Emerging Diffuse Optical Imaging Technologies for Precision Medicine

DR&D4：精密医学的新兴漫反射光学技术 项目PI：Arjun Yodh，博士 摘要 这项提议旨在开发和利用精密医学的漫反射光学技术。漫反射光学是一种 生物医学光学领域，使用近红外(NIR)光非侵入性探测定位的活组织 组织表面(深层组织)以下几毫米到几厘米。近红外光在组织中强烈散射，但 吸收弱；因此，它可以在组织中穿透很远的距离。在这种情况下，轻型运输是很好的 近似为扩散过程。使用这种扩散模型，可以定量地分离组织 从组织吸收的散射，从而进行深部组织的光学光谱。对这些问题的分析 反过来，光学光谱可以确定组织发色团的浓度。扩散的使用 方程还使组织光学和生理特性的断层图像重建成为可能。这个 建议的工作使用两种类型的漫反射光谱(DOS)，频域(FD-DOS)和 宽带(BDOS)漫反射光谱学，用于测量组织吸收和散射，进而 允许定量测定重要生理参数的组织浓度，例如 氧化和脱氧血红蛋白、脂质和水，以及氧化和还原形式的细胞色素-C-氧化酶。这个 拟议的工作还利用了一种称为漫射相关光谱的性质不同的光学技术 (分布式控制系统)，探测散射在对血流敏感的组织中的光的时间波动。这个 结合来自FD-DOS/DCS的血氧饱和度和血流信息，可以推导出 基于血流动力学的组织氧代谢(CMRO2)的定量信息。组合在一起 BDO/FD-DOS和BDOS-单独可用于得出线粒体(细胞)新陈代谢的指标。这些 组织新陈代谢的互补指标为了解组织健康提供了一个新的窗口。 拟议的项目将在临床研究应用方面提供独特的好处。这项技术是便携的， 与多种测量环境兼容，并提供独特的诊断功能 动态生理监测。这些能力，以及相对较低的光学设备成本， 补充中心正在开发的MRI方法。TRD4的每个目标都涉及技术 有潜力促进患者个体化治疗的需求，即精准医学。目标1侧重于 实时床边测量大脑毛发覆盖区域的脑血流量；它具有即时 在脑损伤患者重症监护研究和神经调节实时监测中的应用 治疗。目标2开发宽带光谱仪器并将其与FD-DOS相结合进行测量 细胞色素-c-氧化酶(CCO)的浓度有氧化和还原两种形式；CCO是一种分子 线粒体功能的生物标志物。同时进行的CCO和血流动力学测量应阐明 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 心肺复苏后有关大脑健康的警告。目标3开发、调整和应用传统数据和新兴数据 提高漫反射光学工具(来自AIMS 1，2)在脑损伤诊断中的价值的科学分析策略 这些工具还将在我们的服务项目中对癌症的诊断具有价值。每个应用程序 拥有个性化患者护理(精准医疗)的前景。

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).