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The number of people affected by degenerative diseases of the retina increases notably due to the longer life expectancy. The weakening of the sight concerns especially older people, who suffer from degeneration of the retina and its retinal pigment epithelium (RPE) monolayer. Currently, these degenerative diseases of the retina are incurable. Cell transplantation of healthy RPE cells is considered to be a potential treatment for these diseases. Due to the unlimited self-renewal capacity and pluripotency human pluripotent stem cells (hPSCs) are considered as possible cell sources for transplantation purposes. However, the current differentiation protocols for RPE cells from hPSCs are inefficient and result in low yields. The aim of this thesis was to study whether biodegradable poly(L-lactide) (PLLA) microparticles and commercial biostable cellulose anion exchange diethylaminoethyl (DE) 53 microparticles could be exploited in increasing the efficacy of differentiation of hPSCs into RPE cells. In addition, the potential of the microparticle culture system for stem cell maintenance in feeder-free conditions was evaluated. The attachment and proliferation of hPSCs on microparticles were analyzed by immunofluorescence analysis and microscopy. The success of differentiation of RPE from stem cells in microparticle cultures was evaluated by inspecting the appearance of pigmentation in cultures as well as by investigating the expression of RPE maturation markers on gene expression levels by RT-PCR. The PLLA microparticles did not support the attachment and proliferation of hPSCs in feeder-free conditions. The poor performance of PLLA particles in cell culture studies might be due to the hydrophobic nature of the particle surfaces. In contrast, hPSCs attached, proliferated and maintained their pluripotency on DE 53 particles. Furthermore, the hPSCs were successfully differentiated into RPE cells on these DE 53 particles. However, the differentiation efficacy did not outperform the conventional differentiation protocol. This was the first study in which the hPSCs were successfully differentiated into RPE cells on microparticles. Microparticles are far from being routinely used in hPSC maintenance and differentiation to mature cell types. More long-term and large-scale studies need to be conducted in the future. Nevertheless, at the moment they seem appealing and promising with a possibility to grow stem cells in large-scale and cost effectively. The microparticle culture systems set challenges for the cell analysis due to their 3-dimensional structure and autofluorescence property. Therefore, novel methods for characterization, analysis and imaging of microparticle culture systems should be developed. /Kir12

Advances in measurement technology and wireless signal transfer have enabled the design of new, smaller and portable—even plaster-like—electrocardiographic (ECG) measurement devices that enable patient monitoring at home or in emergency situations. The development of new, miniaturized biomedical sensors has opened up possibilities for their application, but also set new demands on signal analysis and interpretation. In particular, the new small wireless systems often utilize bipolar electrodes that have a shorter interelectrode distance (IED) and different electrode locations from those of the standard 12-lead system. This affects the quality and the information content of the signal. The general objective of this thesis was to evaluate the performance of short IED precordial bipolar ECG leads and to determine their optimal location. This thesis adopted three methods to assess the properties of new bipolar precordial ECG leads: modeling, body surface potential map (BSPM) data, and exercise ECG data. First, two realistic, three-dimensional (3D) thorax models and lead field analysis were used to evaluate whether modeling of the measuring sensitivity of ECG leads could be used as a tool for designing new ECG leads. Second, BSPM data was used to study whether short-distance bipolar leads (IED approximately 6 cm) provide an ECG signal that is adequate for clinical utilization. Third, BSPM data was used to define where a bipolar ECG lead should be located in order to maximize the ECG signal strength within healthy subjects. Finally, the value of bipolar leads for diagnosing two major cardiac conditions—left ventricular hypertrophy (LVH) and coronary artery disease (CAD)—was assessed. It was found that the modeled measuring sensitivity corresponds to the changes in actual ECG signal strength, so modeling can be useful, especially in cases where in vivo measurements are impossible such as in designing implantable applications. Based on ECG data from 236 healthy subjects, all studied bipolar ECG leads with a short IED (approximately 6 cm) provided a detectable signal when compared to a low noise level of 15 μV and considering the P-wave as the smallest parameter. The optimal location of the bipolar lead was diagonally near the chest electrodes of the standard precordial leads V2, V3, and V4 (to maximize QRS amplitude), or above the chest electrodes of leads V1 and V2 (to maximize P-wave amplitude). In the selected clinical applications, LVH and CAD, the performance of bipolar leads was surprisingly good. In differentiating LVH (n=305) and healthy subjects (n=236), the performance of a correctly positioned small bipolar lead was similar to that of the traditional Sokolow-Lyon method. When differentiating CAD (n=255) patients from non-CAD (n=126) or low-likelihood of CAD (n=198) subjects, the overall performance of bipolar lead CM5 corresponded to that of standard lead V5. These results indicate that short IED bipolar leads provide a signal that is adequate for clinical use. Furthermore, the performance of these leads was shown to be similar or even superior to that of the commonly used standard leads. It can be concluded that when correctly positioned, short IED bipolar leads are useful and can give additional value for clinical diagnostics. These results provide promising information on the applicability and potential of short IED bipolar ECG leads, and demonstrate that they are worth developing further.

Electroencephalography (EEG) is the recording of potential fluctuations originating from electrical activity of brain. It is used in diagnosis of neurological disorders, monitoring the depth of anaesthesia and evaluation of sleep. A possible application is long-term continous monitoring of intensive care unit (ICU) patients, with the aim to detect epileptic seizure activity. Currently this is not practised due to poor usability of the available equipment. This thesis is part of a project which aims to develop a novel solution which solves the usability problem. Adding to that, the solution contains an algorithm for automatic online epileptic seizure detection, which enables immediate treatment of patients once epileptic seizures occur. This leads to an increased patient outcome at ICUs. An important factor contributing to poor usability of current EEG equipment is the electrode contact. To ensure good signal quality, skin under the electrodes needs to be prepared by abrasion for example. This is time-consuming especially when multiple electrodes are used. Adding to that, skin preparation damages skin which is undesired especially in long-term applications, as the the presence of electrode and electrolytic gel causes irritation and possibly an infection risk. The quality of the electrode contact is quantified by its electrical impedance. In this thesis the relationship of electrode contact impedance to total electrode contact noise and motion artifact magnitude are studied. These both are factors contributing to biopotential signal quality. Sintered silver-silverchloride electrodes are used in the work. Contact impedance is defined as the magnitude of the impedance vector at 20 Hz. Contact noise is studied by measuring impedance-noise data pairs (n=122) at two body sites of volunteer subjects using two different electrode gels. A univariate analysis of variance is implemented on the data pairs. Motion artifact magnitude is studied with impedanceartifact magnitude data pairs (n=33) while producing a horizontal motion to the electrode. The behavior of the seizure detection algorithm is also studied by adding different amounts of noise to EEG signals, and assessing how its behavior changes. The results show that electrode contact impedance can be used as a rough predictor of total contact noise. With contact impedance in the range of 20 k or less, the contact noise is expected to settle at RMS values less than 5 μV at a 30 Hz bandwidth. It was also found the that the type of electrolytic gel can have a significant effect on total contact noise. Motion artifact magnitude was found to decrease with decreasing contact impedance. With larger contact impedance values, the variations of motion artifact magnitudes were larger. The behavior of the seizure detection algorithm was found to change significantly with a small amount of noise added to EEG signals. By comparing that amount of noise to the measured contact noise data, it can be seen that it is well within the measured values.

