Experimental study of the POP technique: focus on the physical basis of the process.

INTRODUCTION: Central or peripheral vascular access devices have been in use for many decades. However, despite adequate care and maintenance, complete occlusion may occur, and its impact cannot be overlooked. A new procedure using a percussion technique has been published and referred as 'the POP technique'. METHODS: A hydrodynamic bench was used permitting both the recording of the movement of the piston with a fast camera and the pressure variations in the polyurethane and silicone catheters while connected to 2- and 3-piece syringes. RESULTS: The results are twofold. First the upward movement of the piston leads to the installation of a saturation vapour pressure in the body of the syringe. During this sequence, the clot is submitted to a force of aspiration. Then the release of the plunger leads to a pulse pressure whose dynamics and intensity are dependent of the types of syringes and catheters. CONCLUSIONS: The experiments bring to light the importance of practical features such as the orientation of the syringe and the nature of the polyurethane or silicone catheters. Then the analysis enables the definition of practical rules for safe practice of the POP technique. This study will impact clinicians as many may be tempted to use the technique in hope to resolve the occlusion safely, in a timely manner.

New method for estimating arterial pulse wave velocity at single site.

The clinical importance of measuring local pulse wave velocity (PWV), has encouraged researchers to develop several local methods to estimate it. In this work, we proposed a new method, the sum-of-squares method [Formula: see text], that allows the estimations of PWV by using simultaneous measurements of blood pressure (P) and arterial diameter (D) at single-location. Pulse waveforms generated by: (1) two-dimensional (2D) fluid-structure interaction simulation (FSI) in a compliant tube, (2) one-dimensional (1D) model of 55 larger human systemic arteries and (3) experimental data were used to validate the new formula and evaluate several classical methods. The performance of the proposed method was assessed by comparing its results to theoretical PWV calculated from the parameters of the model and/or to PWV estimated by several classical methods. It was found that values of PWV obtained by the developed method [Formula: see text] are in good agreement with theoretical ones and with those calculated by PA-loop and D2P-loop. The difference between the PWV calculated by [Formula: see text] and PA-loop does not exceed 1% when data from simulations are used, 3% when in vitro data are used and 5% when in vivo data are used. In addition, this study suggests that estimated PWV from arterial pressure and diameter waveforms provide correct values while methods that require flow rate (Q) and velocity (U) overestimate or underestimate PWV.

Mechanical characteristics of plastic base Ports and impact on flushing efficacy.

BACKGROUND: Three types of totally implantable venous access devices, Ports, are currently in use: titanium, plastic (polyoxymethylene, POM), and mixed (titanium base with a POM shell). Physics theory suggests that the interaction between a non-coring needle (NCN, made of stainless steel) and a plastic base would lead to the stronger material (steel) altering the more malleable material (plastic). OBJECTIVES: To investigate whether needle impacts can alter a plastic base's surface, thus potentially reducing flushing efficacy. STUDY DESIGN AND METHODS: A Port made of POM was punctured 200 times with a 19-gauge NCN. Following the existing guidelines, the needle tip pricked the base with each puncture. The Port's base was then examined using a two-dimensional optical instrument, and a bi-dimensional numerical simulation using COMSOL® was performed to investigate potential surface irregularities and their impact on fluid flow. RESULTS: Each needle impact created a hole (mean depth, 0.12 mm) with a small bump beside it (mean height, 0.02 mm) the Reynolds number Rek≈10. A numerical simulation of the one hole/bump set showed that the flushing efficacy was 60% that of flushing along a flat surface. DISCUSSION: In clinical practice, the number of times a Port is punctured depends on patient and treatment characteristics, but each needle impact on the plastic base may increase the risk of decreased flushing effectiveness. Therefore, the more a plastic Port is accessed, the greater the risk of microorganisms, blood products, and medication accumulation. CONCLUSIONS: Multiple needle impacts created an irregular surface on the Port's base, which decreased flushing efficacy. Clinical investigation is needed to determine whether plastic base Ports are associated with an increased risk of Port infection and occlusion compared to titanium base Ports.

Bioluminescence-Based Tumor Quantification Method for Monitoring Tumor Progression and Treatment Effects in Mouse Lymphoma Models.

