Purpose: The purpose of this study was two-fold: (1) determine if muscle activation was greater in a BFR exercise condition compared to non-BFR exercise condition using MRI T2 mapping, and (2) determine if the muscle activation for both BFR and non-BFR exercise conditions differs between postbariatric surgery individuals and individuals in 2 control groups. Methods: Three groups participated: (1) a normal-BMI group, (2) a postbariatric surgery group, and (3) a matched group for the surgery individuals. Ultrasound imaging was used to find the optimal BFR pressure for each participant. All participants participated in both BFR and non-BFR exercises. Using a 3-Telsa MRI, a T2 map was imaged prior to and immediately following exercise. Analyses included within-group-across-condition comparisons and within-condition-across-group comparisons. The outcome variable of interest was the change in muscle activation determined via T2 mapping. Results: There was no statistical difference in the increase in muscle activation between BFR and non-BFR exercise conditions (p-value range 0.1091 to 0.9166). When comparing groups across conditions, we found that the surgery group elicited a significantly greater increase in activation compared to the normal-BMI group in every condition (p-value range 0.0014 to 0.0217) and in several muscles when compared to the matched group (p-value range 0.0060 to 0.0311). Other muscles compared to the matched group were not significantly different (p-value range 0.0683 to 0.129). No difference was found between the control groups (p-value range 0.2041 to 0.9557) in muscle activation for either condition. Conclusion: These results did not suggest a difference between BFR exercise and non-BFR exercise for the calf-raise protocol. Postbariatric surgery patients elicited an equal muscle activation response in some conditions and a greater muscle activation response in others when compared to both control groups. Further research is needed to determine whether a greater intensity or duration of exercise is needed to elicit an acute response to BFR and what factors are contributing to the increased muscle activation seen in the postbariatric surgery group.

<div> <p> Essential tremor (ET) is one of the most common movement disorders, characterized by kinetic tremor in the upper extremities with additional cranial tremor often present in the neck or jaw. While it is well established that ET is primarily a cerebellar disorder, recent investigations have shown more widespread pathological effects throughout the brain. Furthermore, the neurodegenerative nature of ET is still disputed and requires additional investigation. Additionally, the link between ET and Parkinson’s disease (PD) is of special interest, as it can be challenging to clinically differentiate these diseases.</p> <p> While post-mortem studies have helped to further the pathological understanding of these diseases, non-invasive in-vivo techniques allow for more accurate diagnosis in the clinic. With a more accurate diagnosis comes a more targeted treatment, and hopefully an improved remediation of the disease. My thesis seeks to further investigate the neurodegenerative hypothesis of ET as well as explore magnetic resonance imaging (MRI) biomarkers for potential differences in ET and PD. </p> <p>These aims will be accomplished in three steps. First, gray matter volume loss in the cerebellum was investigated using voxel-based morphometry and the Spatially Unbiased Infra-Tentorial Template (SUIT) atlas on a lobule level. High resolution 3D T1-weighted MRI images were acquired on 47 ET cases and 36 controls. The cerebellum was segmented into 34 lobules using the SUIT atlas. Percent gray matter was calculated as the ratio of lobule gray matter volume divided by total lobule volume. No significant differences were identified between ET cases and controls in any of the 34 lobules. However, nine lobules had significantly decreased percent gray matter in ET cases with head or jaw tremor (n = 27) compared to controls. Also, 11 lobules had significantly decreased percent gray matter in ET cases with voice tremor (n = 22) compared to controls. This result confirms, with increased regional accuracy, gray matter volume loss in the cerebellum of ET cases.</p> <p>Second, gray matter volume loss beyond the cerebellum, in the cerebrum, was investigated using voxel-based morphometry. High resolution 3D T1-weighted MRI images were acquired on 47 ET cases and 36 controls for processing in SPM12. The processing steps of SPM12 were updated to include a higher resolution atlas and set of tissue probability maps to optimize the segmentation and normalization of each subject image. After segmentation, normalization, and smoothing, a voxel-wise statistical analysis was performed to identify clusters of gray matter volume in ET cases compared to controls. ET cases showed decreased gray matter volume in the bilateral superior temporal region and the anterior and posterior cingulate cortex. These results, in combination with previous work provide support of wide-spread neurodegeneration in ET using optimized methodology.</p> <p>Third, we applied T2* mapping to determine relative iron concentrations in the substantia nigra (SN) and globus pallidus (GP) in ET and PD cases. Three separate studies were independently investigated to validate the reproducibility and detectability of group differences using T2* mapping. The first study (ET study) acquired T2* maps on 21 ET cases and 12 matched controls, the second study (PD study 1) acquired T2* maps on 10 PD cases and 7 controls, and the third study (PD study 2) acquired T2* maps on 21 PD cases and 17 controls. Regions of interest (ROIs) were manually placed in the SN and GP for each subject and group differences were calculated independently for each study using a linear regression model with age and sex as covariates. A significant decrease in T2* was found in PD study 1 and PD study 2 in the right SN in PD cases compared to their respective controls, indicating increased iron deposition. No significant difference was found in the ET group compared to their respective controls in the SN. No significant differences were found in any of the three studies in the GP. These results provide evidence for a difference in brain iron regulation in the pathology of ET and PD.</p> <p>Together, these thesis aims provide additional evidence in support of the neurodegenerative hypothesis of ET using updated methodology and present a quantitative imaging difference between groups of ET and PD cases. </p> </div> <br>

