Noninvasive deep-tissue single-cell imaging and nanoprobe development

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。

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.