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Percutaneously absorbed carbon dioxide enhances blood flow. The mechanism by which it does so is unclear, but we hypothesized that it involves bicarbonate ions. BALB/c mice were bathed in neutral bicarbonate ionized water (NBIW) and showed increased blood bicarbonate levels and blood flow via phosphorylation of peripheral vascular endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO). Phosphorylation of eNOS and NO production were also increased in human umbilical vein endothelial cells cultured in medium containing NBIW, and NBIW showed reactive oxygen species scavenging activity. In a double-blind, randomized study in men and women aged 30 to 59 years with subjective cold intolerance, bathing in NBIW elevated body temperature faster than bathing in a control solution and improved chills and sleep quality. Taken together, our results show that percutaneously absorbed carbon dioxide changes to bicarbonate ions, which act directly on endothelial cells to increase NO production by phosphorylation of eNOS and thus improve blood flow. [ABSTRACT FROM AUTHOR]

Endothelial cells and pericytes are highly dynamic vascular cells and several subtypes, based on their spatiotemporal dynamics or molecular expression, are believed to exist. The interaction between endothelial cells and pericytes is of importance in many aspects ranging from basic development to diseases like cancer. Identification of spatiotemporal dynamics is particularly interesting and methods to studies these are in demand. Here we describe the technical details of a method combining the benefits of high resolution intravital imaging and whole-mount histology. With intravital imaging using an adapted light weight dorsal skinfold chamber we identified blood flow patterns and spatiotemporal subtypes of endothelial cells and pericytes in a 4D (XYZ, spatial+T, time dimension) manner as representative examples for this model. Thereafter the tissue was extracted and stained as a whole-mount, by which the position and volumetric space of endothelial cells as well as pericytes were maintained, to identify molecular subtypes. Integration of the two imaging methods enabled 4D dissection of endothelial cell–pericyte association at the molecular level. [ABSTRACT FROM AUTHOR]

The current work analyzes the effects of concentric ballooned catheterization and heat transfer on the hybrid nano blood flow through diseased arterial segment having both stenosis and aneurysm along its boundary. A fractional second-grade fluid model is considered which describes the non-Newtonian characteristics of the blood. Governing equations are linearized under mild stenosis and mild aneurysm assumptions. Precise articulations for various important flow characteristics such as heat transfer, hemodynamic velocity, wall shear stress, and resistance impedance are attained. Graphical portrayals for the impact of the significant parameters on the flow attributes have been devised. The streamlines of blood flow have been examined as well. The present finding is useful for drug conveyance system and biomedicines. [ABSTRACT FROM AUTHOR]

Magnetic resonance elastography (MRE) is a reliable noninvasive method for assessment of hepatic stiffness. Liver stiffness is known to be affected by elevated postprandial portal blood flow in patients with chronic liver disease. The goal of this study was to determine whether food intake affects liver stiffness in the absence of known liver disease. We evaluated 100 volunteers (35 men and 65 women) who met inclusion criteria. The subjects had two MRE examinations, first while fasting and then 30 min after a test meal. Fourteen subjects also had two additional MRE exams 1 h 30 min and 2 h 30 min after the meal. Liver stiffness was measured by placing the largest possible polygon ROIs on the four widest liver slices and calculated as a mean of stiffness values from each slice. The correlation of liver stiffness values before and after the meal was assessed using a paired t-test. To evaluate the relationship between the change in postprandial liver stiffness and fasting liver stiffness values, linear regression was performed. The liver stiffness values in the fasting state ranged from 1.84 to 2.82 kPa, with a mean of 2.30 ± 0.23 kPa (95% CI 2.25–2.34). At 30 min after the meal, liver stiffness values ranged from 2.12 to 3.50 kPa, with a mean of 2.70 ± 0.28 kPa (95% CI 2.64–2.75), demonstrating a systematic postprandial increase by 0.40 ± 0.23 kPa (17.7 ± 3.5%). Meal intake significantly increases liver stiffness in healthy individuals, which persists for at least 2 h 30 min. Patients should fast for 3–4 h before MRE examinations to avoid fibrosis overstaging due to postprandial liver stiffness augmentation. [ABSTRACT FROM AUTHOR]

Whether post injectional acute intraocular pressure (IOP) increase is associated with decreased peripapillary and macular perfusion is still under debate. Here, we investigated early changes in the choroidal and retinal blood flow using OCTA imaging in a cohort of patients undergoing anti-VEGF intravitreal injections (IVI) for macular edema following retinal vein occlusion and diabetic retinopathy. In this prospective single-center, observational study, the pre- and post-IVI changes in retinal perfusion were examined via assessment of vessel length density (VLD) and vessel density (VD) in deep and superficial capillary segmentations (DCP and SCP), foveal avascular zone (FAZ) in SCP, as well as flow signal deficits in the choriocapillaris segmentation. Mean IOP significantly changed over the study course (p = 0.000; ANOVA). Measurements at 5 min post-IVI (33.48 ± 10.84 mmHg) differed significantly from baseline (17.26 ± 2.41 mmHg, p = 0.000), while measurements from one day, one week, and one-month post-IVI did not (p = 0.907, p = 1.000 and p = 1.000 respectively). In comparison to baseline, no changes in OCTA parameters, including FAZ, VD, VLD, and FV, were detected 5 min post-IVI. No significant alterations in OCTA parameters were observed during study course. Increased IOP spikes were detected post-IVI; however, no potential permanent ischemic retinal damage was suspected. [ABSTRACT FROM AUTHOR]

We recently documented that cardiopulmonary resuscitation (CPR) generates the same level of cardiac output (CO) and mean arterial pressure (MAP) during both normothermia (38 °C) and hypothermia (27 °C). Furthermore, continuous CPR at 27 °C provides O2 delivery (ḊO2) to support aerobic metabolism throughout a 3-h period. The aim of the present study was to investigate the effects of extracorporeal membrane oxygenation (ECMO) rewarming to restore ḊO2 and organ blood flow after prolonged hypothermic cardiac arrest. Eight male pigs were anesthetized and immersion cooled to 27 °C. After induction of hypothermic cardiac arrest, CPR was started and continued for a 3-h period. Thereafter, the animals were rewarmed with ECMO. Organ blood flow was measured using microspheres. After cooling with spontaneous circulation to 27 °C, MAP and CO were initially reduced to 66 and 44% of baseline, respectively. By 15 min after the onset of CPR, there was a further reduction in MAP and CO to 42 and 25% of baseline, respectively, which remained unchanged throughout the rest of 3-h CPR. During CPR, ḊO2 and O2 uptake (V̇O2) fell to critical low levels, but the simultaneous small increase in lactate and a modest reduction in pH, indicated the presence of maintained aerobic metabolism. Rewarming with ECMO restored MAP, CO, ḊO2, and blood flow to the heart and to parts of the brain, whereas flow to kidneys, stomach, liver and spleen remained significantly reduced. CPR for 3-h at 27 °C with sustained lower levels of CO and MAP maintained aerobic metabolism sufficient to support ḊO2. Rewarming with ECMO restores blood flow to the heart and brain, and creates a "shockable" cardiac rhythm. Thus, like continuous CPR, ECMO rewarming plays a crucial role in "the chain of survival" when resuscitating victims of hypothermic cardiac arrest. [ABSTRACT FROM AUTHOR]

Fluid flow shear stresses are strong regulators for directing the organization of vascular networks. Knowledge of structural and flow dynamics information within complex vasculature is essential for tuning the vascular organization within engineered tissues, by manipulating flows. However, reported investigations of vascular organization and their associated flow dynamics within complex vasculature over time are limited, due to limitations in the available physiological pre-clinical models, and the optical inaccessibility and aseptic nature of these models. Here, we developed laser speckle contrast imaging (LSCI) and side-stream dark field microscopy (SDF) systems to map the vascular organization, spatio-temporal blood flow fluctuations as well as erythrocytes movements within individual blood vessels of developing chick embryo, cultured within an artificial eggshell system. By combining imaging data and computational simulations, we estimated fluid flow shear stresses within multiscale vasculature of varying complexity. Furthermore, we demonstrated the LSCI compatibility with bioengineered perfusable muscle tissue constructs, fabricated via molding techniques. The presented application of LSCI and SDF on perfusable tissues enables us to study the flow perfusion effects in a non-invasive fashion. The gained knowledge can help to use fluid perfusion in order to tune and control multiscale vascular organization within engineered tissues. [ABSTRACT FROM AUTHOR]

