Enhancement of Thrombolysis In Vivo Without Skin and Soft Tissue Damage by Transcutaneous Ultrasound

Luo, Hao; Birnbaum, Yochai; Fishbein, Michael C.; Peterson, Thomas; Nagai, Tomoo; Nishioka, Toshihiko; Siegel, Robert J.

doi:10.1016/s0049-3848(98)00002-4

Cited by 73 publications

(27 citation statements)

References 8 publications

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“…In these experiments, a 26.5-kHz ultrasound transducer was used to recanalize thrombosed iliofemoral arteries in dogs with minimal complications. In the next 25 years, further studies using catheter-based or transcutaneous ultrasound focused mainly on the ability of ultrasound to enhance the effect of fibrinolytic agents in recanalizing acutely thrombosed arteries [2,3,4,5,6,7,8]. …”

Section: Ultrasound-augmented Tpa Thrombolysismentioning

confidence: 99%

Microbubbles for Thrombolysis of Acute Ischemic Stroke

Meairs

Culp

2009

Cerebrovasc Dis

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Improved treatment of acute ischemic stroke with ultrasound and microbubbles in combination with thrombolytic drugs shows great promise, but the optimal techniques, indications, and contraindications have not yet been well defined. Moreover, details such as microbubble dosage, delivery, required thrombolytic drug dosage, and optimal ultrasound characteristics all remain uncertain. Recent results suggest that ultrasound and microbubbles may be effective in clot lysis of ischemic stroke without additional thrombolytic drugs. Moreover, targeting thrombus with specific immunobubbles may improve the efficacy of sonothrombolysis. Safety remains a major concern in the further development of ultrasound-enhanced thrombolysis and extensive animal work is required to define the most promising methods to translate into human application.

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Section: Ultrasound-augmented Tpa Thrombolysismentioning

confidence: 99%

Microbubbles for Thrombolysis of Acute Ischemic Stroke

Meairs

Culp

2009

Cerebrovasc Dis

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“…Other in vivo applications include the delivery of large molecules to sites such as interstitial tissues through micro-vessel rupture (Bao et al 1998;Dalecki et al 1997;Lu et al 2003;Price et al 1998) and blood clot lysis (Luo et al 1998;Porter et al 2001;Tachibana and Tachibana 1995). Microbubbles loaded with a bioactive substance can be destroyed in a target organ or tissue, thus allowing for the local delivery of therapeutics (Blomley et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Cavitation Threshold of Microbubbles in Gel Tunnels by Focused Ultrasound

Sassaroli

Hynynen

2007

Ultrasound in Medicine & Biology

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The investigation of inertial cavitation in micro-tunnels has significant implications for the development of therapeutic applications of ultrasound such as ultrasound-mediated drug and gene delivery. The threshold for inertial cavitation was investigated using a passive cavitation detector with a center frequency of 1 MHz. Micro-tunnels of various diameters (90 to 800 μm) embedded in gel were fabricated and injected with a solution of Optison™ contrast agent of concentrations 1.2% and 0.2% diluted in water. An ultrasound pulse of duration 500 ms and center frequency 1.736 MHz was used to insonate the microbubbles. The acoustic pressure was increased at one second intervals until broadband noise emission was detected. The pressure threshold at which broadband noise emission was observed was found to be dependent on the diameter of the micro-tunnels, with an average increase of 1.2 to 1.5 between the smallest and the largest tunnels, depending on the microbubble concentration. The evaluation of inertial cavitation in gel tunnels rather than tubes provides a novel opportunity to investigate microbubble collapse in a situation that simulates in vivo blood vessels better than tubes with solid walls do.

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“…[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] US thrombolytic therapy with the use of an intravascular catheter has also been performed, which leads to earlier recanalization. 22,23 We have previously reported that low-frequency, low-intensity US penetrates the cranium and enhances thrombolysis in vitro.…”

mentioning

confidence: 99%

Can Transcranial Ultrasonication Increase Recanalization Flow With Tissue Plasminogen Activator?

Ishibashi

Aoki

Onoue

et al. 2002

Stroke

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Background and Purpose-In thrombolytic therapy for acute ischemic stroke, it is essential to obtain rapid thrombolysis before ischemic neuronal injury occurs. To develop a new technique of thrombolysis for acute ischemic stroke, the effect of transcranially applied ultrasound (TUS) on thrombolysis was examined. Methods-An occlusion model of rabbit femoral artery was produced with thrombin after establishment of stenotic flow and endothelial damage. After stable occlusion was confirmed, monteplase (mtPA) was administered intravenously, and ultrasound (490 kHz, 0.13 W/cm 2 ) was applied through a piece of temporal bone (TUS group; nϭ9). The control group received mtPA alone (tissue plasminogen activator [tPA] group; nϭ12). To verify the efficacy of TUS, femoral artery flow was measured during the procedure. Results-The recanalization ratio was 16.7% (2 of 12) in the tPA group and 66.7% (6 of 9) in the TUS group. The recanalization ratio in the TUS group was higher than that in the tPA group (Pϭ0.03). Patency flow ratio, which was defined as recanalization flow divided by baseline flow, of the TUS group (44.6Ϯ13.9%) was significantly greater than that of the tPA group (9.9Ϯ6.8%) at 60 minutes (Pϭ0.025). Patency flow ratio became higher in the TUS group than in the tPA group between 20 and 30 minutes from the start of thrombolysis. Conclusions-Low-frequency and low-intensity TUS enhanced thrombolysis by mtPA in a rabbit femoral artery occlusion model. This technique should be clinically useful for thrombolysis in acute ischemic stroke.

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Enhancement of Thrombolysis In Vivo Without Skin and Soft Tissue Damage by Transcutaneous Ultrasound

Cited by 73 publications

References 8 publications

Microbubbles for Thrombolysis of Acute Ischemic Stroke

Microbubbles for Thrombolysis of Acute Ischemic Stroke

Cavitation Threshold of Microbubbles in Gel Tunnels by Focused Ultrasound

Can Transcranial Ultrasonication Increase Recanalization Flow With Tissue Plasminogen Activator?

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