Magnetic resonance imaging (MRI) has become the most important modality for assessment of pathological changes in the knee cartilage. The assessment of the cartilage is usually made by a set of anatomical MRI images with different sequences. Newer techniques, that map various in MRI parameters, have been developed and allows changes in an earlier stage of the disease. One of these techniques is T2 mapping. The goal of this thesis was to compare this newer technique, T2 mapping, with the standard MRI assessment for assessment of articular cartilage on distal femur in the knee. The purpose was to assess the cartilage with these two different methods and analyze its outcomes. Eight subjects were included in this study and scanned with a 3.0 T or 1.5 T MRI machine. A specific MRI knee protocol was used for the standard MRI assessment, and a multi-echo sequence was used for the T2 mapping. The T2 map was created and analyzed in the program IntelliSpace Portal. Both the standard MRI assessment and the T2 map showed changes in the knee cartilage. The result showed either indication for damage cartilage or healthy cartilage. The standard assessment showed cartilage lesion in three subjects and no lesion in five subjects. The same outcomes were with the T2 mapping. However, not all results were equal. The T2 mapping also showed higher values in the trochlea area where no indications for changes were found in the standard assessment. This study showed similar results for both the standard assessment and the T2 map. Both methods could identify damage and is, therefore, useful for assessment of the knee cartilage. The outcomes of the different methods differ, and the assessment is therefore made in different ways. The T2 mapping can be analyzed both visual and quantitative. The outcomes were both a color map of the knee but also results in graphs and values. The standard assessment is only assessed from grayscale images. The best outcomes from the T2 mapping was when it only was changes within the cartilage and not when the cartilage lesion was adjacent to an underlying bone lesion. Based on what was examined in this work, the best result was when T2 mapping was used together with the anatomical images used in the standard assessment. The conclusion is that the standard assessment is necessary when it comes to make a damage assessment and perform damage marking as for Episurf. The T2 mapping is, however, an interesting method and will be more useful with more applications in the future. It is therefore exciting to keep an eye on the technology and its development. / Magnetisk resonanstomografi (MR) har blivit den viktigaste modaliteten vid bedömning av patologiska förändingar i knäbrosket. Bedömningen av brosket görs vanligtvis med hjälp av anatomiska MR bilder som är skannade med olika sekvenser för att få olika viktningar på bilderna. En nyare teknik, T2 mappning, som kartlägger olika MR prameterar, har utvecklats för att med hjälp av andra parametrar analysera knäbrosket. Den här tekniken har resulterat i att förändringar i brosket kan upptäckas vid ett tidigare stadie i sjukdomsförloppet. Målet med det här examensarbetet var att jämföra de olika teknikerna, T2 mappning och MR-standardbedömningen, för att bedöma ledbrosket på distala lårbenet i knäet. Syftet var att bedöma brosket utifrån dessa olika metoder samt att analysera och jämföra dess resultat. Åtta subjekt ingick i studien och skannades med en 3,0 T eller 1,5 T MR-maskin. Ett specifikt MR-knäprotokoll användes för att skanna sekvenserna som ingick i standard bedömningen och en multi-ekosekvens användes för T2 mappningen. T2-mappningen skapades och analyserades sedan i programmet IntelliSpace Portal. Både standard MR-bedömningen och T2-mappningen visade tydliga förändringar i brosket. Resultatet visade antingen indikationer på skadat eller friskt brosk. Standardbedömningen visade broskskador hos tre subjekt och inga broskskador hos fem subjekt. Samma resultat visades med T2-mappningen. Däremot skilde sig vissa resultat mellan T2 mappningen och standardbedömningen. Då denna studie visade liknande resultat för både standardbedömningen och T2-mappningen, är båda metoderna användbara för bedömning av knäbrosket. De olika metoderna har olika utfall vilket gör att bedömningen sker på olika sätt. I T2 mapping får man ut både en färgkarta över knät men också grafter och värden som kan användas. I standardbedömningen görs bedömningen bara utifrån olika gråskalebilder. T2 mappningen var mest användbar när det var tydliga förändingar i bara brosket och inte när skadan mest var i benet. Det bästa resultatet var däremot när T2 mappning användes tillsammans med standardbedömningen. Slutsatsen är att standardbedömningen är nödvändig när det kommer till att bedömma skador och göra en skademarkering så som för Episurf. T2 mapping är däremot en väldigt intressant teknik men är idag inte en vanlig teknik inom diagnostiken och saknar just nu något tydligt användningsområde. Däremot, finns det stor potential och kommer troligtvis bli vanligare och få fler användingsområden i framtiden.

