Examining LIFU-Aided Liquid Biopsy in Glioblastoma: Overview and Rationale

In this first episode of OncChats: Examining LIFU–Aided Liquid Biopsy in Glioblastoma, Manmeet Singh Ahluwalia, MD, MBA, FASCO, and Michael W. McDermott, MD, both of Baptist Health South Florida, explain how low-intensity focused ultrasound (LIFU) works and the rationale for examining its use in cancer and other conditions.

Ahluwalia: Hello everyone. My name is Manmeet Ahluwalia. I serve as the deputy director and Fernandez Family Foundation Endowed Chair in cancer research, as well as the chief of medical oncology and chief scientific officer of the Miami Cancer Institute, which is part of Baptist Health. I’m pleased to be joined today by my dear friend and incredible colleague, Dr Michael McDermott.

McDermott: Thank you Manmeet. For those in the audience, I currently serve as the chief medical executive officer of Miami Neuroscience Institute. I’m in charge of neurosurgery, neurology, physiatry, and acute rehab services for patients with conditions of the central and peripheral nervous system. I hold the Irma & Kalman Bass Endowed Chair in clinical neuroscience. It’s our pleasure to be able to offer medical services to the patients in South Florida.

Ahluwalia: Thank you so much, Mike. Today, we are gathered via Zoom to talk about low frequency ultrasound and its use in brain tumors. Mike, you’ve been working on this technology recently. Could you explain to our viewers how this technology works? Also, could you talk about non-oncologic avenues where you have used this [technology] to help patients?

McDermott: There are two different frequencies—LIFU and high-intensity focused ultrasound—for medical applications in the brain. A high-intensity focused ultrasound is more energetic and can make lesions in the brain over a period of 50 minutes. Currently, that is used for essential tremor that is disabling and some cases of Parkinsonian-associated tremor, which is disabling. We use LIFU for brain tumor applications with attempts to open the blood–brain barrier and release tumor-associated DNA into the circulation and for non-tumor applications particularly for investigation of the effects on memory function in patients with diagnosed Alzheimer disease. Both of these applications of LIFU are done in the setting of a clinical research trial.

Currently, there’s a state-of-Florida–funded research study for Alzheimer disease that’s planned to accrue 25 patients at several sites. We are one of those sites; I’m the co-principal investigator with Patricia Junquera, MD, FAPA. Once the patients are screened, and we can identify an amyloid-positive site in the brain that may be a good target for us, then we can treat those sites with LIFU. We treat the patient, in that setting, three different times, one week apart, targeting the PET Tau amyloid-positive areas, up to six sites and 40 cc in total volume.

We use a contrast agent from the cardiac ultrasound world called Definity; that is essentially a lipid bilayer sphere containing small gas bubbles. The ultrasound waves that pass through the blood vessels in the brain where the Definity microbubbles are, releases the gases from the microbubbles, which transiently disrupts the blood–brain barrier for about 24 hours.

There is preclinical evidence to suggest that the disruption of the blood–brain barrier is safe, not harmful, and it allows for clearance of some of the Tau proteins. As such, the hypothesis is that repeated treatments will allow for clearance of Tau, which may in some way affect cognitive abilities, and that with clearance, cognitive abilities will either stabilize or improve.

Check back next Tuesday for the next episode in the series.