- For the past 13 years, Dr. Meaghan O’Reilly has been an integral part of Sunnybrook Research Institute’s dynamic Focused Ultrasound Research group.
- She has gained national attention for her research developing focused ultrasound–based therapies for brain and spinal cord disorders.
- Her goal is to use the technology to treat conditions that affect the entire central nervous system.
As the Canada Research Chair in Biomedical Ultrasound, Meaghan O’Reilly, PhD, has been gaining national attention for her research developing focused ultrasound–based therapies for brain and spinal cord disorders. In fact, her overall goal is to use the technology to treat conditions that affect the entire central nervous system. For the past 13 years, Dr. O’Reilly has been an integral part of Sunnybrook Research Institute’s large and dynamic Focused Ultrasound Research group. We interviewed her to learn more about her groundbreaking research.
Focused Ultrasound Work
When and how did you get interested in focused ultrasound?
I first heard about focused ultrasound when I was a master’s student at the University of Oxford in the (now defunct) Master of Science in Biomedical Engineering program. It was a year-long, course-based program with a mini thesis, and Professor Constantin Coussios, PhD, taught two modules in biomedical acoustics. I really enjoyed the acoustics classes, and at the end of all our rotations and modules and eight months of coursework, we had to pick a project for the mini thesis. Everyone wanted to work with Constantin because they thought this focused ultrasound technology was so cool. He had two projects and about eight students lining up to try and get a spot with him. I thought, “Well, that was interesting, but, you know, not that interesting,” because I didn’t want to compete for those spots, and I had planned to go into biomechanics. I thought I would end up working in a gait lab or designing assistive devices, so my mini thesis was on finite element modeling of flatfoot in children.
I defended my mini thesis in September of 2008 and applied for jobs everywhere, including Sunnybrook Research Institute (SRI), because I had previously worked there in the orthopedics laboratory. I knew they had many different research programs, so I looked at all the opportunities. There was a posting for a research assistant or research engineer in focused ultrasound. It didn’t say who it was working with, it just said, “Research assistant needed.” I applied, and the position was working with Professor Kullervo Hynynen, PhD. I got the position and ended up completing my PhD with Kullervo.
What are your areas of interest in focused ultrasound?
I study the use of focused ultrasound to treat diseases of the central nervous system (brain and spinal cord). More specifically, I am interested in detecting, monitoring, mapping, and controlling cavitation in bubble-based therapies in complex environments. Providing treatment through the skull or through intact vertebral bone creates a complex acoustic environment with a lot of potential reverberations and distortion for the sound waves. We are now primarily working on the spine, and it is incredibly interesting because of the first challenge of sonicating through the bone and the next challenge of addressing reverberation of the sound in the canal. These challenges create issues with transmission, monitoring, and mapping cavitation activity.
What mechanisms and clinical indications do you study?
We study blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) opening, mostly for drug delivery. I have some other projects that are getting off the ground, including one comparing bioeffects when the barrier doesn’t open and some orthopedic collaborations that are in the works.
What is the goal of your work?
Our overall goal is to advance BBB and BSCB opening technologies toward widespread clinical adoption. For this to happen, we need robust control, monitoring, and feedback so that the devices can be safely operated with the push of a button. There are still many challenges to solve for appropriately controlling for the correct and desired bioeffect and the level of that bioeffect. We are seeking to reach the same level of development with the spine as in the brain so we can begin treating diseases that are either spinal cord–specific or that impact the entire CNS.
What are your funding sources?
Our work has been funded by the Canadian Institutes of Health Research, both through the Project Grant program and the Canada Research Chair Program, the Natural Sciences and Engineering Research Council of Canada, and a new funding mechanism in Canada called the New Frontiers in Research Fund, which was created to support world-leading interdisciplinary, international, high-risk/high-reward, transformative, and rapid-response Canadian-led research. We have received funding from private foundations, too, such as the Focused Ultrasound Foundation and the Terry Fox Research Institute. We have also previously received operating support from the National Institutes of Health and infrastructure funding from the Canadian Foundation for Innovation John Evans Leaders Fund.
Who are your team members?
I currently have five PhD students, one master’s student, a research associate, a research engineer, and two technical staff members who I share with the other investigators in the SRI Focused Ultrasound Laboratory. Our team was also joined by three undergraduate and four high school students over the summer.
How does your summer internship program work?
SRI has a paid, eight-week-long Focused Ultrasound High School Summer Research Program started by Kullervo that began about 15 years ago. Our fantastic lab manager, Kristina Mikloska, coordinates the program, which now receives about 300 applications each summer! It is an amazing program. My lab gets four of the 25 to 30 students accepted each summer. (Last year, we only had 12 students because of pandemic restrictions, and the year before we were shut down.) The high volume of applications is a testament to the program’s outreach efforts. We have worked to broadly advertise the program and in recent years have started doing science outreach in some of the more socioeconomically and culturally diverse areas of the city to engage with the students and make them aware of our program early so that they complete the courses that are prerequisite for applying. We wanted to diversify our pool of applicants, because for a long time we were mainly receiving applications from students in private schools or schools with specialized enrichment programming. Now our applicant pool is a much better representation of the population of Toronto, and we get students from as far away as Quebec applying to be in the program. Participating in our program helps students get scholarships and access to other valuable opportunities. We are trying, on a small scale, to address the misrepresentation that exists as you go farther along the academic pipeline. If we can recruit diverse people earlier in life and then retain them, we can make a tiny dent.
