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  • 101.
    Alanko, Rosanna
    et al.
    Jönköping University, School of Health and Welfare, HHJ. Prosthetics and Orthotics.
    Oskarsson, Tina
    Jönköping University, School of Health and Welfare, HHJ. Prosthetics and Orthotics.
    Kommunikation mellan patient och ortopedingenjör: En kvalitativ studie2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    En studie har genomförts med syftet att undersöka diabetespatienters tolkning av informationen som ges av deras respektive ortopedingenjör under ett patientmöte samt undersöka vad ortopedingenjören anser sig ha förmedlat för information till patienten under patientmötet. Metoden i studien är kvalitativ där intervjuer med semistrukturerade öppna frågor har använts. I studien ingick två ortopedingenjörer samt två diabetespatienter. Efter avslutade intervjuer har materialet från intervjuerna analyserats och bildat kategorier. Dessa kategorier har sedan använts för att finna skillnader samt likheter mellan ortopedingenjörens och patientens tolkningar. Patientmötens har spelats in för att få möjligheten att se vart missförstånd uppstått. Genomgående i resultatet var att ortopedingenjören anser sig ha förmedlat mer information än vad patienten beskriver under intervjuerna. Några missförstånd upptäcktes men kommunikationen mellan parterna var god.  

  • 102.
    Albano, Amanda
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Exploratory statistical study of long-term variability in echocardiographic indices (echocardiovariability) in healthy and diseased1987Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Heart rate variability, HRV, has been well researched for some decades. The oscillations of the heart rate is studied over a time period of some minutes up to 24 hours, it is measured with electrocardiography, ECG. From this one has concluded that the heart rate signal oscillates in accordance with the respiration, the resistance in the vessels etc.

    The most frequently used examination method of the heart is done with ultrasound, called echocardiography. One interesting variable at a time is measured and it is measured for a single heartbeat. With inspiration ofthe HRV studies this project focuses on some of the variables measured with ultrasound but over time andsimultaneously. The variables of interest are the myocardial motion and the blood flow in the left part ofthe heart, they are measured over two minutes. To complement these variables the well known variables HRand Resp are measured with ECG and added to the analysis.

    The methods used for analysing the variables are first of all descriptive statistics like mean and standard deviation. Secondly spectral analysis is performed to investigate in which frequencies the variables oscillates. Through coherence this is compared with the spectrum for HR where the three peaks have known origin. Finally principal component analysis, PCA, is performed as a method to compare all variables at the same time.

    The analyses are performed on seven measurements from five (5) healthy persons and five measurementsfrom four (4) patients with the disease FAP (“Skelleftesjukan”). The variables are investigated and described for the healthy persons first, then the healthy persons and patients are compared.

    The result from the study shows that most of the echo-variables oscillate in accordance with the respirationand the heart rate. For a healthy person the oscillations are within normal values and the relative deviation isaround 10%. The patients with FAP are most affected in the variables connected to the myocardium apartfrom HR, which is known since before.

    The coherence between the echo-variables and HR is low in one of VLF, very low frequency, or LF, lowfrequency, region and high in the other. In HF, high frequency, region the coherence is high for all variables.

    Finally the PCA was conducted on measurements from all healthy persons as one data set, from one ofthe healthy persons and from one of the patients with FAP. The analysis showed that for healthy personsrespiration is the process causing most variation and all of the echo-variables have a correlation to therespiration. For a patient with FAP the respiration is not as salient. A PCA over blocks of data at different time points however show that the signals are not oscillating in the same way multivariately over the wholetime series.

  • 103.
    Albinsson, John
    et al.
    Lund Univ, Dept Biomed Engn, S-22100 Lund, Sweden..
    Brorsson, Sofia
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS).
    Rydén Ahlgren, Åsa
    Lund Univ, Dept Clin Sci, Clin Physiol & Nucl Med Unit, Malmo, Sweden..
    Cinthio, Magnus
    Lund Univ, Dept Biomed Engn, S-22100 Lund, Sweden..
    Improved tracking performance of lagrangian block-matching methodologies using block expansion in the time domain: In silico, phantom and invivo evaluations2014In: Ultrasound in Medicine and Biology, ISSN 0301-5629, E-ISSN 1879-291X, Vol. 40, no 10, p. 2508-2520Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate tracking performance when an extra reference block is added to a basic block-matching method, where the two reference blocks originate from two consecutive ultrasound frames. The use of an extra reference block was evaluated for two putative benefits: (i) an increase in tracking performance while maintaining the size of the reference blocks, evaluated using in silico and phantom cine loops; (ii) a reduction in the size of the reference blocks while maintaining the tracking performance, evaluated using in vivo cine loops of the common carotid artery where the longitudinal movement of the wall was estimated. The results indicated that tracking accuracy improved (mean - 48%, p<0.005 [in silico]; mean - 43%, p<0.01 [phantom]), and there was a reduction in size of the reference blocks while maintaining tracking performance (mean - 19%, p<0.01 [in vivo]). This novel method will facilitate further exploration of the longitudinal movement of the arterial wall. (C) 2014 World Federation for Ultrasound in Medicine & Biology.

  • 104.
    Alexanderson, H.
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Neurobiol Care Sci & Soc, KI Physiotherapy Clin, Stockholm, Sweden..
    Björklund, Annika
    Mälardalen University, School of Innovation, Design and Engineering, Embedded Systems. Hälsopoolen Rehabil Clin, Stockholm, Sweden..
    Ottosson, C.
    Karolinska Univ Hosp, Rheumatol Clin, Stockholm, Sweden..
    Dastmalchi, M.
    Karolinska Inst, Rheumatol Unit, Stockholm, Sweden..
    Lundberg, I. E.
    Karolinska Inst, Rheumatol Unit, Stockholm, Sweden..
    FATIGUE IN ADULT IDIOPATHIC INFLAMMATORY MYOPATHIES2015In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 74, p. 106-106Article in journal (Other academic)
  • 105.
    Allalou, Amin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Methods for 2D and 3D Quantitative Microscopy of Biological Samples2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    New microscopy techniques are continuously developed, resulting in more rapid acquisition of large amounts of data. Manual analysis of such data is extremely time-consuming and many features are difficult to quantify without the aid of a computer. But with automated image analysis biologists can extract quantitative measurements and increases throughput significantly, which becomes particularly important in high-throughput screening (HTS). This thesis addresses automation of traditional analysis of cell data as well as automation of both image capture and analysis in zebrafish high-throughput screening. 

    It is common in microscopy images to stain the nuclei in the cells, and to label the DNA and proteins in different ways. Padlock-probing and proximity ligation are highly specific detection methods that  produce point-like signals within the cells. Accurate signal detection and segmentation is often a key step in analysis of these types of images. Cells in a sample will always show some degree of variation in DNA and protein expression and to quantify these variations each cell has to be analyzed individually. This thesis presents development and evaluation of single cell analysis on a range of different types of image data. In addition, we present a novel method for signal detection in three dimensions. 

    HTS systems often use a combination of microscopy and image analysis to analyze cell-based samples. However, many diseases and biological pathways can be better studied in whole animals, particularly those that involve organ systems and multi-cellular interactions. The zebrafish is a widely-used vertebrate model of human organ function and development. Our collaborators have developed a high-throughput platform for cellular-resolution in vivo chemical and genetic screens on zebrafish larvae. This thesis presents improvements to the system, including accurate positioning of the fish which incorporates methods for detecting regions of interest, making the system fully automatic. Furthermore, the thesis describes a novel high-throughput tomography system for screening live zebrafish in both fluorescence and bright field microscopy. This 3D imaging approach combined with automatic quantification of morphological changes enables previously intractable high-throughput screening of vertebrate model organisms.

  • 106.
    Allalou, Amin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Curic, Vladimir
    Pardo-Martin, Carlos
    Massachusetts Institute of Technology, USA.
    Yanik, Mehmet Fatih
    Massachusetts Institute of Technology, USA.
    Wählby, Carolina
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Approaches for increasing throughput andinformation content of image-based zebrafishscreens2011In: Proceeding of SSBA 2011, 2011Conference paper (Other academic)
    Abstract [en]

    Microscopy in combination with image analysis has emerged as one of the most powerful and informativeways to analyze cell-based high-throughput screening (HTS) samples in experiments designed to uncover novel drugs and drug targets. However, many diseases and biological pathways can be better studied in whole animals, particularly diseases and pathways that involve organ systems and multicellular interactions, such as organ development, neuronal degeneration and regeneration, cancer metastasis, infectious disease progression and pathogenesis. The zebrafish is a wide-spread and popular vertebrate model of human organfunction and development, and it is unique in the sense that large-scale in vivo genetic and chemical studies are feasible due in part to its small size, optical transparency,and aquatic habitat. To improve the throughput and complexity of zebrafish screens, a high-throughput platform for cellular-resolution in vivo chemical and genetic screens on zebrafish larvae has been developed at Yanik lab at Research Laboratory of Electronics, MIT, USA. The system loads live zebrafish from reservoirs or multiwell plates, positions and rotates them for high-speed confocal imaging of organs,and dispenses the animals without damage. We present two improvements to the described system, including automation of positioning of the animals and a novel approach for brightfield microscopy tomographic imaging of living animals.

