High-Sensitivity DOT for Mapping Human Brain Function

描述(申请人提供)：这项拨款将开发可穿戴式全头部高密度漫反射光学断层扫描(HD-DOT)，用于在临床环境下在床边纵向绘制人类大脑功能图。对健康成年人的功能神经成像使大脑功能图谱成为可能，并使认知神经科学发生了革命性的变化。然而，传统的物流 功能性脑扫描仪(例如，功能磁共振成像)将使用限制为单一的“快照”应用，因此 在快速发展的临床场景中，仅提供非常有限的评估。因此，需要一种能够纵向监测神经状态的床边功能成像设备。长期以来，光学成像一直被认为是一种床边神经成像技术。然而，图像质量一直欠缺，特别是与脑功能成像的黄金标准-功能磁共振成像相比。此外，传统的功能图谱要求受试者执行任务，这在临床人群中是非常有限的。最近的两个事态发展改善了前景。首先，高密度漫反射光学层析成像(HD-DOT)显著提高了图像质量。当与功能磁共振成像的受试者匹配时，HD-DOT现在可以获得5 mm的定位误差和15 mm的点扩散函数半高宽，足以将功能定位到脑回。其次，新出现的绘制大脑内在活动功能连接性(FcDOT)的方法现在可以在不要求任务表现的情况下分析大脑功能。尽管取得了这些进展，但fcDOT的临床应用一直受到覆盖与穿戴性能权衡的限制。中心的光子挑战是光学敏感性--这使设计偏向于更大/更重的光纤--以及覆盖--这使设计偏向于更多的光纤。在将数据注册到解剖学和移除运动伪影方面存在相关挑战。这项提议将解决这些技术挑战，并开发用于床边纵向成像的可穿戴全头FcDOT。Aim 1通过一种新的DOT检测策略解决了光子学/人体工程学方面的挑战，该策略将允许使用更小的纤维(&lt；当前标准的1/30)，并开发一种新型全头低轮廓可穿戴HD-DOT帽。AIM 2将开发一套新的软件工具，以便在临床上实现高保真成像。Aim 3将开发和验证fcDOT，用于绘制健康受试者和慢性中风患者的大脑网络图，并与fcMRI和神经认知测试进行评估。目的4通过测量FcDOT与美国国立卫生研究院卒中评分(NIHSS)的关系，建立FcDOT在急性卒中纵向定位的可行性。这些研究将代表着功能神经成像领域的几项进展的顶峰，这是由于研究团队在神经学、功能神经成像和生物医学光学领域的临床和技术专业知识的独特结合。

DESCRIPTION (provided by applicant): This grant will develop wearable full-head high-density diffuse optical tomography (HD-DOT) for mapping human brain function longitudinally at the bedside in clinical settings. Functional neuroimaging of healthy adults has enabled mapping of brain functions and revolutionized cognitive neuroscience. However, the logistics of traditional functional brain scanners (e.g., fMRI) restrict use to single "snap shot" application and therefore provide only a very limited assessment during rapidly evolving clinical scenarios. Thus there is a need for a bedside functional imaging modality capable of monitoring neurological status longitudinally. Optical imaging has long held promise as a bedside neuroimaging technique. However, image quality has been lacking, particularly in comparison to the gold standard of functional brain imaging - fMRI. Moreover, traditional functional mapping requires subjects to perform tasks, which is very limiting in clinical populations. Two recent developments have improved the outlook. First, high- density diffuse optical tomography (HD-DOT) has improved image quality dramatically. When matched within subjects against fMRI, HD-DOT now can obtain localization errors <5mm, and point spread functions <15 mm FWHM, sufficient to localize functions to gyri. Second, emerging methods for mapping the functional connectivity of intrinsic brain activity (fcDOT) now can assay cerebral function without requiring task performance. Despite these advances, clinical application of fcDOT has been limited by a barrier imposed by a coverage-vs-wearability tradeoff. The central photonic challenges are optical sensitivity - which biases design towards larger/heavier fibers - and coverage - which biases design towards a larger number of fibers. Related challenges exist in registration of data to anatomy and removal of motion artifacts. This proposal will address these technological challenges and develop wearable whole-head fcDOT for longitudinal bedside imaging. Aim 1 addresses photonics/ergonomics challenges with a new detection strategy for DOT that will enable use of smaller fibers (<1/30 of current standard) and development of a novel full-head low-profile wearable HD-DOT cap. Aim 2 will develop a new set of software tools to enable high-fidelity imaging in the clinic. Aim 3 will develop and validate fcDOT for mapping brain networks in healthy subjects and chronic stroke with evaluations against fcMRI and neurocognitive testing. Aim 4 will establish the feasibility of longitudinal fcDOT mapping in acute stroke by measuring the relationship between fcDOT and NIH Stroke Scale (NIHSS). These studies will represent the culmination of several advances in functional neuroimaging made possible by the research teams' unique combination of clinical and technical expertise across the domains of neurology, functional neuroimaging and biomedical optics.