| Magnetic resonance (MR) studies typically involve anatomical imaging. Recently, a new MR technique, functional MR imaging (fMRI) has enabled the measurement of dynamic properties such as blood oxygenation, flow and volume. Nonetheless, imaging is only a recent application of the nuclear magnetic resonance (NMR) phenomenon, which was originally utilized for spectroscopic studies. Lately, the fields of imaging and spectroscopy have evolved into a comprehensive spectroscopic imaging technique. In this thesis, both fMRI and spectroscopic imaging techniques are developed and their performance in characterizing various pathological conditions is evaluated.;In the first part of this dissertation novel stereotaxic devices were developed that can minimize movement of fully conscious rats and marmosets for several hours, without restricting respiratory or physiological functioning. Two fMRI methods, blood oxygenation level dependent (BOLD) and relative cerebral blood flow (rCBF), were used in these studies. Brain activity in response to somatosensory (rats) and olfactory (marmosets) stimulation was measured in the absence of exogenous contrast agents. In the second part of this research, a two-dimensional double-quantum-coherence (2D-DQC) pulse sequence combined with an additional water-suppression scheme was developed and optimized for spectroscopic imaging. With this method, in-vivo lactic acid (LA) concentrations in solid mouse RIF-1 tumors were imaged. All the fMRI and spectroscopic studies were performed with a 2.0 Tesla spectrometer.;fMRI in awake rats showed significant changes in evoked signal intensity. The BOLD changes ranged between 4% to 19% and rCBF changes showed significant increases in local cerebral blood flow ranging from 75% to 85%. Furthermore, the stimulus-evoked changes in BOLD signal under awake conditions (6%-25%) were considerably larger than the equivalent changes in the same animal under propofol-anesthetized conditions (1%-6%). In spectroscopic imaging studies, the optimized 2D-DQC sequence, with an additional tm modulation, filtered out all resonances interfering with the LA-methyl group. With this technique, LA maps were successfully acquired from a solid mouse RIF-1 tumor in vivo. Moreover, the LA mapping was sensitive enough to separate LA concentration in normoxic and hyperoxic conditions.;In conclusion, fMRI can be reliably performed in awake animals. The results indicate that it is advantageous to use fully conscious animals in order to maximize fMRI signal strength and monitor accurately the brain activity. Furthermore, successful imaging of brain activity in awake marmosets extends fMRI to animals with mental capabilities closer to those of humans. Overall, fMRI in awake animals has tremendous potential to identify the brain function associated with mental and cognitive processes. It can also be used to monitor progress and recovery of stroke, understand epileptic seizures, assist in presurgical mapping and evaluate the effects of neuropharmaceuticals. In the spectroscopic imaging studies, the mapping of regional LA distributions under hyperoxic and normoxic conditions was achieved in a mouse RIF-1 tumor. Oxygenation status within solid tumors before and during treatment is extremely valuable for planning therapy and predicting the outcome of cancer. The possibility to better characterize tumor metabolism can assist in therapy planning and the prediction of outcome. In general, the fMRI and spectroscopic imaging methods developed in this dissertation provide a comprehensive and reliable pre-clinical animal modeling for several severe pathological conditions noted in humans. |
