Designing and Testing of Backflow-Free Catheters

2011 ◽  
Vol 133 (6) ◽  
Author(s):  
O. Ivanchenko ◽  
V. Ivanchenko
Keyword(s):  
Porous Media ◽  
Hydraulic Conductivity ◽  
Flow Direction ◽  
Drug Distribution ◽  
Fluid Injection ◽  
Conductivity Anisotropy ◽  
Convection Enhanced Delivery ◽  
Delivery Technique ◽  
Catheter Design ◽  
The Impact

Convection-enhanced delivery (CED) is a drug delivery technique used to target specific regions of the central nervous system (CNS) for the treatment of neurodegenerative diseases and cancer while bypassing the blood–brain barrier (BBB). The application of CED is limited by low volumetric flow rate infusions in order to prevent the possibility of backflow. Consequently, a small convective flow produces poor drug distribution inside the treatment region, which can render CED treatment ineffective. Novel catheter designs and CED protocols are needed in order to improve the drug distribution inside the treatment region and prevent backflow. In order to develop novel backflow-free catheter designs, the impact of the micro-fluid injection into deformable porous media was investigated experimentally as well as numerically. Fluid injection into the porous media has a considerable effect on local transport properties such as porosity and hydraulic conductivity because of the local media deformation. These phenomena not only alter the bulk flow velocity distribution of the micro-fluid flow due to the changing porosity, but significantly modify the flow direction, and even the volumetric flow distribution, due to induced local hydraulic conductivity anisotropy. These findings help us to design backflow-free catheters with safe volumetric flow rates up to 10 μl/min. A first catheter design reduces porous media deformation in order to improve catheter performance and control an agent volumetric distribution. A second design prevents the backflow by reducing the porosity and hydraulic conductivity along a catheter’s shaft. A third synergistic catheter design is a combination of two previous designs. Novel channel-inducing and dual-action catheters, as well as a synergistic catheter, were successfully tested without the occurrence of backflow and are recommended for future animal experiments.

scholarly journals Convection-Enhanced Delivery in silico study for personalized brain cancer treatment

2021 ◽  
Author(s):  
Chryso Lambride ◽  
Vasileios Vavourakis ◽  
Triantafyllos Stylianopoulos
Keyword(s):  
Brain Cancer ◽  
In Silico ◽  
Drug Transport ◽  
Drug Distribution ◽  
Local Drug Delivery ◽  
Patient Specific ◽  
Convection Enhanced Delivery ◽  
Formidable Challenge ◽  
The Impact ◽  
The Brain

Abstract Brain cancer therapy remains a formidable challenge in oncology. Convection-enhanced delivery (CED) is an innovative and promising local drug delivery method for the treatment of brain cancer, overcoming the challenges of the systemic delivery of drugs to the brain. To improve our understanding about CED efficacy and drug transport, we present an in silico methodology for brain cancer CED treatment simulation. To achieve this, a three-dimensional finite element biomechanics formulation is utilized which employs patient-specific brain model representation and is used to predict the drug deposition in CED regimes. The model encompasses nonlinear biomechanics and the transport of drugs in the brain parenchyma. Drug distribution was studied under various patho-physiological conditions of the tumor, in terms of tumor vessel wall pore size and tumor tissue hydraulic conductivity as well as for drugs of various sizes, spanning from small molecules to nanoparticles. Our contribution reports for the first time the impact of the size of the vascular wall pores and that of the therapeutic agent on drug distribution during and after CED. The in silico findings provide useful insights of the spatio-temporal distribution and average drug concentration in the tumor towards an effective treatment of brain cancer.

Kinematical measurement of hydraulic tortuosity of fluid flow in porous media

2015 ◽  
Vol 26 (02) ◽  
pp. 1550017 ◽  
Author(s):  
Y. Jin ◽  
J. B. Dong ◽  
X. Li ◽  
Y. Wu
Keyword(s):  
Porous Media ◽  
Flow Direction ◽  
Estimation Method ◽  
Mean Value ◽  
Calculation Model ◽  
Flow In Porous Media ◽  
Porous Media Flow ◽  
Average Value ◽  
The Mean ◽  
The Impact

It is hard to experimentally or analytically derive the hydraulic tortuosity (τ) of porous media flow because of their complex microstructures. In this work, we propose a kinematical measurement method for τ by introducing the concept of local tortuosity, which is defined as the ratio of fluid particle velocity to its component along the macro flow. And then, the calculation model of τ is analytically deduced in terms of that τ is the mean value of the local tortuosity. To avoid the impact from the singularity of local tortuosity, the velocity is normalized, and τ is then approximated by the ratio of the mean normalized velocity to the average value of its component along the macro-flow direction. The new estimation method is verified by flow through different types of porous media via the lattice Boltzmann method, and the relationships between permeabilities and tortuosities obtained by different methods are examined. The numerical results show that tortuosity by the novel approach is in good agreement with the existing theory, and the kinematic definition of hydraulic tortuosity is also proven.