Tissue engineering is expected to fulfill its promises to produce knowledge, methods, and products that would benefit the health care sector. The need of a degradable construct is a necessity when trying to grow a living tissue inside a porous structure. The fibers offer a unique approach to this, since the porosity can easily be altered with different methods especially using the textile methods. Textile industry on the other hand offers a broad and variable archive of methods to manufacture products and preforms. These preforms can be further used together with the composite technology to further increase the number of applications to which they can be used. When combining different fields of sciences it is possible to manufacture a living tissue, based on fibrous degradable constructs. Thus fibers and fibrous products are versatile preforms that can be shaped and designed to fulfill many of the demands in the field of tissue engineering. The main objective of this thesis was to study the biodegradable medical grade P(L/D)LA 96/4 polymer fibers and the fibrous products manufactured from them. The thermal degradation behavior of this polymer in single screw extruder environment in melt spinning process was studied. The online hot-drawing was used for fiber orientation. The information based on those studies was analyzed and gathered for future optimization of such melt spinning processes. Different batches and fiber diameters were produced using different processing parameters. Textile methods were further introduced to the melt-spun fibers. The effect of the knitting parameters on fiber properties were studied during the hydrolytic degradation and long term storage. These knits were studied as in vivo soft tissue implant preforms, in vitro spinal fusion cage composite preforms, and in vivo temporomandibular jaw implant preforms. Non-woven fabrics were produced from the melt-spun fibers manufactured by hot-drawing and high-speed drawing. These non-woven felts were used for plasma and solvent based wetting enhancement tests accompanied by cell seeding tests. The felts were also used as a component for temporomandibular jaw implant preforms. The results showed increasing degradation in the extruder barrel in regards to the P(L/D)LA 96/4 polymer molecular weight and viscosity. Lactide monomer was induced into the polymer during the melt spinning process due to the temperature and shear. Monomer content also varied according to the polymer residence time. Fiber showed different hydrolytical degradation behavior depending on the monomer amount. Higher monomer content caused rapid degradation of the mechanical properties and molecular weight. We acquired three different degradation profiles for the fibers that were related to the monomer content. The knitted soft tissue implants degraded faster during the hydrolysis than in in vivo. These knitted soft tissue implants acted as real tissue engineered implants; the cells grew and filled in the scaffolds. While the tissue matured in the scaffolds, the measured mechanical properties of the scaffolds improved despite the loss of mechanical strength of an empty scaffold. Non-woven scaffolds increased their wetting capability due to the oxygen plasma treatment. This also enhanced the cell attachment and proliferation.

This master of science thesis introduces an implantable measurement device that can be used to measure oxygen saturation (SpO2) with pulse oximetry methods. The device is intended to be incorporated into a implantable measurement device developed earlier at Tampere University of Technology (TUT). Two prototype devices were built and tested externally on a human subject with number of different measurement setups to determine how it would function in vivo. Respiratory diseases are the cause of approximately 50 % of all mortality in cattle. They can be hard to diagnose in early stages since there are no obvious external symptoms, this can cause outbreaks in groups of cattle. SpO2 gives a good measurement on how the respiratory system is functioning in the cattle by measuring the amount of oxygenated hemoglobin versus deoxygenated hemoglobin. The developed device measures the SpO2 with a probe made out of two light emitting diodes (LED) and a photosensor. In the thesis two types of coating methods where used to seal the probe, 3.5mm layer of medical grade epoxy and 15 µm layer of Parylene-C. The effect of these coatings on the probe components and signals where determined with measurements prior to coating and after. Parylene-C coating had much less effect on the signal acquisition than the epoxy coating, where the amplitude of the non-pulsatile signal increased on average over 1V and the pulsatile part decreased in amplitude. For Parylene-C there was a minor decrease in the amplitude of the non-pulsatile part but the pulsatile part had similar amplitude to non-coated probe. This difference is partially explained with the fact that thicker layer of coating creates internal scattering of light inside the coating. This light hits the photosensor before being absorbed by tissue and thus increases the DC level. A signal processing script was written in MATLAB to calculate the uncalibrated SpO2 from the raw signal. The noise level in all measurements was estimated with the standard deviation since the signal is unambigous and it was concluded that with a moving average filter of 4- or 8-points it is possible to reduce the noise significantly. Thermal radiation of the probe was estimated with test measurement of two different LED drive currents and theoretical calculations, neither case showed any significant increase in temperature. The effect of fat tissue that will surround the implant was also tested in a practical way with cow fat from a local supermarket. According to theory, light penetrates well through fat tissue and this was confirmed with measurements where the increased thickness of fat tissue decreased the amplitude of the signal. By applying a 8-point moving average filter it was possible to acquire a signal through ∼1cm thick layer of tissue with no perfusion. Number of other minor topics were solved some theoretically and others practically. The output of the thesis is a novel device that could be easily implanted in a dairy-cow as well as other mammals. The thesis also presents new information on the effects of coating SpO2 probes and the effects of fat tissue in cattle on the SpO2 signal. Pulse oxygen saturation measurements have not been conducted with an implantable meter before in any type of animal and thus certain uncertainty of measurements can only be eliminated with an implantation of a real device.

Epithelium forms tight membranes that efficiently take part in secretion and absorption between the two lining tissues. A tight membrane of this nature has a low DC conductivity and this is generally used to assess the integrity of cultured epithelium cell layers. Recent studies have shown that impedance spectroscopy gives more information about the electrophysiological structure of the cells. Collaborative research by Department of Biomedical Engineering at Tampere University of Technology and stem cell research group at University of Tampere has shown that electrochemical impedance spectroscopy is useful in assessing the maturity and functionality of differentiated retinal pigment epithelium (RPE) cells. However the time expenditure of the traditional frequency sweeping method is a poor candidate for drug permeability or multichannel studies where several frequency responses have to be measured within a short time. The aim of this Thesis was to develop the front end electronics for fast impedance spectroscopy measurement employing inverse-repeat binary sequence as the broadband excitation signal. Also the DC potential across the cell membrane was to be measured with the device. The developed device was first tested using a custom built test box and plastic film as artificial membrane. In addition several electrode materials were used to study the observed polarization impedances. Further testing with differentiated RPE cell layers was done using the Ussing chamber and the well plate setups that are commonly used in cell culturing studies. All the measured frequency responses were referenced with a commercial device widely used in epithelium research. The observed measurement differences between the device and the reference were largely caused by the load dependent output current of the device and by the electrode polarization taking place at the voltage measurement electrodes. Due to the input current error the relative difference of the measured impedance levels was typically from 5 % to 10 % with load impedances larger than 700 ohms. With lower load impedances the measured relative difference increased rapidly. A method to compensate for the input current error is presented in this thesis. DC potential measurements with the device were not successful as the electrodes used had very high offset voltages. The frequency responses measured with the device give a good measure of the capacitance present in the cell layer. Capacitance of the cell layer can be used to assess the maturity of the cell layer and for such purpose the device suits well. For impedance level measurements the device has a relatively large error margin and further research needs to be done to improve the accuracy and to eliminate the DC current flow. In addition the accuracy of the measurement system would improve by dividing the input stage between the DC potential and frequency response measurements. Also more carefully designed electrodes would help to control the electrode offset voltages. Epiteelisolut muodostavat tiivisliitoksia, jotka ovat tärkeässä roolissa kudosten välillä tapahtuvassa erityksessä sekä absorptiossa. Tiivisliitoksen tasavirtajohtavuus on heikko ja tätä ominaisuutta hyödynnetään yleisesti viljeltyjen epiteelisolukerrosten tiiviyden sähköisessä tarkastelussa. Tutkimukset ovat kuitenkin osoittaneet, että impedanssispektroskopia antaa enemmän tietoa solujen elektrofysiologisesta rakenteesta kuin yksinkertainen resistanssimittaus. Tampereen Teknillisen Yliopiston Biolääketieteen laitos sekä Tampereen Yliopiston kantasolututkimusryhmä ovat yhteistyössä osoittaneet elektrokemiallisen impedanssispektroskopian soveltuvan kantasoluista erikoistettujen retinan pigmenttiepiteelisolujen (RPE) kypsyyden ja toiminnallisuuden arviointiin. Perinteiset taajuuspyyhkäisyä hyödyntävät taajuusvasteanalysaattorit soveltuvat kuitenkin hitaudeltaan heikosti tutkimuksiin, joissa mittauskohteessa tapahtuu nopeita muutoksia tai missä useita taajuusvasteita mitataan lyhyellä aikavälillä. Tämän diplomityön tavoitteena oli kehittää pääteasteen elektroniikka mittausjärjestelmälle, joka hyödyntää laajakaistaista binäärijaksoa herätesignaalina ja mahdollistaa näin huomattavasti nopeamman impedanssispektroskopian. Kehitettävän laitteen tuli myös mitata solukerroksen yli oleva DC potentiaali. Diplomityössä kehitettyä laitetta testattiin aluksi in vitro mittauksia varten kehitetyllä testijärjestelmällä, jossa solukerrosta jäljiteltiin ohuella muovikalvolla. Näissä mittauksissa testattiin myös eri elektrodimateriaalien vaikutus havaittuun polarisaatioimpedanssiin. Viljeltyjen RPE solujen taajuusvasteita mitattiin työssä käyttäen sekä Ussingin kammio- että kuoppalevymittausasetelmia. Laitteella mitattujen taajuusvasteiden hyvyyttä arvioitiin vertaamalla tuloksia kaupallisella taajuusvasteanalysaattorilla mitattuihin vasteisiin. Kehitetyllä laitteella mitattujen vasteiden ero analysaattorilla mitattuihin johtui suurilta osin herätevirran riippuvuudesta kuormasta sekä jännitemittauselektrodien polarisaatioimpedansseista. Yli 700 ohmin kuormilla herätevirrasta aiheutuva virhe oli tyypillisesti 5% – 10 %, kun taas matalimmilla kuormilla virhe kasvoi nopeasti. Tämän virheen kompensoimiseksi on kuitenkin esitetty metodi tässä diplomityössä. Epiteelisolukerroksen yli olevaa DC jännitettä ei onnistuttu mittaamaan johtuen käytettyjen elektrodien korkeista offset-jännitteistä. Tässä diplomityössä kehitetyllä laitteella mitatut taajuusvasteet noudattavat hyvin analysaattorilla mitattujen vasteiden käyrämuotoja ja laite soveltuu täten solukerroksen kapasitanssin arviointiin. Solukerroksen kapasitanssia voidaan käyttää apuna solujen kypsyyden arvioinnissa. Laitteella mitatut impedanssitasot eroavat kuitenkin analysaattorilla mitatuista ja jatkokehitys DC virtojen eliminoimiseksi sekä elektrodien erisuuruisten offset-jännitteiden kompensoimiseksi on suositeltavaa.

