The study of brain nuclei in neuroimaging poses challenges owing to its small size. Many neuroimaging studies have been reported for effectively locating these nuclei and characterizing their functional connectivity with other regions of the brain. Hypothalamus, Locus Coeruleus, and Ventral Tegmental area are such nuclei found in the human brain, which are challenging to visualize owing to their size and lack of tissue contrast with surrounding regions. Resting-state functional magnetic resonance imaging (rsfMRI) analysis on these nuclei enabled researchers to characterize their connectivity with other regions of the brain. An automated method to successfully isolate voxels belonging to these nuclei is still a great challenge in the field of neuroimaging. Atlas-based segmentation is the most common method used to study the anatomy and the functional connectivity of these brain nuclei. However, atlas-based segmentation has shown inconsistency due to variation in brain atlases owing to different population studies. Therefore, in this study, we try to address the research problem of brain nuclei imaging using a clustering-based approach. Clustering-based methods separate of voxels utilizing their structural and functional homogeneity to each other. This type of method can help locate and cluster the voxels belonging to the nuclei. Elimination of erroneous voxels by the use of clustering methods would significantly improve the structural and functional analysis of the nuclei in the human brain. Since several clustering methods are available in neuroimaging studies, the goal of this study is to find a robust model that has less variability across different subjects. Non-parametrical statistical analysis was performed as functional magnetic resonance imaging (fMRI) based studies are corrupted with noise and artefact. Statistical investigation on the fMRI data helps to assess the significant experimental effects.

For many years, microbubbles have been used as ultrasound contrast agents to improve the quality of diagnostics, seeing that they produce more backscattering ultrasound than blood does. Novel types of microbubbles and increased knowledge about their different behaviors have led to other suggested areas of use. One notable example is the poly-vinyl alcohol (PVA) microbubble, which has been discovered to have a unique fracturing mechanism referred to as the pumping-out behavior. The PVA microbubble has the potential to be used, for instance, in local drug delivery of therapeutic gases, but further studies are needed. In this study, the aim was to develop a tool for imaging the pumping-out behavior of the PVA microbubbles. A linear transducer connected to the programmable Verasonics Research System operated by MatLab software was used to achieve it. The designed ultrasound sequences were tested on a tissue-mimicking phantom containing one vessel filled with PVA microbubbles and one with degassed water. The design was divided into two steps. First, an ultrafast imaging sequence, based on plane waves, was developed to achieve adequate acquisition rate for detecting escaping air from the microbubbles. Furthermore, coherent compounding was implemented to compensate for some of the loss in image quality due to the use of plane waves instead of focused waves. The second step of the design was to combine the imaging sequence with destruction pulses so that the pumping-out behavior could be imaged. The designed ultrasound sequence was evaluated by calculating the mean pixel intensities, contrast-to-tissue ratio (CTR), and contrast-to-noise ratio (CNR) of different regions of interest (ROI) in the acquired images. The results of this project agree with the result previously reported in a study of PVA microbubbles made by Kothapalli et al.. Thus, the developed tool can image the pumping-out behavior. However, further improvements to the imaging tool, such as use of a contrast specific method, is recommended for it to become more reliable and useful. In conclusion, the developed imaging tool works for imaging the pumping-out behavior, but improvements should be made. With a useful imaging tool, further studies can be performed to understand the parameters affecting the pumping-out behavior. In the end, the PVA microbubbles can possibly be used as, for example, local drug deliverers in the clinic.

Successful treatment alternatives for chronic pain conditions are limited. One type of chronic pain that can occur is the condition of phantom limb pain, which can occur after the loss of a limb. Many studies have researched the correlation between chronic pain, tactile acuity, and cortical reorganization. Sensory discrimination training has been shown to improve tactile acuity and be beneficial when trying to reduce the intensity and duration of the pain in chronic pain conditions. A device has been developed by the Center for Bionics and Pain Research, and it is intended to train sensory discrimination. How efficiently this device can train sensory discrimination and how much improvements in the tactile acuity in able-bodied participants can be achieved after using the device have been investigated in this study. 16 able-bodied subjects participated in the study. The subjects received five 40 minutes training sessions on five consecutive days. The assessment of the subjects’ tactile acuity was performed before the first training session and after the last training session. The tactile acuity was also assessed after one to two weeks to determine the long-term effect of the training. There were two psychophysical analyses to determine the participants’ tactile acuity, the two-point discrimination test and the monofilament test. The results showed a significant improvement in the two-point discrimination threshold after the five training sessions, thus showing evidence of the improvement in the tactile acuity after using the sensory discrimination training device. There was no significant improvement in the monofilament test.