Poor drug distribution as a possible explanation for the results of the PRECISE trial

2010 ◽  
Vol 113 (2) ◽  
pp. 301-309 ◽  
Author(s):  
John H. Sampson ◽  
Gary Archer ◽  
Christoph Pedain ◽  
Eva Wembacher-Schröder ◽  
Manfred Westphal ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Targets ◽  
Drug Distribution ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Karnofsky Performance Scale ◽  
Convection Enhanced Delivery ◽  
Resection Cavity ◽  
Delivery Technique ◽  
Target Volumes

Object Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. Methods Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. Results Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p < 0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. Conclusions The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED.

scholarly journals DDEL-16. UNDERSTANDING OPTIMAL CONVECTION-ENHANCED DELIVERY PHYSICO-CHEMICAL INFUSION PARAMETERS: THE ROLE OF BBB EFFLUX PUMPS IN DRUG DISTRIBUTION AND CLEARANCE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii286-iii287
Author(s):  
Erica Power ◽  
Liang Zhang ◽  
David Daniels
Keyword(s):  
Drug Concentration ◽  
Efflux Pump ◽  
Drug Distribution ◽  
Efflux Pumps ◽  
Drug Clearance ◽  
Convection Enhanced Delivery ◽  
Efflux Pump Inhibition ◽  
Physico Chemical ◽  
Delivery Technique ◽  
Optimal Drug

Abstract BACKGROUND Diffuse midline gliomas harboring the H3K27M mutation are aggressive and universally fatal brain tumors that primarily occur in children. The blood-brain barrier (BBB) prevents many drugs from reaching the tumor at cytotoxic concentrations and efflux pumps found on the epithelial cells of the BBB rapidly pump drugs out of the brain. Convection enhanced delivery (CED) is a drug delivery technique that bypasses the BBB by directly injecting the drug into the tumor site under a pressure gradient. Further clinical implementation of CED requires understanding drug distribution, as optimal drug physico-chemical properties have never been evaluated. METHODS Sprague Dawley rats underwent a single injection of drug by CED to the brainstem with and without an efflux pump inhibitor. Animals were euthanized at 0, 2, 4, 8, 12 and 24 hours. Their brain drug concentration/distribution was analyzed by MALDI-MSI and plasma drug concentration was measured by LC-MS/MS. RESULTS Drug distribution and brainstem concentration were increased following BBB efflux pump inhibition compared to no pump inhibition controls. Additionally, efflux pump inhibition resulted in slower drug clearance for those drugs that are known pump substrates. CONCLUSIONS BBB efflux pump inhibition resulted in a larger volume of distribution, increased drug concentration and slower drug clearance following CED to the brainstem of known efflux substrates.

scholarly journals Experimental study of the supercritical CO 2 diffusion coefficient in porous media under reservoir conditions

2019 ◽  
Vol 6 (6) ◽  
pp. 181902 ◽  
Author(s):  
Junchen Lv ◽  
Yuan Chi ◽  
Changzhong Zhao ◽  
Yi Zhang ◽  
Hailin Mu
Keyword(s):  
Porous Media ◽  
Diffusion Coefficient ◽  
Oil Recovery ◽  
Carbon Capture ◽  
Carbon Capture And Storage ◽  
Elevated Pressure ◽  
Experimental Results ◽  
Saturated Porous Media ◽  
Reservoir Conditions ◽  
The Impact

Reliable measurement of the CO 2 diffusion coefficient in consolidated oil-saturated porous media is critical for the design and performance of CO 2 -enhanced oil recovery (EOR) and carbon capture and storage (CCS) projects. A thorough experimental investigation of the supercritical CO 2 diffusion in n -decane-saturated Berea cores with permeabilities of 50 and 100 mD was conducted in this study at elevated pressure (10–25 MPa) and temperature (333.15–373.15 K), which simulated actual reservoir conditions. The supercritical CO 2 diffusion coefficients in the Berea cores were calculated by a model appropriate for diffusion in porous media based on Fick's Law. The results show that the supercritical CO 2 diffusion coefficient increases as the pressure, temperature and permeability increase. The supercritical CO 2 diffusion coefficient first increases slowly at 10 MPa and then grows significantly with increasing pressure. The impact of the pressure decreases at elevated temperature. The effect of permeability remains steady despite the temperature change during the experiments. The effect of gas state and porous media on the supercritical CO 2 diffusion coefficient was further discussed by comparing the results of this study with previous study. Based on the experimental results, an empirical correlation for supercritical CO 2 diffusion coefficient in n -decane-saturated porous media was developed. The experimental results contribute to the study of supercritical CO 2 diffusion in compact porous media.

