In vivo imaging of single circulating cells

描述(由申请人提供)：拟议研究的目标是将单细胞无标记光声显微镜(PAM)转化为临床实践。在活体中，PAM已被发明用于早期癌症检测和功能、代谢或分子成像，通过物理集成光学和超声波。与电离x射线辐射不同，光会对健康造成危害，并显示出分子对比。不幸的是，光不能像X射线那样以直线路径穿透生物组织。因此，高分辨率光学成像--如共焦显微镜、双光子显微镜和光学相干断层扫描--被限制在光学扩散极限(皮肤中约1毫米)内的组织深度。PAM突破了这一限制，利用了组织中每单位路径长度的超声散射比光学散射小约1000倍的事实。它对光学吸收对比非常敏感，使其能够比荧光显微镜成像更多的分子。PAM可能是通过体内无标记量化高代谢来最早发现癌症的关键，高代谢是癌症的典型特征。这项技术的拟议立即临床转化将使单个循环细胞，特别是循环肿瘤细胞的体内成像和检测成为可能，用于癌症筛查、检测、预后和监测。对于PAM的临床翻译，我们提出了以下具体目标。目的1.用于循环单个红细胞和肿瘤细胞体内成像的高分辨率无标记PAM。目的2.高通量无标记PAM，用于单个循环肿瘤细胞(CTCs)的活体成像。

DESCRIPTION (provided by applicant): The goal of the proposed research is to translate single-cell label-free photoacoustic microscopy (PAM) into clinical practice. In vivo PAM has been invented for early-cancer detection and functional, metabolic, or molecular imaging by physically integrating optical and ultrasonic waves. Unlike ionizing x-ray radiation, light poses n health hazard and reveals molecular contrasts. Unfortunately, light does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution optical imaging-such as confocal microscopy, two-photon microscopy, and optical coherence tomography-has been restricted to tissue depths within the optical diffusion limit (~1 mm in the skin). PAM breaks through this limitation by taking advantage of the fact that ultrasonic scattering per unit path-length in tissue is ~1000 times less than optical scattering. It is exquisitely sensitive to optica absorption contrasts, enabling it to image far more molecules than fluorescence microscopy. PAM may hold the key to the earliest detection of cancer by in vivo label-free quantification of hyper-metabolism, the quintessential hallmark of cancer. The proposed immediate clinical translation of this technology will enable in vivo imaging and detection of single circulating cell, especially circulating tumor cells for cancer screening, detection, prognosis, and monitoring. We propose the following specific aims to clinically translate PAM. Aim 1. High-resolution label-free PAM for in vivo imaging of circulating single red blood and tumor cells. Aim 2. High-throughput label-free PAM for in vivo imaging of single circulating tumor cells (CTCs).