In this study, the physiological values of volumes of plasma, cells, total blood and the F blood factors were identified in 24 adult tree shrews (Tupaia belangeri; 12 male and 12 female; average BW of 123.9±19.19 g). The two-compartment model method of Evans Blue dye was used to obtain the plasma volume and the venous hematocrit was measured by microhematocrit method. To establish the relationship between body weight (BW) and blood volume of tree shrews, We performed linear fitting for these two datasets. Results were analyzed according to gender and weight (<120g vs.>120g). Statistical significance was assessed using the unpaired student t test and one-way ANOVA. The average volumes per 100g body weight of plasma, red blood cell (RBC) and total blood were 5.42±0.543, 3.24±0.445, and 8.66±0.680ml respectively. The mean body hematocrit, cardiac hematocrit, jugular vein hematocrit, femoral vein hematocrit, and tail vein hematocrit was 37.43±4.096, 39.72±3.219, 43.04±4.717, 40.84±3.041, and 38.71±3.442% respectively. The F cardiac was 0.94±0.072, F jugular vein 0.88±0.118, F femoral vein 0.92±0.111, and the F tail vein 0.97±0.117. Blood volume (ml) was 85.89103×BW (kg). This is the first study to provide the parameters of plasma volume, cell volume, total blood volume and F factor and a baseline for future research on blood physiology of tree shrews.

Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis.

Resting-state brain activity has been widely investigated using blood oxygenation level dependent (BOLD) contrast techniques. However, BOLD signal changes reflect a combination of the effects of cerebral blood flow (CBF), cerebral blood volume (CBV), as well as the cerebral metabolic rate of oxygen (CMRO2). In this study, resting-state brain activation was detected and compared using the following techniques: (a) BOLD, using a gradient-echo echo planar imaging (GE-EPI) sequence; (b) CBV-weighted signal, acquired using gradient and spin echo (GRASE) based vascular space occupancy (VASO); and (c) CBF, using pseudo-continuous arterial spin labeling (pCASL). Reliable brain networks were detected using VASO and ASL, including sensorimotor, auditory, primary visual, higher visual, default mode, salience and left/right executive control networks. Differences between the resting-state activation detected with ASL, VASO and BOLD could potentially be due to the different temporal signal-to-noise ratio (tSNR) and the short post-labeling delay (PLD) in ASL, along with differences in the spin-echo readout of VASO. It is also possible that the dynamics of spontaneous fluctuations in BOLD, CBV and CBF could differ due to biological reasons, according to their location within the brain.

The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences.

Steady-state cerebral blood volume (CBV) is tightly coupled to regional cerebral metabolism, and CBV imaging is a variant of MRI that has proven useful in mapping brain dysfunction. CBV derived from exogenous contrast-enhanced MRI can generate sub-millimeter functional maps. Higher resolution helps to more accurately interrogate smaller cortical regions, such as functionally distinct regions of the hippocampus. Many MRIs have fortuitously adequate sequences required for CBV mapping. However, these scans vary substantially in acquisition parameters. Here, we determined whether previously acquired contrast-enhanced MRI scans ordered in patients with unilateral temporal lobe epilepsy can be used to generate hippocampal CBV. We used intrinsic reference regions to correct for intensity scaling on a research CBV dataset to identify white matter as a robust marker for scaling correction. Next, we tested the technique on a sample of unilateral focal epilepsy patients using clinical MRI scans. We find evidence suggestive of significant hypometabolism in the ipsilateral-hippocampus of unilateral TLE subjects. We also highlight the subiculum as a potential driver of this effect. This study introduces a technique that allows CBV maps to be generated retrospectively from clinical scans, potentially with broad application for mapping dysfunction throughout the brain.

The calculation of extracellular volume (ECV) in cardiac magnetic resonance requires hematocrit, limiting its applicability in clinical practice. Based on the linear relationship between hematocrit and blood T1 relaxivity, a synthetic ECV could be estimated without a blood sample. We aim to develop and test regression models for synthetic ECV without blood sampling in 1.5-T and 3.0-T scanners.

Fluid removal during HD is frequently associated with acute hypotension due to insufficient mobilization of extravascular fluid and subsequent hypovolemia. Large variability in vascular refilling makes dialysis therapy difficult and requires a better understanding of fluid distribution in the individual hemodialysis (HD) patient. Blood volume monitoring was performed by continuous measurement of blood density with a DMA 46 Density Meter (Fa. Chempro, PAAR, Austria) in six patients on regular HD treatment. A body filtration coefficient (CF = extra/intravascular fluid shift) was calculated using a computer model by Schneditz et al (1990) and blood density was measured during a 60-minute ultrafiltration period (1/3 x delta kg/hr = 19 +/- 4 ml/min). Concerning blood density differences (delta f%) and body filtration coefficient (CF) there was a wide inter-individual range (delta f = 2.8-8.0%, CF = 3-9 ml/mm Hg/min), but there was a good intraindividual reproducibility of delta f and CF. A negative correlation (r = -0.95) between delta f and CF could be established. The severity of hypotensive episodes and frequency of interventions correlated well with delta f and CF; severe symptoms occurred with a delta f > 6% and a CF < 4 ml/mm Hg/min. These results suggest that improvement in dialysis therapy can be achieved by blood volume monitoring and classification of "refilling types." By blood volume-controlled computerized sodium and UF profiles, a reduction of hypotensive episodes and emergency intervention might be possible.

