Development of Fast-scanning Hyperspectral Optical-resolution Photoacoustic Microscopy

Description

Metastasis is the spread of cancer cells to new areas of the body via blood or lymphatic circulations. Majority of cancer deaths are related to metastasis. Study of tumor metastasis mechanism can provide guidance and useful information to cancer diagnosis, staging, treatment, and drug development. Previous research has shown that local functional parameters play important roles in tumor growth and metastasis. In vivo high-resolution imaging of the dynamic process of tumor cell spreading into or extravasating from blood or lymphatic vessels, as well as quantification of the local functional parameters, may offer comprehensive information to the study of tumor metastasis. For example, such new imaging capability may uncover the relationship between the local oxygen supply and the tumor cell shedding rate, or may be used to test new cancer drugs. Optical-resolution photoacoustic microscopy (OR-PAM) is an emerging high-resolution functional imaging technique. In the past decade, OR-PAM has demonstrated in vivo imaging of total hemoglobin concentration, blood flow, oxygen saturation, metabolic rate of oxygen, and imaging labeled or non-labeled tumor cells in both shallow and deep tissues. However, due to slow imaging speed, OR-PAM imaging of the dynamic process of tumor metastasis have not been reported. In addition, OR-PAM has not demonstrated simultaneously imaging of the anatomical, functional, metabolic parameters with both high speed and large field of view. Most existing OR-PAM techniques require multiple times of scanning to measure different parameters, making it challenging to record multiple contrasts in real time. This proposal aims at developing high-speed multi-contrast OR-PAM based on a frequency-encoded broad-spectrum laser and a fast polygon scanner, to meet the need in realtime imaging of tumor metastasis in its microenvirment. To achieve this goal, two major technical challenges, slow imaging speed and narrow optical spectrum, will be addressed. A fast multi-wavelength pulsed laser and a fast polygon scanning technique will be developed for OR-PAM. To simultaneously image multiple contrasts, the proposed OR-PAM system will sequentially acquire multiple photoacoustic signals over a broad optical spectrum at each scanning spot. Fast water-immersible polygon scanner will offer up to 3 kHz cross-sectional imaging speed. The new OR-PAM system will be demonstrated in visualizing and quantifying the melanoma tumor metastasis process in vivo. The proposed research provide a new tool in the study of tumor metastasis mechanism, as well as other applications such as high-speed multi-contrast hemodynamic imaging in the brain.