NEW YORK, NY--Columbia University researchers are the first to show that focused ultrasound — a non-invasive technique that uses sound waves to enhance the delivery of drugs into the brain — can be safely used in children being treated for brain cancer.
The focused ultrasound technique, developed by Columbia engineers, was tested in combination with chemotherapy in three children with diffuse midline glioma, a rare and aggressive brain cancerthat is universally fatal.
The study found that focused ultrasound successfully opened the blood-brain barrier in all three patients, allowing the chemotherapy drug to reach the tumors and leading to some improvement in patient mobility. (All three patients eventually died from their disease or complications of COVID.
"Now that we've established the safety and feasibility of focused ultrasound in children, we've opened the door for more trials to try the technique earlier in the course of the disease and with lower systemic but higher brain doses. Our hope is that the technology will improve survival for children with brain cancer," says study leader Stergios Zacharoulis, associate professor of pediatrics at Columbia University's Vagelos College of Physicians and Surgeons and a pediatric oncologist at NewYork-Presbyterian Morgan Stanley Children's Hospital of Children's Hospital of New York.
Columbia has already launched a follow-up trial using focused ultrasound with etoposide, an FDA-approved chemotherapy drug that has shown activity against brain cancer cells.
The challenge of treating brain cancer
Though new therapies are transforming the lives of patients with aggressive tumors such as pancreatic cancer and melanoma, the prognosis for brain cancer has remained stubbornly unchanged for decades. Survival for children with midline glioma, which begins deep within the brainstem, is usually less than one year after diagnosis.
A major impediment to improving survival for brain cancer patients is physical: The blood-brain barrier, which protects the brain from viruses, bacteria, and toxins in the bloodstream, also prevents almost all chemotherapies from reaching brain tumors in sufficient concentration. In the lab, Elisa Konofagou, a professor of biomedical engineering at Columbia, has consistently shown that the barrier can be relaxed safely to allow drugs to permeate the brain and then reinstated.
Many cancer drugs are capable of killing brain cancer cells, suggesting that techniques that permit more drug molecules to pass through the barrier and target the tumor cells have the potential to transform treatment.
How focused ultrasound works
Focused ultrasound opens the blood brain barrier by using sound waves to vibrate tiny lipid-coated gas bubbles within the barrier. As the vibrating bubbles expand and contract, they pry open pathways in the barrier that drugs can pass through.
Most focused ultrasound techniques require the use of MRI machines to guide the sound waves to specific locations in the brain.
"MRIs can be stressful experiences for some of us, but especially for children who find it really difficult to stay still in the machine during the procedure," says Konofagou, who developed the technique. "At Columbia, our innovation was to move the focused ultrasound treatment outside of the MRI machine and perform the treatment in a friendly environment for the child with their family in the room during the procedure."
With the Columbia-designed device, MRI images for navigation planning are obtained before the focused ultrasound treatment with a hand-guided device.
"Patients can rest their heads on a massage table and play on a tablet or read a book during treatment, and the procedure is entirely noninvasive and painless and only lasts for a few minutes," Konofagou says.
More information
The study, " Blood-brain barrier opening with neuronavigation-guided focused ultrasound in pediatric patients with diffuse midline glioma ," was published Nov. 12 in Science Translational Medicine.
Corresponding authors: Stergios Zacharoulis, MD; Elisa Konofagou, PhD; and Cheng-Chia Wu, MD, PhD (now at Virginia Tech and Children's National Hospital).
The research was supported by the National Institutes of Health (grants R01AG03861, R01EB029338, and R56AG038961); the Gary Yael Fegel Foundation; Focused Ultrasound Foundation; St. Baldrick's Foundation; Hannah's Heroes; Sebastian Strong Foundation; Swim Across America; Matheson Foundation; Pediatric Cancer Foundation; Hope and Heroes; Team Jack Foundation; Hyundai Hope on Wheels Hope Scholar Award; Rally Foundation; Stache Strong Foundation; Musella Foundation; VP&S Interdisciplinary Research Initiative Seed Grant; Red Gate Foundation; and Columbia'sAlzheimer's Disease Research Center Research Education Program.
