In Vivo Assessment of Hypoxia Levels in Pancreatic Tumors Using a Dual-Modality Ultrasound/Photoacoustic Imaging System.

Yuhling Wang,Chia-Hui Tsao,De-Fu Jhang,Lun-De Liao,Nai-Jung Chiang,Chiung-Cheng Chuang,Chia-Hua Tsai,Wun-Shaing Chang,Li-Tzong Chen

doi:10.3390/mi12060668

Abstract

Noninvasive anatomical and functional imaging has become an essential tool to evaluate tissue oxygen saturation dynamics in preclinical or clinical studies of hypoxia. Our dual-wavelength technique for photoacoustic (PA) imaging based on the differential absorbance spectrum of oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) can quantify tissue oxygen saturation using the intrinsic contrast property. PA imaging of tissue oxygen saturation can be used to monitor tumor-related hypoxia, which is a particularly relevant functional parameter of the tumor microenvironment that has a strong influence on tumor aggressiveness. The simultaneous acquisition of anatomical and functional information using dual-modality ultrasound (US) and PA imaging technology enhances the preclinical applicability of the method. Here, the developed dual-modality US/PA system was used to measure relative tissue oxygenation using the dual-wavelength technique. Tissue oxygen saturation was quantified in a pancreatic tumor mouse model. The differences in tissue oxygenation were detected by comparing pancreatic samples from normal and tumor-bearing mice at various time points after implantation. The use of an in vivo pancreatic tumor model revealed changes in hypoxia at various stages of tumor growth. The US/PA imaging data positively correlated with the results of immunohistochemical staining for hypoxia. Thus, our dual-modality US/PA imaging system can be used to reliably assess and monitor hypoxia in pancreatic tumor mouse models. These findings enable the use of a combination of US and PA imaging to acquire anatomical and functional information on tumor growth and to evaluate treatment responses in longitudinal preclinical studies.

Highlights

This article is an open access articleHypoxia is a condition present in a wide range of diseases, including stroke [1], pneumonia, cancer [2], sleep apnea [3], etc
We present a dual-modality US/PA imaging system that can be used to assess tissue oxygenation in vivo
The results demonstrated that our dual-wavelength PA technique, based on the measurement of oxygenated and deoxygenated hemoglobin, yields reliable real-time hypoxia data in vivo in an orthotopic pancreatic tumor mouse model

Summary

Introduction

This article is an open access articleHypoxia is a condition present in a wide range of diseases, including stroke [1], pneumonia, cancer [2], sleep apnea [3], etc. Optical imaging techniques, such as diffusion optical imaging (DOI) [4], were used to assess in vivo changes in tissue oxygenation. Photoacoustic (PA) imaging is a rapidly developing technology based on the optical excitation of the molecules by visible or near-infrared (NIR) range pulsed lasers, resulting in a thermoelastic effect of PA signals [4]. By utilizing intrinsic optical absorption along with US detection, PA imaging can provide multiscale resolution and deep tissue penetration [4]. Depending on the intrinsic biological optical contrast agent (i.e., blood or melanin), the PA imaging technique offers anatomical and functional information about normal and abnormal tissues and biological phenomena, such as angiogenesis and changes in SO2 and total hemoglobin concentrations [5]. Some advantages of PA are similar to the advantages of US and optical imaging, such as safety and high spatial resolution [4]

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