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基于功能近红外光谱成像技术的脑功能研究
司娟宁
学位类型工学博士
导师蒋田仔 研究员
2017-05-26
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业模式识别与智能系统
关键词功能近红外光谱成像技术 神经血管耦合 视觉 半球差异 意识障碍
摘要功能近红外光谱成像技术是新近发展起来的一种利用近红外光来检测组织血氧变化的无创新型光学脑功能成像技术。该技术可以同时提取大脑含氧血红蛋白、脱氧血红蛋白以及总血红蛋白的浓度变化,为大脑的功能活动提供更加全面丰富的信息;此外,其具有安全、便携、成本低、良好的“生态效度”、可长时程连续监测等优势。本文以功能近红外光谱成像技术为核心,一方面结合脑电技术开展视觉皮层的神经血管耦合及半球差异研究,另一方面,从本研究中心自研的功能近红外光谱成像设备出发,开展了任务状态下大脑正常功能活动,以及疾病状态下脑功能活动的研究。本文的主要工作包括以下几个方面:
(1)大脑的功能活动包含神经元活动、局部能量代谢、神经递质的释放等多个复杂过程,使其工作的机理很难理解。而基于EEG与fNIRS的多模态融合技术可以获取大脑神经元电活动和血液动力学信息,从而更好的研究脑功能活动的时空特性。视觉诱发功能活动在实际的临床应用中具有非常重要的价值。然而,以往的研究主要集中于调查视觉诱发电位信号(VEP)的幅度对血氧响应的影响,而其另一重要特征—延迟对血氧响应的影响却知之甚少。此外,VEP的幅值和延迟在视觉信息编码中发挥着不同的作用,研究VEP延迟对血氧响应的影响很有意义。本文利用基于EEG与fNIRS的多模态融合技术,提取全视野视觉刺激下大脑功能活动的神经电生理以及血氧信息,不仅从幅值的角度、而且从延迟的角度出发分析二者之间的内在联系。研究表明,VEP信号的幅值与血氧响应之间呈正线性关系;而VEP信号的延迟与血氧响应之间呈负线性关系。
(2)以往关于视觉系统的研究调查了不同对比度全视野刺激或者同一对比度不同视野刺激的视觉功能活动,而对于不同对比度下半视野刺激对应的视觉功能活动及其半球差异性尚不清楚。本文采用基于EEG与fNIRS的多模态融合技术,研究了不同对比度半视野视觉刺激下视网膜拓扑映射及神经元活动、血氧响应、神经血管耦合的半球差异。fNIRS数据的结果表明,半视野刺激下血氧响应呈现期望的对侧激活模式。而EEG数据的结果表明,半视野刺激下,其视野同侧的视觉半球出现较大的诱发电位幅度,而其视野对侧出现极性反转且幅度较低的诱发电位成分,呈现矛盾性侧化。半视野对侧视觉皮层出现的极性反转以及延迟优势,可能是该侧(相比于视野同侧视觉皮层)响应幅度较小的原因之一。此外,神经元电活动以及血氧响应与对比度水平的关系均可以描述为log函数关系。并且,从宏观角度上,随着对比度的增加,神经元电活动的的幅值和延迟特性与血氧响应之间的关系表现为线性关系,只是斜率不同。
(3)基于自主研发的光电同步脑活动检测系统(NEG)展开任务状态下正常大脑功能活动的研究。由于该NEG系统属于医疗器械,在其正式进入临床应用之前,我们设计了几种经典的任务对其血氧检测的工作性能进行评测。研究结果表明,NEG系统在不同的任务中都能很好的检测到对应任务的血氧激活信号,说明该系统具有良好的工作性能,这为该系统进入临床应用具有非常重要的作用,也为进一步推进该系统的优化升级以及产业化进程具有重要意义。
(4)脊髓电刺激(SCS)对于意识障碍(DOC)具有较好的治疗效果,但其潜在的工作机制尚不明确。此外,SCS程控参数的设计是术后治疗的重要环节。目前SCS程控参数的设计主要依赖于临床医生的主观经验以及行为评估,缺乏定量评价手段。针对这一现状,我们首次将fNIRS技术引入针对DOC患者的SCS治疗应用研究中,结合临床数据研究DOC患者在不同刺激间歇期、刺激频率的SCS治疗下的脑血氧变化,旨在揭示SCS的促醒机制,同时也为神经调控治疗的程控参数设计提供指导。研究表明,SCS刺激可以引起DOC患者意识相关脑区血氧信息的改变,且不同参数的SCS刺激对应的血氧活动也随之改变。
其他摘要Functional near-infrared spectroscopy (fNIRS) has emerged as a newly developed non-invasive optical neuroimaging technology, which provides more information about the hemodynamic responses with improved ecological validity by measuring deoxygenated (HbR), oxygenated (HbO), and total (HbT) hemoglobin; moreover, it’s safe, portable, cost-effective, ecological, and can be used for longitudinal monitoring. In this paper, on the one hand, fNIRS was combined with EEG as a multimodal neuroimaging technique to investigate neurovascular couping and hemispheric differences in visual cortex; on the other hand, a self-designed fNIRS system (NEG) was used to investigate the brain activation under several classical tasks as well as to explore the brain activation under brain disorders.
