The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform

Stephen R. Hanson - One of the best experts on this subject based on the ideXlab platform.

  • A Novel Method for Efficient Drug Delivery
    Annals of Biomedical Engineering, 1998
    Co-Authors: Christos P. Markou, David N. Ku, Elizabeth M. Lutostansky, Stephen R. Hanson
    Abstract:

    Local delivery of anti-thrombotic and anti-restenotic drugs is desired to achieve high concentrations of agents which may be rapidly degraded Systemically or which exhibit very short half-lives in vivo . In this article, the operating characteristics of a novel local drug delivery method are described and its effectiveness demonstrated computationally and experimentally. Computational models used a finite volume method to determine the concentration field. Optical dye density measurements of Evans blue in saline were performed in an in vitro steady flow System. Modeling parameters were kept in the physiologic range. Experimental flow visualization studies demonstrated high concentrations of infusate near the vessel wall. Computational studies predicted high, clinically significant drug concentrations along the wall downstream of the infusion device. When the radial infusion velocity is large (infusion flow rate, Q_inf > 0.5% of the main flow rate, Q), the wall concentration of the infused drug remains high, e.g., levels are greater than 80% of the infusate concentration 5 cm downstream of the infusion device. At lower infusion rates (Q_inf < 0.001Q), the drug concentration at the wall decreases exponentially with axial distance to less than 25% of the infusate concentration 5 cm downstream of the infusion device, although therapeutic drug levels are still readily maintained. The near wall drug concentration is a function of flow conditions, infusion rate, and the drug diffusivity. Good agreement was obtained between computational and experimental concentration measurements. Flow simulation and experimental results indicate that the technique can effectively sustain high local drug concentrations for inhibition of thrombosis and vascular lesion formation.

  • Boundary layer drug delivery using a helical catheter.
    Journal of controlled release : official journal of the Controlled Release Society, 1998
    Co-Authors: C P Markou, J E Brown, M D Pursley, Stephen R. Hanson
    Abstract:

    A catheter-based approach for local endovascular drug delivery has been developed. The catheter is deployed percutaneously, while the end of the catheter is in the form of a helix that is placed just proximal to the vascular site to be treated. The helices are in contact with the vessel wall. A number of small holes is drilled in the coils of the catheter through which drug is infused, so that the infused drug remains within the blood fluid 'boundary layer' adjacent to the vessel wall. This approach is expected to be highly efficient for administration of antithrombotic and antiproliferative agents that target processes leading to vascular occlusion, heart attacks, and strokes. The helical catheter was qualitatively evaluated using optical dye density measurements of Evans blue dye infused using an in vitro steady flow System under a physiologic range of conditions. To further demonstrate the efficiency of the technique, its capacity to inhibit thrombosis was evaluated in a baboon thrombosis model. The catheter was inserted into a femoral arteriovenous shunt (blood flow rate = 100 ml/min) and placed proximal to a segment of highly thrombogenic Dacron vascular graft (4.0 mm i.d.). Integrelin (an inhibitor of platelet glycoprotein IIb/IIIa; doses: 0.25-1.0 microg/min) and hirudin (an antithrombin; doses: 10-100 microg/min) were used to inhibit thrombus formation. Experimental flow visualization studies demonstrated that high concentrations of the infused Evans blue dye were retained near the vessel wall. In the animal experiments, platelet deposition on the Dacron graft surface was reduced by 82-97% (Integrelin) and 68-92% (hirudin) over 1-2 h of blood exposure. The local antithrombotic effects produced were found to be 200-fold and 30-fold more efficient than Systemic administration of the same agents. Local drug infusion using the helical catheter approach can achieve high drug concentration levels at target sites, may avoid Systemic effects, and can reduce cost of therapy by reducing total drug requirements.