Dry eye syndrome (DES) is disease of the eye surface, where tear film is ruptured and lubrication or moistness of the corneal and conjunctival epithelia do not work properly. DES is most common in older people, but also people with rheumatoid diseases, damaged corneal epithelia and certain medications are more likely to have DES. There are lubricating and moisturizing eye drops to relieve the symptoms of DES, administered at least twice a day depending on the severity, but they are only palliative. Eye drops for DES are composed of natural and synthetic origin polymers and their blends. Retaining methods are mainly viscosity and adherence to surfaces by weak interactions. In situ gelation by temperature, pH and osmotic change have been under research in recent years. Many studies have concentrated on ambiphilic polymer conjugates, which fit to the oily and aqueous layer of the tear film and have a better ability to carry a hydrophobic therapeutic drug molecule. Interest has also been pointed to mucoadhesive polymers, which are adhering to mucin by covalent bond. Thiolation of the polymer has been seen as a very promising method to achieve better muchoadhesion and thus has been extensively studied. A chitosan and hyaluronan are natural origin polymers, which have been thiolated and these polymer matrixes can be loaded with trehalose or albumin as therapeutic agent. In this thesis the anatomy of the eye, and especially the corneal and precorneal area and the conjunctiva is discussed. Ethiology of DES and commercial available therapies are covered in this thesis, but also therapies under research and corneal simulation methods in vitro. Kuivasilmäisyys on sairaus, jossa silmän sarveiskalvon pinnalla oleva kyynelkalvo rikkoutuu. Sarveis- ja sidekalvon kosteutus ja voitelu häiriintyvät kyynelkalvo epätasapainosta. Kuivasilmäisyys on ikääntyvien ihmisten sairaus, mutta sitä tavataan myös sarveiskalvovaurio- ja reumapotilailla. Joidenkin lääkkeiden käyttöön liittyy sivuoireina kuivasilmäisyyttä. Kuivasilmäisyyteen on saatavilla kaupallisia oireita lievittäviä silmätippoja, jotka kosteuttavat ja voitelevat silmän pintaa, mutta eivät hoida sairautta. Kuivan silmän tipat on valmistettu luonnon polymeereistä tai synteettisistä polymeereistä, joita annostellaan vähintään kahdesti päivässä. Terapeuttisen vaikutuksen kesto perustuu viskositeettiin tai tarttumiseen silmän pintaan heikoilla sidoksilla. In situ geeliytyminen lämpötilan, pH:n tai suolapitoisuuden muutoksesta on ollut tutkijoiden mielenkiinnon kohteena viime vuosina. Myös polymeerien tarttumista limakalvon pintaan (mukoadheesio) heikoilla vuorovaikutuksilla tai vahvemmilla kovalenttisilla sidoksilla on tutkittu. Amfifiliset polymeerit ovat myös vallanneet alaa, sillä niiden oletetaan sopivan kyynelkalvon pinnan öljykerrokseen ja edelleen sen alla olevaan vesikerrokseen. Amfifilisella polymeerillä on myös kyky kantaa hydrofobista lääkemolekyyliä. Polymeerien tiolointiin ja sen tutkimiseen on panostettu viime aikoina paljon. Tiolointi on menetelmä, jolla parannetaan polymeerin mukoadheesiota. Erityistä mielenkiintoa on herättänyt kitosaanin ja hyaluronihapon tiolointi, jolloin myös terapeuttinen molekyyli, kuten trehaloosi tai albumiini voitaisiin ladata polymeerimatriisiin. Tässä kirjallisuusselvityksessä käsitellään silmän anatomiaa erityisesti kyynelkalvon, sarveiskalvon ja sidekalvon osalta. Tässä opinnäytetyössä on käsitelty kuivasilmäisyyteen johtavia syitä ja nykyisiä sekä kehityksen kohteena olevia hoitomenetelmiä. Lopuksi esitellään sarveiskalvon simulointimenetelmiä, joita on käytetty laboratorio-olosuhteissa.

Because of its superior sensitivity toward soft tissues, including neoplasm, MRI imaging is rapidly becoming one of preferred imaging modality. Improving the sensitivity of MRI for the detection of aggressive lymphomas, DLBCL, is vital in the diagnostic workup, staging and treatment planning. It is also useful for the better understanding of treatment outcomes in the disease follow-up process. In this study, the sensitivity of the four MRI sequences, before and after treatment, in delineating the lesion and evaluating the response to treatment is studied. Eighteen patients with histologically proven DLBCL underwent a 3T MR scanning before treatment, and fifteen of them were re-scanned one week after chemotherapy. The four MRI sequences studied are pre and post contrast enhanced T1-weighted imaging, T2-weighted imaging with and without fat suppression. Before treatment all but one patient had not had T2-weighted fat suppression MRI protocol. The four MRI sequence were quantitatively evaluated based on the normalized mean signal intensity calculated from the measured signal intensities of the lesion and normal tissues. The conspicuity level of the tumor was superior on T2-weighted with fat suppression images both before and after treatment. And these difference were significant (p

