Functional and Structural Optical Brain Imaging

功能性和结构性光学脑成像

• 批准号: 8736920
• 负责人: Amir H Gandjbakhche
• 金额: $ 55.1万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8736920
• 关键词: Address; Adult; Age; Agreement; Area; Atlases; Attention; Attention deficit hyperactivity disorder; Auditory; Behavior; Bilateral; Biological; Biophotonics; Blood Vessels; Brain; Brain Injuries; Brain imaging; Brain region; Brodmann' s area; Cerebrum; Child; Childhood; Chronic; Classification; Clinical; Cognitive; Collaborations; Conflict (Psychology); Coupling; Data; Detection; Development; Devices; Diagnostic; Diffuse; Electroencephalogram; Electroencephalography; Emerging Technologies; Environment; Epilepsy; Event-Related Potentials; Fiber; Forehead; Functional Magnetic Resonance Imaging; Functional disorder; Hand; Head; Hematoma; Hemispherectomy; Hemoglobin; Human; Image; Imaging technology; Judgment; Knowledge; Lateral; Left; Legal patent; Licensing; Life; Light; Link; Location; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mediation; Methodology; Methods; Modality; Modeling; Monitor; Morphologic artifacts; Motion; Movement; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; Nature; Near-Infrared Spectroscopy; Noise; Optics; Oxyhemoglobin; Participant; Patients; Pattern; Physiological; Population; Positioning Attribute; Positron-Emission Tomography; Prefrontal Cortex; Process; Relative (related person); Research; Resolution; Rest; Scientist; Side; Signal Transduction; Soldier; Structure; System; TBI Patients; Techniques; Technology; Testing; Therapeutic Intervention; Time; Tissues; Traumatic Brain Injury; Triage; Universities; Variant; Visual; Work; absorption; autism spectrum disorder; base; bench to bedside; cerebrovascular; chromophore; cognitive function; data acquisition; deoxyhemoglobin; detector; hemodynamics; imaging modality; instrument; interest; millisecond; novel; novel strategies; optical imaging; optical sensor; outcome forecast; patient population; photonics; prototype; relating to nervous system; research clinical testing; research study; response; sensor; tool

Imaging of the brain structure and function can help to elucidate different biological/clinical manifestations of Traumatic Brain Injury (TBI) and Autistic Spectrum Disorder (ASD) The idea is to localize brain areas for classification of structural and functional disorders and, ultimately, for therapeutic intervention. While functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are the best suited imaging modalities for the most of the functional brain studies, they have some inherent limitations, particularly in the case of low-functioning TBI or ASD subjects. Difficulties in fMRI data acquisition are mainly due to the non-friendly environment of the measurement system for the children with ASD and ADHD, because they are very sensitive to restrictions on movement. In this regard, patient-friendly NIRS can become an imaging modality of choice. NIRS and, in particular, functional near infrared spectroscopy (fNIRS) is an emerging technology for noninvasive measurements of the local changes in cerebral hemodynamic levels associated with brain activity. Due to the low optical absorption of biological tissues at NIR wavelengths (=700-1000 nm), NIR light can penetrate deep enough to probe the outer layers of brain (i.e., cortex) up to 2-3 cm deep. The NIR absorption spectrum of the tissue is sensitive to changes in the concentration of major tissue chromophores, such as hemoglobin species. Therefore, measurements of temporal variations of backscattered light can capture functionally evoked changes in the outermost cortex, and, thus, can be used to assess the brain functioning. Compared to other well-established brain imaging modalities, such as fMRI and PET, this technique offers unique features, including higher temporal resolution of several milliseconds, and spectroscopic information about temporal variations of both components of hemoglobin Oxy-HbO and deOxy-Hb, while fMRI can assess only deoxy-hemoglobin (Hb) changes. Most importantly for pediatric applications, NIRS instruments are much smaller, less restraining compared to fMRI or PET and can tolerate subject motion to a larger extent that fMRI. These features make the technique appropriate to study children with such problems as ASD as well as TBI patients, when keeping the subjects still for long periods of time is extremely challenging. Due to neuro-vascular coupling local changes in oxyhemoglobin and deoxyhemoglobin levels can serve as an indirect measure of brain activity. At first approximation, these levels are proportional to the intensity of the brain activity. We have used an action complexity judgment task with a varying degree of cognitive load to produce brain activation. Twenty healthy participants were asked to evaluate the complexity of previously normed daily life action (number of steps to achieve the task) and classify the number