Although bioluminescence imaging (BLI) shows promise for monitoring tumor burden in animal models of cancer, these analyses remain mostly qualitative. Here we describe a method for bioluminescence imaging to obtain a semi-quantitative analysis of tumor burden and treatment response. This method is based on the calculation of a luminoscore, a value that allows comparisons of two animals from the same or different experiments. Current BLI instruments enable the calculation of this luminoscore, which relies mainly on the acquisition conditions (back and front acquisitions) and the drawing of the region of interest (manual markup around the mouse). Using two previously described mouse lymphoma models based on cell engraftment, we show that the luminoscore method can serve as a noninvasive way to verify successful tumor cell inoculation, monitor tumor burden, and evaluate the effects of in situ cancer treatment (CpG-DNA). Finally, we show that this method suits different experimental designs. We suggest that this method be used for early estimates of treatment response in preclinical small-animal studies.

Duality of Iron Oxide Nanoparticles in Cancer Therapy: Amplification of Heating Efficiency by Magnetic Hyperthermia and Photothermal Bimodal Treatment.

The pursuit of innovative, multifunctional, more efficient, and safer treatments is a major challenge in preclinical nanoparticle-mediated thermotherapeutic research. Here, we report that iron oxide nanoparticles have the dual capacity to act as both magnetic and photothermal agents. We further explore every key aspect of this magnetophotothermal approach, choosing iron oxide nanocubes for their high efficiency for the magnetic hyperthermia modality itself. In aqueous suspension, the nanocubes' exposure to both: an alternating magnetic field and near-infrared laser irradiation (808 nm), defined as the DUAL-mode, amplifies the heating effect 2- to 5-fold by comparison with magnetic stimulation alone, yielding unprecedented heating powers (specific loss powers) up to 5000 W/g. In cancer cells, the laser excitation restores the optimal efficiency of magnetic hyperthermia, otherwise inhibited by intracellular confinement, resulting in a remarkable heating efficiency in the DUAL-mode (up to 15-fold amplification), with respect to the magnetophotothermal mode. As a consequence, the dual action yielded complete apoptosis-mediated cell death. In solid tumors in vivo, single-mode treatments (magnetic or laser hyperthermia) reduced tumor growth, while DUAL-mode treatment resulted in complete tumor regression, mediated by heat-induced tumoral cell apoptosis and massive denaturation of the collagen fibers, and a long-lasting thermal efficiency over repeated treatments.

Wheezing recognition algorithm using recordings of respiratory sounds at the mouth in a pediatric population.

BACKGROUND: Respiratory diseases in children are a common reason for physician visits. A diagnostic difficulty arises when parents hear wheezing that is no longer present during the medical consultation. Thus, an outpatient objective tool for recognition of wheezing is of clinical value. METHOD: We developed a wheezing recognition algorithm from recorded respiratory sounds with a Smartphone placed near the mouth. A total of 186 recordings were obtained in a pediatric emergency department, mostly in toddlers (mean age 20 months). After exclusion of recordings with artefacts and those with a single clinical operator auscultation, 95 recordings with the agreement of two operators on auscultation diagnosis (27 with wheezing and 68 without) were subjected to a two phase algorithm (signal analysis and pattern classifier using machine learning algorithms) to classify records. RESULTS: The best performance (71.4% sensitivity and 88.9% specificity) was observed with a Support Vector Machine-based algorithm. We further tested the algorithm over a set of 39 recordings having a single operator and found a fair agreement (kappa=0.28, CI95% [0.12, 0.45]) between the algorithm and the operator. CONCLUSIONS: The main advantage of such an algorithm is its use in contact-free sound recording, thus valuable in the pediatric population.

Toward the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction.

Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions. We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increase any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two a dimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation.

Pulsative flushing as a strategy to prevent bacterial colonization of vascular access devices.

Central venous device infections are associated with increased physical and psychological morbidity, mortality, length of stay, and costs. The aim of this study was to prove the efficacy of pulsatile flushing to prevent the bacterial colonization of vascular access devices. One hundred and forty four tests using 576 polyurethane short venous access catheters were performed. Four catheters per test were polluted with a fibronectin-serum albumin solution. Three were filled with a Staphylococcus aureus broth; one served as negative control. One contaminated catheter was not flushed (positive control), and two were flushed (10 mL.sec(-1)) with normal saline solution, either by ten successive boluses of 1 mL each or by one bolus of 10 mL. Each catheter was cultivated. The S. aureus quantity observed after continuous flushing was significantly higher than that observed after pulsative flushing (P<0.001). Unflushed catheters were 20.71 and 6.42 times more polluted than catheters flushed with the pulsative method or the continuous method, respectively. Pulsative flushing was at least twice as effective as continuous flushing in reducing the S. aureus count. Pulsative flushing is more effective than continuous flushing in reducing the endoluminal contamination. Pulsative flushing is a simple, effective, and inexpensive technique to reduce catheter bacterial colonization.

