Computational analysis of diffusion tensor images: application to schizophrenia

描述(申请人提供)：由于弥散张量成像(DTI)对白质(WM)的优越表征，它正越来越多地被用于几种WM疾病的研究。具体地说，DTI在精神分裂症等非局灶性神经发育疾病的研究中发挥着关键作用，在精神分裂症中，WM异常更为复杂和微妙，可能表现为髓鞘形成的变化或连接中断，分布在整个大脑。这导致了对DTI数据进行分组分析的需求越来越大，预计这种分析将更好地阐明这些细微的异常。这就产生了对用于DTI处理和分析的复杂和全自动计算神经解剖学技术的需求，这一点至关重要，因为传统的放射学评估未能发现实质性的脑白质差异。这种方法的开发对DTI数据具有挑战性，因为它需要解决张量数据的高维性和复杂的基本结构所产生的几个数学和技术问题。虽然张量计算的标量图像(如扩散系数和各向异性图)的分析通常被用作张量数据分析的第一步，但这些图像通常从张量中提取有限的信息，因此不能捕捉到病理的全部影响。纤维跟踪也存在类似和附加的限制。该项目试图通过开发直接应用于扩散张量数据的整体的分析方法来缓解这些问题，而不是将中间步骤集中在标量测量上，从而将计算神经解剖学的成熟方法扩展到张量数据。该项目的关键在于开发一套全面的DTI数据形态计量分析工具，旨在促进各种神经成像研究。将在目标2中建立扩散张量场统计分析的综合框架，使用多种学习技术来确定DT测量的基本流形结构，然后对这些流形进行体素统计分析。目标1中DTI数据的WM空间归一化框架的发展将极大地促进这种基于群体的分析，在该框架中，张量以使用定向过滤器获得的丰富和独特的形态特征为特征。最后，在目标3中，这些方法的实用性将在一个具有良好特征的大型数据库中进行测试，这些数据库包括精神分裂症患者、他们的亲属和健康对照组，方法是研究三组患者在结构连接方面的差异，并将这些差异与症状严重程度的临床评级以及情绪和认知的神经心理测量表现相关联。我们期望项目成功完成后，我们将开发出一套通用的、全面的、计算高效的处理和分析工具，用于大规模人群DTI研究，一套用于DTI分析的工具，可用于测试其他涉及白质的疾病的临床假说。

DESCRIPTION (provided by applicant): Owing to the superior characterization of white matter (WM) provided by Diffusion tensor imaging (DTI), it is being increasingly used in the investigation of several WM diseases. Specifically, DTI has a crucial role to play in the study of non-focal neurodevelopmental diseases such as schizophrenia where the WM abnormalities are more complex and subtle and may manifest as changes in myelination or disruptions in connectivity, dispersed over the whole brain. This has led to a growing need for group-based analysis of DTI data that is expected to better elucidate these subtle anomalies. This has generated the need for sophisticated and fully automated computational neuroanatomy techniques for DTI processing and analysis, crucial because the conventional radiological evaluations have failed to detect substantial white matter differences. Development of such methods is challenging for DTI data as it requires the resolution of several mathematical and technical issues arising from the high dimensionality and complex underlying structure of the tensor data. Although analysis of scalar images, such as diffusivity and anisotropy maps, that are computed from tensors is often used as a first step in analysis of tensor data, these images generally extract limited information from the tensors and therefore do not capture the full effect of pathology. Similar and additional limitations are inherent to fiber tracking also. This project seeks to alleviate these issues by developing analysis methods that apply directly to the diffusion tensor data in its entirety, without having intermediate steps concentrate on scalar measures, thereby extending well-established methods of computational neuroanatomy to tensor data. The crux of the project lies in developing a comprehensive set of tools for the morphometric analysis of DTI data, aiming at facilitating a variety of neuro-imaging studies. An integrated framework for the statistical analysis of diffusion tensor fields will be developed in Aim 2, using manifold learning techniques that determine the underlying manifold structure of the DT measures followed by voxel-wise statistical analysis on these manifolds. Such a group-based analysis will be greatly facilitated by the development of a WM-based spatial normalization framework for DTI data in Aim 1, in which tensors are characterized by rich and distinctive morphological signatures obtained using oriented filters. Finally, in Aim 3, the utility of these methods will be tested on a well characterized large database of schizophrenia patients, their relatives and healthy controls, by studying differences in structural connectivity between the three groups and correlating these with clinical ratings of symptom severity and performance on neuropsychological measurements of emotion and cognition. We expect that on successful completion of the project we will have developed a general, comprehensive and computationally efficient processing and analysis tools for large population DTI studies, set of tools for DTI analysis that can be used to test clinical hypotheses in other disorders involving white matter.