  • Boundary layer drug delivery using a helical catheter
    Journal of Controlled Release, 1998
    Co-Authors: Christos P. Markou, J E Brown, M D Pursley, Stephen R. Hanson
    Abstract:

    Abstract Background : A catheter-based approach for local endovascular drug delivery has been developed. The catheter is deployed percutaneously, while the end of the catheter is in the form of a helix that is placed just proximal to the vascular site to be treated. The helices are in contact with the vessel wall. A number of small holes is drilled in the coils of the catheter through which drug is infused, so that the infused drug remains within the blood fluid `boundary layer' adjacent to the vessel wall. This approach is expected to be highly efficient for administration of antithrombotic and antiproliferative agents that target processes leading to vascular occlusion, heart attacks, and strokes. Methods : The helical catheter was qualitatively evaluated using optical dye density measurements of Evans blue dye infused using an in vitro steady flow System under a physiologic range of conditions. To further demonstrate the efficiency of the technique, its capacity to inhibit thrombosis was evaluated in a baboon thrombosis model. The catheter was inserted into a femoral arteriovenous shunt (blood flow rate=100 ml/min) and placed proximal to a segment of highly thrombogenic Dacron vascular graft (4.0 mm i.d.). Integrelin (an inhibitor of platelet glycoprotein IIb/IIIa; doses: 0.25–1.0 μ g/min) and hirudin (an antithrombin; doses: 10–100 μ g/min) were used to inhibit thrombus formation. Results : Experimental flow visualization studies demonstrated that high concentrations of the infused Evans blue dye were retained near the vessel wall. In the animal experiments, platelet deposition on the Dacron graft surface was reduced by 82–97% (Integrelin) and 68–92% (hirudin) over 1–2 h of blood exposure. The local antithrombotic effects produced were found to be 200-fold and 30-fold more efficient than Systemic administration of the same agents. Conclusions : Local drug infusion using the helical catheter approach can achieve high drug concentration levels at target sites, may avoid Systemic effects, and can reduce cost of therapy by reducing total drug requirements.

Christos P. Markou - One of the best experts on this subject based on the ideXlab platform.

  • A Novel Method for Efficient Drug Delivery
    Annals of Biomedical Engineering, 1998
    Co-Authors: Christos P. Markou, David N. Ku, Elizabeth M. Lutostansky, Stephen R. Hanson
    Abstract:

    Local delivery of anti-thrombotic and anti-restenotic drugs is desired to achieve high concentrations of agents which may be rapidly degraded Systemically or which exhibit very short half-lives in vivo . In this article, the operating characteristics of a novel local drug delivery method are described and its effectiveness demonstrated computationally and experimentally. Computational models used a finite volume method to determine the concentration field. Optical dye density measurements of Evans blue in saline were performed in an in vitro steady flow System. Modeling parameters were kept in the physiologic range. Experimental flow visualization studies demonstrated high concentrations of infusate near the vessel wall. Computational studies predicted high, clinically significant drug concentrations along the wall downstream of the infusion device. When the radial infusion velocity is large (infusion flow rate, Q_inf > 0.5% of the main flow rate, Q), the wall concentration of the infused drug remains high, e.g., levels are greater than 80% of the infusate concentration 5 cm downstream of the infusion device. At lower infusion rates (Q_inf < 0.001Q), the drug concentration at the wall decreases exponentially with axial distance to less than 25% of the infusate concentration 5 cm downstream of the infusion device, although therapeutic drug levels are still readily maintained. The near wall drug concentration is a function of flow conditions, infusion rate, and the drug diffusivity. Good agreement was obtained between computational and experimental concentration measurements. Flow simulation and experimental results indicate that the technique can effectively sustain high local drug concentrations for inhibition of thrombosis and vascular lesion formation.

  • Boundary layer drug delivery using a helical catheter
    Journal of Controlled Release, 1998
    Co-Authors: Christos P. Markou, J E Brown, M D Pursley, Stephen R. Hanson
    Abstract:

    Abstract Background : A catheter-based approach for local endovascular drug delivery has been developed. The catheter is deployed percutaneously, while the end of the catheter is in the form of a helix that is placed just proximal to the vascular site to be treated. The helices are in contact with the vessel wall. A number of small holes is drilled in the coils of the catheter through which drug is infused, so that the infused drug remains within the blood fluid `boundary layer' adjacent to the vessel wall. This approach is expected to be highly efficient for administration of antithrombotic and antiproliferative agents that target processes leading to vascular occlusion, heart attacks, and strokes. Methods : The helical catheter was qualitatively evaluated using optical dye density measurements of Evans blue dye infused using an in vitro steady flow System under a physiologic range of conditions. To further demonstrate the efficiency of the technique, its capacity to inhibit thrombosis was evaluated in a baboon thrombosis model. The catheter was inserted into a femoral arteriovenous shunt (blood flow rate=100 ml/min) and placed proximal to a segment of highly thrombogenic Dacron vascular graft (4.0 mm i.d.). Integrelin (an inhibitor of platelet glycoprotein IIb/IIIa; doses: 0.25–1.0 μ g/min) and hirudin (an antithrombin; doses: 10–100 μ g/min) were used to inhibit thrombus formation. Results : Experimental flow visualization studies demonstrated that high concentrations of the infused Evans blue dye were retained near the vessel wall. In the animal experiments, platelet deposition on the Dacron graft surface was reduced by 82–97% (Integrelin) and 68–92% (hirudin) over 1–2 h of blood exposure. The local antithrombotic effects produced were found to be 200-fold and 30-fold more efficient than Systemic administration of the same agents. Conclusions : Local drug infusion using the helical catheter approach can achieve high drug concentration levels at target sites, may avoid Systemic effects, and can reduce cost of therapy by reducing total drug requirements.

