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.
| Durr, Nicholas J; Weisspfennig, Christian T; Holfeld, Benjamin A et al. (2011) Maximum imaging depth of two-photon autofluorescence microscopy in epithelial tissues. J Biomed Opt 16:026008 |
| Hoy, Christopher L; Durr, Nicholas J; Chen, Pengyuan et al. (2008) Miniaturized probe for femtosecond laser microsurgery and two-photon imaging. Opt Express 16:9996-10005 |
| Durr, Nicholas J; Larson, Timothy; Smith, Danielle K et al. (2007) Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods. Nano Lett 7:941-5 |
