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The present article describes a standard instrument for the continuous online determination of retinal vessel diameters, the commercially available retinal vessel analyzer. This report is intended to provide informed guidelines for measuring ocular blood flow with this system. The report describes the principles underlying the method and the instruments currently available, and discusses clinical protocol and the specific parameters measured by the system. Unresolved questions and the possible limitations of the technique are also discussed.
Patients after coarctation repair still have an increased risk of cardiovascular or cerebrovascular events. This has been explained by the persisting hypertension and alterations in the peripheral vessels. However, involvement of the central vessels such as the retinal arteries is virtually unknown. A total of 34 patients after coarctation repair (22 men and 12 women; 23 to 58 years old, age range 0 to 32 years at surgical repair) and 34 nonhypertensive controls underwent structural and functional retinal vessel analysis. Using structural analysis, the vessel diameters were measured. Using functional analysis, the endothelium-dependent vessel dilation in response to flicker light stimulation was assessed. In the patients after coarctation repair, the retinal arteriolar diameter was significantly reduced compared to that of the controls (median 182 μm, first to third quartile 171 to 197; vs 197 μm, first to third quartile 193 to 206; p <0.001). These findings were independent of the peripheral blood pressure and age at intervention. No differences were found for venules. The functional analysis findings were not different between the patients and controls (maximum dilation 3.5%, first to third quartile 2.1% to 4.5% vs 3.6%, first to third quartile 2.2% to 4.3%; p = 0.81), indicating preserved autoregulative mechanisms. In conclusion, the retinal artery diameter is reduced in patients after coarctation repair, independent of their current blood pressure level and age at intervention. As a structural marker of chronic vessel damage associated with past, current, or future hypertension, retinal arteriolar narrowing has been linked to stroke incidence. These results indicate an involvement of cerebral microcirculation in aortic coarctation, despite timely repair, and might contribute to explain the increased rate of cerebrovascular events in such patients.
Air-pulse corneal applanation signal curve parameters for the characterisation of keratoconus
(2011)
Ein 34-jähriger männlicher Patient stellte sich zur Abklärung einer seit dem 9. Lebensjahr bestehenden und im letzten Jahr rasch progredienten Visusminderung beider Augen bei uns vor. Er beschrieb eine subjektiv zunehmende, im Spiegel für ihn selbst sichtbare, weißliche Trübung in der Pupille beidseits und eine starke Blendempfindlichkeit. Nebenbefundlich gab er rezidivierende Konjunktivitiden und morgens verklebte Lider an. Eine Allergie auf Gräserpollen und eine Unverträglichkeit auf Alkohol sowie mehrere Lebensmittel seien ebenfalls bekannt.
Zusätzlich leidet der Patient an stark ausgeprägtem atopischem Ekzem. Dieses wurde nie systemisch, sondern nur bei Bedarf mit kortisonhaltiger Salbe therapiert.
Bilaterale stromale Hornhauttrübungen sind für den Augenarzt eine differenzialdiagnostische Herausforderung. Im folgenden Beitrag werden 2 Patieninnen (30 und 36 Jahre) mit unterschiedlich stark ausgeprägter stromaler diffuser Hornhauttrübung vorgestellt. Patientin 1 war kleinwüchsig (114 cm) und Patientin 2 normal groß (172 cm). Beide Patientinnen wiesen veränderte Gelenkstrukturen an Hand und Fußgelenken sowie diffuse stromale Hornhauttrübungen auf. Des Weiteren lagen eine Mitral- und Aorteninsuffizienz (Patientin 1) bzw. eine Aorteninsuffizienz (Patientin 2) vor. Die stromalen diffusen Hornhauttrübungen ließen im Zusammenhang mit den Gelenkveränderungen ein Scheie-Syndrom vermuten. Therapeutisch ist bei Patienten mit Visusminderung eine (lamelläre) Keratoplastik sinnvoll.
Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself.
Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated.
Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains.
Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.
Purpose: Image analysis by the retinal vessel analyzer (RVA) observes retinal vessels in their dynamic state online noninvasively along a chosen vessel segment. It has been found that high-frequency diameter changes in the retinal artery blood column along the vessel increase significantly in anamnestically healthy volunteers with increasing age and in patients with glaucoma during vascular dilation. This study was undertaken to investigate whether longitudinal sections of the retinal artery blood column are altered in systemic hypertension.
Methods: Retinal arteries of 15 untreated patients with essential arterial hypertension (age, 50.9 ± 11.9 years) and of 15 age-matched anamnestically healthy volunteers were examined by RVA. After baseline assessment, a monochromatic luminance flicker (530–600 nm; 12.5 Hz; 20 s) was applied to evoke retinal vasodilation. Differences in amplitude and frequency of spatial artery blood column diameter change along segments (longitudinal arterial profiles) of 1 mm in length were measured and analyzed using Fourier transformation.
Results: In the control group, average reduced power spectra (ARPS) of longitudinal arterial profiles did not differ when arteries changed from constriction to dilation. In the systemic hypertension group, ARPS during constriction, baseline, and restoration were identical and differed from ARPS during dilation (P < 0.05). Longitudinal arterial profiles in both groups showed significant dissimilitude at baseline and restoration (P < 0.05).