(1) Brain functional activity involves neuronal electrophysiological signal transmission, energy metabolism, and chemical transmitter release, making it difficult to comprehend. Electroencephalography (EEG) and fNIRS have been combined into a multimodal neuroimaging method that captures both electrophysiological and hemodynamic information to explore the spatiotemporal characteristics of brain activity. Because of the significance of visually evoked functional activity in clinical applications, numerous studies have explored the amplitude of the visual evoked potential (VEP) to clarify its relationship with the hemodynamic response. However, relatively few studies have investigated the influence of latency, which has been frequently used to diagnose visual diseases, on the hemodynamic response. Moreover, because the latency and the amplitude of VEPs have different roles in coding visual information, investigating the relationship between latency and the hemodynamic response should be helpful. In this study, checkerboard reversal tasks with graded contrasts were used to evoke visual functional activity. Both EEG and fNIRS were employed to investigate the relationship between neuronal electrophysiological activities and the hemodynamic responses. The VEP amplitudes were linearly correlated with the hemodynamic response, but the VEP latency showed a negative linear correlation with the hemodynamic response.
(2) Most of the studies of visual system have either focused on distinct stimulus contrasts in full visual field or on distinct visual fields with a constant contrast. However, hemispheric differences in neuronal activities, hemodynamic responses, and neurovascular coupling remain unclear. A multimodal neuroimaging technique based on EEG and fNIRS was used with horizontal hemifield visual stimuli with graded contrasts to investigate the retinotopic mapping more fully as well as to explore hemispheric differences in neuronal activity, the hemodynamic response, and the neurovascular coupling relationship in the visual cortex. The fNIRS results showed the expected activation over the contralateral hemisphere for both the left and right hemifield visual stimulations. However, the EEG results presented a paradoxical lateralization, with the maximal response located over the ipsilateral hemisphere but with the polarity inversed components located over the contralateral hemisphere. Our results suggest that the polarity inversion as well as the latency advantage over the contralateral hemisphere cause the amplitude of the VEP over the contralateral hemisphere to be smaller than that over the ipsilateral hemisphere. Both the neuronal and hemodynamic responses changed logarithmically with the level of contrast in the hemifield visual stimulations. Moreover, the amplitudes and latencies of the visual evoked potentials (VEPs) were linearly correlated with the hemodynamic responses despite differences in the slopes.
(3) A self-designed fNIRS system (NEG) was used to investigate the functional activation of the brain. Since the NEG system is one of the medical devices, several classic tasks were conducted to evaluate the performance of hemodynamic detection before it can be used in the clinical environment. The results showed that the hemodynamic responses could be recorded over the corresponding brain areas under different tasks, and suggested that the NEG system has a relatively good performance. The evalutation of the performance of the NEG system has great significance to promote the clinical application and optimization of the system as well as to further promote the process of industrialization.
(4) Spinal cord stimulation (SCS) has relatively good therapeutic effects on patients with disorders of consciousness (DOC), but the underlying mechanism remains unclear. In addition, the design of SCS parameters is an important part of postoperative treatment. At present, the design of SCS parameters mainly depends on the subjective experience and behavior evaluation of clinicians. There is still a lack of evidence-based evaluation method to quantitantively assess the effects of SCS. In view of this situation, we first used fNIRS to investigate the neuromodulation effects of SCS on patients with DOC. Several SCS protocols with different stimulation inter-stimulus intervals and frequencies were conducted to study the brain activation of the patients with DOC. Our research goals were to reveal the mechanism of SCS and to provide guidance for designing SCS parameters. Our results showed that SCS could induce the changes in hemodynamic responses of the brain for patients with DOC; moreover, the changing patterns of hemodynamic responses under different SCS parameters were distinct.
语种中文
文献类型学位论文
条目标识符http://ir.ia.ac.cn/handle/173211/14720
专题毕业生_博士学位论文
作者单位中国科学院自动化研究所
推荐引用方式
GB/T 7714
司娟宁. 基于功能近红外光谱成像技术的脑功能研究[D]. 北京. 中国科学院研究生院,2017.
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