  • Evaluation of Magnetic Resonance Velocimetry for Steady Flow
    Journal of Biomechanical Engineering-transactions of The Asme, 1990
    Co-Authors: David N. Ku, C. L. Biancheri, Roderic I. Pettigrew, J. W. Peifer, Christos P. Markou, H. Engels
    Abstract:

    Whole body magnetic resonance (MR) imaging has recently become an important diagnostic tool for cardiovascular diseases. The technique of magnetic resonance phase velocity encoding allows the quantitative measurement of velocity for an arbitrary component direction. A study was initiated to determine the ability and accuracy of MR velocimetry to measure a wide range of flow conditions including flow separation, three-dimensional secondary flow, high velocity gradients, and turbulence. A steady flow System pumped water doped with manganese chloride through a variety of test sections. Images were produced using gradient echo sequences on test sections including a straight tube, a curved tube, a smoothly converging-diverging nozzle, and an orifice. Magnetic resonance measurements of laminar and turbulent flows were depicted as cross-sectional velocity profiles. MR velocity measurements revealed such flow behavior as spatially varying velocity, recirculation and secondary flows over a wide range of conditions. Comparisons made with published experimental laser Doppler anemometry measurements and theoretical calculations for similar flow conditions revealed excellent accuracy and precision levels. The successful measurement of velocity profiles for a variety of flow conditions and geometries indicate that magnetic resonance imaging is an accurate, non-contacting velocimeter.

K. Helmke - One of the best experts on this subject based on the ideXlab platform.

  • Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF)
    Pediatric Radiology, 1992
    Co-Authors: P. Winkler, K. Helmke
    Abstract:

    An in-vitro steady flow System was designed to determine the lowest flow velocities that can be detected by echographic colour flow imaging and spectral analysis. The flow detection level was determined hydrostatically by reducing the fluid level to below the point at which a flow signal was visible, then increasing the height until the colour flow reappeared. This was confirmed in all instances by spectral analysis. The height (angle-corrected velocity) of the spectral envelope was also determined. Mean volume flow was then obtained by using a graduated cylinder and a stop watch. The lowest hematocrit detectable was identified using a stepwise dilution of packed human red blood cells with 0.9% sodium chloride. Three different PVC-tubes with inner diameters of 2.1 mm, 1.1 mm and 0.51 mm were used. It was found that: 1) echographic flow imaging is remarkably sensitive to low concentrations of scattering particles (lowest hematocrit detected by colour flow and spectrum was 0.003% using the 2.1 mm diameter tube); 2) lowest hematocrit values which allowed detection of true mean flow velocities below 2 cm/sec increased with decreasing lumen: 0.006% for the 2.1 mm tube; 0.22% for the 1.1 mm tube and 1.6% for the 0.51 mm tube; 3) higher velocities and/or greater lumina were necessary to detect hematocrit values below 1%; 4) for a hematocrit between 0.1% and 44% measured mean flow velocities were less than half the values obtained from spectral envelope; 5) the error of spectral flow velocity determination was relatively constant for this hematocrit range (0.1%–44%), but varied with tube size; 6) minimal concentrations of red blood cells could be differentiated from air bubbles by signal intensity at constant receiver gain settings; 7) there was no difference in the height of the velocity envelope between air and red blood cells. The diagnostic, clinical and scientific implications of these findings are discussed.

  • Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF). Part III. In-vitro study of low flow velocity detection related to decreasing particle concentration (hematocrit) and tube lumen.
    Pediatric Radiology, 1992
    Co-Authors: P. Winkler, K. Helmke
    Abstract:

    An in-vitro steady flow System was designed to determine the lowest flow velocities that can be detected by echographic colour flow imaging and spectral analysis. The flow detection level was determined hydrostatically by reducing the fluid level to below the point at which a flow signal was visible, then increasing the height until the colour flow reappeared. This was confirmed in all instances by spectral analysis. The height (angle-corrected velocity) of the spectral envelope was also determined. Mean volume flow was then obtained by using a graduated cylinder and a stop watch. The lowest hematocrit detectable was identified using a stepwise dilution of packed human red blood cells with 0.9% sodium chloride. Three different PVC-tubes with inner diameters of 2.1 mm, 1.1 mm and 0.51 mm were used. It was found that: 1) echographic flow imaging is remarkably sensitive to low concentrations of scattering particles (lowest hematocrit detected by colour flow and spectrum was 0.003% using the 2.1 mm diameter tube); 2) lowest hematocrit values which allowed detection of true mean flow velocities below 2 cm/sec increased with decreasing lumen: 0.006% for the 2.1 mm tube; 0.22% for the 1.1 mm tube and 1.6% for the 0.51 mm tube; 3) higher velocities and/or greater lumina were necessary to detect hematocrit values below 1%; 4) for a hematocrit between 0.1% and 44% measured mean flow velocities were less than half the values obtained from spectral envelope; 5) the error of spectral flow velocity determination was relatively constant for this hematocrit range (0.1%–44%), but varied with tube size; 6) minimal concentrations of red blood cells could be differentiated from air bubbles by signal intensity at constant receiver gain settings; 7) there was no difference in the height of the velocity envelope between air and red blood cells. The diagnostic, clinical and scientific implications of these findings are discussed.

David N. Ku - One of the best experts on this subject based on the ideXlab platform.

  • A Novel Method for Efficient Drug Delivery
    Annals of Biomedical Engineering, 1998
    Co-Authors: Christos P. Markou, David N. Ku, Elizabeth M. Lutostansky, Stephen R. Hanson
    Abstract:

    Local delivery of anti-thrombotic and anti-restenotic drugs is desired to achieve high concentrations of agents which may be rapidly degraded Systemically or which exhibit very short half-lives in vivo . In this article, the operating characteristics of a novel local drug delivery method are described and its effectiveness demonstrated computationally and experimentally. Computational models used a finite volume method to determine the concentration field. Optical dye density measurements of Evans blue in saline were performed in an in vitro steady flow System. Modeling parameters were kept in the physiologic range. Experimental flow visualization studies demonstrated high concentrations of infusate near the vessel wall. Computational studies predicted high, clinically significant drug concentrations along the wall downstream of the infusion device. When the radial infusion velocity is large (infusion flow rate, Q_inf > 0.5% of the main flow rate, Q), the wall concentration of the infused drug remains high, e.g., levels are greater than 80% of the infusate concentration 5 cm downstream of the infusion device. At lower infusion rates (Q_inf < 0.001Q), the drug concentration at the wall decreases exponentially with axial distance to less than 25% of the infusate concentration 5 cm downstream of the infusion device, although therapeutic drug levels are still readily maintained. The near wall drug concentration is a function of flow conditions, infusion rate, and the drug diffusivity. Good agreement was obtained between computational and experimental concentration measurements. Flow simulation and experimental results indicate that the technique can effectively sustain high local drug concentrations for inhibition of thrombosis and vascular lesion formation.

  • Evaluation of Magnetic Resonance Velocimetry for Steady Flow
    Journal of Biomechanical Engineering-transactions of The Asme, 1990
    Co-Authors: David N. Ku, C. L. Biancheri, Roderic I. Pettigrew, J. W. Peifer, Christos P. Markou, H. Engels
    Abstract:

    Whole body magnetic resonance (MR) imaging has recently become an important diagnostic tool for cardiovascular diseases. The technique of magnetic resonance phase velocity encoding allows the quantitative measurement of velocity for an arbitrary component direction. A study was initiated to determine the ability and accuracy of MR velocimetry to measure a wide range of flow conditions including flow separation, three-dimensional secondary flow, high velocity gradients, and turbulence. A steady flow System pumped water doped with manganese chloride through a variety of test sections. Images were produced using gradient echo sequences on test sections including a straight tube, a curved tube, a smoothly converging-diverging nozzle, and an orifice. Magnetic resonance measurements of laminar and turbulent flows were depicted as cross-sectional velocity profiles. MR velocity measurements revealed such flow behavior as spatially varying velocity, recirculation and secondary flows over a wide range of conditions. Comparisons made with published experimental laser Doppler anemometry measurements and theoretical calculations for similar flow conditions revealed excellent accuracy and precision levels. The successful measurement of velocity profiles for a variety of flow conditions and geometries indicate that magnetic resonance imaging is an accurate, non-contacting velocimeter.