The work presented in this dissertation involves the development of parametric magnetic resonance imaging (MRI) techniques that can be used in a clinical set up. In the first chapter an introduction of basic magnetic resonance physics is given. The introduction covers the source to tissue magnetization, the origin of the detectable signal, the relaxation mechanisms, and the imaging principles. In the second chapter T₂ estimation - the main parametric MRI technique addressed in this work - is introduced and the problem associated with T₂ estimation from highly undersampled fast spin-echo (FSE) data is presented. In Chapter 3, a novel model-based algorithm with linearization by principal component analysis (REPCOM) is described. Based on simulations, physical phantom and in vivo data, the proposed algorithm is shown to produce accurate and stable T₂ estimates. In Chapter 4, the concept of indirect echoes associated with the acquisition of FSE data is introduced. Indirect echo correction using the extended phase graph approach is then studied for standard sampled data. A novel reconstruction algorithm (SERENADE) is presented for the reconstruction of decay curves with indirect echoes from highly undersampled data. The technique is evaluated using simulations, physical phantom and in vivo data; decay curves with indirect echoes are shown to be accurately recovered by this technique. Chapter 5 is dedicated to correcting the partial volume effect (PVE) in T₂ estimation. For the case of small lesions within a background tissue, PVE affects T₂ estimation which in turn affects lesion classification. A novel joint fitting algorithm is proposed and compared to conventional fitting algorithms using fully sampled spin-echo (SE) images. It is shown that the proposed algorithm is more accurate, robust, and insensitive to region of interest drawing than the conventional fitting algorithms. Because the acquisition of fully sampled SE images is long, the technique is combined with a thick refocusing slice approach in order to be able to use undersampled FSE data and reduce the acquisition time to a breath hold (~ 20 s). The final chapter summarizes the results presented in the dissertations and discusses areas for future work.