Precise dispensing of droplets is a crucial step for acquiring reliable blood diagnostic results. When the source sample volume is limited, the need for precise dispensing of submicroliter and nanoliter quantities is especially important. In this paper, we developed a positive-displacement high-precision dispensing technique using a nickel electroformed tube with an inner diameter accuracy of [Formula: see text] or less. When dispensing variation of 100 nL was evaluated by using a photometric method, the most stable coefficients of variation (CV) were observed for a tube thickness of [Formula: see text] with hydrophobic treatment, where the average CV value was 1.3%, i.e., 1.3 nL. Furthermore, the glucose concentration of 100- and 200-nL animal-based control serum was colorimetrically measured using enzymatic reactions without drying and mixing reagents. The CV value was approximately 6.36% at 100 nL and 3.23% at 200 nL, suggesting that several biochemical panels can be precisely measured even from less than one drop of blood. This positive-displacement dispenser ensures zero contamination and almost-zero dead volume, thus it would be useful for multi-panel clinical blood testing.

Knowledge on sex differences in myocardial perfusion, blood volume (MBV), and extracellular volume (ECV) in healthy individuals is scarce and conflicting. Therefore, this was investigated quantitatively by cardiovascular magnetic resonance (CMR). Healthy volunteers (n = 41, 51% female) underwent CMR at 1.5 T. Quantitative MBV [%] and perfusion [ml/min/g] maps were acquired during adenosine stress and at rest following an intravenous contrast bolus (0.05 mmol/kg, gadobutrol). Native T1 maps were acquired before and during adenosine stress, and after contrast (0.2 mmol/kg) at rest and during adenosine stress, rendering rest and stress ECV maps. Compared to males, females had higher perfusion, ECV, and MBV at stress, and perfusion and ECV at rest (p < 0.01 for all). Multivariate linear regression revealed that sex and MBV were associated with perfusion (sex beta -0.31, p = 0.03; MBV beta -0.37, p = 0.01, model R2 = 0.29, p < 0.01) while sex and hematocrit were associated with ECV (sex beta -0.33, p = 0.03; hematocrit beta -0.48, p < 0.01, model R2 = 0.54, p < 0.001). Myocardial perfusion, MBV, and ECV are higher in female healthy volunteers compared to males. Sex is an independent contributor to perfusion and ECV, beyond other physiological factors that differ between the sexes. These findings provide mechanistic insight into sex differences in myocardial physiology.

In order to establish the involvement of particular neurochemical brain groups in the response to blood volume expansion, we analyzed Fos-labeling in combination with immunolabeling for serotonin, tyrosine hydroxylase, vasopressin and oxytocin, 90 min after a sham or i.v. isotonic blood volume expansion (BVE) in unanesthetized, unrestrained rats. We also examined the changes in concentration of oxytocin, atrial natriuretic peptide and vasopressin plasma, induced by blood volume load, to confirm our previous studies. The results demonstrate the participation of specific paraventricular and supraoptic nucleus groups of cells (oxytocinergic-vasopressinergic), serotoninergic dorsal raphe nucleus cells and catecholaminergic A1/A2/A6 groups (in the caudal ventrolateral medulla, nucleus of the solitary tract and locus coeruleus respectively), in the regulatory response to BVE. They provide detailed neuroanatomical evidence to support previous observations showing the contribution of these neurochemical systems in the neural, behavioral and endocrine response to isotonic BVE.

Scoliosis surgery is usually associated with severe bleeding. Various systemic strategies for blood conservation were applied, while the local techniques get less attention. The preemptive use of sufficient volume for proper tissue infiltration at two levels was applied. The local epinephrine may control bleeding without reliance upon deliberate hypotension, permitting a higher tissue perfusion.

Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps ). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Ps were overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis.

A vascular component is increasingly recognized as important in Alzheimer's disease (AD). We measured cerebral blood volume (CBV) in patients with probable AD or Mild Cognitive Impairment (MCI) and in elderly non-demented subjects using a recently developed Vascular-Space-Occupancy (VASO) MRI technique. While both gray and white matters were examined, significant CBV deficit regions were primarily located in white matter, specifically in frontal and parietal lobes, in which CBV was reduced by 20% in the AD/MCI group. The regions with CBV deficit also showed reduced tissue structural integrity as indicated by increased apparent diffusion coefficients, whereas in regions without CBV deficits no such correlation was found. Subjects with lower CBV tended to have more white matter lesions in FLAIR MRI images and showed slower psychomotor speed. These data suggest that the vascular contribution in AD is primarily localized to frontal/parietal white matter and is associated with brain tissue integrity.

