L. Goubergrits - Academia.edu (original) (raw)

Papers by L. Goubergrits

SIGLEAvailable from TIB Hannover: F03B152 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Tech... more SIGLEAvailable from TIB Hannover: F03B152 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDeutsche Forschungsgemeinschaft (DFG), Bonn (Germany)DEGerman

IFMBE Proceedings, 2009

ABSTRACT Cerebral aneurysms are potentially life threatening. Computational fluid dynamics with n... more ABSTRACT Cerebral aneurysms are potentially life threatening. Computational fluid dynamics with non-invasive imaging methods can determine biofluidmechanical parameters of aneurysms. This study investigate the impact of the imaging techniques — magnetic resonance imaging (MRI), computed tomography (CT) and rotational angiography (3DRA) - to geometry reconstruction and calculated wall shear stress (WSS) distributions in a model of a basilaris artery. The comparison of the reconstructed geometries shows that the MRI and the 3DRA based reconstructions with mean 0.097 mm and 0.1 mm Hausdorff surface distance to the original geometry are better than the CT based reconstruction with mean 0.242 mm by similar resolutions of about 0.13 mm3 voxel sizes. Comparison of calculated mean WSS shows partially good correlation for the whole aneurysm bifurcation surface (4.02 Pa in the original geometry, 3.06 Pa in the CT, 3.62 Pa in the MRI and 4.17 Pa in the 3DRA based models).

IFMBE Proceedings, 2009

ABSTRACT Patient specific analysis of cerebral aneurysm hemodynamics is based on methods of compu... more ABSTRACT Patient specific analysis of cerebral aneurysm hemodynamics is based on methods of computational fluid dynamics (CFD) and non-invasive medical imaging. The flow results are influenced by the reconstructed geometry, especially by the length of the reconstructed parent vessel. To investigate the influence of the length of the parent vessel, rotational angiography data (3DRA) of three cerebral aneurysms were used. The aneurysms were segmented and three models of each aneurysm with different vessel lengths were generated. For these nine models, flow simulations were performed using the CFD program FLUENT. The objective was the analysis of the wall shear stress (WSS) distributions at the aneurysm dome. The results show that the reconstructed parent vessel should be as long as possible - the minimum length should be at least 6 times the diameter of the inlet vessel.

Informatik aktuell

Patientenspezifische Strömungs-und die Geometrieanalyse von Aneurysmen basiert auf der 3D-Rekonst... more Patientenspezifische Strömungs-und die Geometrieanalyse von Aneurysmen basiert auf der 3D-Rekonstruktion aus Daten, die mit modernen Methoden der Bildgebung (z.B. CT und MRT) gewonnen werden. Die unterschiedlichen Charakteristika der Bildgebungsverfahren und die damit verbundenen Unsicherheiten führen zu Variationen der rekonstruierten Geometrien, die sich auf die numerische Berechnung von Strömungsparametern, wie z.B. die Wandschubspannung, auswirken können. Basierend auf CT-und MRT-Aufnahmen eines anatomisch realistischen Referenzmodells eines zerebralen Aneurysmas der Arteria Basilaris vergleichen wir die rekonstruierten Geometrien und die hierin simulierten Blutströmungen. Die Segmentierung und Rekonstruktion des Aneurysmas erfolgte mit Hilfe des Programms AMIRA. Die numerischen Strömungsberechnungen wurden mit dem Strömungslöser FLUENT durchgeführt.

Heart and vessels, 1997

After many years of research, various left ventricular assist systems (LVADs) are now entering cl... more After many years of research, various left ventricular assist systems (LVADs) are now entering clinical practice and are exposed to wider application. Currently, we are seeing a change in concept: after the successful application of LVADs as a bridge to transplant, today the permanent use of these devices is attracting the attention of the scientific community. LVADs based on pulsatile blood pumps necessarily contain many discrete elements. However, by integration of parts they can be made fairly simple and safe. Thrombo-embolic complications can be reduced by better design of the valves, avoiding stagnant flow altogether.

