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Multi-Scale Molecular Photoacoustic Tomography of Gene Expression

Cai, Xin and Li, Li and Krumholz, Arie and Guo, Zijian and Erpelding, Todd N. and Zhang, Chi and Zhang, Yu and Xia, Younan and Wang, Lihong V. (2012) Multi-Scale Molecular Photoacoustic Tomography of Gene Expression. PLoS ONE, 7 (8). Art. No. e43999. ISSN 1932-6203. PMCID PMC3428330.

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Photoacoustic tomography (PAT) is a molecular imaging technology. Unlike conventional reporter gene imaging, which is usually based on fluorescence, photoacoustic reporter gene imaging relies only on optical absorption. This work demonstrates several key merits of PAT using lacZ, one of the most widely used reporter genes in biology. We show that the expression of lacZ can be imaged by PAT as deep as 5.0 cm in biological tissue, with resolutions of ∼1.0 mm and ∼0.4 mm in the lateral and axial directions, respectively. We further demonstrate non-invasive, simultaneous imaging of a lacZ-expressing tumor and its surrounding microvasculature in vivo by dual-wavelength acoustic-resolution photoacoustic microscopy (AR-PAM), with a lateral resolution of 45 µm and an axial resolution of 15 µm. Finally, using optical-resolution photoacoustic microscopy (OR-PAM), we show intra-cellular localization of lacZ expression, with a lateral resolution of a fraction of a micron. These results suggest that PAT is a complementary tool to conventional optical fluorescence imaging of reporter genes for linking biological studies from the microscopic to the macroscopic scales.

Item Type:Article
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Wang, Lihong V.0000-0001-9783-4383
Additional Information:© 2012 Cai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received April 10, 2012; Accepted July 27, 2012; Published August 27, 2012. This work was supported in part by National Institutes of Health Grant Nos. R01 EB000712, R01 EB008085, R01 CA134539, and U54 CA136398. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. The authors have read the journal’s policy and have the following conflicts: LVW has a financial interest in Microphotoacoustics, Incorporated, and Endra, Incorporated. Todd N. Erpelding is an employee of Philips Research North America. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. The other authors have declared that no competing interests exist. The authors appreciate Prof. James Ballard’s close reading of the manuscript. Author Contributions: Conceived and designed the experiments: LL XC AK LVW. Performed the experiments: LL XC AK ZG TNE CZ. Analyzed the data: XC LL. Contributed reagents/materials/analysis tools: YZ YX. Wrote the paper: XC LL LVW.
Funding AgencyGrant Number
NIHR01 EB000712
NIHR01 EB008085
NIHR01 CA134539
NIHU54 CA136398
PubMed Central ID:PMC3428330
Record Number:CaltechAUTHORS:20160810-103931840
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Official Citation:Cai X, Li L, Krumholz A, Guo Z, Erpelding TN, et al. (2012) Multi-Scale Molecular Photoacoustic Tomography of Gene Expression. PLoS ONE 7(8): e43999. doi:10.1371/journal.pone.0043999
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:69537
Deposited By: Tony Diaz
Deposited On:10 Aug 2016 18:13
Last Modified:10 Aug 2016 18:13

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