Pseudomonas Aeruginosa is an opportunistic bacterium which is involved in nosocomial infections and which causes increasing concern in healthcare due to its high antibiotic resistance. During an infection by P.aeruginosa, the bacteria proliferate in the host’s organism by leveraging motility abilities. One of them, twitching motility, is a surface-specific translocation system. To power twitching, P.aeruginosa performs cycles of extension, attachment, and retraction of Type IV pili (T4P), which are long and thin extracellular filaments. On top of allowing cellular traction, T4P can transmit a signal induced by a contact with a solid surface leading to specific biological responses. In particular, we suspect that T4P retraction is triggered in very short timescales by the attachment of the tip of the pilus to a surface. However, the nature of the signal generated by surface contact, and how it is sensed by the cell, are unknown. The aim of this master project is to gain knowledge on how this machinery is coordinated by the cell upon solid surface contact, and particularly investigate the signal induced by surface contact.  To study T4P behavior during extension and retraction, we used label-free interferometric scattering microscopy (iSCAT), a high time and spatial resolution microscopy technology. We aimed at bringing out T4P movements by attaching bacteriophages on their body and tracking their relative position over extension and retraction events. To do so, we first fabricated microstructures in which we confined the cells in order to improve image quality and increase the odds of binding bacteriophages to T4P. Then, we were able to visualize bindings of DMS3 bacteriophages on T4P. During extension and retraction, we identified phage lateral movements around the pilus axis, which we were unable to see on non-retracting pili. Our results therefore support the hypothesis of T4P helical movements. The nature of the signal generated by tip contact and how it is sensed by the cell remains to be elucidated. Nevertheless, we elevated iSCAT to a new application by visualizing the interaction between T4P and bacteriophages.

Tractography is a tool that is often used to study structural brain connectivity from diffusion magnetic resonance imaging data. Despite its ability to visualize fibers in the white brain matter, it results in a high number of invalid streamlines. For the sake of research and clinical applications, it is of great interest to reduce this number and so improve the quality of tractography. Over the years, many solutions have been proposed, often with a need for ground truth data. As such data for tractography is very difficult to generate even with expertise, it is meaningful to instead use methods like reinforcement learning that does not have such a requirement. In 2021 a deep reinforcement learning tractography network was published: Track-To-Learn. There is however still room for improvement in the reward function of the framework and this is what we focused on in this thesis. Firstly we successfully reproduced some of the published results of Track-To-Learn and observed that almost 20 % of the streamlines were anatomically plausible. Continuously we modified the reward function by giving a reward boost to streamlines which started or terminated within a specified mask. This addition resulted in a small increase of plausible streamlines for a more realistic dataset. Lastly we attempted to include anatomical filtering in the reward function. The produced results were however not enough to draw any valid conclusions about the influence of the modification. Nonetheless, the work of this thesis showed that including further fiber specific anatomical constraints in the reward function of Track-To-Learn could possibly improve the quality of the generated tractograms and would be of interest in both research and clinical settings.

