Improving Brain Tumor Characterization and Management Using 1H and Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging

Magnetic resonance spectroscopic imaging (MRSI) has been used for the evaluation of properties of a number of different metabolites within tissue in the body. In the case of brain tumors, 1H MRSI has been widely used due to its ability to measure metabolic profiles that are visibly altered in cancerous tissue. Recent developments in the technology required to implement dynamic nuclear polarization have enabled the acquisition of 13C MRSI data for probing cancer metabolism. The goal of this dissertation was to develop new methods for the characterization and management of brain tumors using 1H and hyperpolarized 13C MRSI. Four distinct projects are included in this dissertation. The first examines the feasibility of using combined information from 1H MRI and MRSI for radiation target definition in a retrospective study using data from patients with gliomas. The second implemented a new lactate-edited 3D 1H MRSI sequence on a 3 Tesla (T) MRI scanner in an attempt to assess lactate in patients with gliomas. The third focus evaluated the feasibility of using 13C MRSI with hyperpolarized [1-13C]-pyruvate as a substrate for the evaluation of in vivo tumor metabolism in a rat brain tumor model from a human glioblastoma xenograft. Finally, these 13C metabolic imaging techniques were used for the detection of early response to therapy in a rat brain tumor model. These projects show that the combination of MRI and 1H MRSI or hyperpolarized 13C MRSI is likely to be extremely important for targeting focal therapy and evaluating treatment effects. The specialized lactate-edited 3D 1H MRSI sequences that were used detected lactate in patients with brain tumors at both 1.5 T and 3 T, which means that brain lactate can be evaluated in a routine clinical setting to study its potential as a marker for prognosis and response to therapy. The data from hyperpolarized 13C MRSI studies indicate that metabolic imaging with hyperpolarized [1-13C]-pyruvate provides a new tool that would be valuable for clinical neuro-oncologists to use in monitoring tumor response to therapy