Dual Excitation Catheter-delivered Laser Ultrasound Thrombolysis (DECLUT) for Deep Vein Thrombosis (DVT) Treatment Deep-vein thrombosis (DVT), or the formation of clots in the deep veins of the legs, affects two million Americans per year. DVT can cause pulmonary embolism (PE), which is fatal in >0.1 million cases annually in the US alone, presents as sudden death in 20-25% of cases. Recent innovative DVT treatment techniques, such as pharmacological dissolution or fibrinolysis, mechanical fragmentation and sonothrombolysis, showed progressive results. However, the low thrombolysis efficiency, vein injury associated severe regional dysfunction, the relatively large size of clot debris, risk of recurrent and distal embolism are key limitations for effective DVT treatments. More recently, research on ultrasound thrombolysis using multifrequency ultrasound excitations, combined continuous wave and laser ultrasound excitations, and excitations using microbubbles (MBs) showed promising lytic rate, but these demonstrated methods used transducers with relatively large aperture and are not applicable to integrated catheter for intravascular thrombolysis. In this project, a dual excitation catheter-delivered laser ultrasound thrombolysis (DECLUT) technology is proposed to address the existing challenges in DVT treatments. In specific, a 7-French catheter integrated with a small aperture dual frequency high intensity ultrasound transducer, a laser ultrasound transducer, and a micro-tube for delivery of MBs and lytic agent (t-PA) will be designed, prototyped and characterized, followed by in-vitro and ex-vivo thrombolysis tests. With the proposed technique, fast clot dissolution can be expected because of the use of MBs and the dual-ultrasound excitation; safe clot-dissolving can be achieved due to the minimal use of lytic agent, the reduced physical contact to the target clot and the minimal acoustic exposure of the surrounding vessel wall. The proposed DECLUT technology provides a new tool enabling physicians in more accurate, fast and safe DVT treatment, and facilitating the development of novel intravascular drugs and device therapies. In addition to DVT treatments and other intravascular thrombolysis, the proposed DECLUT technique will be also be useful in minimal invasive cancer treatment and targeted drug delivery.

Public Health Relevance

Deep-vein thrombosis (DVT), or the formation of clots in the deep veins of the legs, affects two million Americans per year. DVT induced pulmonary embolism (PE) is one of the leading cause of mortality and morbidity ? yet technologies for fast and safe DVT and PE treatment are critically lacking. The goal of this project is to demonstrate a new and effective DVT treatment using dual excitation catheter-delivered laser ultrasound thrombolysis (DECLUT). DECLUT technology provides a new tool enabling rapid and safe PE treatments and other intravascular thrombolysis, and has the potential to have a significant impact on minimal invasive tumor treatments and targeted drug delivery.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
1R41HL154735-01
Application #
10074079
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Ochocinska, Margaret J
Project Start
2020-08-15
Project End
2021-07-31
Budget Start
2020-08-15
Budget End
2021-07-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Sonovascular, LLC
Department
Type
DUNS #
107532374
City
Chapel Hill
State
NC
Country
United States
Zip Code
27517