High-resolution iron mapping to study the role of brain iron complexes in the basal forebrain in neuropsychiatric disorders.

高分辨率铁图谱研究基底前脑中的脑铁复合物在神经精神疾病中的作用。

• 批准号: 2108879
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2108879
• 关键词: resolution; iron; mapping; study; role

The mechanisms of brain iron changes underlying neurodegenerative diseases are largely unknown. One hypothesis suggests that erythrocytes leak through an impaired blood-brain barrier leading to activation of microglia. This results in intracellular deposition of haemosiderin, a disorganised iron storage complex which contains unbound iron ions. In this state, iron is neurotoxic producing free radicals and causing oxidative stress. The nucleus basalis of Meynert is a cholinergic basal forebrain nucleus which is affected early in the course of many neuropsychiatric disorders. Brain iron can be detected using gradient-echo MRI with areas of high iron appearing hypo-intense in magnitude images. Advanced susceptibility mapping at high field is needed for reliable quantification. Disentangling the mechanisms that lead to iron-mediated neurotoxicity is at the frontier of multidisciplinary research and clinical imaging. Moreover, non-invasive iron mapping using MRI provides a mechanistic biomarker for disease prediction that can be exploited in future clinical trials.

神经退行性疾病背后的脑铁变化的机制在很大程度上是未知的。一种假设认为，红细胞通过受损的血脑屏障渗漏，导致小胶质细胞激活。这会导致血铁血黄素在细胞内沉积，这是一种含有游离铁离子的无序铁存储复合体。在这种状态下，铁具有神经毒性，会产生自由基并导致氧化应激。Meynert基底核是胆碱能的前脑基底核，在许多神经精神障碍的病程早期都会受到影响。使用梯度回波磁共振成像可以检测到脑铁，高铁区域在大小图像上看起来是低信号的。为了可靠地定量，需要在高场下进行先进的磁化率测绘。解开导致铁介导的神经毒性的机制处于多学科研究和临床成像的前沿。此外，使用MRI的非侵入性铁标记物为疾病预测提供了一个机械性的生物标记物，可以在未来的临床试验中使用。