Diffuse Optical Brain Imaging

漫反射光学成像(DOI)使我们能够获得组织中的血流动力学响应。已经证明，我们可以通过检测神经-血管耦合的影响，将其与大脑中的功能事件联系起来。DOI的现有技术受到许多因素的限制，但最严重的是缺乏可行的临床应用。在这个项目中，我们的目标是患有穿透性脑损伤(TBI)和自闭症谱系障碍(ASD)患者的退伍军人(位于儿童人口的高端)。这些患者是低功能人群，通常是儿科人群。 在2011财年期间，我们已经获得了一笔从板凳到床边的拨款，以资助后一项研究，并延长了神经康复医学中心对前一项研究的资助。我们再次接受了神经科学学会的几份报告，并就我们的各种项目提交了几篇关键论文。我们已经完成了基于光纤的仪器的开发，并通过我们在Drexel的合作者完成了第二台仪器的组装)。我们已经开始在我们的实验室和乔治敦的其他合作者实验室使用仪器进行研究。后者是一种与脑电相结合的DOI仪器。 临床上，我们正在继续对健康志愿者进行测试，并从脑外伤受试者那里获得了一些初步数据。我们有一个通过NICHD的现场IRB来测试我们在NICHD的原型系统，用于两个项目，包括神经心理学评估。除了我们对认知任务(事件复杂性判断任务、言语工作记忆任务和多任务)的测试外，我们还进一步开发了一种休息状态和功能连接的方法。对于休息/功能状态连通性，用于评估功能连通性的现有技术，例如相关和数据驱动分解，通常假定大脑信号在记录持续时间内是时间平稳的。这样的假设将导致检测不到大脑参与区域之间存在的功能连接的动态变化。我们一直在研究时频分析技术，以捕捉在静息状态和基于任务的实验中跨前额叶皮质连接的动态行为。随着神经心理学评估的加入，我们正在为我们的ASD研究提供基础，一旦完成，我们将能够使用NIMH的现有数据来确定患者队列，以与我们的健康受试者群体紧密匹配。 从理论上讲，我们目前正在完成技术的开发，以解决当前DOI技术的缺点。我们已经确定了一种使用立体定向成像的方法，使我们能够将我们的光学数据与MNI图谱共同配准，精度与类似的MRI实验相匹配。目前，这需要存在特定于患者的MRI，我们的重点是消除这一要求的能力，因为这可能不适用于我们的目标患者群体。在开发加速光学图像重建的新技术方面也取得了初步成果。目前，光学数据的三维成像技术需要专家用户几天或最多几个小时才能重建。我们正在开发新的方法，使用我们的地图集方法和分析功能的组合来解决DOI的这两个问题。 我们与NINDS的合作已经完全开发出一种基于光纤的成像器，该成像器已添加到我们的阵列设备中，用于DOI技术的比较和对比。这个特殊的系统还增加了我们的设备可以接触到的大脑区域，将我们的前额叶皮质扩大到包括运动皮质和视觉皮质。此外，我们正在与Drexel的合作者一起开发一个完全微型化的系统。实现了光发射机和光接收机的初步设计，并对各个模块的功能进行了实验验证。发射机采用四路垂直腔面发射激光二极管，并利用梯度折射率(GRIN)透镜技术实现了优异的光收集效率。我们目前正在努力整合这些模块。这些项目将结合在一起，生产用于近红外功能成像的完全可穿戴的DOI。我们的理论研究也将运动伪影作为一种信号而不是噪声来考察。初步结果表明，如果我们能够通过头盔接口(仪器专家正在研究的过程)模拟成像系统相对于对象的运动，我们应该能够进一步将光学信号提高到该领域前所未有的精度和量化水平。 大脑项目的最后一部分涉及结构成像。我们开发了一种新的方法来检测快速手持设备中的血肿。这种方法将极大地帮助对血肿的存在进行分类，并极大地提高更昂贵的有限访问技术(如CT或MRI)的使用效率。理论结果表明，该设备将工作，以检测硬脑膜血肿，也有可能映射它们与简单的手持设备。在CT或MRI无法获得的情况下，这样的设备可能对辅助外科干预至关重要。正在开发的方法已经在模体上用原型成像器进行了初步测试，初步结果表明，更多的源和更多的探测器在更高密度的范例下进行更好的近红外成像可能是不正确的。事实上，用更小的设备可以实现类似质量的更快的结构成像。不幸的是，这些方法不能应用于功能成像。

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 number of factors, but most strongly by the absence of viable clinical applications where they may be applied. In this project we are targeting veterans (at the upper end of the pediatric population) with penetrating Traumatic Brain Injury (TBI) and Autistic Spectrum Disorder (ASD) patients. These patients are low-functioning and typically pediatric populations. Over the course of the 2011 fiscal year we have secured a Bench to Bedside grant to fund the latter study and extended the funding for the former study under the Center for Neuro-Rehabilitative Medicine. We have again had several presentations accepted at the Society for Neuroscience and have several key papers in submission on our various projects. We have completed the development of our fiber based instrument and are finishing assembling a second instrument through our collaborators at Drexel). We have commenced studies using instruments at our lab and at our other collaborators lab in Georgetown. The latter is a DOI instruments combined with EEG. Clinically we are continuing testing with healthy volunteers and have some initial data from TBI subjects. We have an in-place IRB through NICHD to test our prototype systems here at NICHD for both projects including a neuropsychological evaluation. Alongside our tests for cognitive tasks (event complexity judgment task, a verbal working memory task, and a multi-task) we have further developed an approach for resting state and functional connectivity. For the resting/functional state connectivity existing techniques such as correlation and data-driven decompositions, for assessing functional connectivity, generally assume temporal stationary for the brain signals over the duration of the recording. Such an assumption would result in not detecting the dynamic changes that exist in functional connectivity between engaged regions of the brain. We have been