Q&A: How brain imaging is propelling discovery
The ability to see our living, active human brain in detailed pictures is having a revolutionary impact on our understanding of mental illnesses and addictions, and exposing potential new opportunities for treatment.
This year alone, newly announced discoveries by scientists in the Campbell Family Mental Health Research Institute at CAMH have identified the role of brain inflammation in depression and in Alzheimer's disease, and differences in the brain networks of people with severe schizophrenia. These important findings have all been made possible through the use of brain imaging.
CAMH's 2015 Campbell Family Mental Health Research Symposium, held on November 9, highlighted breakthroughs in brain imaging. We asked Dr. Isabelle Boileau, Clinical Research Scientist in the Research Imaging Centre and Head of the Addiction Imaging Research Group at CAMH, to explain the powerful ways that brain imaging is making an impact.
What are the different kinds of brain imaging at CAMH, and what does each show you?
One is positron emission tomography (PET), a nuclear medicine tool. Participants receive a dose of a radioactive chemical, called a radiotracer or a probe, which travels through the blood and attaches to a specific target in the brain. With PET, for example, we can look at brain chemistry. This includes the receptors and transporters that neurotransmitters – and the medications we take – attach to. Neurotransmitters are the chemicals that send messages from one nerve cell to another in our body. We can also look at enzymes, which accelerate chemical reactions.
At CAMH, Dr. Alan Wilson, Chief Radiochemist with the Research Imaging Centre, has developed a number of probes, driving innovative research. Both here at CAMH and in the broad research community, these novel probes have given us the tools to learn about systems in the human body that are poorly understood, including the endocannabinoid system and the D3 receptor system.
Magnetic resonance imaging (MRI) gives us very detailed information about the brain's structure and function, including our brain’s “wiring” or neural circuits. With functional MRI (fMRI), we can observe which parts of the brain are working when a person is performing an activity.
By combining both types of imaging, the hope is that scientists will not only be able to identify dysfunction in neurochemistry that is involved in disease symptoms, but how these neurochemical “abnormalities” affect the way a person’s brain functions and responds when completing tasks.
Seeing the human brain in three ways (from left):
An MRI image, showing brain structure; a PET image, showing binding of a dopamine receptor probe (the red areas depict high binding); and a PET image (showing binding of a dopamine probe) overlaid on top of an MRI image to show which brain structures are involved
Why are both PET and MRI useful in understanding what’s happening in the brain?
There are advantages and disadvantages of using each type of imaging individually.
With PET, a key advantage is that you can study a specific system in the brain based on the radiotracer you’re using. A disadvantage is that, because PET uses radioactivity, there is a limited number of times that it is safe for a person to be scanned.
With MRI, a person can be scanned as many times as desired, so this allows you to perform long-term studies on the same person. For example, you can look at brain structure over time and what atrophy occurs in parts of the brain throughout the course of a disease. You can also see how a disease or a treatment affects the way a person’s brain responds when completing a specific task.
The image we obtain with PET doesn’t contain detailed information about anatomy, so we usually superimpose the images we receive from PET and MRI. By putting one image of top of the other, we can see where the signal is happening in the brain – in other words, which brain structures are involved.
Both types of imaging are valuable because they can address completely different questions. For example, PET can look at neurochemistry, and MRI complements this by giving a very detailed structural picture of the brain and its neural functions.
Increasingly, we are turning to studies that include both types of imaging. These studies combining PET and MRI can be complex at the statistical level, but the results are fascinating. For example, we are investigating the relationship between the levels of an enzyme that metabolizes the brain’s cannabis-like chemical, called anandamide, and the activity in brain circuits involved in emotion. These studies can help us understand the role of this system in mood and anxiety.
We are also incorporating genetics. For example, as part of every PET study, we collect blood to determine the person's genetic makeup, a process known as genotyping. This is important because the binding of the radiotracer could be affected by the individual’s genotype. Genotyping allows us to better interpret our PET data.
How do you use brain imaging in your research?
Dr. Alan Wilson has developed a radiotracer that targets the D3 dopamine receptor. In the past, animal studies showed that D3 is elevated in addictions. We’ve been able to show this in the brains of people who have addictions.
Another area of my research is investigating an enzyme in the brain called fatty acid amide hydrolase. This enzyme metabolizes anandamide, a cannabis-like substance naturally occurring in the brain. We are using MRI and PET imaging to develop models about the role of this enzyme and behaviour in disease.
How has brain imaging advanced treatment for mental illnesses and addictions to date?
One example with PET is that it’s been possible to track how a person responds to existing psychiatric medications. We've been able to show if medications are attaching to the receptors they’re targeting, and how much binding you need to obtain a treatment response. So it’s enabled us to see the effect of a medication.
How do you expect brain imaging will advance treatment in the future?
Brain imaging is giving us an understanding of the mechanisms that lead to a disorder.
In many cases, the medications we use to treat mental illnesses today were discovered by borrowing drugs developed for other illnesses and hoping they would work for this disorder. Now, by combining imaging modalities, we have a better understanding of the brain chemistry involved in normal human behaviour and in the case of disease, and of how changes in brain chemistry can affect how our brain functions or responds when completing a task.
This will allow us to develop medications or psychosocial treatments that are truly evidence-based.