Noninvasive Mapping of Creatine Kinase Metabolism in Human Muscle Using pH-Insensitive PCrCEST MRI at 3 and 5 T

Phosphocreatine (PCr) recovery after exercise reflects creatine kinase (CK) metabolism and is a key marker of muscle energetics. However, current chemical exchange saturation transfer (CEST)-based PCr imaging (PCrCEST) remains limited by pH-dependent contrast. Here, we present a pH-insensitive PCrCEST strategy that minimizes pH-related signal variability, enabling more reliable in vivo quantification during exercise, when tissue pH may change. Theoretical derivation, simulations, and phantom studies confirmed that PCrCEST signals varied by less than 20% across the physiological pH range when the saturation radial frequency (γB₁) matches the guanidinium proton exchange rate. Under this optimized B₁ condition, kinetic simulations further show that the PCrCEST-derived recovery time constant (τ_PCr) closely follows expected behavior even during dynamic pH changes. The pH-insensitive strategy was implemented at both 3 and 5 T and assessed in human calf muscle during plantar flexion exercise. These results demonstrate that pH-insensitive PCrCEST enabled robust mapping of muscle CK metabolism. The availability of pH-insensitive CEST mapping improves the potential of CEST not only for exercise measurements but also for broader clinical translation.