  • 107.
    Allalou, Amin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Wu, Yuelong
    Ghannad-Rezaie, Mostafa
    Eimon, Peter M.
    Yanik, Mehmet Fatih
    Automated deep-phenotyping of the vertebrate brain2017In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e23379Article in journal (Refereed)
  • 108.
    Almeida, Eduardo Carlos Venancio de
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Development of a wearable sensor system for real-time control of knee prostheses2012Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    It was demonstrated in recent studies that Complementary Limb Motion Estimation (CLME) is robust approach for controlling active knee prostheses. A wearable sensor system is then needed to provide inputs to the controller in a real-time platform. In the present work, a wearable sensor system based on magnetic and inertial measurement units (MIMU) together with a simple calibration procedure were proposed. This sensor system was intended to substitute and extend the capabilities of a previous device based on potentiometers and gyroscopes. The proposed sensor system and calibration were validated with an Optical Tracking System (OTS) in a standard gait lab and first results showed that the proposed solution had a performance comparable to similar studies in the literature.

  • 109.
    Almeida, Nuno
    et al.
    Katholieke University of Leuven, Belgium; GE Vingmed Ultrasound AS, Norway.
    Papachristidis, Alexandros
    Kings Coll Hospital London, England.
    Pearson, Peter
    Kings Coll Hospital London, England.
    Imre Sarvari, Sebastian
    University of Oslo, Norway.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Edvardsen, Thor
    University of Oslo, Norway.
    Monaghan, Mark
    Kings Coll Hospital London, England.
    Gerard, Olivier
    GE Vingmed Ultrasound AS, Norway.
    Samset, Eigil
    GE Vingmed Ultrasound AS, Norway; University of Oslo, Norway.
    Dhooge, Jan
    Katholieke University of Leuven, Belgium.
    Left atrial volumetric assessment using a novel automated framework for 3D echocardiography: a multi-centre analysis2017In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 18, no 9, p. 1008-1015Article in journal (Refereed)
    Abstract [en]

    Aims This study aims at validating a software tool for automated segmentation and quantification of the left atrium (LA) from 3D echocardiography. Methods and results The LA segmentation tool uses a dual-chamber model of the left side of the heart to automatically detect and track the atrio-ventricular plane and the LA endocardium in transthoracic 3D echocardiography. The tool was tested in a dataset of 121 ultrasound images from patients with several cardiovascular pathologies (in a multi-centre setting), and the resulting volumes were compared with those assessed manually by experts in a blinded analysis using conventional contouring. Bland-Altman analysis showed good agreement between the automated method and the manual references, with differences (mean +/- 1.96 SD) of 0.5 +/- 5.7 mL for LA minimum volume and -1.6 +/- 9.7 mL for LA maximum volume (comparable to the inter-observer variability of manual tracings). The automated tool required no user interaction in 93% of the recordings, while 4% required a single click and only 2% required contour adjustments, reducing considerably the amount of time and effort required for LA volumetric analysis. Conclusion The automated tool was validated in a multi-centre setting, providing quantification of the LA volume over the cardiac cycle with minimal user interaction. The results of the automated analysis were in agreement with those estimated manually by experts. This study shows that such approach has clinical utility for the assessment of the LA morphology and function, automating and facilitating the time-consuming task of analysing 3D echocardiographic recordings.

  • 110.
    Almquist, Camilla
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Implementation of an automated,personalized model of the cardiovascularsystem using 4D Flow MRI2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A personalized cardiovascular lumped parameter model of the left-sided heart and thesystemic circulation has been developed by the cardiovascular medicine research groupat Linköping University. It provides information about hemodynamics, some of whichcould otherwise only have been retrieved by invasive measurements. The framework forpersonalizing the model is made using 4D Flow MRI data, containing volumes describinganatomy and velocities in three directions. Thus far, the inputs to this model have beengenerated manually for each subject. This is a slow and tedious process, unpractical touse clinically, and unfeasible for many subjects.This project aims to develop a tool to calculate the inputs and run the model for mul-tiple subjects in an automatic way. It has its basis in 4D Flow MRI data sets segmentedto identify the locations of left atrium (LA), left ventricle (LV), and aorta, along with thecorresponding structures on the right side.The process of making this tool started by calculation of the inputs. Planes were placedin the relevant positions, at the mitral valve, aortic valve (AV) and in the ascending aortaupstream the brachiocephalic branches, and flow rates were calculated through them. TheAV plane was used to calculate effective orifice area of AV and aortic cross-sectional area,while the LV end systolic and end diastolic volumes were extracted form the segmentation.The tool was evaluated by comparison with manually created inputs and outputs,using 9 healthy volunteers and one patient deemed to have normal left ventricular func-tion. The patient was chosen from a subject group diagnosed with chronic ischemic heartdisease, and/or a history of angina, together with fulfillment of the high risk score ofcardiovascular diseases of the European Society of Cardiology. This data was evaluatedusing coefficient of variation, Bland-Altman plots and sum squared error. The tool wasalso evaluated visually on some subjects with pathologies of interest.This project shows that it is possible to calculate inputs fully automatically fromsegmented 4D Flow MRI and run the cardiovascular avatar in an automatic way, withoutuser interaction. The method developed seems to be in good to moderate agreement withthose obtained manually, and could be the basis for further development of the model.

  • 111.
    Almqvist, Ulf
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Sjörs, Anna
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Validation of MobileMe: a psychophysiological recording system – from a motion sickness perspective2006Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    MobileMe is a recently developed system for monitoring and recording physiological variables. It is wireless, and can therefore be suitable for field research, for example when measuring motion sickness symptoms.

    The aim of this thesis was to conclude whether the MobileMe recording system was valid for research studies. A validation study, consisting of two parts and including 10 subjects, was performed. The first part was a laboratory study, where data from MobileMe and a reference equipment were compared. A field study was also performed, onboard a combat boat, to determine the equipment’s validity in uncontrolled environments. Furthermore, the field study included an investigation of motion sickness symptoms, and provided data for evaluation of motion sickness rating scales.

    Statistical results from the laboratory study, and results from evaluation of data from the field study, showed that MobileMe was valid in both controlled and uncontrolled environments.

  • 112.
    Almulla, Youssef
    et al.
    KTH, School of Industrial Engineering and Management (ITM), Energy Technology, Energy Systems Analysis.
    Ramos, Eunice
    KTH, School of Industrial Engineering and Management (ITM), Energy Technology.
    Gardumi, Francesco
    KTH, School of Industrial Engineering and Management (ITM), Energy Technology, Energy Systems Analysis.
    Taliotis, Constantinos
    KTH, School of Industrial Engineering and Management (ITM), Energy Technology, Energy Systems Analysis.
    Lipponen, A.
    Howells, Mark I.
    KTH, School of Industrial Engineering and Management (ITM), Energy Technology, Energy Systems Analysis.
    The role of energy-water nexus to motivate transboundary cooperation: An indicative analysis of the Drina river basin2018In: International Journal of Sustainable Energy Planning and Management, ISSN 2246-2929, E-ISSN 2246-2929, Vol. 18, p. 3-28Article in journal (Refereed)
    Abstract [en]

    Low-carbon hydropower is a key energy source for achieving Sustainable Development Goal 7-sustainable energy for all. Meanwhile, the effects of hydropower development and its operation are complex-and potentially a source of tension on Transboundary Rivers. This paper explores solutions that consider both energy and water to motivate transboundary cooperation in the operation of hydropower plants (HPPs) in the Drina River Basin (DRB) in South-East Europe. Here the level of cooperation among the riparian countries is low. The Open Source energy Modeling System-OSeMOSYS was used to develop a multi-country model with a simplified hydrological system to represent the cascade of HPPs in the DRB; together with other electricity options, including among others: energy efficiency. Results show that improved cooperation can increase electricity generation in the HPPs downstream without compromising generation upstream. It also demonstrates the role of inexpensive hydropower to enhance electricity trade in the region. Implementing energy efficiency measures would reduce the generation from coal power plants, thereby mitigating CO 2 emissions by as much as 21% in 2030 compared to the 2015 levels. In summary, judicious HPP operation and electricity system development will help the Western Balkans reap significant gains.