Magnetic resonance imaging is a widely used medical imaging technique, and accelerated data acquisition is critical for clinical utility. In this thesis, new techniques that incorporate radial acquisition, compressed sensing and sparse regularization for improved rapid imaging are presented. Sufficiently accelerated imaging methods can lead to new applications. Here we demonstrate a solution to lung imaging during forced expiration using accelerated MRI. A technique for dynamic 3D imaging of the lungs from highly undersampled data is developed and tested on six subjects. This method takes advantage of image sparsity, both spatially and temporally, including the use of reference frames called bookends. Sparsity, with respect to total variation, and residual from the bookends, enables reconstruction from an extremely limited amount of data. Dynamic 3D images can be captured at an unprecedented sub-150 ms temporal resolution, using only three (or less) acquired radial lines per slice per time point. Lung volume calculations based on image segmentation are compared to those from simultaneously acquired spirometer measurements. Additionally, accelerated imaging methods can be used to improve upon widely used applications; we also present a technique for improved T₂-mapping. A novel model-based compressed sensing method is extended to include a sparse regularization that is learned from the principal component coefficients. The principal components are determined by a range of T₂ decay curves, and the coefficients of the principal components are reconstructed. These coefficient maps share coherent spatial structures, and a spatial patch--based dictionary is a learned for a sparse constraint. This transformation is learned from the coefficients themselves. The proposed reconstruction is suited for non-Cartesian, multi-channel data. The dictionary constraint leads to parameter maps with less noise and less aliasing for high amounts of acceleration.

<p>MR phase images contain essential information about local magnetic susceptibility sources in the brain, creating a new type of contrast in magnetic resonance imaging (MRI). The goal of this thesis is to demonstrate with a model of the brain how accurately the transformation of phase to susceptibility takes place.</p> <p>A 3D brain model uses the Forward process to calculate magnetic field perturbations caused by susceptibility properties of the tissues in the model. Homodyne High Pass (HP) filter and SHARP algorithm are used to process the simulated phase images. Similarly, MR magnitude data are simulated using tissue properties such as T₁, T₂^* relaxation times and spin density.</p> <p>The halo ring around red nucleus in the real phase data is believed to be an indicator of a capsule around red nucleus. Similar effect is seen in the simulated phase images without including the capsule of red nucleus in the model, this comparison explains that the halo effect may just be entirely or a part of the phase behavior around red nucleus. A negative susceptibility in the internal capsule region, seen in both simulated and real susceptibility maps, is discussed as a possible artifact caused by the processing techniques after comparing the simulated susceptibility maps produced from unprocessed and processed phase data. The brain model is used to determine the optimum echo time of the initial gradient echo sequence in order to produce a high quality susceptibility map with reasonably low error and better time efficiency.</p> / Master of Applied Science (MASc)

Magnetic Resonance Imaging (MRI) is an important diagnostic tool for imaging soft tissue without the use of ionizing radiation. Moreover, through advanced signal processing, MRI can provide more than just anatomical information, such as estimates of tissue-specific physical properties. Signal processing lies at the very core of the MRI process, which involves input design, information encoding, image reconstruction, and advanced filtering. Based on signal modeling and estimation, it is possible to further improve the images, reduce artifacts, mitigate noise, and obtain quantitative tissue information. In quantitative MRI, different physical quantities are estimated from a set of collected images. The optimization problems solved are typically nonlinear, and require intelligent and application-specific algorithms to avoid suboptimal local minima. This thesis presents several methods for efficiently solving different parameter estimation problems in MRI, such as multi-component T2 relaxometry, temporal phase correction of complex-valued data, and minimizing banding artifacts due to field inhomogeneity. The performance of the proposed algorithms is evaluated using both simulation and in-vivo data. The results show improvements over previous approaches, while maintaining a relatively low computational complexity. Using new and improved estimation methods enables better tissue characterization and diagnosis. Furthermore, a sequence design problem is treated, where the radio-frequency excitation is optimized to minimize image artifacts when using amplifiers of limited quality. In turn, obtaining higher fidelity images enables improved diagnosis, and can increase the estimation accuracy in quantitative MRI.