Journal of Visualization, 2004

... One important hemodynamic parameter implicated in the aneurysm growth and rupture is wall she... more ... One important hemodynamic parameter implicated in the aneurysm growth and rupture is wall shear stress. ... With the recent development of the 3D medical imaging it is now possible to reliably simulate blood flow in anatomically realistic vessel geometries. ...

Journal of Biomechanics, 2006

Atherosclerosis, 2011

Blood flow, vascular shape and size and local remodeling of the vascular wall are linked through ... more Blood flow, vascular shape and size and local remodeling of the vascular wall are linked through wall shear stress (WSS) signaling. Inter-individual comparison of shape and WSS is hampered by large differences in size of flow and shape. We performed non-dimensional modeling to discriminate different types of coronary artery remodeling based on WSS patterns and vessel morphology. Blood flow was simulated in three-dimensional reconstructed right coronary artery trees from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) classified by expert visual diagnosis. A discriminant model using low WSS area, a remodeling index, and cross-correlation of WSS in main trunks and complete trees (K) as non-dimensional parameters classified CAD and AnCAD correctly and identified three patients with high risk profile and functional disease in controls. The new model was compared with discriminant analysis of identical cases simulated without side-branches. The inclusion of K (information from side-branches) and replacement of the mean diameter by a non-dimensional remodeling index improved the model. We found significant (p<0.005) gender differences in the remodeling index. The combination of non-dimensional modeling and WSS profiling should be further investigated as a novel diagnostic tool in CAD beyond local stenosis.

Atherosclerosis, 2009

Background: Local wall shear stress (WSS) has an impact on local remodelling of the vessel wall. ... more Background: Local wall shear stress (WSS) has an impact on local remodelling of the vessel wall. WSS in turn strongly depends on local geometry. Our aim was to characterize patterns of local wall shear stress associated with distinct types of remodelling in coronary arteries. Vessel size and flow rates are different between patients, however. To compare distribution patterns of WSS in analogy to fluid-dynamic modelling, non-dimensional WSS/area functions are calculated. Methods: Right coronary arteries from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) were analyzed. Flow simulations were performed in three-dimensionally reconstructed coronary vessels from biplane angiographic projections. Local WSS was normalized as percentage of maximum value in a histogram (100 classes) and corresponding area was expressed as percentage of total area. Results: The normalized WSS distribution was characterized by a single peak with a large lower tie in controls, a loss of the single peak and a stochastic distribution in AnCAD and a narrowing of the lower tie in CAD. Correct classification of 16/17 coronary arteries was feasible by Fisher's discriminant functions based on median WSS, mean diameter, percentage of area with WSS ≤ 0.4 Pa and with WSS ≥ 15 Pa. Conclusion: Normalized WSS distribution might be an efficient tool in comparing wall shear stress between different patient groups. Whether normalized WSS distribution curves are apt to grade severity of disease remains to be investigated.

Atherosclerosis, 2010

Aims: Wall shear stress (WSS) may induce local remodeling of the vascular wall and the WSS patter... more Aims: Wall shear stress (WSS) may induce local remodeling of the vascular wall and the WSS pattern in turn depends on vascular geometry. We aimed to elucidate the impact of side-branches on local WSS. Methods and results: Steady numerical flow simulation studies were performed in three-dimensional reconstructed right coronary artery (RCA) trees. RCA from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) classified by expert visual diagnosis were studied. Then three transient flow simulations were performed with cases representative for each group in order to evaluate the impact of pulsatile flow simulation. As vascular size and flow rates vary considerably between patients, non-dimensional approaches were applied for group comparison. A point-to-point comparison of the WSS in the same tree with and without side-branches revealed local differences in WSS of up to 12.0 Pa. This was caused by a reduction of volume flow of up to 78.7% in the trunk. Differences are not only limited to bifurcation sites but also affect local narrowings and strongly curved segments. The point-to-point comparison of steady and transient simulations found an average increase of WSS of below 7% in transient simulations. No significant differences were found between histograms of pulsatile and steady simulations, showing a high cross-correlation of >0.97. Conclusion: Side-branches must not be neglected in numerical flow simulation (steady and transient) studies. Steady simulations are valid for an assessment of time-averaged WSS distributions.

