Abstract
Blood is a physiological substance with multiple water compartments, which contain water-binding proteins such as hemoglobin in erythrocytes and albumin in plasma. Knowing the water transverse (R2) relaxation rates from these different blood compartments is a prerequisite for quantifying the blood oxygenation level-dependent (BOLD) effect. Here, we report the Carr-Purcell-Meiboom-Gill (CPMG) based transverse (R2CPMG) relaxation rates of water in bovine blood samples circulated in a perfusion system at physiological temperature in order to mimic blood perfusion in humans. R2CPMG values of blood plasma, lysed packed erythrocytes, lysed plasma/erythrocyte mixtures, and whole blood at 3 T, 7 T, 9.4 T, 11.7 T and 16.4 T were measured as a function of hematocrit or hemoglobin concentration, oxygenation, and CPMG inter-echo spacing (τcp). R2CPMG in lysed cells showed a small τcp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than τcp. This was contrary to the tangential dependence in whole blood, where a much slower exchange between cells and blood plasma applies. Whole blood data were fitted as a function of τcp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R2CPMG, and the intercept R20blood at infinitely short τcp was determined. The R20blood values at different hematocrit and the R2CPMG values of lysed erythrocyte/plasma mixtures at different hemoglobin concentration were used to determine the relaxivity of hemoglobin inside the erythrocyte (r2Hb) and albumin (r2Alb) in plasma. The r2Hb values obtained from lysed erythrocytes and whole blood were comparable at full oxygenation. However, while r2Hb determined from lysed cells showed a linear dependence on oxygenation, this dependence became quadratic in whole blood. This possibly suggests an additional relaxation effect inside intact cells, perhaps due to hemoglobin proximity to the erythrocyte membrane. However, we cannot exclude that this is a consequence of the simple tangential model used to remove relaxation contributions from exchange and diffusion. The extensive data set presented should be useful for future theory development for the transverse relaxation of blood.
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