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Geltmeier A.,ASD Advanced Simulation and Design GmbH | Rinner B.,Medical University of Graz | Bade D.,Mechatronic AG | Meditz K.,Medical University of Graz | And 5 more authors.
PLoS ONE | Year: 2015

Treatment options specifically targeting tumour cells are urgently needed in order to reduce the side effects accompanied by chemo- or radiotherapy. Differences in subcellular structure between tumour and normal cells determine their specific elasticity. These structural differences can be utilised by low-frequency ultrasound in order to specifically induce cytotoxicity of tumour cells. For further evaluation, we combined in silico FEM (finite element method) analyses and in vitro assays to bolster the significance of low-frequency ultrasound for tumour treatment. FEM simulations were able to calculate the first resonance frequency of MCF7 breast tumour cells at 21 kHz in contrast to 34 kHz for the MCF10A normal breast cells, which was due to the higher elasticity and larger size of MCF7 cells. For experimental validation of the in silico-determined resonance frequencies, equipment for ultrasonic irradiation with distinct frequencies was constructed. Differences for both cell lines in their response to low-frequent ultrasonic treatment were corroborated in 2D and in 3D cell culture assays. Treatment with ∼ 24.5 kHz induced the death of MCF7 cells and MDA-MB-231 metastases cells possessing a similar elasticity; frequencies of > 29 kHz resulted in cytotoxicity of MCF10A. Fractionated treatments by ultrasonic irradiation of suspension myeloid HL60 cells resulted in a significant decrease of viable cells, mostly significant after threefold irradiation in intervals of 3 h. Most importantly in regard to a clinical application, combined ultrasonic treatment and chemotherapy with paclitaxel showed a significantly increased killing of MCF7 cells compared to both monotherapies. In summary, we were able to determine for the first time for different tumour cell lines a specific frequency of low-intensity ultrasound for induction of cell ablation. The cytotoxic effect of ultrasonic irradiation could be increased by either fractionated treatment or in combination with chemotherapy. Thus, our results will open new perspectives in tumour treatment. © 2015 Geltmeier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Siogkas P.K.,University of Ioannina | Sakellarios A.I.,University of Ioannina | Stefanou K.A.,Biomedical Research Institute FORTH | Tsakanikas V.D.,Biomedical Research Institute FORTH | And 5 more authors.
Proceedings of the IEEE/EMBS Region 8 International Conference on Information Technology Applications in Biomedicine, ITAB | Year: 2010

Atherosclerosis is the most prevalent cardiovascular disease which affects millions of people globally each year. The development of atheroma is directly connected to the interaction of blood flow with the arterial wall. Therefore, the modeling of this interaction is of critical importance for the study of arterial blood flow mechanics and the progression of atherosclerosis. In this study, we use a patient-specific 3-dimensional model of a stenosed Right Coronary Artery (RCA). A revascularization procedure (Percutaneous Coronary Angiography-PCA) is virtually performed to the stenosed model. The distribution of the Wall Shear Stress (WSS) as well as the wall deformation are compared on the two models after solving the coupled mechanical system using the Finite Element Method (FEM). Results concerning areas of low WSS (0-2 Pa) as well as minimum and maximum wall deformation are presented, quantifying the effect of the revascularization process of the artery. © 2010 IEEE.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.5.2 | Award Amount: 18.10M | Year: 2013

