Sound Theory
By Rebecca Montz, EdD, MBA, CNMT, PET, RT(N)(CT), NMTCB(RS)
Radiology Today
Vol. 26 No. 8 P. 18
Low-intensity focused ultrasound shows promise for long COVID treatment.
As long COVID continues to impact millions worldwide, the urgent search for safe, effective, and accessible treatments has never been more critical. Amidst this quest, one of the most promising breakthroughs comes not from new drugs or complex surgeries but from the power of sound.
A recent study published in Frontiers in Bioengineering and Biotechnology reveals that low-intensity focused ultrasound (LIFU) may offer a revolutionary, noninvasive, and drug-free method to target and dismantle amyloid fibrinogen microclots— tiny, resilient blood clots believed to play a central role in the persistent symptoms of long COVID. These debilitating symptoms, ranging from chronic fatigue and brain fog to pain, breathlessness, and cognitive challenges, affect nearly 30% of COVID survivors, posing a significant public health challenge with limited treatment options available.
Spearheaded by researchers at Openwater, a San Francisco-based medical technology company, this study represents a pivotal advancement in developing accessible therapies for postviral chronic conditions. Soren Konecky, PhD, chief technology officer at Openwater, emphasizes that the findings mark a crucial breakthrough in long COVID research by demonstrating that ultrasound technology can break up the microclots linked to these lingering symptoms, without pharmaceuticals or invasive interventions. This insight underscores LIFU’s potential to fundamentally change the way long COVID is treated, offering a safer, nonpharmaceutical alternative that could transform patient care.
Microclot Disruption
Since the early days of the pandemic, scientists have sought to understand why many individuals continue to experience debilitating symptoms long after recovering from COVID. Emerging research now points to amyloid fibrinogen microclots as a potential root cause of long COVID. These misfolded protein clusters resist the body’s natural clot-dissolving processes, obstructing blood flow through tiny capillaries and depriving tissues of oxygen. Unlike typical clots, they are largely unresponsive to standard treatments such as anticoagulants or clotdissolving drugs like recombinant tissue plasminogen activator (rtPA).
Studies have found these microclots not only in long COVID patients but also in individuals with other chronic illnesses, including diabetes, myalgic encephalomyelitis/chronic fatigue syndrome, and dementia, suggesting a broader role in the pathology of chronic disease. According to existing research, these microclots likely drive key features of long COVID, including inflammation, impaired oxygen delivery, and immune system dysregulation. However, with current treatment options offering limited success and carrying potential risks, there is an urgent need for safer, more targeted approaches to address this underlying cause.
To investigate whether sound could safely disrupt these microclots, Openwater researchers created synthetic clots in the lab and tested LIFU at four frequencies— 150 kHz, 300 kHz, 500 kHz, and 1 MHz—under varying conditions, including combinations with microbubbles and rtPA. The study showed that ultrasound at 150 kHz was markedly more effective than higher frequencies, reducing both microclot size and number by as much as threefold. Notably, this impressive clot fragmentation was achieved without the need for any pharmaceutical agents or externally introduced microbubbles, highlighting the potential of LIFU as a powerful standalone therapy. This key finding demonstrates that focused ultrasound alone, when applied at the optimal frequency, can disrupt these difficult-to-treat microclots, circumventing the risks associated with systemic drug administration.
When combined with microbubbles and rtPA, clot dissolution was further enhanced, indicating potential future applications that merge LIFU with existing therapies. Still, LIFU’s efficacy as a standalone, drug-free intervention makes it an especially promising candidate for widespread clinical use.
When ultrasound waves interact with blood clots, a complex process unfolds that helps break down the clots. The primary mechanism behind this effect is a phenomenon called acoustic streaming. When ultrasound waves encounter microbubbles, tiny gas-filled particles, they cause these bubbles to rapidly expand and contract. This dynamic behavior generates localized fluid flows that exert shear forces on the microclots, physically disrupting and fragmenting them.
To validate this theory, the research team compared the impact of ultrasound on plasma samples that were either degassed (bubble free) or untreated. In degassed plasma, where natural microbubble formation was suppressed, no significant clot breakdown occurred. In contrast, untreated plasma containing endogenous bubbles showed substantial clot lysis following ultrasound exposure. This comparison confirmed that the presence of these microbubbles is essential for effective clot disruption.
Additionally, the study also found that at higher ultrasound frequencies, where there is reduced bubble formation, clot fragmentation is also reduced. Adding microbubbles at those higher frequencies restored effectiveness, further demonstrating the importance of microbubbles.
Alternative Solution
Long COVID patients often find themselves navigating a confusing and fragmented treatment landscape. Many available therapies, such as blood filtration procedures (apheresis) or off-label drug regimens, can be expensive, experimental, and difficult to access, particularly for those living in underserved or remote areas. These interventions not only carry potential risks, including infections, bleeding complications, and adverse drug effects, but also present financial and logistical barriers that limit their widespread use. This creates a critical need for treatments that are both safe and accessible on a larger scale.
In this context, LIFU emerges as a highly promising alternative. As a therapy, LIFU has the potential to dramatically improve patient experience by providing a safer, more convenient option. There is potential for LIFU to be administered in outpatient settings, such as clinics or urgent care centers, and eventually even at home, empowering patients with easier and more flexible access to treatment.
Openwater aims to develop a hospitalgrade LIFU device priced at under $500, a goal that could transform the accessibility of advanced medical treatments. This low-cost, portable device not only would be viable in traditional health care environments but also could be integrated into telemedicine platforms and home care settings. It has the potential to significantly change chronic disease management by bringing effective treatment directly to patients, regardless of location or socioeconomic status.
