National Facility for In Vivo MR Imaging of Human Tissue Microstructure

磁共振成像（MRI）扫描仪在世界各地用于医院和研究中对人体进行成像。它们被用来诊断疾病和了解健康身体的运作。在临床环境中，核磁共振扫描仪最常收集的图像显示的物体大小约为1毫米。这些对某些诊断是有用的，但无法在微观长度尺度（千分之一毫米）上捕捉组织特性，在微观长度尺度上可能发生重要的过程，例如在“轴突”（形成不同大脑区域之间连接的细胞）中，或在重要器官的细胞中，如肝脏或肾脏。这种详细的检查通常需要“活组织检查”来移除组织，然后在显微镜下检查。然而，活组织检查只观察很小的组织样本，收集起来可能有风险，例如在大脑中。该项目将发展MRI在微观尺度上量化组织结构的新方法。主要的方法是观察水分子在体内的运动是如何被组织内部的精细结构所阻碍的。虽然扩散核磁共振已经存在了30年，但目前的核磁共振机器限制了我们只能测量相对较大的分子运动。这模糊了我们对组织的了解，使我们无法看到重要的特征，如单个细胞的尺寸，或神经纤维的密度或堆积。通过使MRI对更小的分子运动更敏感，可以使图像更清晰的主要因素是磁场梯度的大幅增加。这些梯度是核磁共振扫描仪内磁场强度的受控变化。我们将与扫描仪制造商合作创建一个系统，该系统产生的梯度比标准MRI机器强7倍。世界上其他地方只有一个类似的系统（在美国），因此我们建议在英国建立一个“组织微观结构体内成像国家设施”，作为先进显微结构成像方法开发和应用的国家中心。我们的第一个科学目标将是实现稳健可靠的测量。我们将开发方法来减少硬件中不可避免的缺陷的影响，以及扫描过程中人移动的影响。大约75%的项目将用于开发新的工程和物理方法，以获得最佳的测量结果。灵敏度的提高将使我们能够以前所未有的详细程度描绘一系列器官中的组织。在大脑中，白质是连接不同区域的“线路”，在许多疾病中受到影响，包括痴呆症、阿尔茨海默病、精神分裂症、抑郁症和多发性硬化症。在标准硬件上的测量无法准确显示白质如何受到这些疾病的影响，但在NMIF上，我们将能够区分轴突（管状结构）的形状或大小的变化，以及髓鞘（包裹轴突的脂肪绝缘层）的变化。这将使我们能够更好地预测白质携带信息的能力。在癌症方面，我们的目标是用先进的显微结构成像技术取代肿瘤活检，能够量化非侵入性细胞的大小和密度。最终目标是为患有一系列衰弱性疾病的患者提供更早、更准确的诊断、更具体、更有针对性的治疗、更好的治疗监测和总体改善的结果。该项目将发展并受益于英国和国际上的学术和工业研究伙伴关系。在药物开发方面有很大的应用潜力，这是英国一个强大的工业部门，用于开发和提供新的有效治疗方法。该项目将有助于保持英国长期以来在神经影像学研究的国际前沿地位。

Magnetic Resonance Imaging (MRI) scanners are used throughout the world to image the human body in hospitals and for research. They are used to diagnose disease and to understand the workings of the healthy body. In clinical settings, MRI scanners most often collect images which show objects down to about 1 mm in size. These are useful for some diagnoses, but are unable to capture tissue properties at microscopic length scales (thousandths of a millimetre), at which important processes may occur, e.g. in the 'axons' (the cells forming connections between different brain areas), or in cells in vital organs, such as the liver or kidney. Such detailed examination usually requires a 'biopsy' to remove tissue which is then examined under a microscope. However, biopsies only look at a tiny sample of tissue and can be risky to collect, e.g. in the brain. This project will develop MRI in new ways to quantify tissue structure at the microscopic scale. The principal method looks at how water molecules moving in the body are impeded by fine structure within the tissue. While diffusion MRI has existed for 30 years, current MRI machines restrict us to measuring only relatively large molecular movements. This blurs our picture of the tissue, prohibiting us from looking at important characteristics, such as the dimensions of individual cells, or the density or packing of nerve fibres.The main factor that can sharpen the picture, by sensitising MRI to smaller molecular movements, is a substantial increase in magnetic field gradients. These gradients are controlled alterations in the magnetic field strength within the MRI scanner. We will partner with a scanner manufacturer to create a system that produces gradients about 7 times stronger than available on standard MRI machines. There is only one similar system anywhere else in the world (in the USA) and we therefore propose to establish a 'National Facility for the In Vivo Imaging of Tissue Microstructure' here in the UK, serving as a national hub for development and application of advanced microstructural imaging methods. Our first scientific aim will be to achieve robust and reliable measurements. We will develop methods to reduced the impact of inevitable imperfections in the hardware, and the effects of the person moving during scanning. About 75% of the project will be spent developing novel engineering and physics methods to obtain the best possible measurements. The increased sensitivity will allow us to characterise tissue in a range of organs to an unprecedented level of detail. In the brain, the white matter is the 'wiring' that interconnects different regions and is affected in many diseases including dementia, Alzheimer's disease, schizophrenia, depression and multiple sclerosis. Measurements on standard hardware lack the ability to show exactly how white matter is affected by these diseases, but at the NMIF we will be able to distinguish any changes in the shape or size of the axons (the tube-like structures), from changes in the myelin (the fatty insulation layer that wraps around axons). This will allow us to make better predictions about the white matter's ability to carry information. In cancer, we aim to replace the tumour biopsy with advanced microstructural imaging, being able to quantify non-invasively cell size, and density. The ultimate goal is to provide earlier and more accurate diagnoses, more specific and better-targeted therapy, improved treatment monitoring and overall improved outcome for patients with a range of debilitating diseases.The project will develop and benefit from academic and industrial research partnerships in the UK and internationally. There is great potential for application in drug development, a strong industrial sector in the UK, for the development and delivery of new and effective treatments. This project will help maintain the UK's longheld position at the the international forefront of neuroimaging research.