Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Goel, Leela; Wu, Huaiyu; Zhang, Bohua; Kim, Jin-Wook; Dayton, Paul A.; Xu, Zhen; Jiang, Xiaoning

doi:10.1038/s41378-020-00228-9

Cited by 51 publications

(24 citation statements)

References 37 publications

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“…Bubble activity is the primary catalyst to promote clot degradation [ 12 ]. Most sonothrombolysis schemes employ exogenous agents such as microbubbles, nanobubbles, or droplets to nucleate bubble activity [ 17 , 18 ]. These methods have a limited thrombus penetration profile [ 19 ] and do not sustain bubble activity for extended periods (< 30 s) [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

et al. 2022

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Deep vein thrombosis is a major source of morbidity and mortality worldwide. For acute proximal deep vein thrombosis, catheter-directed thrombolytic therapy is an accepted method for vessel recanalization. Thrombolytic therapy is not without risk, including the potential for hemorrhagic bleeding that increases with lytic dose. Histotripsy is a focused ultrasound therapy that generates bubble clouds spontaneously in tissue at depth. The mechanical activity of histotripsy increases the efficacy of thrombolytic therapy at doses consistent with current pharmacomechanical treatments for venous thrombosis. The objective of this study was to determine the influence of lytic dose on histotripsy-enhanced fibrinolysis. Human whole blood clots formed in vitro were exposed to histotripsy and a thrombolytic agent (recombinant tissue plasminogen activator, rt-PA) in a venous flow model perfused with plasma. Lytic was administered into the clot via an infusion catheter at concentrations ranging from 0 (control) to 4.54 μg/mL (a common clinical dose for catheter-directed thrombolysis). Following treatment, perfusate samples were assayed for markers of fibrinolysis, hemolysis, and intact red blood cells and platelets. Fibrinolysis was equivalent between the common clinical dose of rt-PA (4.54 μg/mL) and rt-PA at a reduction to one-twentieth of the common clinical dose (0.23 μg/mL) when combined with histotripsy. Minimal changes were observed in hemolysis for treatment arms with or without histotripsy, potentially due to clot damage from insertion of the infusion catheter. Likewise, histotripsy did not increase the concentration of red blood cells or platelets in the perfusate following treatment compared to rt-PA alone. At the highest lytic dose, a refined histotripsy exposure scheme was implemented to cover larger areas of the clot. The updated exposure scheme improved clot mass loss and fibrinolysis relative to administration of lytic alone. Overall, the data collected in this study indicate the rt-PA dose can be reduced by more than a factor of ten and still promote fibrinolysis when combined with histotripsy.

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Section: Introductionmentioning

confidence: 99%

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

et al. 2022

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“…4 ). Fresh microbubbles can enter the ultrasonic field during the durations when there is no high-energy pulsing [ 157 ].…”

Section: Novel Microbubble-based Treatment In Biomedicinementioning

confidence: 99%

The promising shadow of microbubble over medical sciences: from fighting wide scope of prevalence disease to cancer eradication

et al. 2021

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Microbubbles are typically 0.5–10 μm in size. Their size tends to make it easier for medication delivery mechanisms to navigate the body by allowing them to be swallowed more easily. The gas included in the microbubble is surrounded by a membrane that may consist of biocompatible biopolymers, polymers, surfactants, proteins, lipids, or a combination thereof. One of the most effective implementation techniques for tiny bubbles is to apply them as a drug carrier that has the potential to activate ultrasound (US); this allows the drug to be released by US. Microbubbles are often designed to preserve and secure medicines or substances before they have reached a certain area of concern and, finally, US is used to disintegrate microbubbles, triggering site-specific leakage/release of biologically active drugs. They have excellent therapeutic potential in a wide range of common diseases. In this article, we discussed microbubbles and their advantageous medicinal uses in the treatment of certain prevalent disorders, including Parkinson's disease, Alzheimer's disease, cardiovascular disease, diabetic condition, renal defects, and finally, their use in the treatment of various forms of cancer as well as their incorporation with nanoparticles. Using microbubble technology as a novel carrier, the ability to prevent and eradicate prevalent diseases has strengthened the promise of effective care to improve patient well-being and life expectancy.

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“…Clinically, it has been reported that low recanalization rates and higher number of retrieval attempts are associated with brin-rich clots [4]- [8]. It is hypothesized that the mechanical properties of the clots result in different resistance of clots to the thrombolytic treatment: the retracted or brin-rich clots are stiffer and denser than the unretracted or erythrocytes-rich clots, and therefore has lower thrombolysis e ciency [6], [9].…”

Section: Introductionmentioning

confidence: 99%

“…However, there has been no clot characterization using PA imaging in deep tissue, limited by the external light illumination in conventional PACT. There is only a few reported works on USguided intravenous sonothrombolysis [8], [9], [37]. As deep veins are typically several centimeters away from the skin surface, external light illumination provides limited imaging depth due to strong optical scattering of tissue.…”

Section: Introductionmentioning

confidence: 99%

Deep thrombosis characterization using photoacoustic imaging with intravascular light delivery

Tang

Klippel

et al. 2022

Biomed. Eng. Lett.

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Venous thromboembolism (VTE) is a condition in which blood clots form within the deep veins of the leg or pelvis to cause deep vein thrombosis. The optimal treatment of VTE is determined by thrombus properties such as the age, size, and chemical composition of the blood clots. The thrombus properties can be readily evaluated by using photoacoustic computed tomography (PACT), a hybrid imaging modality that combines the rich contrast of optical imaging and deep penetration of ultrasound imaging. With inherent sensitivity to endogenous chromophores such as hemoglobin, multispectral PACT can provide composition information and oxygenation level in the clots. However, conventional PACT of clots relies on external light illumination, which provides limited penetration depth due to strong optical scattering of intervening tissue. In our study, this depth limitation is overcome by using intravascular light delivery with a thin optical ber. To demonstrate in vitro blood clot characterization, clots with different acuteness and oxygenation levels were placed underneath ten-centimeter-thick chicken breast tissue and imaged using multiple wavelengths. Acoustic frequency analysis was performed on the received PA channel signals, and oxygenation level was estimated using multispectral linear spectral unmixing. The results show that, with intravascular light delivery, clot oxygenation level can be accurately measured, and the clot age can thus be estimated. In addition, we found that retracted and unretracted clots had different acoustic frequency spectrum. While unretracted clots had stronger high frequency components, retracted clots had much higher low frequency components due to densely packed red blood cells. The PACT characterization of the clots was consistent with the histology results and mechanical tests.

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Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Cited by 51 publications

References 37 publications

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

The promising shadow of microbubble over medical sciences: from fighting wide scope of prevalence disease to cancer eradication

Deep thrombosis characterization using photoacoustic imaging with intravascular light delivery

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