Hematocrit Fraction Research Articles

Vitamin D3 among neonates born after invitro fertilization compared with neonates from the general population.

Sufficient levels of vitamin D have been associated with higher chances for both clinical pregnancy and live birth among women undergoing assisted reproductive techniques, whereas low levels of maternal vitamin D have been associated with preeclampsia and late miscarriage. In Denmark, subgroups at risk for low vitamin D levels, including neonates and toddlers, are recommended to use supplementation. The aim was to study the level of vitamin D3 among neonates born after invitro fertilization compared with neonates from the general population. In this cohort study a random sample of 1326 neonates representing the general population and 1200 neonates conceived by invitro fertilization born in Denmark from 1995 to 2002 were identified from registries covering the whole Danish population. Information on use of assisted reproduction was collected from the Danish InVitro Fertilization register, ICD-10 code: DZ358F. 25-Hydroxyvitamin D was measured from dried blood spots routinely collected by heel prick 48-72 h after birth and corrected according to the hematocrit fraction for capillary blood of neonates. Linear regression analysis was performed, both crude and adjusted, for predefined putative confounders, identified through directed acyclic graphs. Vitamin D3 analysis could be performed from a total of 1105 neonates from the general population and 1072 neonates conceived by invitro fertilization that were subsequently included in the study. The median vitamin D3 was 24.0 nmol/L (interquartile range [IQR] 14.1-39.3) and 33.0 nmol/L (IQR 21.3-48.8) among neonates from the general population and neonates conceived by invitro fertilization, respectively. The adjusted mean difference between neonates from the general population and those conceived by invitro fertilization was 6.1 nmol/L (95% confidence interval 4.1-8.1). In this study, children born after invitro fertilization have a higher vitamin D3 than a random sample of neonates in Denmark.

Quantitative theory for the transverse relaxation time of blood water.

An integrative model is proposed to describe the dependence of the transverse relaxation rate of blood water protons (R2blood = 1/T2blood ) 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 τcp 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 τcp -dependent relaxation rate dispersion at all four fields using a single average erythrocyte water lifetime, τery = 9.1 ± 1.4 ms, and an averaged diffusional correlation time, τD = 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.

Accounting for the role of hematocrit in between-subject variations of MRI-derived baseline cerebral hemodynamic parameters and functional BOLD responses.

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO2 to maintain constant CMRO2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. © 2017 Wiley Periodicals, Inc.

Quantitative theory for the longitudinal relaxation time of blood water.

To propose and evaluate a model for the blood water T1 that takes into account the effects of hematocrit fraction, oxygenation fraction, erythrocyte hemoglobin concentration, methemoglobin fraction, and plasma albumin concentration. Whole blood and lysed blood T1 data were acquired at magnetic fields of 3 Tesla (T), 7T, 9.4T, and 11.7T using inversion-recovery measurements and a home-built blood circulation system for maintaining physiological conditions. A quantitative model was derived based on multivariable fitting of this data. Fitting of the model to the data allowed determination of the different parameters describing the blood water T1 such as those for the diamagnetic and paramagnetic effects of albumin and hemoglobin, and the contribution of methemoglobin. The model correctly predicts blood T1 at multiple fields, as verified by comparison with existing literature. The model provides physical and physiological parameters describing the effects of hematocrit fraction, oxygenation, hemoglobin concentration, methemoglobin fraction, and albumin concentration on blood water T1 . It can be used to predict blood T1 at multiple fields. Magn Reson Med 76:270-281, 2016. © 2015 Wiley Periodicals, Inc.

Hematocrit and oxygenation dependence of blood 1H2O T1 at 7 tesla

Knowledge of blood (1)H2O T1 is critical for perfusion-based quantification experiments such as arterial spin labeling and cerebral blood volume-weighted MRI using vascular space occupancy. The dependence of blood (1)H2O T1 on hematocrit fraction (Hct) and oxygen saturation fraction (Y) was determined at 7 T using in vitro bovine blood in a circulating system under physiological conditions. Blood (1)H2O R1 values for different conditions could be readily fitted using a two-compartment (erythrocyte and plasma) model, which are described by a monoexponential longitudinal relaxation rate constant dependence. It was found that T1 = 2171 ± 39 ms for Y = 1 (arterial blood) and 2010 ± 41 ms for Y = 0.6 (venous blood), for a typical Hct of 0.42. The blood (1)H2O T1 values in the normal physiological range (Hct from 0.35 to 0.45, and Y from 0.6 to 1.0) were determined to range from 1900 to 2300 ms. The influence of oxygen partial pressure (pO2) and the effect of plasma osmolality for different anticoagulants were also investigated. It is discussed why blood (1)H2O T1 values measured in vivo for human blood may be about 10-20% larger than found in vitro for bovine blood at the same field strength.

The BOLD post-stimulus undershoot, one of the most debated issues in fMRI

This paper provides a brief overview of how we got involved in fMRI work and of our efforts to elucidate the mechanisms underlying BOLD signal changes. The phenomenon discussed here in particular is the post-stimulus undershoot (PSU), the interpretation of which has captivated many fMRI scientists and is still under debate to date. This controversy is caused both by the convoluted physiological origin of the BOLD effect, which allows many possible explanations, and the lack of comprehensive data in the early years. BOLD effects reflect changes in cerebral blood flow (CBF), volume (CBV), metabolic rate of oxygen (CMRO(2)), and hematocrit fraction (Hct). However, the size of such effects is modulated by vascular origin such as intravascular, extravascular, macro and microvascular, venular and capillary, the relative contributions of which depend not only on the spatial resolution of the measurements, but also on stimulus duration, on magnetic field strength and on whether spin echo (SE) or gradient echo (GRE) detection is used. The two most dominant explanations of the PSU have been delayed vascular compliance (first venular, later arteriolar, and recently capillary) and sustained increases in CMRO(2), while post-activation reduction in CBF is a distant third. MRI has the capability to independently measure CBF and arteriolar, venous, and total CBV contributions in humans and animals, which has been of great assistance in improving the understanding of BOLD phenomena. Using currently available MRI and optical data, we conclude that the predominant PSU origin is a sustained increase in CMRO(2). However, some contributions from delayed vascular compliance are likely, and small CBF undershoot contributions that are difficult to detect with current arterial spin labeling technology can also not be excluded. The relative contribution of these different processes, which are not mutually exclusive and can act together, is likely to vary with stimulus duration and type.

