ADVANCES IN MEDICAL IMAGING AT SUNNYBROOK WILL DRAMATICALLY IMPROVE OUTCOMES FOR CANCER, CARDIAC
Sue Walsh, a breast-cancer patient who took part in a trial of an innovative imaging technique called Quantitative Ultrasound, a technology that can pinpoint dead cancer cells.
For seven months, Sue Walsh received chemotherapy for breast cancer at Sunnybrook. The treatment itself wasn’t new, but there was something different this time around: Instead of having to wait six to eight months until the end of the chemo to see if the drugs worked, Sue and her doctors were able to detect the cancer changing within a few weeks of each treatment.
“To be able to tell early on if a treatment is working is truly amazing,” says Sue, a Toronto resident who was part of clinical studies in 2012 for a made-in-Sunnybrook innovation known as QUS (Quantitative Ultrasound), a technology that uses advanced software and ultrasound imaging to pinpoint dead cancer cells. “In my case they could see it was working and that it reinforced what the oncologist’s physical exams were saying – the tumour was shrinking. When they did the biopsy [at the end of the study] to confirm the results, they saw that the number of cancer cells was significantly less.”
Sue’s experience is just one example of how doctors at Sunnybrook are using state-of-the-art medical imaging technology and techniques for the way they diagnose, target the delivery of treatments and track treatment responses to better tailor treatment.
“These are exciting times,” says Dr. Masoom Haider, chief, department of medical imaging at Sunnybrook and senior scientist at Sunnybrook Research Institute’s Odette Cancer Research Program. “Sunnybrook is definitely doing leading-edge work in the area of imaging – from using it to better assess patients to applications where imaging is used to guide the treatment and see how it’s working,”
Imaging projects at Sunnybrook fall into three main categories: diagnostic, therapeutic and “theranostic” – a hybrid of the first two categories. Diagnostic imaging is focused on imaging to detect and characterize disease, while therapeutic uses imaging to guide treatment. In the third category, imaging is used to predict effectiveness of therapy and to provide patients with the greatest benefit from treatment.
To support its advanced imaging projects, Sunnybrook has made a number of recent capital investments, including the purchase of a cyclotron, a machine that creates the radioactive isotopes injected into patients ahead of a positron emission topography (PET) scan of their internal organs.
The isotopes from the cyclotron go into decay within minutes. Having the machine right at Sunnybrook will allow doctors to produce this material on-site, says Dr. Haider. This is more cost-effective and also makes it easier for Sunnybrook scientists to develop new chemical agents that can provide more insight into a wide variety of diseases.
An example of an advanced imaging project in Dr. Haider’s department is the “smart biopsy,” which involves the use of magnetic resonance and ultrasound imaging to diagnose prostate cancer. By fusing magnetic resonance images with ultrasound results, doctors are able to locate and trace a tumour and zero in for a biopsy.
This makes the diagnostic process less painful and disruptive for patients, says Dr. Haider. More importantly, it increases the chances of catching and treating the cancer early, leading to better outcomes.
This novel application of MRI technology made all the difference for Kim Stewart, who learned in the fall of 2012 that his PSA levels were abnormally high.
After a 15-needle biopsy at another medical facility failed to detect cancer, Kim was referred to Sunnybrook, where an MRI-guided biopsy enabled his doctor, Dr. Danny Vesprini, radiation oncologist of Sunnybrook’s Odette Cancer Centre Genitourinary Cancer Care Team, to definitely confirm he had cancer. Kim had surgery last October to remove the cancer and says he is now in the clear.
“Knowing my PSA was very high, but not being able to confirm whether or not I had cancer – that was very confusing and worrying,” he says. “The fact that Sunnybrook was able to find the cancer through the MRI and do a biopsy that took only six needles was pretty amazing.”
Sunnybrook’s work in imaging cuts across a wide range of diseases, from cancer and heart disease to stroke and Alzheimer’s disease. With some imaging projects at Sunnybrook, the technology is homegrown, while in others it’s the application of existing equipment that’s unique and innovative.
What all these projects have in common is their quest to visualize what has long been invisible so doctors can, finally, have the information they need to give their patients the most appropriate and effective care.
“It’s the stuff of science fiction,” says Dr. Sandra Black, Brain Sciences Research Program director at Sunnybrook. “But it’s happening now, and our hope is that it’s going to make a huge difference for patients with serious conditions.”
THERAPEUTIC: PET-MRI WITH
In the future, patients with early-stage Alzheimer’s disease or dementia could come into a hospital, put on an ultrasound helmet and get stem cells or a combination of drugs injected with precision into the affected parts of their brain.
Sounds far-fetched? This cutting-edge treatment could be coming soon to Sunnybrook, thanks to the innovation of its scientists and a multimillion-dollar investment in a PET-MRI system.
The much-anticipated system will be housed in the future Slaight Centre for Image-Guided Brain Therapy and Repair, which is being funded by a $10-million donation from the Slaight Family Foundation at Sunnybrook Research Institute. The PET-MRI system will be modified for integration with a transcranial-focused ultrasound device fashioned as a helmet.
Developed by Sunnybrook scientist Dr. Kullervo Hynynen, the ultrasound device uses ultrasound beams and harmless, tiny gas bubbles to create a temporary opening in the brain’s blood barrier. This allows large molecules, such as growth factors, antibodies and even stem cells, to get into the brain through the barrier posed by tight junctions in the tiny blood vessels called capillaries which otherwise would keep them out. Real-time imaging from the PET-MRI scanner ensures the ultrasound and therapeutics are targeted precisely to a specific area of the brain.
