Investigation of the contribution of total creatine to the CEST Z-spectrum of brain using a knockout mouse model

Lin Chen, Haifeng Zeng, Xiang Xu, Nirbhay N. Yadav, Shuhui Cai, Nicolaas Puts, Peter B Barker, Tong Li, Robert George Weiss, Peter C Van Zijl, Jiadi Xu

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Abstract

The current study aims to assign and estimate the total creatine (tCr) signal contribution to the Z-spectrum in mouse brain at 11.7 T. Creatine (Cr), phosphocreatine (PCr) and protein phantoms were used to confirm the presence of a guanidinium resonance at this field strength. Wild-type (WT) and knockout mice with guanidinoacetate N-methyltransferase deficiency (GAMT−/−), which have low Cr and PCr concentrations in the brain, were used to assign the tCr contribution to the Z-spectrum. To estimate the total guanidinium concentrations, two pools for the Z-spectrum around 2 ppm were assumed: (i) a Lorentzian function representing the guanidinium chemical exchange saturation transfer (CEST) at 1.95 ppm in the 11.7-T Z-spectrum; and (ii) a background signal that can be fitted by a polynomial function. Comparison between the WT and GAMT−/− mice provided strong evidence for three types of contribution to the peak in the Z-spectrum at 1.95 ppm, namely proteins, Cr and PCr, the latter fitted as tCr. A ratio of 20 ± 7% (protein) and 80 ± 7% tCr was found in brain at 2 μT and 2 s saturation. Based on phantom experiments, the tCr peak was estimated to consist of about 83 ± 5% Cr and 17 ± 5% PCr. Maps for tCr of mouse brain were generated based on the peak at 1.95 ppm after concentration calibration with in vivo magnetic resonance spectroscopy.

Original languageEnglish (US)
Article numbere3834
JournalNMR in Biomedicine
Volume30
Issue number12
DOIs
Publication statusPublished - Dec 1 2017

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Keywords

  • chemical exchange saturation transfer (CEST)
  • creatine
  • guanidinoacetate N-methyltransferase deficiency (GAMT−/−)
  • Lorentzian line-shape fitting
  • magnetic resonance spectroscopy (MRS)
  • magnetization transfer
  • phosphate creatine

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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