Conclusions: The retinal artery blood column demonstrates microstructural alterations in systemic hypertension and is less irregular along the vessel axis during vessel dilation. These microstructural changes may be an indication of alterations in vessel wall rigidity, vascular endothelial function, and smooth muscle cells in this disease, leading to impaired perfusion and regulation.
Can vascular function be assessed by the interpretation of retinal vascular diameter changes?
(2011)
Influence of a freeze–thaw cycle on the stress–stretch curves of tissues of porcine abdominal organs
(2012)
The paper investigates both fresh porcine spleen and liver and the possible decomposition of these organs under a freeze–thaw cycle. The effect of tissue preservation condition is an important factor which should be taken into account for protracted biomechanical tests. In this work, tension tests were conducted for a large number of tissue specimens from twenty pigs divided into two groups of 10. Concretely, the first group was tested in fresh state; the other one was tested after a freeze-thaw cycle which simulates the conservation conditions before biomechanical experiments. A modified Fung model for isotropic behavior was adopted for the curve fitting of each kind of tissues. Experimental results show strong effects of the realistic freeze–thaw cycle on the capsule of elastin-rich spleen but negligible effects on the liver which virtually contains no elastin. This different behavior could be explained by the autolysis of elastin by elastolytic enzymes during the warmer period after thawing. Realistic biomechanical properties of elastin-rich organs can only be expected if really fresh tissue is tested. The observations are supported by tests of intestines.
The impact of surgical staplers on tissues has been studied mostly in an empirical manner. In this paper, finite element method was used to clarify the mechanics of tissue stapling and associated phenomena. Various stapling modalities and several designs of circular staplers were investigated to evaluate the impact of the device on tissues and mechanical performance of the end-to-end colorectal anastomosis. Numerical simulations demonstrated that a single row of staples is not adequate to resist leakage due to non-linear buckling and opening of the tissue layers between two adjacent staples. Compared to the single staple row configuration, significant increase in stress experienced by the tissue at the inner staple rows was observed in two and three rows designs. On the other hand, adding second and/or third staple row had no effect on strain in the tissue inside the staples. Variable height design with higher staples in outer rows significantly reduced the stresses and strains in outer rows when compared to the same configuration with flat cartridge.
All cells generate contractile tension. This strain is crucial for mechanically controlling the cell shape, function and survival. In this study, the CellDrum technology quantifying cell's (the cellular) mechanical tension on a pico-scale was used to investigate the effect of lipopolysaccharide (LPS) on human aortic endothelial cell (HAoEC) tension. The LPS effect during gram-negative sepsis on endothelial cells is cell contraction causing endothelium permeability increase. The aim was to finding out whether recombinant activated protein C (rhAPC) would reverse the endothelial cell response in an in-vitro sepsis model. In this study, the established in-vitro sepsis model was confirmed by interleukin 6 (IL-6) levels at the proteomic and genomic levels by ELISA, real time-PCR and reactive oxygen species (ROS) activation by florescence staining. The thrombin cellular contraction effect on endothelial cells was used as a positive control when the CellDrum technology was applied. Additionally, the Ras homolog gene family, member A (RhoA) mRNA expression level was checked by real time-PCR to support contractile tension results. According to contractile tension results, the mechanical predominance of actin stress fibers was a reason of the increased endothelial contractile tension leading to enhanced endothelium contractility and thus permeability enhancement. The originality of this data supports firstly the basic measurement principles of the CellDrum technology and secondly that rhAPC has a beneficial effect on sepsis influenced cellular tension. The technology presented here is promising for future high-throughput cellular tension analysis that will help identify pathological contractile tension responses of cells and prove further cell in-vitro models.
Suburethral slings as well as different meshes are widely used treating stress urinary incontinence and prolaps in women. With the development of MiniSlings and special meshes using less alloplastic material anchorage systems become more important to keep devices in place and to put some tension especially on the MiniSlings. To date, there are many different systems of MiniSlings of different companies on the market which differ in the structure of the used meshes and anchors. A new objective measurement method to compare different properties of MiniSling systems (mesh and anchor) is presented in this article. Ballistic gelatine acts as soft tissue surrogate. Significant differences in parameters like pull-out strength of anchors or shrinkage of meshes under loading conditions have been determined. The form and size of the anchors as well as the structural stability of the meshes are decisive for a proper integration. The tested anchorings sytems showed markedly different mechanical function at their respective load bearing capacity. As the stable fixation of the device in tissue is a prerequisite for a permanet reinforcement, the proposed test system permits further optimisation of anchor and mesh devices to improve the success of the surgical treatment
Autonomous robotic systems for penetrating thick ice shells with simultaneous collecting of scientific data are very promising devices in both terrestrial (glacier, climate research) and extra-terrestrial applications. Technical challenges in development of such systems are numerous and include 3D-navigation, an appropriate energy source, motion control, etc. Not less important is the problem of forward contamination of the pristine glacial environments with microorganisms and biomolecules from the surface of the probe. This study was devoted to establishing a laboratory model for microbial contamination of a newly constructed ice-melting probe called IceMole and to analyse the viability and amount of the contaminating microorganisms as a function of distance. The used bacterial strains were Bacillus subtilis (ATCC 6051) and Escherichia coli (ATCC 11775). The main objective was development of an efficient and reliable in-situ decontamination method of the melting probe. Therefore, several chemical substances were tested in respect of their efficacy to eliminate bacteria on the surface of the melting probe at low temperature (0 - 5 °C) and at continuous dilution by melted water. Our study has shown that at least 99.9% decontamination of the IceMole can be successfully achieved by the injection of 30% (v/v) hydrogen peroxide and 3% (v/v) sodium hypochlorite into the drilling site. We were able to reproduce this result in both time-dependent and depth-dependent experiments. The sufficient amount of 30% (v/v) H₂O₂ or 3% (v/v) NaClO has been found to be approximately 18 L per cm² of the probe’s surface.
