Development of multifunctional Overhauser-enhanced magnetic resonance imaging for concurrent in vivo mapping of tumor interstitial oxygenation, acidosis and inorganic phosphate concentration

Artem A Gorodetskii,Timothy D Eubank,Andrey A Bobko,Benoit Driesschaert,Valery V Khramtsov,Martin Poncelet,Emily Ellis

doi:10.1038/s41598-019-48524-3

Abstract

Tumor oxygenation (pO2), acidosis (pH) and interstitial inorganic phosphate concentration (Pi) are important parameters of the malignant behavior of cancer. A noninvasive procedure that enables visualization of these parameters may provide unique information about mechanisms of tumor pathophysiology and provide clues to new treatment targets. In this research, we present a multiparametric imaging method allowing for concurrent mapping of pH, spin probe concentration, pO2, and Pi using a single contrast agent and Overhauser-enhanced magnetic resonance imaging technique. The developed approach was applied to concurrent multifunctional imaging in phantom samples and in vivo in a mouse model of breast cancer. Tumor tissues showed higher heterogeneity of the distributions of the parameters compared with normal mammary gland and demonstrated the areas of significant acidosis, hypoxia, and elevated Pi content.

Highlights

Solid tumors develop a tissue microenvironment profile significantly different from parent healthy tissue
Noninvasive in vivo multifunctional mapping of tumor microenvironment (TME) parameters such as pO2, pH and phosphate concentration (Pi) may provide a unique insight into understanding mechanisms of tumor pathophysiology and become a useful tool for the development of new therapeutic approaches
We present a multiparametric imaging method for concurrent visualization of spin probe concentration, pO2, extracellular pH, Pi, and anatomical structure using single contrast agent and OMRI technique

Summary

Introduction

Solid tumors develop a tissue microenvironment profile significantly different from parent healthy tissue. Magnetic resonance imaging (MRI) is one of the most successful techniques for anatomical tissue characterization, including tumor neoplasm detection. In contrast to MRI, electron paramagnetic resonance (EPR) techniques are unsuitable for anatomical tissue characterization because of strict reliance on exogenous probes. The double resonance imaging technique, Overhauser MRI (OMRI), combines advantages of both approaches allowing for concurrent anatomical tissue imaging and multifunctional mapping of tissue physiological parameters[25,26,27,28,29]. The variation of EPR saturation power or EPR frequency value allows for measurement of different analytes in solution (e.g., oxygen, pH et cet.)[25]. We present the development of a multifunctional OMRI technique using a monophosphonated trityl probe for concurrent mapping of several functional parameters, namely pO2, pH, Pi, and spin probe concentration

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Conclusion