March 28, 20255 min readSafe, Cheap and Non-Invasive: Ultrasound Could Treat Cancer, Psychiatric Disorders and MoreA bioengineer highlights the potential of low-intensity ultrasound for multiple uses, from enhanced drug delivery to the brain to combating cancerBy Rachel Nuwer edited by Gary Stix Naeblys/Getty Images.If you are a parent, then you probably first laid eyes on your child through an ultrasound procedurethe technology that uses high-frequency sound waves to view soft tissue. It is undeniably one of the most popular imaging tools. But its uses now extend far beyond just prenatal care.One of the best examples is low-intensity focused ultrasound, or LIFU, which delivers sound at lower energetic intensities than traditional ultrasound. It is quickly emerging as a safe, low cost and non-invasive approach for a range of treatments. Researchers are most excited about three promising uses for LIFU that are currently being studied: getting drugs past the blood-brain barrier, improving treatment for some cancers and addressing certain psychiatric conditions.Scientific American talked to Elisa Konofagou, a biomedical engineer at Columbia University, about promising current research and the direction the field is headed. Konofagou designs ultrasound-based technologies for better image and signal processing, and she also specializes in measuring changes to tissues that have been subjected to therapeutic ultrasound. She frequently collaborates with physicians to conduct clinical investigations and to translate the technologies she develops in her lab to real-world settings.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.[An edited transcript of the interview follows.]When did scientists begin to realize that low-intensity focused ultrasound had potential for a broader range of health applications? Theres a paper in Science from 1923 where scientists used focused ultrasound waves to destroy bacteria and red blood cells in frogs. So they knew that there was something happening with ultrasound and biological tissues. By the 1930s, they had started to try to treat nerves with therapeutic ultrasound, and in the 1950s, the brain.What attracted you to the field and made you want to dedicate your career to studying this? The fact that its completely non-invasive, and the fact that you can actually focus it down to a millimeter-size region. It's almost like science fiction to me, because usually if you want to treat somewhere deep in the body, you will have to perform surgery. In this case, you're able to go into a very small region deep in an organ without surgery. This includes the brain. Its a bit difficult to fathom, but LIFU does go through the skull.Your lab is studying how LIFU can be used to get drugs past the blood-brain barrier. Can you tell me more about that work? Some of our work focuses on temporarily opening the blood-brain barrier, a structure that is almost like a filter in the brain and doesnt allow drug molecules to go through. We are partnering with drug companies that have products that arent as efficacious as they are expected to be because theyre stopped by the blood-brain barrier. We have these small micro-bubbles that we inject into the bloodstream. Theyre designed to resonate at the frequencies of ultrasound. We use them in combination with LIFU to mechanically engage the blood vessels at the blood-brain barrier. This relaxes the vessels so the drugs can go through.Were trying to apply this method for Alzheimers treatment, for example. Others have opened the blood-brain barrier to allow an antibody that is aimed to reduce beta amyloid, the plaques that form in the brains of people with the disease, with the objective to increase both the dose of the antibody and the volume of the brain that receives treatment. It was found that the volume of beta amyloid reduces with the volume of opening, and thus the dose of the antibody received. But even without an antibody treatment, our group has found that opening the blood-brain barrier with focused ultrasound alone induces an intrinsic immune response in the brain that reduces beta amyloid and tau. So there are multiple avenues to harness ultrasound for Alzheimers that are worth investigating further.Ive heard that a similar approach can also be used for more targeted cancer treatments? Yes, thats also a very interesting aspect of how you can use LIFU. Very similar to the way that drugs for Alzheimers, Parkinsons and other neurodegenerative diseases do not penetrate the brain in a sufficient therapeutic dose, cancer drugs cant adequately reach tumors in the brain.Our group was the first, for example, to apply LIFU for opening the blood-brain barrier and delivering drugs for the treatment of Diffuse Intrinsic Pontine Gliomas, a rare type of brain tumor that is 100 percent lethal within a year in pediatric patients. We treated six patients aged six to 17 years old in a soon-to-be-published safety study.The patients were initially debilitated because of the tumors occurrence in the area of their brains responsible for mobility. Although we werent able to demonstrate tumor control, we were able to show that the patients exhibited higher ease and comfort with movement immediately after treatment. This is important, because it improves quality of life for these patients. Theyre able to feed themselves, play on their iPad and hug their family members. Were starting a second study next month pairing LIFU with a generic drug to determine whether this combination results in better tumor control.Are you familiar with much of the psychiatric work thats going on with LIFU? Yes, the psychiatric applications seem even more like science fiction! You just have ultrasound reaching into the brainso no bubbles, no drugs, just sound itself. The ultrasound activates neurons and other types of brain cells such as microglia and astrocytes, which are basically there to keep the brain healthy. The cells respond to these mechanical waves, and their connectivity changes. In very layman terms, the ultrasound rewires the brain temporarily. More research is needed on how this works, but we think the rewiring helps by either stimulating or inhibiting brain circuits, which are known to have beneficial effects in treating such conditions.Some psychiatric disorders seem to respond to this. Obsessive-compulsive disorder is the one we know of that responds the most. Some people are also looking at anxiety disorders by focusing the ultrasound on the amygdala. .Weve also seen that, by opening the blood-brain barrier, you can stimulate the brain itself and have whats called neuromodulatory consequences. Were looking at this for treating depression and pain sensation. Our lab is also looking at using LIFU to treat pain by peripheral nerve stimulation outside the brain and spinal cord. Instead of treating the brain, you treat the region of the nerve that causes the pain sensation. Working with neurosurgeons at Columbia, weve shown that LIFU can relieve pain in carpal tunnel syndrome patients for a few days. Were also working with people with neuropathy and nerve tumors.Aside from the fact that this technology is non-invasive, what are some of the other advantages for patients? It is very portable. This means we can take the treatment to the patient, as opposed to taking the patient to the treatment. This is a big advantage especially for elderly patients and those with Alzheimer's. Being portable also means its much less costly, because you dont have to have technicians who maintain it.In your opinion, what are the biggest challenges for moving the field forward? The biggest challenge is convincing the FDA that LIFU is safe, and then getting practitioners to use it more readily. The good news is that high-intensity focused ultrasound (HIFU) has been approved and gotten reimbursement in the U.S. for treating prostate cancer and essential tremors. [HIFU uses higher energy levels to destroy targeted tissue, like tumor cells.] LIFU just stimulates tissue so its safer than HIFU, which ablates tissue. But its newer, so we need to get the FDA to embrace it.Where do you hope the field will be going forward with LIFU? In the future, I think hospitals will have a therapeutic ultrasound suite where you can get treatment for whatever application you needwhether its facilitating and increasing a drug dose in the targeted area, or treating mood and psychiatric disorders.