The aim of this thesis was to develop methods for future solutions to prevent eye diseases caused by the dysfunctions of retinal pigment epithelial (RPE) cells and to restore the vision of blind patients. On a cellular level, the degeneration of RPE cells is often the prime cause of eye diseases such as age-related macular degeneration and some forms of retinitis pigmentosa. RPE cell replacement therapy may provide new solutions for the prevention of eye diseases that lead to blindness. RPE cells differentiated from pluripotent stem cells provide a promising source for cell replacement therapy. However, the functionality of the differentiated cells is still not fully proven. One objective of this thesis was to provide solutions for testing the functionality of differentiated RPE cells. If blindness cannot be cured, artificial vision provided by retinal implant may be considered. The second objective of this thesis was to characterize the electrochemical properties of the different electrode materials used in retinal implants. The electrode materials used in retinal implants should be carefully considered in order to increase the resolution of the implant and to provide stable, safe, and biocompatible charge injection. All the methods used and developed in this thesis were based on bioelectrical phenomena. The electrochemical characterization of five different electrode materials used in retinal implants used electrical impedance spectroscopy (EIS) and cyclic voltammetry (CV) measurements. We considered the effect of electrode size and material on charge capacity and impedance. Atomic force microscopy (AFM) was used to study the surface properties of the studied electrodes. The testing of the materials was done using exactly the same measurement conditions and electrode producing methods to provide easily comparable data. In this thesis, the functionality of RPE cells differentiated from human embryonic stem cells (hESC-RPE) was studied with two different methods. EIS was used to compare the electrical properties between two different RPE cell lines (immortalized human RPE cell line (ARPE-19) and hESC-RPE). To our knowledge, EIS measurements of RPE cells have not been published before. EIS was also used to find out how the barrier properties of hESC-RPE cells differ when the cells are in different stages of maturity. In addition, we developed a method that could be used to study the functionality of hESC-RPE cells with in vitro electroretinography (ERG) measurements: Our hypothesis is that RPE cells enhance the ERG response of the mouse retina and enable longer culturing of the functional retina in vitro. Comparing the ERG responses of a mouse retina alone and of a mouse retina cultured together with hESC-RPE cells could reveal the functionality of hESC-RPE cells. The EIS measurements were in accordance with biological analyses. The hESC-RPE cells resembled morphologically mature RPE, and thus created high transepithelial resistance (TER) indicating high integrity and tight junction formation. The EIS measurements revealed that during the maturation the TER of the cell culture increases, peak phase diagram shifts to lower frequencies, and the capacitance of the epithelium increases. Permeability measurements verified that EIS measurements reveal the tight junction failures and integrity decrease caused by calcium chelation. With the developed setup we were able to measure ERG responses from both the co-culture of retina and RPE and the retina cultured alone. However, due to limited sample size and possibly due to short co-culture time in our culture setup as yet we were not able to prove the hypothesis by showing that RPE cells would enhance the ERG response of the retina in vitro. Both the retina cultured alone and the co-culture responded to light stimulus after one day of culturing. CV and EIS measurements of different electrodes showed that iridium-black (Ir-b) and platinum-black (Pt-b) electrodes were superior, i.e. they had higher charge injection capacity and lower impedance when compared to other tested materials (gold (Au), titaniumnitrate (TiN), titanium (Ti)). Based on our findings we can conclude that novel biocompatible electrode materials that have the potential to be used in implantation are available. In the same way as in this thesis, the electrochemical testing of electrode materials should be done using similar testing methods for every material to enable easy comparison of the results between different materials. At the moment, cell replacement therapy and the use of RPE cells is seriously considered as a choice for eye disease treatment. Our results suggest that EIS is useful when evaluating the overall maturity, integrity, and functionality of the RPE cell culture. In forthcoming cell transplantation therapies, EIS could provide a means to test the validity of stem cell-derived RPE non-invasively and aseptically before implantation. Our initial tests show that studies to test the ability of RPE cells to rescue the photoreceptors in a mouse model by testing ERG responses in vitro should be continued. Even though our results did not produce conclusive evidence, the co-culture of the retina and hESC-RPE cells may be a useful in vitro model for investigating the RPE cell replacement therapy and possible drug releasing materials for the retina.

In this thesis, a cellular automata based modelling software is developed for studying the electrical activation of cardiomyocytes. The mathematical models help to simulate and study different phenomena related to the cardiac activation. They enable flexible studies for healthy and unhealthy tissue and give a better understanding of the behaviour of the electrical propagation in the heart. The models which are implemented with a graphical user interface are easier to use for inexpert users. This makes these programs very helpful for educational purpose as well as valuable tools for research groups. Nowadays, one of the aspects of the research in the cardiac field is the stem cells. Cardiomyocytes derived from stem cells are being grown in the laboratories to be analysed and used in drug screening. The differentiation of the cells in a particular type is not straightforward. There can be several types of cardiac cells (ventricular, atrial or sinoatrial myocytes) in the same cell culture. Patch clamp is used to discern which types of cells were grown and microelectrodes arrays (MEA) are used to measure the electrical signals produced by the cultures. Patch clamp is costly and time consuming process to identify the cells. The main goal of this master thesis is to study the differences in the simulated electrograms (EGM) from the normal electrodes recordings when the type of cell is changed. If there are quantitative changes the EGM, it could be possible to know a priori which type of cardiomyocyte is present in the culture without having a patch clamp study. The model simulates the electrical activity of cell culture with a cellular automaton based on cardiomyocyte action potential and the conduction velocity curves. These curves are known as restitution curves of the cardiac tissue. It is also needed to model the geometry of the cell culture and the MEA electrodes. This geometry and its lead fields calculated with a finite difference model (FDM) are the inputs for the cellular automata. The cellular automata and the FDM model of the cell culture were successfully performed. The results show that there are differences in the EGM when the action potential of each type of cell is set in the model. The biggest difference is between the contractile cells and the pacemaker ones. The cells could be classified a priori with this study, but in the real life there are more factors that are included and not just one type of cell. There is a need to try in vitro models to check this hypothesis.

According to update of Medical Device Directive (MDD) by European Union in 2007, the software as such can be a medical device. The direct consequence of the change of the directive is, that now depending on the intended use of software, the software might be regulated according to the MDD. If the software is classified to be a medical device, manufacturer has to fulfill the requirements of MDD to get CE mark for software. Most of the requirements are fulfilled by using three standards: IEC 62304 Software life cycle processes, ISO 14971 Application of risk management to medical devices and ISO 13485 Quality management systems. The purpose of the thesis is to discuss the influence of regulation to medical device, classified as software, globally and in Europe and also the influence of three mandatory standards. The risk management standard is processed in more detail and the develop-ment of risk management system is based on it. The risk management system was con-structed according to characteristics of medical standalone software. The goal of the thesis was to model the risk factors in the software environment and build the risk man-agement system around the model. The risk management system is based on the Risk factors model, which is developed in this thesis. In the model, the use of software was divided into seven factors that together or alone could contribute a hazardous situation in using the software. The developed risk management system consisted of four parts: preliminary planning, software development, post-production use and operation, and production and post-production information collecting system. The risk management system is one of the essential requirements to launch new medical device. For a software, which is classified as a medical device there is no established a way to fulfill the regulative requirements of risk management system, because the change in the MDD is new. The thesis presents one approach to fulfill the requirements and produce more safe software. /Kir11

The architecture of tissue engineering scaffold has a strong effect on its functionality. The micro-computed tomography (?-CT) is a non-destructive X-ray irradiation based imaging method which has been widely used in scaffold characterization. The technique enables accurate visualization of the internal structures and morphology in two- and three-dimensions. In addition, image data can be used to calculate numerical values for several structural parameters including porosity and pores sizes. In the present study, the structure of five different types of joint scaffolds was studied using two different CT types. Studied scaffolds are designed for small joint (metacarpophalangeal joint) reconstruction. Imaging was performed using Planmeca ProMax 3Ds cone-beam computed tomography (CBCT) and high resolution SkyScan-1072 desktop fan-beam micro-CT. The main purpose of the study was to assess the suitability of Planmeca CBCT for structural characterization and for quality control of porous scaffolds. Main studied scaffold type was P(L/D)LA 96/4 joint scaffold. Motivation for this study comes from the specific properties of Planmeca CBCT which overcome the general limitations of micro-CT. The device is originally designed for dental imaging allowing fast image acquisition and has also a large measuring field which enables imaging the entire implant structure with a single scan. First goal in the present study was to find out the highest image quality which can be achieved with Planmeca device. In practice, different CT imaging parameters were tested and some of the samples were modified with different contrast enhancement techniques before imaging. The quality of obtained images was visually evaluated and the best images were selected for structural parameter determination. A SkyScan micro-CT was used in a comparative study in order to estimate the reliability of Planmeca CBCT study and to compare the suitability of these two devices for scaffold characterization. The spatial resolution of the SkyScan micro-CT was beforehand known to be significantly better than in Planmeca CBCT. Sample modification studies proved that it is very challenging to improve image contrast and use contrast enhancement techniques non-destructively without causing any structural changes to the scaffold. Without using any contrast enhancement, the CBCT image quality was good enough to apply them for image analysis and determine porosity degree and porosity degree distribution of scaffolds. Also glass content of two types of scaffolds was calculated successfully. Pore sizes (pore diameter) could not be calculated due to complex scaffold architecture and lack of sophisticated image analysis program but total pore volume distribution was determined instead. Quality of Planmeca CBCT images was not the best possible due to still poor accuracy and contrast even though the imaging parameters were optimized carefully. Planmeca CBCT characterization cannot be considered reliable because images did not give realistic overview of the scaffold fibrous structure, unlike the micro-CT images did. The use of Planmeca CBCT in the quality control would still be possible but that would require standardization of the CT imaging parameters and image analysis parameters. Parameter standardization would allow comparing the mutual differences in architectures of parallel samples. /Kir11