American Journal of Neuroradiology, 2010

BACKGROUND AND PURPOSE: Coil embolization procedures change the flow conditions in the cerebral a... more BACKGROUND AND PURPOSE: Coil embolization procedures change the flow conditions in the cerebral aneurysm and, therefore, in the near-wall region. Knowledge of these flow changes may be helpful to optimize therapy. The goal of this study was to investigate the effect of the coil-packing attenuation on the near-wall flow and its variability due to differences in the coil structure. MATERIALS AND METHODS: An enlarged transparent model of an ACA aneurysm was fabricated on the basis of CT angiography. The near-wall flow was visualized by using a recently proposed technique called Wall-PIV. Coil-packing attenuation of 10%, 15%, and 20% were investigated and compared with an aneurysmal flow without coils. Then the flow variability due to the coil introduction was analyzed in 10 experiments by using a packing attenuation of 15%. RESULTS: A small packing attenuation of 10% already alters the near-wall flow significantly in a large part of the aneurysmal sac. These flow changes are characterized by a slow flow with short (interrupted) path lines. An increased packing attenuation expands the wall area exposed to the altered flow conditions. This area, however, depends on the coil position and/or on the 3D coil structure in the aneurysm. CONCLUSIONS: To our knowledge, this is the first time the near-wall flow changes caused by coils in an aneurysm model have been visualized. It can be concluded that future hydrodynamic studies of coil therapy should include an investigation of the coil structure in addition to the coil-packing attenuation. ABBREVIATIONS: ACA ϭ anterior cerebral artery; CFD ϭ computational fluid dynamics; GDC ϭ Guglielmi detachable coil; HS1 and HS2 ϭ half-spheres 1 and 2; LIC ϭ line integral convolution; PIV ϭ particle image velocimetry; STL ϭ stereolithography; Wall-PIV ϭ wall particle image velocimetry; WSS ϭ wall shear stress

The Thoracic and Cardiovascular Surgeon

Scientific Reports

The original version of this Article contained a typographical error in the spelling of the autho... more The original version of this Article contained a typographical error in the spelling of the author V. Falk, which was incorrectly given as Falk. This has now been corrected in the PDF and HTML versions of the Article.

PLOS ONE

Colonization of in-dwelling catheters by microbial biofilms is a major concern in patient health ... more Colonization of in-dwelling catheters by microbial biofilms is a major concern in patient health eventually leading to catheter-related blood stream infections. Biofilms are less susceptible to standard antibiotic therapies that are effective against planktonic bacteria. Standard procedure for the detection of microorganisms on the catheter tip is culture. However, viable but non-culturable cells (VBNCs) may be missed. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) as an indicator to visualize and quantify the effect of the antibiotics daptomycin and vancomycin on biofilms in situ. We established an in vitro catheter biofilm model of Staphylococcus epidermidis biofilms on polyurethane catheters. Biofilm activity was measured by FISH and correlated to colony forming units (CFU) data. Digital image analysis was used for quantification of total biofilm mass and the area of the FISH positive biofilm cells. FISH showed a pronounced effect of both antibiotics on the biofilms, with daptomycin having a significantly stronger effect in terms of both reduction of biofilm mass and number of FISH-positive cells. This supports the anti-biofilm capacity of daptomycin. Interestingly, neither antibiotic was able to eradicate all of the FISH-positive cells. In summary, FISH succeeded in visualization, quantification, and localization of antibiotic activity on biofilms. This technique adds a new tool to the arsenal of test systems for anti-biofilm compounds. FISH is a valuable complementary technique to CFU since it can be highly standardized and provides information on biofilm architecture and quantity and localization of survivor cells.

