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Quantitative theory for the transverse relaxation time of blood water.

ABSTRACT: An integrative model is proposed to describe the dependence of the transverse relaxation rate of blood water protons (R_2blood = 1/T_2blood ) on hematocrit fraction and oxygenation fraction (Y). This unified model takes into account (a) the diamagnetic effects of albumin, hemoglobin and the cell membrane; (b) the paramagnetic effect of hemoglobin; (c) the effect of compartmental exchange between plasma and erythrocytes under both fast and slow exchange conditions that vary depending on field strength and compartmental relaxation rates and (d) the effect of diffusion through field gradients near the erythrocyte membrane. To validate the model, whole-blood and lysed-blood R₂ data acquired previously using Carr-Purcell-Meiboom-Gill measurements as a function of inter-echo spacing τ_cp at magnetic fields of 3.0, 7.0, 9.4 and 11.7 T were fitted to determine the lifetimes (field-independent physiological constants) for water diffusion and exchange, as well as several physical constants, some of which are field-independent (magnetic susceptibilities) and some are field-dependent (relaxation rates for water protons in solutions of albumin and oxygenated and deoxygenated hemoglobin, ie, blood plasma and erythrocytes, respectively). This combined exchange-diffusion model allowed excellent fitting of the curve of the τ_cp -dependent relaxation rate dispersion at all four fields using a single average erythrocyte water lifetime, τ_ery = 9.1 ± 1.4 ms, and an averaged diffusional correlation time, τ_D = 3.15 ± 0.43 ms. Using this model and the determined physiological time constants and relaxation parameters, blood T₂ values published by multiple groups based on measurements at magnetic field strengths of 1.5 T and higher could be predicted correctly within error. Establishment of this theory is a fundamental step for quantitative modeling of the BOLD effect underlying functional MRI.

SUBMITTER: Li W

PROVIDER: S-EPMC7322972 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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 (?cp). R2CPMG in lysed cells showed a small ?cp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than ?cp. 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 ?cp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R2CPMG, and the intercept R20blood at infinitely short ?cp 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.

Project description:Magnetic resonance imaging (MRI)-based quantification of the blood-oxygenation-level-dependent (BOLD) effect allows oxygen extraction fraction (OEF) mapping. The multi-parametric quantitative BOLD (mq-BOLD) technique facilitates relative OEF (rOEF) measurements with whole brain coverage in clinically applicable scan times. Mq-BOLD requires three separate scans of cerebral blood volume and transverse relaxation rates measured by gradient-echo (1/T2∗) and spin-echo (1/T2). Although the current method is of clinical merit in patients with stroke, glioma and internal carotid artery stenosis (ICAS), there are relaxation measurement artefacts that impede the sensitivity of mq-BOLD and artificially elevate reported rOEF values. We posited that T2-related biases caused by slice refocusing imperfections during rapid 2D-GraSE (Gradient and Spin Echo) imaging can be reduced by applying 3D-GraSE imaging sequences, because the latter requires no slice selective pulses. The removal of T2-related biases would decrease overestimated rOEF values measured by mq-BOLD. We characterized effects of T2-related bias in mq-BOLD by comparing the initially employed 2D-GraSE and two proposed 3D-GraSE sequences to multiple single spin-echo reference measurements, both in vitro and in vivo. A phantom and 25 participants, including young and elderly healthy controls as well as ICAS-patients, were scanned. We additionally proposed a procedure to reliably identify and exclude artefact affected voxels. In the phantom, 3D-GraSE derived T2 values had 57% lower deviation from the reference. For in vivo scans, the formerly overestimated rOEF was reduced by -27% (p < 0.001). We obtained rOEF = 0.51, which is much closer to literature values from positron emission tomography (PET) measurements. Furthermore, increased sensitivity to a focal rOEF elevation in an ICAS-patient was demonstrated. In summary, the application of 3D-GraSE improves the mq-BOLD-based rOEF quantification while maintaining clinically feasible scan times. Thus, mq-BOLD with non-slice selective T2 imaging is highly promising to improve clinical diagnostics of cerebrovascular diseases such as ICAS.

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Quantitative theory for the transverse relaxation time of blood water.

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