Laser Doppler holography is a planar blood flow imaging technique recently introduced in ophthalmology to image human retinal and choroidal blood flow non-invasively. Here we present a digital method based on the Doppler spectrum asymmetry that reveals the local direction of blood flow with respect to the optical axis in out-of-plane vessels. This directional information is overlaid on standard grayscale blood flow images to depict flow moving towards the camera in red and flow moving away from the camera in blue, as in ultrasound color Doppler imaging. We show that thanks to the strong contribution of backscattering to the Doppler spectrum in out-of-plane vessels, the local axial direction of blood flow can be revealed with a high temporal resolution, which enables us to evidence pathological blood flow reversals. We also demonstrate the use of optical Doppler spectrograms to quantitatively monitor retinal blood flow reversals. [ABSTRACT FROM AUTHOR]

Cerebral hypoperfusion impairs brain activity and leads to cognitive impairment. Left and right common carotid arteries (CCA) are the major source of cerebral blood supply. It remains unclear whether blood flow in both CCA contributes equally to brain activity. Here, CCA blood flow was evaluated using ultrasonography in 23 patients with cerebrovascular diseases. Resting-state brain activity and cognitive status were also assessed using magnetoencephalography and a cognitive subscale of the Functional Independence Measure, respectively, to explore the relationships between blood flow, functional brain activity, and cognitive status. Our findings indicated that there was an association between blood flow and resting-state brain activity, and between resting-state brain activity and cognitive status. However, blood flow was not significantly associated with cognitive status directly. Furthermore, blood velocity in the right CCA correlated with resting-state brain activity, but not with the resistance index. In contrast, the resistance index in the left CCA correlated with resting-state brain activity, but not with blood velocity. Our findings suggest that hypoperfusion is important in the right CCA, whereas cerebral microcirculation is important in the left CCA for brain activity. Hence, this asymmetry should be considered when designing appropriate therapeutic strategies. [ABSTRACT FROM AUTHOR]

Tumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression. [ABSTRACT FROM AUTHOR]

A method was established using a scaffold-bioreactor system to examine the impact pulsatile blood flow has on the decellularized porcine kidney vascular architecture and functionality. These scaffolds were subjected to continuous arterial perfusion of whole blood at normal physiological (650 ml/min and 500 ml/min) and pathophysiological (200 ml/min) rates to examine dynamic changes in venous outflow and micro-/macrovascular structure and patency. Scaffolds subjected to normal arterial perfusion rates observed drops in venous outflow over 24 h. These reductions rose from roughly 40% after 12 h to 60% after 24 h. There were no apparent signs of clotting at the renal artery, renal vein, and ureter. In comparison, venous flow rates decreased by 80% to 100% across the 24 h in acellular scaffolds hypoperfused at a rate of 200 ml/min. These kidneys also appeared intact on the surface after perfusion. However, they presented several arterial, venous, and ureteral clots. Fluoroscopic angiography confirmed substantial alterations to normal arterial branching patterns and patency, as well as parenchymal damage. Scanning electron microscopy revealed that pulsatile blood perfusion significantly disrupted glomerular microarchitecture. This study provides new insight into circumstances that limit scaffold viability and a simplified model to analyze conditions needed to prepare more durable scaffolds for long-term transplantation. [ABSTRACT FROM AUTHOR]

VO2max (maximal oxygen consumption), a validated measure of aerobic fitness, has been associated with better cerebral artery compliance and measures of brain morphology, such as higher cortical thickness (CT) in frontal, temporal and cingular cortices, and larger grey matter volume (GMV) of the middle temporal gyrus, hippocampus, orbitofrontal cortex and cingulate cortex. Single sessions of physical exercise can promptly enhance cognitive performance and brain activity during executive tasks. However, the immediate effects of exercise on macro-scale properties of the brain's grey matter remain unclear. We investigated the impact of one session of moderate-intensity physical exercise, compared with rest, on grey matter volume, cortical thickness, working memory performance, and task-related brain activity in older adults. Cross-sectional associations between brain measures and VO2max were also tested. Exercise did not induce statistically significant changes in brain activity, grey matter volume, or cortical thickness. Cardiovascular fitness, measured by VO2max, was associated with lower grey matter blood flow in the left hippocampus and thicker cortex in the left superior temporal gyrus. Cortical thickness was reduced at post-test independent of exercise/rest. Our findings support that (1) fitter individuals may need lower grey matter blood flow to meet metabolic oxygen demand, and (2) have thicker cortex. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the hemodynamic effect of norepinephrine (NE) on the peak systolic velocity (PSV), diameter, and blood flow of the common carotid artery (CCA) using the point-of-care ultrasound (POCUS) in patients with septic shock. The study involved patients above 18 years old with septic shock. Arterial monitoring, carotid ultrasonography, and transthoracic echocardiography were performed before NE administration (T0). When the mean arterial pressure exceeded 65 mmHg after NE administration (T1), the measurement was repeated. Twenty-four patients (median age 67 [interquartile range: 54–77] years; 42% female) with septic shock were examined in this study. Before (T0) and after (T1) NE administration, the PSV (mean, standard deviation [SD]) changed from 85.3 (21.1) cm/s to 83.5 (23.5) cm/s (p = 0.417); this change was not significant. However, the diameter and blood flow of the CCA increased significantly from 0.6 (0.09) cm and 0.75 (0.27) L/min to 0.66 (0.09) cm and 0.85 (0.27) L/min, respectively (p < 0.001). The diameter of the left ventricular outflow tract (LVOT) remained unchanged, but the velocity time integral of the LVOT increased significantly from 21.7 (4.39) cm to 23.6 (5.14) cm. There was no significant correlation between changes in blood flow of the CCA and changes in cardiac output (coefficient −0.365, p = 0.079). In conclusion, NE increased the diameter and blood flow of the CCA significantly, without changing the PSV in patients with septic shock. [ABSTRACT FROM AUTHOR]

The return of blood flow to ischemic heart after myocardial infarction causes ischemia–reperfusion injury. There is a clinical need for novel therapeutic targets to treat myocardial ischemia–reperfusion injury. Here we screened for targets for the treatment of ischemia–reperfusion injury using a combination of shRNA and drug library analyses in HL-1 mouse cardiomyocytes subjected to hypoxia and reoxygenation. The shRNA library included lentiviral constructs targeting 4625 genes and the drug library 689 chemical compounds approved by the Food and Drug Administration (FDA). Data were analyzed using protein–protein interaction and pathway analyses. EGFR inhibition was identified as a cardioprotective mechanism in both approaches. Inhibition of EGFR kinase activity with gefitinib improved cardiomyocyte viability in vitro. In addition, gefitinib preserved cardiac contractility in zebrafish embryos exposed to hypoxia-reoxygenation in vivo. These findings indicate that the EGFR inhibitor gefitinib is a potential candidate for further studies of repurposing the drug for the treatment of myocardial infarction. [ABSTRACT FROM AUTHOR]

