During resting state the brain exhibits synchronized activity within all major brain networks. Using blood oxygen level dependent (BOLD) resting state functional magnetic resonance imaging (fMRI) based detection it is possible to quantify the degree of correlation, connectivity, between regions of interest and assess information regarding the integrity of the inter-regional functional integration. A newly available multiband echo planar imaging (EPI) fMRI sequence allows for faster scan times which possibly allows us to better examine large-scale networks and increase the understanding of brain function/dysfunction. This thesis will assess how the newly developed sequence compares to a conventional EPI sequence for detecting resting state connectivity of canonical brain networks. The data acquisitions were made on a 3 Tesla scanner using a 32 channel head coil. The hypothesis was that the multiband sequence would produce a better result since it has faster sampling rate, thus more data points in its time-series to support the statistical analyses. Using Pearson’s linear correlation between the average time-series (approximately 12 minutes long) within a seed-region and all voxels contained in the image volume, correlation maps where created for each of the eight participants using data normalized to Montreal Neurological Institute (MNI) space. The resting state networks (RSN) were then found by performing a one sample T-test on group level. Six seed-coordinates, based on literature, where used revealing the the homotopic connections in anterior Hippocampus, Motor cortex, Dorsal attention, Visual and the Default mode network (DMN) as well for an anterior-posterior connection in the DMN. By comparing the maximum T-values within the regions for the RSN no systematic difference could be found between the multiband and conventional fMRI data. Further tests were conducted to evaluate if the sequences would differentiate in their results if the acquisition time was shortened, i.e shortening the time-series in the voxels. However no such difference could be established.Importantly, the results are specific to the 32 channel head coil used in the current study. Presumably recently available and improved coil designs could better exploit the multiband technique.

There is a need for quantitative CT data in radiation therapy. Currently there are only few algorithms that address this issue, for instance the commercial DirectDensity algorithm. In scientific literature, an example of such an algorithm is DIRA. DIRA is an iterative model-based reconstruction method for dual-energy CT whose goal is to determine the material composition of the patient from accurate linear attenuation coefficients. It has been implemented in a two dimensional geometry, i.e., it could process axial scans only.  There was a need to extend DIRA so that it could process projection data generated in helical scanning geometries. The newly developed algorithm (DIRA-3D) implemented (i) polyenergetic semi-parallel projection generation, (ii) mono-energetic parallel projection generation and (iii) the PI-method for image reconstruction. The computation experiments showed that the accuracies of the resulting LAC and mass fractions were comparable to the ones of the original DIRA. The results converged after 10 iterations.

This thesis investigated whether a deep learning model could learn features of Chaos,from the Chaos & Clues evaluation protocol, in a given dermatoscopic image data set. Asuccessful result could be of use in a future decision-support system for when dermatologists examine skin lesions for traces of melanoma (type of skin cancer). The chosen deep learning model (Inception V3) was trained to recognise four classesrelated to Chaos. Anonymous patient data was used, provided by the partnering companyGnosco. The data was partitioned into one or two classes depending on the symmetryproperties found in the corresponding image annotation. More than twenty differentmodel configurations was run to obtain the results in this thesis. The results indicate that the chosen model was not capable of learning features of Chaosfrom the dermatoscopical image data-set. Training the model to recognise features ofChaos resulted in an overfit system with low validation accuracy (close to 30%). The prediction target was changed to contrast the negative results from the Chaos classification. The chosen model was therefore configured to learn two classes, ’melanoma’ and’nevus’. This prediction target yielded a more positive result as the validation accuracywas close to 85%. However, the corresponding confusion matrix showed that these resultsare not trustworthy. It is inconclusive whether the negative results from the Chaos classification stem from thechosen approach or if the data set was insufficient for the task-difficulty. We propose adjustments to the data set for future work which could disclose if the outlined approach isviable or not.

Over 30 000 liver, abdomen, and thigh slices have been acquired by computed tomography for the SCAPIS and IGT study. To utilise the full potential of the large cohort and enable statistical pixel-wise body composition analysis and visualisation of associations with other biomarkers, a point-to-point correspondence between the scans is needed. For this purpose, an inter-subject image registration pipeline that combines the low-level information from CT images with high-level information from segmentation masks have been developed. It uses tissue-specific regularisation and processes images efficiently. The pipeline was used to deform 4603 CT scans of each slice into a respective common reference space in less than 30 hours. All but the ribs in the liver slices and the intra abdominal region of the abdomen were generally registered correctly. Vector and intensity magnitude errors indicating inverse consistency were on average less than 2.5 mm and 40 Hounsfield units respectively. The method may serve as a starting point for statistical pixel-wise body composition analysis, its association with non-imaging data, as well as saliency mapping analysis of the three-slice CT scans from the large SCAPIS and IGT cohorts.

