Human whole-blood ¹H₂O longitudinal relaxation with normal and high-relaxivity contrast reagents: Influence of trans-cell-membrane water exchange

Purpose: Accurate characterization of contrast reagent (CR) longitudinal relaxivity in whole blood is required to predict arterial signal intensity in contrast-enhanced MR angiography (CE-MRA). This study measured the longitudinal relaxation rate constants (R₁) over a concentration range for non-protein-binding and protein-binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0 Tesla (T) under physiologic arterial conditions.

Methods: Relaxivities of gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from 0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be expected in CE-MRA.

Results: In plasma, the ¹H₂O R₂ [CR]-dependence was nonlinear for gadobenate and gadofosveset secondary to CR interactions with the serum macromolecule albumin, and was well described by an analytical expression for effective 1:1 binding stoichiometry. In whole blood, the ¹H₂O R₂ [CR]-dependence was markedly non-linear for all CRs, and was well-predicted by an expression for equilibrium exchange of water molecules between plasma and intracellular spaces using a priori parameter values only.

Conclusion: In whole blood, ²H₂O R₁ exhibits a nonlinear relationship with [CR] over 0 to 18 mM CR. The nonlinearity is well described by exchange of water between erythrocyte and plasma compartments, and is particularly evident for high relaxivity CRs.