of steps as few or many. We used the linear relationship between changes in the oxy/deoxyhemoglobin change and activity complexity to map the activation on the cortex. The mapping was possible with a special registration between MRI anatomical image and the optical sensor. The parametric effect of complexity showed activation in the frontopolar cortex. In our experiments we have found that on average the activation area corresponded to an angle of =95 and =10. Though the localization of the activation may be less precise with fNIRS than fMRI (according to fMRI data, this activation area was located at an angle =93 and =11), the parametric analysis, linking cognitive load to cerebrovascular reactivity may reveal physiological data of greater clinical importance than just the location of the activated area. Our preliminary results, obtained for 2 TBI patients, show that such parametric studies, based on fNIRS, have the potential to become a discriminator of cognitive function in TBI patients. To probe changes in Oxy- and Deoxy-hemoglobin concentrations in the cortex that are caused by brain activity, related to chosen basic tasks, the data are collected at two wavelengths. To assess the brain activation in children of 4-8 years, we have used such tests as standard GO/NO-Go, developed to examine the effects of response inhibition and error processing. The NIRS signal is acquired, while children are performing the GO/NO-GO task. The NIRS sensor, placed on the childs forehead, covered Brodmann areas 9, 10 of the prefrontal cortex (PFC). Initial results of fNIRS assessment of the hemodynamic changes in the cortex indicate that mean activation levels (based on changes in oxy-hemoglobin) obtained from left and right prefrontal cortex during both GO and NO-GO trials are much higher in the case of typical child, compared to that of ASD. This fact indicates the hypo-activation of prefrontal cortex in the ASD group. Studies of resting state and task-based functional connectivity aiming to identify brain regions similar in functional behavior have received increased attention over the past few years. Aside from healthy populations, different patient groups, including patients with ASD, TBI have been the subject of functional connectivity (FC) studies. These studies have identified different connectivity networks in patient groups compared to healthy population. Different imaging modalities have been employed to investigate the brains functional connectivity. We attempt to elucidate features of FC by studying both hemodynamic and neural responses of the brain using different modalities. We recorded hemodynamic activity during the Go/No-Go task from 11 right-handed subjects with probes placed bilaterally over prefrontal areas. Using the data, we presented a reliable detection of fast optical signal (FOS) concurrently with electroencephalogram (EEG) during a Go/No-Go task. According to NIRS the hemodynamic responses showed higher task-related activation (an increase/decrease in oxygenated/deoxygenated hemoglobin, respectively) in the right versus left hemisphere. We have conducted two studies of FC to identify brain regions that are similar in functional behavior. Our more precise and comprehensive presentation of brain FC was achieved by investigating Electroencephalography (EEG) data. We employed a new approach to trace the dynamic patterns of human brain task-based functional connectivity.The EEG signals of 5 healthy subjects were recorded while they performed an auditory oddball and a visual modified oddball tasks. To capture the dynamic patterns of functional connectivity during the execution of each task, EEG signals are segmented into duration that correspond to the temporal windows of previously well-studied event-related potentials (ERPs). For each task, the proposed approach was able to establish a unique sequence of dynamic pattern (observed in all 5 subjects) for brain functional connectivity. The early diagnostics of brain hematomas is known to be crucial for proper therapy and good prognosis. However, in many cases brain traumas occur in places, where imaging modalities, MRI and CT, are not easily accessible. For this reason, there is an urgent need for some portable tool to provide fast initial assessment of the brain injury. Some simplified NIR devices, based on comparison between region of interest (ROI) and contra-lateral side, may not detect the presence of symmetrical bilateral hematomas. Hematoma detector would be clinically viable, if it can provide proper diagnostics for all types of head hematoma. Motion artifacts present a major challenge for conventional NIR imaging, where random errors in the relative positions of the detectors and ROI contribute to measurement noise. We are in the process of patenting this methodology, and a company has already licensed it. We are in negotiation of a collaborative research agreement to bring the technology from bench to bedside.