  • 113.
    Alonso, Fabiola
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Deep brain stimulation: Patient-specific modelling, simulation and visualization of  DBS electric field2019Conference paper (Other (popular science, discussion, etc.))
  • 114.
    Alonso, Fabiola
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Modeling and simulation of DBS – comparison between leads and stimulation modes2014Conference paper (Other academic)
  • 115.
    Alonso, Fabiola
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Models and Simulations of the Electric Field in Deep Brain Stimulation: Comparison of Lead Designs, Operating Modes and Tissue Conductivity2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Deep brain stimulation (DBS) is an established surgical therapy for movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). A thin electrode is implanted in a predefined area of the brain with the use of stereotactic neurosurgery. In the last few years new DBS electrodes and systems have been developed with possibilities for using more parameters for control of the stimulation volume.

    In this thesis, simulations using the finite element method (FEM) have been developed and used for investigation of the electric field (EF) extension around different types of DBS lead designs (symmetric, steering) and stimulation modes (voltage, current). The electrode surrounding was represented either with a homogeneous model or a patient-specific model based on individual preoperative magnetic resonance imaging (MRI). The EF was visualized and compared for different lead designs and operating modes.

    In Paper I, the EF was quantitatively investigated around two lead designs (3389 and 6148) simulated to operate in voltage and current mode under acute and chronic time points following implantation.Simulations showed a major impact on the EF extension between postoperative time points which may explain the clinical decisions to change the stimulation amplitude weeks after implantation. In Paper II, the simulations were expanded to include two leads having steering function (6180, Surestim1) and patient-specific FEM simulations in the zona incerta. It was found that both the heterogeneity of the tissue and the operating mode, influence the EF distribution and that equivalent contact configurations of the leads result in similar EF. The steering mode presented larger volumes in current mode when using equivalent amplitudes. Simulations comparing DBS and intraoperative stimulation test using a microelectrode recording (MER) system (Paper III), showed that several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution and that the DBS EF volume can cover, but also extend to, other anatomical areas.

    Paper IV introduces a method for an objective exploitation of intraoperative stimulation test data in order to identify the optimal implant position in the thalamus of the chronic DBS lead. Patient-specific EF simulations were related to the anatomy with the help of brain atlases and the clinical effects which were quantified by accelerometers. The first results indicate that the good clinical effect in ET is due to several structures around the ventral intermediate nucleus of the thalamus.

  • 116.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Latorre, Malcolm
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Göransson, Nathanael
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Zsigmond, Peter
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wårdell, karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study2016In: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 6, no 3, p. 1-16Article in journal (Refereed)
    Abstract [en]

    New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.

  • 117.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering.
    Latorre, Malcolm
    Linköping University, Department of Biomedical Engineering.
    Zsigmond, Peter
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering.
    Brain Stimulation Steering of the Electric Field: A Patient-Specific Simulation Study2016Conference paper (Refereed)
  • 118.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Vogel, Dorian
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. University of Applied Sciences and Arts Northwestern Switzerland FHNW, 4132 Muttenz, Switzerland.
    Johansson, Johannes
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Hemm, Simone
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. rthwestern Switzerland FHNW, 4132 Muttenz, Switzerland.
    Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems: A Simulation Study2018In: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 8, no 2Article in journal (Refereed)
    Abstract [en]

    The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome

  • 119.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Vogel, Dorian
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Hemm-Ode, Simone
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Institute for Medical and Analytical Technologies and Department of Biomedical Engineering, University of Applied Sciences and Art Northwestern Switzerland.
    Comparison between intraoperative and chronic and deep brain stimulation2017Conference paper (Refereed)
    Abstract [en]

    INTRODUCTION

    The success of the deep brain stimulation (DBS) therapy relies primarily in the localization of the implanted electrode, implying the need of utmost accuracy in the targeting process. Intraoperative microelectrode recording and stimulation tests are a common procedure before implanting the permanent DBS lead to determine the optimal position with a large therapeutic window where side effects are avoided and the best improvement of the symptoms is achieved. Differences in dimensions and operating modes exist between the exploration and the permanent DBS electrode which might lead to different stimulation fields, even when ideal placement is achieved. The aim of this investigation is to compare the electric field (EF) distribution around the intraoperative and the chronic electrode, assuming that both have exactly the same position.

    METHODS

    3D models of the intraoperative exploration electrode and the chronically implanted DBS lead 3389 (Medtronic Inc., USA) were developed using COMSOL 5.2 (COMSOL AB, Sweden). Patient-specific MR images were used to determine the conductive medium around the electrode. The exploration electrode and the first DBS contact were set to current and voltage respectively (0.2mA(V) - 3 mA(V) in 0.1 mA(V) steps). The intraoperative model included the grounded guide tube used to introduce the exploration electrode; for the chronic DBS model, the outer boundaries were grounded and the inactive contacts were set to floating potential considering a monopolar configuration. The localization of the exploration and the chronic electrode was set according to the planned trajectory. The EF was visualized and compared in terms of volume and extension using a fixed isocontour of 0.2 V/mm.

    RESULTS

    The EF distribution simulated for the exploration electrode showed the influence of the parallel trajectory and the grounded guide tube. For an amplitude of e.g. 2 mA/2 V, the EF extension of the intraoperative was 0.6 mm larger than the chronic electrode at the target level; the corresponding difference in volume was 76.1 mm3.

    CONCLUSION

    Differences in the EF shape between the exploration and the chronic DBS electrode have been observed using patient-specific models. The larger EF extension obtained for the exploration electrode responds to its higher impedance and the use of current controlled stimulation. The presence of EF around the guide tube and the influence of the parallel trajectory require further experimental and clinical evaluation.

  • 120.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Comparison of deep brain stimulation systems2014In: Poster Presentations, 2014, Vol. 29, p. 1173-1173, article id Suppl 1Conference paper (Other academic)
    Abstract [en]

    Objective: To quantitatively compare the electric field generated by voltage and current controlled deep brain stimulation systems.

    Background: Traditionally deep brain stimulation (DBS) systems have used voltage control however more recently, current controlled systems have been approved to treat Parkinson's disease and related movement disorders. In the endeavor of understanding the behavior of DBS systems a common approach is the use of computer models suitable to simulate the electric field, current density and other related electric parameters.

    Methods: 2D finite element models based on commercially available DBS systems have been built for each system: I. Model 3389, Medtronic Inc., USA for voltage control; and II. Model 6142, St Jude Medical Inc. USA for current control. The brain tissue has been simplified to homogeneous and isotropic medium. The electric settings correspond to a monopolar configuration, using one of the four contacts available as the active electrode and the outer boundary of the tissue as the reference. Three simulations were performed to mimic different stages of the leads implantation: a) an original stage where the brain tissue is considered as pure gray matter, b) an acute stage that simulates the leakage of cerebral spinal fluid immediately after the electrodes' insertion; and c) a chronic stage mimicking fibrous tissue created around the electrodes some weeks after implantation. Both systems were submitted to the same conditions using as active electrode the third contact from the tip of the lead. The comparison is based on the maximal distance reached by the isopotential of 0.2 V/mm.

    Results: The simulations showed that voltage controlled stimulation systems are more susceptible to changes in the electrical conductivity of the medium i.e. change over time of the tissue around the electrode. This agrees with the adjustment of the stimulation amplitude often necessary a few weeks postoperatively. Current controlled stimulation in turn, presented a linear behavior of the distance reached at different stimulation amplitudes at all stages.

    Conclusions: Current controlled stimulation might be a good option due to its linear behavior over time, nevertheless more studies including a more realistic brain model, different designs of DBS electrodes and different electric parameter, are needed to encourage the use of this type of systems.

  • 121.
    Alonso, Fabiola
    et al.
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Electric Field Comparison of Deep Brain Stimulation Lead Designs - a Stimulation Study2016Conference paper (Refereed)
  • 122.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Latorre, Malcolm
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Comparison of Three Deep Brain Stimulation Lead Designs under Voltage and Current Modes2015In: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2 / [ed] David A. Jaffray, Springer, 2015, Vol. 51, p. 1196-1199Conference paper (Refereed)
    Abstract [en]

    Since the introduction of deep brain stimulation (DBS) the technique has been dominated by Medtronic sys-tems. In recent years, new DBS systems have become available for patients, and some are in clinical trials. The present study aims to evaluate three DBS leads operated in either voltage or current mode. 3D finite element method (FEM) models were built in combination with a neuron model for this purpose. The axon diameter was set to D = 5 μm and simulations performed in both voltage (0.5-5 V) and current (0.5-5 mA) mode. The evaluation was achieved based on the distance from the lead for neural activation and the electric field (EF) extension at 0.1 V/mm. The results showed that the neural activation distance agrees well between the leads with an activation distance dif-ference less than 0.5 mm. The shape of the field at the 0.1 V/mm isopotential surface in 3D is mostly spherical in shape around the activated section of the steering lead.

