Despite centuries of study, the brain remains, for the most part, an enigma. Though researchers have accelerated progress in the past 25 years, there is still much to explore – from the evolution of human consciousness, to the intricacies of memory, to the causes of many of the hundreds of brain disorders. Fortunately, recent advances in technology have been allowing researchers to develop new tools and techniques to aid in their understanding of how the brain works, how the system is interconnected, and how damage from injury or disease can be repaired.
One of the important techniques that has been driving recent developments in brain research is neuroimaging. Neuroimaging (or brain imaging) involves the use of various approaches to non-invasively peek into the brain – to either directly or indirectly visualize the structure or function of the brain.
There are several different types of imaging, and more are being developed every year. While most people are familiar with the different acronyms (MRI, CT, EEG etc), they might not be familiar with the details of how each one works and what information about the brain each method is able to convey. Neuroimaging techniques, for the most part look, at either 1) the structure or anatomy of the brain and changes in this structure due to tumours, injuries, and stroke; or 2) the function of the brain –to visualize the relationship between activity in certain brain areas and specific functions. Newer imaging methods are able to combine the two types and show both structure and function.
Magnetic Resonance Imaging (MRI) is one of the most commonly used neuroimaging methods. An MRI generates images of the brain through the use of magnetic fields and radio waves. Since its development in the 1950s, MRI technology has advanced significantly in both its sophistication and precision, from fuzzy masses on a scan to detail about the brain down to the size of a grain of sand. In addition to improving resolution, scientists are developing new MRI techniques that look at different aspects of the brain. For instance, functional MRI (or fMRI) uses MRI technology to measure brain activity by monitoring blood flow in the brain. It works on the premise that if a certain area of the brain is in use, blood flow to that region will increase.
A relatively new kind of MRI is called diffusion tensor imaging or DTI, and it looks at the movement of water molecules along the white matter tracts in the brain. Aside from providing startlingly beautiful images of the brain (see left), it has proven invaluable for learning about damage to the white matter of the brain, which occurs in traumatic brain injuries for example.
Scientists are embracing these new technologies and techniques and quickly integrating them into their research.
Applications of imaging in brain research
Currently, Alzheimer’s disease (AD) can only be detected when serious mental decline has already occurred. With the aging population, the number of cases of Alzheimer’s disease is expected to increase dramatically, and the pressure to develop earlier detection methods is immense. Neuroimaging is one avenue that holds great promise. It is already used to rule out other conditions that may cause symptoms similar to Alzheimer’s but require different treatment, such as stroke, tumours and trauma. Current research directions involving imaging include looking at the shrinking of specific regions of the brain and developing imaging “markers” that will hopefully help in diagnosing AD earlier.
Similar research in being conducted for autism, where earlier diagnosis (before symptoms appear) can mean earlier intervention and treatment leading to better outcomes for children with this disorder.
In the case of chronic pain, imaging has transformed our understanding of this disorder. Researchers have been able to identify some of the different areas of the brain that are activated in the presence of chronic pain. Beyond helping researchers understand the causes of this debilitating condition, this has also profoundly helped chronic pain sufferers who now have validation that their pain is real.
For multiple sclerosis (MS), MRI studies are used to monitor treatment response and may aid in predicting disease progression in individual patients. In addition, results of imaging studies have led to important insights into the physiological mechanisms of MS
Imaging in Brain Canada projects*
Among our Brain Canada-funded researchers, there are numerous of examples of how imaging is being used to advance our understanding of brain disorders.
