Advances in Focused Ultrasound Technology: Promising New Treatments for Cancer, Alzheimer's and Rare Brain Diseases

Sending low-intensity pulses of focused ultrasound can temporarily open the blood-brain barrier, offering new therapeutic possibilities. (File)

Sound waves beyond human hearing thresholds are commonly utilized in medical applications. These ultrasound waves serve as valuable diagnostic and monitoring tools, and also provide our first glimpses of developing fetuses.

Recent advancements in ultrasound technology now present promising treatment options for patients with cancer, Alzheimer's, and various other conditions.

As a biomedical engineer specializing in focused ultrasound research, I study how concentrated sound energy can be precisely calibrated to treat diverse medical conditions. This technology has experienced remarkable clinical growth recently, with researchers continuously discovering novel therapeutic applications.

Ultrasound technology operates via probes containing materials that convert electrical currents into vibrations and vice versa. When these waves travel through body tissues, they reflect at tissue boundaries. The probe detects these reflections and transforms them into electrical signals that computers process into detailed tissue images.

Scientists discovered over eight decades ago that focusing ultrasonic waves into a rice grain-sized volume could heat and destroy brain tissue, similar to how a magnifying glass concentrates sunlight. Early researchers began exploring focused ultrasound applications for neurological disorders, pain management, and cancer treatment.

Despite these early discoveries, technical challenges prevented clinical applications. For instance, the skull's absorption of ultrasound energy made it difficult to deliver sufficient energy to damaged brain tissue. Researchers eventually solved this problem by integrating large arrays of ultrasound transducers with detailed skull imaging data, allowing for more precise beam targeting.

Only after recent breakthroughs in imaging technology and acoustic physics has ultrasound's clinical potential been fully realized. Hundreds of clinical trials targeting numerous conditions are completed or ongoing. Particularly successful treatments have emerged for essential tremor, with focused ultrasound therapies now routinely performed globally.

The most exciting applications include enhanced brain drug delivery, cancer immunotherapy stimulation, and treatment of rare central nervous system disorders.

The blood-brain barrier represents evolution's sophisticated defense mechanism, protecting our brain through tightly connected cells lining blood vessels. While this barrier prevents harmful substances from entering the brain, it also blocks therapeutic agents from reaching their targets.

Pioneering studies from over two decades ago revealed that low-intensity focused ultrasound pulses could temporarily open this barrier by causing blood vessel microbubbles to oscillate, creating tiny pores that allow bloodstream medications to enter brain tissue specifically where ultrasound is applied.

After extensive safety testing and technology refinement, researchers have developed various devices using focused ultrasound to open the blood-brain barrier for treatment. Clinical trials are currently testing these devices for delivering drugs to treat glioblastoma, brain metastases, and Alzheimer's disease.

Simultaneously, significant progress has occurred in gene therapy development for brain diseases. Animal studies demonstrate that focused ultrasound can facilitate delivery of these genetic therapies across the blood-brain barrier, opening possibilities for human trials.

Cancer immunotherapy teaches patients' immune systems to combat disease. However, certain breast cancers, pancreatic cancers, and glioblastomas remain immunologically "cold" and resistant to traditional immunotherapies.

Research shows focused ultrasound can destroy solid tumors in ways that enhance immune system recognition of cancer cells. The technology transforms tumors into debris that flows to lymph nodes, where immune cells encounter it and initiate specific anti-cancer responses.

Inspired by these advances, the University of Virginia established the world's first focused ultrasound immuno-oncology center in 2022, supporting research and advancing promising approaches to clinical application. Currently, researchers are conducting trials combining focused ultrasound with immunotherapy for advanced melanoma patients.

While focused ultrasound research has primarily targeted devastating prevalent diseases like cancer and Alzheimer's, continued development will likely benefit rare disease patients as well.

My laboratory has particular interest in cerebral cavernous malformation (CCM), a rare condition characterized by uncontrolled blood vessel cell growth forming brain lesions. Though uncommon, these lesions can cause debilitating neurological symptoms when they grow and hemorrhage. Traditional treatments include surgical removal or radiation, both carrying significant risks.

We've discovered focused ultrasound can improve drug delivery to CCMs by opening the blood-brain barrier. Interestingly, we observed that focused ultrasound treatment alone stabilized CCMs in mice, even without medication. While the mechanism remains unclear, extensive safety research on this technique has enabled neurosurgeons to begin designing clinical trials for CCM patients.

With continued research and technological advancement, focused ultrasound shows tremendous promise as a viable treatment option for numerous devastating rare diseases.