Aortic dissection (AD) is one of the fatal and complex conditions. Since there is a lack of a specific treatment guideline for type-B AD, a better understanding of patient-specific hemodynamics and therapy outcomes can potentially control the progression of the disease and aid in the clinical decision-making process. In this work, a patient-specific geometry of type-B AD is reconstructed from computed tomography images, and a numerical simulation using personalised computational fluid dynamics (CFD) with three-element Windkessel model boundary condition at each outlet is implemented. According to the physiological response of beta-blockers to the reduction of left ventricular contractions, three case studies with different heart rates are created. Several hemodynamic features, including time-averaged wall shear stress (TAWSS), highly oscillatory, low magnitude shear (HOLMES), and flow pattern are investigated and compared between each case. Results show that decreasing TAWSS, which is caused by the reduction of the velocity gradient, prevents vessel wall at entry tear from rupture. Additionally, with the increase in HOLMES value at distal false lumen, calcification and plaque formation in the moderate and regular-heart rate cases are successfully controlled. This work demonstrates how CFD methods with non-invasive hemodynamic metrics can be developed to predict the hemodynamic changes before medication or other invasive operations. These consequences can be a powerful framework for clinicians and surgical communities to improve their diagnostic and pre-procedural planning. [ABSTRACT FROM AUTHOR]

To investigate the correlation between posterior pole choroidal blood flow evaluated with digital subtraction indocyanine green angiography and enface optical coherence tomography angiography (OCTA). Imaging in animal study. The anatomy of 2 cynomogulus monkeys was studied. Each monkey was given a 0.75 mg/kg injection of indocyanine green in the saphenous vein. The dynamic angiographic filling sequence was recorded at 15 frames per second using the Heidelberg Spectralis. After image registration, sequential frame subtraction was used to image the dye front moving through the choroid. The OCTA was obtained by frame averaging nine separate choriocapillaris slab flow images obtained from the Zeiss Plex Elite 9000. Posterior pole choriocapillaris filling pattern in relation to the choriocapillaris anatomy as imaged by OCTA. In the posterior pole, the choriocapillaris fills in the pattern of discrete units with variable sizes and shapes. The cycle of dye filling begins in the peripapillary area and progresses toward the periphery in a wavelike manner. This filling pattern repeats in a cyclical manner, consistent with the cardiac cycle. OCTA shows a uniform mesh of vessels. While OCTA shows a uniform meshwork appearance of the choriocapillaris, the dynamic dye angiography suggests an irregular configuration of functional units partitioned by pressure gradients as opposed to structural boundaries. Disturbance of local perfusion pressure within choroidal vasculature may result in abnormal flow patterns, which could be evaluated in the clinic using commercially available equipment. [ABSTRACT FROM AUTHOR]

This study investigates the use of hydralazine to enhance ultrasound hyperthermia for the treatment of hepatocellular carcinoma (HCC) by minimizing flow-mediated heat loss from the tumor. Murine HCC tumors were treated with a continuous mode ultrasound with or without an intravenous administration of hydralazine (5 mg/kg). Tumor blood flow and blood vessels were evaluated by contrast-enhanced ultrasound (CEUS) imaging and histology, respectively. Hydralazine markedly enhanced ultrasound hyperthermia through the disruption of tumor blood flow in HCC. Ultrasound treatment with hydralazine significantly reduced peak enhancement (PE), perfusion index (PI), and area under the curve (AUC) of the CEUS time-intensity curves by 91.9 ± 0.9%, 95.7 ± 0.7%, and 96.6 ± 0.5%, compared to 71.4 ± 1.9%, 84.7 ± 1.1%, and 85.6 ± 0.7% respectively without hydralazine. Tumor temperature measurements showed that the cumulative thermal dose delivered by ultrasound treatment with hydralazine (170.8 ± 11.8 min) was significantly higher than that without hydralazine (137.7 ± 10.7 min). Histological assessment of the ultrasound-treated tumors showed that hydralazine injection formed larger hemorrhagic pools and increased tumor vessel dilation consistent with CEUS observations illustrating the augmentation of hyperthermic effects by hydralazine. In conclusion, we demonstrated that ultrasound hyperthermia can be enhanced significantly by hydralazine in murine HCC tumors by modulating tumor blood flow. Future studies demonstrating the safety of the combined use of ultrasound and hydralazine would enable the clinical translation of the proposed technique. [ABSTRACT FROM AUTHOR]

Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, TI NiRS , of cerebrovascular health. TI NiRS is a novel use of the NiRS technology. TI NiRS is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both TI NiRS and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely transcranial Doppler (TCD) augmentation index, AI TCD , and magnetic resonance imaging (MRI) blood flow pulsatility index, PI MRI . The TI NiRS correlations with Age, CRF, PI MRI and AI TCD all are significant, i.e., r = 0.53 ( p = 0.002 ), r = - 0.44 ( p = 0.011 ), r = 0.45 ( p = 0.012 ) and r = 0.46 ( p = 0.010 ), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform. [ABSTRACT FROM AUTHOR]

The deficiency of protein C (PROC) can be partly rescued by Rex shunt through restoring portal blood flow in children with extra-hepatic portal venous obstruction (EHPVO). However, the decline of PROC is still found in some patients with a normal portal blood flow after Rex shunt. The aim of this study was to identify the candidate miRNAs involving in the decline of PROC and their mechanism. The protein level of PROC was detected by the ELISA assay, and was compared between sick and healthy groups. The expressions of miRNAs and PROC mRNA were measured using qRT-PCR, and were compared between sick and healthy groups. The correlation between PROC and candidate miRNAs was analysed by a Pearson correlation analysis to identify the most significant miRNAs. The expression of PROC mRNA was detected by qRT-PCR in HL-7702 and LX-2 cells tansfected with miRNAs mimics or inhibitors and negative control (NC) mimics, which was compared among the different groups. The rates of liver cells' proliferation and apoptosis were detected in HL-7702 and LX-2 cells tansfected with miRNAs mimics or inhibitors or with overexpressing PROC and negative control mimics by CKK8 assay and flow cytometry, which were compared among the different groups. The expressions of COX-2 and VEGF were measured by qRT-PCR, and were compared between the miRNAs groups and NC group. Western blot was assayed for detecting the protein levels of PROC, COX-2, VEGF, Bcl-2 and Bax, which were compared between the miRNAs groups and NC group. The expression of PROC mRNA was lower, and the expressions of miR-506-3p and miR-124-3p were higher in children with EHPVO than healthy group. PROC mRNA was negatively correlated with the expression of miR-506-3p and miR-124-3p. Compared to the NC group, the transcription activity of PROC was lower after exposure of miR-506 and miR-124 mimics in HL-7702 and LX-2 cells, but this phenomenon was reversed after inhibiting miR-506 and miR-124. The rate of cell proliferation was lower after exposure of miR-506 and miR-124 than the NC group, which was increased after inhibiting miR-506 and miR-124 in HL-7702 cells and overexpressing PROC in LX-2 cells. The apoptotic rate was higher after exposure of miR-506 and miR-124 than the NC group, which was decreased after inhibiting miR-506 and miR-124 in HL-7702 cells and overexpressing PROC in LX-2 cells. The mRNA levels of COX-2 and VEGF were significantly higher after exposure of miR-506 and miR-124 mimics than those in the NC group. The protein levels of PROC and Bcl-2 were down-regulated, and the levels of COX-2, Bax and VEGF were up-regulated after exposure of miR-506 and miR-124 in HL-7702 cells, but this phenomenon was reversed after inhibiting miR-506 and miR-124. MiR-506-3p and miR-124-3p may involve in the decline of PROC in protein and transcriptional level, in which the anti-proliferation and pro-apoptosis role of miR-506-3p and miR-124-3p for liver cells may involve in this mechanism. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is used in the production of plastics approved for contact with feed and food. Upon entering living organisms, BPA, as a potent endocrine disruptor, negatively affects various internal organs and regulatory systems, especially in young individuals. Although previous studies have described the neurotoxic effects of BPA on various tissues, it should be underlined that the putative influence of this substance on the chemical architecture of the urinary bladder intrinsic innervation has not yet been studied. One of the most important neuronal substances involved in the regulation of urinary bladder functions is vasoactive intestinal polypeptide (VIP), which primarily participates in the regulation of muscular activity and blood flow. Therefore, this study aimed to determine the influence of various doses of BPA on the distribution pattern of VIP-positive neural structures located in the wall of the porcine urinary bladder trigone using the double-immunofluorescence method. The obtained results show that BPA influence leads to an increase in the number of both neurons and nerve fibres containing VIP in the porcine urinary bladder trigone. This may indicate that VIP participates in adaptive processes of the urinary bladder evoked by BPA. [ABSTRACT FROM AUTHOR]