Post Mortem Analysis is a software tool built for CERN for hardware commissioning and post mortem event analyzing for the LHC. Magnet Quench Analysis application is a part of the Post Mortem Analysis tool and serves a base for analyzing quench data. It gives a possibility to observe and analyse data collected by the quench protection system. The goal of this work is to study physics phenomena of superconductivity. Quench, quench protection and post quench data are studied in more detail. In addition, it describes how the existing LHC magnet quench analysis was extended to the new Quench Protection System data. Based on the observations from magnet quench analysis, users can determine such parameters as firing times of the triggers and proper operation of the quench protection system. Application was developed using LabVIEW programming language. In this work especially quench detection, energy, location, heater protection and time delays are discussed. It was discovered that automatic quench analysis saves precious time and reduces the need for manual calculations. Biggest problems during the project were found in code modification phase between different LabVIEW versions and programmers. It is possible that further development of the code enhances the possibilities of quench analysis application. Designed methods for dipole magnets can be easily extended for different magnet types such as quadrupoles with changes in the configuration settings. /Kir11

As cone-beam computed tomography (CBCT) is becoming popular in temporal bone imaging, there is a pressing need to improve the quality of images rendered by this device in temporal bone imaging. This prospective cadaver study aims at evaluating the image quality and assessing the changes that result when three different filter combinations, variation in the number of projections, and tube current are used in CBCT temporal bone imaging. The image acquisition was carried out using three filter combinations, Cu-Al, Cu-Cu and Al-Al, with varying thickness and the number of projections was changed from the standard 100% to 150%. Additionally, 8 mA and 12.5 mA were used in all cases. The quality of the acquired images was then qualitatively (visually) and quantitatively (noise analysis) assessed. The visual assessment was carried out by two radiologists with over 20 years’ experience in the field of diagnostic radiology and the noise analysis (standard deviation), an algorithm-based assessment, was done in MATLAB user interface. The results showed that Copper and Aluminum (Cu-Al) filters offered the best image quality when compared with the Cu-Cu (factory-fitted) and Al-Al filter combinations in both visual and algorithm-based assessments. From the results, it was also demonstrated that increasing the number of projections from the standard 100% number of projections to 150% offered a better characterization of the complex temporal bone anatomy in both visual and noise analysis assessments. Finally, changes in the tube current from 8 mA to 12.5 mA resulted in a minimal change of the image quality when visually assessed. However, the effects of the tube current variations increased when the algorithm-based noise analysis was carried out. In conclusion, variations in the material property of the filter, effective filter inter-positioning, and variations in the number of projections optimize the image quality in CBCT temporal bone imaging. /Kir11

This thesis describes the development and evaluation of two portable devices intended for the recording of the electroencephalogram (EEG) in emergency situations. The topic originated from the EEG in Emergency Medicine (EEGEM) project, which seeks to develop the necessary technology and methodology that will help reduce the cost, the preparation time, and the overall complexity associated with EEG nowadays. The work contained herein builds upon the results obtained during previous Master theses that were completed in this project in order to obtain two systems that can be used in to investigate the feasibility and clinical value of EEG in emergency medicine (EM). Before starting the work, a thorough investigation of the EEG signal, which included its origins and its diagnostic potential, was carried out. Existing instrumentation was analyzed as well as factors that influence the quality of the recording. Since the EEG is an established diagnostic tool, it was necessary to follow existing recording guidelines. The recording guidelines of the American Clinical Neurophysiology Society (ACNS) were summarized and employed in the design stages of this study. A review of commercial EEG recorders and quick application EEG caps revealed the absence of an integrated solution for recording this signal in EM. Two systems were developed, one that is able to measure 1 channel of EEG while the other can measure six. The 1-channel system's particularity is that it allows a person's EEG to be displayed on a standard electrocardiogram (ECG) monitor. It features a high input impedance, low noise amplifier that increases the EEG signal's amplitude in order to allow it to be displayed on an ECG monitor. The amount of amplification is dynamically adjusted depending on the peak-to-peak amplitude of the EEG signal. After every gain change, the EEG recording is temporarily interrupted and a sinusoidal signal with an amplitude equivalent to 100 μV at the current gain level is outputted. The user interface is made up of a red, green and blue (RGB) light-emitting diode (LED) unit and a capacitive button that starts/stops the recording. The 6-channel system interfaces with a computer and consists of three parts: a wire-less EEG (WEEG) recording device, a quick-application cap, and recording software that runs on a computer. The WEEG device is able to measure 6 channels of EEG and tri-axial acceleration for the identification of movement artifacts. The recorded data is transmitted to a measurement computer by means of a 2.4 GHz wireless protocol. The author worked with the group from the Department of Automation Science and Engineering (ASE) that developed the previous versions of the device in order to reduce the size of the system and to improve its integration with the measurement computer. An initial prototype of a quick-application electrode cap for out-of-hospital measurements that can be performed by non-EEG specialists was designed by M.Sc. Salmi. It was made up of easily sterilizeable materials that were also elastic. Due to its many straps and adjustment points as well as the floating electrode leads, the band was not easy to apply. This study reports a simplified version of the cap that possesses only two attachment points and can be easily applied even with the patient in the supine position. Also, in the present version, the electrode leads are firmly attached to the cap. The past version of the recording software, which was developed by M.Sc. Pänkälä, had only basic functionality. It displayed the EEG signals, stored them, and allowed the WEEG device to be configured and patient information to be saved. Digital low-pass filtering of the displayed data, the ability to control the vertical sensitivity as well as the time scale, automatic uploading of the recorded file, and an implementation of the aEEG algorithm were added during this thesis. Also, information about the recording can now be stored together with the recorded signals. Furthermore, the software's us-ability was improved by means of a simple graphical user interface (GUI), which makes all functions easily accessible. During the evaluation of the two prototype systems, the electrical and software performance were ascertained. In the electrical tests, the operating time of the device, the common mode rejection (CMR), the frequency response, the noise level, and the signal to noise ratio (SNR) of the two systems were measured. In order to assess the reliability of the software of the two systems, both static and functional tests were conducted. The results obtained from the testing of the systems indicate that they offer similar performance to those offered by commercial EEG recording systems. This demonstrates that they can be used to investigate the clinical indications of EEG in EM. /Kir11

Most severe degenerative diseases of retina are often due to malfunctions of retinal pigment epithelium (RPE). Absence of effective treatments has led to development of cell-biomaterial constructs with the aim of creating RPE equivalents for transplantation. Presently, the poor biocompatibility of allologous and xenologous culture substrata in addition with limited amount of source tissue poses the major issues. Well-defined synthetic substrata together with utilization of human embryonic stem cell-derived RPE cells (hESC RPE) are suggested to be potential solutions. In addition, need exists for an effective method to determine the developmental status of cells during the culturing period. This need could be addressed with automated image analysis. The aim of this thesis was to examine the capability of a few specific cell culture substrata to enable attachment, proliferation and maturation of hESC RPE cells. Study included total of 17 xeno-free synthetic materials including 12 BioMaDe Gelators, Purecoat amine and carboxyl, poly(D,L-lactic-co-glycolic acid) (75:25), poly(D,L-lactic acid) (96:4) and poly(L-lactic acid-co-?-caprolactone) (70:30). In addition five materials with natural-origin were studied including chitosan, type I collagen, Matrigel and Substrate X. Type IV collagen was used as control. Growth and maturation were monitored by taking images with specific time intervals. At the end point cellular developmental status was determined by assessing the expression of maturation specific mRNAs by PCR techniques and proteins by immunofluorescence microscopy. In addition, images were used to determine the potential of ImageJ-software as user-friendly image analysis tool for RPE cell analysis. Study demonstrated poor attachment and cell survival on every xeno-free synthetic substrate with cells retaining their initial developmental phase throughout the culturing period, which was supported by gene expression analysis. On the contrary, cells on natural materials attached and proliferated readily. Maturity was further confirmed with immunofluorescence labeling. Image analysis with ImageJ, in turn, confronted many problems mainly arising from heterogeneity of the images. As a conclusion, xeno-free synthetic materials tested in this study show low potential as RPE cell substrata. However, means to enhance their performance are suggested. Despite the good results obtained with natural materials, their ill-defined structure prone to alterations in physiological conditions remains an obstacle for entering clinical experiments. Further experiments should concentrate on combining the strengths of both approaches, that is, incorporation of attachment-related functional groups into well-defined xeno-free synthetic body. In order to increase image homogeneity imaging conditions should be more carefully considered. This way the benefits of automated image analysis could be more effectively exploited. /Kir11

Magnetic resonance imaging (MRI) is a medical imaging method used mainly for imaging soft tissue, such as the brain. It has various advantages, such as the noninvasive and nonionizing technique used; high contrast and signal-to-noise ratio; and excellent definition of both anatomical and physiological details. Most of the current clinical MRI applications are qualitative. However, to reduce both intra- and interreader variability and thus, possibly, to improve patient diagnosis, treatment, and recovery, advantages may be gained through quantitative means. These include parametric imaging methods, such as T1- and T2-mapping, and analyses, such as histogram analysis, segmentation, and volumetry. These methods, along with qualitative imaging, were studied at various magnetic field strengths in healthy volunteers, non-Hodgkin lymphoma patients, patients with mild traumatic brain injury, and patients with symptoms of Parkinson's disease. Quantitative volumetric analyses using semi-automatic segmentation of both MRI and computed tomographic images were easy and reliable but slow. In the lymphoma patients, the tumor volume was greatly reduced, beginning immediately after the initiation of chemotherapy. A small residual tumor volume six months after the completion of treatment was predictive of survival. Besides percentage volume changes, absolute tumor volumes and their absolute changes during early stages of treatment were considered useful. Several imaging sequences, including both quantitative and qualitative, were correlated with putative iron content. Their clinical correlation and the possibility as early biomarkers of disease progression require further investigation.

