Background: Brain tumour is a disease that can affect the life of the patient, both physically and mentally. Relatives to the patient of brain tumor lives with an uncertainty about how the disease will develop and affect their loved one, which leads to a dramatic change of their everyday life. Method: A qualitative, manifest content analysis with an inductive approach based on biographies. Aim: The aim of this study is to describe women’s experiences of living with a brain tumor. Findings: The result showed that the female patients experienced suffering in living with a brain tumor since they were affected both physically and mentally. To feel dependent on others and to not identify with who you had become, was strong signs on their changed everyday life. Even though these women experienced suffering they could feel hope and gain strength from their surroundings and their relatives. Conclusion: Women that live with brain tumor narrates experiences of difficult changes but also feelings of well-being during the entire course of the disease. These women experienced well-being whenever they accepted the disease, when they got support from their relatives and whenever their feelings where confirmed by the professional carers. All of these aspects contributed to these women’s well-being. / Bakgrund: Hjärntumör är en sjukdom som kan medföra en livsförändring hos patienten med både psykiska och fysiska förändringar. Närstående till de som är drabbade av hjärntumör lever med en stor ovisshet kring hur sjukdomen kan utveckla sig och påverka den sjuka vilket leder till en kamp i deras förändrade vardag. Metod: En kvalitativ, manifest innehållsanalys med en induktiv ansats utifrån självbiografier. Syfte: Syftet är att beskriva kvinnors upplevelser av att leva med en hjärntumör. Resultat: Resultatet visade att kvinnorna upplevde stora motgångar av att leva med hjärntumör då dess konsekvenser tedde sig i både fysiska och kognitiva svikter. Att uppleva ett beroende av andra och att inte längre vara sig lik var starka tecken på de kvinnliga patienternas förändrade vardag. Trots motgångarna upplevde kvinnorna en hoppfullhet och fann kraft i sin omgivning. De närstående till kvinnorna hade en stor betydelse för dem. Slutsats: Studien påvisar att kvinnor som är drabbade av hjärntumör skildrar upplevelser av svåra förändringar men även av välbefinnande under sin sjukdomsperiod. Acceptansen av sjukdomen samt närståendes stöd och vårdens bekräftelse är faktorer som bidrar till välbefinnande trots hjärntumören.

Complex network models of functional connectivity have emerged as a paradigm shift in brain mapping over the past decade. Despite significant attention within the neuroimaging and cognitive neuroscience communities, these approaches have hitherto not been extensively explored in neurosurgery. The aim of this thesis is to investigate how the field of connectomics can contribute to understanding the effects of focal brain lesions and to functional brain mapping in neurosurgery. This datasets for this thesis include a clinical population with focal brain tumours and a cohort focused on healthy adolescent brain development. Multiple network analyses of increasing complexity are performed based upon resting state functional MRI. In patients with focal brain tumours, the full complement of resting state networks were apparent, while also suggesting putative patterns of network plasticity. Connectome analysis was able to identify potential signatures of node robustness and connections at risk that could be used to individually plan surgery. Focal lesions induced the formation of new hubs while down regulating previously established hubs. Overall these data are consistent with a dynamic rather than a static response to the presence of focal lesions. Adolescent brain development demonstrated discrete dynamics with distinct gender specific and age-gender interactions. Network architecture also became more robust, particularly to random removal of nodes and edges. Overall these data provide evidence for the early vulnerability rather than enhanced plasticity of brain networks. In summary, this thesis presents a combined analysis of pathological and healthy development datasets focused on understanding the functional effects of focal brain lesions at a network level. The coda serves as an introduction to a forthcoming study, known as Connectomics and Electrical Stimulation for Augmenting Resection (CAESAR), which is an evolution of the results and methods herein.

