We propose to develop novel photoacoustic endoscopy by miniaturizing photoacoustic imaging probes. The primary motivation is to overcome the depth limitation of existing endoscopic imaging technologies and to provide functional information sensitive to disease states. The improved imaging capabilities have the potential for early detection of cancer in the gastrointestinal tract. In a preliminary study, we demonstrated the feasibility of photoacoustic endoscopy through in situ and ex vivo animal experiments with our endoscopic probe prototype. We will show its full endoscopic imaging potential and develop broader application through various in vivo animal and human experiments. Additionally, we will advance the current technology by constructing smaller endoscopic probes that fit into generic endoscopes and by improving overall system performance.
The specific aims of this project are as follows.
Aim 1. Develop a next-generation photoacoustic endoscope system. We will develop a next-generation photoacoustic endoscopic system and improve the image resolution, field of view, scanning speed, and probe size. We will establish the necessary supporting, peripheral subsystems including a laser source and light delivery path, a stepper motor drive, a data acquisition subsystem, and a master control of all subsystems.
Aim 2. Design and develop a piezoelectric ring probe of improved sensitivity. We will design and engineer ultrasonic transducers optimized for the proposed photoacoustic endoscope. The ultrasonic transducer is an essential component of the photoacoustic endoscopic system. The optimization of photoacoustic endoscopy depends on several transducer parameters: size, noise figure, and sensitivity.
Aim 3. Validate the endoscopic system through phantom and animal experiments. Through phantom experiments, we will validate the performance of the endoscopic system by measuring the spatial resolution, imaging depth, signal-to-noise ratio, and frame rate. Moreover, we will demonstrate its endoscopic imaging potential through various animal experiments. Parts of the gastrointestinal tract, including the esophagus, large intestine, and rectum, and/or parts of the cardiovascular system of animals, will be imaged in vivo or ex vivo.
Aim 4. Image Barrett's esophagus in vivo. First, we will image a series of human esophagus in patients with an established diagnosis of Barrett's esophagus to fine tune the photoacoustic imaging system while simultaneously obtaining mucosal biopsies of the distal esophagus. Second, we will compare the targeted photoacoustic images to the ex vivo histology of esophageal mucosal specimens to develop a classification system for photoacoustic images of Barrett's epithelium. Lastly, we will prospectively assess the agreement between the photoacoustic imaging system and standard clinical practice of 4 quadrant esophageal biopsy in a comparative study. The hypothesis is that ultrasound and photoacoustic imaging technologies in combination provide sufficient spatial resolution and contrast to diagnose Barrett's epithelium and Barrett's-associated neoplasia with high sensitivity and specificity.

Public Health Relevance

Imaging technologies have enabled numerous discoveries in biomedicine and provided early diagnosis of disease. Deep penetrating endoscopic imaging that detects lesions in the gastrointestinal tract will greatly impact healthcare. The proposed technology can potentially provide such a clinical tool.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA157277-04
Application #
8481206
Study Section
Special Emphasis Panel (ZRG1-SBIB-P (02))
Program Officer
Nordstrom, Robert J
Project Start
2010-09-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$520,663
Indirect Cost
$147,683
Name
Washington University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Tang, Min; Zhou, Yong; Zhang, Ruiying et al. (2015) Noninvasive photoacoustic microscopy of methemoglobin in vivo. J Biomed Opt 20:036007
Cash, Kevin J; Li, Chiye; Xia, Jun et al. (2015) Optical drug monitoring: photoacoustic imaging of nanosensors to monitor therapeutic lithium in vivo. ACS Nano 9:1692-8
Yang, Joon-Mo; Li, Chiye; Chen, Ruimin et al. (2015) Optical-resolution photoacoustic endomicroscopy in vivo. Biomed Opt Express 6:918-32
Yang, Joon Mo; Favazza, Christopher; Yao, Junjie et al. (2015) Three-dimensional photoacoustic endoscopic imaging of the rabbit esophagus. PLoS One 10:e0120269
Zhang, Yu Shrike; Yao, Junjie; Zhang, Chi et al. (2014) Optical-resolution photoacoustic microscopy for volumetric and spectral analysis of histological and immunochemical samples. Angew Chem Int Ed Engl 53:8099-103
Zhang, Yu Shrike; Cai, Xin; Yao, Junjie et al. (2014) Non-invasive and in situ characterization of the degradation of biomaterial scaffolds by volumetric photoacoustic microscopy. Angew Chem Int Ed Engl 53:184-8
Liang, Jinyang; Gao, Liang; Li, Chiye et al. (2014) Spatially Fourier-encoded photoacoustic microscopy using a digital micromirror device. Opt Lett 39:430-3
Yao, Junjie; Wang, Lihong V (2014) Sensitivity of photoacoustic microscopy. Photoacoustics 2:87-101
Yao, Junjie; Wang, Lihong V (2014) Photoacoustic Brain Imaging: from Microscopic to Macroscopic Scales. Neurophotonics 1:
Yao, Junjie; Gilson, Rebecca C; Maslov, Konstantin I et al. (2014) Calibration-free structured-illumination photoacoustic flowgraphy of transverse flow in scattering media. J Biomed Opt 19:046007

Showing the most recent 10 out of 81 publications