Bubble columns are aerated liquid filled vertical tubes, which are widely used in biotechnology a... more Bubble columns are aerated liquid filled vertical tubes, which are widely used in biotechnology and chemical engineering. Despite their widespread use, the fluid mechanics in these apparatuses are not yet understood. Therefore, the investigation of the fluid mechanics is necessary. This investigation with optical methods is yet difficult and, for high void fractions, impossible due to the fact that reflection and refraction of light occur on the gas-liquid boundaries. These effects do not occur applying X-rays instead of light. These rays penetrate a multiphase flow in straight lines. The use of X-rays is not new. The medical application of X-ray angiography is a good example. However, Xrays were also applied to multiphase flows. They are used to measure the local time-averaged void fraction in bubble columns by X-ray tomography, to determine the overall void fraction dynamically, and to visualize the flow by an injection of an X-ray absorbing liquid into a bubble column. We developed a new velocimetry method based on X-rays. The liquid in question is seeded with X-ray absorbing particles. These particles have the same density as the liquid. It is assumed that the particles are representing the liquid velocity. Therefore, by the knowledge of the particle motion, the liquid motion is measured. The particle motion is observed from two direction using X-rays to allow a three-dimensional particle tracking. Velocity fields are calculated from the trajectories. One example is shown below: The superficial gas velocity was set to 1 mm/s. The void fraction was about 5 %. The method proved to be suitable to measure the velocity of the liquid phase of a bubble column. The method is a 3-dimensional, 3-component method. The main advantages, compared to optical methods, is that no reflection and refraction problems arise at phase boundaries. Therefore, the application of the method is not limited by a large void fraction or opaque fluids. Like optical methods, the technique is non-intrusive. The time for the acquirement of a 3-dimensional velocity field is small (less than 20 sec). Particle trajectories (left) and velocity field (right).

For the investigation of flow structures in bubble columns it is necessary to measure the local l... more For the investigation of flow structures in bubble columns it is necessary to measure the local liquid velocity. Common optical methods fail in a bubble flow with a large void fraction. The cause is the different refraction index of liquid phase and gaseous phase, which leads to reflection and dispersion. The new X-ray based Particle Tracking Velocimetry (PTV) - called

SIGLEAvailable from TIB Hannover: F03B152 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Tech... more SIGLEAvailable from TIB Hannover: F03B152 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDeutsche Forschungsgemeinschaft (DFG), Bonn (Germany)DEGerman

IFMBE Proceedings, 2009

ABSTRACT Cerebral aneurysms are potentially life threatening. Computational fluid dynamics with n... more ABSTRACT Cerebral aneurysms are potentially life threatening. Computational fluid dynamics with non-invasive imaging methods can determine biofluidmechanical parameters of aneurysms. This study investigate the impact of the imaging techniques — magnetic resonance imaging (MRI), computed tomography (CT) and rotational angiography (3DRA) - to geometry reconstruction and calculated wall shear stress (WSS) distributions in a model of a basilaris artery. The comparison of the reconstructed geometries shows that the MRI and the 3DRA based reconstructions with mean 0.097 mm and 0.1 mm Hausdorff surface distance to the original geometry are better than the CT based reconstruction with mean 0.242 mm by similar resolutions of about 0.13 mm3 voxel sizes. Comparison of calculated mean WSS shows partially good correlation for the whole aneurysm bifurcation surface (4.02 Pa in the original geometry, 3.06 Pa in the CT, 3.62 Pa in the MRI and 4.17 Pa in the 3DRA based models).

IFMBE Proceedings, 2009

ABSTRACT Patient specific analysis of cerebral aneurysm hemodynamics is based on methods of compu... more ABSTRACT Patient specific analysis of cerebral aneurysm hemodynamics is based on methods of computational fluid dynamics (CFD) and non-invasive medical imaging. The flow results are influenced by the reconstructed geometry, especially by the length of the reconstructed parent vessel. To investigate the influence of the length of the parent vessel, rotational angiography data (3DRA) of three cerebral aneurysms were used. The aneurysms were segmented and three models of each aneurysm with different vessel lengths were generated. For these nine models, flow simulations were performed using the CFD program FLUENT. The objective was the analysis of the wall shear stress (WSS) distributions at the aneurysm dome. The results show that the reconstructed parent vessel should be as long as possible - the minimum length should be at least 6 times the diameter of the inlet vessel.