The purpose of this study was to investigate the molecular background of cerebral blood volume (CBV) and vessel size (VS) of capillaries in glioblastoma multiforme (GBM). Both parameters are derived from extended perfusion MR imaging.A prospective case study including 21 patients (median age 66 years, 10 females) was performed. Before operation, CBV and VS of contrast enhancing tumor were assessed. Tissue was sampled from the assessed areas under neuronavigation control. After RNA extraction, transcriptional data was analyzed by Weighted Gene Co-Expression Network Analysis (WGCNA) and split into modules based on its network affiliations. Gene Set Enrichment Analysis (GSEA) identified biological functions or pathways of the genetic modules. These were applied on 484 GBM samples of the TCGA database.Ten modules were highly correlated to CBV and VS. One module was exclusively associated to VS and highly correlated to hypoxia, another one exclusively to CBV showing strong enrichments in the Epithelial Growth Factor (EGF) pathway and Epithelial-to-Mesenchymal-Transition (EMT). Moreover, patients with increased CBV and VS predominantly showed a mesenchymal gene-expression, a finding that could be corroborated by TCGA data.In conclusion, CBV and VS mirror different genetic pathways and reflect certain molecular subclasses of GBM.

Mixed findings regarding the effects of whole-body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non-heat stressed) subjects participated in this protocol. Changes in regional blood volume during heat stress and time control were estimated using technetium-99m labelled autologous red blood cells and gamma camera imaging. Whole-body heating increased internal temperature (> 1.0 degrees C), cutaneous vascular conductance (approximately fivefold), and heart rate (52 +/- 2 to 93 +/- 4 beats min(-1)), while reducing central venous pressure (5.5 +/- 07 to 0.2 +/- 0.6 mmHg) accompanied by minor decreases in mean arterial pressure (all P < 0.05). The heat stress reduced the blood volume of the heart (18 +/- 2%), heart plus central vasculature (17 +/- 2%), thorax (14 +/- 2%), inferior vena cava (23 +/- 2%) and liver (23 +/- 2%) (all P

Managing medical procedures for children with problematic disorders is a challenging approach, especially in the case of blood withdrawal for autism spectrum disorder-affected children. Peripheral blood mononuclear cells (PBMC) represent an important cellular model to study immune responses and drug toxicity. The monocytic cells, a fraction of PBMC, are strongly involved in some pathophysiological processes, such as inflammation and immune system changes. Here, we propose a simple, reliable protocol for obtaining peripheral blood-derived mononuclear cells from small volumes of blood samples.

A reduced central blood volume is reflected by a decrease in mid-regional plasma pro-atrial natriuretic peptide (MR-proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head-down tilt (HDT). We determined plasma MR-proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account.

The hemodynamic balloon model describes the change in coupling from underlying neural activity to observed blood oxygen level dependent (BOLD) response. It plays an increasing important role in brain research using magnetic resonance imaging (MRI) techniques. However, changes in the BOLD signal are sensitive to the resting blood volume fraction (i.e., [Formula: see text]) associated with the regional vasculature. In previous studies the value was arbitrarily set to a physiologically plausible value to circumvent the ill-posedness of the inverse problem. These approaches fail to explore actual [Formula: see text] value and could yield inaccurate model estimation.

The minimal-invasive transplantation of pancreatic islets is a promising approach to treat diabetes mellitus type 1. However, islet transplantation is still hampered by the insufficient process of graft revascularization, leading to a poor clinical outcome. Accordingly, the identification of novel compounds, which accelerate and improve the revascularization of transplanted islets, is of great clinical interest. Previous studies have shown that darbepoetin (DPO)-α, a long lasting analogue of erythropoietin, is capable of promoting angiogenesis. Hence, we investigated in this study whether DPO improves the revascularization of transplanted islets.

The study of biological processes has become increasingly reliant on obtaining high-resolution spatial and temporal data through imaging techniques. As researchers demand molecular resolution of cellular events in the context of whole organisms, correlation of non-invasive live-organism imaging with electron microscopy in complex three-dimensional samples becomes critical. The developing blood vessels of vertebrates form a highly complex network which cannot be imaged at high resolution using traditional methods. Here we show that the point of fusion between growing blood vessels of transgenic zebrafish, identified in live confocal microscopy, can subsequently be traced through the structure of the organism using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) and Serial Block Face/Scanning Electron Microscopy (SBF/SEM). The resulting data give unprecedented microanatomical detail of the zebrafish and, for the first time, allow visualization of the ultrastructure of a time-limited biological event within the context of a whole organism.