P. Winkler - One of the best experts on this subject based on the ideXlab platform.

  • Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF)
    Pediatric Radiology, 1992
    Co-Authors: P. Winkler, K. Helmke
    Abstract:

    An in-vitro steady flow System was designed to determine the lowest flow velocities that can be detected by echographic colour flow imaging and spectral analysis. The flow detection level was determined hydrostatically by reducing the fluid level to below the point at which a flow signal was visible, then increasing the height until the colour flow reappeared. This was confirmed in all instances by spectral analysis. The height (angle-corrected velocity) of the spectral envelope was also determined. Mean volume flow was then obtained by using a graduated cylinder and a stop watch. The lowest hematocrit detectable was identified using a stepwise dilution of packed human red blood cells with 0.9% sodium chloride. Three different PVC-tubes with inner diameters of 2.1 mm, 1.1 mm and 0.51 mm were used. It was found that: 1) echographic flow imaging is remarkably sensitive to low concentrations of scattering particles (lowest hematocrit detected by colour flow and spectrum was 0.003% using the 2.1 mm diameter tube); 2) lowest hematocrit values which allowed detection of true mean flow velocities below 2 cm/sec increased with decreasing lumen: 0.006% for the 2.1 mm tube; 0.22% for the 1.1 mm tube and 1.6% for the 0.51 mm tube; 3) higher velocities and/or greater lumina were necessary to detect hematocrit values below 1%; 4) for a hematocrit between 0.1% and 44% measured mean flow velocities were less than half the values obtained from spectral envelope; 5) the error of spectral flow velocity determination was relatively constant for this hematocrit range (0.1%–44%), but varied with tube size; 6) minimal concentrations of red blood cells could be differentiated from air bubbles by signal intensity at constant receiver gain settings; 7) there was no difference in the height of the velocity envelope between air and red blood cells. The diagnostic, clinical and scientific implications of these findings are discussed.

  • Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF). Part III. In-vitro study of low flow velocity detection related to decreasing particle concentration (hematocrit) and tube lumen.
    Pediatric Radiology, 1992
    Co-Authors: P. Winkler, K. Helmke
    Abstract:

    An in-vitro steady flow System was designed to determine the lowest flow velocities that can be detected by echographic colour flow imaging and spectral analysis. The flow detection level was determined hydrostatically by reducing the fluid level to below the point at which a flow signal was visible, then increasing the height until the colour flow reappeared. This was confirmed in all instances by spectral analysis. The height (angle-corrected velocity) of the spectral envelope was also determined. Mean volume flow was then obtained by using a graduated cylinder and a stop watch. The lowest hematocrit detectable was identified using a stepwise dilution of packed human red blood cells with 0.9% sodium chloride. Three different PVC-tubes with inner diameters of 2.1 mm, 1.1 mm and 0.51 mm were used. It was found that: 1) echographic flow imaging is remarkably sensitive to low concentrations of scattering particles (lowest hematocrit detected by colour flow and spectrum was 0.003% using the 2.1 mm diameter tube); 2) lowest hematocrit values which allowed detection of true mean flow velocities below 2 cm/sec increased with decreasing lumen: 0.006% for the 2.1 mm tube; 0.22% for the 1.1 mm tube and 1.6% for the 0.51 mm tube; 3) higher velocities and/or greater lumina were necessary to detect hematocrit values below 1%; 4) for a hematocrit between 0.1% and 44% measured mean flow velocities were less than half the values obtained from spectral envelope; 5) the error of spectral flow velocity determination was relatively constant for this hematocrit range (0.1%–44%), but varied with tube size; 6) minimal concentrations of red blood cells could be differentiated from air bubbles by signal intensity at constant receiver gain settings; 7) there was no difference in the height of the velocity envelope between air and red blood cells. The diagnostic, clinical and scientific implications of these findings are discussed.