One of the most common acute and chronic cardiovascular disease conditions is aortic stenosis, a disease in which the aortic valve is damaged and can no longer function properly. Moreover, aortic stenosis commonly exists in combination with other conditions causing so many patients suffer from the most general and fundamentally challenging condition: complex valvular, ventricular and vascular disease (C3VD). Transcatheter aortic valve replacement (TAVR) is a new less invasive intervention and is a growing alternative for patients with aortic stenosis. Although blood flow quantification is critical for accurate and early diagnosis of C3VD in both pre and post-TAVR, proper diagnostic methods are still lacking because the fluid-dynamics methods that can be used as engines of new diagnostic tools are not well developed yet. Despite remarkable advances in medical imaging, imaging on its own is not enough to quantify the blood flow effectively. Moreover, understanding of C3VD in both pre and post-TAVR and its progression has been hindered by the absence of a proper non-invasive tool for the assessment of the cardiovascular function. To enable the development of new non-invasive diagnostic methods, we developed an innovative image-based patient-specific computational fluid dynamics framework for patients with C3VD who undergo TAVR to quantify metrics of: (1) global circulatory function; (2) global cardiac function as well as (3) local cardiac fluid dynamics. This framework is based on an innovative non-invasive Doppler-based patient-specific lumped-parameter algorithm and a 3-D strongly-coupled fluid-solid interaction. We validated the framework against clinical cardiac catheterization and Doppler echocardiographic measurements and demonstrated its diagnostic utility by providing novel analyses and interpretations of clinical data in eleven C3VD patients in pre and post-TAVR status. Our findings position this framework as a promising new non-invasive diagnostic tool that can provide blood flow metrics while posing no risk to the patient. The diagnostic information, that the framework can provide, is vitally needed to improve clinical outcomes, to assess patient risk and to plan treatment. [ABSTRACT FROM AUTHOR]

To compare changes in spectral CT iodine densities of hepatic parenchyma and vessels before and after transjugular intrahepatic portosystemic shunt (TIPS) in hepatitis B virus (HBV)-related liver cirrhosis. Twenty-five patients with HBV-related liver cirrhosis who received TIPS for gastroesophageal varices bleeding were recruited. Each patient underwent three phases contrast CT before and after TIPS within 4 weeks, with the raw data reconstructed at 1.25-mm-thick slices. Iodine density (in milligrams per milliliter) was measured on iodine-based material decomposition image. Multiple regions of interest (ROIs) in liver parenchyma, aorta and portal vein were selected from three slices of images. Portal vein trunk was set as the central one, and mean liver parenchymal iodine densities from arterial phase (AP), venous phase (VP) and equilibrium phase (EP) were recorded. Quantitative indices of iodine density (ID), including normalized ID in liver parenchyma for arterial phase (NIDLAP), ID of liver parenchyma for venous phase (IDLVP), ID of portal vein in venous phase (IDPVP) and liver arterial iodine density fraction (AIF), were measured and compared before and after TIPS. Based on Child–Pugh stage, 4, 12 and 9 patients were classified as grade A, B, and C, respectively. Liver volume was comparable before and after TIPS (1110.5 ± 287.4 vs. 1092.0 ± 276.3, P = 0.28). After TIPS, ID was decreased in aorta (146.0 ± 34.5 vs. 120.9 ± 30.7, P < 0.01) whereas increased in liver parenchyma at arterial phase, as demonstrated by IDAP (9.3 ± 3.1 vs. 13.4 ± 4.4 mg/mL) and AIF (0.40 ± 0.11 vs. 0.58 ± 0.11, P < 0.01). For venous or equilibrium phase, quantitative indices remained stable (23.1 ± 4.5 vs. 23.0 ± 5.3, 19.8 ± 4.1 vs. 19.4 ± 4.6) mg/mL (Ps > 0.05). For portal vein, ID and NID were increased after TIPS (23.1 ± 11.7 vs. 36.5 ± 13.0, 16.4 ± 8.5 vs. 31.8 ± 12.8) (P < 0.01). No positive correlation between iodine density and preoperative Child–Pugh score was observed. Based on iodine density measurement, spectral CT as a noninvasive imaging modality may assess hepatic parenchyma and vascular blood flow changes before and after TIPS in HBV-related liver cirrhosis. Clinical registration number: ChiCTR- DDC-16009986. [ABSTRACT FROM AUTHOR]

Microvascular blood flow is crucial for tissue and organ function and is often severely affected by diseases. Therefore, investigating the microvasculature under different pathological circumstances is essential to understand the role of the microcirculation in health and sickness. Microvascular blood flow is generally investigated with Intravital Video Microscopy (IVM), and the captured images are stored on a computer for later off-line analysis. The analysis of these images is a manual and challenging process, evaluating experiments very time consuming and susceptible to human error. Since more advanced digital cameras are used in IVM, the experimental data volume will also increase significantly. This study presents a new two-step image processing algorithm that uses a trained Convolutional Neural Network (CNN) to functionally analyze IVM microscopic images without the need for manual analysis. While the first step uses a modified vessel segmentation algorithm to extract the location of vessel-like structures, the second step uses a 3D-CNN to assess whether the vessel-like structures have blood flowing in it or not. We demonstrate that our two-step algorithm can efficiently analyze IVM image data with high accuracy (83%). To our knowledge, this is the first application of machine learning for the functional analysis of microvascular blood flow in vivo. [ABSTRACT FROM AUTHOR]

After craniofacial trauma, symptoms like swelling and pain occur. Cooling reduces these symptoms but the optimal cooling temperature for a maximum benefit without adverse effects is unclear. 30 participants were cooled at 10 °C, 15 °C, 20 °C, 25 °C and 30 °C for 30 min. Before cooling and at 15, 30, 45 and 60 min after cooling, the skin blood flow, oxygen saturation (SO) and haemoglobin concentration (Hb) were measured by laser Doppler spectrophotometry at 2 mm and 8 mm depth. The skin temperature was measured, and the participant's satisfaction was marked on a visual analogue scale. There were significant differences between males and females in the blood flow, SO and Hb (p < 0.0001). After cooling, the blood flow, SO and Hb was reduced. The measured values rose slightly above the initial values 60 min after cooling. Depending on the cooling temperature the decrease in blood flow, SO and Hb was significantly different. Both sexes were most comfortable with a 25 °C cooling temperature and satisfaction decreased with lower temperatures. Significant differences for the satisfaction between both sexes were measured (10 °C: p < 0.0001, 15 °C: p < 0.0001, 20 °C: p = 0.0168, 25 °C: p = 0.0293). After 60 min, the males and females exhibited mild skin hyperthermia. The optimal cooling temperatures their physiological effects and their perception for females and males were different. For females, around 20 °C is an optimal cooling temperature. For males, it is around 15–20 °C. [ABSTRACT FROM AUTHOR]