Using a tailored dose distribution for personalized radiotherapy with the help of positron emission tomography (PET) might give an edge for successful tumour elimination. One of the main determinants for tumour radioresistance in several solid tumours has been investigated as hypoxia, including head and neck cancer (HNC). Using novel methods of converting radiotracer uptake into partial oxygen pressure distribution in the form of partial pressure maps, it is possible to delineate the hypoxic region of a target to further escalate the treatment dose there, aiming at an increase in tumour control. However, the registration between functional and structural images may have an impact on the effectiveness of dose escalation, and choosing the correct registration method could be imperative. In this master’s thesis, the impact of choosing rigid or deformable image registration between planning-CT and PET/CT images on the characterization of the hypoxic compartment, as well as on the treatment evaluation in terms of tumour control and normal tissue complication, was assessed. This was achieved by, using hypoxic patients of a cohort of 22 HNC patients, creating a separate plan for each registration method, for each patient, and comparing them quantitatively. The results showed that both methods would yield distinctly different dose distributions when planned using the same objectives and constraints in terms of dose level and shape. Furthermore, they both give a distribution of similar quality. However, using rigid registration together with the deformed PET did not render lower results overall in tumour control. Thus, no advantage could be seen in choosing deformable registration over rigid registration when aiming at tumour control.

Around 10% of women in fertile age have endometriosis, despite this there is little known about its origin. It can take years from the first experienced symptoms to an established diagnosis, which is done using invasive methods. A database from the Lucy application containing 11720 questionnaires with up to 41 questions each was examined for signs of associations between lifestyle factors and health indicators with endometriosis. The database was restructured and unusable questionnaires were pruned, leaving 5719 questionnaires for analysis. Questionnaires were assigned a label depending on whether the respondent had an endometriosis diagnosis, some other diagnosis or no diagnosis. Histograms were created for 36 questions to visualize answer distributions among the labels while wordclouds were created for 3 questions to determine commonly used words. Pearson’s chi-square test was performed on 24 questions to determine whether there were statistically significant differences in how respondents answered with regards to their diagnosis. Then, 26 questions were divided between seven question groups based on their similarities. The relative prevalence of endometriosis for every answer alternative was determined and compared withthe average for that group. This was then followed up by a multi-correspondence analysis for every question group. It was found that there are associations between endometriosis and 12 health indicators. These being: affected by infertility, always being tired, regarding own health as bad, having more than 100 birthmarks, severe chronic pelvic pain, dysmenorrhea, regularly whole-body pain, muscle stiffness, neck and shoulder tension, forgetfulness, concentration difficulties, regularly experiencing that stress worsens physical symptoms. No statistically significant association between lifestyle factors and endometriosis could be found in the survey database. There were findings of socioeconomic differences between respondents with endometriosis and those without a diagnosis which may have affected the result. / Runt 10% av kvinnor i fertil ålder har endometrios, trots detta är lite känt om dess ursprung. Det kan gå flera år från första upplevda symptom till en etablerad diagnos, som kräver invasiva metoder. En databas från Lucy applikationen med 11 720 enkäter upp till 41 frågor vardera undersöktes efter tecken på kopplingar mellan livsstilsfaktorer och hälsoindikatorer med endometrios. Som ett första steg omstrukturerades databasen och oanvändbara enkäter sållades bort, vilket lämnar 5719 enkäter för analys. Enkäterna blev tilldelad en etikett baserad på huruvida respondenten hade en endometriosdiagnos, någon annan diagnos eller ingen diagnos. Histogram skapades för 36 frågor för att visualisera svarsfördelningen mellan etiketter medan ordmoln skapades för 3 frågor för att bestämma vanligt förekommande ord. Pearsons chi-kvadrattest utfördes på 24 frågor för att bestämma huruvida det fanns signifikanta statistiska skillnader i hur respondenter svarade med avseende på deras diagnos. 26 frågor blev uppdelade i 7 olika grupper baserade på deras liknelser och den relativa utbredningen av endometrios bestämdes för varje grupp och jämfördes med snittet i varje grupp. Slutligen följdes detta upp med multikorrespondensanalys för varje grupp av frågor. Det hittades associationer mellan endometrios och 12 hälsofaktorer. Dessa var: infertilitet, alltid vara trött, betrakta sin egna hälsa som dålig, ha fler än 100 födelsemärken, uppleva allvarlig kronisk bäckensmärta, dysmenorré, regelbunden helkroppssmärta, muskelstelhet, spändhet i nacke och axlar, glömskhet, koncentrationssvårigheter, regelbundet uppleva att stress förvärrar fysiska symptom. Ingen statistisk signifikant association kunde hittas mellan livsstilsfaktorer och endometrios från undersökningsdatabasen. Det hittades socioekonomiska skillnader mellan respondenter med endometrios och de utan diagnos vilket kan ha påverkat resultatet. / FEMaLe

