The remarkable advances in focused ultrasound (FUS) made at Sunnybrook Research Institute would not be possible without the research infrastructure to develop, hone and validate the technology, preclinically and clinically. The following facilities have enabled the translation of FUS—from fundamental work done in the lab to device development to testing in patients.
Centre for Research in Image-Guided Therapeutics
The Centre for Research in Image-Guided Therapeutics is a 150,000-square foot facility that is unique in its focus and scope. Here, scientists and clinicians are working together to devise new and better ways to detect, diagnose and treat complex diseases. They are using state-of-the-art equipment to analyze images more accurately, build minimally invasive medical devices, synthesize molecules and cells, develop drugs and engineer tissue. Dr. Kullervo Hynynen, director of Physical Sciences at Sunnybrook Research Institute (SRI), is the lead investigator of the centre. It was established by a $75-million award from the Canada Foundation for Innovation (CFI) in 2012. It includes Canada’s first device development lab based in a hospital, within which researchers are designing and fabricating advanced ultrasound transducers and phased arrays.
Focused ultrasound lab
Hynynen is the principal investigator of the focused ultrasound lab at SRI, which comprises about 4,000 square feet and has all of the equipment needed to carry out leading biomedical ultrasound research. It has wet lab research space and an electronic shop for device manufacturing. There is also a tissue culture room for preparing cells for ultrasound experiments. The lab also has a system that exposes living tissues or cells to ultrasound while monitoring the effects under light microscopy at the same time. Researchers also use a scanning laser vibrometer that provides fast and accurate measurements of ultrasound transducer surface vibrations. Only a few researchers in the world have access to such a device. There is also a 2,000-channel radiofrequency driver for advanced phased array research. During the summer, the lab runs a highly competitive summer student research program.
High-intensity focused ultrasound (HIFU) brain system
The ExAblate Neuro is a transcranial MRI-guided focused ultrasound technology that is the only one of its kind that can perform noninvasive brain surgery and therapy. Hynynen partnered with a company, InSightec, to commercialize the device, which accounts for the unique challenges of treating the brain. The helmet-shaped array of adjustable transducers focus sound waves inside the skull to heat and destroy diseased tissue. The device distributes heat evenly and corrects for beam distortion. It enables treatment to be tailored to an individual, because skull shape and thickness vary. It works inside an MR scanner, images from which are used to guide therapy and give immediate feedback on treatment progress.
In 2016, the U.S. Food and Drug Administration and Health Canada approved InSightec’s brain device for treatment of essential tremor, the most common movement disorder. They did so based on a groundbreaking clinical trial showing that focused ultrasound safely and effectively reduces tremor in people for whom nothing else had worked.
MRI-guided focused ultrasound surgery centre
The Philips high-intensity focused ultrasound system is used for surgery to destroy tumours or lesions (for example, uterine fibroids) noninvasively. It can be thought of as “scalpel-free surgery” because no incision is needed. It pairs MRI with high-intensity focused ultrasound to target a lesion. During treatment, feedback from MRI functions as a thermal “map.” It is used first to identify the target and then to guide the ultrasound as it is applied to the therapeutic “hot spot.” The ultrasound energy generates heat and destroys the lesion. Finally, it is used to determine right away if the treatment worked.
Clinical trials testing the efficacy of MRI-guided focused ultrasound to relieve symptoms of uterine fibroids were conducted at Sunnybrook, with excellent results.
The multiphoton microscope images live tissues down to one millimetre deep. The device performs real-time imaging at a microscopic level of brain tissue that is exposed to ultrasound. It is used extensively to study focused ultrasound-mediated drug delivery into the brain in small animal models.
Sunnybrook Research Institute has a next-generation Olympus multiphoton microscope. This specialized tool allows for near infrared light pulses up to 1,600 nanometres deep, which enables imaging of hippocampal neurons to further our understanding of the degenerative processes at work in dementia.
Preclinical 7-tesla MRI System
The Bruker 7T MRI system provides high sensitivity and throughput to enable a wide range of preclinical research. The system allows researchers to image small animals at a higher resolution—up to 40 microns. Researchers using it can test and monitor the effects of ultrasound interactions with tissue, including low-intensity focused ultrasound for targeted delivery of drugs and gene therapy in preclinical models of Alzheimer’s disease. Data acquired from preclinical studies of focused ultrasound treatments are required to obtain regulatory approval for human studies of the technology.
The 3T long-bore MRI system is used for a variety of studies, with a focus on translating research to patient care. It offers high resolution, and quick acquisition and reconstruction of images for faster scanning, which means less time for patients in the magnet.