Functional studies in the central nervous system are often conducted using anesthesia. While the dose-dependent effects of anesthesia on neuronal activity have been extensively characterized in adults, little is known about the effects of anesthesia on cortical activity and cerebral blood flow in the immature central nervous system. Substitution of electrophysiological recordings with the less-invasive technique of optical intrinsic signal imaging (OIS) in vivo allowed simultaneous recordings of sensory-evoked functional response and local blood flow changes in the neonatal rat barrel cortex. Using OIS we characterize the effects of two widely used anesthetics—urethane and isoflurane. We found that both anesthetics suppressed the sensory-evoked optical intrinsic signal in a dose-dependent manner. Dependence of the cortical response suppression matched the exponential decay model. At experimental levels of anesthesia, urethane affected the evoked cortical response less than isoflurane, which is in agreement with the results of electrophysiological recordings demonstrated by other authors. Changes in oxygenation and local blood flow also showed negative correlation with both anesthetics. The high similarity in immature patterns of activity recorded in different regions of the developing cortex suggested similar principles of development regardless of the cortical region. Therefore the indicated results should be taken into account during functional explorations in the entire developing cortex. Our results also point to urethane as the anesthetic of choice in non-survival experimental recordings in the developing brain as it produces less prominent impairment of cortical neuronal activity in neonatal animals. [ABSTRACT FROM AUTHOR]

Dynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg−1 bodyweight−1. Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia–reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min−1) 1.68 (1.02–2.35) versus 2.84 (2.15–3.53), p = 0.002, mean arterial pressure (mmHg) 29.89 (21.65–38.12) versus 52.34 (43.55–61.14), p < 0.001, pulse pressure variation (%) 24.84 (17.45–32.22) versus 9.59 (1.68–17.49), p = 0.004, mean Flux (p.u.) 414.95 (295.18–534.72) versus 327.21 (206.95–447.48), p = 0.006. Receiver operating characteristic analysis revealed an area under the curve of 0.88 (CI 95% 0.73–1.00; p value < 0.001) for pulse pressure variation for predicting a decrease of microcirculatory blood flow. The results of our study show that pulse pressure variation does have the potential to predict decreases of intestinal microcirculatory blood flow due to volume-load after ischemia/reperfusion-injury. This should encourage further translational research and might help to prevent microcirculatory impairment due to excessive fluid resuscitation and to guide fluid therapy in the future. [ABSTRACT FROM AUTHOR]

Optical coherence tomography (OCT) angiography (OCTA) is a non-invasive tool for the in-vivo study of the intraretinal vascular network. It is based on the analysis of motion particles within the retina to reconstruct the paths followed by the erythrocytes, i.e. retinal capillaries. To date, qualitative and quantitative information are based on the morphological features disclosed by retinal capillaries. In the present study, we proposed new quantitative functional metrics, named Total Flow Intensity (TFI), Active Flow Intensity (AFI), and Volume-related Flow Intensity (VFI), based on the processing of the blood flow signal detected by OCTA. We studied these metrics in a cohort of healthy subjects, and we assessed their clinical utility by including a cohort of age-matched patients affected by Stargardt disease. Moreover, we compared TFI, AFI, and VFI to the widely used vessel density (VD) parameter. TFI, AFI, and VFI were able to describe in detail the different properties of the retinal vascular compartment. In particular, TFI was intended as the overall amount of volumetric retinal blood flow. AFI represented a selective measure of voxels disclosing blood flow signal. VFI was developed to put in relationship the volumetric blood flow information with the not vascularized retinal volume. In conclusion, TFI, AFI, and VFI were proposed as feasible functional OCTA biomarkers based on the analysis of retinal blood flow signal. [ABSTRACT FROM AUTHOR]

Quantitative Doppler ultrasound of the carotid artery has been proposed as an instantaneous surrogate for monitoring rapid changes in left ventricular output. Tracking immediate changes in the arterial Doppler spectrogram has value in acute care settings such as the emergency department, operating room and critical care units. We report a novel, hands-free, continuous-wave Doppler ultrasound patch that adheres to the neck and tracks Doppler blood flow metrics in the common carotid artery using an automated algorithm. String and blood-mimicking test objects demonstrated that changes in velocity were accurately measured using both manually and automatically traced Doppler velocity waveforms. In a small usability study with 22 volunteer users (17 clinical, 5 lay), all users were able to locate the carotid Doppler signal on a volunteer subject, and, in a subsequent survey, agreed that the device was easy to use. To illustrate potential clinical applications of the device, the Doppler ultrasound patch was used on a healthy volunteer undergoing a passive leg raise (PLR) as well as on a congestive heart failure patient at resting baseline. The wearable carotid Doppler patch holds promise because of its ease-of-use, velocity measurement accuracy, and ability to continuously record Doppler spectrograms over many cardiac and respiratory cycles. [ABSTRACT FROM AUTHOR]

The coronary slow flow phenomenon (CSFP) is common in coronary angiography, however its impact on left atrial (LA) function is still controversial. This study aims to evaluate the LA structure and function of patients with CSFP using two-dimensional speckle tracking echocardiography (2D-STE). Consecutive patients scheduled for coronary angiography from January 2016 to September 2017 were enrolled in this study. Patients' demographic data, clinical histories, laboratory and angiographic findings were collected and recorded. Diagnostic criteria for CSFP is based on Beltrame et al. proposed in 2012. Meanwhile 139 patients who have no significant stenosis (≤ 40%) and normal blood flow were selected as control. All patients received an echocardiographic examination 24 h before coronary angiography. LA structure and function were measured with echocardiography and 2D-STE. Our results showed that among the 1,954 patients who had received coronary angiography, 512 patients were included in the analysis after the exclusion criteria was implemented. Of those, 101 patients met the CSFP criteria (5.5%). CSFP is mainly seen in LAD (~ 70%). There was no statistical difference in baseline characteristics between the CSFP group and control group, except for a higher proportion of smokers in the CSFP group (P = 0.001). The percentage of monocytes is an independent risk factor for the occurrence of CSFP (P = 0.036) after binary logistic regression analysis. The LA global longitudinal strain (LA-GLS, represents reservoir functions) decreased and LA strain rate at late diastole (LA-SRa, represents booster function) increased in patients with CSFP compared to the control group (P < 0.05). Correlation test of continuous variables by Pearson test suggested that LA-GLS was negatively correlated with TIMI frame count (TFC). We concluded that the percentage of monocytes is an independent risk factor for the CSFP; the LA reservoir and booster functions were impaired in patients with CSFP; LA-GLS is negatively correlated with TFC. [ABSTRACT FROM AUTHOR]

A "carpet plot" is a 2-dimensional plot (time vs. voxel) of scaled fMRI voxel intensity values. Low frequency oscillations (LFOs) can be successfully identified from BOLD fMRI and used to study characteristics of neuronal and physiological activity. Here, we evaluate the use of carpet plots paired with a developed slope-detection algorithm as a means to study LFOs in resting state fMRI (rs-fMRI) data with the help of dynamic susceptibility contrast (DSC) MRI data. Carpet plots were constructed by ordering voxels according to signal delay time for each voxel. The slope-detection algorithm was used to identify and calculate propagation times, or "transit times", of tilted vertical edges across which a sudden signal change was observed. We aim to show that this metric has applications in understanding LFOs in fMRI data, possibly reflecting changes in blood flow speed during the scan, and for evaluating alternative blood-tracking contrast agents such as inhaled CO2. We demonstrate that the propagations of LFOs can be visualized and automatically identified in a carpet plot as tilted lines of sudden intensity change. Resting state carpet plots produce edges with transit times similar to those of DSC carpet plots. Additionally, resting state carpet plots indicate that edge transit times vary at different time points during the scan. [ABSTRACT FROM AUTHOR]

Mimicking angiogenetic processes in vascular territories acquires importance in the analysis of the multi-scale circulatory cascade and the coupling between blood flow and cell function. The present work extends, in several aspects, the Constrained Constructive Optimisation (CCO) algorithm to tackle complex automatic vascularisation tasks. The main extensions are based on the integration of adaptive optimisation criteria and multi-staged space-filling strategies which enhance the modelling capabilities of CCO for specific vascular architectures. Moreover, this vascular outgrowth can be performed either from scratch or from an existing network of vessels. Hence, the vascular territory is defined as a partition of vascular, avascular and carriage domains (the last one contains vessels but not terminals) allowing one to model complex vascular domains. In turn, the multi-staged space-filling approach allows one to delineate a sequence of biologically-inspired stages during the vascularisation process by exploiting different constraints, optimisation strategies and domain partitions stage by stage, improving the consistency with the architectural hierarchy observed in anatomical structures. With these features, the aDaptive CCO (DCCO) algorithm proposed here aims at improving the modelled network anatomy. The capabilities of the DCCO algorithm are assessed with a number of anatomically realistic scenarios. [ABSTRACT FROM AUTHOR]