“Right now intravenous infusions or injections of monoclonal antibodies are inefficient because you get only 1 per cent of them into the brain, and these are very expensive biological treatments,” says Dr. Sandra Black. “But if you could increase their access into the brain and in targeted areas where they are needed, that could be very beneficial.”
Focused ultrasound at high frequency (HiFU) is already being used in trials for other conditions, including treatment of severe tremors, notes Dr. Black. It is called knifeless surgery. Low frequency focused ultrasound (LoFU) is already in trials at Sunnybrook to deliver drugs into brain tumours by opening the blood-brain barrier as the chemotherapy is being infused.
Sunnybrook researchers are hoping they will also soon be able to use focused ultrasound to break up blood clots in the brain vessels of patients with stroke and to get drugs into the brains of people with Alzheimer’s disease. If the preliminary studies continue to go well, they hope to launch the first clinical trials using LoFU in Alzheimer’s disease within the next few years.
DIAGNOSTIC: HEART METABOLIC MRI
A new imaging method pioneered at Sunnybrook is giving doctors new perspective into a patient’s heart, allowing them to detect heart failure at an early stage and identify the best therapy.
Using a new, $2-million imaging system known as a metabolic MRI, Dr. Charles Cunningham, a physicist in the Schulich Heart Research Program, developed a technique for non-invasively measuring the metabolism in the heart muscle, capturing chemical reactions as they occur.
“As the human heart begins to fail, it starts to use glucose instead of fat as its preferred fuel,” explains Dr. Cunningham. “That’s one of the metabolic changes that occur, and there are drugs that reverse that.”
An MRI combined with ultrasound was used to guide
the biopsy and find the occult prostate cancer of
Kim Stewart, shown here with Dr. Laurent Milot.
Dr. Cunningham’s new method uses a “hyper-polarizer” machine to add magnetic signals to pyruvate – a chemical compound produced when the body metabolizes glucose or sugar. When injected into a patient, this magnetized pyruvate can be captured visually using an MRI scanner.
“We make images of the pyruvates as well as other metabolic products such as carbon dioxide and glutamate produced within the heart muscle,” says Dr. Cunningham. “We know what the changes are for those products in early
Magnetic resonance imaging is already used today to visualize the pumping of a patient’s heart. Integrating the hyper polarizer would add a mere 10 minutes to the process and provide significantly more valuable information that may soon help doctors develop an optimal treatment plan for each patient.
Sunnybrook is now getting ready to embark on its first patient studies using this method for cardiovascular imaging. Dr. Cunningham says his team will also be working with drug companies on ways to target the different patterns in metabolic changes from heart disease, which affects about 1.4 million Canadians today and kills close to 50,000 a year.
“There are a lot of different drugs and they have varying degrees of efficacy for different stages of heart failure,” he says. “Our goal with these studies is to be able to identify which patients would be better candidates for certain types of therapy – that would be a huge improvement.”
THERANOSTIC: QUS (Quantitative Ultrasound)
Sunnybrook is making waves in breast cancer treatment with an innovative monitoring technique that can detect within one to four weeks whether or not a patient is responding to chemotherapy.
Known as QUS, the new technology applies specialized software to traditional ultrasound imaging to detect the absence or presence of cell death from chemotherapy.
For women with locally advanced breast cancer receiving pre-surgery chemotherapy, the use of QUS means they’ll no longer need to wait months to find out how the treatment worked.
“About 60 to 70 per cent of the time, chemotherapy could be more effective,” says QUS study lead, Dr. Gregory Czarnota, Sunnybrook’s head of radiation oncology at the Odette Cancer Program, and a senior scientist at Sunnybrook Research Institute. “But the problem with classic diagnostic imaging is that it measures tumour size and extent, and when you’re treating tumours, changes in size take many months to happen.”
With QUS, doctors will know sooner if they need to switch their patient to a different type of drug or treatment method – a move that potentially stands to change the outcome for women with locally advanced breast cancer.
More than 100 women have signed up to participate in a QUS study, and about 85 of these women have finished their tests.
“The results proved that the technology works – that within one and four weeks we can demonstrate whether the chemo was going to work or not,” says Dr. Czarnota. “We’re at the stage now where the technology is being expanded to other centres through the Ontario Institute for Cancer Research.”
THERAPEUTIC: MRI - RADIATION TECHNOLOGY
What if you could deliver cancer treatment with laser-sharp precision, killing only the cancer and leaving normal tissues untouched? That’s a goal Sunnybrook hopes to help accomplish soon.
Last year, Sunnybrook joined a research consortium to develop and test a new system that merges magnetic resonance imaging with radiation therapy. This breakthrough technology, which provides exceptional depictions of a patient’s soft tissues and tumour, could soon make it possible for doctors to track the treatment site in real-time and reduce side-effects from radiation therapy.
Created by Stockholm-based Elekta AB and Royal Philips Electronics in the Netherlands, the new technology represents one of the most exciting developments in radiation technology in the last decade.
QUANTITATIVE ULTRASOUND: AN EYE TO BREAST CANCER
The top row shows a large breast tumour before pre-surgery chemotherapy treatment and (bottom row) after four weeks of treatment, using four different techniques, starting with black-and-white ultrasound on the left.
This graph shows quantitative ultrasound of a case in which the breast cancer tumour is responding to pre-surgery chemotherapy treatment; the blue lines show the tumour before chemo, and the red lines are after treatment.
Each row shows a different tumour’s response to treatment. Red areas show low signal intensity – i.e. a low response to chemotherapy. Yellow shows high signal intensity, signalling a good response.
The top row is a nonresponding case; the two lower rows show tumours responding To treatment over a period that starts pre-treatment and progesses to the eighth week of treatment and (in the final square) just before surgery.
Follow us on Twitter: