University of Calgary researchers with the Hotchkiss Brain Institute in the Cumming School of Medicine are combining expertise and resources to bring the first comprehensive focused ultrasound brain program to Western Canada. Physicians and scientists from the departments of Clinical Neurosciences, Radiology, and Psychiatry have all joined together for this project. Clinical treatments for essential tremor have begun under the direction of neurosurgeon Dr. Zelma Kiss. Research teams will also conduct basic and clinical research under the direction of Bruce Pike, PhD, professor of Radiology and Clinical Neurosciences. We recently interviewed the Calgary team to learn more about the entire program.
Tell me about the site, when was it started, and why.
The program is a collaborative effort involving physicians and scientists from the University of Calgary and Alberta Health Services. About four years ago, Dr. Pike relocated from McGill University in Montreal to join the Hotchkiss Brain Institute in Calgary. He was aware of focused ultrasound for neurosurgery and began to plan a strategy to bring it to Hotchkiss. “I felt strongly that focused ultrasound would become an exciting area for neurosurgery, drug delivery, and neuromodulation,” said Dr. Pike. “In discussions with new colleagues in Calgary we decided to pursue the establishment of a new program.”
The team began the effort to bring focused ultrasound to Calgary a little more than two years ago. They wrote business and scientific plans for how it might work and who would be involved. They started working with donors to make the initial investments. A special group of donors contributed $1.5 million in seed money. The team applied for additional money from the Cumming Medical Research fund to bring the total to $4 million. Then Dr. Pike and colleagues applied for and received an $8 million infrastructure grant from the Canadian Foundation for Innovation. In April 2017, they installed Insightec’s ExAblate 4000 brain system at the Foothills Medical Centre.
How did Dr. Pike first learn about focused ultrasound?
Dr. Pike is an imaging scientist who led the McConnell Brain Imaging Center at the Montreal Neurological Institute for 15 years. With a focus on MRI methods and applications, he worked with neurologists and neurosurgeons on a broad range of diseases. He observed how the expanding field of focused ultrasound developed with keen interest, and felt the excitement about joining that effort.
“I talked to Kullervo Hynynen at the University of Toronto seven or eight years ago about focused ultrasound and its applications in the brain, including neuromodulation,” said Dr. Pike. “I could see how it would be transformative.” Over the years, through scientific advisory boards and other meetings, Dr. Pike got to know the Toronto focused ultrasound group and followed their achievements in the field. Now, he has plans to collaborate with them on basic research and clinical trials.
What types of facilities, space, and equipment will you have at the University of Calgary?
The image science program has several research dedicated imaging centers – one for cardiac patients, one for adult patients, and one for pediatric patients. The Exablate focused ultrasound system is installed in the 12,000-square-foot Seaman Family MR Imaging Center, which has two 3T research scanners. One of the scanners is used for robotic intraoperative neurosurgery under the direction of Dr. Garnette Sutherland. The other scanner, a GE 3T scanner, houses the Exablate Neuro system.
Another facility is the 5,000-square-foot Experimental Imaging Center at the University of Calgary. The preclinical focused ultrasound work will be conducted in this facility, and the CFI grant will fund a preclinical focused ultrasound system in this space. The experimental center has a 9.4T small animal MRI scanner. Samuel Pichardo, PhD, has recently relocated his focused ultrasound research from Thunder Bay, Canada, and is setting up his laboratory in both facilities. Laura Curiel, PhD, arrived this month and will continue her focused ultrasound work with appointments in electrical engineering and biomedical engineering. A large array of additional focused ultrasound equipment will also go into these laboratories.
How many clinical treatments have been performed?
Since May 2017, the focused ultrasound clinical team has treated nine patients with essential tremor. Currently, the procedure is only being conducted on medication-refractory patients with essential tremor diagnosed by a movement disorder neurologist. See video >
Who is on the clinical team?
Dr. Zelma Kiss is the neurosurgeon leading the clinical team. Movement neurologist Davide Martino, MD, PhD, relocated from University College in London, United Kingdom, to join the team. Robert Sevick, MD, is the neuroradiologist, and Richard Falkenstein, MD, is the anesthesiologist. Bruce Pike, PhD, Samuel Pichardo, PhD, and Brad Goodyear, PhD, are the primary scientists. The nurse coordinator is Robyn Rogers, RN.
Which indications will be added after essential tremor?
The team is now purchasing Insightec’s 220 kHz array and will begin conducting clinical trials involving the opening of the blood-brain barrier.
Who are your internal and external collaborators?
Internally, the university has formed an academic committee to expand the functional neurosurgery program. They are looking at investigating obsessive-compulsive disorder (OCD), chronic pain, epilepsy, brain tumors, drug delivery, and Alzheimer’s disease in their program in the coming years. They will also be joining clinical trials that have begun at other centers to form multicenter trials under Health Canada approval.
The University of Calgary’s focused ultrasound program has an external advisory board of well-known names in the field. It includes: Kullervo Hynynen, PhD, from Sunnybrook Research Institute; Jeffrey Elias, MD, from the University of Virginia; and Professor Menashe Zaaroor, a neurosurgeon from Rambam Hospital in Israel. Dr. Zaaroor visited Calgary during a six-month sabbatical to help the team launch the program.
Regionally, the University of Calgary aims to become a focused ultrasound resource for Western Canada. Dr. Tejas Sankar, a neurosurgeon from Edmonton, has already treated one of his essential tremor patients in Calgary.
Which FUS applications and biomechanisms are being investigated?
The University of Calgary will be a brain program for now. Besides treating patients with essential tremor, they have plans to conduct research in the use of focused ultrasound to treat other brain conditions, open the blood-brain barrier, advance drug delivery, and perform neuromodulation.
What types of preclinical research will your team conduct?
Our vision is to ensure that our physics and engineering studies meet the needs of our clinical targets. Projects include fundamental, feasibility, and translational studies. At a fundamental level, projects will concentrate on developing new methods for a high-resolution ultrasound focusing through the skull and gaining more understanding of the mechanisms behind neuromodulation with ultrasound. For feasibility studies, we are aiming to establish new imaging evidence of neuroactivity under the influence of ultrasound. At translational level, we will start exploring how to identify ideal targets for therapy in the brain.
These efforts will also continue existing collaborations in Canada and abroad, which include:
- New focused ultrasound approaches for the treatment of pediatric cancer.
- The validation of hyperthermia therapy using MRI-guided focused ultrasound.
- Facilitating multicenter studies with heterogenous technology by expanding our software platform for the control of focused ultrasound therapy.
“After these few months since my arrival at the University of Calgary, I am amazed by the incredible dynamic of my new organization,” said Dr. Pichardo. “I have complete conviction that the Cumming School of Medicine and the Hotchkiss Brain Institute will take this technology to the next level of high impact in neurosciences, where many more indications and patients will benefit from the discoveries that will take place here.”
What is the role of the Foundation in your work?
University of Calgary researchers are interested in the Foundation’s funding opportunities. They also plan to attend the Symposium and present their research. They are certainly open to collaboration with other focused ultrasound scientists and clinicians.
What is your role in education?
The Pike, Pichardo, and Kiss laboratories have opportunities for post-doctoral and graduate student training in focused ultrasound. They have already begun analyzing focused ultrasound imaging data. As the program grows, they will add clinical fellows, clinician scientists, and a broad range of other trainees. Education is a key component of their mission.
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