title: Multivoxel magnetic resonance spectroscopy identifies enriched foci of cancer stem-like cells in high-grade gliomas.
abstract: OBJECTIVE
  This study investigated the correlation between choline/creatine (Cho/Cr) ratios determined by multivoxel proton magnetic resonance spectroscopy (1H-MRS) and the distribution of cancer stem-like cells (CSLCs) in high-grade gliomas.
  
  
  METHODS
  Sixteen patients with high-grade gliomas were recruited and underwent1H-MRS examination before surgery to identify distinct tumor regions with variable Cho/Cr ratios. Using intraoperative neuronavigation, tumor tissues were accurately sampled from regions with high and low Cho/Cr ratios within each tumor. The distribution of CSLCs in samples from glioma tissue regions with different Cho/Cr ratios was quantified by neurosphere culture, immunohistochemistry, and Western blot.
  
  
  RESULTS
  The mean neurosphere formation rate in tissues with high Cho/Cr ratios was significantly increased compared with that in low Cho/Cr ratio tissues (13.94±5.94 per 100 cells vs 8.04±3.99 per 100 cells,P<0.001). Immunohistochemistry indicated that tissues with high Cho/Cr ratios had elevated expression of CD133, nestin, and CD15, relative to low Cho/Cr ratio tissue samples (23.6%±3.8% vs 18.3%±3.3%, 25.2%±4.5% vs 19.8%±2.8%, 24.5%±3.8% vs 17.8%±2.2%, respectively; allP<0.001). Western blot demonstrated that relative CD133 and nestin protein expression in high Cho/Cr ratio regions was significantly higher than that in low Cho/Cr ratio tissue samples (0.50±0.17 vs 0.30±0.08, 0.45±0.13 vs 0.27±0.07, respectively; bothP<0.001). The protein expression levels of CD133 and nestin were highly correlated with Cho/Cr ratios (r=0.897 andr=0.861, respectively).
  
  
  CONCLUSIONS
  Cho/Cr ratios correlate with the distribution of CSLCs in high-grade gliomas, and this may assist in identifying foci enriched with CSLCs and thus improve the management of high-grade gliomas.
authors.affiliation: Clinical Medicine College, Ningxia Medical University; Department of Neurosurgery, General Hospital of Ningxia Medical University; Ningxia Key Laboratory of Cerebrocranial Diseases, The National Key Laboratory Incubation Base, Yinchuan.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai.
authors.forename: Tianming
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School of Rutgers University, Piscataway, NJ, USA.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Gui
authors.affiliation: Department of Neurosurgery, General Hospital of Ningxia Medical University.
authors.forename: Xilong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, The National Key Laboratory Incubation Base, Yinchuan; Department of Physiology, Ningxia Medical University, Yinchuan, People's Republic of China.
authors.forename: Qikuan
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, General Hospital of Ningxia Medical University.
authors.forename: Hechun
authors.initials: H
authors.lastname: Xia
authors.affiliation: Clinical Medicine College, Ningxia Medical University; Department of Neurosurgery, General Hospital of Ningxia Medical University.
authors.forename: Gaoyang
authors.initials: G
authors.lastname: Qi
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, General Hospital of Ningxia Medical University.
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
keywords: 1H-MRS; Cho/Cr; cancer stem-like cells; choline; creatine; high-grade glioma