Prostate cancer is the most common type of cancer in men in Europe and the USA. Some prostate tumours are regarded as stiffer than the surrounding normal tissue, and therefore it is of interest to be able to reliably measure prostate tissue stiffness. The methods presently used to detect prostate cancer are inexact, and new techniques are needed. In this licentiate thesis resonance sensor technology, with its ability to measure tissue stiffness, was applied to normal and cancerous prostate tissue. A piezoelectric transducer element in a feedback system can be set to vibrate at its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various pathophysiological conditions. An impression-controlled resonance sensor system was used to quantify stiffness in human prostate tissue in vitro using a combination of frequency change and force measurements. Measurements on prostate tissue showed statistically significant (p < 0.001) and reproducible differences between normal healthy tissue and tumour tissue when using a multivariate parameter analysis. Measured stiffness varied in both the normal tissue and tumour tissue group. One source of variation was assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces, different levels of dehydration of the prostates, and actual differences between patients. The prostate specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5–1.7 mm, the maximum coefficient of determination was R2 ≥ 0.60 (p < 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. It is concluded that prostate cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differentiate from cancer. Furthermore, the results of this study indicated that the resonance sensor could be used to detect stiffness variations in human prostate tissue in vitro, and especially due to prostate cancer. This is promising for the development of a future diagnostic tool for prostate cancer.

Malignant gliomas grow infiltrative in the brain and can therefore not be completely removed by neurosurgical means. However, for an optimized oncological treatment it has proven useful to resect as much as possible of tumor. The identification of the tumor in the marginal zone is difficult but crucial. Studies have shown that visualization of the specific enhancement of 5-aminolevulinic acid(5-ALA) in the tumor can help to maximize the resection. The Department of Biomedical Engineering, Linköping University, has developed an optical hand-held probe (HHP) to identify tumor tissue with a high sensitivity by means of fluorescence spectroscopy. The technical design and the optical properties of the probe were gradually developed in a standard neurosurgical setting during resection of malignant gliomas. The device could easily be implemented in the operating room, meeting all requirements in terms of sterile handling and without interference of any kind with other equipment. The integration of the device in a navigation system and its use in combination with a blue light surgical microscope were simple. Measurements in 27 operations during resection of malignant gliomas were compared to results from biopsies from the same tumor locations. The equipment was tested as a stand-alone device (n = 180), integrated in a navigation system or in combination with the blue light microscope (n = 190). A ratiocal culated from the measurements enabled objective and comparable values for different tissue types, in correspondence with the findings from the histopathological examinations and in accordance with the navigation system as well as with the surgical microscope.The marginal zone was explored and tumor fluorescence could be identified beyond the fluorescence as seen through the microscope. A higher sensitivity of the HHP was confirmed; the specificity was lower. The combined use of the HHP with a navigation system and with asurgical microscope was beneficial. / Maligna hjärntumörer växer infiltrerande i hjärnan och kan därförinte helt avlägsnas genom kirurgiska operationer. För en optimerad behandling har det emellertid visat sig vara av värde att avlägsna såmycket som möjligt av tumörvävnaden. Identifiering av tumören i gränszonen är mycket svårt, men avgörande. Studier har visat att visualisering av den specifika laddningen av 5-aminolevulinsyra (5-ALA) i tumören kan bidra till att maximera resektionen. Institutionen för Medicinsk Teknik (IMT) på Linköpings universitet,har utvecklat en liten handhållen optisk prob (HHP) för att identifiera tumörvävnad med hög känslighet med hjälp avfluorescens-spektroskopi. Den tekniska konstruktionen och de optiska egenskaperna hos proben utvecklades stegvis genom testning i flera neurokirurgiska operationer för resektion av maligna gliom. Utrustningen uppfyllde alla krav när det gällde steril hantering i operationssalen och kunde användas utan störningar av något slag med annan operationsutrustning. Integreringen i ett navigerings-system och användningen i kombination med ett kirurgiskt mikroskop för fluorescens-styrd kirurgi var oproblematiska. Mätningar under 27 operationer vid resektion av maligna gliom jämfördes med resultat från biopsier från samma tumörtagningsställen. Utrustningen testades såväl som en fristående enhet (n = 180) och som integrerad i ett navigationssystem eller i kombination med mikroskopet (n =190). En särskild kvot beräknad ur mätningarna möjliggjorde objektiva och jämförbara värden för olika vävnader, i överensstämmelse med resultaten från de vävnadspatologiska undersökningarna och i överensstämmelse med navigationssystemet såväl som med det kirurgiska mikroskopet. Tumörernas gränszon undersöktes och tumörfluorescens kunde identifieras bortom fluorescensen som mikroskopet visade. En högre känslighet hos HHP bekräftades; specificiteten var lägre. Den kombinerade användningen av HHP med ett navigationssystem och med ett kirurgiskt mikroskop visade sig vara fördelaktig.

