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).
Imaging technologies enable numerous discoveries in biomedicine and provide early diagnosis of disease. Single-cell imaging that detects not only tissue structure but also tissue function as well as circulating tumor cells will make even greater impact in biomedicine. The proposed single-cell label-free imaging can potentially detect metastases at an early stage, identify tumor margins accurately, and monitor tumor response to therapy. Thus, it may facilitate earlier therapeutic interventions and curative surgical treatment, and improve survival of cancer patients.
|Lin, Li; Hu, Peng; Shi, Junhui et al. (2018) Single-breath-hold photoacoustic computed tomography of the breast. Nat Commun 9:2352|
|Hsu, Hsun-Chia; Li, Lei; Yao, Junjie et al. (2018) Dual-axis illumination for virtually augmenting the detection view of optical-resolution photoacoustic microscopy. J Biomed Opt 23:1-7|
|Li, Lei; Shemetov, Anton A; Baloban, Mikhail et al. (2018) Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo. Nat Commun 9:2734|
|Imai, Toru; Shi, Junhui; Wong, Terence T W et al. (2018) High-throughput ultraviolet photoacoustic microscopy with multifocal excitation. J Biomed Opt 23:1-6|
|Yao, Junjie; Wang, Lihong V (2018) Recent progress in photoacoustic molecular imaging. Curr Opin Chem Biol 45:104-112|
|Liu, Xiaowei; Wong, Terence T W; Shi, Junhui et al. (2018) Label-free cell nuclear imaging by Grüneisen relaxation photoacoustic microscopy. Opt Lett 43:947-950|
|Hemphill, Ashton S; Shen, Yuecheng; Hwang, Jeeseong et al. (2018) High-speed alignment optimization of digital optical phase conjugation systems based on autocovariance analysis in conjunction with orthonormal rectangular polynomials. J Biomed Opt 24:1-11|
|Zhang, Pengfei; Li, Lei; Lin, Li et al. (2018) High-resolution deep functional imaging of the whole mouse brain by photoacoustic computed tomography in vivo. J Biophotonics 11:|
|Cai, De; Wong, Terence T W; Zhu, Liren et al. (2018) Dual-view photoacoustic microscopy for quantitative cell nuclear imaging. Opt Lett 43:4875-4878|
|Yang, Jiamiao; Shen, Yuecheng; Liu, Yan et al. (2017) Focusing light through scattering media by polarization modulation based generalized digital optical phase conjugation. Appl Phys Lett 111:201108|
Showing the most recent 10 out of 88 publications