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Updated: Sep 15, 2025
Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
Low-intensity ultrasound lysis of amyloid microclots in a lab-on-chip model
Reza Rasouli1, Brad Hartl1, Soren D Konecky1
1Openwater, San Francisco, CA, United States.
Abstract:
Amyloid fibrin(ogen) microclots are misfolded protein aggregates with β-sheet structures that have been associated with Long COVID and numerous thrombo-inflammatory diseases. These microclots persist in circulation and obstruct microvasculature, impair oxygen transport and promote chronic inflammation. Conventional thrombolytic therapies such as recombinant tissue plasminogen activator (rtPA) show limited efficacy against these microclots due to their structure and composition. In this study, we assess the impact of low intensity focused ultrasound (LIFU) stimulation on amyloid microclot fragmentation, the role of cavitation in this process and investigate whether microbubble-assisted ultrasound can enhance their lysis. Amyloid microclot models were generated using freeze-thaw cycles followed by incubation. Microclots were exposed to ultrasound waves at 150, 300, 500 kHz, and 1 MHz under four conditions: ultrasound alone (US), ultrasound with microbubbles (MB + US), ultrasound with rtPA (rtPA + US), and ultrasound with both microbubbles and rtPA (MB + rtPA + US). Low-frequency ultrasound at 150 kHz resulted in a significant clot lysis with up to three-fold reduction in both clot size and the number of large clots. The addition of microbubbles enhanced clot lysis at 150, 300, and 500 kHz. These findings suggest that ultrasound, particularly at 150 kHz is a promising method for amyloid microclot lysis. The combination of ultrasound with microbubbles and rtPA further improved clot fragmentation, rendering it a potential therapeutic tool for conditions like Long COVID.
Insights
Low-frequency ultrasound effectively breaks down amyloid microclots, which are linked to Long COVID. Combining ultrasound with microbubbles and rtPA further enhances clot fragmentation for potential therapeutic use.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Nanotechnology
Background:
- Amyloid microclots, characterized by beta-sheet structures, are implicated in Long COVID and thrombo-inflammatory diseases.
- These persistent circulating microclots impede microvasculature, impairing oxygen transport and promoting chronic inflammation.
- Current therapies like recombinant tissue plasminogen activator (rtPA) have limited efficacy against these specific microclots.
Purpose of the Study:
- To evaluate the efficacy of low-intensity focused ultrasound (LIFU) in fragmenting amyloid microclots.
- To investigate the role of cavitation in ultrasound-mediated microclot lysis.
- To determine if microbubble-assisted ultrasound can enhance microclot lysis.
Main Methods:
- Amyloid microclot models were created using freeze-thaw cycles and incubation.
- Microclots were subjected to ultrasound frequencies (150 kHz, 300 kHz, 500 kHz, 1 MHz) under four conditions: ultrasound alone, ultrasound with microbubbles, ultrasound with rtPA, and ultrasound with microbubbles and rtPA.
- Clot lysis was quantified by measuring changes in clot size and the number of large clots.
Main Results:
- Low-frequency ultrasound (150 kHz) significantly lysed microclots, reducing clot size and large clot numbers by up to threefold.
- Microbubbles enhanced microclot lysis across multiple frequencies (150, 300, and 500 kHz).
- The combination of ultrasound, microbubbles, and rtPA demonstrated superior clot fragmentation.
Conclusions:
- Ultrasound, particularly at 150 kHz, shows promise as a therapeutic approach for amyloid microclot lysis.
- Microbubble-assisted ultrasound significantly improves clot fragmentation.
- Combined therapy (ultrasound, microbubbles, rtPA) offers a potential strategy for treating conditions associated with amyloid microclots, such as Long COVID.
