Program Information
Non-Invasive Assessment of Glioblastoma Tumor Aggressiveness Using Hyperpolarized Magnetic Resonance Imaging and Spectroscopy
T Salzillo1,2*, J Gumin1 , J Lee1 , N Zacharias1 , F Lang1 , P Bhattacharya1 , (1) The University of Texas MD Anderson Cancer Center, Houston, TX, (2) The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX
Presentations
SU-K-708-11 (Sunday, July 30, 2017) 4:00 PM - 6:00 PM Room: 708
Purpose: Glioblastoma is the most common type of brain tumor but has the worst prognosis with minimal improvement of patient outcome in the past 30 years. The primary cause of treatment inefficacy is late diagnosis when tumors have become too advanced. There is a need for innovative techniques to predict prognosis early in a tumor’s evolution for optimal treatment planning. Metabolic imaging is one such technique since metabolic changes in tumors precede anatomical and morphological changes. Additionally, metabolic aberrations are indicative of tumorigenesis. Through in vivo and ex vivo metabolic assays, we sought to show that tumor metabolism correlates with tumor aggressiveness.
Methods: Mice were intracranially injected with patient-derived glioma sphere-forming cells (GSC). The four GSC lines have established genomic profiles and produce distinct survival times in mice. Tumor development was followed with FLAIR, T1-, and T2-weighted MRI. Once tumors reached 100 mm³, hyperpolarized ¹³C MRI experiments were performed to measure the dynamic metabolic flux of pyruvate to lactate. Mice were euthanized and the brains excised. Metabolites were extracted from the tumor samples, and the global, steady-state metabolic profile was interrogated with NMR spectroscopy.
Results: The initial cohort of mice (N=5) served primarily to establish survival curves and optimize pulse sequences. Preliminary data is illustrated in the supplemental information. The most aggressive GSC tumors produced the highest dynamic flux of pyruvate to lactate, while the least aggressive tumors possessed the lowest flux. We identified 25 steady-state metabolite concentrations from NMR analysis of ex vivo tumor samples.
Conclusion: This initial study demonstrates the capability of hyperpolarized MRI to non-invasively measure tumor metabolism in order to stratify GSC-derived tumors based on their aggressiveness. The next step in this experiment is to correlate the in vivo metabolic imaging data with FLAIR, T1-, and T2-weighted MR images and corresponding ex vivo NMR metabolomics data.
Contact Email: