Human whole blood ¹H₂O transverse relaxation with gadolinium-based contrast reagents: Magnetic susceptibility and transmembrane water exchange

Purpose: To characterize transverse relaxation in oxygenated whole blood with extracellular gadolinium-based contrast reagents by experiment and simulation. Methods: Experimental measurements of transverse ¹H₂O relaxation from oxygenated whole human blood and plasma were made at 1.5 and 3.0 Tesla. Spin-echo refocused and free-induction decays are reported for blood and plasma samples containing four different contrast reagents (gadobenate, gadoteridol, gadofosveset, and gadobutrol), each present at concentrations ranging from 1 to 18 mM (i.e., mmol (contrast reagent (CR))/L (blood)). Monte Carlo simulations were conducted to ascertain the molecular mechanisms underlying relaxation. These consisted of random walks of water molecules in a large ensemble of randomly oriented erythrocytes. Bulk magnetic susceptibility (BMS) differences between the extra- and intracellular compartments were taken into account. All key parameters for these simulations were taken from independent published measurements: they include no adjustable variables. Results: Transverse relaxation is much more rapid in whole blood than in plasma, and the large majority of this dephasing is reversible by spin echo. Agreement between the experimental data and simulated results is remarkably good. Conclusion: Extracellular field inhomogeneities alone make very small contributions, whereas the orientation-dependent BMS intracellular resonance frequencies lead to the majority of transverse dephasing. Equilibrium exchange of water molecules between the intra- and extracellular compartments plays a significant role in transverse dephasing. Magn Reson Med 77:2015–2027, 2017.