Karl Helfrich, right, with his wife Lucy during a trip to New Zealand
Five years ago, Karl Helfrich’s world seemed to suddenly shut down. Karl put his head down on his desk and could not speak coherently. Minutes later, he couldn’t recall what he had said.
Karl had been working from home due to the COVID-19 pandemic and happened to be sitting next to his son who immediately knew that something was very wrong.
After a battery of tests, MRI scans revealed a lesion in Karl’s brain that was likely glioma—a growth of cells that are typically malignant—and he was referred to neurosurgeon Antonio Chiocca, MD, PhD, for treatment. (Chiocca is Executive Director of the Center for Tumors of the Nervous System at the Mass General Brigham Cancer Institute.)
After a successful operation to remove the cancerous cells from his brain, Karl began a standard course of chemotherapy and radiation to treat what was now known to be glioblastoma, one of the most common and most aggressive forms of brain cancer. And that’s when he received an unusual invitation.
“I was asked if I wanted to participate in a clinical trial that would use focused ultrasound to disrupt the blood brain barrier,” Karl recalls.
The blood brain barrier, or BBB, is a semipermeable membrane that separates blood from the brain and central nervous system. The barrier acts as a gatekeeper, allowing the selective transport of beneficial products to the brain and filtering out harmful substances. In most cases, the BBB provides a crucial protective function.
In glioma cases such as Karl’s, however, the BBB can limit the amount of chemotherapy drugs that can cross into the brain and reach the tumor site.
Karl, a physical oceanographer who has worked at Woods Hole Oceanographic Institution for more than 35 years, was more familiar with how ultrasound is used to probe the ocean interior such as bottom depth and water motion than their use in medicine.
But he had a strong interest in helping medical science advance, and his background gave him a general understanding of what the research team was hoping to accomplish. “I didn’t understand all of the medical details, but when it came to the physics—I did.”
Roots in Research
Focused ultrasound, or FUS, works by using an acoustic lens to concentrate sound waves at a particular focal point. Individual ultrasound beams can pass through tissue without causing damage, but at the place where those beams converge, tissue is disrupted.
FUS is used to today to treat diseases ranging from uterine fibroids, bone metastases, prostate cancer, essential tremors and Parkinson’s tremors. For treatment of these other conditions, high-intensity ultrasound beams are used to ablate or destroy tissue. But for treating gliomas and other forms of brain cancer, the goal is to create a temporary opening in the BBB that will allow the chemotherapy drugs to travel through and reach the target site in greater numbers.
Investigators theorized that could combine a low-intensity focused ultrasound beam with injectable microbubbles to pry open the BBB near the tumor site.
In simple terms, the low-intensity ultrasound beams make the bubbles oscillate, creating a rhythmic pushing and pulling on the blood vessel walls that disrupts the tight connections between cells that preserves the integrity of the BBB.
Through lab experiments in the BWH Focused Ultrasound Laboratory over the last three decades, researchers such as Nathan McDannold, PhD, have laid a strong foundation of evidence that the combination of FUS and microbubbles could provide a temporary opening in the BBB with the potential to improve treatment outcomes. But clinical trials were needed to know for certain.
Alexandra Golby, MD, a senior neurosurgeon and clinical investigator at Mass General Brigham, led the clinical trial that Karl participated in.
“This is a true example of bench-to-bedside research,” said Golby. “Dr. McDannold and his lab were a big part of this study and were by my side for many of the treatments.”
Beneficial in the Big Picture
As part of the clinical trial, Karl received multiple FUS treatments that were both preceded and followed by an MRI scan. His head was secured in one position for the duration of the procedure, and a jacket filled with water and sealed with Vaseline was placed over his scalp to facilitate the translation of soundwaves.
“It wasn’t very pleasant,” Karl says. “And I knew that for me personally, there might not be much of a benefit. But I also knew that it could be beneficial in the bigger picture [for future glioma patients]. Many people before me have done things that I’ve benefited from. I saw this as a way to give back.”
Gratifying Results
Karl has made a lot of progress in his recovery since his diagnosis five years ago. He still has aphasia—a condition that can make it difficult for him to read, write, and find the right word at times—and an occasional headache. A former bike racer, he’s been able to get back to cycling, a hobby he’s had for more than 40 years.
Karl completed his final treatment as part of the clinical trial, but he still keeps close tabs on the research. In 2025, Golby and colleagues published two papers on their work, one focused on the methods and the other on results in patients. Karl was eager to read them both.
“For the first paper about the methods, all of it made sense to me,” he says. “For the other detailing the results of the clinical trial, I was really curious to see if I could pick myself out!”
The study showed that the combination of FUS and microbubbles helped to safely improve the delivery of a chemotherapy drug—temozolomide—across the BBB. The study also found that patients in the treatment group, including Karl, lived longer than matched controls, an encouraging sign for future clinical trials that could explore delivery of other chemotherapy treatments.
“I don’t know whether I’m doing well today because of the surgery, the radiation, the chemotherapy, the focused ultrasound, my genetics, or some combination,” Karl says. “But it was gratifying to see the results and to know that I had helped.”
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