Have you had any global interns from the Foundation?
Not this year. I had one last year and she is back working with me this year but could not receive the funding two years in a row.
Who are your internal and external collaborators?
Internally, I collaborate with Kullervo Hynynen, PhD, and David Goertz, PhD, who are ultrasound experts, and Bojana Stefanovic, PhD, Greg Stanisz, PhD, Jamie Near, PhD, and Fa-Hsuan Lin, PhD, who are MRI scientists. I collaborate with Arjun Sahgal, MD, and Robert Kerbel, PhD, on leptomeningeal metastases and using focused ultrasound in that context. Gregory Czarnota, MD, PhD, has also been involved in the past.
What are your greatest research achievements?
In 2012, Kullervo and I developed an acoustic emission–based controller for BBB opening (see Radiology). Although it seems like resting on your laurels to be calling out something that is so far back, I consider it a big accomplishment because it has had direct clinical implications. The clinical team now uses a modified version of that controller in clinical trials here at Sunnybrook Health Sciences Centre to select the appropriate treatment exposures, so that work has direct impact. Some of the work that we are now doing in the spine has also created some big firsts preclinically and some exciting steps for translation. I like to hope that, directly or indirectly, my work is going to ultimately impact patients.
Any major disappointments?
It is good for people to know that a lot of research is failure – or finding out what does not work. I read a great book on this topic by the founders of IDEO U, which provides think-outside-the-box online education for design. The book Creative Confidence by David Kelly and Tom Kelly says that truly innovative people (e.g., Elon Musk) tend to say that they have great ideas – and their ideas appear to be successful. The book argues that people who are successful do not necessarily have more good ideas; they just fail more often. They put out more ideas in general and for every idea that is successful, they have had 100 that that failed miserably. We definitely have experienced failure with our research, so I know a lot of things that don’t work. There is always a balance between deciding that a concept is not going to work and deciding that there is a way to make it work. It is not necessarily a waste of time to keep going to try to figure out which one is which.
When do you cut your losses and move on to a whole new idea? The example that I like to give my students comes from my PhD work. I wanted to work on a receiver array for transcranial passive acoustic mapping. I was struggling with a piece of equipment that would catch on fire regularly (among other challenges). It was exceptionally frustrating for the longest time, so we pivoted, and I finished other studies that formed my thesis. We eventually solved the original problem two years later. The takeaway is that sometimes you must pivot.
What do you see as impediments to your success?
I would say bandwidth. Before I was a principal investigator, I had more time to do research and to be productive. When you start your lab, you spend all this time writing funding proposals and things like that. You build a team, and eventually you can afford to pay people. You might have one person working for you at the start. You work and work and finally get your team. We finally have traction and multiple projects underway. We are doing some great science, but we have a lot of other things that would be amazing to do – there is just a bandwidth issue. The pandemic has also been challenging with all of its restrictions.
What is on your research wish list?
I have one fantastic Research Associate who just transitioned from being a postdoctoral fellow. I would love another great postdoc if anyone who reads this is looking for an opportunity, particularly somebody who comes from an ultrasound background. I have been lucky to have fantastic students, but I would love a new postdoc to work for a year or two.
Another thing on my wish list is more MRI time. Our MRI is heavily subscribed, and we can always use more MRI time.
My trainees have been amazing, and I feel like they all deserve a win with respect to their projects this year. They have worked hard. My final wish is for all of them to have a win.
Has the Foundation played a role in your work?
The Foundation has been an important gathering point for our community. The workshops – some of them small and some of them larger – bring together researchers on key topics. For example, the workshop series on Bubble Activity in Therapeutic Ultrasound created good debate over terms like inertial and stable cavitation, our ability to differentiate them, and our ability to use them in predicting or controlling bioeffects. Although we came away without concrete answers on the best path forward, we identified the main gaps as a community. Having those discussions was important. The workshops are useful for those of us working in the field to kind of touch base with one another so we can focus on the things on the critical path. Attending the workshops is also valuable for people who are new to a particular area and they allow trainees to take part in those discussions and get up to speed on what’s important, why it’s important, and where they should be focusing their energies.
The Foundation’s broad support of researchers and focus on the translational aspect of our work have also been invaluable. I have recently received funding from the Foundation, and some of its funding has supported researchers like Nir Lipsman, MD, PhD, at Sunnybrook. Collectively, that funding advances the state of the work here at our institution.
While financial support is incredibly important, providing that conversation and gathering place for stakeholders to have discussions is different than the discussions held at societies, because the real focus becomes how to bring the technology to patients. Societies are important for discussing many aspects of the science, but the Foundation workshops are really focused on taking the next step and the translation. The Focused Ultrasound Foundation brings in the clinician perspective in a way that is different than what we get with other societies.
What comes next?
Our spine research is still a couple of years away from reaching patients. Our big push will be to reach the position where we are ready to treat patients, because there are many people who have exhausted other treatment options. I’m always amazed by the selflessness of the patients in Phase I trials where there is no benefit to them – the treatments really are for future patients. But all clinical trials begin at phase one, so hopefully we can start to make a difference and provide hope for the future.