CEST Z-spectra fitting via Bloch-McConnell equations for pH mapping: in vitro validation and application in healthy and pathological leg muscles

Motivation: Intramuscular pH is a promising biomarker for neuromuscular disease research which can be assessed with ¹H and ³¹P MRS, though these techniques have limitations, such as reduced spatial resolution. Goal(s): Chemical Exchange Saturation Transfer (CEST) enables high-resolution pH mapping by measuring exchange rates between metabolites and free water. Approach: In this study, we used a 3-pool Bloch-McConnell model to fit and extract the exchange rate between creatine and free water. Results: Sensitivity was assessed in vitro within the physiological pH range and in vivo in leg muscles of healthy volunteers, at rest and post-exercise, and in a patient's leg. Impact: This work advances high-resolution pH mapping for neuromuscular disease assessment, offering non-invasive insights into muscle homeostasis. By enhancing sensitivity and spatial resolution in pH measurement, it could improve the monitoring of muscle disorders, benefiting clinical research.