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New Technology Developments for Metabolic Imaging of the Human Abdomen using Hyperpolarized [1-13C]pyruvate

Abstract

Hyperpolarized (HP) 13C magnetic resonance imaging (MRI) is a novel imaging modality that is powerful in its ability to elucidate in vivo human metabolism in a safe, non-invasive manner without ionizing radiation. This can be carried out by using molecular probes such as [1-13C]pyruvate, a molecule of much clinical interest because of its crucial metabolic position. Pyruvate is used in both oxidative phosphorylation and aerobic glycolysis, with the latter pathway being upregulated in cancers due to metabolic reprogramming. Thus, investigating how pyruvate is metabolized in a given tissue can provide researchers and clinicians with a window into the tissue’s metabolic characteristics, such as whether or not it is metabolically behaving in a cancerous manner after chemotherapy. High signal-to-noise ratios (SNR) is achieved through dissolution dynamic nuclear polarization. Upon injection of a solution of hyperpolarized [1-13C]pyruvate, one can acquire dynamic metabolic images and spectroscopic data in the human body with remarkable resolution.HP 13C MRI has found much success for research imaging studies of the brain, prostate, and other organs. This dissertation focuses on new technology developments that I developed to enable the translation of this technology into human abdominal organs, both in cancerous and healthy states. These developments aim to address several challenges including main magnetic field (B0) and transmit magnetic field (B1+) inhomogeneities, low SNR, broad spatial coverage, and fast acquisition techniques. A clinical feasibility study using HP 13C MRI for metastatic prostate cancer tumors demonstrates the promise and feasibility of this imaging modality in quantitating in vivo metabolism. Additionally, a whole-abdomen metabolic imaging approach enabled the characterization of healthy metabolism in the human liver, kidneys, pancreas, and spleen, laying the foundation for designing future investigations of cancer and metabolic diseases in the abdomen.

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