  • 123.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Latorre, Malcolm
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Neural Activation Compared to Electric Field Extension of Three DBS Lead Designs2015Conference paper (Refereed)
    Abstract [en]

    SINCE the introduction of deep brain stimulation (DBS) about 20 years ago, the stimulation technique has been dominated by Medtronic DBS-system setup. In recent years, new DBS systems have become available, of which some are in clinical trials or available to patients [1]. In the present study three different lead designs are investigated via computer simulation:

    Medtronic 3389, St. Jude 6148 and Sapiens SureStim. The aim was to compare the neural activation distance and the electric field (EF) maximum spatial extension for each lead.

    A 3D finite element method model was built using COMSOL Multiphysics 4.4a (COMSOL AB, Stockholm, Sweden) to simulate the electric potential around the DBS lead. Brain tissue was modelled as a homogeneous volume of grey matter (electric conductivity of 0.09 S/m). The electrode-tissue interface was modelled with a 250μm thick peri-electrode space mimicking the fibrous tissue which covers the lead at the chronic stimulation stage (σ = 0.06S/m, equivalent to white matter electric conductivity). The stimulation amplitude was set to 1V in monopolar configuration using C1 electrode or equivalent in all cases. Each simulated electric potential distribution was exported to MatLab (The MathWorks, USA) and used as input to a cable neuron simulation.

    An axon cable model with 21 nodes based on the concept by Åström et al., [2] was set up in MatLab and combined with the exported field distributions. The model considered a 5 μm thick neuron, a pulse width of 60 μs and a drive potential ranging from 0.5 V to 5 V in 0.5 V steps.

    The SureStim lead results showed a shorter neural activation distance and EF extension. The distance to the isolevel of 0.2 V/mm is close to the neural activation distance at each stimulation amplitude, and we conclude that the electric field is a suitable predictor to visualize the stimulated regions.

  • 124.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Zsigmond, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Influence of Virchow-Robin spaces in the Electric Field Distribution in Subthalamic Nucleus Deep Brain Stimulation2019Conference paper (Refereed)
    Abstract [en]

    Objectives: Previous investigations have shown the appearance of cysts i.e. Virchow-Robin spaces (VR) in the basal ganglia and their relationship with parkinsonian symptoms [1-3]. Simulations [4]using the finite element method (FEM) suggests that VR affects the electric field around deep brain stimulation (DBS) electrodes. The aim of the study was to evaluate how the electric field is modified by the presence of cysts in the STN. Methods: The effect of cysts on the electric field around the DBS lead placed in the STN was evaluated using FEM. 3D patient-specific brain models were built with COMSOL 5.2 (COMSOL AB, Sweden) and an in-house developed software [5] to convert a T2 weighted MRI of Parkinsonian patients (ethics approval no: 2012/434-3) into electrical conductivity matrix readable by FEM software. VR was classified as CSF [6]assigning a high electrical conductivity (2.0 S/m). The stimulation amplitudes were set to the clinically programmed values. Depending on the lead used, the stimulation was set to voltage control (3389) or current control (6180, ring mode). The coordinates corresponding to the lowest (first) electrode and the third higher up in the lead, taken from the postoperative CT electrode artefact, were used to localize the leads in the brain model [7]. The electric field was visualized with a 0.2V/mm isosurface. Results: Simulations showed that the electric field distribution is affected by the cysts. The higher conductivity at these regions in the vicinity of the electrode redistributes the electric field pushing it away from the cyst. The same effect occurs regardless of the operating mode or the lead design as long as the directional lead is configured in ring mode. Conclusions: The use of patient-specific models has shown the importance of considering nuances of the patients’ anatomy in the STN. This information can be used to determine the stimulation parameter and to support the analysis of side effects induced by the stimulation. The potential advantage of directional leads can also be assessed by including in the model patient-specific data.

  • 125.
    Alonso Orozco, Fabiola
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Finite Element Method Modelling and Simulations for Comparisonbetween Deep Brain Stimulation Electrodes2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The Deep Brain Stimulation (DBS) is an invasive therapy that alleviates the symptoms of several neurological disorders by electrically stimulating specific regions of the brain, generally within the basal ganglia. Until now Medtronic DBS system is the only approved by the Food and Drug Administration, nevertheless European and Australian countries  have recently approved St. Jude DBS systems to treat Parkinson’s disease and related movement disorders.

         Traditionally, voltage-controlled stimulation (the type of systems provided by Medtronic) has been used and clinicians are familiar with its settings; however the knowledge about systems based in current-controlled stimulation (St. Jude systems) is rather scarce. One of the key factors for a successful therapy is the optimal selection of the electrical parameters for stimulation. Due to the critical zone where the surgery is performed, modeling and simulations of DBS systems have been extensively used to observe how the electric field is distributed in the brain tissue and ultimately to help the clinicians to select the best parameters.

         In this thesis two finite element models of the DBS systems mentioned above have been developed; five examinations were designed, based on the physical and electrical differences between the systems, to observe and quantitatively compare the electric field distribution.

        The aim of this thesis was to investigate the differences between two representative models of each company but moreover to contribute with information regarding current-controlled stimulation.

    The results obtained are expected to be useful for further investigations where the magnitude and distribution of the electric field generated by this type of electrodes are needed.

  • 126.
    Alonso-Fernandez, Fernando
    et al.
    Halmstad University, School of Information Technology, Halmstad Embedded and Intelligent Systems Research (EIS), CAISR - Center for Applied Intelligent Systems Research.
    Bigun, Josef
    Halmstad University, School of Information Technology, Halmstad Embedded and Intelligent Systems Research (EIS), CAISR - Center for Applied Intelligent Systems Research.
    Englund, Cristofer
    RISE Viktoria, Gothenburg, Sweden.
    Expression Recognition Using the Periocular Region: A Feasibility Study2018In: 2018 14th International Conference on Signal-Image Technology & Internet-Based Systems (SITIS) / [ed] Gabriella Sanniti di Baja, Luigi Gallo, Kokou Yetongnon, Albert Dipanda, Modesto Castrillón-Santana & Richard Chbeir, Los Alamitos: IEEE Computer Society, 2018, p. 536-541Conference paper (Refereed)
    Abstract [en]

    This paper investigates the feasibility of using the periocular region for expression recognition. Most works have tried to solve this by analyzing the whole face. Periocular is the facial region in the immediate vicinity of the eye. It has the advantage of being available over a wide range of distances and under partial face occlusion, thus making it suitable for unconstrained or uncooperative scenarios. We evaluate five different image descriptors on a dataset of 1,574 images from 118 subjects. The experimental results show an average/overall accuracy of 67.0%/78.0% by fusion of several descriptors. While this accuracy is still behind that attained with full-face methods, it is noteworthy to mention that our initial approach employs only one frame to predict the expression, in contraposition to state of the art, exploiting several order more data comprising spatial-temporal data which is often not available.

  • 127.
    Alonso-Fernandez, Fernando
    et al.
    Halmstad University, School of Information Technology, Halmstad Embedded and Intelligent Systems Research (EIS), CAISR - Center for Applied Intelligent Systems Research.
    Farrugia, Reuben
    University of Malta, Msida, Malta.
    Bigun, Josef
    Halmstad University, School of Information Technology, Halmstad Embedded and Intelligent Systems Research (EIS), CAISR - Center for Applied Intelligent Systems Research.
    Very Low-Resolution Iris Recognition Via Eigen-Patch Super-Resolution and Matcher Fusion2016In: 2016 IEEE 8th International Conference on Biometrics Theory, Applications and Systems (BTAS), Piscataway: IEEE, 2016, article id 7791208Conference paper (Refereed)
    Abstract [en]

    Current research in iris recognition is moving towards enabling more relaxed acquisition conditions. This has effects on the quality of acquired images, with low resolution being a predominant issue. Here, we evaluate a super-resolution algorithm used to reconstruct iris images based on Eigen-transformation of local image patches. Each patch is reconstructed separately, allowing better quality of enhanced images by preserving local information. Contrast enhancement is used to improve the reconstruction quality, while matcher fusion has been adopted to improve iris recognition performance. We validate the system using a database of 1,872 near-infrared iris images. The presented approach is superior to bilinear or bicubic interpolation, especially at lower resolutions, and the fusion of the two systems pushes the EER to below 5% for down-sampling factors up to a image size of only 13×13.

