The exchange rate of creatine CEST in mouse brain

Area of Science:

• Neuroimaging
• Biophysics
• Magnetic Resonance Imaging

Background:

• Chemical Exchange Saturation Transfer (CEST) imaging is a powerful technique for visualizing metabolites in vivo.
• Creatine (Cr) and guanidinium (Guan) are important metabolites in the brain, and their CEST signals can provide valuable physiological information.
• Understanding the exchange rates and pH sensitivity of these CEST signals is crucial for accurate interpretation of in vivo MRI data.

Purpose of the Study:

• To estimate the in vivo exchange rate of creatine (Cr) CEST in the mouse brain.
• To evaluate the pH sensitivity of guanidinium (Guan) CEST in the mouse brain.
• To investigate the contribution of CrCEST to the overall GuanCEST signal under varying conditions.

Main Methods:

• Utilized polynomial and Lorentzian line-shape fitting (PLOF) on Z-spectra acquired at 11.7T to extract CEST signals.
• Employed wild-type (WT) and guanidinoacetate N-methyltransferase deficient (GAMT-/-) mice to isolate the CrCEST signal.
• Applied two-step Bloch-McConnell (BM) fitting to quantify CrCEST exchange rate and pH response, with hypercapnia used to induce pH changes.

Main Results:

• CrCEST signal was found to be 20-25% of GuanCEST signal at 1.95 ppm for B1 fields between 0.8 and 2 μT.
• The in vivo CrCEST exchange rate was determined to be approximately 240-480 s⁻¹, significantly lower than in vitro values (~1000 s⁻¹).
• CrCEST and amineCEST signals demonstrated high sensitivity to pH changes in WT mouse brains under specific B1 conditions.

Conclusions:

• The in vivo CrCEST exchange rate is notably slow, necessitating adjustments in MRI acquisition parameters for optimal CrCEST imaging.
• CrCEST significantly influences the observed pH-dependent behavior of GuanCEST signals, particularly under different B1 field strengths.
• These findings enhance the understanding of CEST-based metabolite quantification and pH mapping in the brain.