“Tools like Openwater’s Open-LIFU are showing promise for noninvasive treatments to chronic conditions we currently treat with pharmaceuticals or complex procedures,” Konecky says. He sees this innovation as part of a larger shift toward health care solutions that prioritize efficiency, precision, and patient-centered accessibility, signaling a new era in medical care delivery that could benefit millions living with chronic illnesses.
Broader Clinical Potential
Beyond its promising application for long COVID, LIFU is emerging as a versatile tool with the potential to transform multiple medical specialties. Ultrasound already plays a fundamental role in IR, where real-time imaging guides minimally invasive procedures. LIFU technology could be integrated into these image-guided workflows, allowing clinicians to precisely target affected areas and apply therapeutic ultrasound noninvasively. This approach could enhance the precision and safety of interventions, reducing the need for more invasive surgeries or systemic treatments.
In addition to IR, LIFU’s ability to interact with microbubbles to enhance drug delivery presents new possibilities in neurology and oncology. Many neurological disorders and brain tumors pose significant challenges due to the blood-brain barrier, which limits the penetration of drugs into affected tissues. By activating microbubbles with focused ultrasound, LIFU can temporarily increase tissue permeability, improving the delivery and efficacy of targeted therapies where conventional drug administration often falls short. This capability could open new avenues for treating complex diseases that currently have limited options.
Furthermore, as AI and advanced imaging technologies continue to evolve, LIFU devices integrated with AI may one day autonomously identify clot locations, adjust ultrasound parameters, and tailor treatments in real time. This fusion of ultrasound with AI-driven precision medicine promises to elevate the effectiveness of therapy, making it more responsive to individual patient needs and dynamic physiological conditions. This concept envisions a future where LIFU is not just a single-use tool but a smart, adaptable technology integrated across various clinical settings, potentially improving treatment paradigms far beyond the scope of long COVID.
While the laboratory findings around LIFU are promising, there remains a considerable journey before this technology can be widely adopted in clinical practice. Moving from controlled in vitro experiments to real-world patient treatments involves navigating a complex array of biological and logistical challenges. One major hurdle is the dynamic nature of blood flow within the human body, which can influence how effectively ultrasound waves interact with microclots in vivo. Additionally, considerable variability in tissue composition and physiological responses across diverse patient populations adds another layer of complexity, necessitating adaptable treatment protocols.
Aside from the biological factors, the path to clinical adoption requires rigorous regulatory approval processes and comprehensive safety validations. Establishing standardized treatment guidelines that can be applied to the broad spectrum of long COVID symptoms, and potentially other clot-related disorders, is essential to ensure consistent and effective patient outcomes. These efforts must be backed by extensive preclinical and clinical trials designed to fine-tune dosing parameters, confirm safety, and demonstrate reproducibility.
Potential Impact
The toll of long COVID extends far beyond its physical symptoms. For many patients, the condition has become a prolonged and exhausting battle that affects nearly every aspect of daily life—mental, emotional, social, and economic. Individuals suffering from persistent fatigue, brain fog, pain, or shortness of breath often describe feeling dismissed or misunderstood by the health care system. The invisible nature of their symptoms, combined with the lack of established treatments, has led many to feel isolated and abandoned. At the same time, they face mounting medical bills, loss of income due to reduced work capacity, and a diminished quality of life that affects both them and their families.
In this context, the prospect of a treatment that is not only effective but also noninvasive, affordable, and accessible becomes especially compelling. A therapy that doesn’t rely on costly hospital stays, invasive procedures, or systemic medications with risky side effects could be transformative, not just for individuals but for entire communities dealing with the long-term fallout of the pandemic. The potential impact of LIFU centers on its ability to break down microclots without the need for drugs or invasive procedures. This innovative therapeutic pathway addresses a suspected root cause of long COVID symptoms, opening the door to more effective and patientfriendly care for the many thousands still suffering from ongoing, often debilitating, post-COVID complications.
LIFU is an example of how existing technologies can be reimagined to tackle some of the most pressing challenges in modern medicine. By harnessing the physics of sound, something both fundamental and widely accessible, researchers are charting a new path for noninvasive therapies that could shift the landscape of chronic disease treatment. What began as a targeted approach to address the lingering symptoms of long COVID may, in fact, open doors to therapeutic breakthroughs for a range of other conditions rooted in microvascular dysfunction.
While the initial research has focused on long COVID, the implications of LIFU extend well beyond this application. This approach could also prove beneficial to treating other microvascular clotting disorders, including those seen in diabetes, chronic fatigue syndrome, and even neurodegenerative diseases. Developing a safe, portable, and scalable method for microclot resolution could reshape not only how we treat long COVID but how we approach an entire class of chronic conditions that have lacked effective solutions.
As Openwater advances toward clinical trials and commercial product development, their work is drawing the attention of researchers, clinicians, and policymakers alike. The promise of a lowcost, user-friendly LIFU device, capable of delivering hospital-grade therapy outside traditional clinical settings, is particularly compelling in a world grappling with postpandemic health crises and rising rates of chronic illness. In the measured pulse of an ultrasound wave lies a quiet revolution, one that may redefine how we heal from long COVID and beyond.
— Rebecca Montz, EdD, MBA, CNMT, PET, RT(N)(CT), NMTCB(RS), has worked at the Mayo Clinic Jacksonville and University of Texas MD Anderson Cancer Center in Houston as a nuclear medicine and PET technologist.