Informatik aktuell

Patientenspezifische Strömungs-und die Geometrieanalyse von Aneurysmen basiert auf der 3D-Rekonst... more Patientenspezifische Strömungs-und die Geometrieanalyse von Aneurysmen basiert auf der 3D-Rekonstruktion aus Daten, die mit modernen Methoden der Bildgebung (z.B. CT und MRT) gewonnen werden. Die unterschiedlichen Charakteristika der Bildgebungsverfahren und die damit verbundenen Unsicherheiten führen zu Variationen der rekonstruierten Geometrien, die sich auf die numerische Berechnung von Strömungsparametern, wie z.B. die Wandschubspannung, auswirken können. Basierend auf CT-und MRT-Aufnahmen eines anatomisch realistischen Referenzmodells eines zerebralen Aneurysmas der Arteria Basilaris vergleichen wir die rekonstruierten Geometrien und die hierin simulierten Blutströmungen. Die Segmentierung und Rekonstruktion des Aneurysmas erfolgte mit Hilfe des Programms AMIRA. Die numerischen Strömungsberechnungen wurden mit dem Strömungslöser FLUENT durchgeführt.

Heart and vessels, 1997

After many years of research, various left ventricular assist systems (LVADs) are now entering cl... more After many years of research, various left ventricular assist systems (LVADs) are now entering clinical practice and are exposed to wider application. Currently, we are seeing a change in concept: after the successful application of LVADs as a bridge to transplant, today the permanent use of these devices is attracting the attention of the scientific community. LVADs based on pulsatile blood pumps necessarily contain many discrete elements. However, by integration of parts they can be made fairly simple and safe. Thrombo-embolic complications can be reduced by better design of the valves, avoiding stagnant flow altogether.

Journal of Visualization, 2004

... One important hemodynamic parameter implicated in the aneurysm growth and rupture is wall she... more ... One important hemodynamic parameter implicated in the aneurysm growth and rupture is wall shear stress. ... With the recent development of the 3D medical imaging it is now possible to reliably simulate blood flow in anatomically realistic vessel geometries. ...

Journal of Biomechanics, 2006

Atherosclerosis, 2011

Blood flow, vascular shape and size and local remodeling of the vascular wall are linked through ... more Blood flow, vascular shape and size and local remodeling of the vascular wall are linked through wall shear stress (WSS) signaling. Inter-individual comparison of shape and WSS is hampered by large differences in size of flow and shape. We performed non-dimensional modeling to discriminate different types of coronary artery remodeling based on WSS patterns and vessel morphology. Blood flow was simulated in three-dimensional reconstructed right coronary artery trees from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) classified by expert visual diagnosis. A discriminant model using low WSS area, a remodeling index, and cross-correlation of WSS in main trunks and complete trees (K) as non-dimensional parameters classified CAD and AnCAD correctly and identified three patients with high risk profile and functional disease in controls. The new model was compared with discriminant analysis of identical cases simulated without side-branches. The inclusion of K (information from side-branches) and replacement of the mean diameter by a non-dimensional remodeling index improved the model. We found significant (p<0.005) gender differences in the remodeling index. The combination of non-dimensional modeling and WSS profiling should be further investigated as a novel diagnostic tool in CAD beyond local stenosis.

