Quantitative Guanidinium CEST-Based pH Mapping at 3 T in Healthy and Pathological Muscle

Area of Science:

• Biomedical Engineering
• Magnetic Resonance Imaging
• Skeletal Muscle Physiology

Background:

• Intramuscular pH is a key biomarker for muscle diseases.
• Magnetic Resonance Spectroscopy (MRS) offers sensitive pH measurements but faces limitations in acquisition time and spatial resolution.
• Chemical Exchange Saturation Transfer (CEST) is an emerging technique for high-resolution pH mapping due to its sensitivity to pH-dependent chemical exchange rates.

Purpose of the Study:

• To develop and validate a CEST-based method for sensitive, high-resolution in vivo pH mapping of skeletal muscle.
• To assess the method's ability to detect subtle pH changes in healthy and diseased muscle.
• To evaluate the potential of CEST-based pH mapping as a biomarker for neuromuscular disorders.

Main Methods:

• Utilized a three-pool model and the Bloch-McConnell analytical solution to estimate the exchange rate (kex,guan2.0) at 3T.
• Assessed the sensitivity of the CEST-based pH measurement in a phantom across the physiological pH range.
• Applied the method to measure in vivo pH in the leg muscles of healthy controls (rest and post-exercise) and individuals with neuromuscular disease.

Main Results:

• CEST-based pH measurements showed a strong correlation with analytical pH meter readings in phantoms (R² = 0.97, p < 0.001).
• The method detected subtle in vivo pH variations as small as 0.02 pH units.
• Significantly decreased pH was observed in exercised muscles (p < 0.001), and significantly increased pH in pathological muscles (p < 0.05).

Conclusions:

• CEST enables sensitive, high-resolution pH mapping in skeletal muscle.
• The technique can distinguish between healthy and pathological muscle tissue.
• CEST-based pH mapping holds significant potential as a noninvasive biomarker for muscle diseases.