L’IRM est de plus en plus utilisée pour diagnostiquer et évaluer un très grand nombre de pathologies. Cette technique présente cependant deux inconvénients majeurs. En effet, les examens restent encore très longs (notamment en imagerie 3D) et la quantification est très difficile par rapport à d’autres modalités comme la tomographie par émission de positons. L’objectif de ce travail de thèse a été de diminuer significativement les temps d’acquisition nécessaires pour l’imagerie volumique et de développer des techniques quantitatives robustes, permettant d’effectuer des suivis longitudinaux.Pour cela, des méthodes innovantes ont été développées à très haut champ magnétique (7T) et validées sur des modèles murins sains et pathologiques. Trois développements majeurs sont ressortis de cette thèse. Tout d’abord, une mesure rapide des temps de relaxation longitudinale (T1) a été développée.Cette méthode basée sur une approche Look-Locker a été couplée avec un échantillonnage en empilement de spirales et a permis d’obtenir au niveau cardiaque des cartes T1 en 3D sur des souris saines et des modèles d’infarctus du myocarde en moins de 15 minutes. Ensuite, une approche dite« spiral-in » a été couplée avec une méthode de multi-échos de spin afin d’accélérer la mesure des temps de relaxation transversale (T2). Cette méthode a permis d’obtenir des cartes T2 en 3D sur des cerveaux de souris saines et métastatiques en moins de 20 minutes. Enfin, une approche hybride couplant les avantages de l’acquisition spiralée et ceux de l’échantillonnage radial a été développée.Cette méthode a été couplée avec une technique de Golden-Angle pour échantillonner aléatoirement l’espace de Fourier et a permis pour la première fois de visualiser une angiographie 3D d’un foie de souris en respiration libre en moins de 12 minutes. Toutes les méthodes développées dans ce travail ont été validées au niveau de leur robustesse et démontrent que l’IRM peut être une technique à la fois rapide et quantitative. Ces développements pourront être transférés vers la clinique dans de futurs travaux. / MRI is more and more used to diagnose and assess a wide range of pathologies. However, this technique is still limited by two disadvantages. Indeed, the acquisition times are too long(especially in 3D) and the quantification is still difficult compared to other techniques like positron emission tomography. The aim of this PhD project was to significantly reduce acquisition times required for 3D imaging and to develop robust quantitative techniques allowing longitudinal studies.To these ends, innovative methods have been developed at very high magnetic field (7T) and validated on healthy and diseased mouse models. Three major developments arose from this work. Firstly, a fast measurement of the longitudinal relaxation time (T1) has been developed. This method based on a Look-Locker approach was coupled with a sampling using stack-of-spirals and allowed to get T1 mapsin 3D in healthy and myocardial infarction models in less than 15 minutes. Then, a "spiral-in" approach was coupled with a multi spin echoes acquisition to accelerate the measurement of the transverse relaxation time (T2). This method allowed to get T2 maps in 3D of healthy and metastatic mouse brains in less than 20 minutes. Finally, a hybrid approach combining the advantages of the spiral acquisition with those of the radial sampling has been developed. This method has been coupled with a Golden-Angle technique for randomly sampling the k-space and allowed for the first time to display a 3Dangiography of a mouse liver in free breathing in less than 12 minutes. All the protocols developed inthis PhD project were validated in terms of robustness and showed that MRI can be a technique both rapid and quantitative. These developments will be transferred to the clinic in future works.

Children with high-risk SHH/TP53-mut and Group 3 medulloblastoma (MB) have a 5-year overall survival of only 40%. Innovative approaches to enhance survival while preventing adverse effects are urgently needed. We investigated an innovative therapy approach combining irradia- tion (RT), decitabine (DEC), and abacavir (ABC) in a patient-derived orthotopic SHH/TP53-mut and Group 3 MB mouse model. MB-bearing mice were treated with DEC, ABC and RT. Mouse survival, tumor growth (BLI, MRT) tumor histology (H/E), proliferation (Ki-67), and endothelial (CD31) staining were analyzed. Gene expression was examined by microarray and RT-PCR (Ki-67, VEGF, CD31, CD15, CD133, nestin, CD68, IBA). The RT/DEC/ABC therapy inhibited tumor growth and enhanced mouse survival. Ki-67 decreased in SHH/TP53-mut MBs after RT, DEC, RT/ABC, and RT/DEC/ABC therapy. CD31 was higher in SHH/TP53-mut compared to Group 3 MBs and decreased after RT/DEC/ABC. Microarray analyses showed a therapy-induced downregulation of cell cycle genes. By RT-PCR, no therapy-induced effect on stem cell fraction or immune cell inva- sion/activation could be shown. We showed for the first time that RT/DEC/ABC therapy improves survival of orthotopic SHH/TP53-mut and Group 3 MB-bearing mice without inducing adverse effects suggesting the potential for an adjuvant application of this multimodal therapy approach in the human clinic.

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