Det är känt att humant trombocytantigen (HPA) kan innebära komplikationer vid transfusion av trombocyter. Om en patient erhåller trombocyter med humant trombocytantigen som personen redan utvecklat antikroppar emot kan komplikationer som feber, påskyndad nedbrytning av trombocyter som ger trombocytopeni samt post-transfusion purpura uppstå eftersom immunförsvaret då ser trombocyterna som fientliga. Från den 14:e veckan under graviditeten kan alloantikroppar från modern passera placentabarriären över till fostret. Om humant trombocytantigen skiljer mellan moder och foster kan modern utveckla antikroppar. Dessa antikroppar kan då förstöra fostrets trombocyter. Detta leder till en lägre koncentration av trombocyter hos barnet. I värsta fall kan detta leda till hjärnblödning med dödlighet på ca.20%. Om barnet överlever födseln kommer denne födas med fetal/neonatal alloimmuniserad trombocytopeni (FNAIT), d.v.s. medfödd trombocytopeni. Målet med denna studie var att utveckla en multiplex PCR-screen, snabbt positivt/negativt svar för högfrekventa Humant trombocytantigen alleler baserat på de mest frekventa som förekommer i dansk befolkning: HPA 1a, -2a, -3a, -5a, -15a och -15b med Extract-N-AmpTMblood kit. Negativa prov från screening genomgick allelic discrimination real-tids PCR för konfirmering av sann HPA- genotyp. En lyckad multiplex screenmix innehållande HPA 1a, -2a, -5a samt -15a genomfördes. Då HPA - 3a bildade ospecifika band fick denna plockas bort ur mixen. För HPA 15b bildades ingen PCR- produkt och kunde därför inte inkluderas. Totalt screenades 44 blodgivare från Region Skåne varav fyra var negativa för 15a. Detta konfirmerades med allelic discrimination där dessa genotypades till 15b och i likhet med den multipla screeningen inte visade amplifiering av 15a. Vidare optimering krävs där nya primers för 3a samt 15b måste designas för att skapa en komplett högfrekvent human trombocytantigen screen.

