Thromboembolism in blood vessels poses a serious risk of stroke,heart attack,and even sudden death if not properly managed.Sonothrombolysis combined with ultrasound contrast agents has emerged as a promising approach ...Thromboembolism in blood vessels poses a serious risk of stroke,heart attack,and even sudden death if not properly managed.Sonothrombolysis combined with ultrasound contrast agents has emerged as a promising approach for the effective treatment of thromboembolism.Recent reports have highlighted the potential of intravascular sonothrombolysis as a safe and effective treatment modality for deep vein thrombosis(DVT).However,its efficiency has not been validated through in vivo testing of retracted clots.This study aimed to develop a miniaturized multidirectional transducer featuring two 4-layer lead zir-conate titanate(PZT-5A)stacks with an aperture size of 1.4 mm1.4 mm,enabling both forward-and side-looking treatment.Integrated into a custom two-lumen 10-French(Fr)catheter,the capability of this device for intravascular sonothrombolysis was validated both in vitro and in vivo.With low-dose tissue plasminogen activators and nanodroplets,the rotational multidirectional transducer reduced the retracted clot mass(800 mg)by an average of 52%within 30 min during in vitro testing.The lysis rate was significantly higher by 37%than that in a forward-viewing transducer without rotation.This improvement was particularly noteworthy in the treatment of retracted clots.Notably,a long-retracted clot(>10 cm)was successfully treated within 40 min in vivo by creating a flow channel with a diameter>4 mm in a porcine DVT model.In conclusion,these findings strongly suggest the potential of this technique for clinical applications in sonothrombolysis,offering a feasible solution for effectively treating thromboembolism,particularly in challenging cases involving retracted clots.展开更多
This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis(CVST).This is a topic of substantial importance since current...This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis(CVST).This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20%to 40%of the cases,and the incidence of CvST has increased since the outbreak of the coronavirus disease 2019 pandemic.Compared with conventional anticoagulant or thrombolytic drugs,sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves.However,previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes(e.g.,recanalization within 30 min)in treating large,completely occluded veins or arteries.Here,we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wavematter interaction-induced shear stress to enhance the lytic rate substantially.Our in vitro experiment showed that the lytic rate was increased by at least 64.3%compared with the nonvortex endovascular ultrasound treatment.A 3.1-g,7.5-cm-long,completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot invitro.Furthermore,we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins.This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.展开更多
基金supported by National Institute of Health(NIH)grants(R01HL141967 and R21EB027304).
文摘Thromboembolism in blood vessels poses a serious risk of stroke,heart attack,and even sudden death if not properly managed.Sonothrombolysis combined with ultrasound contrast agents has emerged as a promising approach for the effective treatment of thromboembolism.Recent reports have highlighted the potential of intravascular sonothrombolysis as a safe and effective treatment modality for deep vein thrombosis(DVT).However,its efficiency has not been validated through in vivo testing of retracted clots.This study aimed to develop a miniaturized multidirectional transducer featuring two 4-layer lead zir-conate titanate(PZT-5A)stacks with an aperture size of 1.4 mm1.4 mm,enabling both forward-and side-looking treatment.Integrated into a custom two-lumen 10-French(Fr)catheter,the capability of this device for intravascular sonothrombolysis was validated both in vitro and in vivo.With low-dose tissue plasminogen activators and nanodroplets,the rotational multidirectional transducer reduced the retracted clot mass(800 mg)by an average of 52%within 30 min during in vitro testing.The lysis rate was significantly higher by 37%than that in a forward-viewing transducer without rotation.This improvement was particularly noteworthy in the treatment of retracted clots.Notably,a long-retracted clot(>10 cm)was successfully treated within 40 min in vivo by creating a flow channel with a diameter>4 mm in a porcine DVT model.In conclusion,these findings strongly suggest the potential of this technique for clinical applications in sonothrombolysis,offering a feasible solution for effectively treating thromboembolism,particularly in challenging cases involving retracted clots.
基金support from the National Institutes of Health(grant numbers R01HL141967,R41HL154735,and R21EB027304)support from the National Science Foundation(grant number CMMI-2142555)。
文摘This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis(CVST).This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20%to 40%of the cases,and the incidence of CvST has increased since the outbreak of the coronavirus disease 2019 pandemic.Compared with conventional anticoagulant or thrombolytic drugs,sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves.However,previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes(e.g.,recanalization within 30 min)in treating large,completely occluded veins or arteries.Here,we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wavematter interaction-induced shear stress to enhance the lytic rate substantially.Our in vitro experiment showed that the lytic rate was increased by at least 64.3%compared with the nonvortex endovascular ultrasound treatment.A 3.1-g,7.5-cm-long,completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot invitro.Furthermore,we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins.This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.