Polypropylene is a thermoplastic mass production plastic, which is currently one of the most commonly used plastics. By chemical structure polypropylene is one of the simplest polymers. The simplicity of the structure affects to rather versatile properties of polypropylene. These versatile and modifiable properties of polypropylene are reason for why it is still of interest to researchers. This Master of Science thesis introduces properties of polypropylene in common level. One of the main goals for this thesis was to study sustainability of polypropylene. The sustainability is studied with Life Cycle Assessment. In a Life Cycle Assessment study energy consumptions and greenhouse gas emissions of polypropylene and some other plastics, which are used in mobile phones, were compared. The thesis also gives an overview of biopolypropylene and biorefinery concepts as well as some possibilities of raw materials of biorefinery are introduced. Also market and industry trends of polypropylene now and in the future are considered. By the end the reader will also have a basic knowledge of materials used in mobile phones in general and more specifically about plastics. In plastics are focused plastic materials which might be replaceable with some a polypropylene plastic. At the moment some amount of polypropylene plastics are used in mobile phones, but not in structural parts like covers or frames. Another main goal of this thesis was to examine if polypropylene plastics could be used more in mobile phones than currently and suitability of their manufacturing methods. This was done by comparing plastics and by testing injection moldability of selected polypropylene plastics. The plastics were chosen to injection moldability test by their mechanical properties. Reference materials were plastic materials whose are currently used in mobile phones. The three selected polypropylene plastics were injection molded to mobile phone cover like test pieces. By these test plastics injection moldability and some of their properties, like shrinking, were studied. After the injection molding test it is clear if the selected plastics could be processed to wanted shapes by injection molding. Test pieces mechanical properties suitability for wanted use was not studied with injection molding tests. /Kir11 Polypropeeni on kestomuovi ja se on myös yksi käytetyimmistä muoveista. Kemialliselta rakenteeltaan polypropeeni on yksi yksinkertaisimmista polymeereistä ja tämä suhteellisen yksinkertainen kemiallinen rakenne vaikuttaa polypropeenin monipuolisiin ominaisuuksiin. Nämä monipuoliset muunneltavat ominaisuudet ovatkin syy miksi polypropeeni edelleen kiinnostaa tutkijoita. Diplomityössä polypropeenin ominaisuuksia esitellään yleisellä tasolla. Yksi tämän diplomityön tärkeimmistä tavoitteista oli selvittää polypropeenin ominaisuuksia kestävän kehityksen kannalta. Näitä ominaisuuksia tarkastellaan työssä elinkaaritutkimuksen avulla. Elinkaaritutkimus, joka suoritettiin tätä työtä varten, vertaa polypropeenin ja eräiden matkapuhelimissa käytettyjen muovien energian kulutusta ja tuottamia kasvihuonekaasuja. Tässä työssä esitellään myös biopolypropeeni sekä käsitteenä, että mahdollisena tulevaisuuden materiaalina. Myös biojalostuksen periaate ja joitain sen mahdollisia raaka-aineita esitellään. Työssä tarkastellaan myös sekä polypropeenin nykyiset että tulevat markkinat ja teollisuuden kehityssuunnat. Diplomityössä käsitellään myös materiaalien käyttöä matkapuhelimissa sekä yleisesti että tarkemmin muovimateriaalien osalta. Muovimateriaaleissa keskitytään muoveihin, jotka voisivat olla mahdollisesti korvattavissa polypropeenimuoveilla. Tällä hetkellä polypropeenimuoveja käytetään matkapuhelimissa jonkin verran, muttei rakenteellisissa osissa kuten kuorissa. Toinen tärkein päämäärä diplomityölle onkin selvittää voitaisiinko polypropeenimuoveja käyttää matkapuhelimissa laajemmin kuin nykyisin. Tätä mahdollisuutta tutkitaan vertailemalla muovien ominaisuuksia kirjallisuudesta sekä käytännössä ruiskuvalutesteillä. Ruiskuvalutesteihin muovit valittiin mekaanisten ominaisuuksien perusteella käyttämällä vertailuarvoina joidenkin tällä hetkellä matkapuhelimissa käytössä olevia muovimateriaalien arvoja. Testaus suoritettiin kolmelle polypropeenimuoville ruiskuvalamalla muovit matkapuhelimen kuoren kaltaisiksi testikappaleiksi. Ruiskuvalutesteillä tutkitaan muovien valettavuutta sekä joitain muovin ominaisuuksia, kuten kutistumista. Ruiskuvalutestien tuloksista selviää, kuinka hyvin testatut polypropeenimuovit sopivat halutunlaisten osien tuottamiseen ruiskuvalulla. Nämä testit eivät kuitenkaan kerro sitä, soveltuvatko testikappaleiden mekaaniset ominaisuudet haluttuun käyttöön.

Tässä työssä tehtiin kirjallisuuskatsaus trakeasta kuultavien hengitysäänien instrumentointiin, normaaleihin ja epätavallisiin trakeasta kuultaviin ääniin. Katsauksessa havaittiin, että hengitysäänten rekisteröintiin käytettävien sensoreiden suunnittelulla voidaan vaikuttaa rekisteröityihin ääniin. Erityisesti ilmakytkettyjen kontaktimikrofonien ilmakammiolla voi olla suuri vaikutus mitattuihin ääniin. Normaalien trakeahengitysäänien alkuperä on aeroakustinen. Ilmavirtauksen nopeuden kasvaessa laminaarinen virtaus irtautuu henkitorven seinämästä ja virtaukseen syntyy pyörteitä. Virtaus on muuttunut turbulenttiseksi. Kun nämä pyörteet kulkeutuvat kapeikon läpi, mikä voi olla pelkkä muutos henkitorven poikkipinta-alassa, osa pyörteen liike-energiasta muuttuu akustiseksi häiriöksi. Tämän lisäksi kirjallisuuskatsauksessa tutkittiin epätavallisten trakeasta kuultavien hengitysäänten syntyä. Avoimen, osittain ahtautuneen ja kokonaan ahtautuneen hengitystien tapaukset tarkasteltiin erikseen Sterling-vastusmallin avulla. Kuorsausta ja kudosvärinää havaittiin tilanteessa, jolloin hengitystie oli osittain ahtautunut. Pirkanmaan sairaanhoitopiirin unilaboratoriossa käytetylle trakeaäänien rekisteröintilaitteistolle tehtiin laatumittauksia. Mittauksissa havaittiin, että mikrofonissa oli hieman harmonista vääristymää ja käytetyn äänikortin taajuusvaste ei ollut suora, kun näytteenottotaajuutena oli 11kHz. Yhteenvetona voidaan sanoa, että eri tutkimusryhmien tulisi käyttää laadultaan korkeatasoisia mittalaitteita, kun trakeasta kuuluvia hengitysääniä rekisteröidään. Jos näin toimittaisiin, korkealaatuinen trakea-hengitysääni voisi tuoda uutta tietoa unen hengitysfysiologiaan liittyen. Nykyisessä tilanteessa eri tutkimusryhmien mittaukset eivät ole täysin vertailukelpoisia keskenään ja tämän vuoksi tieteellistä luotettavuutta on vaikea saavuttaa.

