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Proceedings Paper

Photoacoustic spectroscopic imaging of intra-tumor heterogeneity and molecular identification
Author(s): Keith M. Stantz; Bo Liu; Minsong Cao; Daniel R. Reinecke; Kathy Miller; Robert A. Kruger
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Paper Abstract

Purpose. To evaluate photoacoustic spectroscopy as a potential imaging modality capable of measuring intra-tumor heterogeneity and spectral features associated with hemoglobin and the molecular probe indocyanine green (ICG). Material and Methods. Immune deficient mice were injected with wildtype and VEGF enhanced MCF-7 breast cancer cells or SKOV3x ovarian cancer cells, which were allowed to grow to a size of 6-12 mm in diameter. Two mice were imaged alive and after euthanasia for (oxy/deoxy)-hemoglobin content. A 0.4 mL volume of 1 μg/mL concentration of ICG was injected into the tail veins of two mice prior to imaging using the photoacoustic computed tomography (PCT) spectrometer (Optosonics, Inc., Indianapolis, IN 46202) scanner. Mouse images were acquired for wavelengths spanning 700-920 nm, after which the major organs were excised, and similarly imaged. A histological study was performed by sectioning the organ and optically imaging the fluorescence distribution. Results. Calibration of PCT-spectroscopy with different samples of oxygenated blood reproduced a hemoglobin dissociation curve consistent with empirical formula with an average error of 5.6%. In vivo PCT determination of SaO2 levels within the tumor vascular was measurably tracked, and spatially correlated to the periphery of the tumor. Statistical and systematic errors associated with hypoxia were estimated to be 10 and 13%, respectively. Measured ICG concentrations determined by contrast-differential PCT images in excised organs (tumor, liver) were approximately 0.8 μg/mL, consistent with fluorescent histological results. Also, the difference in the ratio of ICG concentration in the gall bladder-to-vasculature between the mice was consistent with excretion times between the two mice. Conclusion. PCT spectroscopic imaging has shown to be a noninvasive modality capable of imaging intra-tumor heterogeneity of (oxy/deoxy)-hemoglobin and ICG in vivo, with an estimated error in SaO2 at 17% and in ICG at 0.8 μg/mL in excised tissue. Ongoing development of spectroscopic analysis techniques, probe development, and calibration techniques are being developed to improve sensitivity to both exogenous molecular probes and (oxy/deoxy)-hemoglobin fraction.

Paper Details

Date Published: 6 March 2006
PDF: 12 pages
Proc. SPIE 6086, Photons Plus Ultrasound: Imaging and Sensing 2006: The Seventh Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, 608605 (6 March 2006); doi: 10.1117/12.645106
Show Author Affiliations
Keith M. Stantz, Purdue Univ. (United States)
Indiana Univ. (United States)
Bo Liu, Purdue Univ. (United States)
Minsong Cao, Purdue Univ. (United States)
Daniel R. Reinecke, OptoSonics, Inc. (United States)
Kathy Miller, Indiana Univ. (United States)
Robert A. Kruger, OptoSonics, Inc. (United States)

Published in SPIE Proceedings Vol. 6086:
Photons Plus Ultrasound: Imaging and Sensing 2006: The Seventh Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics
Alexander A. Oraevsky; Lihong V. Wang, Editor(s)

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