Noninvasive deep-tissue single-cell imaging and nanoprobe development

非侵入性深部组织单细胞成像和纳米探针开发

• 批准号: 10015308
• 负责人: Steven Chu
• 金额: $ 54.96万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-05 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015308
• 关键词: Acoustics; Address; Anatomy; Animals; Biological; Biology; Biomedical Research; Biophysics; Blood; Cell Culture Techniques; Cell physiology; Cells; Cellular Structures; Cellular biology; Characteristics; Chemistry; Communities; Complex; Data; Department of Energy; Development; Diagnosis; Disease; Engineering; Exposure to; Fluorescence Microscopy; Frequencies; Funding; Generations; Goals; Image; Imaging technology; Individual; Ionizing radiation; Lasers; Letters; Light; Location; Magnetic Resonance Imaging; Mission; Molecular; Molecular Target; Mus; Nanotechnology; Near-infrared optical imaging; Noise; Optics; Organism; Penetration; Performance; Physiologic pulse; Physiological; Physiology; Pigments; Play; Positron-Emission Tomography; Radiology Specialty; Research; Resolution; Role; Signal Transduction; Specialist; Specificity; Techniques; Technology; Time; Tissue imaging; Tissues; Transducers; Ultrasonic Transducer; Ultrasonography; Work; X-Ray Computed Tomography; anatomic imaging; base; biological research; cancer imaging; cellular imaging; cellular targeting; cost; imaging modality; imaging probe; in vivo; innovation; instrument; light scattering; lymph nodes; malignant breast neoplasm; molecular imaging; mouse model; multidisciplinary; multimodality; nanoparticle; nanoprobe; new technology; non-invasive imaging; novel; novel imaging technology; optical imaging; photoacoustic imaging; prototype; real-time images; response; single molecule; sound; synergism; technology research and development

PROJECT SUMMARY / ABSTRACT This research in response to the PAR-17-045 “Focused Technology Research and Development” proposes to develop a non-invasive, deep-tissue imaging technology with single-cell sensitivity based on ultrasound and photoacoustic imaging. Ultrasound imaging uses sound wave to provide anatomic information of tissue, and offers many desirable characteristics--fast, real-time imaging, low cost, deep tissue penetration, high spatial resolution and no exposure to ionizing radiation. However, the presence of significant speckle noise greatly compromises the imaging quality and resolution. Photoacoustic (PA) imaging uses non-ionizing laser pulse excitation to generate ultrasound emission that is detectable by ultrasound transducers. It combines the spectroscopic- based specificity and high-contrast of optical imaging at deep-tissue location (~ a few cms). However, blood and pigments generate high intrinsic background signals, which significantly limit the in vivo sensitivity in detecting molecular and cellular targets. This research will explore innovative engineering and nanotechnology to address these challenges to enable non-invasive, deep-tissue imaging technology with single-cell sensitivity. Aim 1 will develop nonlinear difference-frequency generation for ultrasound imaging to provide highly contrasted anatomic information. Aim 2 will develop photoswtichable photoacoustic nanoparticles to enable near-infrared photoswitchable photoacoustic imaging and provide single cell imaging sensitivity. Aim 3 will integrate ultrasound imaging with photoswitchable photoacoustic imaging to image tumor lymph nodes and demonstrate the synergy of Aim 1 and Aim 2 techniques in obtaining high-contrast anatomical and molecular information in deep tissue of living subjects. At the end of the 4 years period of funding, the research will produce an instrument prototype and novel nanoparticles that can be used for speckle-free acoustic (anatomic tissue information), photoswitchable photoacoustic imaging (single-cell molecular and cell information). It is expected that this new imaging technology will provide unprecedented opportunity in acquiring information on biological molecules in complex, native physiological settings and enable many fundamental biology discoveries.

项目概要/摘要 这项研究响应 PAR-17-045“重点技术研究和开发” 提议开发一种基于单细胞敏感性的非侵入性深层组织成像技术 超声和光声成像。 超声成像利用声波提供组织的解剖信息，并提供许多 理想的特性——快速、实时成像、低成本、深层组织穿透、高空间分辨率和 没有暴露于电离辐射。然而，显着散斑噪声的存在极大地损害了 成像质量和分辨率。光声 (PA) 成像使用非电离激光脉冲激发 产生可由超声换能器检测到的超声发射。它结合了光谱- 基于深层组织位置（约几厘米）光学成像的特异性和高对比度。然而，血 和颜料产生高内在背景信号，这显着限制了体内敏感性 检测分子和细胞目标。 这项研究将探索创新工程和纳米技术来应对这些挑战 实现具有单细胞灵敏度的非侵入性深层组织成像技术。目标1将发展非线性 用于超声成像的差频生成可提供高对比度的解剖信息。目的 2 将开发可光开关的光声纳米粒子，以实现近红外光可开关 光声成像并提供单细胞成像灵敏度。 Aim 3 将超声成像与 光切换光声成像对肿瘤淋巴结进行成像并证明目标 1 的协同作用 目标 2 获得活体深层组织高对比度解剖和分子信息的技术 科目。 在 4 年资助期结束时，该研究将生产出仪器原型和新颖的 可用于无散斑声学（解剖组织信息）、光可切换的纳米粒子 光声成像（单细胞分子和细胞信息）。预计这种新成像 技术将为获取复杂的生物分子信息提供前所未有的机会， 原生生理环境并促成许多基础生物学发现。