Time to read: 01:41
Published on MedED: 17 September 21
Type of article: Review
MedED Catalogue Reference: MG001
Sources: Nature Open/Nanosystems and Microengineering, Informed by Medgadet.com
Category: Radiology & Imaging
Cross-Category: Ultrasound
Keywords: nanodroplets, DVT, sonothrombolysis, ultrasound
Traditional DVT treatments face notable limitations. Blood clots in DVT are often described as “older, denser, stiffer, and retracted,”¹ making them particularly resistant to dissolution. For instance, tissue plasminogen activator (tPA) therapy typically requires over 24 hours to be effective, and the high doses needed (1000 μg/ml) significantly increase the risk of internal bleeding.¹ Mechanical thrombectomy also has its challenges, including endothelial damage and the potential creation of large clot fragments that could cause pulmonary embolism.¹
To address these challenges, a recent study explores nanodroplets (NDs) as a novel solution for DVT treatment. These NDs act as contrast agents for sonothrombolysis, a process that uses ultrasound (US) delivered through a forward-viewing intravascular (FVI) sub-megahertz transducer. The ultrasound activates the nanodroplets, transforming them into rapidly expanding and vibrating microbubbles (MBs). These microbubbles generate forces that weaken and break down clots.¹
The nanodroplets themselves are composed of lipid spheres filled with low-boiling-point liquid perfluorocarbons (PFCs). Their small size allows them to infiltrate even the tiniest crevices of a clot. When activated by ultrasound, the PFCs convert into microbubbles that vibrate and disrupt the clot's structure. Even in cases where the clot is not fully dissolved, the microbubbles inflict sufficient structural damage to allow other therapies, such as clot-dissolving drugs, to complete the treatment effectively.4
This innovative approach has yielded promising results:
The study demonstrated the successful use of low-boiling-point phase-change nanodroplets in intravascular sonothrombolysis. Combining nanodroplets with tPA and ultrasound significantly improved the breakdown of retracted clots, potentially advancing current treatment options. Furthermore, the FVI transducer enabled nanodroplet-mediated sonothrombolysis for both retracted and unretracted clots, using a lower peak negative pressure (PNP) compared to other high-intensity sonothrombolysis techniques.¹
Despite these promising findings, the authors acknowledge that the experiments were conducted in vitro using a venous flow model, not in live human conditions. Additional research is required to assess the safety of ND-mediated sonothrombolysis, particularly concerning clot debris size and the potential for vessel damage.¹
Nanodroplet technology represents a potentially revolutionary advance in DVT treatment, offering a safer and more effective alternative to traditional methods. However, further clinical validation will be essential for its integration into routine practice.
Access the original research investigation here
Goel, L., Wu, H., Zhang, B. et al. Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots. Microsyst Nanoeng 7, 3 (2021). https://doi.org/10.1038/s41378-020-00228-9