  • 128.
    Alrifaiy, Ahmed
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    A gastight microfluidic system combined with optical tweezers and optical spectroscopy for electrophysiological investigations of single biological cells2011Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke affects around 20 million people around the world every year. Clinically, stroke is a result of brain damage due to the shortage of oxygen delivered to the nerve cells. To minimize suffering and costs related to the disease, extensive research is performed on different levels. The focus of our research is to achieve fundamental understanding on how the lack of oxygen in brain tissue activates intrinsic biomolecular defense mechanisms that may reduce brain damage. More knowledge may hopefully lead to new therapeutic and preventive strategies on the molecular level for individuals in the risk zone for stroke or those who have just suffered a stroke. The area of study is based on the discovery of a hemoprotein called neuroglobin (Ngb), which is found in various regions in the brain, in the islets of Langerhans, and in the retina. Several studies have shown that Ngb seems to have a protective function against hypoxia-related damage. However, until now, it has not been understood how Ngb affects the nerve system and protects neurons from damage. The well-established patch-clamp technique is routinely used to measure and analyze the electrophysiological activity of individual biological cells. To perform accurate patchclamp experiments, it is important to create well-controlled physiological conditions, i.e. different oxygen levels and fast changes of nutrients and other biochemical substances. A promising approach is to apply lab-on-a-chip technologies combined with optical manipulation techniques. These give optimal control over fast changing environmental conditions and enable multiple readouts. The conventional open patch-clamp configuration cannot provide adequate control of the oxygen content. Therefore, it was substituted by a gas-tight multifunctional microfluidic system, a lab-on-a-chip, with an integrated patch-clamp micropipette. The system was combined with optical tweezers and optical spectroscopy. Laser tweezers were used to optically guide and steer single cells towards the fixed micropipette. Optical spectroscopy was used to investigate the biochemical composition of the sample. The designed, closed lab-on-a-chip acted as a multifunctional system for simultaneous electrophysiological and spectroscopic experiments with good control over the oxygen content in the liquid perifusing the cells. The system was tested in a series of experiments: optically trapped human red blood cells were steered to the fixed patch-clamp pipette within the microfluidic system. The oxygen content within the microfluidic channels was measured to 1 % compared to the usual 4-7 %. The trapping dynamics were monitored in real-time while the spectroscopic measurements were performed simultaneously to acquire absorption spectra of the trapped cell under varying environments. To measure the effect of the optical tweezers on the sample, neurons from rats in a Petri dish were optically trapped and steered towards the patch-clamp micropipette where electrophysiological investigations were performed. The optical tweezers had no effect on the electrophysiological measurements. Similar investigations within a closed microfluidic system were initiated and showed promising results for further developments of a complete lab-on-a-chip multifunctional system for reliable patch-clamp measurements. The future aim is to perform complete protocols of patch-clamp electrophysiological investigations while simultaneously monitoring the biochemical composition of the sample by optical spectroscopy. The straightforwardness and stability of the microfluidic chip have shown excellent potential to enable high volume production of scalable microchips for various biomedical applications. The subsequent ambition is to use this system as a mini laboratory that has benefits in cell sorting, patch-clamp, and fertilization experiments where the gaseous and the biochemical content is of importance. The long-term goal is to study the response of individual neurons and defense mechanisms under hypoxic conditions that may establish new ways to understand cell behavior related to Ngb for various diseases such as stroke, Alzheimer’s and Parkinson’s.

  • 129.
    Alrifaiy, Ahmed
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lab on a chip for electrophysiological measurements with control of the oxygen content: optical manipulation and spectroscopic analysis of biological cells2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke affects nearly 20 million people around the world every year. Clinically, stroke is a result of brain damage due to the shortage of oxygen delivered to the nerve cells. To minimize suffering and costs related to the disease, extensive research is performed on different levels. The focus of our research is to achieve fundamental understanding on how the lack of oxygen in brain tissue activates intrinsic biomolecular defense mechanisms that may reduce brain damage. More knowledge may hopefully lead to new therapeutic and preventive strategies on the molecular level for individuals in the risk zone for stroke or those who have just suffered a stroke.The area of study is based on the discovery of a hemoprotein called neuroglobin (Ngb), which is found in various regions in the brain, in the islets of Langerhans, and in the retina. Several studies have shown that Ngb seems to have a protective function against hypoxia-related damage. However, until now, it has not been understood how Ngb affects the nerve system and protects neurons from damage.The well-established patch-clamp technique is routinely used to measure and analyze the electrophysiological activity of individual biological cells. To perform accurate patchclamp experiments, it is important to create well-controlled physiological conditions, i.e. different oxygen levels and fast changes of nutrients and other biochemical substances. A promising approach is to apply lab on a chip technologies combined with optical manipulation techniques. These give optimal control over fast changing environmental conditions and enable multiple readouts.The conventional open patch-clamp configuration cannot provide adequate control of the oxygen content. Therefore, the aim of the thesis was to design and test a multifunctional microfluidic system, lab on a chip (LOC), that can achieve normoxic, anoxic and hypoxic conditions. The conventional patch clamp configuration was substituted by a gas-tight LOC system with an integrated patch-clamp micropipette. The system was combined with optical tweezers, optical sensor and optical spectroscopy.Optical tweezers were used to trap and guide single cells through the LOC microchannels towards the fixed micropipette. Optical spectroscopy was essential to investigate the biochemical composition of the biological samples. The developed, gas-tight LOC acted as a multifunctional system for simultaneous electrophysiological and spectroscopic experiments with good control over the oxygen content in the liquid perifusing the cells. The system was tested in series of experiments: optically trapped cells (red blood cells from human and chicken and nerve cells) were steered to the fixed patch-clamp pipette within the LOC system. The oxygen content within the microfluidic channels was measured to ∼ 1% compared to the usual 4-7% found in open system. The trapping dynamics were monitored in real-time while the spectroscopic measurements were performed simultaneously to acquire absorption spectra of the trapped cell under varying environments. To measure the effect of the laser tweezers on the sample, neurons from rats in a Petri dish were optically trapped and steered towards the patch-clamp micropipette where electrophysiological investigations were performed. The optical tweezers had no effect on the electrophysiological measurements.The future aim is to perform complete protocols of patch-clamp electrophysiological investigations while simultaneously monitoring the biochemical composition of the sample by optical spectroscopy. The straightforwardness and stability of the microfluidic chip have shown excellent potential to be applied for various biomedical applications. The subsequent ambition is to use this system as a mini laboratory that has benefits in cell sorting, patch-clamp and fertilization experiments where the gaseous and the biochemical content is of importance.The long-term goal is to study the response of individual neurons and defense mechanisms under hypoxic conditions that may establish new ways to understand cell behavior related to Ngb for various diseases such as stroke, Alzheimer’s and Parkinson’s.

  • 130.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Bitaraf, Nazanin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Druzin, Michael
    Umeå universitet, Integrativ Medicinsk Biologi, Fysiologi.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Hypoxia on a chip: a novel approach for patch-clamp studies in a microfluidic system with full oxygen control2012In: World Congress on Medical Physics and Biomedical Engineering, May 26-31, 2012, Beijing, China / [ed] Mian Long, Berlin: Encyclopedia of Global Archaeology/Springer Verlag, 2012, p. 313-316Conference paper (Refereed)
    Abstract [en]

    Here a new approach to perform patch-clamp investigations under anoxic and normoxic conditions on nerve cells from Sprague Dawley rats is presented. A patch-clamp micropipette is integrated within a poly-methyl methacrylate (PMMA) based microchip giving optimal control over the oxygen content and the biochemical environment. Nerve cells were trapped by optical tweezers and steered towards the patch-clamp micropipette within the micro-channels. Several experiments were performed to show proof of principle. The oxygen content within the microfluidic chamber was measured to 0.5-1.5 %. The photo-induced effect of the optical tweezers on the nerve cells was investigated in an open Petri dish. The optical trapping did not influence measurements. The microfluidic system was further tested in patch-clamp experiments. This approach showed significant advantages regarding the tuning of the oxygen content and may be used in various electrophysiological investigations of single cells demanding optimal control of the surroundings.

  • 131.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Bitaraf, Nazanin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Druzin, Michael
    Umeå universitet, Integrativ Medicinsk Biologi, Fysiologi.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Patch-clamp measurements on a chip with full control over the oxygen content2012In: Journal of Biochips & Tissue Chips, ISSN 2153-0777, Vol. 2, no 1, p. 1-5Article in journal (Refereed)
  • 132.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Bitaraf, Nazanin
    Lindahl, Olof
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Development of microfluidic system and optical tweezers for electrophysiological investigations of an individual cell2010In: Optical Trapping and Optical Micromanipulation VII: 1 - 5 August 2010, San Diego, California, United States ; [part of SPIE optics + photonics] / [ed] Kishan Dholakia; Gabriel C. Spalding, Bellingham, Wash: SPIE - International Society for Optical Engineering, 2010Conference paper (Refereed)
    Abstract [en]

    We present a new approach of combining Lab-on-a-chip technologies with optical manipulation technique for accurate investigations in the field of cell biology. A general concept was to develop and combine different methods to perform advanced electrophysiological investigations of an individual living cell under optimal control of the surrounding environment. The conventional patch clamp technique was customized by modifying the open system with a gas-tight multifunctional microfluidics system and optical trapping technique (optical tweezers).The system offers possibilities to measure the electrical signaling and activity of the neuron under optimum conditions of hypoxia and anoxia while the oxygenation state is controlled optically by means of a spectroscopic technique. A cellbased microfluidics system with an integrated patch clamp pipette was developed successfully. Selectively, an individual neuron is manipulated within the microchannels of the microfluidic system under a sufficient control of the environment. Experiments were performed to manipulate single yeast cell and red blood cell (RBC) optically through the microfluidics system toward an integrated patch clamp pipette. An absorption spectrum of a single RCB was recorded which showed that laser light did not impinge on the spectroscopic spectrum of light. This is promising for further development of a complete lab-on-a-chip system for patch clamp measurements.