Electroosmotically driven capillary transport of typical non-Newtonian biofluids in rectangular microchannels

In this paper, a detailed theoretical model is developed for studying the capillary filling dynamics of a non-Newtonian power-law obeying fluid in a microchannel subject to electrokinetic effects. Special attention is devoted to model the effects of the electroosmotic influences in the capillary advancement process, variable resistive forces acting over different flow regimes, and the dynamically evolving contact line forces, in mathematically closed forms. As an illustrative case study, in which the flow parameters are modeled as functions of the hematocrit fraction in the sample, the capillary dynamics of a blood sample are analyzed. Flow characteristics depicting advancement of the fluid within the microfluidic channel turn out to be typically non-linear, as per the relative instantaneous strengths of the capillary forces, electroosmotic forces and viscous resistances. Non-trivial implications of the blood hematocrit level and the imposed electric field on the progression of the capillary front are highlighted, which are expected to be of significant consequence towards the dynamics of electroosmotically aided capillary filling processes of biofluidic samples.

Analytical solutions for velocity, temperature and concentration distribution in electroosmotic microchannel flows of a non-Newtonian bio-fluid

In this paper, analytical solutions are derived, describing the transport characteristics of a non-Newtonian fluid flow in a rectangular microchannel, under the sole influence of electrokinetic forces. Apart from estimating the fully-developed velocity and temperature distributions, an explicit expression is derived for solutal concentration distribution within the microchannel. Finally, as an illustrative case study, the flow behaviour of a blood sample is analyzed, in which the flow parameters are modeled as functions of the hematocrit fraction in the sample. It is revealed that a higher hematocrit fraction may result in significant reductions in species concentration levels, on account of stronger dispersions in the velocity profiles, characterized by more significant viscous effects. It is also demonstrated that cases in which characteristic length scale of RBC suspensions turns out to be consequential relative to the microchannel dimensions, a significant augmentation in the electroosmotic transport may occur. Such observations can be of particular significance in the design of electroosmotically actuated bio-microfluidic systems as efficient solutal carriers.

Population pharmacokinetics of tacrolimus in adult kidney transplant recipients.

The aims of this study were to investigate the population pharmacokinetics of tacrolimus in adult kidney transplant recipients and to identify factors that explain variability. Population analysis was performed on retrospective data from 70 patients who received oral tacrolimus twice daily. Morning blood trough concentrations were measured by liquid chromatography-tandem mass spectrometry. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F), with the use of NONMEM (GloboMax LLC, Hanover, Md). Factors screened for influence on these parameters were weight, age, gender, postoperative day, days of tacrolimus therapy, liver function tests, creatinine clearance, hematocrit fraction, corticosteroid dose, and potential interacting drugs. CL/F was greater in patients with abnormally low hematocrit fraction (data from 21 patients only), and it decreased with increasing days of therapy and AST concentrations (P <.01). Average parameter estimates were as follows: CL/F = 31.8 L/h (hematocrit <0.33), CL/F = 24.2 L/h (hematocrit >0.33), and V/F = 2080 L. Marked interindividual variability (42% to 111%) and residual random error (3.7 ng/mL) were observed. On the basis of the derived model, a patient with normal AST (20 U/L) or high AST (200 U/L) concentrations 7 days after commencement of therapy would require a tacrolimus dose of 4.6 mg or 4.0 mg, respectively, to achieve a steady-state trough concentration of 10 ng/mL. The population pharmacokinetics of tacrolimus in adult kidney transplant recipients showed wide variability. Thus it is not possible to use a standard tacrolimus dose as an empiric predictor of concentration in this population. An understanding of factors that influence the pharmacokinetics of tacrolimus may assist in drug dosage decisions.

Quantitative assessment of changes in blood CO(2) tension mediated by the haldane effect.

Adequate assessment of circulatory and gas-exchange interactions may involve the quantification of the Haldane effect (HE) and of the changes in blood PCO(2) mediated by changes in Hb-O(2) saturation and O(2)-linked CO(2) binding. This is commonly prevented by the complexity of the involved calculations. To simplify the task, a large series of patient measurements has been processed by regression analysis, thus developing an accurate fit for this quantification (v-a) PCO(2)HE + 0.460 [(a-v) HbO(2)]0.999e0.015(PvCO(2))-0.852(Hct) (n = 247, r(2) = 0. 99, P << 0.001), where (v-a)PCO(2 HE) is the reduction in venous PCO(2) (Pv(CO(2)), Torr) allowed by the chemical binding of CO(2) in blood due to the HE (Torr), (a-v)HbO(2) is the arteriovenous difference in Hb-bound O(2) (ml/dl), and Hct is hematocrit fraction. Values of (v-a)PCO(2 HE) estimated by this expression compared well with the results of previously published experiments. This formula is useful in assessing the impact of HE on Pv(CO(2)) and venoarterial PCO(2) gradient and the survival advantage offered by HE in extreme conditions. Use may be extended to all investigative and clinical settings in which changes in blood O(2) saturation and O(2)-linked CO(2) binding must be converted into the corresponding changes in dissolved CO(2) and PCO(2).