Atherosclerosis, 2009

Background: Local wall shear stress (WSS) has an impact on local remodelling of the vessel wall. ... more Background: Local wall shear stress (WSS) has an impact on local remodelling of the vessel wall. WSS in turn strongly depends on local geometry. Our aim was to characterize patterns of local wall shear stress associated with distinct types of remodelling in coronary arteries. Vessel size and flow rates are different between patients, however. To compare distribution patterns of WSS in analogy to fluid-dynamic modelling, non-dimensional WSS/area functions are calculated. Methods: Right coronary arteries from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) were analyzed. Flow simulations were performed in three-dimensionally reconstructed coronary vessels from biplane angiographic projections. Local WSS was normalized as percentage of maximum value in a histogram (100 classes) and corresponding area was expressed as percentage of total area. Results: The normalized WSS distribution was characterized by a single peak with a large lower tie in controls, a loss of the single peak and a stochastic distribution in AnCAD and a narrowing of the lower tie in CAD. Correct classification of 16/17 coronary arteries was feasible by Fisher's discriminant functions based on median WSS, mean diameter, percentage of area with WSS ≤ 0.4 Pa and with WSS ≥ 15 Pa. Conclusion: Normalized WSS distribution might be an efficient tool in comparing wall shear stress between different patient groups. Whether normalized WSS distribution curves are apt to grade severity of disease remains to be investigated.

Atherosclerosis, 2010

Aims: Wall shear stress (WSS) may induce local remodeling of the vascular wall and the WSS patter... more Aims: Wall shear stress (WSS) may induce local remodeling of the vascular wall and the WSS pattern in turn depends on vascular geometry. We aimed to elucidate the impact of side-branches on local WSS. Methods and results: Steady numerical flow simulation studies were performed in three-dimensional reconstructed right coronary artery (RCA) trees. RCA from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) classified by expert visual diagnosis were studied. Then three transient flow simulations were performed with cases representative for each group in order to evaluate the impact of pulsatile flow simulation. As vascular size and flow rates vary considerably between patients, non-dimensional approaches were applied for group comparison. A point-to-point comparison of the WSS in the same tree with and without side-branches revealed local differences in WSS of up to 12.0 Pa. This was caused by a reduction of volume flow of up to 78.7% in the trunk. Differences are not only limited to bifurcation sites but also affect local narrowings and strongly curved segments. The point-to-point comparison of steady and transient simulations found an average increase of WSS of below 7% in transient simulations. No significant differences were found between histograms of pulsatile and steady simulations, showing a high cross-correlation of >0.97. Conclusion: Side-branches must not be neglected in numerical flow simulation (steady and transient) studies. Steady simulations are valid for an assessment of time-averaged WSS distributions.

American Journal of Neuroradiology, 2010

BACKGROUND AND PURPOSE: Coil embolization procedures change the flow conditions in the cerebral a... more BACKGROUND AND PURPOSE: Coil embolization procedures change the flow conditions in the cerebral aneurysm and, therefore, in the near-wall region. Knowledge of these flow changes may be helpful to optimize therapy. The goal of this study was to investigate the effect of the coil-packing attenuation on the near-wall flow and its variability due to differences in the coil structure. MATERIALS AND METHODS: An enlarged transparent model of an ACA aneurysm was fabricated on the basis of CT angiography. The near-wall flow was visualized by using a recently proposed technique called Wall-PIV. Coil-packing attenuation of 10%, 15%, and 20% were investigated and compared with an aneurysmal flow without coils. Then the flow variability due to the coil introduction was analyzed in 10 experiments by using a packing attenuation of 15%. RESULTS: A small packing attenuation of 10% already alters the near-wall flow significantly in a large part of the aneurysmal sac. These flow changes are characterized by a slow flow with short (interrupted) path lines. An increased packing attenuation expands the wall area exposed to the altered flow conditions. This area, however, depends on the coil position and/or on the 3D coil structure in the aneurysm. CONCLUSIONS: To our knowledge, this is the first time the near-wall flow changes caused by coils in an aneurysm model have been visualized. It can be concluded that future hydrodynamic studies of coil therapy should include an investigation of the coil structure in addition to the coil-packing attenuation. ABBREVIATIONS: ACA ϭ anterior cerebral artery; CFD ϭ computational fluid dynamics; GDC ϭ Guglielmi detachable coil; HS1 and HS2 ϭ half-spheres 1 and 2; LIC ϭ line integral convolution; PIV ϭ particle image velocimetry; STL ϭ stereolithography; Wall-PIV ϭ wall particle image velocimetry; WSS ϭ wall shear stress

The Thoracic and Cardiovascular Surgeon

Scientific Reports

The original version of this Article contained a typographical error in the spelling of the autho... more The original version of this Article contained a typographical error in the spelling of the author V. Falk, which was incorrectly given as Falk. This has now been corrected in the PDF and HTML versions of the Article.

