title: Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness.
abstract: Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression. The current study was aimed to investigate if CrCEST MRI can also be useful for differentiating gliomas with different degrees of aggressiveness.
  
  
  
  Intracranial 9L gliosarcoma and F98 glioma bearing rats with matched tumor size were scanned with a 9.4 T MRI scanner at two time points. CEST Z-spectra were collected using a customized sequence with a frequency-selective rectangular saturation pulse (B1= 50 Hz, duration = 3 s) followed by a single-shot readout. Z spectral data were fitted pixel-wise with five Lorentzian functions, and maps of CrCEST peak amplitude, linewidth, and integral were produced. For comparison, single-voxel proton MR spectroscopy (1H-MRS) was performed to quantify and compare the total Cr concentration in the tumor.
  
  
  
  CrCEST contrasts decreased with tumor progression from weeks 3 to 4 in both 9L and F98 phenotypes. More importantly, F98 tumors had significantly lower CrCEST integral compared to 9L tumors. On the other hand, integrals of other Z-spectral components were unable to differentiate both tumor progression and phenotype with limited sample size.
  
  
  
  Given that F98 is a more aggressive tumor than 9L, this study suggests that CrCEST MRI may help differentiate gliomas with different aggressiveness.
authors.affiliation: Department of Radiology and the Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA. kcai@uic.edu.|Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA. kcai@uic.edu.
authors.forename: Kejia
authors.initials: K
authors.lastname: Cai
authors.affiliation: Department of Radiology and the Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Rong-Wen
authors.initials: RW
authors.lastname: Tain
authors.affiliation: Department of Radiology and the Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.|Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Xiaohong Joe
authors.initials: XJ
authors.lastname: Zhou
authors.affiliation: Department of Radiology and the Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Damen
authors.affiliation: Department of Radiology and the Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.|Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Scotti
authors.affiliation: The Center for Magnetic Resonance and Optical Imaging, Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Hari
authors.initials: H
authors.lastname: Hariharan
authors.affiliation: Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK.
authors.forename: Harish
authors.initials: H
authors.lastname: Poptani
authors.affiliation: The Center for Magnetic Resonance and Optical Imaging, Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Reddy
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002454:Cell Differentiation; D003401:Creatine / Q000737:chemistry*; D005910:Glioma / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009361:Neoplasm Invasiveness; D011916:Rats, Inbred F344; D012815:Signal Processing, Computer-Assisted
chemical_list: D003401:Creatine
keywords: Aggressiveness; CEST; Creatine; Glioma