Inferring in Vivo Cytoarchitectural Borders in the Medial Temporal Lobe

描述（由申请人提供）：标准结构脑成像方案导致图像无法分辨小于1- 2mm的结构。实现显著更高的分辨率将具有基本的临床和神经科学价值，因为它将允许在体内检测和分析皮层的细胞结构特征，以及海马、丘脑和杏仁核等大脑区域的亚结构。不幸的是，这种分辨率很难在体内获得，因为信噪比随着每个体素的线性维度的三次幂而下降。虽然最近的一些研究已经将这个极限推到了1A毫米以下，但这是以非常长的扫描时间和专门的成像硬件为代价的，即使这样，相对于用MRI可视化细胞结构相关性所需的分辨率，这仍然是一个粗糙的分辨率。在这里，我们采取了一种不同的方法，并建议对离体组织样本进行成像，包括组织块和整个半球，其中非常高分辨率是可以获得的，在lOOujns的顺序上。在这些图像中，细胞结构特征的许多MR特征是明显的，因此它们可以用于构建模型，包括这些细胞结构定义的边界。对于那些与MR无法区分的特征，我们建议对组织进行组织学分析，并使用交叉模态配准技术将组织学信息传递回模型。然后提出了高维映射程序，将这些模型从超高分辨率成像和组织学中获得，映射回更标准分辨率的体内数据，以预测给定细胞结构边界在体内数据中每个位置发生的概率。我们关注内侧颞叶的皮质区域，因为它们具有重要的临床意义，因为它们被认为是阿尔茨海默病最早的位点之一，对正常的记忆功能至关重要。更准确地定位这些皮质区域的能力将是早期诊断AD的关键一步，也是评估潜在临床干预措施疗效的关键一步。

DESCRIPTION (provided by applicant): Standard structural brain imaging protocols result in images that cannot resolve structures smaller than 1- 2mm in size. Achieving significantly higher resolution would be of fundamental clinical and neuroscientific value, as it would allow the in-vivo detection and analysis of cytoarchitectural features of the cortex, as well as substructures of brain regions such as the hippocampus, thalamus and amygdala. Unfortunately, such resolution is extremely difficult to obtain in-vivo, as the signal-to-noise ratio goes down with the third power of the linear dimension of each voxel. While some recent studies have pushed this limit to under 1A mm, this is at the cost of extremely long scan sessions and specialized imaging hardware, and even this is still a coarse resolution relative to what is required to visualize correlates of the cytoarchitecture with MRI. Here we take a different approach, and propose to image ex-vivo tissue samples, both blocks of tissue and whole hemispheres, in which exceedingly high-resolution is obtainable, on the order of lOOujns. In these images, many MR signatures of cytoarchitectural features are apparent, and hence they can be used for the construction of models including these cytoarchitectonically defined boundaries. For those features that are not distinguishable from the MR, we propose to perform histological analysis of the tissue, and use cross modal registration techniques to transfer the information from the histology back to the models. High dimensional mapping procedures are then proposed to map these models, obtained from ultra high-resolution imaging and histology, back to the more standard resolution in-vivo data to predict the probability of a given cytoarchitectural boundary occurring at each location in the in-vivo data. We focus on cortical areas in the medial temporal lobe as they are of great clinical relevance, as they are thought to be one of the earliest loci of Alzheimer's disease, and are critical to normal memory function. The ability to more accurately localize these cortical regions would be a critical step in the early diagnosis of AD, and in the assessment of the efficacy of potential clinical interventions.