Harvard Researcher Increasing Brain Regions that can be Targeted by FUS

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FUSF Research Award recipient: Nathan McDannold, Harvard Medical School, USA

Nathan McDannold, PhD, started working in focused ultrasound research as a physics graduate student in 1996. “I was looking for a medical physics project and sort of stumbled into the field,” he recalls.

Fifteen years later, McDannold has established himself as one of the world’s leading focused ultrasound researchers. “What has kept me interested has been the promise of this technology to significantly help a large number of patients, the technical challenges involved, and the large number of applications that are possible with FUS,” he says. “The two main applications that I’m working on right now are using ultrasound instead of surgery to ablate tumors and targeted drug delivery.”

McDannold, who heads the Focused Ultrasound Laboratory in the Department of Radiology at Harvard Medical School, became the Focused Ultrasound Surgery Foundation’s first Research Award recipient in 2007. At the time, he was investigating how to ablate tumors in very deep brain structures without overheating the skull or damaging the brain and nerves around it.  His research goal was to make focused ultrasound lesions right next to the optic nerve while preserving its function.

Building on research performed by others, McDannold and his collaborator, Natalia Vykhodtseva, PhD, demonstrated that brain tissue could be ablated without any heat using low power focused ultrasound pulses to activate microbubbles injected into the circulation. “This really focuses the energy to the micro-bubbles themselves instead of the rest of the tissue,” McDannold explains. “We’re very happy about the results but we need to really look at this over a long period of time and make sure that we’re not causing any more subtle damage that’ll show up later.”

McDannold says the study is now complete and that a manuscript is under development. “We have submitted a proposal to the NIH to continue this project,” he adds.

2011 Research Award

Last month, McDannold received his second FUSF Research Award totaling $112,002, which will enable him to advance his work even further. His co-investigator is Margaret Livingstone, PhD, a professor in the Department of Neurobiology at Harvard Medical School. McDannold discusses that project and more in the interview below.

Q. What is your overall research goal, and how do your first and second FUSF research awards fit into this big picture?

McDannold:  We are trying to expand the areas in the brain that can be targeted by FUS. Brain tumors and other disorders are ideal targets for a noninvasive technique like FUS. Most of our laboratory’s current research is dedicated to the use of FUS for ablation and targeted drug delivery in the brain. Both of the projects that have been funded by the FUSF are part of this goal. In the first, we hoped to find a way to target tumors or other structures near the skull base, where surgery can be extremely challenging. In the current proposal, we will try a slightly different approach that also can be used to expand regions in the brain that can be safely targeted by FUS.

Q. How will your new project advance the field of MR-guided FUS? What “chokepoint” will it address or eliminate?

McDannold: We hope to expand the number of patients with brain tumors or other central nervous system (CNS) diseases that can be treated with FUS instead of having to undergo surgery or other invasive procedures. Current technology limits FUS to targets that are distant from the skull. We hope that by using microbubbles, that we can ablate tissue with less energy. We hope that we can answer a lot of questions about the safety of this approach by ing the method using a realistic animal model and a FUS device made for patient use.

Q. What types of patients could benefit most from the treatments that emerge from your research?

McDannold: Brain tumor patients, primarily.

Q. What has FUSF funding meant to you and your work?

McDannold: The first FUSF gave us the opportunity to obtain pilot data that we hope will be turned into a long-term project. We probably would not have been able to obtain this funding through other mechanisms. Our new award is aimed at answering a pressing question about the safety of a particular FUS approach for brain tumor ablation. We had a unique opportunity to do this work, and the FUSF was able to quickly get us the funding needed to do this work before this opportunity passed.

Overall, it is fantastic to have dedicated funding for FUS projects. It is a way to obtain funding for completely new projects that, if successful, can be turned around for funding by other sources. It helps us move quickly to answer pressing questions that are holding up the progress of the field overall.

Q. Is there anything else you’d like to add?

McDannold: While my FUSF awards have been for work that is far from ready for clinical s, my collaborators’ experience with the foundation on FUSF clinical trials has been extremely positive, and those efforts are most appreciated. Also, the workshops put on by the FUSF are fantastic and get better every year.