Nathan McDannold, PhD, has put tremendous effort into the brain applications of focused ultrasound and worked with Kullervo Hynynen to become one of the first to open the blood-brain barrier. His work in drug delivery and neurodegenerative diseases is sure to change the way that medicine is practiced. A medical physicist, he has been a participant in the care of every focused ultrasound patient treated at BWH since 1996.
Q. When and how did you get interested in FUS?
I started as a graduate student at Tufts, where I applied to the medical physics program. Tufts suggested that I work under Dr. Cormac, a Nobel Prize winner who developed CT scan, but he was retired. So I called every medical physicist in Boston, and I found Kullervo Hynynen. My first project with Kullervo was on MR temperature mapping and thermal dosing to monitor thermal ablation with focused ultrasound.
Q. What are your areas of interest in FUS?
I am interested in almost everything. My primary research areas are currently related to the brain, both for ablative therapies with and without microbubbles, and targeted drug delivery through blood-brain barrier (BBB) disruption.
Q. What mechanisms and clinical indications do you study?
Most of my funding right now is from the National Cancer Institute (NCI), so it is brain tumor related. But I’m interested in all brain applications including neurodegenerative diseases, functional neurosurgery, and neuromodulation.
Q. What is the goal of your work?
My goal is to get the therapies to patients. The unique tool that we are using for drug delivery and BBB disruption–focused ultrasound–will allow us to really change the way that some diseases are treated.
Q. What are your funding sources?
The National Institutes of Health, including NCI and the NIBIB, along with the Focused Ultrasound Foundation.
Q. Who are your team members?
Right now we have about 15 people, including faculty, post-docs, graduate and undergraduate students, and visiting fellows from the Netherlands (Marie Curie fellowship), Turkey, and Portugal (a master’s student).We also have a Visiting Professor from Taiwan.
Q. Who are your internal and external collaborators?
Internally, I work with Clare Tempany, Alex Golby (a neurosurgeon), Fiona Fennessy (a radiologist), and Travis Tierny (who is about to leave for functional neurosurgery). We also have Seung-Schik Yoo and Bruno Madore (working on liver motion tracking for thermometry and other applications in the MRI environment). I have additional collaborators in both prostate and neurology. For external collaboration, I have shared grants with Tyrone Porter at Boston University, Barbara Waszczak at Northeastern University, Greg Clement in Cleveland, and a subcontract with Kullervo Hynynen at Sunnybrook in Toronto.
Q. What are your grea achievements? Any major disappointments?
What comes to mind is the work that Kullervo Hynynen and I did in discovering the BBB disruption along with the work that we’ve done validating MR temperature mapping. For disappointments – I can’t say that I have any.
Q. What do you see as impediments to your success?
Time – everything takes longer and is much harder than I had hoped for clinical translation.
Q. What is your research wish list?
I would like to do a clinical trial on drug delivery in the brain. I would like to get more interest from drug companies on developing these ultrasound-enhanced therapies.
Q. Did the Foundation play a role in your work?
Yes, absolutely. Their two previous grants allowed me to get the data I needed to obtain a program project grant from NCI. It’s a P-01 grant with direct costs of almost $3 million per year. Ferenc and I were co-PIs on that grant before he passed away. A lot of the preliminary work was made possible by the FUS Foundation.
Q. How many patient treatments have you attended?
We have a long history at BWH of having medical physicists involved in patient treatment. Since 1996, I’ve been in the room for every patient treatment—either watching [previous physicist] Kullervo Hynynen operate the system or operating it myself.
Q. Do you have a clinical highlight story?
After the uterine fibroid treatments, it takes some time to clear the room and store the equipment. One afternoon I went upstairs to get lunch, and the patient that we had just treated was also there having lunch.
Q. Any follow-up funding opportunities?
We are working on a method for neuromodulation where we deliver neurotransmitters to the brain after BBB disruption, and we are seeking funding for that project. Another BBB project in the Alzheimer’s arena also needs to be funded. It seems that new ideas are always coming up here, and we have one that we have submitted to the Foundation.
Q. What comes next?
In the next five years, I’m hoping to see progress in clinical translation. There are also new methods of ultrasound-enhanced microbubble therapy that could move treatments out of the MRI, opening up things even more.
- Nathan McDannold is Guest Speaker at UVA Center of Excellence
- Researcher Interview: Nathan McDannold, PhD, Brigham & Women’s Hospital (Video)
- Harvard Researcher Increasing Brain Regions that can be Targeted by FUS
- Brigham and Women’s Hospital Awarded $6.3 million Grant from the National Cancer Institute to Study the Use of Focused Ultrasound to Treat Brain Tumors
Key FUS Publications
Aryal M, Park J, Vykhodtseva N, Zhang YZ, McDannold N. Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model. Phys Med Biol. 2015 Mar 21;60(6):2511-27.
Aryal M, Vykhodtseva N, Zhang YZ, McDannold N. Multiple sessions of liposomal doxorubicin delivery via focused ultrasound mediated blood-brain barrier disruption: a safety study. J Control Release 2015 Apr 28;204:60-9.
Aryal M, Arvanitis CD, Alexander PM, McDannold N. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system. Adv Drug Deliv Rev 2014 Jun;72:94-109.
McDannold N, Arvanitis CD, Vykhodtseva N, Livingstone MS. Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. Cancer Res 2012 Jul 15;72(14):3652-63.
Arvanitis CD, Livingstone MS, Vykhodtseva N, McDannold N. Controlled ultrasound-induced blood-brain barrier disruption using passive acoustic emissions monitoring. PLoS One 2012;7(9):e45783.
McDannold N, Vykhodtseva N, Hynynen K. Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. Ultrasound Med Biol 2008 May;34(5):834-40.
Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 2001 Sep;220(3):640-6.