Inferring in Vivo Cytoarchitectural Borders in the Medial Temporal Lobe

描述（由申请人提供）：标准脑结构成像方案产生的图像无法分辨尺寸小于1- 2 mm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体、丘脑和杏仁核等脑区的亚结构。不幸的是，这样的分辨率是非常难以在体内获得的，因为信噪比随着每个体素的线性尺寸的三次方而下降。虽然最近的一些研究已经将该限制推到1A mm以下，但这是以极长的扫描会话和专门的成像硬件为代价的，并且即使这样，相对于用MRI可视化细胞结构的相关性所需的分辨率，这仍然是粗略的分辨率。在这里，我们采取不同的方法，并提出对离体组织样本（组织块和整个半球）进行成像，其中可获得极高的分辨率，大约为100 μ ns。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包括这些细胞结构定义的边界的模型。对于那些无法与MR区分的特征，我们建议对组织进行组织学分析，并使用交叉模式配准技术将信息从组织学转移回模型。高维映射程序，然后提出映射这些模型，从超高分辨率成像和组织学，回到更标准的分辨率在体内的数据，以预测在体内数据中的每个位置发生的一个给定的细胞结构边界的概率。我们专注于内侧颞叶的皮质区域，因为它们具有很大的临床意义，因为它们被认为是阿尔茨海默病的最早位点之一，并且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AD早期诊断和评估潜在临床干预措施疗效的关键步骤。

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.