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It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we Show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progressio.
Stent graft visualization and planning tool for endovascular surgery using finite element analysis
(2014)
Purpose: A new approach to optimize stent graft selection for endovascular aortic repair is the use of finite element analysis. Once the finite element model is created and solved, a software module is needed to view the simulation results in the clinical work environment. A new tool for Interpretation of simulation results, named Medical Postprocessor, that enables comparison of different stent graft configurations and products was designed, implemented and tested. Methods Aortic endovascular stent graft ring forces and sealing states in the vessel landing zone of three different configurations were provided in a surgical planning software using the Medical Imaging Interaction Tool Kit (MITK) Software system. For data interpretation, software modules for 2D and 3D presentations were implemented. Ten surgeons evaluated the software features of the Medical Postprocessor. These surgeons performed usability tests and answered questionnaires based on their experience with the system.
Results: The Medical Postprocessor visualization system enabled vascular surgeons to determine the configuration with the highest overall fixation force in 16 ± 6 s, best proximal sealing in 56±24 s and highest proximal fixation force in 38 ± 12 s. The majority considered the multiformat data provided helpful and found the Medical Postprocessor to be an efficient decision support system for stent graft selection. The evaluation of the user interface results in an ISONORMconform user interface (113.5 points).
Conclusion: The Medical Postprocessor visualization Software tool for analyzing stent graft properties was evaluated by vascular surgeons. The results show that the software can assist the interpretation of simulation results to optimize stent graft configuration and sizing.
There are several intra-operative use cases which require the surgeon to interact with medical devices. We used the Leap Motion Controller as input device and implemented two use-cases: 2D-Interaction (e.g. advancing EPR data) and selection of a value (e.g. room illumination brightness). The gesture detection was successful and we mapped its output to several devices and systems.
Plasma polymerization is used for the modification and control of surface properties of a highly transparent, thermoplastic elastomeric silicone copolymer, GENIOMER® 80 (G80). PEG-like diglyme plasma polymer films were deposited with ether retentions varying between 20% and 70% as measured by X-ray photoelectron spectroscopy analysis which did not affect the transparency of the substrate. Films with ether retentions of greater than 70% inhibit protein binding (bovine serum albumin and fibrinogen) and cell proliferation. A short oxygen plasma pretreatment enhances the adhesion and stability of the film as shown by protein binding and cell adhesion experiments. The transparency of the material and the stability of the coating makes this material a versatile bulk material for technical (e.g., lab-on-a-chip) and biomedical (e.g., intraocular lens) applications. The G80/plasma polymer composite is stable against vigorous washing and storage over 5 months and, therefore, offers an attractive alternative to poly(dimethylsiloxane).
Intra-operative fluoroscopy-guided assistance system for transcatheter aortic valve implantation
(2014)
A new surgical assistance system has been developed to assist the correct positioning of the AVP during transapical TAVI. The developed assistance system automatically defines the target area for implanting the AVP under live 2-D fluoroscopy guidance. Moreover, this surgical assistance system works with low levels of contrast agent for the final deployment of AVP, reducing therefore long-term negative effects, such as renal failure in the elderly and high-risk patients.
Positively charged metallic oxides prevent blood coagulation whereas negatively charged metallic oxides are thrombogenic. This study was performed to examine whether this effect extends to metallic oxide nanoparticles. Oscillation shear rheometry was used to study the effect of zinc oxide and silicon dioxide nanoparticles on thrombus formation in human whole blood. Our data show that oscillation shear rheometry is a sensitive and robust technique to analyze thrombogenicity induced by nanoparticles. Blood without previous contact with nanoparticles had a clotting time (CT) of 16.7 ± 1.0 min reaching a maximal clot strength (CS) of 16 ± 14 Pa (G') after 30 min. ZnO nanoparticles (diameter 70 nm, +37 mV zeta-potential) at a concentration of 1 mg/mL prolonged CT to 20.8 ± 3.6 min and provoked a weak clot (CS 1.5 ± 1.0 Pa). However, at a lower concentration of 100 µg/mL the ZnO particles dramatically reduced CT to 6.0 ± 0.5 min and increased CS to 171 ± 63 Pa. This procoagulant effect decreased at lower concentrations reaching the detection limit at 10 ng/mL. SiO2 nanoparticles (diameter 232 nm, −28 mV zeta-potential) at high concentrations (1 mg/mL) reduced CT (2.1 ± 0.2 min) and stimulated CS (249 ± 59 Pa). Similar to ZnO particles, this procoagulant effect reached a detection limit at 10 ng/mL. Nanoparticles in high concentrations reproduce the surface charge effects on blood coagulation previously observed with large particles or solid metal oxides. However, nanoparticles with different surface charges equally well stimulate coagulation at lower concentrations. This stimulation may be an effect which is not directly related to the surface charge.
