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Coming theses from other universities

  • Quality assurance for magnetic resonance imaging (MRI) in radiotherapy Author: Mary Adjeiwaah Link: Publication date: 2019-11-08 06:00

    The use of Magnetic Resonance Imaging (MRI) in the radiotherapy (RT) treatment planning workflow is increasing. MRI offers superior soft-tissue contrast compared to Computed Tomography (CT) and therefore improves the accuracy in target volume definitions. There are, however concerns with inherent geometric distortions from system- (gradient nonlinearities and main magnetic field inhomogeneities) and patient-related sources (magnetic susceptibility effect and chemical shift). The lack of clearly defined quality assurance (QA) procedures has also raised questions on the ability of current QA protocols to detect common image quality degradations under radiotherapy settings. To fully implement and take advantage of the benefits of MRI in radiotherapy, these concerns need to be addressed.

    In Papers I and II, the dosimetric impact of MR distortions was investigated. Patient CTs (CT) were deformed with MR distortion vector fields (from the residual system distortions after correcting for gradient nonlinearities and patient-induced susceptibility distortions) to create distorted CT (dCT) images. Field parameters from volumetric modulated arc therapy (VMAT) treatment plans initially optimized on dCT data sets were transferred to CT data to compute new treatment plans. Data from 19 prostate and 21 head and neck patients were used for the treatment planning. The dCT and CT treatment plans were compared to determine the impact of distortions on dose distributions. No clinically relevant dose differences between distorted CT and original CT treatment plans were found. Mean dose differences were < 1.0% and < 0.5% at the planning target volume (PTV) for the head and neck, and prostate treatment plans, respectively. 

    Strategies to reduce geometric distortions were also evaluated in Papers I and II. Using the vendor-supplied gradient non-linearity correction algorithm reduced overall distortions to less than half of the original value. A high acquisition bandwidth of 488 Hz/pixel (Paper I) and 488 Hz/mm (Paper II) kept the mean geometric distortions at the delineated structures below 1 mm. Furthermore, a patient-specific active shimming method implemented in Paper II significantly reduced the number of voxels with distortion shifts > 2 mm from 15.4% to 2.0%.

    B0 maps from patient-induced magnetic field inhomogeneities obtained through direct measurements and by simulations that used MR-generated synthetic CT (sCT) data were compared in Paper III. The validation showed excellent agreement between the simulated and measured B0 maps.

    In Paper IV, the ability of current QA methods to detect common MR image quality degradations under radiotherapy settings were investigated. By evaluating key image quality parameters, the QA protocols were found to be sensitive to some of the introduced degradations. However, image quality issues such as those caused by RF coil failures could not be adequately detected.

    In conclusion, this work has shown the feasibility of using MRI data for radiotherapy treatment planning as distortions resulted in a dose difference of less than 1% between distorted and undistorted images. The simulation software can be used to produce accurate B0 maps, which could then be used as the basis for the effective correction of patient-induced field inhomogeneity distortions and for the QA verification of sCT data. Furthermore, the analysis of the strengths and weaknesses in current QA tools for MRI in RT contribute to finding better methods to efficiently identify image quality errors.

  • Nasal obstruction – impact on insomnia symptoms and sleep-disordered breathing Author: Caroline Bengtsson Link: Publication date: 2019-11-07 10:07

    Background: Nasal obstruction is very common in the general population, but the role of nasal obstruction in sleep quality is not clear. Nasal obstruction is also prevalent in patients with obstructive sleep apnoea (OSA) and may contribute to poor adherence to continuous positive airway pressure (CPAP) treatment.

    Aims: To investigate the impact of subjective nasal obstruction, as a single symptom or as part of chronic rhinosinusitis (CRS), in both objective and subjective sleep quality, in three different population based cohorts. Another aim was to investigate the usefulness of the Sinonasal Outcome Test-22 (SNOT-22) and peak nasal inspiratory flow (PNIF) in the treatment of OSA patients.