Aims: Thrombotic complications due to activation of platelets and plasmatic clotting factors belong still to the most investigated topics in the field of study of patho-physiological mechanisms. Mathematical modeling of thrombotic reactions is established and validated in test cases. Aim of this study is to experimentally evaluate and computationally simulate platelets under the influence of well-defined shear flow conditions. Platelet behaviour and reactions are experimentally reproduced, measured and used for validation of the numerical simulation. Methods: A mathematical model of platelet activation, adhesion and aggregation has been implemented into a finite element CFD (Computational Fluid Dynamics) code. The approach is based on the advective and diffusive transport equations for resting platelets, activated platelets and platelet released agonists. Adhesion rates for the reactive surfaces depend on the hemocompatibility properties of the surface and the local shear rate. Experiments with citrate-anticoagulated freshly-drawn whole blood are performed in a perfusion flow chamber as well as in a system of rotating cylinders for Couette and Taylor-vortex flow. Different biomaterials are used. The activation, drop of platelet concentration, adhesion and aggregation are quantified using scanning electron microscopy (SEM) and flow cytometry. Results: Regions and flow conditions with a high potential for thrombus growth could be identified. The experiments clearly show the influence of the blood contacting material and flow properties. By means of SEM diverse platelet adhesion patterns are observed. Numerical analysis can explain the patterns and the degree of thrombus formation. Conclusion: The numerical method shows good agreement with experimental data indicating a possible prediction of initiation of activation and detection of the local adhesion areas in connection with the role of Von-Willebrand-Factor.
Purpose of Study: Thrombosis-related complications are among the leading causes for morbidity and mortality in patients who depend on artificial organs. For the prediction of platelet behavior both the flow conditions inside the device and the thrombogenic properties of the blood-contacting surfaces must be considered. Platelet reactions under the influence of well-defined shear rates are experimentally evaluated and numerically simulated. The approach is intended for the analysis of VAD and oxygenator design.
Methods Used: A mathematical model of platelet activation, adhesion and aggregation has been implemented into a finite element CFD (Computational Fluid Dynamics) code. The approach is based on the advective and diffusive transport equations for resting and activated platelets and platelet released agonists. Experiments with citrate-anticoagulated freshly-drawn whole blood are performed in a perfusion flow chamber as well as in a system of rotating cylinders for Couette and Taylor-vortex flow. Different biomaterials are used. The activation, adhesion and aggregation are quantified using scanning electron microscopy and flow cytometry.
Summary of Results: Regions and flow conditions with a high potential for thrombus growth could be identified. The experiments clearly show the influence of the blood contacting material and governing shear rates. Numerical analysis can explain observed adhesion patterns and the degree of thrombus formation
The MicroMed DeBakey ventricular assist device is an axial flow pump designed for providing long-term support to end-stage heartfailure patients. Previously, we presented computational analysis of the blood pump flow. From the analysis, we were able to identify regions of high shear and recirculating flow that may cause blood damage, for example, deformation and fragmentation of the red blood cell (RBC). This mechanical hemolysis can be predicted using a tensor-based blood damage model that is based on the physical properties of the RBCs, for example, the relaxation time of the RBC membrane. However, an extensive and detailed analysis was complicated by the fact that the previous method predicts hemolysis along a finite number of pathlines traversed by the RBCs, possibly omitting parts of the flow domain. Furthermore, it is computationally expensive and is not easily parallelizable.
Here, we propose a new method to estimate hemolysis. The method is based on treating the shape of droplet (tensor) as a field variable, like velocity in the Navier-Stokes system. The governing equation for the RBC shape is treated by least-squares finite element method and the volume conservation of the RBC is augmented by Lagrangian multiplier. Unlike the previous method, the proposed method can visualize areas of high RBC strain that is potentially dangerous for mechanical hemolysis. Also, the amount of plasma-free hemoglobin and, consequently, normalized index of hemolysis can be computed as a byproduct. The method is tested in a simple shear flow for validation and an artery graft flow is chosen to show its potential usefulness. Finally, the method is applied to the blood damage estimation for the pump.