Preoperative Imaging of Glioblastoma Patients using Hyperpolarized 13C Pyruvate: Potential Role in Clinical Decision Making

Background Glioblastoma remains incurable despite treatment with surgery, radiation therapy, and cytotoxic chemotherapy, prompting the search for a metabolic pathway unique to glioblastoma cells. 13C MR spectroscopic imaging with hyperpolarized pyruvate can demonstrate alterations in pyruvate metabolism in these tumors. Methods Three patients with diagnostic MRI suggestive of a glioblastoma were scanned at 3T 1-2 days prior to tumor resection using a 13C/ 1H dual-frequency RF coil and a 13C/ 1H-integrated MR protocol, which consists of a series of 1H MR sequences (T2 FLAIR, arterial spin labeling and contrast-enhanced (CE) T1) and 13C spectroscopic imaging with hyperpolarized [1- 13C]pyruvate. Dynamic spiral chemical shift imaging was used for 13C data acquisition. Surgical navigation was used to correlate the locations of tissue samples submitted for histology with the changes seen on the diagnostic MR scans and the 13C spectroscopic images. Results Each tumor was histologically confirmed to be a WHO grade IV glioblastoma with isocitrate dehydrogenase wild type. Total hyperpolarized 13C signals detected near the tumor mass reflected altered tissue perfusion near the tumor. For each tumor, a hyperintense [1- 13C]lactate signal was detected both within CE and T2-FLAIR regions on the 1H diagnostic images (p = 0.008). [ 13C]Bicarbonate signal was maintained or decreased in the lesion but the observation was not significant (p = 0.3). Conclusions Prior to surgical resection, 13C MR spectroscopic imaging with hyperpolarized pyruvate reveals increased lactate production in regions of histologically confirmed glioblastoma.