Photoacoustic monitoring of tumor and normal tissue response to radiation.

Laurie J Rich,Mukund Seshadri

doi:10.1038/srep21237

Abstract

Hypoxia is a recognized characteristic of tumors that influences efficacy of radiotherapy (RT). Photoacoustic imaging (PAI) is a relatively new imaging technique that exploits the optical characteristics of hemoglobin to provide information on tissue oxygenation. In the present study, PAI based measures of tumor oxygen saturation (%sO2) were compared to oxygen-enhanced magnetic resonance imaging (MRI) measurements of longitudinal relaxation rate (R1 = 1/T1) and ex-vivo histology in patient derived xenograft (PDX) models of head and neck cancer. PAI was utilized to assess early changes (24 h) in %sO2 following RT and chemoRT (CRT) and to assess changes in salivary gland hemodynamics following radiation. A significant increase in tumor %sO2 and R1 was observed following oxygen inhalation. Good spatial correlation was observed between PAI, MRI and histology. An early increase in %sO2 after RT and CRT detected by PAI was associated with significant tumor growth inhibition. Twenty four hours after RT, PAI also detected loss of hemodynamic response to gustatory stimulation in murine salivary gland tissue suggestive of radiation-induced vascular damage. Our observations illustrate the utility of PAI in detecting tumor and normal tissue hemodynamic response to radiation in head and neck cancers.

Highlights

Hypoxia is a major cause of resistance to radiotherapy (RT) and a well-documented prognostic factor in solid tumors including head and neck squamous cell carcinomas (HNSCC)[1,2]
We first compared Photoacoustic imaging (PAI) measures of tumor oxygen saturation (%SO2) with oxygen-enhanced magnetic resonance imaging (OE-MRI), a non-invasive imaging technique that is currently being examined as a biomarker of tumor oxygenation in patients[17]
Experimental studies were conducted in patient-derived xenograft (PDX)-HNSCC to examine tumor response to hyperoxia using PAI and OE-MRI

Summary

Introduction

Hypoxia is a major cause of resistance to radiotherapy (RT) and a well-documented prognostic factor in solid tumors including head and neck squamous cell carcinomas (HNSCC)[1,2]. Studies of hypoxia involved the use of oxygen-sensitive polarographic electrodes to measure the partial pressure of oxygen (pO2) in tumors[2,3] While this method is sensitive, it is invasive and limited in providing spatial information on oxygenation levels throughout the tumor. Non-invasive imaging methods offer the potential to longitudinally monitor dynamic temporal changes occurring within the tumor microenvironment and allow us to map the spatial heterogeneity in tumor oxygenation[4] Conventional imaging methods such as magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) have been utilized to study tumor vascularity and oxygenation in animal models and in patients[5,6]. For the first time, that PAI can detect early changes in oxygenation of tumor and normal tissues following radiation

Methods

Results

Conclusion