Compensating the Influence of Tremors on Impedance Measurements Through Fourier Analysis.

Electrical mpedance measurements are a promising method for detecting structural changes in tissue and can be used in oncology to differentiate between healthy and tumorous tissue areas. The impedance measurements are so sensitive that they are not only affected by changes in the tissue itself, but also by a fluctuating contact force between sensor and tissue. In this work, the correlation between impedance measurements and movements during the measuring process, such as physiological tremors, are analyzed. To do this, impedance measurements are taken on pig bladders and the sensor-tissue contact force is simultaneously recorded. The tremor frequencies are directly visible in the Fourier transform of the impedance measurement. To counteract these effects, a Butterworth filter is used to filter out tremor frequencies and remove unwanted artefacts. Additionally, placing an spring on top of the impedance sensor helped to achieve a steadier contact force between sensor and tissue to also remove low frequency disturbances in the impedance measurements.Clinical relevance- This approach can help to obtain more reliable impedance measurements on tissue both for ex vivo and in vivo applications.

An Enhanced Synthetic Cystoscopic Environment for Use in Monocular Depth Estimation.

As technology advances and sensing devices improve, it is becoming more and more pertinent to ensure accurate positioning of these devices, especially within the human body. This task remains particularly difficult during manual, minimally invasive surgeries such as cystoscopies where only a monocular, endoscopic camera image is available and driven by hand. Tracking relies on optical localization methods, however, existing classical options do not function well in such a dynamic, non-rigid environment. This work builds on recent works using neural networks to learn a supervised depth estimation from synthetically generated images and, in a second training step, use adversarial training to then apply the network on real images. The improvements made to a synthetic cystoscopic environment are done in such a way to reduce the domain gap between the synthetic images and the real ones. Training with the proposed enhanced environment shows distinct improvements over previously published work when applied to real test images.

In-plane Strain Analysis by Correlating Geometry and Visual Data Through a Gradient-Based Surface Reconstruction.

Abnormalities in tissue can be detected and analyzed by evaluating mechanical properties, such as strain and stiffness. While current sensor systems are effective in measuring longitudinal properties perpendicular to the measurement sensor, identifying in-plane deformation remains a significant challenge. To address this issue, this paper presents a novel method for reconstructing in-plane deformation of observed tissue surfaces using a fringe projection sensor specifically designed for measuring tissue deformations. The method employs the latest techniques from computer vision, such as differentiable rendering, to formulate the in-plane reconstruction as a differentiable optimization problem. This enables the use of gradient-based solvers for an efficient and effective optimization of the problem optimum. Depth information and image information are combined using landmark correspondences between the respective image observations of the undeformed and deformed scenes. By comparing the reconstructed pre- and post-deformation geometry, the in-plane deformation can be revealed through the analysis of relative variations between the corresponding models' geometries. The proposed reconstruction pipeline is validated on an experimental setup, and the potential for intraoperative applications is discussed.

Cystoscopic depth estimation using gated adversarial domain adaptation.

Monocular depth estimation from camera images is very important for surrounding scene evaluation in many technical fields from automotive to medicine. However, traditional triangulation methods using stereo cameras or multiple views with the assumption of a rigid environment are not applicable for endoscopic domains. Particularly in cystoscopies it is not possible to produce ground truth depth information to directly train machine learning algorithms for using a monocular image directly for depth prediction. This work considers first creating a synthetic cystoscopic environment for initial encoding of depth information from synthetically rendered images. Next, the task of predicting pixel-wise depth values for real images is constrained to a domain adaption between the synthetic and real image domains. This adaptation is done through added gated residual blocks in order to simplify the network task and maintain training stability during adversarial training. Training is done on an internally collected cystoscopy dataset from human patients. The results after training demonstrate the ability to predict reasonable depth estimations from actual cystoscopic videos and added stability from using gated residual blocks is shown to prevent mode collapse during adversarial training.

Robotic radical cystectomy - more precision needed?

