Direct Measurements of Microstructure from MRI

这项研究将产生一种新的成像范式，称为主动成像。传统的成像技术是由物理学家设计的；如果医学或生物学研究人员在不同类型的材料之间提供了有用的对比度，或者与有趣的效果相关，就可以使用它们。医学成像的最新趋势是向定量成像技术发展，该技术将组织的生物物理模型与传统成像技术相结合，以提供与特定应用相关的更具体的信息。主动成像将这一想法扩展到更完全地利用生物物理模型来设计成像技术本身。更具体地说，该技术使用优化算法来搜索图像的组合，这些图像提供了有关生物物理模型的最多信息和对生物相关数量的最佳估计。例如，阿尔茨海默病攻击和破坏脑细胞。它会在脑组织上留下空洞，并沉积不寻常的蛋白质。在显微镜下，阿尔茨海默氏症患者的脑组织看起来与正常组织非常不同，但在磁共振成像(MRI)等标准技术的图像上，这种差异并不明显。即使像扩散张量成像这样对组织微结构敏感的技术，也只能显示中等对比度。一种更广泛的技术被称为扩散磁共振，它测量组织中水分子的散射。组织的微观结构控制着散射模式，因此扩散磁共振成像提供了有关微观结构的信息。扩散张量磁共振只提供了对阿尔茨海默氏症的微观结构变化不敏感的散射模式的特定特征。然而，我们可以通过几乎无限多的其他方法来调整扩散张量MRI的灵敏度。主动成像将使用阿尔茨海默氏症微观结构变化的模型来找到对这些变化最敏感的扩散磁共振测量的精确组合，并最成功地将它们与正常组织或其他疾病区分开来。该项目考虑了三种疾病：阿尔茨海默氏症、多发性硬化症和局灶性皮质发育不良(癫痫的常见原因)。每一种都有脑组织微结构的特征异常，而目前的成像技术并不能可靠地揭示这些异常。该项目将构建异常的生物物理模型，并使用主动成像来设计能够揭示这些异常的扩散磁共振技术。该项目还将使用主动成像来调整扩散磁共振，以揭示正常脑组织的特定微观结构特征，如白质中轴突的大小和密度。目前还没有一种技术可以在活体受试者身上成像这些特征，但这些信息将提供关于大脑结构和功能的基本新信息。主动成像范例扩展到几乎任何其他成像技术，包括其他磁共振成像技术、X射线或光学断层扫描或正电子发射断层扫描(PET)。虽然该项目专注于扩散磁共振成像的主动成像，但它也旨在启动后续项目，以探索在其他疾病(如癌症)和其他成像技术中的应用。

The research will produce a new imaging paradigm called active imaging . Traditional imaging techniques are designed by physicists; medical or biological researchers use them if they provide useful contrast between different types of material or correlate with interesting effects. Recent trends in medical imaging are towards quantitative imaging techniques that combine biophysical models of tissue with traditional imaging techniques to provide more specific information relevant to particular applications. Active imaging extends this idea to exploit biophysical models more completely to design the imaging techniques themselves. More specifically, the technique uses optimization algorithms to search for combinations of images that provide the most information about the biophysical model and the best estimates of biologically relevant quantities.For example, Alzheimer's diseaseattacks and destroys brain cells. It leaves holes in brain tissue and deposits of unusual proteins. Brain tissue from Alzheimer's patients looks very different to normal tissue under a microscope, but the differences are not apparent on images from standard techniques like magnetic resonance imaging (MRI). Even techniques like diffusion-tensor MRI, which has acute sensitivity to tissue microstructure, show only moderate contrast. A broader class of technique, called diffusion MRI, measures the scattering of water molecules in tissue. The tissue microstructure controls the scatter pattern and so diffusion MRI provides information about the microstructure. Diffusion-tensor MRI provides only particular features of the scatter pattern that happen to be insensitive to the microstructural changes in Alzheimer's. However, we can tune the sensitivity of diffusion MRI in an almost infinite number of other ways. Active imaging will use a model of the microstructural changes in Alzheimer's to find the precise combination of diffusion MRI measurements that is most sensitive to those changes and discriminates them most successfully from normal tissue or other diseases.The project considers three diseases: Alzheimer's, multiple sclerosis and focal cortical dyplasia (a common cause of epilepsy). Each has characteristic abnormalities in brain tissue microstructure that current imaging techniques do not reveal reliably. The project will construct biophysical models of the abnormalities and use active imaging to devise diffusion MRI techniques that reveal them. The project will also use active imaging to tune diffusion MRI to reveal specific microstructural features of normal brain tissue, such as size and density of axons in white matter. No current technique can image these features in live subjects, but the information would provide fundamental new information about the structure and function of the brain. The active-imaging paradigm extends to almost any other imaging technique including other MRI techniques, X-ray or optical tomography or positron-emission tomography (PET). Although the project focusses on active imaging for diffusion MRI, it also aims to initiate follow-on projects to explore applications to other diseases (such as cancers) and other imaging techniques.