On April 22, MIT’s Technology Review reported thata start up company, Perfusion Technologies, has designed a headset to deliver ultrasound waves throughout the brain, thus disrupting the normally impervious blood-brain barrier so cancer drugs can pass though. According to the report, the company claims its approach is simpler and cheaper than the MR-guided focal drug delivery methods being explored by other brain researchers.
Joy Polefrone, director of the Foundation’s FUS-mediated Drug Delivery Program, has written the following letter to the editor to express her concerns about the safety and monitoring issues surrounding Perfusion’s technology:
Dear Editor,
As the Director of a program in Focal Drug Delivery at the Focused Ultrasound Surgery Foundation (www.fusfoundation.org), I would like to point out that significant factual information was absent from the April 22 article titled Opening Up the Brain with Ultrasound. In addition, I would like to express my organization’s substantial concern about this company’s plans to move its research into clinical applications before addressing the critical safety and monitoring parameters endorsed by the research community in ultrasound applications in the brain.
The premise of the article – that ultrasound can be used to non-invasively open the blood brain barrier and allow for drug delivery to the brain – is accurate and supported by extensive preclinical studies in the scientific literature (1). Yet, the implication that a simpler and cheaper approach of opening the whole brain without the aid of microbubbles offers value over a focused approach with microbubbles is unproven and potentially dangerous for several reasons:
- It is unknown if delivery of an agent to the whole brain is as well-tolerated as exposure to a smaller region of the brain.
- Perfusion Technologies has not published evidence to indicate that this approach is free of toxicity to the brain, nor has it published or validated by peer review the results of its animal studies evidencing the delivery of large moleucules safety to the brain.
- The absence of monitoring is a significant concern, as complications could arise including temperature elevation, intracranial bleeding and even death if not approached with care.
- We are not aware of any reports published in peer-reviewed journals that have shown that ultrasound alone (without microbubbles) can reliably produce blood brain barrier disruption without also producing damage to the brain. If reading the comments by Dr. McDannold with this perspective in mind, one can quickly note that his statements were pointing to the lack of evidence of safety and efficacy for Perfusion’s approach.
Currently, magnetic resonance imaging (MRI) is the only non-invasive imaging technique coupled with ultrasound that enables monitoring of critical structures of the brain as well as change in temperature. A literature review indicates that most leaders in this field have chosen to pursue ultrasound coupled with MRI for brain applications.
The FUS Foundation strongly believes in the promise of using focused ultrasound to deliver drugs to the brain. We have funded research to perform the necessary experiments in hopes of assuring safe and effective translation into human clinical trials. We believe research that doesn’t include sufficient monitoring and assurance of safety is a dangerous disservice to the field and to the many patients who could ultimately benefit from this revolutionary technology.
- Hynynen K (2008) Ultrasound for drug and gene delivery to the brain. (Translated from eng) Adv Drug Deliv Rev 60(10):1209-1217 (in eng).
- McDannold N, Vykhodtseva N, Raymond S, Jolesz FA, & Hynynen K (2005) MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits. (Translated from eng) Ultrasound Med Biol 31(11):1527-1537 (in eng).