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Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging: Pulse Sequence Development for Compressed Sensing Rapid Imaging and Preclinical Liver Studies

Abstract

The use of in vivo 13C nuclear magnetic resonance spectroscopy to probe metabolic pathways for the study of normal and disease physiology has traditionally been limited by low sensitivity. However, recent technological advances utilizing dynamic nuclear polarization have enabled on the order of 50,000-fold enhancement of liquid-state polarization of metabolically active 13C substrates, allowing for rapid imaging detection of their metabolism in vivo. A key design challenge, though, for this type of metabolic imaging is the rapid decay associated with the hyperpolarized signal, which necessitates fast imaging strategies for optimal speed and spatial coverage. Through this dissertation research, a new random undersampling approach--compressed sensing--was applied for the first time to hyperpolarized MR imaging. An initial blipped, random undersampling pulse sequence was developed to enable 2-fold accelerated imaging. Subsequently, enhancements to the pulse sequence were developed to achieve 7.53-fold acceleration, and the limits of undersampling with and without noise were explored in simulations. Numerous potential applications exist for hyperpolarized 13C spectroscopic imaging, among which include studying normal liver metabolism and characterizing diseased liver physiology. In this work, hyperpolarized 13C technology was used to detect a change in liver metabolic state for the first time, demonstrating decreased hyperpolarized alanine in fasted rat liver in vivo. Then in novel preclinical work, changes in hyperpolarized lactate and alanine were investigated in disease progression and regression studies with transgenic liver cancer mice, demonstrating the potential for future patient studies with hyperpolarized 13C spectroscopic imaging.

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