Simultaneous imaging of a lacZ-marked tumor and microvasculature morphology in vivo by Dual-wavelength photoacoustic microscopy

Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA 63130.
Journal of innovative optical health sciences 10/2008; 1(2):207-215. DOI: 10.1142/S1793545808000212
Source: PubMed


Photoacoustic molecular imaging, combined with the reporter-gene technique, can provide a valuable tool for cancer research. The expression of the lacZ reporter gene can be imaged using photoacoustic imaging following the injection of X-gal, a colorimetric assay for the lacZ-encoded enzyme β-galactosidase. Dual-wavelength photoacoustic microscopy was used to non-invasively image the detailed morphology of a lacZ-marked 9L gliosarcoma and its surrounding microvasculature simultaneously in vivo, with a superior resolution on the order of 10 μm. Tumor-feeding vessels were found, and the expression level of lacZ in tumor was estimated. With future development of new absorption-enhancing reporter-gene systems, we anticipate this strategy can lead to a better understanding of the role of tumor metabolism in cancer initiation, progression, and metastasis, and in its response to therapy.

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Available from: Konstantin Maslov
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    • "In many scenarios however, such as the detection of early stage tumors, an endogenous contrast agent alone is insufficient to provide enough information. In these cases, optimized exogenous contrast agents were employed to provide better signal/contrast for photoacoustic imaging [3] [4] [5] [6] [7] [8] [9] [10]. However, in order to capture high resolution images of a tumor in deep tissue, the availability of an effective contrast agent is essential. "
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    • "None of the current mainstream molecular imaging modalities can visualize gene expression at both microscopic and macroscopic levels. Previous works have suggested a new approach to imaging gene expression in vivo using photoacoustic tomography (PAT) based on optical absorption [7], [8], [9]. In our previous work, a single-scale single−/dual-wavelength photoacoustic system was used to non-invasively and simultaneously image the morphology of a lacZ-marked 9 L gliosarcoma and its surrounding microvasculature in vivo [7], [8]. "
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    ABSTRACT: 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.
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