Investigation on application of singular value decomposition filter in element domain for extraction of ultrasonic echoes from blood cells in jugular veins

The singular value decomposition (SVD) based clutter filter is commonly applied to beamformed signals for the visualization of echo signals from flowing blood cells. In this paper, the SVD-based clutter filter is applied to signals directly acquired from ultrasonic elements before beamforming to be compared with the conventional strategy by evaluating contrast and standard deviation (SD) in the filtered images. As a result, the contrast was improved from 10.7 ± 3.6 dB to 18.3 ± 4.6 dB, and the SD was slightly improved from 3.78 ± 0.69 dB to 3.07 ± 0.74 dB in measurement of a right jugular vein.

Venous activation of MEK/ERK drives development of arteriovenous malformation and blood 2 flow anomalies with loss of Rasa1

Vascular malformations develop when growth pathway signaling goes awry in the endothelial cells lining blood vessels. Arteriovenous malformations (AVMs) arise where arteries and veins abnormally connect in patients with loss of RASA1, a Ras GTPase activating protein, and, as we show here, in zebrafish rasa1 mutants. Mutant fish develop massively enlarged vessels at the connection between artery and vein in the tail vascular plexus. These AVMs progressively enlarge and become filled with slow-flowing blood and have a greater drop in pulsatility from the artery to the vein. Expression of the flow responsive transcription factor klf2a is diminished in rasa1 mutants, suggesting changes in flow velocity and pattern contribute to the progression of vessel malformations. Migration of endothelial cells is not affected in rasa1 mutants, nor is cell death or proliferation. Early developmental artery-vein patterning is also normal in rasa1 mutants, but we find that MEK/ERK signaling is ectopically activated in the vein as compared to high arterial activation seen in wildtype animals. MEK/ERK signaling inhibition prevents AVM development of rasa1 mutants, demonstrating venous MEK/ERK drives the initiation of rasa1 AVMs. Thus, rasa1 mutants show overactivation of MEK/ERK signaling causes AVM formation, altered blood flow and downstream flow responsive signaling.

Potential of High Dimensional Radiomic Features to Assess Flowing Blood Components in Non-contrast CT Scans

Background: To assess the potential of radiomic features to quantify components of flowing blood to non-invasively predict moderate-to-severe anemia in non-contrast enhanced CT scans. Methods: One hundred patients (median age, 69 years; range, 19–94 years) who received CT scans of the thoracolumbar spine and blood-testing for hemoglobin and hematocrit levels ± 24h between 08/2018 and 11/2019 were retrospectively included. Intraaortic blood was segmented using a spherical volume of interest with consecutive radiomic analysis. Feature selection was performed applying analysis of correlation and collinearity. The final feature set was obtained to differentiate moderate-to-severe anemia. Random forest machine learning was applied and predictive performance was assessed. A decision-tree was obtained to propose a cut-off value of CT Hounsfield units (HU).Results: High correlation with hemoglobin and hematocrit levels was shown for first-order radiomic features (p<0.001 to p=0.032). The top 3 features showed high correlation to hemoglobin values (p) and minimal collinearity (r) to the top ranked feature Median (p<0.001), Energy (p=0.002, r=0.387), Minimum (p=0.032, r=0.437). Median (p<0.001) and Minimum (p=0.003) differed in moderate-to-severe anemia compared to non-anemic state. Median yielded superiority to the combination of Median and Minimum (p(AUC)=0.015, p(precision)=0.017, p(accuracy)=0.612) in the predictive performance employing random forest analysis. A Median HU value ≤ 36.5 indicated moderate-to-severe anemia (accuracy=0.90, precision=0.80).Conclusions: First-order radiomic features correlate with hemoglobin levels and may be feasible for the prediction of moderate-to-severe anemia. High dimensional radiomic features did not inherit the potential to augment the data in our exemplary use case of flowing blood component assessment.Trial registration: Retrospectively registered.

Quantifying MRI T1 relaxation in flowing blood: implications for arterial input function measurement in DCE-MRI

Objectives: To investigate the feasibility of accurately quantifying the concentration of MRI contrast agent in flowing blood by measuring its T1 in a large vessel. Such measures are often used to obtain patient-specific arterial input functions for the accurate fitting of pharmacokinetic models to dynamic contrast enhanced MRI data. Flow is known to produce errors with this technique, but these have so far been poorly quantified and characterised in the context of pulsatile flow with a rapidly changing T1 as would be expected in vivo. Methods: A phantom was developed which used a mechanical pump to pass fluid at physiologically relevant rates. Measurements of T1 were made using high temporal resolution gradient recalled sequences suitable for DCE-MRI of both constant and pulsatile flow. These measures were used to validate a virtual phantom that was then used to simulate the expected errors in the measurement of an AIF in vivo. Results: The relationship between measured T1 values and flow velocity was found to be non-linear. The subsequent error in quantification of contrast agent concentration in a measured AIF was shown. Conclusions: The T1 measurement of flowing blood using standard DCE- MRI sequences are subject to large measurement errors which are non-linear in relation to flow velocity. Advances in knowledge: This work qualitatively and quantitatively demonstrates the difficulties of accurately measuring the T1 of flowing blood using DCE-MRI over a wide range of physiologically realistic flow velocities and pulsatilities. Sources of error are identified and proposals made to reduce these.

