We are metal heads. Our brains need iron, copper, manganese and zinc to function, yet there is growing evidence that these metals may play a role in Alzheimer's disease, Parkinson's disease multiple sclerosis and other illnesses.
Canadian scientists are developing new imaging techniques to accurately map and measure metals in the brain, a crucial step toward learning more about why they are so essential, as well as understanding the damage they can cause under some circumstances.
Why is there so much copper and zinc in the plaques that clog the brains of patients with Alzheimer's disease, the most common form of dementia? Does too much manganese cause brain damage related to Parkinson's disease? What role do iron and other metals play in the lesions found in the brains of patients with multiple sclerosis?
These are the kinds of questions that Nicholas Bock at McMaster University in Hamilton, Ont., and Helen Nichol at the University of Saskatchewan in Saskatoon hope to be able to answer with brain imaging.
"How do you measure metal in the brain of a living person? Right now there is no way to actually do that," said Dr. Bock, who runs the Brain Metal Imaging Laboratory in Hamilton, Ont.
Iron, zinc, copper and manganese are different from metals like lead or mercury, which are neurotoxins and can cause serious brain damage when they are ingested or inhaled. In contrast, these biological metals play a number of helpful roles and are involved, for example, in the production of neurotransmitters, the chemicals that transmit signals between brain cells. We ingest these metals in our food, but researchers don't fully understand how the brain metabolizes and recycles them.
"It has to be perfectly in balance. If there is too little, the brain stops functioning. Too much, and there is tissue damage," said Dr. Bock.
He was recently awarded $120,000 from the Canadian Foundation for Innovation to help him develop a way to use magnetic resonance imaging to measure manganese and other metals in the brain. Manganese can make regions of the brain appear brighter on a MRI scan, he said, but so can other compounds or tissue damage. He plans to give increasingly large doses of the metal to rats and then scan their brains to see if he can link the higher levels of manganese to the level of brightness in the images.
He also hopes to follow up with a study of steel-mill workers and welders who were exposed to high levels of manganese at work. In some cases, these workers develop symptoms similar to Parkinson's disease and have damage in the same areas of the brain.
A recent study in the U.S. found that people who live near a steel factory or another source of manganese emissions are at a higher risk of developing Parkinson's disease, a progressive, incurable neurological disorder with a wide array of symptoms including tremors, stiffness and loss of speech.
Brain imaging may also prove essential to understanding the role metals play in multiple sclerosis. The build up of iron in the brain is part of a controversial theory about MS proposed by Italian doctor Paolo Zamboni. He suspects that the neurological disorder can be caused when blocked veins impede the flow of blood from the brain, which may then cause inflammation, iron deposits and brain lesions.
In Saskatoon, Dr. Nichol is investigating with the help of a synchrotron, a source of brilliant light that can analyze the microstructure of material down to the level of the atom.
"With the synchrotron, we can see iron in the brain quite clearly, it is really the best way to look at metals," said Dr. Nichol.
It only works, however, on tissue removed from a cadaver. But Dr. Nichol and her colleagues, Mark Haacke, an adjunct professor at McMaster, and Sultan Darvesh at Dalhousie University, did parallel scans. They took images of the same tissue with both the synchrotron and a magnetic resonance imager.
This, combined with pathology, allowed them to be confident that MRIs can be used to identify iron deposits in the brains of MS patients.
It is still unclear, however, what role the deposits play in MS, since they are also seen in other neurological disorders.
Dr. Zamboni is urging patients to wait for further clinical trials before undergoing so-called "liberation therapy," which involves improving the flow of blood from the brain.
MS can cause loss of balance, heat sensitivity, impaired speech, paralysis and other symptoms. It is characterized by lesions on the brain.
Dr. Nichol and her colleagues, whose work is funded by the Saskatoon City Hospital Foundation, recently found that large chronic lesions in the brains of MS patients are devoid of zinc, copper and iron.
"We need to understand it. You want to stop things before the brain damage cannot be reversed."