Research

Teaming Up to Transform Pediatric Brain Cancer Treatment

An engineer and a physician are working together to pioneer a new approach using focused ultrasound to treat dozens of brain diseases.

July 02, 2025
Grant Currin

Pontine glioma is a cancerous brain tumor that strikes five- and six-year-olds. The prognosis is grim, with few children living more than a year after diagnosis.

“Despite decades of research, there’s hardly anything we can do for these patients, beyond making them comfortable,” says Stergios Zacharoulis, a pediatric oncologist at Columbia University Irving Medical Center and associate professor at Columbia’s Vagelos College of Physicians and Surgeons

It’s an especially frustrating condition because researchers have developed several drugs that can kill the tumor. Unfortunately, giving the drugs in a meaningful and effective way to a patient has proven impossible. In a cruel irony, the barrier that protects the brain from viruses, bacteria, and toxins also protects the tumor from drugs that could extend the patient’s life. 

In a groundbreaking collaboration, Zacharoulis and biomedical engineer Elisa Konofagou are developing a system that uses sound waves to gently open this barrier in the brain long enough for treatment. Now in phase I/II clinical trials, the new method could transform treatment for cancers like pontine glioma as well as dozens of other conditions of the brain.

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Elisa Konofagou and researcher in lab
At work in the Konofagou lab. Credit: Rudy Diaz

Konofagou has spent more than two decades advancing the science of focused ultrasound, a technique that uses sound waves to treat disease without surgery or radiation. Her cross-disciplinary lab has developed new ways to use ultrasound for drug delivery, tumor ablation, neuromodulation, and more. In 2024, she received the Focused Ultrasound Foundation’s Visionary Award for her contributions to the field, and Columbia, led by her lab, was recently named a Center of Excellence by the Focused Ultrasound Foundation.

“With pontine glioma, Alzheimer’s, and so many other neurological diseases, we don’t have nearly enough treatment options — sometimes there are none at all,” says Konofagou, who is the Robert and Margaret Hariri Professor of Biomedical Engineering at Columbia Engineering and professor of radiology and of neurological sciences at Columbia. “That’s why we’re working on these problems.”

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MRI of the blood-brain barrier opening in a diffuse midline glioma patient using the focused ultrasound system; In green indicated by a red arrow shows the volume of opening at 2.44 cm3
MRI of the blood-brain barrier opening in a diffuse midline glioma patient using the focused ultrasound system; In green indicated by a red arrow shows the volume of opening at 2.44 cm3. Credit: The Konofagou lab

How does focused ultrasound help?

Konofagou: The blood vessels that lead to the brain are lined with special cells that sort of “hold hands” to keep larger molecules like viruses and bacteria from getting through. With focused ultrasound, we start by injecting minuscule bubbles into the bloodstream. Then we use focused sound waves in the ultrasonic range to make the bubbles vibrate, opening a path the drugs can follow to reach the tumor. 

Zacharoulis: Pontine gliomas are very complex tumors. Focused ultrasound solves the biggest problem by enabling us to get the drugs into the brain at the right concentration. 

What is the treatment like from a patient’s perspective?

Konofagou: It’s entirely noninvasive. The patient stays in their own wheelchair and rests their head on a massage pillow with a window. They can play on an iPad and see their family in the room. The focused ultrasound comes from a specialized speaker that rests on the skull. We use it to activate the bubbles for a few minutes before injecting the drugs, which are already approved. 

Zacharoulis: The patient comes in for this treatment three times a week. They are awake — there is no pain, so there is no need for anesthesia. That means we don’t have to starve a sick child three times a week because there is no risk of aspiration. It’s also free from the side effects of conventional chemotherapy, like hair loss, mouth sores, and infection. We’ve seen practically zero side effects. 

How have patients responded to the treatment?

Zacharoulis: We’re now in the second phase of clinical trials, which means we’re studying the treatment in more patients and refining the protocol. Our first trial showed that the method is physically safe and can successfully open the blood-brain barrier in children — something that had never been done before. In this next phase, we’re treating more patients, targeting multiple tumor sites, and beginning to test additional drugs. 

Konofagou: Two of our first three patients even showed temporary improvement in their symptoms, which was encouraging, especially considering how advanced their tumors were.

What’s the future of this technology? 

Zacharoulis: The aim of the treatment is to establish safe opening of the blood brain barrier to allow sufficient drug concentrations into the tumor. Eventually, this treatment should extend survival.

Konofagou: Focused ultrasound gives us very precise control over the blood-brain barrier in a number of contexts. For example, gene therapy is a promising platform for treating several neurodegenerative diseases, but those molecules are gigantic. By adjusting the parameters, we can use ultrasound to create passageways that are exactly the right size.


Lead Photo Caption: Collaborators Elisa Konofagou (right) with Stergios Zacharoulis, photographed at Columbia University Irving Medical Center.
Lead Photo Credit: Rudy Diaz