Non Ivasive Optical Imaging of the Human Brain

描述(由申请人提供)： 漫反射光学成像(DOI)本身提供了同时非侵入性地测量大脑皮层中的神经元和血管信号的可能性。然而，尽管血流动力学信号的光学测量已经确立，但神经元激活(快速信号)的光学测量才刚刚出现，需要进一步的优化和验证。我们的假设是，目前非侵入性测量神经元快速信号的光学技术的局限性并不是由神经元激活的光学效应的内在特征决定的，而是一种不太理想的实验方法的结果。我们将通过改进仪器、刺激方案和信号处理来增加我们对快速信号测量的稳健性，然后通过在动物(大鼠和猴子)和成人受试者身上进行非侵入性测量来评估其效率、重复性和可靠性(目标1)。一旦光学技术被优化：(1)我们将通过确定快信号的空间和光谱特征来检验快信号的散射起源的假设(目标2)。(2)我们将通过将快速光信号与大鼠的侵入性电生理测量以及人类的脑电/脑磁图测量相关联，来验证快速光信号作为神经元活动的测量方法(目标3)。最后，(3)我们将探索FAST和血流动力学诱发反应之间的宏观神经-血管关系(目标4)。同时进行电生理学和脑电/脑磁图测量的快速信号的验证研究将导致研究电磁信号和快速信号背后的不同现象如何在时间、空间和幅度上相互关联。对快(神经元)和慢(血流动力学)现象敏感的数量的同时和共定位光学测量将通过揭示神经-血管耦合的幅度/空间/时间特征来促进我们对脑生理学的理解，这是现有成像技术所无法实现的。该项目的长期目标是将DOI应用于婴儿正常脑发育的研究，以及成人和儿童脑血管疾病和精神综合征的诊断和随访。

DESCRIPTION (provided by applicant): Diffuse optical imaging (DOI) alone offers the possibility of simultaneously and non-invasively measuring neuronal and vascular signals in the brain cortex. However, while the optical measurement of hemodynamic signals is well established, optical measurement of neuronal activation (the fast signal) is just emerging and requires further optimization and validation. Our hypothesis is that the current limitations of optical techniques for noninvasive measurement of the neuronal fast signal are not determined by intrinsic features of the optical effect of neuron activation, but rather are the result of a less-than-optimal experimental approach. We will increase the robustness of our measure of the fast signal by improving the instrumentation, the stimulation protocols, and the signal processing, and then assess its efficiency, reproducibility, and reliability with noninvasive measurement in animals (rats and monkeys) and adult human subjects (Aim 1). Once the optical technique is optimized: (1) We will test the hypothesis of a scattering origin of the fast signal (Aim 2) by determining its spatial and spectral features. (2) We will validate the fast optical signal as a measure of neuronal activity by correlating the fast signal with invasive electrophysiology measures in rats and EEG/MEG measures in humans (Aim 3). Finally, (3) we will explore the macroscopic neuro-vascular relationship between fast and hemodynamic evoked responses (Aim 4). The validation study of the fast signal with concurrent electrophysiology, and EEG/MEG measurements will lead to the investigation of how different phenomena that underlie the electromagnetic and the fast signals correlate temporally, spatially, and in amplitude. The simultaneous and co-localized optical measurement of quantities sensitive to fast (neuronal) and slow (hemodynamic) phenomena will advance our understanding of brain physiology by revealing amplitude/spatial/temporal features of neuro-vascular coupling not currently accessible with existing imaging techniques. The long-term objective of this project is to apply DOI to the study of normal brain development in infants, and to the diagnosis and follow-up of cerebrovascular diseases and psychiatric syndromes in adults and children.