Creatine mapping of the brain at 3T by CEST MRI.

Kexin Wang, Jianpan Huang, Licheng Ju, Su Xu, Rao P Gullapalli, Yajie Liang, Joshua Rogers, Yuguo Li, Peter C M van Zijl, Robert G Weiss, Kannie W Y Chan, Jiadi Xu
Author Information
  1. Kexin Wang: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, Maryland, USA. ORCID
  2. Jianpan Huang: Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, China. ORCID
  3. Licheng Ju: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, Maryland, USA.
  4. Su Xu: Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  5. Rao P Gullapalli: Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  6. Yajie Liang: Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  7. Joshua Rogers: Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  8. Yuguo Li: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, Maryland, USA.
  9. Peter C M van Zijl: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, Maryland, USA.
  10. Robert G Weiss: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  11. Kannie W Y Chan: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ORCID
  12. Jiadi Xu: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, Maryland, USA. ORCID

Abstract

PURPOSE: To assess the feasibility of CEST-based creatine (Cr) mapping in brain at 3T using the guanidino (Guan) proton resonance.
METHODS: Wild type and knockout mice with guanidinoacetate N-methyltransferase deficiency and low Cr and phosphocreatine (PCr) concentrations in the brain were used to assign the Cr and protein-based arginine contributions to the GuanCEST signal at 2.0 ppm. To quantify the Cr proton exchange rate, two-step Bloch-McConnell fitting was used to fit the extracted CrCEST line-shape and multi-B Z-spectral data. The pH response of GuanCEST was simulated to demonstrate its potential for pH mapping.
RESULTS: Brain Z-spectra of wild type and guanidinoacetate N-methyltransferase deficiency mice show a clear Guan proton peak at 2.0 ppm at 3T. The CrCEST signal contributes ∼23% to the GuanCEST signal at B  = 0.8 μT, where a maximum CrCEST effect of 0.007 was detected. An exchange rate range of 200-300 s was estimated for the Cr Guan protons. As revealed by the simulation, an elevated GuanCEST in the brain is observed when B is less than 0.4 μT at 3T, when intracellular pH reduces by 0.2. Conversely, the GuanCEST decreases when B is greater than 0.4 μT with the same pH drop.
CONCLUSIONS: CrCEST mapping is possible at 3T, which has potential for detecting intracellular pH and Cr concentration in brain.

Keywords

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Grants

  1. P41 EB031771/NIBIB NIH HHS
  2. R01 HL149742/NHLBI NIH HHS
  3. R01 AG080104/NIA NIH HHS
  4. P50 HD103538/NICHD NIH HHS
  5. R21 AG074978/NIA NIH HHS
  6. R01 NS127344/NINDS NIH HHS
  7. R01 HL063030/NHLBI NIH HHS

MeSH Term

Brain
Creatine
Mice, Knockout
Movement Disorders
Protons
Mice
Animals
Magnetic Resonance Imaging
Guanidinoacetate N-Methyltransferase
Language Development Disorders

Chemicals

Creatine
Protons
Guanidinoacetate N-Methyltransferase

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