Evaluating dynamic contrast-enhanced and photoacoustic CT to assess intra-tumor heterogeneity in xenograft mouse models

Keith M. Stantz; Bo Liu; Minsong Cao; Dan Reinecke; Mario Dzemidzic; Yun Liang; Robert Kruger

doi:10.1117/12.654056

20 March 2006 Evaluating dynamic contrast-enhanced and photoacoustic CT to assess intra-tumor heterogeneity in xenograft mouse models

Keith M. Stantz, Bo Liu, Minsong Cao, Dan Reinecke, Mario Dzemidzic, Yun Liang, Robert Kruger

Author Affiliations +

Proceedings Volume 6143, Medical Imaging 2006: Physiology, Function, and Structure from Medical Images; 61431F (2006) https://doi.org/10.1117/12.654056
Event: Medical Imaging, 2006, San Diego, California, United States

Abstract

Purpose: To evaluate photoacoustic CT spectroscopy (PCT-S) and dynamic contrast-enhanced CT (DCE-CT) ability to measure parameters - oxygen saturation and vascular physiology - associated with the intra-tumor oxygenation status. Material and Methods: Breast (VEGF165 enhance MCF-7) and ovarian (SKOV3x) cancer cells were implanted into the fat pads and flanks of immune deficient mice and allowed to grow to a diameter of 8-15 mm. CT was used to determine physiological parameters by acquiring a sequence of scans over a 10 minute period after an i.v. injection of a radio-opaque contrast agent (Isovue). These time-dependent contrast-enhanced curves were fit to a two-compartmental model determining tumor perfusion, fractional plasma volume, permeability-surface area produce, and fractional interstitial volume on a voxel-by-voxel basis. After which, the tumors were imaged using photoacoustic CT (Optosonics, Inc., Indianapolis, IN 46202). The near infrared spectra (700-910 nm) within the vasculature was fit to linear combination of measured oxy- and deoxy-hemoglobin blood samples to obtain oxygen saturation levels (SaO₂). Results: The PCT-S scanner was first calibrated using different samples of oxygenated blood, from which a statistical error ranging from 2.5-6.5% was measured and a plot of the hemoglobin dissociation curve was consistent with empirical formula. In vivo determination of tumor vasculature SaO₂ levels were measurably tracked, and spatially correlated to the periphery of the tumor. Tumor depend variations in SaO₂ - 0.32 (ovarian) and 0.60 (breast) - and in vascular physiology - perfusion, 1.03 and 0.063 mL/min/mL, and fractional plasma volume, 0.20 and 0.07 - were observed. Conclusion: Combined, PCT-S and CED-CT has the potential to measure intra-tumor levels of tumor oxygen saturation and vascular physiology, key parameters associated with hypoxia.

Citation Download Citation

Keith M. Stantz, Bo Liu, Minsong Cao, Dan Reinecke, Mario Dzemidzic, Yun Liang, and Robert Kruger "Evaluating dynamic contrast-enhanced and photoacoustic CT to assess intra-tumor heterogeneity in xenograft mouse models", Proc. SPIE 6143, Medical Imaging 2006: Physiology, Function, and Structure from Medical Images, 61431F (20 March 2006); https://doi.org/10.1117/12.654056

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