Noninvasive deep-tissue single-cell imaging and nanoprobe development

项目摘要/摘要 本研究响应PAR-17-045《重点技术研究与开发》 建议开发一种具有单细胞灵敏度的非侵入性、深部组织成像技术，基于 超声波和光声成像。 超声成像使用声波来提供组织的解剖信息，并提供了许多 理想的特点--快速、实时成像、低成本、深层组织渗透、高空间分辨率和 不暴露在电离辐射中。然而，显著斑点噪声的存在极大地损害了 成像质量和分辨率。光声成像采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波发射。它结合了光谱- 基于深部组织位置的光学成像的特异性和高对比度(~几厘米)。然而，血液 而色素产生高本底信号，这显著限制了体内对 探测分子和细胞目标。 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将发展成非线性 用于超声成像的差频产生以提供高对比度的解剖信息。目标 2将开发可光敏的光声纳米颗粒，使近红外光开关成为可能 光声成像，并提供单细胞成像灵敏度。AIM 3将把超声成像与 光开关光声成像对肿瘤淋巴结的成像和AIM-1的协同作用 和Aim 2在生命深层组织中获取高对比度的解剖和分子信息的技术 研究对象。 在四年的资助期结束时，这项研究将产生一个仪器原型和新的 可用于无斑点声学(解剖组织信息)、可光切换的纳米颗粒 光声成像(单细胞分子和细胞信息)。预计这种新的成像技术 技术将为获取复杂生物分子的信息提供前所未有的机会， 原生的生理环境，并使许多基本的生物学发现。

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.