Time Domain-Diffuse Correlation Spectroscopy (TD-DCS)

 描述（由申请人提供）：脑血流量（CBF）的连续无创床旁监护仪可用于诊断和管理与缺血或血管自动调节不足相关的任何脑损伤或疾病。手术期间或任何重症监护环境中的连续CBF监测将有助于患者管理，以改善脑预后。近红外光谱（NIRS）可以测量血红蛋白浓度（HbT）和氧合（SO2），但不测量脑灌注只能部分评估脑血流动力学。扩散相关光谱（DCS）是一种新兴的光学模式，连续和无创地监测CBF使用近红外连续光。DCS通过量化由移动的红细胞的动态散射产生的光的时间波动来测量血流指数（CBFi）。随着我们和其他几个研究小组最近在临床应用中取得的积极成果，越来越多的研究人员开始采用DCS技术。与NIRS一样，脑外层污染DCS脑血流量估计，并且为了正确量化绝对CBFi值，需要了解所研究组织的光学特性。对于这个R21，我们建议开发一种全新的技术，时域DCS（TD-DCS），通过采用新的长相干脉冲激光器，并检测每个脉冲中的光子到达时间和跨脉冲的时间门控自相关衰减。通过在时域而不是连续波（CW）模式下操作DCS，我们将能够利用时间分辨反射光谱（TRS）的许多优点。正如我们的Monte Carlo模拟所示，通过评估不同时间门的自相关函数，使用TD-DCS，我们将能够区分通过组织的短光子路径和长光子路径，并实现比使用CW照明更高的大脑灵敏度。此外，这种对大脑的高度敏感性 可以在较短的源-检测器间隔下实现，从而允许检测到更高数量的光子。此外，TRS分析将使我们能够评估大脑光学特性，并提高受试者之间绝对CBFi比较的可靠性。时间标记光子到达将使来自同一数据流的多个分析成为可能，从而首次在单次测量中同时定量HbT、SO2和CBF。通过这项建议，我们将建立第一个TD-DCS原型，并开发协同TD和DCS的方法和分析程序，以实现上级性能，同时保持成本效益。我们将评估最佳操作参数，并在模型中表征和测试原型。最后，我们将在人类受试者中展示系统性能。这一初步可行性研究将为更大规模的研究提供动力。这种方法有可能克服目前脑血流动力学血氧测定方法的局限性。

 DESCRIPTION (provided by applicant): A continuous noninvasive bedside monitor of cerebral blood flow (CBF) will be useful for diagnosis and management of any brain injury or disease associated with ischemia or inadequate vascular autoregulation. Continuous CBF monitoring during surgery or in any intensive care setting will help with patient management to improve cerebral outcomes. Near-infrared spectroscopy (NIRS) can measure hemoglobin concentration (HbT) and oxygenation (SO2) but without measuring cerebral perfusion can only partially assess cerebral hemodynamics. Diffuse correlation spectroscopy (DCS) is an emerging optical modality to monitor CBF continuously and noninvasively using near-infrared continuous light. DCS measures an index of blood flow (CBFi) by quantifying the temporal fluctuations of light generated by the dynamic scattering of moving red blood cells. Following recent positive results with several clinical applications, obtained by us and several other groups, more and more researchers are starting to adopt DCS technology. As with NIRS, extra-cerebral layers contaminate DCS cerebral blood flow estimates and, to correctly quantify absolute CBFi values, knowledge of the optical properties of the investigated tissue are needed. For this R21, we propose to develop a completely brand new technique, time-domain DCS (TD-DCS), by employing novel long coherence pulsed lasers and detecting both photon arrival times in each pulse and time-gated autocorrelation decay across pulses. By operating DCS in time-domain instead of continuous-wave (CW) mode, we will be able to exploit the many advantages of time-resolved reflectance spectroscopy (TRS). As shown by our Monte Carlo simulations, by evaluating the autocorrelation function over different time gates, with TD-DCS we will be able to differentiate between short and long photon paths through the tissue and achieve higher sensitivity to the brain than by using CW illumination. Further, this high sensitivity to the brain can be achieved at shorter source-detector separations, allowing for a higher number of detected photons. In addition TRS analysis will allow us to evaluate cerebral optical properties and improve the reliability of absolute CBFi comparisons between subjects. Time-tagging photon arrivals will enable multiple analyses from the same data stream allowing for the first time, simultaneous quantification of HbT, SO2, and CBF within a single measurement. With this proposal we will build the first TD-DCS prototype and develop synergistic TD and DCS methods and analysis procedures to achieve superior performances while retaining cost effectiveness. We will evaluate the optimal operation parameters and characterize and test the prototype in phantoms. Finally, we will demonstrate system performance in human subjects. This initial feasibility study will provide motivation for larger studies. This method has the potential to overcome the limitations of present cerebral hemodynamic oximetry methods.