Quantification of hemoglobin concentration and oxygen saturation in phantom and animal model using photoacoustic computed tomography spectroscopy scanner

Bo Liu, Purdue University

Abstract

Purpose: The objective of this study is to develop the calibration and analytical methodologies necessary to quantify the hemoglobin status (C tHb and SaO2) within xenograft tumor models using photoacoustic computed tomography (PCT) imaging modailty. Material and Methods: In this thesis, a step-wise approach is performed to develop, quantify, and validate CtHb and SaO2 measurements using photoacoustic methods. These three steps include developing a calibration phantom, utilizing and validating these techniques in-vivo, and finally performing a study to quantify the hemoglobin status of solid tumors in breast cancer xenograft mouse models. Through the formation of a novel phantom mimicking an arterial blood vessel, the hemoglobin concentration and oxygen saturation levels can be varied over a wide range of values consistent with tissue physiology. The data obtained from this phantom are used to calculate a physical parameter we dubbed kappa (κ), which represents the efficiency at which a molecule converts optically absorbed energy into an acoustic signal. This constant defines the thermoacoustic properties needed to quantify the near infrared (NIR) optical absorption of hemoglobin based on the 3-D reconstructed PCT intensities of the blood phantom. A key component of this analysis is with the development of a Monte Carlo Simulation Code to compute the photon propagation and the local energy deposition within the phantom or tissue. Based on the measurements of these constants and the development of spectroscopic analytical methods, a range of hemoglobin concentrations and oxygen saturation levels are compared to co-oximeter values (Gold Standard), and their uncertainties determined. This quantification method is then used to measure the hemoglobin status of the aterial and venous blood vessel in the tail of an athymic nude mouse. These PCT-S measurements are also compared to Gold Standard techniques, co-oximeter and pulse-oximetry. Finally, three different breast cancer xenograft mouse models (MCF-7, MCF-7/VEGF, and MDA-MB-231) are acquired using PCT spectroscopic methods to calculate the CtHb and SaO2 parametric maps using the analytical techniques previous developed. The vascular heterogeneous features of three tumor models are are compared with direct pO2 measurements by inserting an oxygen sensing probe (Gold Standard) into the tumor. Results: The calibrated Kappa value for hemoglobin molecule in blood (e.g., red blood cells) is (1.89± 0.043)×1011 pu/J (pu is photoacoustic unit) with a 2.3% statistic error. This results in an 0.12g/dL uncertainty for CtHb and 2.3% for SaO2, both values are within the uncertainty of hospital co-oximeter. In-vivo mouse tail PCT measurement shows an acceptable CtHb result compared with the ex-vivo co-oximeter measurements. PCT spectroscopy results are also validated when compared to measurements obtained from a small animal pulsed oximeter, which monitors the oxygen saturation change in the artery. PCT-S can also detect changes in the oxygen saturation level in the tail vessels of mice after adjusting the oxygen-to-nitrogen ratio the mouse breaths. Finally, PCT spectroscopic scans acquired in three types of breast tumors demonstrate differing patterns of CtHb and SaO2 both in their magnitude and spatial heterogeneity, which is consistent with oxygen probe measurements. Conclusion: This study has developed the methods necessary to provide an absolute quantification of the hemoglobin status in blood phantoms, in vivo mouse tail, and tumors using PCT spectroscopy. Monitoring the hemoglobin status and the local and temporal changes of these parameters in a tumor using PCT spectroscopy offers a novel in vivo tool in cancer research.

Degree

Ph.D.

Advisors

Stantz, Purdue University.

Subject Area

Biochemistry|Medical imaging|Oncology

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