During the development of the neural tissue of the nervous system, supporting neuroglial cells and the extracellular matrix (ECM) guide the migration of the immature functional neurons, provide them with a scaffold to grow on and aid in the formation of synapses. ECM provides the neurons with various guidance cues that guide the migration of the neurons and the extension of the neurites. The micrometre and even nanometre guidance cues can also be incorporated into neuronal cultures in vitro to study the effect of the guidance cues and to develop small neuronal networks with a desired architecture. Three-dimensional neurocage structures were fabricated from Ormocomp®, a polymer-ceramic hybrid material, by two-photon polymerisation for this study. In this study these structures were tested with neuronal cells differentiated from human embryonic stem cells (hESC). The neurocages were attached to microscope glass slide samples, each sample containing approximately ten neurocages. The neurocages were first coated with laminin, an ECM protein, to enable the adhesion of the cells to the glass surface. The cell suspension was then applied and the cells were cultured to observe their growth and to study the guidance effects of the neurocages. During the study eight individual experiments were carried out to optimise both the application methods for the laminin solution and the cell suspension and the growth of the cells. This study utilised both simple manual methods and two different micromanipulator set-ups in the application of the laminin solution and the cell suspension. It was concluded that the best method to apply the laminin solution was the micromanipulator set-up SU2, which utilised automated micromanipulator placement and pressure regulation. The cell suspension, on the other hand, could be easily applied onto the samples by placing droplets of the solution onto the medium covering each sample. As the cell population in the culture was small, conditioned medium taken from another neuronal cell culture was tested to increase the viability of the cell cultures of this study. The conditioned medium had a clear positive effect and the use of conditioned medium in future studies is therefore recommended. During the study it was found that the cells initially inside the neurocages did not attach to the glass bottom even when the insides of the neurocages were accurately coated with the laminin solution. In contrast, the cells outside the neurocages generally attached to the glass bottom well and had a tendency to migrate towards the neurocages and over the structure walls into them. Therefore, it was concluded that the material Ormocomp® was not harmful to neuronal cells and it even seemed to attract them. Furthermore, the cells that had migrated into the neurocages readily stayed inside them and extended neurites along the edges of the neurocages. This indicated that the neurite guidance properties of the structures were very promising. /Kir11

Magnetic resonance imaging (MRI) is a valuable tool for medical diagnosis, as it is a non-invasive technique that allows superior visualisation of soft tissues. Because of the vast growth of the acquired information from medical images the development of new computer-aided diagnosis (CAD) systems has become increasingly important. The application of texture analysis (TA) in the diagnostic interpretation of MR images has become a rapidly expanding field of research. The goal of this thesis was to test the feasibility of texture analysis methods in diagnostic radiology. In this dissertation, texture analysis was applied to three different clinical materials. This study investigates whether the texture could be used to discriminate breast cancer and visible and non-visible changes in brain MRI of mild traumatic brain injuries and multiple sclerosis patients and, if so, which is the optimal texture analysis method for these applications. This study showed that TA could provide a quantitative method to aid radiologists in the detection and classification of pathological findings. A case-specific selection of the texture parameters from histogram-, co-occurrence-, run-length- and wavelet- based methods would be the optimal solution for the evaluated clinical applications. However, larger study samples are needed to further validate these findings. Another conclusion was that the texture analysis process should be simplified considerably and implemented in other CAD systems to be considered for clinical use in the future.

In the 21st century the trend in healthcare is towards the early detection and prevention of disease and from hospitalization to increased personalization. The novel wearable and implantable systems for electrocardiographic (ECG) and electroencephalographic (EEG) measurements are being developed to enable monitoring of people during their everyday lives or in emergency situations. The objectives of these novel devices and bioelectrical measurements in general are to register signals arising from a certain region of interest (ROI). The aim might be to direct the measurement to a limited area of the cardiac muscle, such as an apical region of ventricles. This is of particular interest when monitoring different cardiac arrhythmias or changes in activation of a certain segment of the myocardium after infarction. The sensitivity of an ideal measurement should give greater and more intense focus on these target areas than on other areas of the volume conductor, thus yielding more specific and better quality measurements. When designing novel measurement devices and setups it would be beneficial to know where to locate the electrodes in order to measure the target signals and monitor their source regions as efficiently as possible. This is especially important in the application of wearable or implantable measurement systems when there is a limit to the number and location of recording electrodes. The selection of the electrode system should be based on quantitative analysis of certain characteristics such as sensitivity distributions. Because different electrode setups are suitable for different measurement purposes or conditions it would be beneficial to be able to evaluate their sensitivity properties before conducting the actual measurements. The modelling of bioelectric measurements provides an effective means of studying sensitivity distributions. The present thesis introduces a novel quantitative analysis method called region of interest sensitivity ratio (ROISR) for the evaluation of bioelectric measurement setups through the modelling of sensitivity distributions. ROISR is applied to analyse the specificity of EEG and ECG measurement setups to a certain ROI within brain and heart. Using simulations and measurements, the thesis proposes that the ROISR method developed here has a strong correlation to the signal-to-noise ratio (SNR) of a measurement and thus provides an efficient tool for the analysis and development of bioelectric measurement setups. In the thesis the sensitivity distribution analysis is also applied to the analysis of the effects of the dimensions of an implantable ECG device on measurement. The interelectrode distance was found to be the major factor in implant design that determines sensitivity. Other parameters related to implant dimensions have only a minor effect on the average sensitivity of the measurement. It was also observed here that implanting the electrodes deeper under the skin has major effects on the local sensitivities in heart muscle which may affect the morphology of the measured ECG.

Some bioceramics are known to have osteoconductive or osteoinductive potential and excellent bone bonding properties. However, they do not have the required mechanical properties, especially bending properties, to replace bone tissue due to their brittle behavior. Polymeric biomaterials have in many cases more acceptable mechanical behavior, but most of the polymers do not have the properties to facilitate bone tissue healing. Composites of osteoconductive component and polymeric biomaterial could be ideal for bone tissue implant material due to the option to tailor their mechanical properties and osteoconductivity to meet the specific requirements of each application. The main objective of this thesis was to study self-reinforced osteoconductive bioabsorbable composites composed of either bioactive glass 13-93 or -tricalcium phosphate as a filler material and different copolymers of polylactide and polyglycolide as a matrix material. The composites studied were compounded using a twin-screw extruder. The samples containing 0 – 50 weight-% of filler material were further selfreinforced by die-drawing to achieve better mechanical properties and porous structure. By self-reinforcing, for example, the shear strength of the plain matrix polymer poly-L/D-lactide 96/4 could be increased by 150 % at best (from 43 MPa to 120 MPa). Selfreinforcing also made initially brittle samples ductile. Compounding and selfreinforcing together turned out to be a suitable method for achieving a homogeneous filler distribution. Different composite compositions were characterized by determining the changes in mechanical properties, thermal properties, molecular weight, mass loss and water absorption in phosphate buffered saline (PBS) at 37 °C for up to 104 weeks. The bioactivity of certain samples and the changes in pH of the buffer solution were also defined. The results showed that the addition of the osteoconductive filler material impaired the initial mechanical properties of the composites. Osteoconductive filler addition was also observed to modify the degradation kinetics and material morphology of the matrix material. The overall degradation rate of the matrix polymer was observed to be delayed when filler material was added. This was thought to be due to the neutralizing capability of the osteoconductive filler materials. All composites studied exhibited certain degradation behavior depending on the filler and matrix material used and their proportions as well as on microstructural, macrostructural and environmental factors. Thus it is difficult to predict the exact degradation profile for a certain composite composition. The optimal combination of the matrix polymer and the filler material will be largely dependent on the application planned. When the optimal composition of the composite is found, self-reinforced osteoconductive bioabsorbable composites can be considered as a potential implant material for small bone fracture fixations.

Electrical neuroimaging is a contemporary functional imaging method that evolves electroencephalography (EEG) beyond traditional signal analysis. It exploits the millisecond temporal resolution of EEG and integrates it with its spatial resolution, which is mapped according to the measurement sensitivity distribution of the measurement leads. This thesis assesses the EEG measurement sensitivity distribution according to the influence of tissue conductivities, electrode placement, electrode type, and geometries upon volume conductor head models. The conductivity of the skull is correlated with the age of the patient, recognizing that juveniles have higher spatial resolution than adults. Surface electrodes are compared with subdermal electrodes and are found to be non-interchangeable because the subdermal electrodes measure electric activity from one-eighth the volume of their surface-electrode counterparts. More accurate geometrical definitions naturally yield more precise forward and inverse calculations; however, a stochastically deformable generic head model based on anthropometric data addresses the void in imaged and segmented heads of different ages, genders and head shapes. Comprehensively, the investigation of these three key areas improves the knowledge of the EEG measurement sensitivity distributions, which will conceivably translate into clinical improvements in the diagnostics of brain functionality.

