Emerging Diffuse Optical Imaging Technologies for Precision Medicine

TR&D4：用于精准医疗的新兴漫射光学技术 项目PI：Arjun Yodh，PhD 摘要 该提案旨在开发和利用扩散光学技术进行精准医疗。漫射光学是一种 生物医学光学领域，其使用近红外（NIR）光来非侵入性地探测位于 在组织表面（深层组织）以下毫米至厘米。NIR光在组织中强烈散射，但在组织中被吸收。 吸收较弱;因此，它可以在组织中长距离穿透。在这些条件下，光传输很好， 近似为扩散过程。使用该扩散模型，可以定量地分离组织 来自组织吸收的散射，从而进行深层组织的光谱学。分析这些 光谱又允许确定组织发色团的浓度。扩散的使用 方程还使得能够进行组织光学和生理特性的层析成像图像重建。的 拟议的工作使用两种类型的扩散光谱（DOS），频域（FD-DOS）和 宽带（bDOS）漫射光谱，以测量组织吸收和散射，这又 允许定量测定重要生理参数的组织浓度 氧合血红蛋白和脱氧血红蛋白、脂质和水，以及细胞色素c氧化酶的氧化和还原形式。的 所提出的工作还利用了一种称为漫射相关光谱学的定性不同的光学技术 (DCS)其探测在对血流敏感的组织中散射的光的时间波动。的 来自FD-DOS/DCS的氧饱和度和血流信息的组合可用于导出 基于血流动力学的组织氧代谢（CMRO 2）的定量信息。相结合 bDOS/FD-DOS和bDOS-单独可用于导出线粒体（细胞）代谢的度量。这些 组织代谢的补充度量提供了进入组织健康的新窗口。 拟议的项目将在临床研究应用中提供独特的好处。这项技术是便携式的， 与广泛的测量环境兼容，并提供独特的诊断功能， 动态生理监测这些能力，以及光学设备相对较低的成本， 补充该中心正在开发的MRI方法。TRD 4的每个目标都涉及技术 有可能促进患者个体化治疗的需求，即，精准医疗目标1侧重于 在被头发覆盖的大脑区域进行脑血流的实时床边测量;它具有即时的 用于脑损伤患者的重症监护研究和神经调节的真实的实时监测 治疗目的2开发宽带光谱仪器，并将其与FD-DOS结合起来进行测量 氧化和还原形式的细胞色素c氧化酶（CCO）浓度; CCO是一种分子 线粒体功能的生物标志物。同时进行CCO和血流动力学测量， 组织损伤的机制，例如，氧输送与线粒体功能障碍，并可能提供早期 心肺复苏术后的大脑健康警告目标3开发、调整和应用传统和新兴数据 提高漫射光学工具（来自目标1，2）在脑损伤诊断中的价值的科学分析策略 这些工具也将对我们服务项目中的癌症诊断具有价值。每个应用 为个性化患者护理（精准医疗）带来希望。

TR&D4: Emerging Diffuse Optical Technologies for Precision Medicine Project PI: Arjun Yodh, PhD Abstract This proposal aims to develop and utilize diffuse optical technologies for precision medicine. Diffuse optics is a field of biomedical optics that uses near-infrared (NIR) light to non-invasively probe living tissues located millimeters to centimeters below tissue surfaces (deep tissues). NIR light is strongly scattered in tissue but is weakly absorbed; thus, it can penetrate long distances in tissue. Under these conditions, light transport is well approximated as a diffusive process. Using this diffusion model, it is possible to quantitatively separate tissue scattering from tissue absorption and thus to carry out optical spectroscopy of deep tissues. Analysis of these optical spectra, in turn, permits determination of the concentration of tissue chromophores. Use of the diffusion equation also enables tomographic image reconstruction of tissue optical and physiological properties. The proposed work uses two types of Diffuse Optical Spectroscopy (DOS), frequency-domain (FD-DOS) and broadband (bDOS) diffuse optical spectroscopy, to measure tissue absorption and scattering, which in turn permits quantitative determination of the tissue concentrations of important physiological parameters such as oxy- and deoxy-hemoglobin, lipid and water, and both oxidized and reduced forms of cytochrome-c-oxidase. The proposed work also utilizes a qualitatively different optical technique called Diffuse Correlation Spectroscopy (DCS), which probes temporal fluctuations of light scattered in tissue that are sensitive to blood flow. The combination of oxygen saturation and blood flow information from FD-DOS/DCS can be used to derive quantitative information about tissue oxygen metabolism (CMRO2) based on hemodynamics. The combination of bDOS/FD-DOS and bDOS-alone can be used to derive metrics of mitochondrial (cellular) metabolism. These complementary metrics of tissue metabolism provide a new window into tissue health. The proposed projects will provide unique benefits in clinical research applications. The technology is portable, compatible with a wide range of measurement environments, and offers unique diagnostic capabilities for dynamic physiological monitoring. These capabilities, and the comparatively low cost of optical devices, complement the MRI methods under development in the center. Each aim of TRD4 addresses technological needs with potential to facilitate individualized treatment for patients, i.e., precision medicine. Aim 1 focuses on real-time bedside measurements of cerebral blood flow in regions of the brain covered by hair; it has immediate applications in intensive care studies of brain-injured patients and for real time monitoring of neuromodulation therapies. Aim 2 develops broadband spectroscopic instrumentation and combines it with FD-DOS to measure cytochrome-c-oxidase (CCO) concentration in both its oxidized and reduced forms; CCO is a molecular biomarker for mitochondrial function. Concurrent CCO and hemodynamics measurements should elucidate mechanisms of tissue injury, e.g., oxygen delivery versus mitochondrial malfunction, and could provide early warnings about brain health following CPR. Aim 3 develops, adapts, and applies traditional and emerging data science analysis strategies to enhance the value of diffuse optics tools (from Aims 1,2) for brain injury diagnosis and management; the tools will also have value for diagnosis of cancer in our Service Projects. Each application holds promise for individualizing patient care (precision medicine).