  • 133.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering.
    Bitaraf, Nazanin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ett mikroflödessystem för multipla undersökningar av enstaka biologiska celler under hypoxiska förhållanden2011Conference paper (Refereed)
    Abstract [sv]

    Introduktion: Syftet med studien är att studera enstaka nervcellers respons vid syrebrist i ett mikroflödessystem för att förstå nervcellens respons vid stroke. Målet med studien var att utveckla ett slutet mikroflödessystem som ger optimal kontroll av den omgivande miljön och samtidigt möjliggöra elektrofysiologiska undersökningar under kontrollerade syreförhållande. Material och metoder: Mikroflödescellen utvecklades för ett inverterat mikroskop, utrustad med en optisk pincett och optisk spektroskopi samt patch-clamp för elektrofysiologiska studier på en enstaka nervcell. Istället för att föra en pipett mot en cell i ett öppet system fångades en enskild cell optiskt i ett slutet mikroflödessystem och fördes mot en fixerad patch-clamp mikropipett. Cellen utsattes för olika syrehalter och övervakades av ett UV-Vis spektroskop medan cellens elektrofysiologiska aktivitet registreras med patch-clamp. Det slutna mikroflödessystemet med integrerad mikropipett, kopplades till ett pumpsystem för införandet av celler och buffert med olika kemiska egenskaper och syrehalter. I ett inverterat mikroskop integrerades optisk pincett, UV-Vis spektrometer och patch-clamp. Resultat och diskussion: För att pröva konceptet fångades och fördes en röd blodcell optiskt mot mikropipetten som befann sig på en fast position i mikroflödescellen. Cellens syrebindningstillstånd varierades genom att tillsätta syrefri eller syresatt buffert och registrerades med UV-Vis spektrometern. I ett vidare experiment manipulerades en nervcell optiskt i ett öppet system mot patch-clamp pipetten och elektrofysiologiska mätningar utfördes. Vi kunde verifiera att den optiska pincetten inte påverkade den elektrofysiologiska mätningen. För närvarandet utförs elektrofysiologiska mätningar i det slutna mikroflödessystemet för att se hur nervcellerna reagerar under varierande syrehalt. Genom mätningarna hoppas vi att få mer kunskap om försvarsmekanismerna som igångsätts av neuroner under syrefattiga förhållanden.

  • 134. Alrifaiy, Ahmed
    et al.
    Lindahl, Olof
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ett mikroflödessystem med optisk pincett och UV- vis för studier på enskilda biologiska celler2010Conference paper (Other academic)
  • 135.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Patch-clamp electrophysiological measurements on single cells under hypoxic conditions in microfluidic systems2012Conference paper (Refereed)
  • 136.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Lindahl, Olof
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Polymer-based microfluidic devices for pharmacy, biology and tissue engineering2012In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 4, no 3, p. 1349-1398Article in journal (Refereed)
    Abstract [en]

    This paper reviews microfluidic technologies with emphasis on applications in the fields of pharmacy, biology, and tissue engineering. Design and fabrication of microfluidic systems are discussed with respect to specific biological concerns, such as biocompatibility and cell viability. Recent applications and developments on genetic analysis, cell culture, cell manipulation, biosensors, pathogen detection systems, diagnostic devices, high-throughput screening and biomaterial synthesis for tissue engineering are presented. The pros and cons of materials like polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), polystyrene (PS), polycarbonate (PC), cyclic olefin copolymer (COC), glass, and silicon are discussed in terms of biocompatibility and fabrication aspects. Microfluidic devices are widely used in life sciences. Here, commercialization and research trends of microfluidics as new, easy to use, and cost-effective measurement tools at the cell/tissue level are critically reviewed.

  • 137.
    Alrifaiy, Ahmed
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Ramser, Kerstin
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    How to integrate a micropipette into a closed microfluidic system: absorption spectra of an optically trapped erythrocyte2011In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 2, no 8, p. 2299-2306Article in journal (Refereed)
    Abstract [en]

    In July 2011 a new concept of a closed microfluidic system equipped with a fixed micropipette, optical tweezers and a UV-Vis spectrometer was presented [Biomed. Opt. Express 2, 2299 (2011)]. Figure 1 showed falsely oriented mirrors. To clarify the design of the setup, this erratum presents a correct schematic

  • 138.
    Alsadi, Zeyneb
    Linköping University, Department of Biomedical Engineering.
    Diffuse correlation spectroscopy for estimation of coagulation thickness: a phantom study2019Independent thesis Advanced level (degree of Master (Two Years)), 300 HE creditsStudent thesis
    Abstract [en]

    The objective of this preliminary study was to determine the potential of diffuse correlation spectroscopy (DCS) for assessment of coagulation depth. Coagulation of tissue can occur due to a number of different reasons such as thermal or electrical burns or radiofrequency ablation. DCS is a non-invasive optical technique which can be used to determine the optical and dynamic properties of tissue by fitting a theoretical model of photon propagation in multiply scattering tissue to experimental data obtained from measurements. The DCS measurements were performed on two-layered phantom models that represent healthy tissue with high flow properties with a layer of coagulated tissue with low flow properties on top. Three different phantom models were prepared using gelatin-Intralipid gels, PDMS, and nylon as an upper layer, and an Intralipid solution was used for the bottom layer for all three phantoms. DCS measurements were performed on all three phantom models with varying thicknesses of the upper layers, and varying source-detector separations. The acquired data from the DCS measurement were analyzed in MATLAB in order to obtain the electric field temporal autocorrelation function. A theoretical model describing photon propagation in a two-layered medium was fitted to the obtained data in order to extract the desired parameters. The results showed that the thickness of the gelatin-Intralipid gels could be extracted within a 0.5 mm certainty and the thickness of the PDMS phantoms could also be extracted within approximately 0.7 mm. For the nylon phantoms, the results obtained were not good because the fitting was not successful and the thickness was not extracted appropriately. There is potential in DCS for assessment of burn wound depth but further research and development has to be done in the field in order to obtain more accurate and reliable results.

  • 139.
    Alsaeede, Mustafa
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Test and Evaluation of a Novel Passive Tool Used For Blood Dilution in Hematology Analyzers2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Executive Summary

    The Complete Blood Count (CBC) is considered one of the most commonly performed screening tests in medical diagnostics. The CBC is performed using a hematological analyzer, which counts the numbers and types of different cells within the blood. However, due to the high concentration of cells in the blood samples to be counted, the dilution process is considered an essential factor for obtaining accurate counting results. Below is an investigation for an invention of a unique method and device for blood sample dilution in hematology analyzers. As mentioned, before starting an analysis a hematology cell counter device must dilute a precise defined volume of a whole blood sample with a diluent reagent (in this study 20ml of a blood sample is diluted with 4,5ml of diluent reagent). This dilution process must be accurate and repeatable with a high precision to produce the target dilution ratio (here 1:200). Exclusive to almost all hematology analyzers today, shear values (SV) are used to obtain highly precise volumes. These SV components are however very costly and add a higher complexity to the systems. This thesis was therefore aimed as an experimental evaluation for a novel passive dilution tool called shearing block (SB), which could possibly then replace the SV and be used in the coming Haematology Analyzer Devices manufactured by Boule Medical AB. The SB has the advantages of being low cost, having a simple mechanism, being much more flexible for integration with any microfluidic system and also eliminates the need for complex control systems or equipment, thereby lowering the need for calibration and maintenance. If a SB could replace the SV with an equally precise accuracy on the 20ml blood volume it would be highly beneficial.