    Methods and results: In paper I (the SHE-study), a community-based sample of 400 women were investigated with polysomnography and questions on sleep quality, daytime- and nasal symptoms. Women with nasal obstruction at night (n=30) had significantly higher prevalence of several night time symptoms and excessive daytime sleepiness (EDS), but the polysomnography was normal.

    In paper II (the GA2LEN study, n= 26, 647) and paper III (RHINE II and RHINE III studies, n= 5, 145) questionnaires on sleep quality, daytime- and nasal symptoms were used, and CRS was defined according to the epidemiological diagnostic criteria of the European Position Paper of Rhinosinusitis and Nasal Polyps (EPOS). In paper II, sleep problems were highly prevalent in CRS, and there was a dose-response relationship between the disease severity of CRS and sleep problems. The addition of persistent allergic rhinitis to CRS further increased the risk of sleep problems.

    In paper III, 2.7% of individuals without nasal symptoms at baseline had developed CRS at follow-up 10 years later. Strong associations between incident CRS and impaired sleep quality and EDS were found. Three insomnia symptoms at baseline increased the risk for CRS at follow-up.

    In paper IV, 197 OSA patients initiating CPAP treatment were investigated before starting CPAP and at the follow-up 3-4 weeks later. SNOT-22 scores were generally high among all OSA patients indicating a large sinonasal disease burden, and improved among those with CPAP adherence ≥ 4 hours/night. A low PNIF value increased the risk for poor CPAP adherence.

    Conclusions: Subjective nasal obstruction at night impairs subjective sleep quality in women, but does not affect objective sleep quality. CRS impairs subjective sleep quality, and insomnia symptoms may be a risk factor for CRS. SNOT-22 and PNIF may be useful tools in the treatment of OSA patients.

  • Predictors of Alcohol Misuse : Role of MAOA Genotype, Methylation, Transcription, and Negative and Positive Environmental factors Author: Megha Bendre Link: Publication date: 2019-11-06 08:56

    Alcohol misuse is a risk factor for alcohol use disorder (AUD). Gene-environment interactions contribute to the risk or resilience for AUD. A functional polymorphism in the promoter of the monoamine oxidase A gene (MAOA-uVNTR), in interaction with negative environment (Eneg), is associated with alcohol misuse and AUD. Men carrying short (MAOA-S), and women carrying long (MAOA-L), MAOA-uVNTR alleles who experienced maltreatment or poor parent-child relationships are at increased susceptibility to alcohol misuse and AUD. This thesis assessed whether the association of MAOAxEneg with the risk of AUD is moderated by MAOA methylation or positive environment and whether MAOA methylation-associated changes in MAOA expression in the stress- and reward-related brain regions is an underlying mechanism.

    The thesis reveals that the association of MAOAxEneg with alcohol misuse is moderated by MAOA methylation in men, but not in women. In the clinical sample, men carrying MAOA-S allele who experienced maltreatment and had low MAOA methylation displayed higher alcohol-related problems than those without maltreatment or MAOA-L carriers with and without maltreatment. Furthermore, the quality of the parent–child relationship moderated the association of MAOAxEneg with alcohol misuse in a sex- and AUD stage-dependent manner. In the non-clinical sample of adolescents, girls carrying MAOA-L allele who experienced maltreatment and poor parent–child relationship displayed higher alcohol consumption, whereas those with average or good parent–child relationship had lower alcohol consumption. In the clinical sample of adolescents, however, no such association was observed. These results suggest that a good parent–child relationship protects MAOA susceptibility genotype carriers exposed to maltreatment during the early stages of alcohol use. The preclinical studies revealed that the male rats exposed to Eneg and alcohol had higher CpG-specific Maoa promoter methylation, which was associated with lower Maoa expression in the nucleus accumbens than the control rats. Thus, MAOA methylation-associated changes in MAOA expression in the nucleus accumbens might mediate the effect of environment on alcohol use.

    The thesis contributes to the understanding of biological mechanisms underlying MAOAxEnvironment effect and the critical role of MAOA methylation and positive environment in moderating risk and resilience for AUD. Also, the identification of subgroups may benefit from personalised interventions for AUD.