Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model

Kleven, Robert T.; Karani, Kunal; Hilvert, Nicole; Ford, Samantha M; Mercado-Shekhar, Karla P.; Racadio, John M.; Rao, Marepalli B.; Abruzzo, Todd; Holland, Christy K.

doi:10.1038/s41598-021-83442-3

Cited by 13 publications

(7 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vessel patency during thrombolysis has been shown to be correlated with D-dimer [ 50 ], providing some validity to the generalizability to these findings. Future studies should incorporate flow as a metric of thrombolytic efficacy and treatment outcome [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…A clinical US contrast agent (UCA), Definity, was studied in a preclinical animal model of vascular occlusion along with 220 kHz pulsed US. In this porcine cerebral thromboembolism model, recanalization of the occluded vessel in vivo was up to 45 min faster with ultrasound, tPA, and microbubbles …”

Section: Interaction Of Ultrasound With Biological Systems: Physical ...mentioning

confidence: 93%

“…In this porcine cerebral thromboembolism model, recanalization of the occluded vessel in vivo was up to 45 min faster with ultrasound, tPA, and microbubbles. 114 Preclinical and Clinical Data. Since the first clinical trials in 2013, the exploration of ultrasound-mediated therapeutic delivery has come a long way.…”

Section: Interaction Of Ultrasound Withmentioning

confidence: 99%

Ultrasound-Enabled Therapeutic Delivery and Regenerative Medicine: Physical and Biological Perspectives

Bansal

Jha

Bhatia

et al. 2021

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

The role of ultrasound in medicine and biological sciences is expanding rapidly beyond its use in conventional diagnostic imaging. Numerous studies have reported the effects of ultrasound on cellular and tissue physiology. Advances in instrumentation and electronics have enabled successful in vivo applications of therapeutic ultrasound. Despite path breaking advances in understanding the biophysical and biological mechanisms at both microscopic and macroscopic scales, there remain substantial gaps. With the progression of research in this area, it is important to take stock of the current understanding of the field and to highlight important areas for future work. We present herein key developments in the biological applications of ultrasound especially in the context of nanoparticle delivery, drug delivery, and regenerative medicine. We conclude with a brief perspective on the current promise, limitations, and future directions for interfacing ultrasound technology with biological systems, which could provide guidance for future investigations in this interdisciplinary area.

show abstract

“…The employment of the US to improve thrombolysis therapy is known as sonothrombolysis [ 141 , 142 ]. Figure 4 shows sonothrombolysis during severe vascular occlusion caused by blood clots.…”

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

View full text Add to dashboard Cite

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.

show abstract

Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model

Cited by 13 publications

References 68 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

Ultrasound-Enabled Therapeutic Delivery and Regenerative Medicine: Physical and Biological Perspectives

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

Contact Info

Product

Resources

About