PLOS ONE

Colonization of in-dwelling catheters by microbial biofilms is a major concern in patient health ... more Colonization of in-dwelling catheters by microbial biofilms is a major concern in patient health eventually leading to catheter-related blood stream infections. Biofilms are less susceptible to standard antibiotic therapies that are effective against planktonic bacteria. Standard procedure for the detection of microorganisms on the catheter tip is culture. However, viable but non-culturable cells (VBNCs) may be missed. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) as an indicator to visualize and quantify the effect of the antibiotics daptomycin and vancomycin on biofilms in situ. We established an in vitro catheter biofilm model of Staphylococcus epidermidis biofilms on polyurethane catheters. Biofilm activity was measured by FISH and correlated to colony forming units (CFU) data. Digital image analysis was used for quantification of total biofilm mass and the area of the FISH positive biofilm cells. FISH showed a pronounced effect of both antibiotics on the biofilms, with daptomycin having a significantly stronger effect in terms of both reduction of biofilm mass and number of FISH-positive cells. This supports the anti-biofilm capacity of daptomycin. Interestingly, neither antibiotic was able to eradicate all of the FISH-positive cells. In summary, FISH succeeded in visualization, quantification, and localization of antibiotic activity on biofilms. This technique adds a new tool to the arsenal of test systems for anti-biofilm compounds. FISH is a valuable complementary technique to CFU since it can be highly standardized and provides information on biofilm architecture and quantity and localization of survivor cells.

Bubble columns are aerated liquid filled vertical tubes, which are widely used in biotechnology a... more Bubble columns are aerated liquid filled vertical tubes, which are widely used in biotechnology and chemical engineering. Despite their widespread use, the fluid mechanics in these apparatuses are not yet understood. Therefore, the investigation of the fluid mechanics is necessary. This investigation with optical methods is yet difficult and, for high void fractions, impossible due to the fact that reflection and refraction of light occur on the gas-liquid boundaries. These effects do not occur applying X-rays instead of light. These rays penetrate a multiphase flow in straight lines. The use of X-rays is not new. The medical application of X-ray angiography is a good example. However, Xrays were also applied to multiphase flows. They are used to measure the local time-averaged void fraction in bubble columns by X-ray tomography, to determine the overall void fraction dynamically, and to visualize the flow by an injection of an X-ray absorbing liquid into a bubble column. We developed a new velocimetry method based on X-rays. The liquid in question is seeded with X-ray absorbing particles. These particles have the same density as the liquid. It is assumed that the particles are representing the liquid velocity. Therefore, by the knowledge of the particle motion, the liquid motion is measured. The particle motion is observed from two direction using X-rays to allow a three-dimensional particle tracking. Velocity fields are calculated from the trajectories. One example is shown below: The superficial gas velocity was set to 1 mm/s. The void fraction was about 5 %. The method proved to be suitable to measure the velocity of the liquid phase of a bubble column. The method is a 3-dimensional, 3-component method. The main advantages, compared to optical methods, is that no reflection and refraction problems arise at phase boundaries. Therefore, the application of the method is not limited by a large void fraction or opaque fluids. Like optical methods, the technique is non-intrusive. The time for the acquirement of a 3-dimensional velocity field is small (less than 20 sec). Particle trajectories (left) and velocity field (right).

For the investigation of flow structures in bubble columns it is necessary to measure the local l... more For the investigation of flow structures in bubble columns it is necessary to measure the local liquid velocity. Common optical methods fail in a bubble flow with a large void fraction. The cause is the different refraction index of liquid phase and gaseous phase, which leads to reflection and dispersion. The new X-ray based Particle Tracking Velocimetry (PTV) - called