Purpose: To compare hyperpolarized MRI with conventional MRI for the detection of glioblastoma and evaluation of radiotherapy treatment response.
Methods: Athymic mice were intracranially implanted with patient-derived glioblastoma stem cells. The median survival of the mice was 34 days. Tumor volume was determined with Tâ‚‚-weighted MRI every 3 days, and the in vivo conversion of hyperpolarized [1-Â¹Â³C]pyruvate to lactate was measured using repeated pulse-acquired spectroscopy every 7 days. This conversion was quantified using the metric nLac (the ratio of lactate divided by lactate+pyruvate signal). Tumors were excised 1 day after each hyperpolarization experiment and prepared for NMR spectroscopy to measure the steady-state concentrations of 25 metabolites. On Days 25 and 27, half of the mice received 5 Gy whole brain irradiation, and hyperpolarization experiments were performed on Days 41 and 48. Each of these measurements was compared to those made in healthy athymic mice. Statistical analysis was conducted using two-tailed T-tests, corrected for multiple comparisons, and significance was attributed to p-values less than 0.05.
Results: Statistically significant increases in tumor volume from conventional MRI scans were observed starting on Day 23 compared to baseline measurements. From the hyperpolarization experiments, nLac was significantly elevated in tumor-bearing mice compared to control mice beginning on Day 14. Significant increases in the ex vivo concentrations of valine, alanine, glycine, phosphocholine and glycero-phosphocholine metabolites were observed by Day 34. Following radiotherapy, nLac steadily decreased and was significantly reduced compared to untreated mice on Day 48. Tumor volume had shrunk, but not significantly, by Day 48.
Conclusion: During glioblastoma development, hyperpolarized MRI detected tumors by measuring pyruvate-to-lactate conversion prior to conventional MRI measuring anatomic volume. Furthermore, hyperpolarized MRI evaluated treatment response following radiotherapy before tumors shrunk by a significant amount. This project has demonstrated the value that hyperpolarized MRI could bring to the clinic.