The DementiA Research Enabled by IT project responds to the European Parliaments 2011 resolution for a European Initiative on Alzheimers disease and other dementias, and the EU Year of the Brain 2014 Initiative. It delivers the first patient-specific predictive models for early differential diagnosis of dementias and their evolution. Its mechanistic/phenomenological models of the ageing brain account simultaneously for the patient-specific multiscale biochemical, metabolic and biomechanical brain substrate, as well as for genetic, clinical, demographic and lifestyle determinants. It investigates the effect of metabolic syndrome, diabetes, diets, exercise, and pulmonary conditions on the ageing brain, as environmental factors influencing onset and evolution of dementias.\n\nAn integrated clinical decision support platform will be validated/ tested by access to a dozen databases of international cross-sectional and longitudinal studies, including exclusive access to a population study that has tracked brain ageing in more than 10,000 individuals for over 20 years (Rotterdam Study).\n\nEnabling more objective, earlier, predictive and individualised diagnosis and prognosis of dementias will support health systems worldwide to cope with the burden of 36M patients that, due to ageing societies, will increase to 115M by 2050. Worldwide costs are estimated to 450B annually. In 2012, the WHO declared dementia a global health priority.\n\nOur consortium assembles highly recognised engineering, physical, biomedical and clinical scientists, and industrial partners experienced in exploiting VPH technologies in healthcare. Co-operation with infrastructure projects like VPH-Share, related international Physiome efforts, and other dementia research consortia is assured, allowing European researchers from different disciplines to contribute to share resources, methods and generate new knowledge.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.5.3 | Award Amount: 9.27M | Year: 2008

ARTreat targets at providing a patient-specific computational model of the cardiovascular system, used to improve the quality of prediction for the atherosclerosis progression and propagation into life-threatening events that need to be treated accordingly. ARTreat will provide a three-level patient model describing the 3d arterial tree anatomy, the patient-specific blood flow and blood particle dynamics and the biological processes that lead to the creation and progression of atherosclerotic plaques. ARTreat will apply the developed patient-specific model on two main applications: the clinical decision support and the training. ARTreat will produce two decision support tools to assist clinical cardiologists into providing personalized treatment selection and real-time, on- the-fly advice during invasive interventions, such stent positioning. The aim is to minimize future therapy costs, by providing higher than even possible personalized treatment support. The same patient-specific model will also be used to develop a real-case simulator training, which will support realistic hands-on skill development training to clinical cardiologists. Finally, ARTreat is coupled with advanced clinical support tools for plaque characterization, and the discovery of new knowledge; associations among heterogeneous data, that can improve the predictive power of the patient-model. It thus supports the medical expert into programming the accumulated knowledge into the existing model and generating an adaptive patient-specific computational tool. Key market players AGFA and SORIN will exploit the ARTreat applications to provide new sophisticated solutions to their product range, while all academic and ITcompany partners will accumulate significant experience on the new generation patient-specific healthcare services.

Hubner S.,Leibniz Institute for Catalysis | Kressirer S.,Friedrich - Schiller University of Jena | Kralisch D.,Friedrich - Schiller University of Jena | Bludszuweit-Philipp C.,ASD Advanced Simulation and Design GmbH | And 6 more authors.
ChemSusChem | Year: 2012

Short diffusion paths and high specific interfacial areas in microstructured devices can increase mass transfer rates and thus accelerate multiphase reactions. This effect can be intensified by the application of ultrasound. Herein, we report on the design and testing of a novel versatile setup for a continuous ultrasound-supported multiphase process in microstructured devices on a preparative scale. The ultrasonic energy is introduced indirectly into the microstructured device through pressurized water as transfer medium. First, we monitored the influence of ultrasound on the slug flow of a liquid/liquid two-phase system in a channel with a high-speed camera. To quantify the influence of ultrasound, the hydrolysis of p-nitrophenyl acetate was utilized as a model reaction. Microstructured devices with varying channel diameter, shape, and material were applied with and without ultrasonication at flow rates in the mLmin-1 range. The continuous procedures were then compared and evaluated by performing a simplified life cycle assessment. A promising combination indeed: The combination of ultrasound and microstructures can increase interfacial areas between immiscible phases and thus enhance multiphase reactions. We report on the design, testing and evaluation of a novel modular setup for a continuous ultrasound-supported liquid/liquid two-phase process in microstructured devices. Ultrasonication is effected indirectly through pressurized water as transmission medium for an improved energy input. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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