investigating time-frequency analysis techniques to capture the dynamic behavior of connectivity across the prefrontal cortex, at both resting-state and task-based experiments. With the inclusion of neuropsychological evaluation we are well on our way to providing the basis for our ASD study, once complete we will be able to use the existing data from NIMH to identify a patient cohort to closely match our healthy subject population. Theoretically we are currently finishing the development of techniques to handle the shortcomings of current DOI techniques. We have identified an approach using stereotactic imaging that allows us to co-register our optical data to the MNI atlas with accuracy matching that of similar MRI experiments. Currently this requires the existence of a patient specific MRI and our focus is on the ability to remove this requirement as this may not be available for our target patient populations. Initial results have also been done on developing novel techniques to accelerate optical image reconstruction. Currently techniques for 3 dimensional imaging of optical data require days or at best hours to reconstruct by expert users. We are developing novel approaches using a combination of our atlasing approach and analytical functions to address both these issues with DOI. Our collaboration with NINDS has fully developed a fiber based imager which has added to our array devices for comparison and contrast of DOI techniques. This particular system has also increased the areas of the brain accessible to our devices expanding us away from the prefrontal cortex to include motor and visual cortices. Also we have a fully miniaturized system under development in association with our collaborators at Drexel. Initial designs for optical transmitter and receiver have been implemented and the functionality of each module has been verified experimentally. Quad vertical cavity surface emitting laser diodes are used in the transmitter, and the system takes advantage of Gradient-Index (GRIN) lens technology to achieve excellent optical collection efficiency. We are currently working on the integration of the modules. These projects will combine to produce fully wearable DOI for Near Infrared functional imaging. Our theoretical research is also examining motion artifact as a signal instead of noise. Initial results suggest that if we can model the motion of our imaging system relative to the subject via the helmet interface (a process being worked on by our instrumentalists), we should further be able to enhance optical signals to an unprecedented level of accuracy and quantitation in the field. The final part of the brain project involves structural imaging. We have developed a novel approach to detect hematomas in a rapid handheld device. This approach would greatly help for the triaging for the presence of hematomas and greatly increase the efficiency of use of more expensive limited access technologies such as CT or MRI. Theoretical results indicate the device will work to detect Dural hematomas and also that the potential to map them with a simple handheld device exists. Such a device could be critical to aiding in surgical interventions where CT or MRI is unavailable. The approach being developed has undergone initial testing with a prototype imager on phantoms and initial results suggest that the more sources and more detectors at higher density paradigm for better near infra-red imaging may not be correct. In fact it may be possible to achieve faster structural imaging of similar quality with smaller devices. Unfortunately such approaches cannot be applied to functional imaging.