M.A. / Primary malignant brain tumours (PMBTs) are devastating diagnoses that result in the swift deterioration of neurological functioning. The life expectancy of the patient from the time of diagnosis is between three and 12 months. This illness trajectory is characterised by loss of functional abilities such as walking, talking and writing; increasing cognitive impairments such as loss of executive functioning, speech difficulties and problems with comprehension; and the presence of neuropsychiatric symptoms such as depression, anxiety, apathy and aggression. Since treatment is primarily palliative rather than curative, family members and specifically spouses are required to care for PMBT patients in the home setting. The daily challenges of caring for a spouse with a PMBT have a significant impact on the emotional functioning of the caregiver. Although other studies have examined the experiences of various family members of PMBT patients, this research is the first phenomenological study, which investigates the emotional experiences in particular, with a focus on female spouses of PMBT patients. Other studies have also failed to describe the experience of caregivers throughout the entire course of the illness trajectory, that is, from pre-diagnostic symptoms, until the time of death. Therefore, this study attempts to enter the life-world of female spouses of PMBT patients in order to describe their emotional experiences from the time that prediagnostic symptoms manifested, throughout the disease trajectory, and until the death of the patient. A descriptive phenomenological method of enquiry was chosen to achieve this end. Three female spouses of PMBT patients were sourced and interviewed for the purposes of this study. Their husbands had passed away from a PMBT approximately three years prior. Open-ended interviews were conducted in order to elicit their emotional experiences during their husbands’ illness trajectory. The interviews were transcribed verbatim with the inclusion of non-verbal cues where relevant. This data was then analysed using a sequential phenomenological approach. Common themes were integrated to form the essential structure of a female spouse’s emotional experience of her husband’s PMBT illness. These themes were also discussed in conjunction with the literature review to support their validity. The themes that emerged fell within four distinct time periods. The period before diagnosis, at diagnosis, during the course of the illness and at the time of death. Themes that emerged during the research interview were found to be pertinent and were also discussed.

Manual segmentation of brain tumours is a time consuming process, results often show high variability, and there is a call for automation in clinical practice. In this thesis the use of deep convolutional networks for automatic glioma segmentation in MRI is investigated. The implemented networks are evaluated on data used in the brain tumor segmentation challenge (BraTS). It is found that 3D convolutional networks generally outperform 2D convolutional networks, and that the best networks can produce segmentations that closely resemble human segmentations. Convolutional networks are also evaluated as feature extractors with linear SVM classifiers on top, and although the sensitivity is improved considerably, the segmentations are heavily oversegmented. The importance of the amount of data available is investigated as well by comparing results from networks trained on both 2013 and the greatly extended 2014 data set, but it is found that the method of producing ground-truth was also a contributing factor. The networks does not beat the previous high-scores on the BraTS data, but several simple improvement areas are identified to take the networks further. / Manuell segmentering av hjärntumörer är en tidskrävande process, segmenteringarna är ofta varierade mellan experter, och automatisk segmentering skulle vara användbart för kliniskt bruk. Den här rapporten undersöker användningen av deep convolutional networks (ConvNets) för automatisk segmentering av gliom i MR-bilder. De implementerade nätverken utvärderas med hjälp av data från brain tumor segmentation challenge (BraTS). Studien finner att 3D-nätverk har generellt bättre resultat än 2D-nätverk, och att de bästa nätverken har förmågan att ge segmenteringar som liknar mänskliga segmenteringar. ConvNets utvärderas också som feature extractors, med linjära SVM som klassificerare. Den här metoden ger segmenteringar med hög känslighet, men är också till hög grad översegmenterade. Vikten av att ha mer träningsdata undersöks också genom att träna på två olika stora dataset, men metoden för att få fram de riktiga segmenteringarna har troligen också stor påverkan på resultatet. Nätverken slår inte de tidigare rekorden på BraTS, men flera viktiga men enkla förbättringsområden är identifierade som potentiellt skulle förbättra resultaten.