Anisotropic polyvinyl alcohol hydrogel phantom for shear wave elastography in fibrous biological soft tissue: a multimodality characterization.

Shear wave elastography imaging techniques provide quantitative measurement of soft tissues elastic properties. Tendons, muscles and cerebral tissues are composed of fibers, which induce a strong anisotropic effect on the mechanical behavior. Currently, these tissues cannot be accurately represented by existing elastography phantoms. Recently, a novel approach for orthotropic hydrogel mimicking soft tissues has been developed (Millon et al 2006 J. Biomed. Mater. Res. B 305-11). The mechanical anisotropy is induced in a polyvinyl alcohol (PVA) cryogel by stretching the physical crosslinks of the polymeric chains while undergoing freeze/thaw cycles. In the present study we propose an original multimodality imaging characterization of this new transverse isotropic (TI) PVA hydrogel. Multiple properties were investigated using a large variety of techniques at different scales compared with an isotropic PVA hydrogel undergoing similar imaging and rheology protocols. The anisotropic mechanical (dynamic and static) properties were studied using supersonic shear wave imaging technique, full-field optical coherence tomography (FFOCT) strain imaging and classical linear rheometry using dynamic mechanical analysis. The anisotropic optical and ultrasonic spatial coherence properties were measured by FFOCT volumetric imaging and backscatter tensor imaging, respectively. Correlation of mechanical and optical properties demonstrates the complementarity of these techniques for the study of anisotropy on a multi-scale range as well as the potential of this TI phantom as fibrous tissue-mimicking phantom for shear wave elastographic applications.

Impact of the shape of the implantable ports on their efficiency of flow (injection and flushing).

Now widely used, totally implantable venous access devices allow mid- and long-term, frequent, repeated, or continuous injection of therapeutic products by vascular, cavitary, or perineural access. The effective flushing of these devices is a key factor that ensures their long-lasting use. We present experimental results and a numerical simulation to demonstrate that the implementation of rounded edge wall cavities improves flushing efficiency. We use the same approaches to suggest that the deposit amount may be reduced by the use of rounded edge wall cavities.

Heat-generating iron oxide nanocubes: subtle "destructurators" of the tumoral microenvironment.

Several studies propose nanoparticles for tumor treatment, yet little is known about the fate of nanoparticles and intimate interactions with the heterogeneous and ever-evolving tumor environment. The latter, rich in extracellular matrix, is responsible for poor penetration of therapeutics and represents a paramount issue in cancer therapy. Hence new strategies start aiming to modulate the neoplastic stroma. From this perspective, we assessed the efficacy of 19 nm PEG-coated iron oxide nanocubes with optimized magnetic properties to mediate mild tumor magnetic hyperthermia treatment. After injection of a low dose of nanocubes (700 µg of iron) into epidermoid carcinoma xenografts in mice, we monitored the effect of heating nanocubes on tumor environment. In comparison with the long-term fate after intravenous administration, we investigated spatiotemporal patterns of nanocube distribution, evaluated the evolution of cubes magnetic properties, and examined nanoparticle clearance and degradation processes. While inside tumors nanocubes retained their magnetic properties and heating capacity throughout the treatment due to a mainly interstitial extracellular location, the particles became inefficient heaters after cell internalization and transfer to spleen and liver. Our multiscale analysis reveals that collagen-rich tumor extracellular matrix confines the majority of nanocubes. However, nanocube-mediated hyperthermia has the potential to "destructure" this matrix and improve nanoparticle and drug penetration into neoplastic tissue. This study provides insight into dynamic interactions between nanoparticles and tumor components under physical stimulation and suggests that nanoparticle-mediated hyperthermia could be used to locally modify tumor stroma and thus improve drug penetration.

Homothety ratio of airway diameters and site of airway resistance in healthy and COPD subjects.

