The objective of this project is to combine hyperpolarized C-13 imaging and H-1 MR spectroscopic imaging (MRSI) data in order to detect differences in dynamic and steady state metabolism that can be used to improve the evaluation of patients with glioblastoma (GBM). This is an important clinical problem because conventional anatomic imaging can provide ambiguous results that make it difficult to decide whether patients have responded to therapy or show signs of disease progression. While current H-1 MRSI methods give robust measures of the spatial extent of abnormal metabolism through values of the choline to N-acetylaspartate index (CNI), additional parameters are required to improve the specificity for distinguishing recurrent tumor from treatment related effects and to detect rapid changes that occur following treatment. Hyperpolarized C-13 pyruvate imaging is a new MR imaging method that provides information about dynamic changes in metabolism and has provided promising results in pre-clinical and patient studies of GBM. Understanding how the dynamic data obtained using hyperpolarized C13 pyruvate imaging can be combined with the more established steady state H-1 MRSI parameters and conventional anatomic imaging is critical for determining how to utilize the results obtained for making decisions about patient care.
Specific Aim 1 will apply these two metabolic imaging strategies to patients with newly diagnosed GBM at the pre-RT and the first post-RT follow-up scan. Rates of conversion of pyruvate to lactate and bicarbonate will be evaluated in normal appearing brain, the anatomic lesion and the CNI lesion in order to determine whether they will improve the definition of residual tumor.
Specific Aim 2 will use metabolic imaging to target locations for tissue sampling in patients undergoing surgery for suspected recurrence. The goal will be to validate H-1 and C-13 parameters as markers of recurrent tumor vs treatment related effects.
Specific Aim 3 will obtain metabolic imaging from patients who are suspected to have recurrent GBM and are being treated with standard of care therapies. The hypothesis being tested is that lactate/pyruvate will be decreased at the 7-day scan, and the choline to N-acetylaspartate index (CNI) will be decreased at the 6-8 week scan relative to the pre-treatment scan. This will be critical for determining whether these metabolic markers can be used as early indicators of response to therapy.
The purpose of this project is to develop non-invasive markers for assessing tumor aggressiveness and monitoring response to therapy for patients with gliobastoma by integrating two Magnetic Resonance (MR) metabolic imaging strategies with conventional anatomic imaging. The first method is H-1 MR spectroscopic imaging, which provides steady state metrics that describe tumor burden and predict overall survival. The second method is hyperpolarized C-13 imaging, which is a novel technology for monitoring dynamic changes in the magnitude and rate of conversion of pyruvate to its metabolic products. We will use the information obtained to differentiate normal brain, tumor and treatment related effects in order to improve the clinical evaluation of patients with GBM.
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