PURPOSE OF REVIEW: Recently, several trials as well as registry-data analyses investigating the role of robot-assisted radical cystectomy with extra or intracorporal urinary diversion were completed and follow up matured. This review aims to comment on the current evidence-based findings and interpret the future role of the robotic approach as a part of the treatment of bladder cancer. RECENT FINDINGS: Numerous trials and registry-data analyses revealed no significant differences in progression-free and overall survival after open radical cystectomy or robot-assisted radical cystectomy irrespective of urinary diversion. Perioperative parameters, especially intraoperative blood loss, transfusions, thromboembolic events, wound infections and hospitalization were significantly increased in open radical cystectomy. Patients' convalescence, and especially early postsurgical quality of life, was improved by the robotic approach. The highly demanding surgery itself displayed by a flat learning curve required more than 130 surgeries per institution to reach a stable plateau of complications. The performance of high-quality radical cystectomy irrespective of the approach was significantly increased in high-volume centres. Local recurrence occurs in 11% after radical cystectomy. Current research focuses on intraoperatively usable detection methods and instruments to minimize the risk of residual tumour cells. SUMMARY: Taken together, the total intracorporal approach in radical cystectomy holds the potential to improve perioperative parameters and reduces hospitalization without impairing oncological performance of the procedure. To provide best results for the patient radical cystectomy and especially the technically challenging total intracorporal procedure will gain importance in bladder cancer treatment but should be limited to high-volume centres.

Enhancing Tissue Impedance Measurements Through Modeling of Fluid Flow During Viscoelastic Relaxation.

OBJECTIVE: Bladder cancer recurrence is an important issue after endoscopic urological surgeries. Additional sensor information such as electrical impedance measurements aim to support surgeons to ensure that the entirety of the tumor is removed. The foundation for differentiating lies in the altered sodium contents and cell structures within tumors that change their conductivity and permittivity. Mechanical deformations in the tissue expel fluid from the compressed area and pose a great difficulty, as they also lead to impedance changes. It is crucial to determine if this effect outweighs the alterations due to the tumorous tissue properties. METHODS: Impedance measurements under ongoing viscoelastic relaxation are taken on healthy and tumorous tissue samples from human bladders and breasts. A fluid model to account for extra- and intracellular fluid flow under compression is derived. It is based on the fluid content within the individual tissue compartments and their outflow via diffusion. RESULTS: After an initial deformation, the tissue relaxes and the impedance increases. The proposed model accurately represents these effects and validates the link between fluid flow under mechanical deformation and its impact on tissue impedance. A method to compensate for these undesired effects of fluid flow is proposed and the measurements are assessed in terms of differentiability between tumorous and healthy tissue samples. CONCLUSION: The electrical parameters are found to be promising for differentiation even under varying mechanical deformation, and the distinction is additionally improved by the proposed compensation approach. SIGNIFICANCE: Electrical impedance measurements show great potential to support urologist during endoscopic surgeries.

Detection Limits of Tetrapolar Impedance Sensors for Tissue Differentiation.

Cancer recurrence is an important issue in bladder tumor resections, because tissue cannot generously be removed from the thin bladder wall without impacting its functionality. Electrical impedance measurements during an operation aim to support the surgeon in making the decision which tissue areas to preserve, because physiological changes in tissue due to cancerous mutations can be detected by their altered electrical characteristics. This work investigates the detection limits of tetrapolar sensors when the impedance of heterogeneous tissue is measured. To do this, a finite element analysis is carried out where the sensors are placed on a dielectric medium with inclusions of different sizes, conductivity, and locations relative to the sensor. It is shown that a sensor with four electrodes in a square performs poorly in comparison to a sensor where the electrodes are symmetrically shaped as rings around one center electrode. This is mainly due to its enlarged regions of negative sensitivity. Based on the results, a third, optimized sensor geometry is proposed that shows superior performance to the other sensors in terms of geometry factor, sensitivities, and tumor detection. In simulation, it can reliably detect tumors with only half the radius of the sensor surface. Smaller tumor fractions cannot be detected by either sensor.

