Translating brain magnetic resonance imaging signals to iron and myelin to appraise Alzheimer's disease

将脑磁共振成像信号转化为铁和髓磷脂以评估阿尔茨海默病

• 批准号: 2604976
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2604976
• 关键词: Translating; brain; magnetic; resonance; imaging

Aim of the PhD Project:To determine the individual and combined contributions of iron and myelin to multi-modality quantitative magnetic resonance imaging (QMRI) signals.Project DescriptionIron accumulates in the brain with ageing, with advancing age being the major risk factor for neurodegenerative diseases such as Alzheimer's Disease (AD; ). Indeed, iron dyshomeostasis is a feature of AD [3] and iron chelation therapy is undergoing a clinical trial for AD.Quantitative magnetic resonance imaging MRI (QMRI) methods are sensitive to iron content (to differing extents and specificities). The So Lab and others have shown T2* values compared to T1 and T2, correlated best with iron. Unusually, the So Lab has correlated QMRI data with quantitative spatial iron measurements obtained by synchrotron radiation X-ray fluorescence (SRXRF), rather than rely on quantitative bulk iron analyses or non-quantitative histochemical iron staining.Myelin is also known to significantly modulate QMRI signals and the situation is further complicated by the high iron content of myelin itself. Myelin is formed from the wrapping of oligodendrocyte membranes around axons and functions as "electrical insulation" to ensure fast nerve conduction. Conventionally, myelin is assessed by (immuno)histochemical staining and qualitative, rather than quantitative.Generally, relationships between QMRI with iron and/or myelin are evaluated by ex vivo QMRI of brain samples and then sectioning of the sample for correlative iron and/or myelin histology as mentioned above. Disparate resolutions between such diverse data types and artefacts from histological processing contributes to inaccuracies/ambiguities, especially when co-registering datasets. Using bespoke high signal-to-noise MRI coils (previously developed by the So lab with PulseTeq Ltd), thin sections of brain tissues will undergo high resolution QMRI prior to quantitative iron and myelin mapping by SRXRF/laser-ablation-inductive coupled plasma-mass spectrometry (LA-ICP-MS) and desorption electrospray ionisation-mass spectroscopic (DESI-MSI)/Raman imaging, respectively. Uniquely, multi-modality imaging will be performed at comparable resolutions with minimal sample displacement between modalities. High resolution QMRI of thin brain samples is challenging but made possible using bespoke MRI coils. In this manner, registration errors between datasets are minimised and determination of accurate pixel-wise relationships between individual QMRI, iron and myelin imaging datasets are possible. Notably, lipid composition and myelin structural information can also be obtained to determine relationships between QMRI and specific lipid types/myelin structure.In this project, we aim to correlate iron- and myelin-sensitive QMRI signals with quantitative state-of-the-art physiochemical iron and myelin mapping developed by So and Bergholt Labs, respectively. Age-matched control and AD brain samples will be obtained from the Brain Bank for Dementia (which Dr So has previously accessed) and analysed, for potential future translation to monitoring iron chelation therapies in man. While AD is often considered a grey matter disease, white matter myelin has also been shown to be deranged. Teasing apart contributions of myelin and iron to multimodality QMRI measurements aids true assessment of the roles of iron dyshomeostasis and myelin dysfunction in AD for identification of novel AD therapeutics and monitoring.

博士项目的目的：确定铁和髓磷脂对多模式定量磁共振成像（QMRI）信号的个体和综合贡献。Projectiondrescementionroiron在大脑中积聚在大脑中随着衰老而积聚，而前进的年龄是神经退行性疾病的主要危险因素，例如阿尔茨海默氏病（Alzheimer's ant Alzheimer's ant）。实际上，铁植物抑制剂是AD [3]的一个特征，而铁螯合疗法正在接受AD的临床试验。质量磁共振成像MRI（QMRI）方法对铁含量（对不同的广泛性和特异性）敏感。与T1和T2相比，SO实验室和其他实验室显示了T2*值，这与铁最好。 Unusually, the So Lab has correlated QMRI data with quantitative spatial iron measurements obtained by synchrotron radiation X-ray fluorescence (SRXRF), rather than rely on quantitative bulk iron analyses or non-quantitative histochemical iron staining.Myelin is also known to significantly modulate QMRI signals and the situation is further complicated by the high iron content of myelin itself.髓磷脂是由在轴突周围的少突胶质细胞膜包裹而形成的，并用作“电绝缘”，以确保快速神经传导。从传统上讲，髓磷脂是通过（免疫）组织化学染色和定性评估的，而不是定性的，而不是定量。从基因上讲，QMRI与铁和/或髓磷脂之间的关系通过脑样本的外体QMRI评估，然后通过在上述相关铁和/或髓磷脂组织学的样品切片中进行了体内QMRI。这种不同的数据类型与组织学处理中的人工制品之间的分歧分辨率有助于不准确/歧义，尤其是在共同注册数据集时。使用定制的高信号到噪声MRI线圈（以前由SO LAB带有Pulseteq Ltd开发），脑组织的薄段将在定量的铁和髓磷脂映射之前通过SRXRF/Laser-laser-laser-lase-abl-ander-topuctiation-toplair-诱导 - 降低了desopled plassm-masm-masm-m-m-ass-m-ass-miCPRANE-la-aSs-la-aSs-la-sicp-micpms）进行高分辨率qMRI光谱（DESI-MSI）/拉曼成像。独特的是，多模式成像将以可比较的分辨率进行，而模态之间的样本位移最小。瘦大脑样品的高分辨率QMRI具有挑战性，但使用定制的MRI线圈使其成为可能。以这种方式，数据集之间的注册误差被最小化，并确定单个QMRI，铁和髓磷脂成像数据集之间的精确像素关系。值得注意的是，还可以获得脂质成分和髓磷脂结构信息，以确定QMRI与特定脂质类型/髓磷脂结构之间的关系。在此项目中，我们旨在将铁素敏感的QMRI信号与量化的最先进的生理学铁和髓磷脂映射相关，并由类似于这些实验室和Bergholt的实验室所开发。年龄匹配的对照和AD脑样品将从脑库中获得痴呆症（SO先前已经访问过的DR），并进行了分析，以便将来转化以监测人类中的铁螯合疗法。虽然AD通常被认为是灰质疾病，但白质髓磷脂也被证明被杂乱无章。分开髓磷脂和铁对多模式QMRI测量的贡献有助于对铁dyshomeostasis和髓磷脂功能障碍在AD中的作用进行真正的评估，以识别新型AD疗法和监测。