The most common cause of chronic mesenteric ischaemia is atherosclerosis which results in limitation of blood flow to the gastrointestinal tract. This pilot study aimed to evaluate 4D flow MRI as a potential tool for the analysis of blood flow changes post-prandial within the mesenteric vessels. The mesenteric vessels of twelve people were scanned; patients and healthy volunteers. A baseline MRI scan was performed after 6 h of fasting followed by a post-meal scan. Two 4D flow datasets were acquired, over the superior mesenteric artery (SMA) and the main portal venous vessels. Standard 2D time-resolved PC-MRI slices were also obtained across the aorta above the coeliac trunk, superior mesenteric vein, splenic vein and portal vein (PV). In the volunteer cohort there was a marked increase in blood flow post-meal within the PV (p = 0.028), not seen in the patient cohort (p = 0.116). Similarly, there were significant flow changes within the SMA of volunteers (p = 0.028) but not for the patient group (p = 0.116). Our pilot data has shown that there is a significant haemodynamic response to meal challenge in the PV and SMA in normal subjects compared to clinically apparent CMI patients. Therefore, the interrogation of mesenteric venous vessels exclusively is a feasible method to measure post-prandial flow changes in CMI patients. [ABSTRACT FROM AUTHOR]

We investigated morphological changes of retinal arteries to determine their association with the blood flow and systemic variables in type 2 diabetes patients. The patients included 47 non-diabetic retinopathy eyes, 36 mild or moderate nonproliferative diabetic retinopathy (M-NPDR) eyes, 22 severe NPDR (S-NPDR) eyes, 32 PDR eyes, and 24 normal eyes as controls. The mean wall to lumen ratio (WLR) measured by adaptive optics camera was significantly higher in the PDR groups than in all of the other groups (all P < 0.001). However, the external diameter of the retinal vessels was not significantly different among the groups. The mean blur rate (MBR)-vessel determined by laser speckle flowgraphy was significantly lower in the PDR group than in the other groups (P < 0.001). The WLR was correlated with MBR-vessel (r = − 0.337, P < 0.001), duration of disease (r = 0.191, P = 0.042), stage of DM (r = 0.643, P < 0.001), systolic blood pressure (r = 0.166, P < 0.037), and presence of systemic hypertension (r = 0.443, P < 0.001). Multiple regression analysis demonstrated that MBR-vessel (β = − 0.389, P < 0.001), presence of systemic hypertension (β = 0.334, P = 0.001), and LDL (β = 0.199, P = 0.045) were independent factors significantly associated with the WLR. The increased retinal vessel wall thickness led to a narrowing of lumen diameter and a decrease in the blood flow in the PDR group. [ABSTRACT FROM AUTHOR]

Changes in blood flow velocity play a crucial role during pathogenesis and progression of cardiovascular diseases. Imaging techniques capable of assessing flow velocities are clinically applied but are often not accurate, quantitative, and reliable enough to assess fine changes indicating the early onset of diseases and their conversion into a symptomatic stage. Magnetic particle imaging (MPI) promises to overcome these limitations. Existing MPI-based techniques perform velocity estimation on the reconstructed images, which restricts the measurable velocity range. Therefore, we developed a novel velocity quantification method by adapting the Doppler principle to MPI. Our method exploits the velocity-dependent frequency shift caused by a tracer motion-induced modulation of the emitted signal. The fundamental theory of our method is deduced and validated by simulations and measurements of moving phantoms. Overall, our method enables robust velocity quantification within milliseconds, with high accuracy, no radiation risk, no depth-dependency, and extended range compared to existing MPI-based velocity quantification techniques, highlighting the potential of our method as future medical application. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a chronic autoimmune disease that affects tens of millions of people. Diabetes mellitus is one of the strongest factors in the development of cerebrovascular diseases. In this study we used NOD.CB17 Prkdcscid mice and the pharmacological model of type 1 diabetes mellitus of different duration to study changes in the cerebral vasculature. We used two combined approaches using magnetic resonance angiography both steady and transient CFD blood flow modeling. We identified the influence of type 1 diabetes on the architectonics and hemodynamics of the large blood vessels of the brain as the disease progresses. For the first time, we detected a statistically significant change in angioarchitectonics (the angles between the vessels of the circle of Willis, cross-sections areas of vessels) and hemodynamic (maximum blood flow rate, hydraulic resistance) in animals with diabetes duration of 2 months, that is manifested by the development of asymmetry of cerebral blood flow. The result shows the negative effect of diabetes on cerebral circulation as well as the practicability of CFD modeling. This may be of extensive interest, in pharmacological and preclinical studies. [ABSTRACT FROM AUTHOR]

With the development of 5th generation (5G) mobile networks people of different ages will be exposed in the upper part of the microwave spectrum. From the perspective of non-ionizing radiation dosimetry, an accurate analysis of age-dependent electromagnetic power deposition and resulting heating is required. In this study, we evaluate the effect of age on exposure at 26 GHz and 60 GHz. A near-surface tissue model illuminated by a plane wave is used to asses the exposure considering both frequency-independent and frequency-dependent limits. The age-related variation of the skin thickness and tissue electromagnetic properties has been considered. Moreover, the blood flow decrease rate has been taken into account to assess the age-dependent heating. Our results demonstrate that the overall variations of the power density, specific absorption rate (SAR) and heating in the near-surface tissues are limited to about 10–15%. These variations are mainly due to the tissue permittivity and blood flow change with age. In contrast to the transmitted power density that increases with age, the peak SAR decreases at both frequencies. The peak steady-state heating increases from 5 to 70 years old by roughly 11% at 26 GHz and 13% at 60 GHz. [ABSTRACT FROM AUTHOR]

The purpose of the study was to evaluate the retinal blood flow in patients with acute central serous chorioretinopathy (CSC) over an observational period of 1 month using swept-source optical coherence tomography (SS-OCTA), focusing especially on changes in the area of subretinal fluid (A-SRF). We correlated these findings with conventional indocyanine green angiography (ICGA). ICGA and SS-OCTA images were collected and analyzed of 12 eyes of 12 patients. The A-SRF was annotated and a qualitative analysis of choriocapillaris, the vessel density (VD) and perfusion density (PD) of the retinal superficial capillary plexus (SCP) and the deep capillary plexus (DCP) was performed in A-SRF and the unaffected remaining area (RA). The VD and PD in the DCP were statistically significantly lower in A-SRF than in the RA at baseline. (VD: p = 0.014; PD: p = 0.036). After 1 month, there was a statistically significant difference in the VD and PD of the DCP (VD: p = 0.015; PD: p = 0.014), and for the PD of the SCP between the A-SRF and the RA (p = 0.015), with lower values in the A-SRF. We found low perfused areas in choriocapillaris corresponding to hypofluorescent areas on ICGA. In conclusion there is a difference in VD and VD of the DCP in the area of SRF in acute CSC. These alterations may lead to a chronic change in the microvasculature and potentially to morphological changes. [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine whether multiparametric non-contrast MR imaging including diffusion-weighted imaging (DWI), arterial spin labeling (ASL), and amide proton transfer (APT) weighted imaging can help differentiate malignant from benign salivary gland lesions. The study population consisted of 42 patients, with 31 benign and 11 malignant salivary gland lesions. All patients were evaluated using DWI, three-dimensional pseudo-continuous ASL, and APT-weighted imaging on 3 T MR imaging before treatment. Apparent diffusion coefficient (ADC), tumor blood flow (TBF), and APT-related signal intensity (APTSI) values within the lesion were compared between the malignant and benign lesions by Mann–Whitney U test. For each parameter, optimal cutoff values were chosen using a threshold criterion that maximized the Youden index for predicting malignant lesions. The performance of ADC, TBF, APTSI, individually and combined, was evaluated in terms of diagnostic ability for malignant lesions. Diagnostic performance was compared by McNemar test. APTSI was significantly higher in malignant lesions (2.18 ± 0.89%) than in benign lesions (1.57 ± 1.09%, p = 0.047). There was no significant difference in ADC or TBF between benign and malignant lesions (p = 0.155 and 0.498, respectively). The accuracy of ADC, TBF, and APTSI for diagnosing malignant lesions was 47.6%, 50.0%, and 66.7%, respectively; whereas the accuracy of the three parameters combined was 85.7%, which was significantly higher than that of each parameter alone (p = 0.001, 0.001, and 0.008, respectively). Therefore, the combination of ADC, TBF, and APTSI can help differentiate malignant from benign salivary gland lesions. [ABSTRACT FROM AUTHOR]

