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).

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA186567-02
Application #
8739639
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Nordstrom, Robert J
Project Start
2013-09-23
Project End
2018-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington University
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Liu, Yan; Shen, Yuecheng; Ma, Cheng et al. (2016) Lock-in camera based heterodyne holography for ultrasound-modulated optical tomography inside dynamic scattering media. Appl Phys Lett 108:231106
Zhou, Yong; Liang, Jinyang; Wang, Lihong V (2016) Cuffing-based photoacoustic flowmetry in humans in the optical diffusive regime. J Biophotonics 9:208-12
Lin, Li; Yao, Junjie; Li, Lei et al. (2016) In vivo photoacoustic tomography of myoglobin oxygen saturation. J Biomed Opt 21:61002
Yao, Junjie; Kaberniuk, Andrii A; Li, Lei et al. (2016) Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe. Nat Methods 13:67-73
Yao, Junjie; Xia, Jun; Wang, Lihong V (2016) Multiscale Functional and Molecular Photoacoustic Tomography. Ultrason Imaging 38:44-62
Gao, Liang; Wang, Lihong V (2016) A review of snapshot multidimensional optical imaging: measuring photon tags in parallel. Phys Rep 616:1-37
Hai, Pengfei; Yao, Junjie; Li, Guo et al. (2016) Photoacoustic elastography. Opt Lett 41:725-8
Ma, Jun; Shi, Junhui; Hai, Pengfei et al. (2016) Grueneisen relaxation photoacoustic microscopy in vivo. J Biomed Opt 21:66005
Hemphill, Ashton S; Tay, Jian Wei; Wang, Lihong V (2016) Hybridized wavefront shaping for high-speed, high-efficiency focusing through dynamic diffusive media. J Biomed Opt 21:121502
Shen, Yuecheng; Liu, Yan; Ma, Cheng et al. (2016) Focusing light through biological tissue and tissue-mimicking phantoms up to 9.6 cm in thickness with digital optical phase conjugation. J Biomed Opt 21:85001

Showing the most recent 10 out of 57 publications