Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making

Abstract

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.

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study

“…Previous clinical studies using 13 C MRI with hyperpolarized [1- 13 C]pyruvate have demonstrated the feasibility of imaging GBM metabolism in patients across a spectrum of clinical presentations, all performed following some form of treatment ( 19 – 23 ). Moreover, a correlation between gene expression and lactate labeling has not been demonstrated previously ( 19 – 25 ). In this exploratory study, we have characterized hyperpolarized [1- 13 C]pyruvate metabolism in participants with treatment-naive isocitrate dehydrogenase wild-type GBM by using hyperpolarized 13 C MRI.…”

Spin Hyperpolarization in Modern Magnetic Resonance

“…As mentioned earlier, most studies focus on detecting and following prostate cancers , and the potential metastasis to bone and liver (Figure ). Other studies have also shown the great potential of d DNP for detecting breast cancer, or brain metabolism and glioblastoma . More recently, detection of renal tumors and even whole abdomen metabolism was reported.…”

“…Other studies have also shown the great potential of dDNP for detecting breast cancer, 367 or brain metabolism 370 and glioblastoma. 371 More recently, detection of renal tumors 372 and even whole abdomen metabolism 373 was reported.…”

Dynamic 13C MR spectroscopy as an alternative to imaging for assessing cerebral metabolism using hyperpolarized pyruvate in humans

“…Recent advances in clinical translation of HP pyruvate imaging 15 has enabled metabolic imaging of the human brain in healthy subjects 16,17 and patients with brain tumors 17–20 or TBI 21 . Most previous human brain studies focused on imaging altered lactate production in intracranial malignancies 18,19 .…”