scholarly journals Waterfall Algorithm as a tool of investigation the geometrical features of granular porous media

2021 ◽  
Author(s):  
Wojciech Sobieski
Keyword(s):  
Particle Size ◽  
Porous Media ◽  
Lattice Boltzmann ◽  
Granular Media ◽  
Density Ratio ◽  
Geometrical Features ◽  
Granular Porous Media ◽  
Collision Density ◽  
Boltzmann Method ◽  
The Impact

AbstractThe paper describes the so-called Waterfall Algorithm, which may be used to calculate a set of parameters characterising the spatial structure of granular porous media, such as shift ratio, collision density ratio, consolidation ratio, path length and minimum tortuosity. The study is performed for 1800 different two-dimensional random pore structures. In each geometry, 100 individual paths are calculated. The impact of porosity and the particle size on the above-mentioned parameters is investigated. It was stated in the paper, that the minimum tortuosity calculated by the Waterfall Algorithm cannot be used directly as a representative tortuosity of pore channels in the Kozeny or the Carman meaning. However, it may be used indirect by making the assumption that a unambiguous relationship between the representative tortuosity and the minimum tortuosity exists. It was also stated, that the new parameters defined in the present study are sensitive on the porosity and the particle size and may be therefore applied as indicators of the geometry structure of granular media. The Waterfall Algorithm is compared with other methods of determining the tortuosity: A-Star Algorithm, Path Searching Algorithm, Random Walk technique, Path Tracking Method and the methodology of calculating the hydraulic tortuosity based on the Lattice Boltzmann Method. A very short calculation time is the main advantage of the Waterfall Algorithm, what meant, that it may be applied in a very large granular porous media.

scholarly journals Advanced Constitutive Modeling of the Thixotropic Elasto-Visco-Plastic Behavior of Blood: Steady-State Blood Flow in Microtubes

Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 367
Author(s):  
Konstantinos Giannokostas ◽  
Yannis Dimakopoulos ◽  
Andreas Anayiotos ◽  
John Tsamopoulos
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Constitutive Model ◽  
Blood Plasma ◽  
Constitutive Modeling ◽  
Flow Direction ◽  
Momentum Balance ◽  
Plastic Behavior ◽  
Flow Investigation ◽  
The Impact

The present work focuses on the in-silico investigation of the steady-state blood flow in straight microtubes, incorporating advanced constitutive modeling for human blood and blood plasma. The blood constitutive model accounts for the interplay between thixotropy and elasto-visco-plasticity via a scalar variable that describes the level of the local blood structure at any instance. The constitutive model is enhanced by the non-Newtonian modeling of the plasma phase, which features bulk viscoelasticity. Incorporating microcirculation phenomena such as the cell-free layer (CFL) formation or the Fåhraeus and the Fåhraeus-Lindqvist effects is an indispensable part of the blood flow investigation. The coupling between them and the momentum balance is achieved through correlations based on experimental observations. Notably, we propose a new simplified form for the dependence of the apparent viscosity on the hematocrit that predicts the CFL thickness correctly. Our investigation focuses on the impact of the microtube diameter and the pressure-gradient on velocity profiles, normal and shear viscoelastic stresses, and thixotropic properties. We demonstrate the microstructural configuration of blood in steady-state conditions, revealing that blood is highly aggregated in narrow tubes, promoting a flat velocity profile. Additionally, the proper accounting of the CFL thickness shows that for narrow microtubes, the reduction of discharged hematocrit is significant, which in some cases is up to 70%. At high pressure-gradients, the plasmatic proteins in both regions are extended in the flow direction, developing large axial normal stresses, which are more significant in the core region. We also provide normal stress predictions at both the blood/plasma interface (INS) and the tube wall (WNS), which are difficult to measure experimentally. Both decrease with the tube radius; however, they exhibit significant differences in magnitude and type of variation. INS varies linearly from 4.5 to 2 Pa, while WNS exhibits an exponential decrease taking values from 50 mPa to zero.

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