R1ρ sensitivity to pH and other compounds at clinically accessible spin-lock fields in the presence of proteins

Numerous human diseases involve abnormal metabolism, and proton exchange is an effective source of magnetic resonance imaging (MRI) contrast for assessing metabolism. One MRI technique that capitalizes on proton exchange is R₁ relaxation in the rotating frame (R_1ρ). Here, we investigated the sensitivity of R_1ρ to various proton-exchange mechanisms at spin-lock pulses within Food and Drug Administration (FDA) safety guidelines for radiofrequency-induced heating. We systematically varied pH known to change the rate of proton exchange as well as the glucose and lysine concentrations, thus changing the number of amide, hydroxyl and amine exchangeable sites in a series of egg-white albumin phantoms. The resulting effects on quantitative relaxation time measurements of R_1ρ, R₁ and R₂ were observed at 3 T. Using spin-lock amplitudes available for human imaging (less than 23.5 μT) at near physiologic temperatures, we found R_1ρ was more sensitive to physiologic changes in pH than to changes in glucose and lysine concentrations. In addition, R_1ρ was more sensitive to pH changes than R₁ and R₂. Models of proton exchange fitted to the relaxation measurements suggest that amide groups were the primary source of pH sensitivity. Together, these experiments suggest an optimal spin-lock amplitude for measuring pH changes while not exceeding FDA-subject heating limitations.