Bakgrund: Varje år drabbas cirka 1200 personer av hjärntumör. En hjärntumör påverkarpatienter fysiskt- och psykiskt. Det kan innebära allvarliga symtom, biverkningar avbehandling samt en förändrad livssituation. För att underlätta vården behöver patienterförklara deras upplevelser. Syfte: Att sammanställa och belysa forskning som beskriverpatienters upplevelser av vård vid hjärntumör. Metod: Litteraturöversikt av tolvvetenskapliga artiklar som analyserades enligt analysgranskning för litteraturöversikt.Resultat: Resultatet framkom tre teman: 1. Behov av kontinuerligt stöd och information 2.Mötet som är avgörande för ett meningsfullt liv 3. Uppleva utanförskap. Subteman var: 1.Att uppleva behov av att erhålla information; Att uppleva behov av stöd 2. Att få en godvårdrelation och kommunikation; Osäkerhet och rädsla i vårdmöten 3. Uppleva bristandedelaktighet; Att förlora sin autonomi Konklusion: Stöd och en god, trygg vårdrelation krävsför att patienter ska uppnå gott välbefinnande. God och individualiserad information behövsnär de fysiska- och psykiska förändringarna sker för patienten. Känslor av utanförskap ochförlorad autonomi drabbar patienterna. Kliniska implikationer: Studien belyser patientersupplevelser av vård vid hjärntumör. Sjuksköterskor får i denna studie ökad kunskap ochförståelse för hur dessa patienter bör vårdas i syfte att ge en god omvårdnad med respekt förpatientens rätt till självbestämmande och välbefinnande. / Background: Every year, around 1,200 people suffer from brain tumors. A brain tumor havephysical as well as psychological affects on these patients. It can cause serious symptoms,side effects of treatment and a changed life situation. To facilitate care, patients need toexplain their experiences. Aim: To compile and illustrate research that describes patientsexperiences of care when suffering from a brain tumour. Method: Literature review oftwelve scientific articles that were analyzed according to the method of analysis for literaturereview. Result: The result revealed three themes: 1. The need for continuous support andinformation. 2. The meeting that is crucial for a meaningful life. 3. To experience exclusion.The subthemes were: 1. To experience the need of obtaining information; To experienceneeds of support. 2. To acquire a good caring relationship and communication; Insecuritiesand fear of care meetings. 3. To experience lack of participation; To lose their autonomy.Conclusion: Support and comforting, safe caring relationship is required in order forpatients to experience appropriate well-being. Kind and individualised information arerequired when the physical and psychological changes takes place for the patients. Feelingsof exclusion and lack of autonomy affects patients. Clinical implications: This studyillustrates the patients experiences of care when suffering from a brain tumour. In this studynurses achieve increased knowledge and understanding about how these patients should becared for in order to provide good care with respect for the patients right of self determinationand well-being.

The pediatric population is highly impacted by brain tumours, as they are the most common type of solid tumour affecting children. Medical advances have improved the survival rate of children with brain tumours, but many survivors still experience late effects. In adulthood, 18% of pediatric brain tumour (PBT) survivors have reported cardiovascular issues such as strokes, blood clots, and angina, but little is known about the cardiovascular health of these survivors during childhood. The primary objective of this thesis was to measure the proportion of PBT survivors with values of body mass index (BMI), waist circumference (WC), and aerobic fitness meeting the cut-offs associated with unfavourable cardiovascular health (BMI≥+2 SDs, WC≥90th percentile, and % peak oxygen uptake (VO2peak) predicted<85%). The secondary objective was to observe the effects of 12 weeks of exercise training on the BMI, WC, blood pressure (BP), and aerobic fitness of PBT survivors and describe the feasibility of an exercise training program for this population. In this thesis, 32 PBT survivors who had all received cranial radiation were included (age=12.3±3.4 years, age at diagnosis=7.0±2.5 years, time since treatment completion=4.5±2.8 years, 21/32 male). While WC was measured for 13/32 participants, BMI and aerobic fitness were measured for all. Of the participants, 5/32 children completed a 12-week pilot exercise program consisting of two group and two in-home exercise sessions per week. A control group (n=2, age=14.8±3.6 years, 1/2 male) and an intervention group (n=5, age=15.0±2.3, 3/5 male) had BMI, WC, BP, and aerobic fitness measurements taken pre- and post-training. Of the participants, 15.6% (5/32) had a BMI≥+2 SDs, 30.7% had a WC≥90th percentile, and 86.7% had a %VO2peak predicted<85%. In total, 81% (26/32) of the participants had at least one identified biomarker reflecting unfavourable cardiovascular health. A training effect was only observed in BP (change of +9%). The exercise program was feasible with an adherence rate of 88% (21/24) to the group and in-home sessions. All (5/5) participants completed the program without injuries or adverse events during the training program. Findings from this thesis indicate that 81% brain tumour survivors have at least one biomarker indicating unfavourable cardiovascular health in childhood. This thesis also provides novel information to be considered before implementing exercise as a therapy for improving the cardiovascular health of survivors. Future additional research is required to determine the appropriate duration, frequency, and intensity of aerobic exercise to stimulate a training effect on these cardiovascular biomarkers. / Thesis / Master of Science (MSc)