Malignant melanoma is the deadliest form of skin cancer. If correctly diagnosed in time, the expected five-year survival rate can increase up to 97 %. Therefore, exploring various methods for early detection can contribute with tools which can be used to improve detection of disease and finally to make sure that help is given in time. The purpose of this work was to investigate the performance and behavior of different convolutional neural network (CNN) architectures and to explore whether presegmenting clinical images would improve the prediction results on a binary classifier system. For the purposes of this paper, the two selected CNNs were Inception v3 and DenseNet201. The networks were pretrained on ImageNet and transfer learning techniques such as feature extraction and fine-tuning were used to extract the features of the training set. Batch size was varied and five-fold cross-validation was applied during training to find the optimal number of epochs for training. Evaluation was done on the ISIC test set, the PH2 dataset and a combined set of images from Karolinska University Hospital and FirstDerm, where the latter was also cropped to evaluate presegmentation. The achieved results for the ISIC test set were AUCs of 0.66 for Inception v3 and 0.71 for DenseNet201. For the PH2 test set, the AUCs were 0.82 and 0.73. The results for the Karolinska and FirstDerm set were 0.49 and 0.42. Presegmenting the latter test set resulted in AUCs of 0.58 and 0.51. In conclusion, quality of images could have a big impact on the classification performance. Batch size seems to affect the performance and could thus be an important hyperparameter to tune. Ultimately, the Inception v3 architecture seems to be less affected by different variability why selecting this architecture for a real-world clinical image application could be more suitable. However, the networks performed much worse than state of the art results in previous papers and the conclusions are based on rather inconclusive results. Therefore more research has to be done to verify the conclusions. / Malignt melanom är den dödligaste formen av hudcancer. Om en korrekt diagnos sätts tillräckligt tidigt kan den femåriga överlevnadsgraden uppgå till 97 %. Detta gör att forskningen efter metoder för tidigarelagd upptäckt kan bidra med verktyg som i sin tur kan användas till att upptäcka sjukdom och slutligen bidra till att hjälp sätts in i tid. Målet med detta arbete var att undersöka prestanda och beteende för olika faltningsbara neurala nätverk (CNN) och att undersöka ifall försegmentering av kliniska bilder kunde förbättra resultaten i ett binärt klassificeringssystem. De utvalda faltningsbara neurala nätverksarkitekturerna var Inception v3 och DenseNet201. Nätverken var förträanade på ImageNet och "Transfer-learning"-metoder som feature extraction och fine-tuning användes för att extrahera features från träningsuppsättningen. Batch size varierades och femtalig korsvalidering användes för att hitta det optimala antalet träningsepoker. Utvärderingen gjordes med bilder i testset från ISIC, PH2 och Karolinska och FirstDerm. Bilderna i den senare datamängden beskärdes för att utvärdera försegmenteringen av kliniska bilder. De uppnådda resultaten för ISIC testmängden var AUC-värden på 0.66 för Inception v3 och 0.71 för DenseNet201. För PH2 låg AUC-värdena på 0.82 respektive 0.73. Resultaten för testmängden med bilder frön Karolinska och FirstDerm var 0.40 och 0.42. Försegmenteringen av den sistnämnda testmängden gav AUC-värden på 0.58 och 0.51. Sammanfattningsvis kan bildkvalitet ha en stor inverkan på ett nätverks klassificeringsprestanda. Batch size verkar också påverka resultaten ochkan därför vara en viktig hyperparameter att stämma. Slutligen verkar Inception v3 vara mindre känslig för olika typer av variabiltet vilket görvalet av denna arkitektur mer lämplig ifall en riktig applikation ska byggas för detektion av exempelvis kliniska bilder. Det som bör understrykas i detta arbete är att resultaten var mycket sämre än det som bäst uppvisats i föregående rapporter och att slutasatserna är baserade på relativt ickeövertygande värden. Därför efterkrävs mer forskning för att styrka slutsatserna.

