TRACKING NEURONAL FIBERS IN LIVING HUMAN BRAIN BY MRI

我们建议扩展我们的开发，使用磁共振成像(MRI)来跟踪人脑衬里的神经纤维。该方法称为扩散张量跟踪(DTT)，根据扩散张量编码的MRI数据(DT-MRI)重建神经元纤维束的连续三维轨迹。与其他方法相比，磁共振程序是非侵入性的，能够研究人类特有的连接解剖学，并与同一个体受试者的fMRI激活直接相关，这可能会揭示用于人类任务的神经元连接。非侵入性DTT方法对于揭示人类与语言等认知功能相关的联系尤其重要，这些联系不能从非人类灵长类动物的研究中推断出来。对于目标I，我们将进一步加强当前从DT-MRI数据中对三维全脑纤维轨迹的计算，并开发和改进选择不同纤维组的方法，特别是包括由功能磁共振定义的区域之间的连接。对于AIM II，我们将通过计算机模拟和实验数据的重测评估来评估DTT纤维轨迹的准确性和精确度。在Aim III中，我们将评估DTT的能力，以已知的猴子神经解剖学为标准，确定体感和视觉系统中由fMRI定义的初级感觉和高级区域之间的连通性。视觉研究将涉及视网膜定位功能磁共振成像，以识别更高的视觉区域，并选择膝盖骨钙束的功能亚群，以及运动感知研究，以激活视觉皮质以外的远程认知区域。对于第四个目标，我们将通过将病变到皮质的DTT投影与视网膜原位功能磁共振成像中的皮质缺陷和膝盖骨钙束局限性病变患者的视野缺陷相关联，来研究DTT在表征白质病变的功能效应方面的潜在临床应用。在目标V中，我们将比较视力正常、早期失明和晚期失明受试者的视皮层连接，以评估失明年龄对视觉系统发育和组织的影响。这项拟议研究的成功完成将为研究正常和疾病中人脑的发育、功能组织和重组提供一套经过测试的工具。

We propose to extend our developments with magnetic resonance imaging (MRI) for tracking neuronal fibers in the lining human brain. The method, called diffusion tensor tracking (DTT), reconstructs continuous threedimensional trajectories of neuronal fiber bundles from diffusion tensor-encoded MRI data (DT-MRI). Compared to other methods, the MR procedure is non-invasive, capable of studying connectional anatomy unique to humans, and amenable to direct correlation with fMRI activations in the same individual subjects, which potentially will uncover the neuronal connections used for human tasks. Noninvasive DTT methods are especially important for revealing connections in humans associated with cognitive functions like language that cannot be extrapolated from non-human primate studies. For Aim I we will further enhance current computations of three- dimensional whole-brain fiber trajectories from DT-MRI data and develop and refine methods for selecting different fiber groups, especially including connections between regions defined by fMRI. For Aim II we will evaluate the accuracy and precision of DTT fiber trajectories by computer simulation and test-retest evaluation of experimental data. In Aim III we will assess the ability of DTT to determine the connectivity between fMRI-defined primary sensory and higher-order regions in the somatosensory and visual systems using known monkey neuroanatomy as a standard. The visual studies will involve retinotopic fMRI mapping to identify higher visual areas and to select functional subsets of the geniculocalcarine tract, and motion perception studies to activate remote cognitive regions outside the visual cortex. For Aim IV we will examine the potential clinical utility of DTT to characterize the functional effects of white matter lesions by correlating the lesion-to-cortex DTT projections with cortical defects in retinotopic fMRI and with visual field defects in patients with focal lesions of the geniculocalcarine tract. In Aim V, we will compare visual cortex connections in sighted, early- and late-blind subjects to assess the effects of age of blindness on the development and organization of the visual system. Successful completion of the proposed research will provide a set of tested tools for interrogating the development, functional organization, and reorganization of the human brain in normal and disease.