Applications of proton magnetic resonance spectroscopic imaging in radiation therapy of malignant glioma

Diagnosis and treatment of neoplasms of the brain has remained a challenge to the clinician. Magnetic resonance spectroscopic imaging (MRSI) has been used to visualize spatial metabolic relationships in addition to conventional anatomic imaging. In this thesis project, MRSI was used to evaluate and improve current pre- and post-radiation therapy diagnostic procedures for patients with malignant glioma.; Spectroscopic imaging data were acquired from brain tumor patients before and after treatment with either focal radiosurgery and external beam radiotherapy. Existing techniques were used to acquire and reconstruct MRSI data, while techniques for simultaneously registering and analyzing imaging, spectroscopy, and radiation dose information were developed as part of this thesis project.; To assess the utility of including MRSI data in the radiation treatment planning process, the relationship of patient outcome to the extent to which the pre-treatment spectroscopic abnormality was irradiated was determined statistically for patients undergoing Gamma Knife (GK) radiosurgery. It was found that patients with tumor-suggestive spectral voxels outside the radiosurgical target had poorer changes in contrast enhancing volume, times-to-further-treatment, and survival times relative to patients whose tumor-suggestive voxels were restricted to the radiation target.; Methods for viewing four-dimensional spectroscopic imaging data within the radiotherapy planning environment were developed in conjunction with radiation oncologists and neurooncologists. The reproducibility of these techniques was verified, and they were used to plan radiation therapies to target regions of spectroscopic interest.; The response of gliomas and surrounding brain tissue to radiation was assessed using MRSI. Reductions in metabolite levels within the radiation target were observed within six months of Gamma Knife treatment. Tumor recurrence was observed through increased choline and reduced NAA levels, most commonly prior to radiologically-evident tumor progression. A number of spectral response patterns were identified in patients who received fractionated radiotherapy. The correlation of these patterns with anatomy and with dose suggests that they represent cellular radiation damage and in some cases subsequent repair.; The results presented here demonstrate the utility of magnetic resonance spectroscopic imaging in the evaluation of malignant glioma before and after radiotherapy, and encourage further use of the technique in the clinic as well as in scientific research.