Improving the Specificity of Lung Cancer Diagnosis with acidoCEST MRI

Abstract

Acido-Chemical Exchange Saturation Transfer (acidoCEST) Magnetic Resonance Imaging (MRI) is a non-invasive method for creating spatial maps of the extracellular pH (pHe) in solid tissues in vivo. Cancer cells are known to export increased quantities of lactic acid into the extracellular space as a result of glycolytic metabolic processes. Localized tissue acidosis can therefore function as a cancer biomarker, and acidoCEST MRI may be an impactful tool for increasing the specificity of imaging results. My work has focused on applying acidoCEST MRI to the diagnosis of lung cancer, where low-dose CT screening tests have a false positive rate of 95%. Chapter 1 discusses recent advances in MRI for the diagnosis, prognosis and management of pulmonary disease. Chapter 2 refers to a published manuscript reprinted in Appendix A which describes a method comparison study wherein I determined that the exchange rate (kex) of amide protons quantified by endogenous CEST MRI could not serve as a proxy measurement for pHe quantified by acidoCEST MRI. Chapter 3 describes a study in which I determined that lung tumors and valley fever granulomas in preclinical murine models have significantly different pHe. Chapter 4 discusses future directions of inquiry towards diagnostic CEST MRI methods for lung cancer including: application of endogenous CEST MRI, further development of the BSL-2 compatible murine valley fever model, and potential improvements to acidoCEST MRI image acquisition and analysis methods to aid in future clinical translation.