     

    The set hypothesis was that the dilution process via the SB, will only be affected by blood viscosity. Through changing the blood’s viscosity, via changing the hematocrit concentration (HCT) and blood sample temperature, this study aimed to conclude if this gave a significant effect on the blood sample dilution via the SB. This was achieved through two performed experiments both including the same control group (CG) along with a test group (TG). All tests were performed using the same blood sample, the same reference measuring device (Medonic M32) and experimental setup. The experimental setup included the control group, CG, (N=30) consisting of 20µl blood samples aspirated through an electronic pipette in room temperature condition being mixed with 4,5ml of diluent reagent that had been automatically dispensed by the Medonic M32 instrument. The 20µl blood together with the 4,5ml diluent resulted in the targeted 1:200 dilution ratio. The test group, TG, (where N=30 for each respective group) was diluted through the SB through a fully automated process for the targeted 1:200 dilution. All diluted blood samples were then analyzed on the Medonic M32 for all hematology parameters and the hemoglobin (HGB) parameter was used as an indicator to quantify the blood volume in the TG runs as compared to the CG reference runs. Two test groups (TG) were analyzed: the first investigating the effect of the HCT and the second of the sample temperature on the blood volume (before dilution) in the SB. The HCT concentration levels were tested at 15%, 27%, 33% and 58% with samples and test run and kept at a constant 25°C. The second test group investigated the effect of 15°C, 25°C, 35°C and 39°C on a blood sample with a constant HCT of 33%.

    The main aim of this experimental study was to validate the SB simulation. However, the experiments results, showed that the diluted blood volume via SB was strongly influenced by changes in hematocrit concentration and that the unwanted additional blood volume, was increasing directly proportionally with hematocrit concentration.  On the other hand, there seemed to be no apparent change in the blood volume on the SB diluted samples for the various temperature differences between 15-35°C. To conclude, the experiments results were not consistent with predictions of SB simulation model and there are two reasons that could explain that. Firstly, in the simulation the blood was approximated with a homogeneous fluid with a given viscosity. The second reason is the mismatch between the dilution process via the SB and the simulation (the simulation started with an idealized initial status, whereas the SB channel was prefilled by blood). This means that the simulation excluded any effect that may occur as a convection effect during blood flow inside the channel and whilst encountering diluent reagent. These two reasons explain why the results of the simulation was not consistent with that of the experiments, regarding the unwanted blood volume. Therefore, a new simulation is required. Recommendations for future actions: undoubtedly there are several optimizations that may increase the accuracy of the proposed SB design such as; removing the diluent's reservoir for eliminating the effect of bubbles, changing the geometrical angles or use a smaller diameter for the inlets and outlets of the microchannels to reduce the convection and diffusion effect, (which in turn would reduce the unwanted blood volume). Therefore, determining the best SB's microchannel structure to perform the dilution process with minimum unwanted blood volume remains a near future next step follow-up project.

  • 140.
    Altgärde, Noomi
    Linköping University, Department of Physics, Chemistry and Biology.
    Local release of lithium from sol-gel coated orthopaedic screws: an in vitro and in vivo study2009Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

     

    In orthopaedic practice, fractures are usually stabilised with metal screws or rods. This is done in order to keep the fracture parts in place during the rather slow healing process. The healing time can potentially be reduced by local- or systemic treatment with different bone promoting drugs. In later years, lithium, otherwise used to treat bipolar disease, has shown promise to be such a drug.

     

    The aim of this master thesis was to find a way to coat metal bone screws with lithium and to characterise the coating. The coating was to be designed in such a way that it could release lithium to the surrounding bone tissue.

     

    Lithium chloride was incorporated into a titanate sol-gel and attached to silicon wafers and stainless steel screws by dip coating. Wafers were used for initial in vitro studies of how lithium changed coating characteristics. This was studied using ellipsometry, AFM and SEM. Lithium is most probably physisorbed and not incorporated into the network building up the sol-gel. Coating structure is changed as more lithium is incorporated. For large amounts of lithium, the nanoparticles normally formed when curing the sol-gel are inhibited. One effect of this is reduced bioactivity, seen as a reduced ability for calcium phosphate crystals to nucleate on the coating when immersed in simulated body fluid.

    Lithium release was investigated using AAS. Lithium is released from the coating, showing a burst effect. By changing the number of coating layers used, the release profile can be partly altered. The coating was also applied to screws, showing good attachment, and the lithium release profile was similar to the one seen from wafers.

    Finally, a screw model was used in rats to assess the effect of local lithium treatment from screws and systemic lithium treatment on fracture healing. In the model, a screw was inserted in tibia, mimicking a fracture. When the bone around the screw was healed, a pullout test was performed, giving information about the strength of the bone surrounding the screw. No significant difference could be found for either local- or systemic lithium treatment compared to control. However, when evaluating the strength of intact bone in a similar way, a positive effect of systemic lithium treatment could be seen. Therefore, it is still likely that lithium has a positive effect on bone and further studies are needed to fully evaluate its role in fracture healing.

     

  • 141.
    Altmann, Brigitte
    et al.
    University of Freiburg, Germany.
    Karygianni, Lamprini
    University of Freiburg, Germany.
    Al-Ahmad, Ali
    University of Freiburg, Germany.
    Butz, Frank
    University of Freiburg, Germany.
    Bächle, Maria
    University of Freiburg, Germany.
    Adolfsson, Erik
    RISE - Research Institutes of Sweden, Materials and Production, IVF.
    Fürderer, Tobias
    Courtois, Nicolas
    Palmero, Paola
    Politecnico di Torino, Italy.
    Follo, Marie
    University of Freiburg, Germany.
    Chevalier, Jérôme
    Université de Lyon, France.
    Steinberg, Thorsten
    University of Freiburg, Germany.
    Kohal, Ralf Joachim
    University of Freiburg, Germany.
    Assessment of Novel Long-Lasting Ceria-Stabilized Zirconia-Based Ceramics with Different Surface Topographies as Implant Materials2017In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 27, no 40, article id 1702512Article in journal (Refereed)
    Abstract [en]

    The development of long-lasting zirconia-based ceramics for implants, which are not prone to hydrothermal aging, is not satisfactorily solved. Therefore, this study is conceived as an overall evaluation screening of novel ceria-stabilized zirconia-alumina-aluminate composite ceramics (ZA8Sr8-Ce11) with different surface topographies for use in clinical applications. Ceria-stabilized zirconia is chosen as the matrix for the composite material, due to its lower susceptibility to aging than yttria-stabilized zirconia (3Y-TZP). This assessment is carried out on three preclinical investigation levels, indicating an overall biocompatibility of ceria-stabilized zirconia-based ceramics, both in vitro and in vivo. Long-term attachment and mineralized extracellular matrix (ECM) deposition of primary osteoblasts are the most distinct on porous ZA8Sr8-Ce11p surfaces, while ECM attachment on 3Y-TZP and ZA8Sr8-Ce11 with compact surface texture is poor. In this regard, the animal study confirms the porous ZA8Sr8-Ce11p to be the most favorable material, showing the highest bone-to-implant contact values and implant stability post implantation in comparison with control groups. Moreover, the microbiological evaluation reveals no favoritism of biofilm formation on the porous ZA8Sr8-Ce11p when compared to a smooth control surface. Hence, together with the in vitro in vivo assessment analogy, the promising clinical potential of this novel ZA8Sr8-Ce11 as an implant material is demonstrated. 

  • 142.
    Altmann, Brigitte
    et al.
    University Medical Center Freiburg, Germany.
    Rabel, Kerstin
    University Medical Center Freiburg, Germany.
    Kohal, Ralf J.
    University Medical Center Freiburg, Germany.
    Proksch, Susanne
    University Medical Center Freiburg, Germany.
    Tomakidi, Pascal
    University Medical Center Freiburg, Germany.
    Adolfsson, Erik
    RISE - Research Institutes of Sweden, Materials and Production, IVF.
    Bernsmann, Falk
    NTTF Coatings GmbH, Germany.
    Palmero, Paola
    Politecnico di Torino, Italy.
    Fürderer, Tobias
    MOESCHTER GROUP Holding GmbH, Germany.
    Steinberg, Thorsten
    University Medical Center Freiburg, Germany.
    Cellular transcriptional response to zirconia-based implant materials2017In: Dental Materials, ISSN 0109-5641, E-ISSN 1879-0097, Vol. 33, no 2, p. 241-255Article in journal (Refereed)
    Abstract [en]

    Objective To adequately address clinically important issues such as osseointegration and soft tissue integration, we screened for the direct biological cell response by culturing human osteoblasts and gingival fibroblasts on novel zirconia-based dental implant biomaterials and subjecting them to transcriptional analysis. Methods Biomaterials used for osteoblasts involved micro-roughened surfaces made of a new type of ceria-stabilized zirconia composite with two different topographies, zirconium dioxide, and yttria-stabilized zirconia (control). For fibroblasts smooth ceria- and yttria-stabilized zirconia surface were used. The expression of 90 issue-relevant genes was determined on mRNA transcription level by real-time PCR Array technology after growth periods of 1 and 7 days. Results Generally, modulation of gene transcription exhibited a dual dependence, first by time and second by the biomaterial, whereas biomaterial-triggered changes were predominantly caused by the biomaterials’ chemistry rather than surface topography. Per se, modulated genes assigned to regenerative tissue processes such as fracture healing and wound healing and in detail included colony stimulating factors (CSF2 and CSF3), growth factors, which regulate bone matrix properties (e.g. BMP3 and TGFB1), osteogenic BMPs (BMP2/4/6/7) and transcription factors (RUNX2 and SP7), matrix collagens and osteocalcin, laminins as well as integrin ß1 and MMP-2. Significance With respect to the biomaterials under study, the screening showed that a new zirconia-based composite stabilized with ceria may be promising to provide clinically desired periodontal tissue integration. Moreover, by detecting biomarkers modulated in a time- and/or biomaterial-dependent manner, we identified candidate genes for the targeted analysis of cell-implant bioresponse during biomaterial research and development.