Our objective was to evaluate whether a decrease in the homothety ratio (h: diameter of child/parent bronchus, constant over generations) explains the shift in airway resistance toward periphery in chronic obstructive pulmonary disease (COPD). Using a validated computational model of fluid motion, we determined that reduced values of h (<0.76) were associated with a shift in resistance toward periphery. The calculated luminal diameters of terminal bronchioles using normal h (0.80-0.85) or reduced h (0.70-0.75) fitted well with measured micro-CT values obtained by McDonough et al. (N. Engl. J. Med., 2011; 365:1567-75) in control and COPD patients, respectively. A semi-analytic formula of resistance using tracheal dimensions and h was developed, and using experimental data (tracheal area and h from patients [Bokov et al., Respir. Physiol. Neurobiol., 2010; 173:1-10]), we verified the agreement between measured and calculated resistance (r=0.42). In conclusion, the remodeling process of COPD may reduce h and explain the shift in resistance toward lung periphery.

Power port contrast medium flushing and trapping: impact of temperature, an in vitro experimental study.

PURPOSE: The use of totally implantable venous access devices (TIVADs) certified as "high pressure resistant" or "power port" has begun to spread worldwide as a safe procedure for power contrast injection. Owing to the thermo-rheological properties of the contrast media, the primary aim of this work is to present an in vitro experimental impact study concerning the impact of the temperature level on flushing efficiency after contrast medium injection. Moreover, we report experimental data that confirms the role of needle bevel orientation. The secondary aim is to answer the following questions: Is there significant device contrast medium trapping after contrast medium injection? Is saline flushing efficient? And, finally, is it safe to inject contrast medium through an indwelled port catheter? RESULTS: The experimental results show that in addition to hydrodynamics, temperature is a key parameter for the efficiency of device flushing after contrast medium injection. It appears that this is the case when the cavity is incompletely rinsed after three calibrated flushing volumes of 10 mL saline solution, even by using the Huber needle bevel opposite to the port exit. This leads to a potentially important trapped volume of contrast medium in the port, and consequently to the possibility of subsequent salt precipitates and long term trisubstituted benzene nuclei delivery that might impair the solute properties, which may be further injected via the power port later on. CONCLUSION: We thus suggest, in TIVADS patients, the use of a temporary supplementary intravenous line rather than the port to perform contrast medium injections in daily radiology routine practice.

Correlation between classical rheometry and supersonic shear wave imaging in blood clots.

The assessment of coagulating blood elasticity has gained importance as a result of several studies that have correlated it to cardiovascular pathologic conditions. In this study we use supersonic shear wave imaging (SSI) to measure viscoelastic properties of blood clots. At the same time, classical rheometry experiments were carried out on the same blood samples taken within the first few seconds of coagulation. Using SSI, phase velocities of the shear wave indicated increasing dispersion with time. In all cases, the frequency bandwidth of propagating shear waves changed from 20-50 Hz at the first few min of coagulation to around 300 Hz toward the end of experiments. Using the values of G' and G″ from the rheometry studies, the theoretical shear wave velocities were calculated and correlated with SSI measurements. Results of the two techniques were in very good agreement, confirming that SSI provides accurate measurements of viscoelastic properties as corroborated by conventional rheometric measurements.

Flushing ports of totally implantable venous access devices, and impact of the Huber point needle bevel orientation: experimental tests and numerical computation.

The use of totally implantable venous access devices developed as a medical device allowing mid- and long-term, frequent, repeated, or continuous injection of therapeutic products, by vascular, cavitary, or perineural access. The effective flushing of these devices is a central element to assure long-lasting use. Our experimental work demonstrates that directing the Huber point needle opening in the diametrically opposite direction of the implantable port exit channel increases the flushing efficiency. These results are consolidated by numerical computations, which support recommendations not only for their maintenance, but also for their use.

Shear wave elastography quantification of blood elasticity during clotting.

Deep venous thrombosis (DVT) affects millions of people worldwide. A fatal complication occurs when the thrombi detach and create a pulmonary embolism. The diagnosis and treatment of DVT depends on clot's age. The elasticity of thrombi is closely related to its age. Blood was collected from pigs and anticoagulated using ethylenediaminetetraacetic acid (EDTA). Coagulation was initiated using calcium ions. Supersonic shear wave imaging was used to generate shear waves using 100 µs tone bursts of 8 MHz. Tracking of the shear waves was done by ultrafast imaging. Postprocessing of the data was done using Matlab(®). Two-dimensional (2-D) maps of elasticity were obtained by calculating the speed of shear wave propagation. Elasticity varied with time from around 50 Pa at coagulation to 1600 Pa at 120 min after which the elasticity showed a natural decreased (17%) because of thrombolytic action of plasmin. Ejection of the serum from the clot showed a significant decrease in the elasticity of the clot next to the liquid pool (65% decrease), corresponding to the detachment of the clot from the beaker wall. The use of a thrombolytic agent (Urokinase) on the coagulated blood decreased the shear elasticity close to the point of injection, which varied with time and distance. Supersonic imaging proved to be useful mapping the 2-D clot's elasticity. It allowed the visualization of the heterogeneity of mechanical properties of thrombi and has potential use in predicting thrombi breakage as well as in monitoring thrombolytic therapy.