Head-down bed rest (HDBR) has previously been shown to alter cerebrovascular and autonomic control. Previous work found that sustained HDBR (≥ 20 days) attenuates the hypercapnic ventilatory response (HCVR); however, little is known about shorter-term effects of HDBR nor the influence of HDBR on the hypoxic ventilatory response (HVR). We investigated the effect of 4-h HDBR on HCVR and HVR and hypothesized attenuated ventilatory responses due to greater carotid and brain blood flow. Cardiorespiratory responses of young men (n = 11) and women (n = 3) to 5% CO2 or 10% O2 before and after 4-h HDBR were examined. HDBR resulted in lower HR, lower cardiac output index, lower common carotid artery flow, higher SpO2, and higher pulse wave velocity. After HDBR, tidal volume and ventilation responses to 5% CO2 were enhanced (all P < 0.05), yet no other changes in cardiorespiratory variables were evident. There was no influence of HDBR on the cardiorespiratory responses to hypoxia (all P > 0.05). Short-duration HDBR does not alter the HVR, yet enhances the HCVR, which we hypothesize is a consequence of cephalic CO2 accumulation from cerebral congestion. [ABSTRACT FROM AUTHOR]

Monitoring of human tissue hemodynamics is invaluable in clinics as the proper blood flow regulates cellular-level metabolism. Time-domain diffuse correlation spectroscopy (TD-DCS) enables noninvasive blood flow measurements by analyzing temporal intensity fluctuations of the scattered light. With time-of-flight (TOF) resolution, TD-DCS should decompose the blood flow at different sample depths. For example, in the human head, it allows us to distinguish blood flows in the scalp, skull, or cortex. However, the tissues are typically polydisperse. So photons with a similar TOF can be scattered from structures that move at different speeds. Here, we introduce a novel approach that takes this problem into account and allows us to quantify the TOF-resolved blood flow of human tissue accurately. We apply this approach to monitor the blood flow index in the human forearm in vivo during the cuff occlusion challenge. We detect depth-dependent reactive hyperemia. Finally, we applied a controllable pressure to the human forehead in vivo to demonstrate that our approach can separate superficial from the deep blood flow. Our results can be beneficial for neuroimaging sensing applications that require short interoptode separation. [ABSTRACT FROM AUTHOR]

The need for the estimation of the number of microbubbles (MBs) in cardiopulmonary bypass surgery has been recognized among surgeons to avoid postoperative neurological complications. MBs that exceed the diameter of human capillaries may cause endothelial disruption as well as microvascular obstructions that block posterior capillary blood flow. In this paper, we analyzed the relationship between the number of microbubbles generated and four circulation factors, i.e., intraoperative suction flow rate, venous reservoir level, continuous blood viscosity and perfusion flow rate in cardiopulmonary bypass, and proposed a neural-networked model to estimate the number of microbubbles with the factors. Model parameters were determined in a machine-learning manner using experimental data with bovine blood as the perfusate. The estimation accuracy of the model, assessed by tenfold cross-validation, demonstrated that the number of MBs can be estimated with a determinant coefficient R2 = 0.9328 (p < 0.001). A significant increase in the residual error was found when each of four factors was excluded from the contributory variables. The study demonstrated the importance of four circulation factors in the prediction of the number of MBs and its capacity to eliminate potential postsurgical complication risks. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a chronic, steno-occlusive cerebrovascular disorder of unknown etiology. Surgical treatment is the only known effective method to restore blood flow to affected areas of the brain. However, there are lack of generally accepted noninvasive tools for therapeutic outcome monitoring. As dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) is the standard MR perfusion imaging technique in the clinical setting, we investigated a dataset of nineteen pediatric MMD patients with one preoperational and multiple periodic DSC MRI examinations for four to thirty-eight months after indirect revascularization. A rigid gamma variate model was used to derive two nondeconvolution-based perfusion parameters: time to peak (TTP) and full width at half maximum (FWHM) for monitoring transitional bolus delay and dispersion changes respectively. TTP and FWHM values were normalized to the cerebellum. Here, we report that 74% (14/19) of patients improve in both TTP and FWHM measurements, and whereof 57% (8/14) improve more noticeably on FWHM. TTP is in good agreement with Tmax in estimating bolus delay. Our study data also suggest bolus dispersion estimated by FWHM is an additional, informative indicator in pediatric MMD monitoring. [ABSTRACT FROM AUTHOR]

Ballistocardiography (BCG) and Seismocardiography (SCG) assess the vibrations produced by cardiac contraction and blood flow, respectively, by means of micro-accelerometers and micro-gyroscopes. From the BCG and SCG signals, maximal velocities (VMax), integral of kinetic energy (iK), and maximal power (PMax) can be computed as scalar parameters, both in linear and rotational dimensions. Standard echocardiography and 2-dimensional speckle tracking imaging echocardiography were performed on 34 healthy volunteers who were infused with increasing doses of dobutamine (5–10–20 μg/kg/min). Linear VMax of BCG predicts the rates of left ventricular (LV) twisting and untwisting (both p < 0.0001). The linear PMax of both SCG and BCG and the linear iK of BCG are the best predictors of the LV ejection fraction (LVEF) (p < 0.0001). This result is further confirmed by mathematical models combining the metrics from SCG and BCG signals with heart rate, in which both linear PMax and iK strongly correlate with LVEF (R = 0.7, p < 0.0001). In this setting of enhanced inotropism, the linear VMax of BCG, rather than the VMax of SCG, is the metric which best explains the LV twist mechanics, in particular the rates of twisting and untwisting. PMax and iK metrics are strongly associated with the LVEF and account for 50% of the variance of the LVEF. [ABSTRACT FROM AUTHOR]

We investigated the relationship between aqueous cytokine levels, changes in ocular blood flow, and morphological and functional improvements after intravitreal ranibizumab injection (IRI) in treatment-naïve eyes with center-involving diabetic macular edema (DME). Thirty-three eligible patients with DME (33 eyes) were recruited. At the first IRI, we collected a sample of aqueous humor from each eye and measured levels of the cytokines/chemokines. Mean blur rate (MBR) was used to evaluate retinal and choroidal flow by laser speckle flowgraphy at the time of the first IRI and 1 month later. One month after IRI, both retinal and choroidal MBR had significantly decreased from baseline. The reduction ratio of the retinal MBR was significantly correlated with aqueous levels of monocyte chemotactic protein (MCP)-1 and interleukin-8, and with reduction of central macular thickness, but not with improvement of best corrected visual acuity. The reduction ratio of choroidal MBR showed no statistical correlation with any cytokine levels or changes in clinical parameters. We conclude that IRI reduces both retinal and choroidal blood flow in treatment-naïve DME. Reduction of retinal blood flow correlated with regression of morphological pathology, which is regulated by the initial aqueous levels of some cytokines. [ABSTRACT FROM AUTHOR]

