Assessments of Tumor Metabolism with CEST and DCE MRI

Abstract

This dissertation begins with a comprehensive review of the assessment of tumor metabolism highlighting the various applications of chemical exchange saturation transfer (CEST) MRI. The acidoCEST MRI technique is shown to be the imaging application suffering from the least amount of pitfalls in the quantitative assessment of tumor metabolism. Positron emission tomography (PET) and MR imaging modalities can be simultaneously and successfully synergized to study tumor metabolism during a course of a mitochondrial complex 1 inhibitor drug therapy in the treatment of pancreatic tumors in mouse models. Intramodal imaging with endogenous MRI or acidoCEST MRI and dynamic contrast-enhanced (DCE) MRI can also be sequentially performed to evaluate specific tumor biomarkers and tumor cell perfusion and uptake of gadolinium-based contrast agents or T2ex-based contrast agents in gadobenate dimeglumine (MultiHance®, Bracco Imaging Inc., Milan, Italy) and D-maltose. Machine learning-based classification of tumor models, as well as other pathological conditions, is a valid and helpul approach to CEST and DCE MR analysis. Pancreatic ductal adenocarcinoma tumor models varying in levels of hypoxia such as Hs 766T, MIA PaCa-2 and SU.86.86, have been classified using specific training classifiers on endogenous CEST MRI and DCE MRI datasets. Intramodal MR imaging has also been applied to other pathologies: namely, in imaging of bacterial infections and inflammation. Immunocompetent CBA/J mouse models of infections and MDA-MB-231 mouse models of breast cancer were injected and infused with the T2ex contrast agent D-maltose for DCE MRI. D-maltose infusion has shown to differentiate bacterially infected pathology from inflamed tissue pathology.