The researchers at Penn State College of Engineering set out to develop a technology with which blood clots in deep veins can be located and imaged. It turns out that their work may not only be able to identify blood clots, but also be able to treat them.
The team, led by Scott Medina, Assistant Professor of Biomedical Engineering, published its findings in Advance Healthcare Materials.
Deep vein thrombosis is the formation of blood clots in deep veins, typically in a person’s legs. It’s a life-threatening clotting condition that, if left untreated, can cause fatal pulmonary embolism – when the blood clot travels to the lungs and blocks an artery. To manage DVT and prevent these life-threatening complications, it is important to be able to identify, monitor, and treat them quickly. “
Scott Medina, Assistant Professor of Biomedical Engineering, Penn State
The challenge, according to Medina, is that current diagnostic imaging methods lack the resolution required to precisely locate potential breeding grounds for clots and monitor the clots in real time. DVT can sometimes present as swelling and pain in a person’s leg, which can then be examined by ultrasound.
“Ultrasound is not good for diagnosing DVT,” said Medina. “It can tell you that an area of fluid flow looks strange, possibly related to a clot – but maybe not. They do blood tests to look for factors and together you can potentially make a diagnosis of a clot. “
Once a clot is diagnosed, a doctor can either order medication to dissolve it or a procedure that involves looping a probe around the clot to grab it and physically remove it from the body. However, the drugs may not be enough to break up the clot or they could cause bleeding problems elsewhere in the body, while the procedural option is invasive and carries risks, including potential infections.
To better identify the location, composition, and size of clots, which will provide information on how to treat them, Medina and his team used a particle approach developed in 2017. The so-called nanopepsisomes (NPeps) comprise a shell around a droplet of fluorine-based oil similar to liquid Teflon. The surface of the shell contains a molecule that finds and binds a protein on the surface of activated platelets, an important cellular component of clots.
“The particles attach to the surface of the clot, we use ultrasound, and the droplet turns into gas and forms a bubble under the shell,” said Medina. “It provides excellent contrast for imaging. The bubbles appear right where the clots form.”
But, said Medina, a secret unfolded as they tested their technique. To analyze the diagnosis and treatment of clots, the researchers first induce clots in bovine veins by injecting an enzyme that triggers clot formation.
“The enzyme generally induces clots 100% of the time – but when we applied the particles, we only saw clots about 30% of the time,” said Medina. “We had to ask ourselves: do the particles not only bind to the clots, but somehow break them down?”
The team tested their hypothesis, but the researchers would lose the bladder signal every time after 15 minutes of ultrasound.
“We believe that once our particles begin to decorate the clot, they saturate the surface and inhibit the mechanisms of further clot growth,” said Medina. “And under the ultrasound, the particles disrupt the clot or prevent it from continuing. While we do not yet understand the underlying mechanism, it is clear that these particles can image and treat clots in real time. “
The researchers plan to further study how the particles disrupt the clot and develop more control over the behavior of the particles.
Source:
Journal reference:
Sloand, JN, et al. (2021) Ultrasound-responsive nanopepsisomes enable synchronous spatial imaging and inhibition of clot growth in deep vein thrombosis. Advanced healthcare materials. doi.org/10.1002/adhm.202100520.