Background The aging population, particularly in Sweden, has heightened the need for innovative solutions in long-term elder care. This demographic shift results in a wealth of health data, from vital signs to social interactions. Accurate documentation of this data is crucial for providing effective care. However, there is a lack of systematic understanding of the types of health data collected in Swedish elder care. This study aims to bridge the gap between idealized and actual documentation practices. Methods The method combines literature reviews with qualitative techniques such as interviews, aiming to thoroughly understand the documentation of health data in Swedish long-term care facilities for older adults. By coding and categorizing the content into manageable data, researchers can identify patterns, trends, and relationships within the media being studied. Results Current documentation practices in Swedish long-term elder care were examined, revealing a variety of health data types collected, including personal information, assessments, care plans, and incident reports. Legal guidance from the Social Authority is deemed insufficient by managers, particularly concerning the Act on Coherent Documentation (SVOD).Documentation practices vary among municipalities due to operational differences and municipal autonomy. These findings highlight complexities and gaps, necessitating further research and improvement efforts. Conclusion Within the context of long-term elder care in Sweden, effective documentation practices play a crucial role. However, there is vagueness surrounding the specific health data that should be and is documented. This is what has been revealed in my study, drawing from interviews with multiple informants. While digital documentation offers promise, addressing complexity requires coordinated efforts. Streamlining regulations, enhancing interoperability, and improving usability are essential steps toward improving elder care documentation practices. / Bakgrund Den åldrande befolkningen i världen, och särskilt i Sverige, har ökat behovet av innovativa lösningar inom äldreomsorgen då denna demografiska förändring har resulterat i en ackumuleringen av stora mängder hälsodata. För att kunna tillhandahålla effektiv vård så är det viktigt att den samlade hälsodatan dokumenteras korrekt. Det finns dock en brist i den systematiska förståelsen för vilka typer av hälsodata som samlas in inom svensk äldreomsorg. Syftet med denna studie är därför att undersöka klyftan mellan hur hälsodata bör dokumenteras enligt lagar och regler, och hur det faktiskt dokumenteras i praktiken. Metoder Studien kombinerar dokumentanalyser med intervjuer, och har som mål att djupgående förstå dokumentationen av hälsoinformation i svenska vård-och omsorgsboenden. Genom att koda och kategorisera resultatet från dokumentanalyserna och intervjudata kunde mönster, trender och relationer inom det studerade materialet identifieras. Resultat Nuvarande dokumentationspraxis inom svensk äldreomsorg undersöktes. Resultatet visade att en mängd olika typer av hälsoinformation samlas in, däribland personlig information, bedömningar, vårdplaner och incidentrapporter. Juridisk vägledning från Socialstyrelsen bedöms vara otillräcklig av chefer, särskilt när det gäller lagen om sammanhållen dokumentation (SVOD). Dokumentationspraxis varierar mellan kommuner på grund av operativa skillnader samt det kommunala självstyret. Dessa resultat belyser problemet med hur hälsoinformation dokumenteras och de brister som kräver ytterligare forskning och förbättringsåtgärder. Slutsats Inom ramen för äldreomsorgen i Sverige spelar effektiva dokumentationsmetoder en avgörande roll. Det råder dock oklarhet kring vad för hälsoinformation som bör och faktiskt dokumenteras. Detta är vad som avslöjats i denna studie, baserat på intervjuer med flera informanter. Även om digital dokumentation är fördelaktigt så kräver hanteringen av de påvisade problemensamordnade insatser. Förtydligandet av regelverk, förbättrad interoperabilitet och ökadanvändbarheten är viktiga steg mot att förbättra dokumentationspraxis inom äldreomsorgen.