Fasplattorna i transmissionselektronmikroskop (TEM) används i dagsläget för att förbättra kontrasten men har vissa nackdelar som, till exempel, bidrag av brus och låg upplösning. En eventuell lösning till detta problem är en elektronfasplatta som utnyttjar fältpotentialen hos en extern elektronstråle som skapar en potentialövergång för TEM:ets primära elektronstråle vilket skiftar dess fas. Målet med detta projekt var att designa en elektronkanon genom att simulera ett elektrostatiskt linssystem som skall skapa en elektronfasplatta med en viss ström och stråltjocklek. Designen av dessa linssystem gjordes i CAD-programmet Solid Edge och simuleringarna utfördes i COMSOL Multiphysics. Från simuleringarna framgår det att det är möjligt att designa en elektronkanon som kan skapa en elektronfasplatta med stråltjockleken ~1,8 µm och strömmen ~10 µA. Simuleringarna visade dock att en förflyttning in i mikroskopet inte var möjligt för elektronkanonen eftersom elektronfasplattans stråltjocklek inte kunde bevaras. Slutsatserna var, för att lyckas förflytta elektronfasplattan måste partikelinteraktioner i elektronstrålen och sfäriska aberrationer för linserna minskas genom att antingen byta till magnetiska linser eller implementera CS-correctorer. / The problem with today’s phase plates in transmission electron microscopes (TEM), that are used to improve contrast, are their noise contributions and low resolution. A potential solution to this problem is an electron phase plate which utilize the field potential of an external electron beam that creates a potential crossing for the primary electron beam in the TEM and hence shifts their phase. The aim of this project was to design an electron gun by simulating an electrostatic lens system that should produce an electron phase plate with a certain current and crossover. The lens system design was created in the CAD-software Solid Edge and the simulations were performed in COMSOL Multiphysics. The simulations showed that it is possible to design an electron gun which is able to produce an electron phase plate with a crossover of ~1,8 µm and a current of ~10 µA. The simulations however showed that the electron gun was unable to transfer the electron phase plate into the microscope whilst maintaining its crossover size. The conclusions were, to successfully transfer the electron phase plate, the particle interactions in the electron beam and the spherical aberrations of the lenses must be reduced either by changing to magnetic lenses or by implementing CS-correctors.

The long-term performance of TAH pumps needs to be demonstrated. Reliability tests are performed to measure its ability to operate for months, or years, without failure. Real Heart is currently constructing test rigs for this purpose. Software for documenting test rig conditions is also required. Thus, the objective of this study is to assist in developing reliability test rig software.  The software is written in LabVIEW and is hosted on a CompactRIO controller. Requirements include sampling of sensor data, logging, and alarms. Additionally, a PC dashboard is constructed for monitoring real-time data, reviewing logs, as well as controls for acquisition. Results of this study present a foundation for the test rig software. It features a modular architecture which allows for future scalability. The process of development involves research of hardware/software, establishing a reference design and to build and validate each module through test simulations. Data acquisition is set up with the NI-DAQmx API. It features automatic configuration for thermocouple, as well as custom signal scaling of the pressure and flow transducers. However, grouping of data and synchronization for logging and alarms was a challenge. The producer/consumer design pattern is implemented for grouping data as well as synchronization for logging and alarms. / Det artificiella hjärtats långsiktiga prestanda måste demonstreras. Tillförlitlighetstester utförs för att mäta pumparnas förmåga att fungera i månader eller år utan att gå sönder. Real Heart bygger för närvarande testriggar för detta ändamål. Programvara för att dokumentera testriggens förhållanden behövs också. Därför är syftet med denna studie att hjälpa företaget med att utveckla programvara för tillförlitlighetstestriggar.  Programvaran är skriven i LabVIEW och används på en CompactRIO-kontroller. Den kommer inkludera provtagning av sensordata, loggning och alarm. Dessutom är en PC-instrumentpanel konstruerad för övervakning av realtidsdata, granskning av loggar samt kontroll av datainsamling. Resultaten av denna studie utgör en grund för testriggens programvara. Den har en modulär arkitektur som möjliggör framtida uppskalning. Utvecklingsprocessen involverar studier av hårdvara/programvara, upprättande av en referensdesign, samt att bygga och validera varje modul genom testsimuleringar. Datainsamling genomförs med NI-DAQmx API. Den har automatisk konfiguration för temperatur, samt anpassad signalskalning av tryck- och flödesgivare. Designmönstret producent/konsument implementerades för gruppering av data, samt synkronisering för loggning och alarm.