Fluid–structure interactions (FSI) based study of low-density lipoproteins (LDL) uptake in the left coronary artery

The purpose of this study is to compare the effect of the different physical factors on low-density lipoproteins (LDL) accumulation from flowing blood to the arterial wall of the left coronary arteries. The three-dimensional (3D) computational model of the left coronary arterial tree is reconstructed from a patient-specific computed tomography angiography (CTA) image. The endothelium of the coronary artery is represented by a shear stress dependent three-pore model. Fluid–structure interaction ($$FSI$$ FSI ) based numerical method is used to study the LDL transport from vascular lumen into the arterial wall. The results show that the high elastic property of the arterial wall decreases the complexity of the local flow field in the coronary bifurcation system. The places of high levels of LDL uptake coincide with the regions of low wall shear stress. In addition, hypertension promotes LDL uptake from flowing blood in the arterial wall, while the thickened arterial wall decreases this process. The present computer strategy combining the methods of coronary CTA image 3D reconstruction, $$FSI$$ FSI simulation, and three-pore modeling was illustrated to be effective on the simulation of the distribution and the uptake of LDL. This may have great potential for the early prediction of the local atherosclerosis lesion in the human left coronary artery.

Ultrasound Doppler-guided real-time navigation of a magnetic microswarm for active endovascular delivery

Swarming micro/nanorobots offer great promise in performing targeted delivery inside diverse hard-to-reach environments. However, swarm navigation in dynamic environments challenges delivery capability and real-time swarm localization. Here, we report a strategy to navigate a nanoparticle microswarm in real time under ultrasound Doppler imaging guidance for active endovascular delivery. A magnetic microswarm was formed and navigated near the boundary of vessels, where the reduced drag of blood flow and strong interactions between nanoparticles enable upstream and downstream navigation in flowing blood (mean velocity up to 40.8 mm/s). The microswarm-induced three-dimensional blood flow enables Doppler imaging from multiple viewing configurations and real-time tracking in different environments (i.e., stagnant, flowing blood, and pulsatile flow). We also demonstrate the ultrasound Doppler–guided swarm formation and navigation in the porcine coronary artery ex vivo. Our strategy presents a promising connection between swarm control and real-time imaging of microrobotic swarms for localized delivery in dynamic environments.

Fibrinogen function achieved through multiple covalent states

Disulfide bonds link pairs of cysteine amino acids and their formation is assumed to be complete in the mature, functional protein. Here, we test this assumption by quantifying the redox state of disulfide bonds in the blood clotting protein fibrinogen. The disulfide status of fibrinogen from healthy human donor plasma and cultured human hepatocytes are measured using differential cysteine alkylation and mass spectrometry. This analysis identifies 13 disulfide bonds that are 10–50% reduced, indicating that fibrinogen is produced in multiple disulfide-bonded or covalent states. We further show that disulfides form upon fibrin polymerization and are required for a robust fibrin matrix that withstands the mechanical forces of flowing blood and resists premature fibrinolysis. The covalent states of fibrinogen are changed by fluid shear forces ex vivo and in vivo, indicating that the different states are dynamic. These findings demonstrate that fibrinogen exists and functions as multiple covalent forms.

Hemostatic Enhancement via Chitosan Is Independent of Classical Clotting Pathways—A Quantitative Study

Hemostasis is a process causing bleeding to stop, and it is known from the literature that hemostasis can be enhanced using chitosan on wound gauzes. We proposed here a continuous flow-through device, with the test blood flowing through the gauze sample at a constant flow rate and the pressure drop across the gauze measured, for assessing the hemostatic performance of the gauze. Experiments were performed using the device with both whole blood and washed blood (with clotting factors and platelets removed from the whole blood), and their results agree with each other within 10% discrepancy, indicating quantitatively that hemostatic enhancement via chitosan is essentially independent of classical clotting pathways, which was demonstrated qualitatively through animal tests in the literature. The proposed device and method can be applied for evaluating quantitatively the hemostatic performance of various gauzes in a flowing blood environment (in comparison with static tests) with less test blood (20–60% less, in comparison with that of a flow-through device driven by a constant pressure gradient), and are thus, helpful for designing better wound gauzes. In particular, it is effective to enhance the hemostatic performance further (additional 30%) through acidification (changing the amino group to the ammonium group) of the gauze for chitosan-based wound gauzes.

Glycoprotein VI is not a Functional Platelet Receptor for Fibrin Formed in Plasma or Blood

Glycoprotein VI (GPVI), a platelet collagen receptor, is crucial in mediating atherothrombosis. Besides collagen, injured plaques expose tissue factor (TF) that triggers fibrin formation. Previous studies reported that GPVI also is a platelet receptor for fibrinogen and fibrin. We studied the effect of anti-GPVI antibodies and inhibitors of GPVI signaling kinases (Syk and Btk) on platelet adhesion and aggregate formation onto immobilized fibrinogen and different types of fibrin under arterial flow conditions. Fibrin was prepared from isolated fibrinogen (“pure fibrin”), recombinant fibrinogen (“recombinant fibrin”), or generated more physiologically from endogenous fibrinogen in plasma (“plasma fibrin”) or by exposing TF-coated surfaces to flowing blood (“blood fibrin”). Inhibition of GPVI and Syk did not inhibit platelet adhesion and aggregate formation onto fibrinogen. In contrast anti-GPVI antibodies, inhibitors of Syk and Btk and the anti-GPIb antibody 6B4 inhibited platelet aggregate formation onto pure and recombinant fibrin. However, inhibition of GPVI and GPVI signaling did not significantly reduce platelet coverage of plasma fibrin and blood fibrin. Plasma fibrin contained many proteins incorporated during clot formation. Advanced optical imaging revealed plasma fibrin as a spongiform cushion with thicker, knotty, and long fibers and little activation of adhering platelets. Albumin intercalated in plasma fibrin fibers left only little space for platelet attachment. Pure fibrin was different showing a dense mesh of thin fibers with strongly activated platelets. We conclude that fibrin formed in plasma and blood contains plasma proteins shielding GPVI-activating epitopes. Our findings do not support a role of GPVI for platelet activation by physiologic fibrin.