Magnetic Resonance Techniques in the Study of Physiology and Metabolism.

Magnetic resonance can be used to explore functional properties of organs and tissues in addition to their anatomic structure. This work addresses the application of nuclear magnetic resonance (NMR) to studies of renal function and of intermediary metabolism. The most clinically useful measure of renal function is glomerular filtration rate (GFR). This is the rate at which plasma is filtered from the vascular space into the urinary space of the kidney. In this work, a previously proposed method to measure single-kidney GFR using gadolinium-based contrast agents is implemented and analyzed. The method relies on measurement of longitudinal relaxation time (T1) in flowing blood. Through simulation and phantom studies, several possible sources of error in T1 estimation and their impact on GFR calculations are explored. Intermediary metabolism is critical to many aspects of cellular and organ function because of its roles in energy utilization and storage, amino acid synthesis, and DNA synthesis. Carbon 13 (13C) nuclear magnetic resonance spectroscopy can be useful in probing metabolic pathways because of the ability to distinguish metabolites on the basis of their chemical shifts. This work focuses on NMR techniques for the study of metabolism with 13C. First, a method to study metabolism of prostate cancer cells in primary culture is developed using 13C3 labeled pyruvate as a metabolic substrate and observing incorporation of the label into downstream metabolites lactate, alanine, glutamate and aspartate. The results demonstrate highly reproducible metabolite enrichments and suggest the possibility of in vitro metabolic characterization of normal and neoplastic cells, as well as potential usefulness in in vivo studies. A second technique focuses on the use of 13C spectroscopy to characterize tissue in vivo. In vivo 13C spectroscopy has been limited by the low sensitivity of the 13C nucleus, which results from its small gyromagnetic ratio and low natural abundance. Recently, however, hyperpolarization of the 13C nucleus has been demonstrated with an increase in sensitivity of four to five orders of magnitude over thermal equilibrium studies. The possibility of observing in vivo real-time metabolism has been demonstrated with hyperpolarized 13C1 pyruvate, with metabolism to 13C 1 lactate, 13C1 alanine, and 13C bicarbonate. Fast spectroscopic imaging is required because the hyperpolarized signal decays with T1. Other motivations for fast imaging include monitoring of bolus dynamics, metabolism in flowing blood, and myocardial metabolism. In this work, a method taking advantage of the sparse spectrum associated with metabolism of hyperpolarized 13C 1 pyruvate is developed. Using a least squares approach and minimizing an appropriate cost function, choice of imaging pulse sequence, imaging parameters, and imaging duration can be optimized. Spiral chemical shift imaging is shown to offer advantages over other methods in obtaining metabolic images in as fast as 70 milliseconds. The technique is implemented in a phantom containing 13C labelled metabolites and shown to produce image quality in 70 milliseconds comparable to that of a reference pulse sequence that would require 15 seconds of imaging time. In addition, a second reconstruction technique is demonstrated to allow for incorporation of main magnetic field inhomogeneity into the reconstruction while maintaining the rapid imaging time.