Dual-slope method for enhanced depth sensitivity in frequency-domain near-infrared spectroscopy

项目摘要 在这个生物工程研究项目中，我们建议开发一种新的频域近场技术， 红外光谱法（FD-NIRS），旨在非侵入性地实现对更深组织的选择性灵敏度 扩散光谱学和成像。一种对深层组织更敏感的技术 可以对非侵入式光学诊断和监测产生广泛的影响， 在脑血氧测定和功能性脑成像中尤其重要。所提出的技术是基于 相位双斜率的新概念（这是在FD-NIRS中测量的调制光信号的相位）， 这需要最少两个光源和两个光学检测器放置在组织上 特别安排。除了实现对更深组织的选择性灵敏度之外，相位双斜率还被 对仪器漂移和运动伪影（尖峰除外）的敏感性较弱，这是非常理想的特性 用于稳健的测量。首先，我们将使用扩散理论和蒙特卡罗模拟来识别 源/检测器几何布置和强度调制频率， 相位双斜率适用于各种非均匀层状介质。第二，我们将实施最优相位 使用商用FD-NIRS仪器的双斜率条件，以证明对组织样 幻影，我们将设计特殊的源探测器阵列成像的基础上摩尔彭罗斯 相位双斜率测量的雅可比矩阵的伪逆。第三，我们将设计和建造一个 专用的紧凑型、可穿戴、无光纤且具有成本效益的FD-NIRS设备， 相位双斜率法在日常条件下对自由移动对象的适用性，以及 护理应用。第四，我们将进行人体研究，进行技术性能测试（骨骼肌 在血管闭塞期间），并证明相位双斜率法用于功能性 大脑成像（在认知激活期间的前额叶皮层）。特别是，后一项研究将阐明 相对血流量/血容量对皮质血流动力学的贡献， 测量在行走时执行认知任务的受试者。该项目的总体目标是 通过开发特殊的技术来推进生物组织的漫射光学测量领域， FD-NIRS数据的收集和分析，以提高质量，可靠性和非信息内容 侵入性NIRS在研究和临床应用中的应用。

PROJECT SUMMARY In this Bioengineering Research project, we propose to develop a novel technique for frequency-domain near- infrared spectroscopy (FD-NIRS) that aims to achieve selective sensitivity to deeper tissue in non-invasive diffuse optical spectroscopy and imaging. A technique that features a stronger sensitivity to deeper tissue relative to superficial tissue can have a broad impact on non-invasive optical diagnostics and monitoring and is especially important in cerebral oximetry and functional brain imaging. The proposed technique is based on the new concept of phase dual-slopes (this is the phase of the modulated optical signal measured in FD-NIRS), which requires a minimum of two light sources and two optical detectors placed on the tissue according to a special arrangement. In addition to achieving selective sensitivity to deeper tissue, phase dual slopes are weakly sensitive to instrumental drifts and motion artifacts (except spikes), which is a highly desirable property for robust measurements. First, we will use diffusion theory and Monte Carlo simulations to identify source/detector geometrical arrangements and intensity modulation frequencies that optimize performance of the phase dual-slope for a variety of heterogeneous layered media. Second, we will implement optimal phase dual-slope conditions with a commercial FD-NIRS instrument to demonstrate effectiveness on tissue-like phantoms, and we will design special source-detector arrays for imaging based on the Moore-Penrose pseudoinverse of the Jacobian matrix for phase dual-slope measurements. Third, we will design and build a dedicated compact, wearable, fiber-less, and cost-effective FD-NIRS device for further broadening the applicability of the phase dual-slope method to freely moving subjects in everyday conditions, and for point-of- care applications. Fourth, we will perform human studies for technical performance tests (in skeletal muscle during vascular occlusions) and to demonstrate the effectiveness of the phase dual-slope method for functional brain imaging (in the prefrontal cortex during cognitive activation). In particular, the latter study will elucidate the relative blood flow/blood volume contributions to cortical hemodynamics and will allow for dual-task measurements in subjects performing cognitive tasks while walking. The broad objective of this project is to advance the field of diffuse optical measurements of biological tissue by developing special techniques for collection and analysis of FD-NIRS data to enhance the quality, reliability, and information content of non- invasive NIRS in research and clinical applications.