Mapping Brain Metals With Magnetic Resonance Imaging

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Magnetic resonance imaging (MRI) provides unrivaled soft-tissue contrast in the brain and is the premiere modality for neuroimaging. It is also very sensitive to the presence of the paramagnetic transition metals iron (Fe) and manganese (Mn) in tissue. These biometals are essential for healthy brain function, although they can be toxic at high concentrations and the brain’s metabolism can fail if their levels are too low. It would be ideal if MRI could accurately measure Fe and Mn concentrations in living brains in animals and humans to investigate the role of those elements in brain disease. Unfortunately, MRI is not very specific, and Fe, Mn, and other tissue components, including myelin, all affect the MR signal. This means that in a commonly imaged disease such as multiple sclerosis (MS), where Fe and myelin concentrations are both potentially changing in the brain, it is difficult to know which is responsible for observed changes in an MR image. Fortunately, there are many different MR parameters that can be mapped in the brain with imaging, and each parameter differs in its specificity and sensitivity towards Fe, Mn, and myelin. The focus of our research program is to exploit this fact and develop a robust MRI protocol that can quantify Fe and Mn in brain regions by measuring several relevant MR parameters. While other researchers have investigated how Fe, Mn, and myelin influence the MRI signal, their work has been based largely on physical models of those tissue components. Our approach is unique, in that we will develop various rat systems with altered Fe, Mn, and myelin levels in the brain, then measure these concentrations in vivo. By correlating the actual concentrations in brain regions with changes we measure in MR parameters, we will be able to create accurate empirical models for predicting Fe and Mn concentrations in future studies from MRI alone. Our laboratory has the strong expertise in animal science, neuroscience, radiation physics, and imaging needed to ensure the success of this research program. Highly qualified personnel (HQP) have helped to establish our new laboratory over the last five years as the only one in the world capable of in-house measurements of transition metal concentrations on excised fresh brain tissue. For this, we use analytical techniques based on x-Rays or neutrons (produced at the McMaster nuclear reactor). With the arrival of a new 7 Tesla MRI specimen scanner this year, a new crop of HQP will begin projects to correlate these measures with MRI in our novel rat system for Fe and Mn overexposure and deficiency, and severe myelin loss. Canada is renowned for developing advanced neuroimaging techniques and our program will bolster this reputation by providing researchers worldwide with a verified protocol for measuring Fe and Mn concentrations in living brains. This will greatly aid research in animals into the role these biometals play in brain disease and will also clarify the interpretation of human clinical MRIs in metal-related disease.