At present, elderly people are surfing from dementia and Alzheimer’s disease across the world. The aged population has been increasing and will continue to do so in the coming decades. Those elderly who are suffering from dementia and Alzheimer's disease require continuous attention. So these people need a responsible person (either a nurse or family caretaker) to look after and provide support in any case of emergency. The number of these patients is dramatically increasing. This is difficult to care for them all by hiring a personal caretaker for each patient. Consequently, with the help of electronics and computer technology, scientists currently develop efficient and user-friendly devices that can help look after a patient easily or even remotely. Hence it is possible to look after not only a single patient but also monitor a number of patients at the same time. In this thesis, after a brief study about elderly tracking devices, the limitation was identified, and relevant improvements were suggested for the devices. A survey has been conducted to present the opinion of consumer of LDS Finder and Teltonika HandHeld tracking devices. A website was developed in which relevant information is available regarding the availability of the tracking devices for the elderly.

Local drug delivery devices are advantageous for use in pharmaceutical therapies to control tissue reaction at implant site. Tissue healing and regeneration is a multistep process, control of which is challenging. The presence of a therapeutic dose of several active agents at suitable time frames during tissue healing and regeneration could lead to optimal outcome of the implant. A scaffold where cells can attach and proliferate can considerably enhance the regeneration of tissue. To obtain the suitable dose and release period of drug, the control of the release rate from biodegradable polymeric devices has been based on the degradation behavior of polymer and the diffusion rate of the drug from the polymer matrix. In addition, most of the drug-releasing materials carry only a single agent lacking the possibility for enhanced therapeutic effect. The main objective in this thesis was to manufacture biodegradable drug-releasing composites with controlled drug release. To enhance the tissue ingrowth, three studies of drug releasing nanofiber scaffolds for use as a component in composite are also introduced. In polymer composites, the control of the drug release rate was achieved by a combination of components having different release profiles into one piece, i.e. a multicomponent rod. These rods were intended for use in bone fixation. In addition, studies are presented of the development of multidrug-releasing biodegradable polymer composites in the form of multilayered and multiphase composites. The manufacturing methods of components comprise multiple melt and solvent-based polymer processing techniques (electrospinning, melt extrusion, fiber spinning, compression molding, and emulsion evaporation method). The biodegradable polymers that were used in these studies are based on lactic acid and its copolymers. The selection of active agents was based on the control of inflammatory reactions and hence, they comprised the well-known anti-inflammatory agents, diclofenac sodium and dexamethasone. A third agent, bone-forming bisphosphonate was also loaded in the multilayer composite, which was aimed at bone applications as tissue guiding material. The release kinetics and some explanatory studies on microstructures, thermal properties, and mechanical properties were performed. The results showed that the use of slowly degradable or high molecular weight faster degradable biodegradable polymers in drug-loaded nanofibers can extend the release to almost three months. In addition, with slowly degrading polymer the microstructure was maintained after the drug release. The release from multicomponent rods can be controlled by combining the components with different release profiles. However, the mechanical strength of the rods was unsatisfactory and only one rod type could be used in low stress applications, such as cranio-maxillofacial fixation. In the drug release studies, it was found that the drug release from multilayer composite was dependent on the processing variables. The manufactured multilayer composite had suitable release profiles for possible use in bone guidance applications. The drug release rates from the multiphase fiber composite could be varied by loading agents in different polymer phases, i.e. components, thus offering the possibility to vary the release of different agents as desired.

Electroencephalography (EEG) is a convenient technique for studying the function of the brain non-invasively from the surface of the scalp. The greatest advantages of EEG are its temporal resolution on a millisecond scale and its affordability compared to other non-invasive techniques employed to register brain activity. The development in amplifier technology, computerized signal processing methods and modern EEG caps make the application of multichannel EEG systems a feasible objective. Nowadays measurement systems of up to 256 electrodes and over are available. It is thus important to evaluate the benefits obtained with the multichannel systems when different functions of the brain are being studied. In this thesis two opposite applications of multichannel EEG are investigated. The first of these deals with superficial sources and concerns improving the spatial resolution of inverse cortical potential distribution. The other application concerns the modification of the measurement sensitivity distributions of EEG leads to improve the signal-to-noise ratio (SNR) of signals generated deep within the brain. When studying the spatial resolution of cortical potential distribution, special attention was given to an examination of the effect of measurement noise and relative skull resistivity on the estimation of accuracy of the inverse solution. A three-layer spherical head model was applied with new realistic estimates for skull resistivity. The measurement noise levels were estimated in realistic measurement environments, bearing in mind that when the cortical potential distribution is studied as a solution of the inverse problem, the entire brain activity is considered as the desired signal. The results of the theoretical evaluation show that with the new realistic estimates for relative skull resistivity, the application of up to 128 - 256 electrodes improves the spatial resolution of cortical potential distribution. To improve the SNR of signals generated by deep EEG sources, multielectrode EEG leads were developed. Theoretically a multielectrode EEG lead consists of two terminals, which are both connected through a resistor network to several electrodes on the surface of the scalp. Reciprocity and lead field theorems were applied to modify the sensitivity distribution of a multielectrode lead to be optimal for deep brain sources. The results of preliminary experimental evaluation conducted by studying brainstem auditory evoked potentials show that with a multielectrode EEG lead consisting of 114 electrodes, it is sufficient to average 45 % of the number of epochs needed with bipolar leads to obtain a similar SNR. The results of the theoretical study demonstrate that further improvements can be obtained by such steps as optimizing the electrode positions.

Two-dimensional (2D) mammography plays a most important role in all aspects of breast cancer detection, diagnosis and treatment. Although it is well known that 2D mammography has limitations and it is not capable of detecting all breast cancers, there is no question that mammography is an important imaging technique for detecting and diagnosing breast cancer. Challenges of 2D mammography are structured noise which is created by the overlap of normal dense tissue structures within the breast. This may obscure the findings causing lesions to be missed (reduction of diagnostic sensitivity). Breast tissue may also simulate the presence of a cancer that does not actually exist. This causes a loss of diagnostic specificity. Currently 2D mammography is the only x-ray imaging modality accepted for breast cancer screening, but for years researchers have tried to find improved technologies and new methods to supplement 2D mammography and provide better sensitivity and specificity. Digital breast tomosynthesis (DBT) is a method that was first described many years ago, but could not be easily applied until the development of fast read-out digital detectors. The goal of breast tomosynthesis is to make available a method for screening and diagnostic mammography which provides higher sensitivity and specificity than routine mammography. This study presents digital breast tomosynthesis in diagnostic mammography by comparing digital breast tomosynthesis and screen-film or digital mammograms clinical performance, evaluates Tuned Aperture Computed Tomography (TACT) capability as a 3D breast reconstruction algorithm in the limited angle tomosynthesis system, and demonstrates technical and clinical performance of a real-time amorphous-selenium (a-Se) flat-panel detector (FPD) in full field digital breast tomosynthesis. The analyses of breast tomosynthesis have shown the following clinical benefits: improvement of overall lesion detection and analysis, increased accuracy to either confirm or exclude a suspected abnormality and in particular detection capability of small breast cancers. The results indicate that breast tomosynthesis has the potential to significantly advance diagnostic mammography, as well as screening mammography in the future. Tomosynthesis studies have already shown a promise. Based on this clinical study, tomosynthesis of the breast will increase specificity. Study also suggests that tomosynthesis might facilitate the detection of cancers at an earlier stage and a smaller size than is possible in 2D mammography. Digital breast tomosynthesis is a new breast imaging modality which has proved to have advantages over 2D mammography. Breast tomosynthesis will lead to the earlier breast cancer detection and diagnosis and will keep the false positive rate as low as possible. Keywords: digital breast tomosynthesis (DBT), breast cancer, three-dimensional (3D), tuned aperture computed tomography (TACT), amorphous selenium (a-Se), digital mammography (DM), flat panel detector (FPD)