Ventricular Assist Devices (VADs) are mechanical pumps used to off-load a deceased heart, primarily in late stage congestive heart failure patients. VAD employment may facilitate cardiac recovery, but most often provides time before a suitable heart transplant can be found. Lately, long term use VAD systems have been introduced as an alternative to a heart transplant. Traditionally, design of VADs has employed either displacement based pump technologies or radial-flow pumps, also known as rotodynamic pumps. A displacement pump induces a mechanical force on a fluid contained within a defined space, hence giving it motion. Radial-flow pumps impart momentum to a fluid, most often by placing a rotating device in the fluid. This thesis introduces a novel pumping concept, combining features from both displacement and radial-flow pumps. A first prototype, the VivicorTM pump, has been designed, fabricated and evaluated In Vitro, the results reported in this thesis. The In Vitro evaluation of the VivicorTM pump provides evidence of a pump with mechanical self-regulation based on pump pre-load level, much like a displacement pump. The VivicorTM pump also displays pulsating outflow in combination with an inflow both during pump systole and diastole. The latter provides potential advantages over traditional displacement pumps as smaller cannulae or catheters can be used, facilitating miniaturization. Continuos filling throughout the pumping cycle also require less pressure to be exerted on the fluid, compared to displacement pumps, limiting the risk of mechanical damage to the pumped fluid. The In Vitro evaluation has also provided further insights on necessary design modifications in the second-generation VivicorTM prototype, currently planned. The VivicorTM pumping technology is highly interesting for further development and evaluation for use in ventricular assist applications. / QC 20101129

Several signal processing approaches have been developed to overcome the effect of stray capacitances in Electrical Bioimpedance Spectroscopy (EBIS) measurements. EBIS measurements obtained with textile-enabled instrumentation are more vulnerable to stray capacitances. Currently, the most widespread approach for correcting the effect of stray capacitances in EBIS is the time delay ( Td) compensation method, which also has several drawbacks. In this study, the Td method is revisited and its limitations and its lack of a scientific basis are demonstrated. To determine better ways to overcome the effect of stray capacitances, a simplified measurement model is proposed that is based on previous models of artefacts in EBIS measurements described in the literature. The model consists of a current divider with a parasitic capacitance (Cpar) in parallel with the load. Cpar creates a pathway for the measurement current to leak away from the load, provoking a capacitive leakage effect. In this thesis, three approaches with different limitations are proposed to overcome the capacitive leakage effect. The first approach estimates Cpar and subtracts it from the measurements, thus finding the load. Cpar can be estimated because the susceptance of biological tissue is null at infinite frequency. Therefore, at high frequencies, the susceptance of the tissue can be neglected, and the slope of the susceptance of the measurement is Cpar. The accuracy of Cpar depends on the maximum frequency measured and the value of Cpar. Therefore, it may not be possible to accurately estimate small values of Cpar in the typical frequency ranges used in EBIS. The second and third approaches use the Cole fitting process to estimate the Cole parameters, which form the basis for most EBIS applications. Because the conductance of the measurement is free from the effect of Cpar, performing Cole fitting on the conductance avoids the effect of Cpar in the fitting process. With a poor skin-electrode contact, this approach may not be sufficiently accurate. The third approach would be to perform the Cole fitting on the modulus with a reduced upper frequency limit because the modulus and the low-medium frequencies are very robust against the effect of artefacts. In this approach, a slight capacitive leakage effect is unavoidable. Since it is common to find tainted measurements, especially among those obtained with textile-enabled instrumentation, it is important to find viable methods to avoid their effect. The three methods studied showed that they could reduce the effect of tainted measurements. / QC 20120313

Fat intra-body communication is a newly proven concept that is built on using human fat tissues as a communication channel for electromagnetic waves inside the body. This allows for two implanted external devices to connect through an intra-body closed-loop communication channel. This concept utilizes the fact that the fat tissues have low dielectric properties and are located between two tissue layers, skin and muscle, which have high dielectric permittivity and high loss tangent so that the signal propagates and confines with lower losses within the fat tissue. In this study, the eligibility of using monkey fat tissues as a communication channel for intra-body communication is being investigated. This comes as a first step in a long process of testing implementing medical devices, mainly prosthetic limbs, on non-human primates using fat-IBC at microwave frequencies. To be able to do that, an experimental characterization of ex-vivo monkey fat, skin, and muscle tissues to explore their dielectric properties compared to those of humans is being carried out. This study of the dielectric properties of monkey tissues is the first of its kind to be carried out on two samples of ex-vivo monkey tissues. Calf tissues have also been investigated in the study to get an insight on the potential differences between human and non-human body tissues in general before doing measurements on monkey tissues. For the measurements, an RF network analyzer and an open-ended coaxial probe method have been implemented. Phantoms that mimic the human tissues have been fabricated to be used as a reference point. The initial investigation demonstrates that calf fat tissues have much higher dielectric properties than human fat tissues. Monkey fat, muscle, and skin tissues showed many similarities to human tissues regarding their dielectric properties. This indicates that monkey tissues can be used for fat intra-body communication. Future numerical and analytical modeling of the monkey tissues needs to be conducted to confirm and strengthen this finding.

