Emerging Diffuse Optical Imaging Technologies for Precision Medicine

用于精准医疗的新兴漫射光学成像技术

• 批准号: 10490834
• 负责人: ARJUN G. YODH
• 金额: $ 17.83万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490834
• 关键词: Address; Anterior; Biological Markers; Blood flow; Brain; Brain Injuries; Brain region; Breathing; Cerebrovascular Circulation; Cerebrum; Clinical; Clinical Research; Collection; Complement; Data Analyses; Data Science; Development; Devices; Diagnosis; Diffuse; Diffusion; Doctor of Philosophy; Environment; Equation; Euthanasia; Event; Exercise; Exhibits; Fiber; Fingers; Frequencies; Gases; Hair; Hair Root; Head; Health; Heart Arrest; Hemoglobin; Heterogeneity; Human; Hypoxia; Imaging technology; Intensive Care; Light; Lipids; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Measurable; Measurement; Measures; Mechanics; Metabolism; Methods; Microdialysis; Mitochondria; Modeling; Monitor; Motor Cortex; Nervous System Trauma; Noise; Optical Methods; Optics; Oxidative Phosphorylation; Oxides; Oxygen; Parietal; Patients; Physiologic Monitoring; Physiological; Positioning Attribute; Process; Property; Pyruvate; Research; Resolution; Rest; Scalp structure; Series; Services; Signal Transduction; Skeletal Muscle; Spectrum Analysis; Surface; System; Techniques; Technology; Time; Tissue Extracts; Tissues; Validation; Variant; Water; Work; absorption; base; brain health; brain research; brain tissue; cancer diagnosis; cancer therapy; chromophore; classification algorithm; comparative; cost; cytochrome c oxidase; detector; diagnostic value; diffuse optical spectroscopy and imaging; frontal lobe; healthy volunteer; hemodynamics; image reconstruction; improved; individualized medicine; injured; instrument; instrumentation; light scattering; machine learning algorithm; malignant breast neoplasm; metabolic abnormality assessment; metabolic imaging; millimeter; molecular marker; neuroregulation; novel; optical spectra; personalized care; personalized management; porcine model; portability; pre-clinical; precision medicine; pressure; real time monitoring; spatiotemporal; statistical and machine learning; success; tissue injury; tissue reconstruction; tomography; tool; treatment response

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).

TR&D4：用于精准医疗的新兴漫射光学技术 项目负责人：Arjun Yodh 博士 抽象的 该提案旨在开发和利用漫射光学技术进行精准医疗。漫射光学是 生物医学光学领域，使用近红外 (NIR) 光非侵入性地探测位于的活体组织 组织表面以下几毫米到几厘米（深层组织）。近红外光在组织中强烈散射，但 吸收较弱；因此，它可以长距离穿透组织。在这些条件下，光传输效果良好 近似为扩散过程。使用这种扩散模型，可以定量分离组织 组织吸收的散射，从而进行深层组织的光谱分析。分析这些 反过来，光谱可以测定组织发色团的浓度。扩散的利用 方程还能够重建组织光学和生理特性的断层扫描图像。这 拟议的工作使用两种类型的漫射光谱（DOS），频域（FD-DOS）和 宽带 (bDOS) 漫反射光谱，用于测量组织吸收和散射，进而测量组织吸收和散射 允许定量测定重要生理参数的组织浓度，例如 氧合和脱氧血红蛋白、脂质和水，以及细胞色素c氧化酶的氧化和还原形式。这 拟议的工作还利用了一种性质不同的光学技术，称为漫相关光谱 （DCS），它探测对血流敏感的组织中散射光的时间波动。这 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（CMRO2）的定量信息。组合 bDOS/FD-DOS 和 bDOS-only 可用于导出线粒体（细胞）代谢的指标。这些 组织代谢的补充指标为了解组织健康提供了一个新的窗口。 拟议的项目将为临床研究应用提供独特的优势。该技术具有便携性， 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。这些功能以及光学设备相对较低的成本， 补充了该中心正在开发的 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，即精准医疗。目标 1 侧重于 床边实时测量头发覆盖的大脑区域的脑血流量；它有立即的 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 疗法。 Aim 2 开发宽带光谱仪器并将其与 FD-DOS 结合进行测量 氧化型和还原型细胞色素 C 氧化酶 (CCO) 浓度； CCO是一种分子 线粒体功能的生物标志物。同时进行的 CCO 和血流动力学测量应能阐明 组织损伤的机制，例如氧气输送与线粒体功能障碍，并且可以提供早期 心肺复苏后有关大脑健康的警告。目标 3 开发、调整和应用传统和新兴数据 科学分析策略，以提高漫射光学工具（来自目标 1,2）在脑损伤诊断中的价值 和管理；这些工具对于我们服务项目中的癌症诊断也具有价值。每个申请 有望实现个性化患者护理（精准医疗）。