Carotid circumferential wall stress homeostasis in early remodeling: theoretical approach and clinical application.

PURPOSE: To assess the influence of cardiovascular risk factors on arterial wall growth and the remodeling process. METHODS: In a theoretical part, we used a well-established relationship linking the rate of thickening of the arterial wall to the circumferential wall stress (CWS) increase. In a clinical part, we measured the intima-media thickness (IMT) in 166 subjects with increased cardiovascular risk score but no treatment for hypertension or hypercholesterolemia, no diabetes, and no cardiovascular disease. Far wall IMT and lumen diameter were measured along the right carotid artery by high-resolution ultrasonography and computerized image analysis. RESULTS: A decreasing linear relationship between IMT and CWS was deduced from the theoretical model, implying that an increase in CWS would result in an IMT increase, and that the higher the IMT-CWS slope, the higher the thickening response. Subjects with advanced age, renal insufficiency, high 10-year Framingham risk, carotid atherosclerosis, and advanced atherosclerosis at other sites had sharper IMT-CWS slope (p < 0.05), in agreement with the homeostasis of CWS hypothesis. CONCLUSIONS: The IMT increase responding to a CWS increase was greater in high-risk patients.

Flushing of intravascular access devices (IVADs) - efficacy of pulsed and continuous infusions.

PURPOSE: To compare, under controlled conditions similar to practical situations, the efficacy of pulsed and continuous infusion for flushing IVADs. For both of them different flow rates, flushing volumes, and times were tested. METHODS: The PU catheter lumens were filled with a mixture of fibronectin and bovine albumin to simulate physiologic protein depot. Flushing was performed with normal saline. An adapted pump controlled the flow rates. Efficacy was measured by the amount of albumin recovered from the lumen of the tested devices. Flow rate, volumes, and times tested were based upon values reported and/or measured in nursing practices. We compared: (A) single 10 mL bolus and 6 flushing times, (B) continuous infusion of 500 mL in 24 hours, (C) 10 successive boluses 1 mL flushed in 0.5 s each and 6 different time intervals between each bolus. Statistics were performed using the Mann and Whitney U test. RESULTS: In group A, the maximum percentage of recovered protein (79.1% was achieved with the 10 mL bolus flushed in 2.5. In group B, 77% of protein was recovered at 24h. In group C: maximum efficacy (90 +/- 3%) was obtained when the time interval between 2 boluses was 0.4 s. CONCLUSIONS: We conclude that hydrodynamics has a determinant effect on the efficacy and that the adjunction of an intermittent component in the flow increases it. Flow type and the time interval between 2 boluses are the 2 critical variables.

Toward the modeling of mucus draining from the human lung: role of the geometry of the airway tree.

Mucociliary clearance and cough are the two main natural mucus draining methods in the bronchial tree. If they are affected by a pathology, they can become insufficient or even ineffective, then therapeutic draining of mucus plays a critical role to keep mucus levels in the lungs acceptable. The manipulations of physical therapists are known to be very efficient clinically but they are mostly empirical since the biophysical mechanisms involved in these manipulations have never been studied. We develop in this work a model of mucus clearance in idealized rigid human bronchial trees and focus our study on the interaction between (1) tree geometry, (2) mucus physical properties and (3) amplitude of flow rate in the tree. The mucus is considered as a Bingham fluid (gel-like) which is moved upward in the tree thanks to its viscous interaction with air flow. Our studies point out the important roles played both by the geometry and by the physical properties of mucus (yield stress and viscosity). More particularly, the yield stress has to be overcome to make mucus flow. Air flow rate and yield stress determine the maximal possible mucus thickness in each branch of the tree at equilibrium. This forms a specific distribution of mucus in the tree whose characteristics are strongly related to the multi-scaled structure of the tree. The behavior of any mucus distribution is then dependent on this distribution. Finally, our results indicate that increasing air flow rates ought to be more efficient to drain mucus out of the bronchial tree while minimizing patient discomfort.