In-Vivo Real-Time Contrast-Free Ultrasonic Blood Flow Velocity Profile Measurement

2012 ◽  
Author(s):  
G. G. Koutsouridis ◽  
N. Bijnens ◽  
P. J. Brands ◽  
F. N. van de Vosse ◽  
M. C. M. Rutten
Keyword(s):  
Velocity Profile ◽  
Real Time ◽  
Ex Vivo ◽  
Accurate Estimation ◽  
Profile Measurement ◽  
Processing Unit ◽  
Local Pressure ◽  
Measured Velocity

Recently, Ultrasonic Perpendicular Velocimetry (UPV) based algorithms, as opposed to commonly used Doppler technique (Figure 1), were applied to Radio Frequency (RF)-data acquired in an in-vitro setup [1,3]. Thus, the estimation of velocity components perpendicularly to the ultrasound beam and the simultaneous and accurate assessment of wall position and axial velocity profiles were made feasible. By integrating the measured velocity profile an accurate flow estimation was made possible. Furthermore, the ratio between the changes in flow Q(t) and the changes in cross-sectional area of the vessel A(t) was found to offer an accurate estimation of the local Pulse Wave Velocity (PWV). By combining the PWV with the diameter waveform, accurate local pressure estimation was obtained indicating that a non-invasive pressure assessment by means of ultrasound is feasible [3]. However, the abovementioned method is time consuming due to the data size and the post-processing procedure required. Additionally, the Fast Fourier Transform (FFT) on Butterworth Band Pass Filters (BPF) for vessel’s wall removal requires contrast agents dispersion in the fluid for the application of UPV. A real-time approach, of the previously described techniques, was applied [2] in-vitro using a Blood Mimicking Fluid (BMF), as contrast agent, resembling the rheological (shear thinning) and acoustical (backscattering) properties of blood and ex-vivo using BMF or contrast-free real blood implementing Wavelet Transform (WT) filtering. The use of a Graphics Processing Unit (GPU) [4], succeeded in considerable acceleration and WT [5] filtering on the rough RF-data, in improvement of the discrimination between reflections from the vessel wall and scattering from small particles. In this research the method is extended to include in-vivo measurements.

scholarly journals Real-Time Wireless Platform for In Vivo Monitoring of Bone Regeneration

Sensors ◽  
2020 ◽  
Vol 20 (16) ◽  
pp. 4591 ◽  
Author(s):  
Pablo Blázquez-Carmona ◽  
Manuel Sanchez-Raya ◽  
Juan Mora-Macías ◽  
Juan Antonio Gómez-Galán ◽  
Jaime Domínguez ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Real Time ◽  
Ex Vivo ◽  
Low Cost ◽  
Bone Lengthening ◽  
Bone Callus ◽  
Reliable Solution ◽  
Regeneration Processes

For the monitoring of bone regeneration processes, the instrumentation of the fixation is an increasingly common technique to indirectly measure the evolution of bone formation instead of ex vivo measurements or traditional in vivo techniques, such as X-ray or visual review. A versatile instrumented external fixator capable of adapting to multiple bone regeneration processes was designed, as well as a wireless acquisition system for the data collection. The design and implementation of the overall architecture of such a system is described in this work, including the hardware, firmware, and mechanical components. The measurements are conditioned and subsequently sent to a PC via wireless communication to be in vivo displayed and analyzed using a developed real-time monitoring application. Moreover, a model for the in vivo estimation of the bone callus stiffness from collected data was defined. This model was validated in vitro using elastic springs, reporting promising results with respect to previous equipment, with average errors and uncertainties below 6.7% and 14.04%. The devices were also validated in vivo performing a bone lengthening treatment on a sheep metatarsus. The resulting system allowed the in vivo mechanical characterization of the bone callus during experimentation, providing a low-cost, simple, and highly reliable solution.

scholarly journals Modeling Immune Checkpoint Inhibitor Efficacy in Syngeneic Mouse Tumors in an Ex Vivo Immuno-Oncology Dynamic Environment

2020 ◽  
Vol 21 (18) ◽  
pp. 6478
Author(s):  
Daniel T. Doty ◽  
Julia Schueler ◽  
Vienna L. Mott ◽  
Cassie M. Bryan ◽  
Nathan F. Moore ◽  
...  
Keyword(s):  
Real Time ◽  
Mouse Models ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Ex Vivo ◽  
Confocal Imaging ◽  
Checkpoint Blockade ◽  
Syngeneic Mouse