In Dynamic Contrast Enhanced MRI there are several steps from the initial signal to obtaining the pharmacokinetic parameters for tumor characterization. The aim of this work was to validate the steps in the flow of data focusing on T1-mapping, Contrast Agent (CA)-quantification and the pharmacokinetical (PK) model, using a digital phantom of a head. In the Digital Phantom tissues are assigned necessary values to obtain both a regular and contrast enhanced (using Parker AIF) representation and simulating an SPGR signal. The data analysis was performed in a software called MICE, as well as the Digital Phantom developed at the department of Radiation Sciences at Umeå University. The method of variable flip angles for the T1-mapping was analyzed with respect to SNR and number of flip angles, finding that the median value in each tissue is correct and stable. A "two point" inversion recovery sequence was tested with optimal combination of inversion times for white matter and CSF and obtaining correct T1-values when the inversion times were close to the tissue T1, otherwise with large deviations seen. Three different methods for CA-quantification were analyzed and a large underestimation was found assuming a linearity between signal and CA-concentration mainly for vessels at about 60%, but also for other tissue such as white matter at about 15%, improving when the assumption was removed. Still there was a noticeable underestimation of 30% and 10% and the quantification was improved further, achieving a near perfect agreement with the reference concentration, taking the T2*-effect into account. Applying Kety-model, discarding the vp-term, Ktrans was found to be stable with respect to noise in the tumor rim but ve noticeably underestimated with about 50%. The effect of different bolus arrival time, shifting the AIF required in the PK-model with respect to the CA-concentration, was tested with values up to 5 s, obtaining up to about 5% difference in Ktrans as well as the effect of a vascular transport function obtained by the means of an effective mean transit time up to 5 s and up to about 5% difference in Ktrans.

The use of non-ionizing radiation in the magnetic resonance imaging (MRI) made it a safer diagnostic technique in comparison to the X-ray imaging method. MRI can also produce soft tissue images with a very high contrast without contrast agent which is another advantage that made MRI an important imaging technique for studying the mechanism of the deep brain stimulation (DBS) and for targeting the desired regions in the brain that should be stimulated. For these and other advantages, the number of MRI examinations have increased hugely around the world including Sweden. Despite the consideration that MRI is a safe modality, it is not free from risks and hazards. The radiofrequency (RF)-induced heating of the tissues and the metallic implants is one of the safety concerns in MRI which certainly includes patients with DBS implant.The purpose of this project, motivated by the dangers accompanying the RF-induced heating in implantable DBS lead, is to investigate the effect of the exposure to the RF fields in MRI on these leads. After temperature measurements were made, the observations were focused on the amount of temperature increase, and the time required for the temperature to increase and then to decrease to its initial value. Some factors that could affect the lead temperature were studied and that includes the effect of the lead configuration, the lead surrounding medium, the exposure level, and the orientation of the lead coil with respect to the RF field.The result showed that the temperature of the lead (placed in air) increased more but slower when the lead was formed as a coil than when it was randomly configured. It was also showed that the lead coil temperature rise was higher and faster when the coil was placed in air than when it was immersed in deionized water or in saline. The lead coil temperature rise was higher, but slower when the coil was immersed in saline compared to deionized water. Also, exposure level affected the temperature rise such that the higher exposure level showed higher and faster temperature rise of the lead coil. When the lead coil was placed in air and oriented perpendicular to the strongest magnetic field component, its temperature increased higher and faster. On the other hand, the results when the lead coil was immersed in deionized water or in saline showed a deviation from when it was placed in air such that two magnetic field components had the same effect on the lead coil temperature. The time required for the temperature to decrease to its initial value, after the end of the exposure, depended on the magnitude of the RF magnetic flux density, orientation of the lead coil with respect to the RF magnetic field, and the lead surrounding medium. The stronger RF magnetic field is, the longer time is for the temperature to decrease. Consequently, when the lead coil was directed perpendicularly to the strongest component of the RF magnetic field, it took longer time for the temperature to decrease. The time for the temperature to decrease was longer when the lead coil was immersed in water (deionized or saline) than when the lead coil was placed in air. It also took longer time for the temperature to decrease when the lead coil was immersed in saline than in deionized water.