A rupturing abdominal aortic aneurysm (AAA) has a mortality rate of 50% while an elective repair has a mortality rate of 3-8%. Screening programmes with ultrasound are used in some countries to detect AAA at an early stage. Ultrasound is however very observer bias and dependent on the observer's experience. The study was performed in Vietnam, a country that have experienced exceptional economic growth with increasing risk factors for cardiovascular diseases but has no national screening programme. The aim of this study was to examine the interobserver variability when measuring the abdominal aorta with ultrasound on young adults in Vietnam. The abdominal aorta was measured in the longitudinal and the transverse axis by two different observers using the leading edge to leading edge method. Participants in this study were 31 voluntary students, 16 men and 15 women in the ages 18-26 years, from the Da Nang university of medical technology and pharmacy and the design was a cross-sectional study with a quantitative approach. The study showed a significant difference between the longitudinal measurements but not between the transverse measurements. Despite this statistical significance, the observers' differences were within the recommended limit of 5 mm. / Ett rupturerande bukaortaaneurysm har en dödlighet på 50% medan förebyggande vaskulär kirurgi har en dödlighet på 3-8%. Screeingprogram med ultraljud används i vissa länder för att upptäcka bukaortaaneurysm i ett tidigt skede innan de rupterar. Ultraljudsundersökningen är dock väldigt beroende på utövarens erfarenhet och utbildning. Studien genomfördes i Vietnam, ett land som genomgått stor ekonomisk tillväxt men även en ökning av riskfaktorer för kardiovaskulära sjukdomar. Vietnam har dock inget nationellt screeningprogram för bukaortaaneurysm. Syftet med studien var att undersöka observatörsvariationen vid mätning av bukaortan med ultraljud på unga vuxna i Vietnam. Populationen var ung för att minska patologiska fynd. Bukaortan mättes med metoden leading edge to leading edge, både i det longitudinella och i det transversella snittet av två olika utövare. Observatörerna var två studenter från Biomedicinska analytikerprogrammet med inriktning klinisk fysiologi, Jönköpings Universitet. Deltagare i studien var 31 frivilliga studenter, 16 män och 15 kvinnor i åldrarna 18-26 år, från Da Nang University of medical technology and pharmacy och designen var en tvärsnittsstudie med kvantitativ ansats. Studien visade en signifikant skillnad i de longitudinella mätningarna men inte i de transversella mätningarna. Trots denna statistiska signifikans var observatörernas differenser inom den rekommenderade gränsen på 5 mm.

This thesis presents a real time software program written in MATLAB using off-the-self MEMS sensors from Shimmer-Research®. Parallel to the software development, a proof of concept was conducted using the produced program to quantify stride length, stride length variance and stride time for patients diagnosed with Parkinson's disease. Results from testing showed that the system measured the mean stride length error to 2.4% of stride length and a standard deviation of 13.7% of stride length. Results from testing further showed a stride time error of 2.70% of individual stride times with a standard deviation of 1.89%. The system shows promise as a pedagogical, gait analysis training tool for physiotherapists as well as in academic teaching. The system is flexible and data processing functions can be readily re-programmed with other or additional processing features while maintaining user feedback, storage and plotting functionalities implemented in the current version of the program.