Geometric Mapping Evaluation for Real-Time Local Sensor Simulation.

Medical augmented reality and simulated test environments struggle in accurately simulating local sensor measurements across large spatial domains while maintaining the proper resolution of information required and real time capability. Here, a simple method for real-time simulation of intraoperative sensors is presented to aid with medical sensor development and professional training. During a surgical intervention, the interaction between medical sensor systems and tissue leads to mechanical deformation of the tissue. Through the inclusion of detailed finite element simulations in a real-time augmented reality system the method presented will allow for more accurate simulation of intraoperative sensor measurements that are independent of the mechanical state of the tissue. This concept uses a coarse, macro-level deformation mesh to maintain both computational speed and the illusion of reality and a simple geometric point mapping method to include detailed fine mesh information. The resulting system allows for flexible simulation of different types of localized sensor measurement techniques. Preliminary simulation results are provided using a real-time capable simulation environment and prove the feasibility of the method.

2D to 3D Segmentation: Inclusion of Prior Information using Random Walk Kalman Filters.

Augmented reality is a quickly advancing field that has the potential to provide surgeons with computer generated diagnostic results during surgery. Visual classification of diseased tissue generated during a diagnostic procedure, for example, trans-urethral cystoscopy of the urinary bladder, can aid a surgeon during the following resection to ensure no tissue is inadvertently missed. Work with 2D segmentation of camera images is well developed and frameworks already exist to fuse this data real-time in a 3D reconstruction. These existing frame-works, however, maintain only the most recent segmentation information when building the 3D reconstruction. This work proposes a method to build a 3D point cloud classification using random walk Kalman filters. The method enables retention of prior classification information and additionally provides a framework to include additional sensor classifications contributing to a single, final 3D segmentation result. The method is demonstrated using a simulated environment intended to emulate the inside of a human bladder.

Multi-Physical Tissue Modeling of a Human Urinary Bladder.

A multi-physical model of a human urinary bladder is an essential element for the potential application of electrical impedance spectroscopy during transurethral resection surgery, where measurements are taken at different fill levels inside the bladder. This work derives a multi-physical bladder tissue model that incorporates the electrical impedance properties with dependence on mechanical deformation due to filling of the bladder. The volume and ratio of the intracellular to extracellular tissue fluid heavily influence the electrical impedance characteristics and thus provide the connection between the mechanical and electrical domains. Modeling the fluid within the tissue links both the physical and histological processes and enables useful inferences of the properties from empiric observations. This is demonstrated by taking impedance measurements at different fill volumes. The resulting model provides a tool to analyze impedance measurements during surgery at different stress levels. In addition, this model can be used to determine patient-specific tissue parameters.

Geometry Factor Determination for Tetrapolar Impedance Sensor Probes.

Even after successful tumor resection, cancer recurrence remains an important issue for bladder tumors. Intra-operative tissue differentiation can help for diagnostic purposes as well as for ensuring that all cancerous cells are completely removed, therefore, decreasing the risk of recurrence. It has been shown that the electrical properties of tumors differ from healthy tissue due to an altered physiology. This work investigates three sensor configurations to measure the impedance of tissue. Each relies on a four terminal measurement and has a distinct electrode arrangement either inline or as a square. Analytical expressions to calculate the geometry factor of each sensor based on Laplace's equation are derived. The results are verified experimentally and in a finite element simulation. Furthermore, several measurements on pig bladders, both fresh and from frozen storage, are carried out with each sensor.It is shown that the calculated and simulated geometry factors yield the same results and are suitable and uncomplicated methods to determine the geometry factor without an experimental setup. These methods also allow for sensor optimization by knowing the measured potentials before the actual fabrication of the sensor. Moreover, conductivity values close to listed data are obtained for pig bladders, which validates the sensors. Ultimately, the square electrode configuration turns out to be a valid option for minimally invasive sensors, which are necessary for the envisaged application of transurethral bladder cancer diagnostics and surgery. This arrangement both assures reliable data and allows for easier miniaturization than the inline electrode placement.

