We propose to develop high-resolution microwave-induced thermoacoustic tomography (TAT) and laser-induced photoacoustic tomography (PAT) by adapting a clinical ultrasound imaging system. These three compatible imaging modalities share the same ultrasound detection system and provide complementary contrasts. The long-term goal is to provide a clinical tool for the early functional monitoring of breast neoadjuvant therapy (chemo- or hormone therapy). Many breast cancer patients receive neoadjuvant treatment to reduce tumor size and enable breast conserving therapy that would otherwise have not been possible. A sensitive method of detecting response to therapy might allow earlier adjustments in treatment, and thus, result in better outcomes. Furthermore, if drug choices are not resulting in response, prompt and early changes in drug regimens will alleviate some of the unnecessary morbidity that patients suffer during treatment while awaiting response to therapy. TAT/PAT is based on the generation of thermoacoustic/photoacoustic waves by the safe deposition of short-pulsed electromagnetic energy into the breast. Each microwave/laser pulse causes a rapid temperature rise on the order of 10 millidegrees. The ultrasonic emission due to thermoelastic expansion is detected with an array of ultrasonic transducers and then used to reconstruct an image. TAT and PAT are designed to overcome the poor spatial resolution of pure microwave and pure optical imaging yet to retain the high contrasts. In terms of spatial resolution, pure microwave imaging suffers from strong diffraction due to long microwave wavelength, whereas pure optical imaging suffers from strong optical scattering in tissue. Ultrasonic waves can propagate in tissue with relatively low scattering and can therefore provide good spatial resolution. The applicants have demonstrated speckle-free images at high resolution (as low as 0.5 mm). We hypothesize that the combined contrasts from TAT and PAT as well as ultrasonography can accurately predict breast neoadjuvant therapeutic response. TAT measures dominantly water/sodium contrast, whereas PAT measures blood volume and blood oxygenation contrasts.
The specific aims are as follows: 1. Development of the TAT/PAT breast imaging system. 2. Adaptation of a Philips clinical ultrasound imaging system. 3. Phantom study: Validate the proposed imaging system with tissue phantoms. 4. In vivo study: First, image a small number of human breasts to fine tune the imaging system. Second, image human breasts and perform statistical analysis retrospectively. Third, image human breasts and validate the imaging system prospectively.

Public Health Relevance

Imaging technologies have enabled numerous discoveries in biomedicine and provided early diagnosis of disease. Functional imaging that detects not only tissue structure but also tissue function will make even greater impact in biomedicine. The proposed thermoacoustic and photoacoustic imaging technologies can potentially provide a clinical tool for the early functional monitoring of breast neoadjuvant therapy (chemo- or hormone therapy).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA134539-05
Application #
8461471
Study Section
Special Emphasis Panel (ZRG1-SBIB-S (50))
Program Officer
Nordstrom, Robert J
Project Start
2009-05-01
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
5
Fiscal Year
2013
Total Cost
$508,137
Indirect Cost
$154,576
Name
Washington University
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Garcia-Uribe, Alejandro; Erpelding, Todd N; Krumholz, Arie et al. (2015) Dual-Modality Photoacoustic and Ultrasound Imaging System for Noninvasive Sentinel Lymph Node Detection in Patients with Breast Cancer. Sci Rep 5:15748
Hennen, Stella N; Xing, Wenxin; Shui, Ying-Bo et al. (2015) Photoacoustic tomography imaging and estimation of oxygen saturation of hemoglobin in ocular tissue of rabbits. Exp Eye Res 138:153-8
Li, Lei; Yeh, Chenghung; Hu, Song et al. (2014) Fully motorized optical-resolution photoacoustic microscopy. Opt Lett 39:2117-20
Liang, Jinyang; Gao, Liang; Li, Chiye et al. (2014) Spatially Fourier-encoded photoacoustic microscopy using a digital micromirror device. Opt Lett 39:430-3
Zhou, Yong; Yao, Junjie; Maslov, Konstantin I et al. (2014) Calibration-free absolute quantification of particle concentration by statistical analyses of photoacoustic signals in vivo. J Biomed Opt 19:37001
Yao, Da-Kang; Zhang, Chi; Maslov, Konstantin et al. (2014) Photoacoustic measurement of the Grüneisen parameter of tissue. J Biomed Opt 19:17007
Gao, Liang; Zhu, Liren; Li, Chiye et al. (2014) Nonlinear light-sheet fluorescence microscopy by photobleaching imprinting. J R Soc Interface 11:20130851
Yao, Junjie; Wang, Lidai; Li, Chiye et al. (2014) Photoimprint photoacoustic microscopy for three-dimensional label-free subdiffraction imaging. Phys Rev Lett 112:014302
Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang et al. (2014) Label-free photoacoustic microscopy of peripheral nerves. J Biomed Opt 19:16004
Wang, Lihong V; Gao, Liang (2014) Photoacoustic microscopy and computed tomography: from bench to bedside. Annu Rev Biomed Eng 16:155-85

Showing the most recent 10 out of 127 publications