Mapping Brain Metals With Magnetic Resonance Imaging

磁共振成像(MRI)在大脑中提供无与伦比的软组织对比，是神经成像的首选手段。它对组织中顺磁性过渡金属铁(Fe)和锰(Mn)的存在也非常敏感。这些生物金属对健康的大脑功能是必不可少的，尽管它们在高浓度下可能是有毒的，如果它们的水平太低，大脑的新陈代谢可能会失效。 如果核磁共振能够准确地测量动物和人类活体大脑中的铁和锰浓度，以研究这些元素在脑部疾病中的作用，那将是最理想的。不幸的是，MRI不是非常特异，铁、锰和其他组织成分，包括髓鞘，都会影响MR信号。这意味着，在多发性硬化症(MS)等常见的成像疾病中，大脑中的铁和髓磷脂浓度都可能发生变化，很难知道哪种疾病是导致磁共振图像中观察到的变化的原因。 幸运的是，有许多不同的磁共振参数可以通过成像在大脑中进行定位，每个参数对铁、锰和髓鞘的特异性和敏感度都不同。我们的研究计划的重点是利用这一事实并开发一种强大的MRI方案，该方案可以通过测量几个相关的MR参数来量化大脑区域的铁和锰。 虽然其他研究人员已经研究了铁、锰和髓鞘如何影响核磁共振信号，但他们的工作主要是基于这些组织成分的物理模型。我们的方法是独一无二的，因为我们将建立不同的大鼠系统，改变大脑中的铁、锰和髓鞘水平，然后在体内测量这些浓度。通过将大脑区域的实际浓度与我们在磁共振参数中测量的变化相关联，我们将能够创建准确的经验模型，用于在未来仅通过MRI进行的研究中预测铁和锰的浓度。 我们的实验室在动物科学、神经科学、辐射物理和成像方面拥有确保这项研究计划成功所需的强大专业知识。在过去的五年里，高素质的人员(HQP)帮助我们建立了新的实验室，成为世界上唯一能够在内部测量切除的新鲜脑组织中过渡金属浓度的实验室。为此，我们使用基于x射线或中子(在麦克马斯特核反应堆产生)的分析技术。随着今年新的7特斯拉MRI标本扫描仪的到来，新的HQP将开始项目，将这些措施与我们的新型大鼠系统中的MRI相关联，以治疗铁和锰的过度暴露和缺乏，以及严重的髓鞘丢失。 加拿大以开发先进的神经成像技术而闻名，我们的计划将为世界各地的研究人员提供经过验证的测量活体大脑中铁和锰浓度的方案，从而提高这一声誉。这将极大地帮助动物研究这些生物金属在脑部疾病中所起的作用，并将澄清人类临床磁共振成像在金属相关疾病中的解释。

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.