The immune checkpoint blockade represents a revolution in cancer therapy, with the potential to increase survival for many patients for whom current treatments are not effective. However, response rates to current immune checkpoint inhibitors vary widely between patients and different types of cancer, and the mechanisms underlying these varied responses are poorly understood. Insights into the antitumor activities of checkpoint inhibitors are often obtained using syngeneic mouse models, which provide an in vivo preclinical basis for predicting efficacy in human clinical trials. Efforts to establish in vitro syngeneic mouse equivalents, which could increase throughput and permit real-time evaluation of lymphocyte infiltration and tumor killing, have been hampered by difficulties in recapitulating the tumor microenvironment in laboratory systems. Here, we describe a multiplex in vitro system that overcomes many of the deficiencies seen in current static histocultures, which we applied to the evaluation of checkpoint blockade in tumors derived from syngeneic mouse models. Our system enables both precision-controlled perfusion across biopsied tumor fragments and the introduction of checkpoint-inhibited tumor-infiltrating lymphocytes in a single experiment. Through real-time high-resolution confocal imaging and analytics, we demonstrated excellent correlations between in vivo syngeneic mouse and in vitro tumor biopsy responses to checkpoint inhibitors, suggesting the use of this platform for higher throughput evaluation of checkpoint efficacy as a tool for drug development.

scholarly journals Activated neutrophil fluorescent imaging technique for human lungs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas H. Craven ◽  
Tashfeen Walton ◽  
Ahsan R. Akram ◽  
Emma Scholefield ◽  
Neil McDonald ◽  
...  
Keyword(s):  
Real Time ◽  
Ex Vivo ◽  
Optical Signal ◽  
Neutrophil Activation ◽  
Fluorescent Imaging ◽  
Human Neutrophil Elastase ◽  
Clinical Criteria ◽  
Integral Process

AbstractNeutrophil activation is an integral process to acute inflammation and is associated with adverse clinical sequelae. Identification of neutrophil activation in real time in the lungs of patients may permit biological stratification of patients in otherwise heterogenous cohorts typically defined by clinical criteria. No methods for identifying neutrophil activation in real time in the lungs of patients currently exist. We developed a bespoke molecular imaging probe targeting three characteristic signatures of neutrophil activation: pinocytosis, phagosomal alkalinisation, and human neutrophil elastase (HNE) activity. The probe functioned as designed in vitro and ex vivo. We evaluated optical endomicroscopy imaging of neutrophil activity using the probe in real-time at the bedside of healthy volunteers, patients with bronchiectasis, and critically unwell mechanically ventilated patients. We detected a range of imaging responses in vivo reflecting heterogeneity of condition and severity. We corroborated optical signal was due to probe function and neutrophil activation.

scholarly journals Refinement of a mouse cardiovascular model: Development, application and dissemination

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 593
Author(s):  
Kirk A. Taylor ◽  
Michael Emerson
Keyword(s):  
Real Time ◽  
Light Transmission ◽  
Ex Vivo ◽  
Model Development ◽  
Cell Counting ◽  
Real Time Monitoring ◽  
Mortality Models ◽  
Typical Experiment

European and UK legislation requires all animal procedures to be conducted with consideration to reduction, refinement and replacement. In this review, 3Rs developments are discussed in the field of platelet biology and thromboembolism. Platelet research requires the use of animal models, and mice are widely used in the field. When working in vitro, conventional light transmission techniques have been scaled down allowing reduction in animal numbers. In vivo, vascular injury models are widely used and work is ongoing to develop ex vivo approaches that use fewer animals. Thromboembolic mortality models, which inflict considerable pain and suffering, have also been used widely. A published and characterised refinement of this mortality model allows real-time monitoring of radiolabelled platelets under general anaesthesia and reduces both the severity level and the numbers of mice used in a typical experiment. This technique is more sensitive than the mortality approach and has opened up new avenues of research, which would not have been feasible by using death as an end-point. To drive uptake of real-time monitoring, a more simplistic approach has been developed involving micro-sampling and cell counting. Thromboembolic mortality models should therefore be considered obsolete due to the emergence of 3Rs models with improved scientific outcomes and that can be implemented relatively easily.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

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