This study aimed to identify factors affecting anterior knee pain (AKP) after anterior cruciate ligament reconstruction (ACLR) with hamstring tendon autograft using ultrasonography. Forty-two patients were evaluated by ultrasound, 6 months after ACLR. The thickness of the superficial part of the infrapatellar fat pad was measured, as well as the thickness change ratio between the two angles. Color Doppler evaluated the rate of blood flow in the fat pad. AKP was assessed with the Kujala Scale. The correlations between AKP and age, body mass index, the thickness change ratio, and the grade of increased blood flow were examined. Independent variables showing significant correlations with AKP were used for multiple linear regression analysis. There were significant correlations between AKP and age (r = − 0.68), body mass index (r = − 0.37), the thickness change ratio of the fat pad (r = 0.73) and the grade of increased blood flow (r = − 0.42), respectively. Age and the thickness change ratio of the fat pad affected the AKP score (R2 = 0.56). After ACLR, older age and a decrease in the thickness change ratio of the superficial area of the infrapatellar fat pad appear to affect post-operative AKP after 6 months. [ABSTRACT FROM AUTHOR]

Retinal blood flow (RBF) information has the potential to offer insight into ophthalmic health and disease that is complementary to traditional anatomical biomarkers as well as to retinal perfusion information provided by fluorescence or optical coherence tomography angiography (OCT-A). The present study was performed to test the functional attributes and performance of the XyCAM RI, a non-invasive imager that obtains and assesses RBF information. The XyCAM RI was installed and used in two different settings to obtain video recordings of the blood flow in the optic nerve head region in eyes of healthy subjects. The mean blood flow velocity index (BFVi) in the optic disc and in each of multiple arterial and venous segments was obtained and shown to reveal a temporal waveform with a peak and trough that correlates with a cardiac cycle as revealed by a reference pulse oximeter (correlation between respective peak-to-peak distances was 0.977). The intra-session repeatability of the XyCAM RI was high with a coefficient of variation (CV) of 1.84 ± 1.13% across both sites. Artery-vein comparisons were made by estimating, in a pair of adjacent arterial and venous segments, various temporal waveform metrics such as pulsatility index, percent time in systole and diastole, and change in vascular blood volume over a cardiac cycle. All arterial metrics were shown to have significant differences with venous metrics (p < 0.001). The XyCAM RI, therefore, by obtaining repeatable blood flow measurements with high temporal resolution, permits the differential assessment of arterial and venous blood flow patterns in the retina that may facilitate research into disease pathophysiology and biomarker development for diagnostics. [ABSTRACT FROM AUTHOR]

Circulation through cerebral collaterals can maintain tissue viability until reperfusion is achieved. However, collateral circulation is time limited, and failure of collaterals is accelerated in the aged. Remote ischemic perconditioning (RIPerC), which involves inducing a series of repetitive, transient peripheral cycles of ischemia and reperfusion at a site remote to the brain during cerebral ischemia, may be neuroprotective and can prevent collateral failure in young adult rats. Here, we demonstrate the efficacy of RIPerC to improve blood flow through collaterals in aged (16–18 months of age) Sprague Dawley rats during a distal middle cerebral artery occlusion. Laser speckle contrast imaging and two-photon laser scanning microscopy were used to directly measure flow through collateral connections to ischemic tissue. Consistent with studies in young adult rats, RIPerC enhanced collateral flow by preventing the stroke-induced narrowing of pial arterioles during ischemia. This improved flow was associated with reduced early ischemic damage in RIPerC treated aged rats relative to controls. Thus, RIPerC is an easily administered, non-invasive neuroprotective strategy that can improve penumbral blood flow via collaterals. Enhanced collateral flow supports further investigation as an adjuvant therapy to recanalization therapy and a protective treatment to maintain tissue viability prior to reperfusion. [ABSTRACT FROM AUTHOR]

Administration of hemoglobin-based oxygen carriers (HBOCs) into the systemic circulation is a potential strategy to relieve solid tumor hypoxia in order to increase the effectiveness of chemotherapeutics. Previous computational analysis indicated that the oxygen (O2) status of the tumor and HBOC O2 affinity may play a role in increased O2 delivery to the tumor. However, no study has experimentally investigated how low- and high-affinity HBOCs would perform in normoxic and hypoxic tumors. In this study, we examined how the HBOC, polymerized human hemoglobin (PolyhHb), in the relaxed (R) or tense (T) quaternary state modulates O2 delivery to hypoxic (FME) and normoxic (LOX) human melanoma xenografts in a murine window chamber model. We examined microcirculatory fluid flow via video shearing optical microscopy, and O2 distributions via phosphorescence quenching microscopy. Additionally, we examined how weekly infusion of a 20% top-load dose of PolyhHb influences growth rate, vascularization, and regional blood flow in the FME and LOX tumor xenografts. Infusion of low-affinity T-state PolyhHb led to increased tissue oxygenation, decreased blood flow, decreased tumor growth, and decreased vascularization in hypoxic tumors. However, infusion of both T-state and R-state PolyhHbs led to worse outcomes in normoxic tumors. Of particular concern was the high-affinity R-state PolyhHb, which led to no improvement in hypoxic tumors and significantly worsened outcomes in normoxic tumors. Taken together, the results of this study indicate that the tumor O2 status is a primary determinant of the potency and outcomes of infused PolyhHb. [ABSTRACT FROM AUTHOR]

Currently, there is no noninvasive method available for simultaneous measurements of tidal volume and stroke volume. Electrical impedance tomography (EIT) has been used for regional lung ventilation imaging. Cardiac EIT imaging, however, has not been successful due to the technical difficulty in extracting weak cardiogenic components. Instead of regional imaging, in this paper, we use the EIT technique to simultaneously measure two global variables of tidal volume and stroke volume. Time-varying patterns of boundary voltage data originating from lung ventilation and cardiac blood flow were extracted from measured boundary voltage data using the principal component analysis (PCA) and independent component analysis (ICA). The source consistency theory was adopted to separately synthesize time-series of boundary voltage data associated with lung ventilation and cardiac blood flow. The respiratory volume signal (RVS) and cardiac volume signal (CVS) were extracted from reconstructed time-difference EIT images of lung ventilation and cardiac blood flow, respectively. After calibrating the volume signals using the mechanical ventilator and the invasive transpulmonary thermodilution (TPTD) method, tidal volume and stroke volume were computed as valley-to-peak values of the RVS and CVS, respectively. The difference in the tidal volume data between EIT and mechanical ventilator was within ± 20 ml from six pigs. The difference in the stroke volume data between EIT and TPTD was within ± 4.7 ml from the same animals. The results show the feasibility of the proposed method as a new noninvasive cardiopulmonary monitoring tool for simultaneous continuous measurements of stroke volume and tidal volume that are two most important vital signs. [ABSTRACT FROM AUTHOR]

To evaluate retrobulbar hemodynamics in patients with optic disc drusen (ODD) by color Doppler imaging. A prospective study included 52 patients with bilateral ODD and 50 age-matched controls. Blood flow in the central retinal artery (CRA) in both eyes was evaluated. Peak-systolic velocity (PSV), end-diastolic velocity (EDV), and the resistivity index (RI) were measured. Mean values of the blood flow Doppler parameters were compared between the patients with ODD and the controls. Both PSV and EDV in the CRA were significantly lower in patients with ODD than in the controls (p < 0.001). The RI in the CRA of ODD patients was significantly higher than in the controls (p < 0.001). Women with ODD presented with significantly lower values of PSV and EDV than men (p = 0.05 and p = 0.03, respectively). Arterial hypertension, cigarette smoking and location of ODD in the left or right eye did not exert a significant effect on the blood flow in the CRA. Blood flow in the CRA is considerably disturbed in patients with ODD. This disturbance might result from mechanical stenosis of the vascular wall caused by the drusen. Color Doppler ultrasound is a useful method in the assessment of retrobulbar hemodynamics in ODD. [ABSTRACT FROM AUTHOR]