Improvement of Acetaldehyde Production in Zymomonas mobilis by Engineering of Its Aerobic Metabolism.

Acetaldehyde is a valuable product of microbial biosynthesis, which can be used by the chemical industry as the entry point for production of various commodity chemicals. In ethanologenic microorganisms, like yeast or the bacterium Zymomonas mobilis, this compound is the immediate metabolic precursor of ethanol. In aerobic cultures of Z. mobilis, it accumulates as a volatile, inhibitory byproduct, due to the withdrawal of reducing equivalents from the alcohol dehydrogenase reaction by respiration. The active respiratory chain of Z. mobilis with its low energy-coupling efficiency is well-suited for regeneration of NAD+ under conditions when acetaldehyde, but not ethanol, is the desired catabolic product. In the present work, we sought to improve the capacity Z. mobilis to synthesize acetaldehyde, based on predictions of a stoichiometric model of its central metabolism developed herein. According to the model analysis, the main objectives in the course of engineering acetaldehyde producer strains were determined to be: (i) reducing ethanol synthesis via reducing the activity of alcohol dehydrogenase (ADH), and (ii) enhancing the respiratory capacity, either by overexpression of the respiratory NADH dehydrogenase (NDH), or by mutation of other components of respiratory metabolism. Several mutants with elevated respiration rate, decreased alcohol dehydrogenase activity, or a combination of both, were obtained. They were extensively characterized by determining their growth rates, product yields, oxygen consumption rates, ADH, and NDH activities, transcription levels of key catabolic genes, as well as concentrations of central metabolites under aerobic culture conditions. Two mutant strains were selected, with acetaldehyde yield close to 70% of the theoretical maximum value, almost twice the previously published yield for Z. mobilis. These strains can serve as a basis for further development of industrial acetaldehyde producers.

Cooperative and distinct functions of MK2 and MK3 in the regulation of the macrophage transcriptional response to lipopolysaccharide.

The p38MAPK downstream targets MAPKAP kinases (MK) 2 and 3 are critical for the regulation of the macrophage response to LPS. The extents to which these two kinases act cooperatively and distinctly in regulating LPS-induced inflammatory cytokine expression are still unclear. To address this uncertainty, whole transcriptome analyses were performed using bone marrow-derived macrophages (BMDM) generated from MK2-/- or MK2/3-/- animals and their wild-type littermates. The results suggest that in BMDM, MK2 and MK3 not only cooperatively regulate the transcript expression of signaling intermediates, including IL-10, IL-19, CXCL2 and the IL-4 receptor (IL-4R)α subunit, they also exert distinct regulatory effects on the expression of specific transcripts. Based on the differential regulation of gene expression by MK2 and MK3, at least six regulatory patterns were identified. Importantly, we confirmed our previous finding, which showed that in the absence of MK2, MK3 negatively regulates IFN-ß. Moreover, this genome-wide analysis identified the regulation of Cr1A, NOD1 and Serpina3f as similar to that of IFN-ß. In the absence of MK2, MK3 also delayed the nuclear translocation of NFκB by delaying the ubiquitination and subsequent degradation of IκBß, reflecting the substantial plasticity of the response of BMDM to LPS.

A novel finite element model-based navigation system-supported workflow for breast tumor excision.