  • 143.
    Alvarez, Victor
    et al.
    KTH.
    Halldin, Peter
    KTH.
    Kleiven, Svein
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    The Influence of Neck Muscle Tonus and Posture on Brain Tissue Strain in Pedestrian Head Impacts2014In: 58th SAE Stapp Car Crash Conference, STAPP 2014, Vol. 58Article in journal (Refereed)
    Abstract [en]

    Pedestrians are one of the least protected groups in urban traffic and frequently suffer fatal head injuries. An important boundary condition for the head is the cervical spine, and it has previously been demonstrated that neck muscle activation is important for head kinematics during inertial loading. It has also been shown in a recent numerical study that a tensed neck musculature also has some influence on head kinematics during a pedestrian impact situation. The aim of this study was to analyze the influence on head kinematics and injury metrics during the isolated time of head impact by comparing a pedestrian with relaxed neck and a pedestrian with increased tonus. The human body Finite Element model THUMS Version 1.4 was connected to head and neck models developed at KTH and used in pedestrian-to-vehicle impact simulations with a generalized hood, so that the head would impact a surface with an identical impact response in all simulations. In order to isolate the influence of muscle tonus, the model was activated shortly before head impact so the head would have the same initial position prior to impact among different tonus. A symmetric and asymmetric muscle activation scheme that used high level of activation was used in order to create two extremes to investigate. It was found that for the muscle tones used in this study, the influence on the strain in the brain was very minor, in general about 1-14% change. A relatively large increase was observed in a secondary peak in maximum strains in only one of the simulated cases. 

  • 144.
    Alvarez, Victor S
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Neuronic Engineering.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Medical Engineering, Neuronic Engineering.
    Importance of Windscreen Modelling Approach for Head Injury Prediction2016In: 2016 IRCOBI Conference Proceedings - International Research Council on the Biomechanics of Injury, 2016Conference paper (Refereed)
    Abstract [en]

    The objective of this study is to evaluate the capability of two modelling approaches in capturing  both accelerations and deformations from head impacts, and to evaluate the effect of modelling approach on  brain injury prediction. The first approach is a so‐called smeared technique, in which the properties of the two  glass  sheets and  the intermediate  polyvinyl  butyral  (PVB) are  combined and  divided into  two  coinciding  shell layers, of which one can fracture. The second approach consists of three shell layers, representing the glass and  PVB,  separated by  the  distance of  their  thickness, using a non‐local  failure criterion  to initiate  fracture in  the  glass.  The  two  modelling  approaches  are  compared  to  impact  experiments  of  flat  circular  windscreens,  measuring  deformations  and  accelerations  as  well  as  accelerations  from  impacts  against  full  vehicle  windscreens.  They  are  also  used  to  study  head‐to‐windscreen  impacts  using  a  detailed  Finite  Element  (FE)  model,  varying  velocity,  impact  direction  and  impact  point.  Only  the  non‐local  failure  model  is  able  to  adequately  capture  both  the accelerations and  deformations  of an  impactor. The FE  head model  simulations  also reveal that the choice of modelling approach has a large effect on the both localisation of the strain in the  brain and the characteristics of the strain‐time curve, with a difference in peak strain between 8% and 40%.  

  • 145.
    Ambarki, Khalid
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindqvist, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Petterson, E
    Warntjes, JBM
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Evaluation of automatic measurement of the intracranial volume based on quantitative MR imaging2012In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 33, no 10, p. 1951-1956Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation.

    MATERIALS AND METHODS: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded.

    RESULTS: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P > .25). The mean difference between the reference and automatic measurement was -4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were -0.47 ± 17.95 mL (-0.01 ± 1.24%) and -1.26 ± 17.68 mL (-0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were <1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds).

    CONCLUSIONS: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.

  • 146. Ambrosi, D.
    et al.
    Ateshian, G. A.
    Arruda, E. M.
    Cowin, S. C.
    Dumais, J.
    Goriely, A.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Mechanics, Biomechanics.
    Humphrey, J. D.
    Kemkemer, R.
    Kuhl, E.
    Olberding, J. E.
    Taber, L. A.
    Garikipati, K.
    Perspectives on biological growth and remodeling2011In: Journal of the mechanics and physics of solids, ISSN 0022-5096, E-ISSN 1873-4782, Vol. 59, no 4, p. 863-883Article, review/survey (Refereed)
    Abstract [en]

    The continuum mechanical treatment of biological growth and remodeling has attracted considerable attention over the past fifteen years. Many aspects of these problems are now well-understood, yet there remain areas in need of significant development from the standpoint of experiments, theory, and computation. In this perspective paper we review the state of the field and highlight open questions, challenges, and avenues for further development.

  • 147.
    Ammendrup, Katrin
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Framework for Wireless Acquisition of Surface EMG and Real-Time Control2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Muscle driven devices are controlled or powered with muscle activation. These devices open up the possibility of offering patients with limited muscle function to automatically control assistive devices - for instance exoskeletons - with input from their own muscles. This solution would help a number of patient groups suffering from common conditions, such as spinal cord injuries, stroke and cerebral palsy.

    To use muscle activation as input it is necessary to have a way to communicate with the mus- cles. Electromyography (EMG) is a technology used to gain information about muscle function and activation. It is performed by measuring and analyzing electrical signals conducted by the muscles during activation. Activation and activation level can be seen from analyzed EMG signal. EMG signals are frequently measured and analyzed afterwards, however, to use it as a controlling an assistive devices, real time analysis is necessary. In this thesis real time acquisi- tion and analysis of EMG was performed. The measured signal was used as an input to control a simple MATLAB computer game.

    The EMG of a muscle of the forearm, Brachioradialis, was measured with Myon Aktos sys- tem. The measured signal was written to a server as soon as the measurements were acquired. MATLAB was used to connect to the server and performing the signal analysis. The analysis was kept simple in order to limit delay.

    The result showed that it was possible to acquire real time signal with this method. The delay was negligible, both for the testing and for the game play.

    Showing that it is possible to play a game with muscle activation supports the idea of a motor that can be controlled automatically with muscle input. Future work should focus on understanding movement intent with respect to EMG and on analyzing multiple signals from different muscles at the same time.

  • 148. Anderson, C.
    et al.
    Andersson, T.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Changes in skin circulation after microdialysis probe insertion visualized by laser Doppler perfusion imaging1994In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 102, no 5, p. 807-811Article in journal (Refereed)
    Abstract [en]

    Microdialysis makes possible in vivo estimation of endogenous and exogenous substances in the dermal extracellular space. Insertion of the microdialysis probe and its subsequent presence in the skin may affect both the reactivity of the skin test site and the measurement of target substances. Laser Doppler flowmetry is a non-invasive method for estimating cutaneous blood flow. A further development of this technique, laser Doppler perfusion imaging, has been used to study the time course of the circulatory changes caused in the area of microdialysis probe insertion. Laser Doppler perfusion imaging was performed prior to, during, and after microdialysis probe insertion in the skin of the ventral forearm in three subjects. Probe insertion caused an increase in skin blood perfusion in the whole test area. About 15 min after probe insertion, the flare, which is presumed to be of chiefly axon reflex origin, began to subside and the circulatory response could be seen to center around the site of insertion and the tip of the probe. Skin perfusion levels had returned to near normal levels within 60 min. Local anesthesia of the point of guide insertion inhibited the flare, but did not affect circulatory reactivity in the skin nearby. Both microdialysis and laser Doppler perfusion imaging seem to be promising new methods in dermatologic research.

  • 149. Anderson, C.
    et al.
    Svensson, .
    Sjögren, F.
    Andersson, T.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Human in vivo microdialysis technique can be used to measure cytokines in contact reactions.1995In: Current Problems in Dermatology, ISSN 1421-5721, E-ISSN 1662-2944, Vol. 23, p. 121-130Article in journal (Refereed)
  • 150.
    Andersson, Britt
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Svängande sensorer hittar prostatacancer2010In: medtechinfo.comArticle in journal (Other (popular science, discussion, etc.))
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