Several diseases occur due to asbestos exposure. Until today, asbestos predicted mortality and morbidity will increase because of the long latency period. Actually, the methods to investigate asbestos related disease are mostly invasive. Therefore, the aim of the present paper was to investigate, whether signals in human breath could be correlated to Asbestos related lung diseases using a multi-capillary column (MCC) connected to an ion mobility spectrometer (IMS) as non-invasive method. Here, the breath samples of 10 mL of 25 patients suffering from asbestos related diseases. This group includes patients with asbestos related pleural thickening with and without pulmonary fibrosis. Twelve healthy persons constitute the control group and the breath samples are compared with those of the BK4103 patients. In total 83 peaks are found in the IMS-Chromatogram. A discrimination was possible with p-values <0.001 for two peaks (99.9 %), <0.01 (99 %) for 5 peaks and <0.05 (95 %) for 17 peaks. The most discrimination peaks alpha pinene and 4-ethyltoluol were identified among some others with lower p-values. The corresponding Box-and-Whisker-Plots comparing both groups are presented. In addition, a decision tree including all peaks was created that shows a differentiation with alpha pinene between BK4103 (pleural plaques group) and the control group. In addition, the sensitivity was calculated to 96 %, specificity was 50 %, positive and negative predictive values were 80 % and 86 %. Ion mobility spectrometry was introduced as non-invasive method to separate both groups Asbestos related and healthy. Naturally, the findings need further confirmation on larger population groups, but encourage further investigations, too.
The number of publications in the field of breath analysis using different types of ion mobility spectrometers (IMS) has increased over the last few years. In this paper, the publications between 2010 and 2013 are reviewed with respect to different types of IMS such as differential mobility spectrometers, high-field asymmetric waveform ion mobility spectrometers and multi-capillary columns coupled to conventional IMS. The analytes detected by IMS and declared with significance to a specific medical question were considered further with respect to medical and analytical questions. In total, 42 different analytes were found to be detected using IMS on a high significance level and were compared to findings using other analytical methods with respect to the individual analyte.
Children undergoing systemic chemotherapy often suffer from severe immunosuppression usually associated to severe neutropenia (neutrophils < 0.5 x 109/l). Clinical courses during those periods range from asymptomatic to septic general conditions. Development of septic symptoms can be very fast and life-threatening. Swift detection of risk factors in those patients is therefore needed. So far no early, rapid and reliable marker or tool exists. Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column (IMS-MCC) can analyze more than 600 volatile components from exhaled air within a few minutes and hence is a potential, rapid detection-tool. As a proof of concept we measured the exhaled breath of 11 patients with neutropenia and 10 healthy controls ranging from 3 to 18 years of age at the time of measurement. Ten milliliters breath samples were taken at the outpatient clinic and analyzed with an onsite IMS-MCC (BreathDiscovery, B&S Analytik, Dortmund, Germany). Dead-space-volume was adapted to two groups (small 250 ml, large 500 ml). Interestingly 59 differing peaks were measured. Eleven were significantly different (p ≤ 0.05), three of which highly significant (p ≤ 0.01) in Mann-Whitney-Rank-Sum-testing. The corresponding analytes used in the decision tree are 2-Propanol, D-Limonene and Acetone. The analytes with the lowest rank sum identified are 2-Hexanone, Iso-Propylamine and 1-Butanol. Eventually we were able to show a three-step-decision-tree, which discerns the 21 samples except one from each group. Sensitivity was 90 % and specificity was 91 %. Naturally these findings need further confirmation within a bigger population. Our pilot-study proves that Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column is a feasible rapid diagnostic tool in the setting of a pediatric oncology out-patient clinic for patients 3 years and older. Our first results furthermore encourage additional analysis as to whether patients at risk for septic events during immunosuppression can be diagnosed in advance by rapidly assessing risk factors such as Neutropenia in exhaled breath.
Background: Conventional methods for lung cancer detection including computed tomography (CT) and bronchoscopy are expensive and invasive. Thus, there is still a need for an optimal lung cancer detection technique. Methods: The exhaled breath of 50 patients with lung cancer histologically proven by bronchoscopic biopsy samples (32 adenocarcinomas, 10 squamous cell carcinomas, 8 small cell carcinomas), were analyzed using ion mobility spectrometry (IMS) and compared with 39 healthy volunteers. As a secondary assessment, we compared adenocarcinoma patients with and without epidermal growth factor receptor (EGFR) mutation. Results: A decision tree algorithm could separate patients with lung cancer including adenocarcinoma, squamous cell carcinoma and small cell carcinoma. One hundred-fifteen separated volatile organic compound (VOC) peaks were analyzed. Peak-2 noted as n-Dodecane using the IMS database was able to separate values with a sensitivity of 70.0% and a specificity of 89.7%. Incorporating a decision tree algorithm starting with n-Dodecane, a sensitivity of 76% and specificity of 100% was achieved. Comparing VOC peaks between adenocarcinoma and healthy subjects, n-Dodecane was able to separate values with a sensitivity of 81.3% and a specificity of 89.7%. Fourteen patients positive for EGFR mutation displayed a significantly higher n-Dodecane than for the 14 patients negative for EGFR (p<0.01), with a sensitivity of 85.7% and a specificity of 78.6%. Conclusion: In this prospective study, VOC peak patterns using a decision tree algorithm were useful in the detection of lung cancer. Moreover, n-Dodecane analysis from adenocarcinoma patients might be useful to discriminate the EGFR mutation.