Magnetic resonance imaging (MRI) is a powerful imaging tool for diagnostics, which AMRA uses to segment and quantify certain anatomical regions. This thesis investigate the possibilities of using deep learning for the particular task of AMRAs segmentation, both for ordinary regions (fat and muscle regions) and injured muscles.The main approach performs muscle and fat segmentation separately, and compares results for three approaches; a full resolution approach, a down-sample approach (trained on down-sampled images) and an ensemble approach (uses voting among the 7 best networks).The results shows that deep learning segmentation is possible for the task, with satisfactory results. The down-sampled approach works best for fat segmentation, which can be related to the inconsistently over-segmented ground truth fat masks. It is therefore unnecessary with the additional resolution, which might only impair the performance. The down-sampled approach achieves better results also for muscle segmentation. Ensemble learning does in general not improve the neither the segmentation dice score nor the biomarker predictions. Injured muscles are more difficult to predict due to smaller muscles in the particular used dataset, and an increased data versatility. As a summary, deep learning shows great potential for the task. The results are overall satisfactory (mostly for a down-sampled approach), but further work needs to be done for injured muscles in order to make it clinically useful.

Glaucoma, a leading cause of blindness worldwide, results in gradual vision loss if untreated due to retinal ganglion cell degeneration. Optical coherence tomography (OCT) machine measures retinal nerve fiber layers and the optic nerve head (ONH), with Považay et al. introducing the Pigment Epithelium – Inner limit of the retina Minimal Distance Averaged Over 2π Radians (PIMD-2π) for quantifying nerve fiber cross-sections. PIMD, defined as the distance between the Optic nerve head Pigment epithelium Central Limit (OPCL) and the Inner limit of the Retina Closest Point (IRCP), shows promise for earlier glaucoma detection compared to visual field assessments. The objective of this research is to enhance the Auto-PIMD program for calculating PIMD lengths in OCT images, aiding healthcare professionals in diagnosing glaucoma. Originally based on the 2D U-Net framework, this study proposes a replacement of the deep learning model framework and introduces a novel experimental procedure aimed at refining the accuracy of OPCLs calculation. Leveraging the nnU-Net model, commonly employed for semantic segmentation in medical imaging, the computational process entails segmenting vitreous masks and OPCLs. Utilizing a dataset of 78 OCT images provided by Uppsala University, experiments were conducted in both cylindrical domain (using 2D U-Net and nnU-Net cylindrical architecture) and Cartesian domain (nnU-Net Cartesian architecture). Qualitative and graphical analysis of the obtained OPCLs coordinate points demonstrates the nnU-Net frameworks' ability to yield points close to true voxel values(mean Euclidean distance of nnU-Net cylindrical architecture: 1.665; mean Euclidean distance of nnU-Net Cartesian architecture: 2.4495), contrasting with the higher uncertainties of the 2D U-Net architecture(mean Euclidean distance: 10.6827). Moreover, the nnU-Net Cartesian architecture eliminates human bias stemming from manual ONH center selection for cylindrical coordinate expansion. Examination of PIMD length calculations reveals all three methods effectively distinguishing between glaucoma patients and healthy subjects, with the nnU-Net-based methods displaying greater stability. This study contributes to refining OPCLs coordinate point accuracy and underscores the potential of the Auto-PIMD program in glaucoma diagnosis. / Glaukom, som är en av de främsta orsakerna till blindhet i världen, leder till gradvis synförlust om det inte behandlas på grund av degeneration av ganglieceller i näthinnan. Med optisk koherenstomografi (OCT) mäts nervfiberlagren i näthinnan och synnervshuvudet (ONH), och Považay et al. introducerade Pigmentepitel - Näthinnans inre gräns Minimal Distance Averaged Over 2π Radians (PIMD-2π) för att kvantifiera tvärsnitt av nervfibrer. PIMD, definierat som avståndet mellan den centrala gränsen (OPCL) för optikusnervhuvudets pigmentepitel och den inre gränsen för näthinnans närmaste punkt (IRCP), visar lovande resultat för tidigare upptäckt av glaukom jämfört med synfältsbedömningar. Syftet med denna forskning är att förbättra Auto-PIMD-programmet för beräkning av PIMD-längder i OCT-bilder, vilket hjälper vårdpersonal att diagnostisera glaukom. Denna studie, som ursprungligen baserades på 2D U-Net-ramverket, föreslår en ersättning av ramverket för djupinlärningsmodellen och introducerar ett nytt experimentellt förfarande som syftar till att förfina noggrannheten i OPCL-beräkningen. Med hjälp av nnU-Net-modellen, som ofta används för semantisk segmentering inom medicinsk bildbehandling, innebär beräkningsprocessen segmentering av glaskroppsmasker och OPCL. Med hjälp av ett dataset med 78 OCT-bilder från Uppsala universitet genomfördes experiment i både cylindrical domän (med 2D U-Net och nnU-Net cylindrical arkitektur) och kartesisk domän (nnU-Net kartesisk arkitektur). Kvalitativ och grafisk analys av de erhållna OPCL-koordinatpunkterna visar att nnU-Net-ramverken kan ge punkter som ligger nära sanna värden(genomsnittligt euklidiskt avstånd för nnU-Nets polära arkitektur: 1,665; genomsnittligt euklidiskt avstånd för nnU-Net kartesisk arkitektur: 2,4495), i motsats till de högre osäkerheterna i 2D U-Net-arkitekturen(genomsnittligt euklidiskt avstånd: 10,6827). Dessutom eliminerar den kartesiska arkitekturen i nnU-Net mänsklig partiskhet som härrör från manuellt val av ONH-centrum för polär koordinatexpansion. Granskning av PIMD-längdsberäkningar visar att alla tre metoderna effektivt skiljer mellan glaukompatienter och friska försökspersoner, där de nnU-Net-baserade metoderna uppvisar större stabilitet. Denna studie bidrar till att förbättra noggrannheten i OPCL:s koordinatpunkter och understryker potentialen i Auto-PIMD-programmet vid glaukomdiagnos.