<p>Bmi1 is a member of the Polycomb Group proteins and has been demonstrated as being vital in stem cell regulation. Bmi1 is overexpressed in many cancers, including glioblastoma, and has been shown to regulate cancer cell self-renewal and proliferation both <em>in vitro</em> and <em>in vivo</em>. This study aimed to determine if Bmi1 modulates brain tumour initiating cell properties using a spontaneous primary glioblastoma cell line and a commercial glioblastoma cell line. To determine the role of Bmi1 in glioblastoma cells, stem cell assays and <em>in vivo</em> analysis of tumour formation was performed on both control cells and Bmi1 knockdown cells. In both cell lines, Bmi1 was found to play a positive regulatory role in stem cell properties. When Bmi1 was knocked down in brain tumour initiating cells, properties such as self-renewal, proliferation and tumour formation were impaired compared to control cells. This study supports recent literature which shows that Bmi1 regulates stem cell properties in glioblastoma cells and supports the potential use of Bmi1 as a therapeutic target in glioblastoma brain tumours.<strong><br /> </strong></p> / Master of Science (MSc)

<p><strong>Background</strong>: Health-related quality of life (HRQL) studies have inconsistently identified a burden of pain in survivors of brain tumours in childhood, with limited exploration of this morbidity.</p> <p><strong>Objective: </strong>To explore the HRQL, with a focus on pain, in survivors greater than 10 years from diagnosis of a primary brain tumour in childhood or adolescence.</p> <p><strong>Methods:</strong> A cross-sectional study was undertaken using Health Utilities Index (HUI) questionnaires. Location of pain was queried using a homunculus and a colour-analog scale facilitated the reporting of severity. Single-attribute HRQL scores for participants with and without pain were compared. Stability of pain over a decade was established using available HUI2/3 data from the same cohort with imputation for missing variables.</p> <p><strong>Results:</strong> Twelve males and 13 females out of 37 eligible subjects participated in this study. Participants (mean time from diagnosis of 19.7 years) had mean multi-attribute HRQL scores of 0.79 (SD of 0.23) for HUI2 and 0.69 (SD of 0.29) for HUI3. Thirteen (52%) participants reported pain, with ranges in severity and location of the discomfort. Participants with pain had considerably greater burdens of morbidity in sensation and emotion than those without pain. Pain also increased from the initial interview (10 years prior) to the final interview.</p> <p><strong>Conclusion:</strong> As a group, long-term survivors of brain tumours in childhood have diminished overall HRQL. However there is variability between subjects. Pain appeared to be a persistent and significant burden in a subset of individuals, with those experiencing pain reporting greater severity of morbidities in other attributes.</p> / Master of Science (MSc)

