigs, and nonhuman primates, to investigate the use of this technique in the aforementioned pathological conditions. We found 46 animal studies, from which 14 evaluated intracranial thrombosis [3,[20][21][22][23][54][55][56][57][58][59][60][61][62], 24 extracranial thrombosis [57,, and 8 other vascular and cardiovascular conditions [84][85][86][87][88][89][90][91].…”

Section: Preclinical Animal Studiesmentioning

confidence: 99%

Sonothrombolysis: State-of-the-Art and Potential Applications in Children

Ward,

Martinez-Correa,

Tierradentro-García

et al. 2023

Children

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In recent years, advances in ultrasound therapeutics have been implemented into treatment algorithms for the adult population; however, the use of therapeutic ultrasound in the pediatric population still needs to be further elucidated. In order to better characterize the utilization and practicality of sonothrombolysis in the juvenile population, the authors conducted a literature review of current pediatric research in therapeutic ultrasound. The PubMed database was used to search for all clinical and preclinical studies detailing the use and applications of sonothrombolysis, with a focus on the pediatric population. As illustrated by various review articles, case studies, and original research, sonothrombolysis demonstrates efficacy and safety in clot dissolution in vitro and in animal studies, particularly when combined with microbubbles, with potential applications in conditions such as deep venous thrombosis, peripheral vascular disease, ischemic stroke, myocardial infarction, and pulmonary embolism. Although there is limited literature on the use of therapeutic ultrasound in children, mainly due to the lower prevalence of thrombotic events, sonothrombolysis shows potential as a noninvasive thrombolytic treatment. However, more pediatric sonothrombolysis research needs to be conducted to quantify the safety and ethical considerations specific to this vulnerable population.

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Low-Frequency Therapeutic Ultrasound with Varied Duty Cycle: Effects on the Ischemic Brain and the Inner Ear

Cited by 8 publications

References 22 publications

Safety of Low-Frequency Transcranial Ultrasound in Permanent Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats

Safety of Low-Frequency Transcranial Ultrasound in Permanent Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats

Low-frequency low-intensity ultrasound with contrast agent for the treatment of subcutaneous tumors in mice

Sonothrombolysis: State-of-the-Art and Potential Applications in Children

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