MRI is used to produce images of tissue in the body. DTI, specifically, makes it possible to track the effects of nerves where they are in the brain. This project includes a shell script and a guide for using the FMRIB Software Library, followed by StarTrack and then Trackvis in order to track difficult areas in the brain. The focus is on the trigeminal nerve (CN V). The method can be used to compare nerves in the same patient, or as a comparison to a healthy brain.

A personalized cardiovascular lumped parameter model of the left-sided heart and thesystemic circulation has been developed by the cardiovascular medicine research groupat Linköping University. It provides information about hemodynamics, some of whichcould otherwise only have been retrieved by invasive measurements. The framework forpersonalizing the model is made using 4D Flow MRI data, containing volumes describinganatomy and velocities in three directions. Thus far, the inputs to this model have beengenerated manually for each subject. This is a slow and tedious process, unpractical touse clinically, and unfeasible for many subjects.This project aims to develop a tool to calculate the inputs and run the model for mul-tiple subjects in an automatic way. It has its basis in 4D Flow MRI data sets segmentedto identify the locations of left atrium (LA), left ventricle (LV), and aorta, along with thecorresponding structures on the right side.The process of making this tool started by calculation of the inputs. Planes were placedin the relevant positions, at the mitral valve, aortic valve (AV) and in the ascending aortaupstream the brachiocephalic branches, and flow rates were calculated through them. TheAV plane was used to calculate effective orifice area of AV and aortic cross-sectional area,while the LV end systolic and end diastolic volumes were extracted form the segmentation.The tool was evaluated by comparison with manually created inputs and outputs,using 9 healthy volunteers and one patient deemed to have normal left ventricular func-tion. The patient was chosen from a subject group diagnosed with chronic ischemic heartdisease, and/or a history of angina, together with fulfillment of the high risk score ofcardiovascular diseases of the European Society of Cardiology. This data was evaluatedusing coefficient of variation, Bland-Altman plots and sum squared error. The tool wasalso evaluated visually on some subjects with pathologies of interest.This project shows that it is possible to calculate inputs fully automatically fromsegmented 4D Flow MRI and run the cardiovascular avatar in an automatic way, withoutuser interaction. The method developed seems to be in good to moderate agreement withthose obtained manually, and could be the basis for further development of the model.

Digital medical atlases can contain anatomical information which is valuable for medical doctors in diagnosing and treating illnesses. The increased availability of such atlases has created an interest for computer algorithms which are capable of integrating such atlas information into patient specific dataprocessing. The field of medical image registration aim at calculating how to match one medical image to another. Here the atlas information could give important hints of which kinds of motion are plausible in different locations of the anatomy. Being able to incorporate such atlas specific information could potentially improve the matching of images and plausibility of image registration - ultimately providing a more correct information on which to base health care diagnosis and treatment decisions. In this licentiate thesis a generic signal processing framework is derived : Global Linear Optimization (GLO). The power of the GLO framework is first demonstrated quantitatively in a very high performing image denoiser. Important proofs of concepts are then made deriving and implementing three important capabilities regarding adaptive filtering of vector fields in medica limage registration: Global regularization with local anisotropic certainty metric. Allowing sliding motion along organ and tissue boundaries. Enforcing an incompressible motion in specific areas or volumes. In the three publications included in this thesis, the GLO framework is shown to be able to incorporate one each of these capabilities. In the third and final paper a demonstration is made how to integrate more and more of the capabilities above into the same GLO to perform adaptive processing on relevant clinical data. It is shown how each added capability improves the result of the image registration. In the end of the thesis there is a discussion which highlights the advantage of the contributions made as compared to previous methods in the scientific literature. / Dynamic Context Atlases for Image Denoising and Patient Safety