Early Cancer Detection with Two-Photon Luminescence From Gold Nanorods

描述(由申请人提供)： 近红外(NIR)波长的双光子成像是一种强大的工具，它能够以标准组织学的分辨率和细节研究厚重的人体组织样本的拓扑和分子信息，而不需要外部荧光团。这项技术可以提供非常高灵敏度的非侵入性成像，使其成为体内诊断和检测癌前病变的极佳候选者。使用近红外波长的超短激光脉冲，我们可以激发特定的细胞内和细胞外分子和荧光团，如黄素、弹性蛋白和NADH。这些分子的激发使组织形态、细胞新陈代谢和分子途径能够直接可视化。本研究项目的目标是使用金纳米棒作为造影剂来增强双光子信号和相关的成像深度，以表征和检测体内肿瘤病变的形态和化学变化。具体地说，我们将使用金纳米棒的强双光子发光(TPL)特性来增强组织深处肿瘤细胞的TPM成像的图像对比度。此外，金纳米棒的大近场散射特性将被用来增强来自本征荧光团的双光子自发荧光(TPAF)信号。增强的双光子信号将提供与使用有机染料的双光子成像一样低的平均功率。在接下来的几年里，我们设想开发一种新的成像方式，称为“等离子体双光子成像”，可以更好地描绘肿瘤。这项研究旨在补充正在进行的开发一种微型内窥镜探头的工作，该探头能够同时在体内成像生化和形态变化，以便更好地描绘癌前病变。这种工具可以作为一种非侵入性且经济有效的筛查和诊断技术。

DESCRIPTION (provided by applicant): Two-photon imaging at near-infrared (NIR) wavelengths is a powerful tool that permits the investigation of the topology and molecular information of thick human tissue samples with the resolution and detail of standard histology without the need for extrinsic fluorophores. This technique can provide non-invasive imaging with very high sensitivity making it an excellent candidate for in vivo diagnosis and detection of precancerous lesions. Using ultrashort laser pulses at NIR wavelengths, we can excite specific intracellular and extracellular molecules and fluorophores such as flavins, elastin, and NADH. Excitation of these molecules enables direct visualization of tissue morphology, cell metabolism, and molecular pathways. The goal of this research project is to enhance two photon signal and the associated imaging depth using gold nanorods as contrast agents for the characterization and detection of in vivo morphological and chemical changes in tumor lesions. Specifically, we will use strong two photon luminescence (TPL) properties of gold nanorods to enhance image contrast in TPM imaging of tumor cells deep in the tissue. In addition, the large near-field scattering properties of gold nanorods will be used enhance the signal of two photon autofluorescence (TPAF) from intrinsic fluorophores. The enhanced two-photon signal will provide imaging with average powers as low as those used in two photon imaging with organic dyes. Over the next few years, we envision developing a new imaging modality called "plasmonic two-photon imaging" that can provide better delineation of tumors. This study is designed to complement ongoing work for the development of a miniaturized endoscopic probe capable of simultaneously imaging in vivo both biochemical and morphological changes, for the better delineation of precancerous lesions. Such a tool can be employed as a noninvasive and cost effective screening and diagnostic technique.