Mapping Brain Metals With Magnetic Resonance Imaging

利用磁共振成像绘制脑金属图谱

• 批准号: RGPIN-2014-04368
• 负责人: Bock, Nicholas
• 金额: $ 1.6万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=633319
• 关键词: Mapping; Brain; Metals; Magnetic; Resonance

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.

磁共振成像（MRI）提供了无与伦比的大脑软组织对比度，是神经成像的首要模式。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至关重要，尽管它们在高浓度下可能有毒，如果它们的水平过低，大脑的新陈代谢可能会失败。如果MRI能够准确测量动物和人类活大脑中的Fe和Mn浓度，以研究这些元素在大脑疾病中的作用，那将是理想的。不幸的是，MRI不是很特异，铁，锰和其他组织成分，包括髓鞘，都影响MR信号。这意味着在常见的成像疾病中，如多发性硬化症（MS），其中Fe和髓鞘浓度在大脑中都可能发生变化，很难知道哪一个是导致MR图像中观察到的变化的原因。幸运的是，有许多不同的MR参数可以通过成像在大脑中映射，并且每个参数对Fe，Mn和髓鞘的特异性和敏感性都不同。我们的研究计划的重点是利用这一事实，并开发一个强大的MRI协议，可以量化铁和锰在大脑区域通过测量几个相关的MR参数。虽然其他研究人员已经研究了铁，锰，髓鞘如何影响MRI信号，他们的工作一直主要基于这些组织成分的物理模型。我们的方法是独特的，因为我们将开发各种大鼠系统，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测量的MR参数变化相关联，我们将能够创建准确的经验模型，用于预测未来仅从MRI进行的研究中的Fe和Mn浓度。我们的实验室在动物科学，神经科学，辐射物理学和成像方面拥有强大的专业知识，以确保这项研究计划的成功。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，成为世界上唯一一个能够在内部测量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，HQP的一批新成员将开始项目，在我们的新型大鼠系统中将这些测量与MRI相关联，以检测铁和锰的过量和缺乏，加拿大以开发先进的神经成像技术而闻名，我们的项目将通过为世界各地的研究人员提供一个经过验证的方案来测量脑组织中的铁和锰浓度，活的大脑这将极大地帮助动物研究这些生物金属在脑疾病中的作用，也将澄清人类临床MRI在金属相关疾病中的解释。