Focused Ultrasound–Enabled Liquid Biopsy Offers Early Insight into Glioblastoma Treatment Response

A collaboration between Northwestern Medicine and the University of Michigan has resulted in a new liquid biopsy technique that may allow clinicians to determine whether glioblastoma treatments are working much earlier than current methods allow. The research, recently published in Nature Communications, suggests this approach could help guide therapy decisions after just one treatment cycle.

The study builds on clinical trials of the SonoCloud device, a low-intensity focused ultrasound system developed by French company Carthera. The device is used to temporarily open the blood-brain barrier (BBB) following chemotherapy in patients with glioblastoma. Investigators collected blood samples before, during, and after the procedure to determine whether this method could enable liquid biopsies. These tests are designed to analyze biological fluids like blood for cancer biomarkers, offering a noninvasive way to assess tumor activity.

To study this possibility, researchers analyzed blood samples using a device called the GlioExoChip, developed in the University of Michigan's chemical engineering lab. The chip captures tumor-derived exosomes, small vesicles that carry proteins, lipids, RNA, and DNA from tumor cells. These exosomes can provide insights into how a tumor is responding to therapy.

The study team included Adam M. Sonabend, MD, Director of Translational Neurooncology at Northwestern Medicine and principal investigator of the clinical trial, as well as chemical engineer Nagrath Sunitha, PhD, and graduate student Abha Kumari from the University of Michigan. Mark Youngblood, MD, PhD, a neurosurgery resident at Northwestern, also played a key role in the analysis.

By comparing exosome levels before and after each treatment, the team found changes that were associated with tumor cell death and patient survival. Compared with healthy controls, patients with glioblastoma showed distinct exosomal profiles, and these changed in ways that correlated with the effectiveness of treatment.

“Instead of waiting months, after one dose we can know if a given treatment is working,” said Sonabend in a statement from Northwestern. “That is huge for glioblastoma patients. It could potentially prevent patients from getting prolonged treatments that are ineffective, thus also avoid unnecessary side effects.”

Suzanne LeBlang, MD, Director of Clinical Relationships at the Focused Ultrasound Foundation, also commented on the potential of the approach. “A blood test following focused ultrasound-mediated BBB opening could tell us early whether a therapy is working. This helps patients stay on effective treatments or move to better options sooner, when time matters most.”

While these early results are promising, the researchers note that further studies are needed to validate their findings before the test can be adopted in routine clinical practice.

The work was supported by the National Institutes of Health, the Lou and Jean Malnati Brain Tumor Institute, the Department of Defense, the American Brain Tumor Association, Tap Cancer Out, the University of Michigan Forbes Institute for Cancer Discovery, and the Focused Ultrasound Foundation.