Cerebral venous sinus thrombosis (CVST) is a clot in the veins that drain blood away from the brain, and is one of the most common causes of stroke in young people. Early diagnosis and anticoagulant therapy can minimize the damage and mortality associated with CVST, but current treatments fail in some 20–40% of cases.
To improve clinical outcomes, a research team headed up at North Carolina State University and Georgia Institute of Technology has developed a novel vortex ultrasound tool designed to break down blood clots in the brain. The device, which the team describe in Research, eliminated clots faster than existing techniques, and could restore blood flow through a completely blocked in vitro model of CVST in just 8 min.
In a technique known as sonothrombolysis, ultrasound is used to cavitate microbubbles surrounding a clot, causing it to break down. Compared with conventional anticoagulant or thrombolytic drugs that dissolve the blood clot, sonothrombolysis has potential to remarkably reduce the required treatment time. Previous strategies, however, have not been clinically effective when treating large, completely occluded veins or arteries.
What’s different about this new approach is that instead of using conventional planar ultrasound, the team has developed a novel vortex transducer that creates a helical wavefront, in which the ultrasound swirls tornado-style as it moves forward. This vortex ultrasound induces a shear stress parallel to the clot’s front surface, which mechanically disrupts the clot fibrin networks layer by layer to dissolve the clot more efficiently. The shear stress also loosens the clot structure, improving the delivery of microbubbles and any thrombolytic agents.
“Our previous work looked at various techniques that use ultrasound to eliminate blood clots using what are essentially forward-facing waves,” explains co-corresponding author Xiaoning Jiang from NC State University in a press statement. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront. Based on our in vitro testing, this approach eliminates blood clots more quickly than existing techniques, largely because of the shear stress induced by the vortex wave.”
Generating a helical wave
The researchers created a vortex ultrasound transducer using a 2 x 2 array of small-aperture, low-frequency (1.8 MHz) piezoelectric transducers. Assembling the array with a quarter-wavelength (0.21 mm) shift between the forward-viewing surfaces of neighbouring transducers induces the physical phase delay required to generate a helical wavefront.
The transducer array is small enough to fit into a 3.0 mm-diameter catheter, with a lumen to deliver the microbubble cavitation agents and drugs. This catheter can then be fed through the circulatory system to the site of the blood clot.
In tests on a blood vessel phantom, the vortex transducer recanalized the entire length of a 50 mm clot (restoring blood flow) within a 30 min treatment, while a nonvortex transducer achieved less than 50% of clot lysis (breakdown) and did not recanalize the vessel. Comparing clot lysis speed, the vortex transducer had an absolute lysis rate of 53.9 mg/min, 64.3% higher than that of nonvortex transducer-based thrombolysis (32.8 mg/min).
“Based on available data, pharmaceutical interventions to dissolve CVST blood clots take at least 15 hours, and average around 29 hours,” notes co-corresponding author Chengzhi Shi from Georgia Tech. “During in vitro testing, we were able to dissolve an acute blood clot in well under half an hour.”
Safe and effective
Jiang, Shi and collaborators tested their vortex transducer in a 3D-printed model of the cerebral venous sinus. They found that a completely blocked blood vessel was fully recanalized in only 8 min of treatment. The acute clot mass was 3.1±0.3 g before treatment and 1.2±0.4 g after, corresponding to a reduction rate of 7.66 %/min and a lysis speed of 237.5 mg/min. The team note that these values are significantly higher than those recently reported for drug-free endovascular sonothrombolysis (1.3–2.5 %/min; 2–4.6 mg/min).
‘Ultrasound drill’ and nanodroplets break apart blood clots
Analysis of the clot debris revealed that most particles were less than 100 µm in size, reducing the risk of dangerous embolus formation. To further assess the treatment safety, the researchers applied vortex ultrasound to ex vivo canine jugular veins, observing no damage to the blood vessel walls. They also determined that vortex ultrasound does not cause substantial damage to red blood cells.
Next, the researchers plan to perform tests in an animal model. If these are successful, they hope to pursue clinical trials. “In severe cases of CVST and in patients with massive, fully blocked venous clots and who cannot be effectively treated with medications that are currently available, the vortex ultrasound thrombolysis technology may become a life-saving treatment in the future,” they conclude.