Imaging is proving very useful for research into desperately needed brain therapeutics. The brain is protected from foreign items by a tight barrier, known as the blood-brain-barrier (BBB). Though this is useful to prevent toxins and other potentially harmful substances from reaching the brain, it also prevents potentially life-saving drugs from reaching its targets in the brain. Through a partnered grant between Brain Canada and CQDM and funding from Health Canada through the Canada Brain Research Fund, Dr. Yoganathan of Kalgene Pharmaceuticals is Principal Investigator on a project that is trying to breach the blood brain barrier. Dr. Yoganathan and his team are trying to sneak a molecule into the brain to help treat Alzheimer’s disease. Imaging is crucial to providing evidence that the drug has in fact managed to cross the BBB into the brain and is doing what it is supposed to do (in this case bind amyloid, a substance associated with the development of Alzheimer’s). More info on this project
It is estimated that one in five youth suffer from a mental disorder and that 75% of chronic and persistent serious mental illnesses (SMI) begin in young people between the ages of 10-24. Understanding the interplay of risk factors that determine the onset of SMI relies on understanding the effects that key risk factors exert on the neurobiology of the developing brain. For a Brain Canada team grant, Dr. Jean Addington and her team are using a multifaceted approach to try and be able to predict serious mental illness. Their project involves following a large group of youth in both Calgary and Toronto, aged 14-25, who are at different stages of risk for developing SMI. They assess a wide range of clinical and psychosocial factors in order to determine the ones that can be used to predict key outcomes. Included in this is brain scans of each study participant to investigate whether neuroimaging can be useful to help distinguish youth who will develop SMI from those who will not. (Click here for more information on this project)
In the area of brain cancer, Dr. David Stojdl and his team are developing a new and different way to treat brain tumours. Their lab has custom-built an oncolytic (cancer) virus specifically for the treatment of the devastating brain cancer Glioblastoma multiforme (GBM). The Farmington virus kills brain cancer cells but leaves normal healthy tissue intact, and is one of the only oncolytic viruses in the world that can be safely injected at high doses into the brain. For their Canadian Cancer Society Impact grant, with funding from Brain Canada and Health Canada, through the Canada Brain Research Fund, the team has re-designed the Farmington virus with the ability to trigger a patient’s own immune system to fight their brain tumour. MRI imaging is used to provide evidence that the tumour is shrinking in response to the virus. (Click here for more information on this project)
Current limitations of imaging
While neuroimaging has advanced considerably, there remain several challenges and limitations. Other Brain Canada-funded projects are tackling some of the issues currently associated with neuroimaging.
One of the limitations to neuroimaging is the cost. For many small start-ups, such as new biotechs, the cost of imaging technology can be prohibitive. A team in Nova Scotia, has come up BIOTIC, an innovative way to allow these small companies access to state-of-the-art imaging machinery. BIOTIC is a hospital-based medical imaging research facility that focuses on the clinical and commercial translation of new neuroscience technologies. Through their Brain Canada platform grant, the are helping companies get a foothold in the hospitals and test out their technology in a cost effective way within a rigorous scientific and ethical framework. (For more information on this project, please click here)
While neuroimaging has advanced considerably, there remain several challenges and limitations.
One of the outputs of neuroimaging is data – massive amounts of data in the form of high-resolution images. This causes a problem for researchers who need to be able to easily store, share and analyze the images, as they need increasingly more powerful computing systems. Dr. Alan Evans and his team at the Montreal Neurological Institute have developed the Canadian Brain Imaging Research Platform (CBRAIN), a web portal that provides researchers with the tools to overcome the large-scale data processing challenges of neuroimaging. The platform connects 300+ researchers in brain imaging centres across Canada and around the world, enhancing the ease with which researchers can share complex 3D and 4D brain imaging data collected from large multi-centre research projects. Through a Brain Canada platform grant, the platform is currently being used to uncover the causes of major neurological disorders impacting society, including autism, Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. (Click here for more information on CBRAIN)
Currently, neuroimaging research is hindered by a lack of standardization, both in terms of image acquisition and the post-processing analysis of acquired images. What this means is that in many instances, the images from one study are not comparable with results from other study, or that images from different research sites (even different research sites within one university) are not comparable. Dr. Christopher Anderson and his team are using their Brain Canada platform grant to address these consistency issues across University of Manitoba departments. They have developed the Manitoba Neuroimaging Platform that allows researchers from different departments at the University of Manitoba, who work with imaging data on different diseases, to process their data in a fast, harmonized and reliable way. The platform provides high computer power, post processing software, an environment of interdisciplinary exchange and enables the processing of large amounts imaging data on different neurologic disorders.
Next frontier in imaging
The next frontier for neuroimaging is artificial intelligence (AI). Far from the alarmist fears of robots taking over the world, AI and imaging has the potential to truly revolutionize the field. AI and neuroimaging are a perfect match. Machine learning, a sub-field of artificial intelligence, involves developing algorithms to allow machines to learn from data by analyzing the data, finding patterns and making predictions.
Neuroimaging will continue to be a major driver in advancing our understanding of the brain and brain disorders, and lead to more precise and earlier diagnosis and improved outcomes for people.
The more data for the algorithms, the more “learning” and the better the accuracy. With imaging, there is no shortage of data. Researchers are developing algorithms that can sift through brain scans in a fraction of the time it would take humans and identify patterns and outliers. This is already being applied in some areas, such as in identifying brain tumours.
With exponentially improving computing capabilities, advances in imaging technology, the joining of AI with imaging, along with the ingenuity of our talented brain researchers – neuroimaging will continue to be a major driver in advancing our understanding of the brain and brain disorders, and lead to more precise and earlier diagnosis and improved outcomes for people.
*Funding for these projects is provided by Brain Canada, Health Canada, through the Canada Brain Research Fund, and other partners.