Protein-induced water ¹H MR frequency shifts: Contributions from magnetic susceptibility and exchange effects

Defining the biophysics underlying the remarkable MRI phase contrast reported in high field MRI studies of human brain would lead to more quantitative image analysis and more informed pulse sequence development. Toward this end, the dependence of water ¹H resonance frequency on protein concentration was investigated using bovine serum albumin (BSA) as a model system. Two distinct mechanisms were found to underlie a water ¹H resonance frequency shift: (i) a protein-concentration-induced change in bulk magnetic susceptibility, causing a shift to lower frequency, and (ii) exchange of water between chemical-shift distinct environments, i.e., free (bulk water) and protein-associated ("bound") water, including freely exchangeable ¹H sites on proteins, causing a shift to higher frequency. At 37 °C the amplitude of the exchange effect is roughly half that of the susceptibility effect.