How focused ultrasound is transforming modern medicine

Sound waves that sit above the upper limit of human hearing are widely used in healthcare.

Often referred to as ultrasound, these high-frequency waves help clinicians spot and track disease, and they are also what makes it possible to see early images of a new baby.

Recent progress means that people living with illnesses ranging from cancer to neurodegenerative conditions such as Alzheimer’s may soon see new benefits from this technology.

I am a biomedical engineer, and my work focuses on how focused ultrasound - directing sound energy into a precisely defined volume - can be adjusted and controlled to help treat a range of disorders.

In the last few years, clinical use of focused ultrasound has expanded substantially, and researchers are still identifying additional ways it could be used to tackle disease.

A brief history of focused ultrasound technology

Ultrasound is produced by a probe that contains a material able to convert electrical current into vibrations, and to convert vibrations back into electrical signals. As the waves move through the body, they bounce off interfaces between different types of tissue. The probe registers these echoes and turns them into electrical signals, which computers then use to build images of the tissues.

More than 80 years ago, researchers discovered that concentrating ultrasonic waves into a space roughly the size of a grain of rice could heat and destroy brain tissue. The principle is similar to using a magnifying glass to focus sunlight until it sets a dry leaf alight.

With that in mind, early teams explored whether focused ultrasound might help with neurological conditions, pain and even cancer.

Even so, major technical barriers initially prevented focused ultrasound from being used routinely in the clinic. One key issue was that the skull absorbs ultrasound energy, making it difficult to transmit beams with sufficient strength to reach injured brain tissue.

Over time, investigators addressed this by combining large arrays of ultrasound transducers - the components that translate between electrical signals and vibrations - with imaging-based details about skull shape and density. This made it possible to tune the beams far more accurately towards their intended targets.

Only after recent advances in imaging tools and acoustic physics has ultrasound’s clinical potential begun to be realised. Hundreds of clinical trials designed to treat dozens of conditions have either been completed or are currently in progress.

One area where results have been particularly striking is essential tremor, which causes involuntary shaking, most often affecting the hands. Focused ultrasound for essential tremor is now carried out routinely at many sites worldwide.

In my view, some of the most promising directions for focused ultrasound include boosting drug delivery to the brain, prompting immune responses against cancer and treating rare disorders of the central nervous system.

Focused ultrasound for delivering drugs to the brain

The blood-brain barrier is evolution’s remarkably effective way of keeping harmful substances away from the body’s most vital organ. It is formed by cells that line the inside of blood vessels and are joined extremely tightly.

Because of this structure, only certain kinds of molecules are permitted to enter the brain, helping protect against toxins and pathogens. Yet that same protection creates a major challenge in treatment, because it can also stop therapies from reaching where they need to act.

Pioneering research from more than 20 years ago showed that low-intensity pulses of focused ultrasound can temporarily open the blood-brain barrier by making microbubbles in the blood vessels oscillate.

As these microbubbles move, they push and pull on the vessel walls, briefly creating tiny openings that allow medicines circulating in the bloodstream to pass into the brain. Crucially, the blood-brain barrier only opens in the precise area where focused ultrasound is applied.

After many years spent assessing safety and refining control over the delivered ultrasound energy, researchers have produced several focused ultrasound devices intended specifically to open the blood-brain barrier for treatment.

Clinical trials are now underway to evaluate whether these devices can deliver drugs into the brain to treat conditions including glioblastoma, brain metastases and Alzheimer’s disease.

At the same time, there has been major progress in gene therapies for a wide range of brain disorders. Gene therapy aims to repair or replace faulty genetic material in order to treat a particular disease.

Using gene therapy in the brain is especially difficult, because these treatments typically cannot cross the blood-brain barrier.

Studies in animals indicate that focused ultrasound, by opening the blood-brain barrier, can help deliver gene therapies to their intended targets in the brain - paving the way for this approach to be tested in people.

Focused ultrasound and stimulating immune responses against cancer

Cancer immunotherapy works by directing a patient’s own immune system to attack the disease. However, many people - particularly those with breast cancer, pancreatic cancer and glioblastoma - have tumours that are immunologically "cold", meaning they do not respond to conventional immunotherapies.

Researchers have found that focused ultrasound can destroy solid tumours in ways that help the immune system identify and eliminate cancer cells more effectively.

One mechanism is that focused ultrasound can break tumours down into debris that then quite literally travels to the lymph nodes. When immune cells in the lymph nodes come into contact with this debris, they can trigger an immune response targeted specifically at the cancer.

Building on these advances, the University of Virginia established the world’s first focused ultrasound immuno-oncology centre in 2022 to support research in this field and move the most promising strategies into clinical care.

For instance, colleagues of mine are conducting a clinical trial at the centre to examine the combination of focused ultrasound and immunotherapy for patients with advanced melanoma.

Focused ultrasound for treating rare diseases

So far, focused ultrasound research has largely centred on the most widespread and devastating conditions, such as cancer and Alzheimer’s disease. However, I believe that continued progress - along with broader clinical adoption - will ultimately help people living with rare diseases as well.

One uncommon condition that my laboratory is especially interested in is cerebral cavernous malformation, or CCM. CCMs are brain lesions that arise when the cells forming blood vessels begin to grow uncontrollably. Although they are rare, if these lesions enlarge and bleed, they can lead to severe neurological symptoms.

The most common approach for CCM is surgical removal of the lesions. However, some CCMs sit in parts of the brain that are hard to reach, increasing the risk of side effects. Radiotherapy is another possibility, but it can also cause serious adverse effects.

We found that opening the blood-brain barrier with focused ultrasound can enhance drug delivery to CCMs. In addition, we observed that focused ultrasound treatment alone could prevent CCMs from continuing to grow in mice, even when no drug was given.

Although we do not yet know how focused ultrasound is stabilising CCMs, the large body of evidence on the safety of this method in patients treated for other conditions has enabled neurosurgeons to start planning clinical trials to test it in people with CCM.

With further research and technical advances, I am hopeful that focused ultrasound could become a realistic treatment option for many devastating rare diseases.

Richard J. Price, Professor of Biomedical Engineering, University of Virginia

This article is republished from The Conversation under a Creative Commons licence. Read the original article.