HIGH-SENSITIVITY DOT FOR MAPPING HUMAN BRAIN FUNCTION

描述(由申请人提供)：健康成人大脑的非侵入性功能成像使脑功能的空间和时间组织图成为可能，并使认知神经科学发生了革命性的变化。功能神经成像越来越多地被用作临床诊断和预后的工具，并被用来观察大脑发育。它在疾病和发育研究中不断扩大的应用需要新的、更灵活的功能神经成像工具。许多情况不适合核磁共振扫描仪的后勤，例如在重症监护病房的受试者，或者其他可能需要镇静剂进行成像的受试者，如婴儿和幼儿。此外，传统的功能神经成像方法使用的行为范式不适合这些相同的受试者。幼儿无法完成许多任务，手术室或重症监护病房中的昏迷患者无法可靠地执行任务。漫反射光学成像(DOI)是一种新兴的非侵入性技术，具有独特的便携性和血流动力学对比能力，可以在丰富的或临床环境中记录诱发的脑功能。然而，尽管DOI具有独特的优势，但作为功能映射的标准工具，DOI一直受到空间分辨率低、深度渗透有限以及缺乏可靠和可重复的映射的限制。虽然脑活动的DOI通常使用具有稀疏成像阵列的地形来执行，但高密度阵列和断层成像算法提供了一种显著提高图像质量的方法。除了图像质量限制外，以前的DOI还采用了限制性的基于任务的行为范例。最近用功能磁共振成像探索的另一种方法，利用不同大脑区域之间休息状态波动的时间相关性来绘制功能连接的空间图谱。这笔赠款的目标是开发用于绘制静息状态功能连接的DOT方法，以研究儿童大脑功能的发展。我们最近证明了DOT原型的可行性，它解决了通道间串扰中的几个基本挑战，并能够对成人视觉皮质进行断层扫描(Zeffet)。艾尔PNAS 2007)。为了满足绘制扩展的人类大脑功能网络的额外需求，这笔赠款将实现三个发展目标：第一，我们将开发第二代仪器，在深度穿透、皮质覆盖和盖子耐磨性方面进行必要的改进；第二，我们将创建将大脑血红蛋白的DOT图投影到参考图谱空间的算法；第三，我们将开发确定静息状态下功能连通性的方法。这些技术发展将在成年人身上得到验证，成年人可以与详细的诱发反应和功能磁共振进行比较。这些步骤将为应用DOT研究幼儿的大脑功能奠定坚实的基础；这是一个用目前的神经成像技术难以解决的问题。公共卫生相关性：扩散光学断层扫描(DOT)技术具有可佩戴的成像帽、便携性和全面的血红蛋白成像对比度的优势，因此在绘制脑功能图方面具有巨大的潜力。我们将开发新的高灵敏度仪器、脑图谱配准算法和无任务行为范例，以实现改进的DOT脑图。这些步骤将使DOT能够应用于幼儿大脑功能的研究；这是一个用目前的神经成像技术难以解决的问题。

DESCRIPTION (provided by applicant): Non-invasive functional imaging of the healthy adult human brain has enabled mapping of the spatial and temporal organization of brain functions and revolutionized cognitive neuroscience. Increasingly, functional neuroimaging is being used as a diagnostic and prognostic tool in the clinical setting and to view brain development. Its expanding application in the study of disease and development necessitates new, more flexible functional neuroimaging tools. Many situations are not suitable to MRI scanner logistics, such as subjects who are in an intensive care unit or subjects who might otherwise require sedation for imaging, such as infants and young children. Furthermore, traditional functional neuroimaging methods use behavioral paradigms not suited to these same subject groups. Young children cannot attend to many tasks, and unconscious patients in the operating room or intensive care cannot reliably perform tasks. Diffuse optical imaging (DOI), an emerging, non-invasive technique with unique portability and hemodynamic contrast capabilities, can record evoked brain function in enriched or clinical environments. However, despite unique strengths, DOI as a standard tool for functional mapping has been limited by low spatial resolution, limited depth penetration, and a lack of reliable and repeatable mapping. Though DOI of brain activity is commonly performed using topography with sparse imaging arrays, high-density arrays and tomography algorithms provide a means to dramatically increase image quality. In addition to image quality restrictions, previous DOI has employed restrictive task-based behavioral paradigms. An alternate method, recently explored with fMRI, uses temporal correlations in the resting state fluctuations between different brain regions to spatially map functional connections. The goal of this grant is to develop DOT methods for mapping resting state functional connectivity in order to study the childhood development of brain functions. We recently demonstrated the feasibility of a DOT prototype that solves several basic challenges in inter-channel cross talk and enables tomography of the adult visual cortex (Zeff et. al. PNAS 2007). To meet the additional demands mapping extended brain function networks in humans, this grant will achieve three development goals: first, we will develop a second generation instrument with the necessary improvements in depth penetration, cortical coverage, and cap wear-ability; second, we will create algorithms for projecting DOT maps of cerebral hemoglobin into a reference atlas space and third we will develop methods for determining function connectivity in the resting state. These technical developments will be validated in adults within whom comparisons can be made to detailed evoked responses and to fMRI. These steps will establish a strong foundation for applying DOT to study how brains function in young children; a question not readily addressed with current neuroimaging techniques. PUBLIC HEALTH RELEVANCE: Diffuse optical tomography (DOT) techniques have great potential for mapping brain functions due to the advantages of a wearable imaging cap, portability, and comprehensive hemoglobin imaging contrasts. We will develop new high-sensitivity instrumentation, brain atlas registration algorithms and task-less behavioral paradigms to enable improved DOT brain mapping. These steps will enable application of DOT to studies of brain function in young children; a question not readily addressed with current neuroimaging techniques.