In the case of female breast cancer, a breast-conserving excision is often desirable. This surgery is based on preoperatively gathered MRI, mammography, and sonography images. These images are recorded in multiple patient positions, e. g., 2D mammography images in standing position with a compressed breast and 3D MRI images in prone position. In contrast, the surgery happens in supine or beach chair position. Due to these different perspectives and the flexible, thus challenging, breast tissue, the excision puts high demands on the physician. Therefore, this publication presents a novel eight-step excision support workflow that can be used to include information captured preoperatively through medical imaging based on a finite element (FE) model. In addition, an indoor positioning system is integrated in the workflow in order to track surgical devices and the sonography transducer during surgery. The preoperative part of the navigation system-supported workflow is outlined exemplarily based on first experimental results including 3D scans of a patient in different patient positions and her MRI images. Graphical Abstract Finite Element model based navigation system supported workflow for breast tumor excision is based on eight steps and allows inclusion of information from medical images recorded in multiple patient positions.

IL-1ß and TNFα Differentially Influence NF-κB Activity and FasL-Induced Apoptosis in Primary Murine Hepatocytes During LPS-Induced Inflammation.

Macrophage-derived cytokines largely influence the behavior of hepatocytes during an inflammatory response. We previously reported that both TNFα and IL-1ß, which are released by macrophages upon LPS stimulation, affect Fas ligand (FasL)-induced apoptotic signaling. Whereas TNFα preincubation leads to elevated levels of caspase-3 activity and cell death, pretreatment with IL-1ß induces increased caspase-3 activity but keeps cells alive. We now report that IL-1ß and TNFα differentially influence NF-κB activity resulting in a differential upregulation of target genes, which may contribute to the distinct effects on cell viability. A reduced NF-κB activation model was established to further investigate the molecular mechanisms which determine the distinct cell fate decisions after IL-1ß and TNFα stimulation. To study this aspect in a more physiological setting, we used supernatants from LPS-stimulated bone marrow-derived macrophages (BMDMs). The treatment of hepatocytes with the BMDM supernatant, which contains both IL-1ß and TNFα, sensitized to FasL-induced caspase-3 activation and cell death. However, when TNFα action was blocked by neutralizing antibodies, cell viability after stimulation with the BMDM supernatant and FasL increased as compared to single FasL stimulation. This indicates the important role of TNFα in the sensitization of apoptosis in hepatocytes. These results give first insights into the complex interplay between macrophages and hepatocytes which may influence life/death decisions of hepatocytes during an inflammatory reaction of the liver in response to a bacterial infection.

Finite Element Breast Simulation for Sonography Image Registration.

In case of female breast cancer, a breast conserving excision is often necessary. For this purpose, information from multiple medical imaging techniques have to be combined. Sonography imaging is essential for dense breast tissue and the only medical imaging technique available during surgery. During sonography of the outer breast quadrants the woman is usually in contralateral posterior oblique position, being in supine orientation while holding her ipsilateral arm over the head. Thus, these images cannot be directly registered with MRI or mammography images because these imaging technologies are performed in other patient positions with hands on the side of the body. Thus, we present a novel Finite Element approach how to enable a sonography image registration by showing the first time how to transfer the supine position with the arm straight on side into a supine position with the ipsilateral arm over the head which can be used to include information from MRI or mammography images. This approach is shown and validated with 3D scanner breast surface data as proof of concept. When comparing the simulation result with a 3D surface scan in supine orientation with the arm over the head, a mean surface distance error of 1.57 mm is achieved.

Establishing and monitoring of urethral sphincter deficiency in a large animal model.

BACKGROUND: Different methods for induction and monitoring of urethral sphincter deficiency were explored in a large animal model. METHODS: Sphincter deficiency was established in female pigs by dilatation and cauterization, and amount and frequencies of voiding were monitored and explored by pad test. Sphincteric closure pressures were recorded prior to and immediately after treatment of each animal, and on day 21 by two techniques: standard urethral pressure profilometry (s-UPP) and high-definition urethral pressure profilometry (HD-UPP). Tissue samples of the urethrae were analyzed by histochemistry (AZAN- and Sirius Red staining) and by immunohistochemistry detecting desmin and fast-myosin to depict muscular tissues. RESULTS: After 3 weeks of observation animals treated by dilatation plus electrocautery presented with sphincter deficiency: measurements by both, s-UPP and HD-UPP demonstrated the maximal closure pressure reduced to baseline levels and a diminished area under the curve. Histological analyses documented, that dilatation yielded a pitted connective tissue and cauterization lead to muscle damage. Animals treated by either dilatation only or proximal injury only recovered within 3 weeks. By pad test no significant differences between untreated and treated animals or between the differently treated groups were recorded. CONCLUSION: Significant urethral sphincter deficiency can be induced in female pigs by a combination of urethral dilatation and distal electrocautery. Sphincter deficiency can be measured by standard and high-definition urethral pressure profilometry. It was maintained over 21 days after induction and correlated with visible changes in the tissue structure of the distal urethra.

