Increased choline levels coincide with enhanced proliferative activity of human neuroepithelial brain tumors

Abstract

Proton MR spectroscopy ((1)H MRS)-visible total choline-containing compounds (tCho-compounds) are derivatives of membrane phospholipids and, in part, may act as a long-term second-messenger system for cellular proliferation. Experimental evidence suggests increasing concentrations of tCho-compounds during cellular proliferation. The present study was conducted in order to test the hypothesis that in vivo measurements of tCho-concentrations using (1)H MRS allow assessment of the proliferative activity of neuroepithelial brain tumors presurgically. Single-voxel (1)H MRS (PRESS, TR 1500 ms, TE 135 ms) was performed in 101 patients with neuroepithelial brain tumors prior to surgery and 19 healthy volunteers. Histological diagnoses were confirmed postsurgically according to the WHO classification. Measured tCho-compound signal intensities were corrected for coil loading, numbers of acquisitions and voxel size, and tCho concentrations calculated as institutional arbitrary units. They were matched with the mean immunohistochemical marker of cell proliferation, the Ki-67 (MIB.1) labeling index, using correlation analysis according to Spearman. Compared with low-grade tumors (i.e. WHO grade I/II) and normal white brain matter, high-grade tumors (i.e. WHO grade III/IV) revealed significantly (p < 0.05) elevated labeling indices paralleled by increasingly elevated tCho-concentrations. In contrast tCho-concentrations in low-grade tumor did not differ significantly from physiological values. A highly significant positive correlation (p < 0.0001, r(2) = 0.81) was found between the tCho-concentration and the labeling index. It was concluded that the determination of tCho-concentrations using in vivo (1)H MRS could provide a novel and noninvasive assessment of the proliferative activity of neuroepithelial brain tumors, pointing at (1)H MRS as a useful method for differentiating proliferating from non-proliferating tissues. Hence, potential indications for the clinical application of (1)H MRS are grading tumors presurgically, early detection of anaplastic transformation, and monitoring treatment.

Choline by magnetic spectroscopy and dynamic contrast enhancement curve by magnetic resonance imaging in neoadjuvant chemotherapy for invasive breast cancer

“…Changes in choline signal are reportedly useful for evaluating response to treatment in many types of tumors (26)(27)(28). Choline elevation has also been confirmed to be a sensitive and specific marker of response to treatment for breast cancer (17,20).…”

Lactate, choline, and creatine levels measured by vitro 1H‐MRS as prognostic parameters in patients with non‐small‐cell lung cancer

“…The Cho signal is thought to be attributable predominantly to water-soluble glycerophosphocholine and phospocholine (18), and to correlate with in vitro measures of cell density and phospholipid metabolism (19). Because Cho is characteristically elevated in some malignant tumors, its concentration as measured by MRS has been expected to be an indicator of grade of malignancy (20) and prognosis (21). In addition to vascular prolif- eration, cellularity, mitotic activity, nuclear pleomorphism, and necrosis are important criteria for the histopathologic grading of gliomas.…”

Multimodality Assessment of Brain Tumors and Tumor Recurrence

“…5)] (62). Choline as part of cell membrane phospholipids correlates well with the Ki-67 proliferation marker in gliomas (62,63). A cutoff of 1.6 for normalized choline values was found to be predictive of high-grade astrocytomas.…”