Glioblastoma (GBM) is a very aggressive and invasive tumour that relapses within nine months of diagnosis and remains incurable despite advances in multimodal therapy including surgical resection, chemotherapy and radiation. Poor patient outcome has been correlated to specific markers of brain tumour initiating cells (BTIC) and intratumoural heterogeneity (ITH), which have also been associated with treatment resistance and tumour recurrence. ITH can be explained at the cellular level by the existence of multiple populations of cancer cells, including some which have acquired stemness properties like self-renewal, proliferation, and multilineage differentiation, also known as cancer stem cells (CSCs). In brain tumours, CSCs or BTICs, have been shown to be resistant to both chemotherapy and radiation treatment, allowing them to escape therapy and consequently generate for tumour recurrence. As a result, therapies that focus on targeting the BTIC compartment within the bulk GBM tumour would provide better treatment and prognosis for patients. To profile GBM BTICs we conducted two transcriptomic screens. The first compared GBM BTICs to neural stem cells (NSCs), their healthy counterparts, and for the second we developed a pipeline utilizing a dynamic BTIC patient-derived xenograft (PDX) model of human GBM recurrence allowing for the profiling of GBM BTICs at engraftment, after chemoradiotherapy delivery in a phase we have termed "minimal residual disease" (MRD), and at tumour recurrence. In this study, Dickkopf-1 (DKK1) was identified as a potential therapeutic target for GBM from each transcriptomic screen and was studied using short hairpin knockdowns, blockade with monoclonal antibodies, and subsequent functional stem cell assays. / Thesis / Master of Science (MSc) / Glioblastoma (GBM) is a very aggressive tumour that relapses within nine months of diagnosis and remains incurable despite chemotherapy, radiation, and surgery. Relapse is believed to be caused by the presence of a wide variety of cell types, including cancer stem cells (CSCs), which have been shown to be resistant to both chemotherapy and radiation in GBM. As a result, therapies that focus on targeting the CSCs within the bulk GBM tumour would provide better treatment for patients. In this study, we analyzed this cell population by conducting two screens. The first compared the level at which genes are expressed in GBM CSCs in comparison to how they are expressed in their healthy counterparts, neural stem cells, whereas the second compared the primary patient GBM tumour to its relapsed form in a mouse model of the disease. In this study, the protein Dickkopf-1 (DKK1) was identified and validated as a potential therapeutic target of GBM using well established molecular and stem cell functional assays.

<p>Brain tumour can be a chronic disease that affects individuals in many aspects. The course of events in the disease, the treatment and prognosis has an effect on the physical, as well as mental and social health and therefore influences individuals’ quality of life and wellbeing. The aim of this study was to describe the experience of quality of life and living with a brain tumour as an adult. A descriptive systematic literature study was used to analyze eleven scientific articles. The analysis resulted in four categories, physical changes involves difficulties in the daily life, emotional distress involves suffering, to feel anxiety at the thought of death and feel the need of social support. The result showed that people that lived with a brain tumour were submitted to changes that had a negative effect on their daily life. They experienced an emotional distress and suffering that further added in a negative way on their daily life. The constant threat of death leads to a feeling of death anxiety. To be able to cope with their everyday life and manage the process that the disease brought it was important to have social support and understanding from their next of kin and surroundings. The knowledge about this disease and the consequences it has for the single individual contributes to a greater understanding for the person that is affected. Further research about experiences amongst people that lives with serious diseases is necessary so that they get treated adequately and get help and understanding within the care system. This literature study shows that people who lived with brain tumor experienced sadness and depression that made its mark on daily life. Together with constant worries and the mental fatigue brought these problems to each individual.</p> / <p>Hjärntumör kan vara en kronisk sjukdom som påverkar människan på många olika sätt. Sjukdomens förlopp, behandling och prognos inverkar på den fysiska psykiska och sociala hälsan och därmed påverkar människors livskvalitet och välbefinnande. Syftet med denna litteraturstudie var att beskriva upplevelse av livskvalitet och att leva med hjärntumör hos vuxna människor. En beskrivande systematisk litteraturstudie användes för att analysera de elva vetenskapliga artiklarna. Analysen resulterade i fyra kategorier: fysiska förändringar medför svårigheter i det dagliga arbetet, känslomässig påfrestning innebär lidande, att känna dödsångest och att känna behov av socialt stöd. Resultatet visade att människorna som levde med hjärntumör var utsatta för förändringar som hade inverkan på det dagliga livet. De upplevde en känslomässig påfrestning och lidande som ytterliggare negativt påverkade livskvalitet. Det ständiga hotet om döden skapade känsla av dödsångest. För att kunna klara av vardagen och gå igenom den processen som sjukdomen förde med sig var det viktigt att känna socialt stöd och förståelse från närstående och omgivningen. Kunskapen om denna sjukdom och vilka konsekvenser den har för den enskilde individen bidrar till ökad förståelse för den drabbades livssituation. Vidare forskning om upplevelser hos människor som lever med svåra sjukdomstillstånd är nödvändig för att de människorna ska få adekvat bemötande, hjälp och förståelse i vården. Denna litteraturstudie visar att människor som levde med hjärntumör upplevde nedstämdhet och depression som präglade det dagliga livet. I kombination med ständig oro och den mentala tröttheten medförde det problem för den enskilda människan.</p>