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Every brain imaging tool only shows a piece of a puzzle. Dr. David Mikulis wants doctors to see the whole picture.

Thomas Bollmann

Dr. David Mikulis has dedicated most of his almost 40-year career to understanding how the human brain functions. But the Krembil Brain Institute researcher is quick to admit that the roughly one and a quarter kilogram organ is still a bit of a mystery – not just to him, but to the wider scientific community as well.

Scientists are still trying to decipher how the jolts of electrical currents jumping between brain cells, helped along by chemicals that bridge the gap between those cells, become our thoughts, feelings and actions. “The brain is so complex, it’s still the tip of the iceberg trying to understand how it works,” he says.

Imaging techniques have contributed enormously to that understanding, he says, but one strategy alone can’t provide all the answers. Instead, Dr. Mikulis is trying to “stitch” various techniques together to see more of, and learn more about, the brain. His efforts, and those of others worldwide, are allowing physicians to more accurately diagnose, and catch earlier, different forms of dementia.

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Putting the pieces together

Every imaging technique provides a piece or two of the brain map. A computed tomography (CT) scan shows the brain’s structure by gluing together X-ray images from different angles. Magnetic resonance imaging (MRI) is similar, but it makes out the brain’s structure using magnetic fields. Tracking a radioactive dye injected into the bloodstream, a process called positron emission tomography (PET), can show the brain’s chemical processes.

Scientists can also image the location and timing of electrical and magnetic fields produced by the firing of small groups of neurons through electroencephalography (EEG) and magnetoencephalography (MEG). “It’s kind of nice having systems that do different things – they complement each other,” says Dr. Mikulis.

However, no single technique gives scientists an overall view of all the levels of the brain’s structure and function at one time. Stitching those various maps together, Dr. Mikulis says, is the next advancement in imaging technology.

There are two ways to make this work. One is to combine the knowledge of neuroimaging scientists, who visualize larger chunks, or networks, of the brain, and computational neuroscientists, who create computer models of how brains cells work together. The neuroimaging scientists, provide the big picture and the neuroscientists build a brain from the ground up.

Another is to apply artificial intelligence (AI) to brain-imaging data. Dr. Mikulis explains that computer machine learning systems can find patterns in millions of images that might be missed by the human eye.

“Advanced image processing and artificial-intelligence methodology will [drive] some of the major improvements in this area until something completely new and unexpected comes along,” Dr. Mikulis says. To this end, Krembil has hired several computational neuroscientists with AI expertise.

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Knowing how a healthy brain works as a single, integrated whole is the first step to understanding what happens when that structure is altered.

The dementia diagnosis problem

Through imaging, scientists now have a better understanding of how brain injury changes a person's daily functioning or mood. Dementia however, the group of diseases characterized by the slow decline in mental processes, including memory and thought, has proven difficult to diagnose, let alone treat or prevent.

Physicians typically rely on an exclusionary approach to figure out the cause of dementia. Alzheimer’s dementia is established after first ruling out other causes of dementia-like symptoms, such as tumours, blood vessel diseases, or thyroid problems, using imaging or blood tests. They then run patients through a series of psychological tests to try to tease apart subtle differences in symptoms.

More recently, neurologists have been able to see brain changes associated with different forms of dementia. The most common form, Alzheimer’s disease, is characterized by brain shrinkage, particularly in the areas associated with memory, which can be seen using MRI. Other signs of Alzheimer’s are the buildup of clumps of protein called beta-amyloid plaques, or abnormal structures called neurofibrillary tangles, both of which can be identified using PET. The second most common form of dementia, vascular dementia, is due to blood flow being cut off to parts of the brain, causing the cells in that area to die. Diagnosis therefore relies on CT or MRI scans that can show a series of mini-strokes.

Better imaging will also allow physicians to more accurately diagnose different forms of dementia or catch brain changes early, says Dr. Mikulis. For example, new research suggests subtle changes in brain blood flow may trigger Alzheimer’s in people with genes that make them prone to the disease. Tiny pulsing blood vessels, he explains, move the brain’s cleaning fluid through the brain. If the blood vessels aren’t pumping properly, the brain may not be able to clear out beta-amyloid proteins, and they’ll then start to build up.

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Dr. Mikulis and his team developed a way to see how well these tiny vessels pulse, by combining MRI with a system that dilates blood vessels using carbon dioxide. “It is the only method of its kind” says Dr. Mikulis, “this method combined with other imaging tools could be very effective in identifying individuals at risk of dementia.”

Other neuroscientists are developing ways to detect Alzheimer’s early through improved imaging. Dr. Dmitriy Yablonskiy, a radiology professor at Washington University School of Medicine, and colleagues discovered a new signal in MRI scans that directly relates to the number of neurons and their connections. They used the signal to show that Alzheimer’s patients had smaller brain memory centres, called hippocampi, than healthy people, and that the cells in that area were beginning to decay even before more obvious signs were visible.

“The goal would be that we can start screening a population of people, say above 50 years old, as is done with other routine tests such as mammograms” says Dr. Yablonskiy. “Eventually, pharmaceutical companies will find a way to at least halt this process. A cure will be more accessible [with early detection].”

“Imaging tools will be extremely useful to us in not only making the diagnosis earlier, but instituting treatments earlier,” adds Dr. Mikulis. More detailed imaging might also reveal previously unknown causes of dementia, which could provide the basis for a cure.

He is realistic, but also optimistic, about the future of imaging and the role it can play in that search. “We’re pretty advanced right now, but there are still patients that baffle us. I think we’re getting closer all the time.”

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