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Validating Hemoglobin Saturation and Dissolved Oxygen in Tumors Using Photoacoustic Computed Tomographic Spectroscopic Imaging

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J Sick

J Burnett1 , J Sick1*, N Cao3 , B Liu1 , H Nakshatri2 , M Mendonca2 , K Stantz1,2 , (1) Purdue University, West Lafayette, Indiana,(2) Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, (3) University of Washington Medical Center, Seattle, WA,


TH-AB-209-5 (Thursday, August 4, 2016) 7:30 AM - 9:30 AM Room: 209

Purpose: Photoacoustic computed tomographic spectroscopy (PCT-S) provides intra-tumor measurements of oxygenation with high spatial resolution (0.2mm) and temporal fidelity (1-2 minutes) without the need for exogenous agents or ionizing radiation, thus providing a unique in vivo assay to measure SaO₂ and investigate acute and chronic forms of hypoxia. The goal of this study is to validate in vivo SaO₂ levels within tail artery of mice and the relationship between SaO₂ and pO₂ within subcutaneous breast tumors using PCT-S imaging, pulse oximetry and an OxyLite probe.

Methods: A closed circuit phantom was fabricated to control blood oxygenation levels, where SaO₂ was measured using a co-oximeter and pO₂ using an Oxylite probe. Next, SaO₂ levels within the tail arteries of mice (n=3) were measured using PCT-S and pulse oximetry while breathing high-to-low oxygen levels (6-cycles). Finally, PCT-S was used to measure SaO₂ levels in MCF-7, MCF-7-VEGF165, and MDA-MB-231 xenograft breast tumors and compared to Oxylite pO₂ levels values.

Results: SaO₂ and pO₂ data obtained from the calibration phantom was fit to Hill’s equation: P50=23.2mmHg and Hill’s constant(n)=2.26. Cycling of the tail artery SaO₂ levels between 88 and 52% demonstrated a linear relationship (r2=0.96) and a 3.2% uncertainty between PCT-S values relative to pulse oximetry. Scatter plots of localized PCT-S measured SaO2 and Oxylite pO₂ levels in MCF-7/MCF7-VEGF165 and MDA-MD-231 breast tumors were fit to Hill’s equation: P50=17.2 and 20.7mmHg, and n=1.76 and 1.63. These results are consistent with sigmoidal form of Hill’s equation, where the lower P₅₀ value is indicative of an acidic tumor microenvironment.

Conclusion: The results demonstrate photoacoustic imaging can be used to measure SaO₂ cycling and intra-tumor oxygenation, and provides a powerful in vivo assay to investigate the role of hypoxia in radiation, anti-angiogenic, and immunotherapies.

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