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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

基本信息

批准号：
10222719
负责人：
Steven Chu
金额：
$ 54.96万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-05 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10222719
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

项目摘要

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.

项目总结/摘要本研究响应PAR-17-045“重点技术研究和开发” 建议开发一种非侵入性的、具有单细胞灵敏度的深层组织成像技术，超声和光声成像。超声成像利用声波来提供组织的解剖信息，并且提供了许多理想的特性-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，显著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的超声发射。它结合了光谱- 基于在深层组织位置（~几厘米）的光学成像的特异性和高对比度。不过血和色素产生高的固有背景信号，这显著限制了在体内的灵敏度，检测分子和细胞目标。这项研究将探索创新的工程和纳米技术，以解决这些挑战，使非侵入性，深层组织成像技术与单细胞灵敏度。目标1将发展非线性用于超声成像的差频生成，以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，光声成像并提供单细胞成像灵敏度。Aim 3将把超声成像与光可切换光声成像对肿瘤淋巴结进行成像并证明Aim 1的协同作用和Aim 2技术在活体深部组织中获得高对比度解剖和分子信息科目在4年的资助期结束时，该研究将产生一个仪器原型和新颖的可用于无斑点声学（解剖组织信息）、光可切换光声成像（单细胞分子和细胞信息）。预计这种新的成像技术技术将提供前所未有的机会，自然的生理环境，使许多基本的生物学发现。