大脑结构和功能的成像可以有助于阐明创伤性脑损伤（TBI）和自闭症谱系障碍（ASD）的不同生物学/临床表现（ASD）的想法是将大脑区域定位为结构和功能障碍的分类，并最终用于治疗干预。尽管功能磁共振成像（fMRI）和正电子发射断层扫描（PET）是大多数功能性脑研究的最佳成像方式，但它们具有一些固有的局限性，尤其是在低功能的TBI或ASD主题的情况下。 fMRI数据获取的困难主要是由于对ASD和ADHD儿童的测量系统的不友好环境，因为它们对运动的限制非常敏感。在这方面，对患者友好的NIR可以成为选择的成像方式。 NIR，尤其是近红外光谱（FNIRS）是一种新兴技术，用于无创测量与脑活动相关的脑血动力学水平的局部变化。由于在NIR波长（= 700-1000 nm）处生物组织的光学吸收较低，因此NIR光可以渗透到足够深的地方，以探测大脑的外层（即皮层），深度为2-3厘米。组织的NIR吸收光谱对主要组织发色团（例如血红蛋白种类）的浓度变化敏感。因此，测量反向散射光的时间变化可以捕获最外层皮质的功能诱发的变化，因此可以使用来评估大脑功能。与其他良好的大脑成像方式（例如fMRI和PET）相比，该技术提供了独特的功能，包括更高的时间分辨率，包括几毫秒的时间分辨率，以及有关血红蛋白氧气HBO和脱氧HB组成部分的时间变化的光谱信息，而FMRI仅评估脱氧蛋白（HB）的变化。最重要的是，对于儿科应用，NIRS仪器比fMRI或PET相比要小得多，限制较小，并且可以在fMRI的范围内忍受受试者的运动。这些功能使该技术适合研究患有ASD和TBI患者等问题的儿童，在长时间保持受试者时，这些技术仍然非常具有挑战性。 由于神经血管耦合氧气血红蛋白和脱氧血红蛋白水平的局部变化可以作为脑活动的间接度量。首先，这些水平与大脑活性的强度成正比。 我们使用了具有不同程度的认知负荷的动作复杂性判断任务来产生大脑激活。要求20名健康的参与者评估先前规范的日常生活行动的复杂性（完成任务的步骤数），并将步骤数分为少或多个。 我们使用了氧/脱氧血红蛋白变化的变化与活性复杂性之间的线性关系来绘制皮质上的激活。 可以在MRI解剖图像和光学传感器之间进行特殊注册，可以进行映射。复杂性的参数效应显示在额压皮质中的激活。 在我们的实验中，我们发现平均而言，激活区域对应于= 95和= 10的角度。尽管FNIRS的本地化的定位可能不如FMRI更精确（根据fMRI数据，该激活区域的位置位于角度= 93和= 11），但是参数分析，将认知负荷与脑血管反应联系起来可能揭示出比仅仅仅在激活区域的位置的临床重要性的生理重要性数据。我们为2名TBI患者获得的初步结果表明，基于FNIRS的这种参数研究有可能成为TBI患者认知功能的歧视者。 为了探测由大脑活动引起的皮层中的氧和脱氧血红蛋白浓度的变化，与所选的基本任务有关，数据以两个波长收集。为了评估4-8岁儿童的大脑激活，我们使用了标准GO/NO-GO之类的测试来检查响应抑制和错误处理的影响。在孩子执行GO/NO-GO任务时，获得了NIRS信号。 NIRS传感器放置在Childs额头上，覆盖了前额叶皮层（PFC）的Brodmann区域9、10。 FNIRS评估皮层血液动力学变化的初步结果表明，与ASD相比，在GO和NO-GO试验中，在GO和No-GO试验期间从左右额叶皮质中获得的平均激活水平（基于氧气血红蛋白的变化）要高得多。这一事实表明，ASD组中前额叶皮层的过度激活。 在过去几年中，旨在识别功能行为相似的大脑区域的静止状态和基于任务的功能连接性旨在识别大脑区域。除了健康的人群外，包括ASD患者在内的不同患者组，TBI是功能连通性（FC）研究的主题。与健康人群相比，这些研究已经确定了患者群体中不同的连通性网络。已经采用了不同的成像方式来研究大脑功能连通性。我们试图通过使用不同的方式研究大脑的血液动力学和神经反应来阐明FC的特征。我们从11个右撇子受试者进行的《 GO/NO-GO任务》中记录了血液动力学活动，并在前额叶区域将双侧放置在双侧。使用数据，我们在GO/NO-GO任务中同时介绍了与脑电图（EEG）同时同时检测快速光学信号（FOS）。根据NIRS，血液动力学反应显示与右半球相对于左半球的任务相关激活（分别增加/减少）。我们已经对FC进行了两项研究，以识别功能行为相似的大脑区域。通过研究脑电图（EEG）数据，我们对大脑FC的更精确和全面的表现。我们采用了一种新方法来追踪基于人脑的功能连接的动态模式。在执行听觉奇数球和视觉修改的奇数球任务时，记录了5个健康受试者的脑电图信号。为了捕获每个任务执行过程中功能连接性的动态模式，将EEG信号分割为与以前研究过的事件相关电位（ERP）的时间窗口相对应的持续时间。 对于每个任务，提出的方法能够建立一个独特的动态模式序列（在所有5个受试者中观察到），以实现大脑功能连接性。 众所周知，脑血肿的早期诊断对于适当的治疗和良好的预后至关重要。但是，在许多情况下，脑部创伤发生在成像模式，MRI和CT的地方，不容易访问。因此，迫切需要一些便携式工具来对脑损伤进行快速初步评估。基于目标区域（ROI）和相互侧面的比较，一些简化的NIR设备可能无法检测到对称双侧血肿的存在。如果血肿探测器可以为所有类型的头部血肿提供适当的诊断，那么血肿检测器将在临床上可行。运动伪像是常规NIR成像的主要挑战，其中检测器的相对位置的随机误差和ROI有助于测量噪声。我们正在为该方法申请专利，并且一家公司已经获得了许可。我们正在谈判一项协作研究协议，以将技术从长凳带到床边。