Microbubble Mediated Thrombus Dissolution with Diagnostic Ultrasound for the Treatment of Chronic Venous Thrombi

Shelby Kutty, Juefei Wu, James M Hammel, Feng Xie, Shunji Gao, Lucas K. Drvol, John Lof, Stanley J Radio, Stacey L. Therrien, David Alan Danford, Thomas Richard Porter

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo. Methods and Results: A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1-1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm2 respectively in Group A; compared to 0.24 and 0.21 cm2 in Group B (p = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment. Conclusions: Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.

Original languageEnglish (US)
Article numbere51453
JournalPloS one
Volume7
Issue number12
DOIs
StatePublished - Dec 12 2012

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microbubbles
Microbubbles
Catheters
catheters
Ultrasonography
Dissolution
Thrombosis
Ultrasonics
Central Venous Catheters
swine
Therapeutics
superior vena cava
Safety testing
safety testing
Echocardiography
Swine
therapeutics
Fibrinolytic Agents
embolism
echocardiography

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Microbubble Mediated Thrombus Dissolution with Diagnostic Ultrasound for the Treatment of Chronic Venous Thrombi. / Kutty, Shelby; Wu, Juefei; Hammel, James M; Xie, Feng; Gao, Shunji; Drvol, Lucas K.; Lof, John; Radio, Stanley J; Therrien, Stacey L.; Danford, David Alan; Porter, Thomas Richard.

In: PloS one, Vol. 7, No. 12, e51453, 12.12.2012.

Research output: Contribution to journalArticle

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abstract = "Background: Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo. Methods and Results: A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1-1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3{\%} MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm2 respectively in Group A; compared to 0.24 and 0.21 cm2 in Group B (p = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment. Conclusions: Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.",
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AU - Kutty, Shelby

AU - Wu, Juefei

AU - Hammel, James M

AU - Xie, Feng

AU - Gao, Shunji

AU - Drvol, Lucas K.

AU - Lof, John

AU - Radio, Stanley J

AU - Therrien, Stacey L.

AU - Danford, David Alan

AU - Porter, Thomas Richard

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N2 - Background: Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo. Methods and Results: A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1-1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm2 respectively in Group A; compared to 0.24 and 0.21 cm2 in Group B (p = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment. Conclusions: Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.

AB - Background: Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo. Methods and Results: A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1-1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm2 respectively in Group A; compared to 0.24 and 0.21 cm2 in Group B (p = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment. Conclusions: Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.

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