Improving the performance of interferometric imaging through the use of disturbance feedforward.

In this paper, we present a disturbance compensation technique to improve the performance of interferometric imaging for extremely large ground-based telescopes, e.g., the Large Binocular Telescope (LBT), which serves as the application example in this contribution. The most significant disturbance sources at ground-based telescopes are wind-induced mechanical vibrations in the range of 8-60 Hz. Traditionally, their optical effect is eliminated by feedback systems, such as the adaptive optics control loop combined with a fringe tracking system within the interferometric instrument. In this paper, accelerometers are used to measure the vibrations. These measurements are used to estimate the motion of the mirrors, i.e., tip, tilt and piston, with a dynamic estimator. Additional delay compensation methods are presented to cancel sensor network delays and actuator input delays, improving the estimation result even more, particularly at higher frequencies. Because various instruments benefit from the implementation of telescope vibration mitigation, the estimator is implemented as a separate, independent software on the telescope, publishing the estimated values via multicast on the telescope's ethernet. Every client capable of using and correcting the estimated disturbances can subscribe and use these values in a feedforward for its compensation device, e.g., the deformable mirror, the piston mirror of LINC-NIRVANA, or the fast path length corrector of the Large Binocular Telescope Interferometer. This easy-to-use approach eventually leveraged the presented technology for interferometric use at the LBT and now significantly improves the sky coverage, performance, and operational robustness of interferometric imaging on a regular basis.

Rapid Sampling of Escherichia coli After Changing Oxygen Conditions Reveals Transcriptional Dynamics.

Escherichia coli is able to shift between anaerobic and aerobic metabolism by adapting its gene expression, e.g., of metabolic genes, to the new environment. The dynamics of gene expression that result from environmental shifts are limited, amongst others, by the time needed for regulation and transcription elongation. In this study, we examined gene expression dynamics after an anaerobic-to-aerobic shift on a short time scale (0.5, 1, 2, 5, and 10 min) by RNA sequencing with emphasis on delay times and transcriptional elongation rates (TER). Transient expression patterns and timing of differential expression, characterized by delay and elongation, were identified as key features of the dataset. Gene ontology enrichment analysis revealed early upregulation of respiratory and iron-related gene sets. We inferred specific TERs of 89 operons with a mean TER of 42.0 nt/s and mean delay time of 22.4 s. TERs correlate with sequence features, such as codon bias, whereas delay times correlate with the involvement of regulators. The presented data illustrate that at very short times after a shift in oxygenation, extensional changes of the transcriptome, such as temporary responses, can be observed. Besides regulation, TERs contribute to the dynamics of gene expression.

Deformable mirrors for intra-cavity use in high-power thin-disk lasers.

We present deformable mirrors for the intra-cavity use in high-power thin-disk laser resonators. The refractive power of these mirrors is continuously adaptable from -0.7 m-1 to 0.3 m-1, corresponding to radii of curvature ranging between 2.86 m (convex) and 6.67 m (concave). The optimized shape of the mirror membrane enables a very low peak-to-valley deviation from a paraboloid deformation over a large area. With the optical performance of our mirrors being equal to that of standard HR mirrors, we were able to demonstrate the tuning of the beam quality of a thin-disk laser in a range of M2 = 3 to M2 = 1 during laser operation at output powers as high as 1.1 kW.