Diffuse Optical Brain Imaging

功能和结构光学脑成像

AMIR GANDJBAKHCHE (? to ?) $5,175,098

Project ID: ZIAHD008882 (NICHD)

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Abstract

Diffuse Optical Imaging (DOI) allows us access to the hemodynamic response in tissue. It has been shown that we can by detecting the effects of neuro-vascular coupling relate this to functional events in the brain. Existing technologies in DOI are limited by a variety of factors, but most strongly by the absence of viable clinical applications where they may be applied. We have over the last year identified two key groups where functional optical imaging would be the only available functional tool, thus providing DOI with a real and necessary clinical use. These groups are young epilepsy sufferers who have had radical hemispherectomies and veterans with penetrating Traumatic Brain Injury (TBI). In identifying these groups we have also been examining the current shortcomings of DOI. These limitations are related to absolute quantitation of oxy/de-oxy hemoglobin in tissue and the problems surrounding physiological noise and the instrument-user interface. In the case of our two patients populations these factors will be key to developing viable tools. A further limitation of DOI is the depth of penetration, in this work we consider this an advantage in our move towards real-time imaging. We have identified an approach that uses the lack of depth to reduce the complexity of the inverse problem in a manner that unlike existing foreshortening techniques does not bias the data. The challenge in DOI in our patient groups is the presence of non diffusive sub-domains such as cerebro-spinal fluid and metallic fragments. These inclusions strongly affect the data and when modeled with existing diffusive models produce inaccurate data. We have developed theoretical models to handle this aspect of the modeling problem with some success. The next step will be to characterize their effect on the inverse problem. We must also consider quantitation as a key issue if we are to address neuro-plasticity or long term variational effects in functional imaging. No current imaging system can really provide accurate absolute data on the strength and locality of a functional event. We have begun work on a novel algorithm that shows the possibility to be able to absolutely reconstruct information and provide enhanced localization of the effect. Currently we are working on construction of a fiber based imaging system in collaboration with NINDS. The hardware is being developed based on new theoretical models of how to handle the fiber connection angle problem in DOI. A novel headset is being designed which should give greater control and accuracy over fiber placements involving a multi component headset with sectioned formed panels. Various mathematical models are currently under investigation to accelerate the imaging process towards real-time. An engineering based FEM using regular grids with irregular surfaces is being developed. This will reduce memory costs and simplify the meshing procedure making imaging faster and more efficient. This will also couple directly to the deformable plate model allowing the use of generic head models for specific patients. In collaboration with Drexel University, we are currently working on a novel LRD based system. Using the techniques developed for our fiber based model we aim to use novel LRDs with an enhanced dynamic range to create a wearable DOI interface. Such a system will involve wireless technologies to transmit data from a moving subject to an imaging base station and should radically change the available paradigms to functional imaging. Existing techniques exist in optical imaging to handle background physiological noise from tissues not of interest (e.g. scalp and skull). Various approaches including model-based systems and using short range source detectors averaged over the head are currently used. We are developing a model that will use information derived from unique access to 'noise only'data in hemispherectomy patients to infer how useful such models are. We aim to test inter and intra patient models and determine how statistically significant these effects are and whether generic models or background averaging are sufficient. Finally we have submitted an Invention Report relating to a novel instrument design intended to detect hematomas. It is designed to assist in the triage of patients with all forms of TBI. The ability to identify and triage for the presence of hematoma would greatly increase efficiency of use of more expensive and limited access systems such as CT and MRI. The development of this instrument into an imaging system capable of mapping the hematoma would also be beneficial in the case of the need for emergency in field surgery to remove pressure and in countries where economic limits mean access to CT and MRI is not standard and is under investigation.

漫射光学成像（DOI）使我们能够获得组织中的血液动力学反应。已经表明，通过检测神经血管耦合的影响，我们可以将其与大脑中的功能事件联系起来。 DOI中的现有技术受到许多因素的限制，但最强烈的原因是缺乏可行的临床应用。最初我们的目标是那些患有根治性半球切除术的年轻癫痫患者，以及具有穿透性创伤性脑损伤（TBI）的退伍军人（在儿科人群的上端）。今年，通过我们的持续推广，我们确定了第三个关键人群，即自闭症谱系障碍（ASD）患者。这些患者功能低下，通常是儿科人群。在2010财年的过程中，我们开展了合作，为我们的一种新型仪器创意获得了专利，并在神经科学学会接受了多次演示。我们正在实验室（通过我们在Drexel的合作者）和我们在乔治城的其他合作实验室组装各种仪器。后者是结合脑电图的DOI仪器。临床上我们现在开始与健康的志愿者进行初步测试。我们正在等待我们新批准的IRB的协议号，通过NICHD在NICHD开始测试我们的原型系统。为了进行功能性脑成像实验，我们在E-prime软件中开发了许多认知任务（事件复杂性判断任务，口头工作记忆任务和多任务）。将准确记录每个刺激的呈现时间，这将用于数据分析。我们还致力于数据处理技术，从光学数据中提取脑血流动力学反应。使用事件复杂性任务与Georgetown合作进行初始实验。主成分分析（PCA）和独立成分分析（ICA）已应用于数据，以消除噪声和运动伪影成分。相应的提取血液动力学反应证实了该技术，因为它们与先前的fMRI研究结果相关。此外，与NIMH的合作者，我们目前正在讨论对ASD患者有用的合适功能研究，一旦我们获得了健康志愿者的初步数据，我们将在年轻成人或儿科人群中开展ASD患者的研究。从理论上讲，我们目前正在研究各种方法来处理当前DOI技术的缺点。我们目前的主要重点是解决DOI的地图集和注册问题。这个领域是研究的热门话题，但不像MRI那样Talairach和MNI地图集成为事实上的标准，DOI没有这样的标准方法。部分原因是重建方法缺乏确定性，部分原因是共同注册数据的问题。作为项目的一部分，我们一直致力于更好地定量和定位光学信号。我们目前的重点是通过将数据映射到不同的坐标来重新寻址和注册。我们目前正在完成一篇论文，其基于将光学数据移动到极性/球形基础的原理（其灵敏度和分辨率更自然）。通过这样做，我们可以基于2D表面流形的有效配准直接在3D体积中记录数据。这种方法还将结合我们正在开发的描述光学成像在分形维数中的灵敏度的工作。这将结合起来，使我们能够为DOI演化更为复杂的人脑大脑概率功能图谱。我们与NINDS的合作继续开发新的基于光纤的成像仪，以添加到我们选择的设备中，用于DOI技术的比较和对比。此外，我们还与Drexel的合作伙伴共同开发了一个完全小型化的系统。已经实现了光发射器和接收器的初始设计，并且已经通过实验验证了每个模块的功能。在发射器中使用四个垂直腔表面发射激光二极管，并且该系统利用梯度指数（GRIN）透镜技术来实现优异的光学收集效率。我们目前正致力于模块的集成。这些项目将结合起来，为近红外功能成像生成完全可穿戴的DOI。我们的理论研究还将运动伪影检测为信号而不是噪声。初步结果表明，如果我们可以通过头盔界面模拟我们的成像系统相对于受试者的运动（我们的乐器主义者正在进行的过程），我们应该进一步能够将光学信号增强到前所未有的准确度和定量水平在该领域。最后，我们提交并获得了一项旨在检测血肿的新型仪器设计的初始专利。它旨在帮助所有形式的TBI患者进行分类。识别和分类血肿存在的能力将大大提高使用更昂贵和有限的访问系统（例如CT和MRI）的效率。目前，我们正在研究完整的理论模型来测试设计。一旦完成，该模型将允许我们快速进入初始原型。 NIR建模的当前现状也受到该项目的挑战。初步结果表明，更高密度的更多光源和探测器更适合成像的范例正受到挑战。该项目的初步结果表明，改进的仪器和建模的计算边界引入的误差之间将存在良好的平衡。