PurposeMulti-shot diffusion-weighted EPI allows an increase in image resolution and reduced geometric distortions and can be combined with chemical-shift encoding (Dixon) to separate water/fat... Show morePurposeMulti-shot diffusion-weighted EPI allows an increase in image resolution and reduced geometric distortions and can be combined with chemical-shift encoding (Dixon) to separate water/fat signals. However, such approaches suffer from physiological motion-induced shot-to-shot phase variations. In this work, a structured low-rank-based navigator-free algorithm is proposed to address the challenge of simultaneously separating water/fat signals and correcting for physiological motion-induced shot-to-shot phase variations in multi-shot EPI-based diffusion-weighted MRI.Theory and MethodsWe propose an iterative, model-based reconstruction pipeline that applies structured low-rank regularization to estimate and eliminate the shot-to-shot phase variations in a data-driven way, while separating water/fat images. The algorithm is tested in different anatomies, including head–neck, knee, brain, and prostate. The performance is validated in simulations and in-vivo experiments in comparison to existing approaches.ResultsIn-vivo experiments and simulations demonstrated the effectiveness of the proposed algorithm compared to extra-navigated and an alternative self-navigation approach. The proposed algorithm demonstrates the capability to reconstruct in the multi-shot/Dixon hybrid space domain under-sampled datasets, using the same number of acquired EPI shots compared to conventional fat-suppression techniques but eliminating fat signals through chemical-shift encoding. In addition, partial Fourier reconstruction can also be achieved by using the concept of virtual conjugate coils in conjunction with the proposed algorithm.ConclusionThe proposed algorithm effectively eliminates the shot-to-shot phase variations and separates water/fat images, making it a promising solution for future DWI on different anatomies. Show less
Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) are characterized by progressive loss of muscle function combined with an increase in fat tissue in muscle. In some muscles this... Show moreDuchenne and Becker muscular dystrophy (DMD and BMD, respectively) are characterized by progressive loss of muscle function combined with an increase in fat tissue in muscle. In some muscles this process of ‘fat replacement’ starts earlier or progresses faster than in others and this occurs in a consistent temporal pattern. In addition, even within muscles fat replacement seems to progress heterogeneously. Evidently there are factors that vary between and within muscles which cause differential fat replacement of muscle tissue, but these are currently unknown. The identification of factors that influence this process of muscle degeneration could support the selection of current, and the development of future, therapies.The aim of part 1 of this thesis was to identify differences between muscles that are related to muscle fat replacement over time. These can provide therapeutical targets for, and support the design of, future clinical trials in DMD and BMD. Part 2 aimed to develop new approaches to study intramuscular differences in muscle physiology and mechanics in healthy muscle. These can be applied in neuromuscular disease in the future, and can be related to intramuscular differences in disease progression. Show less
In Becker muscular dystrophy (BMD), muscle weakness progresses relatively slowly, with a highly variable rate among patients. This complicates clinical trials, as clinically relevant changes are... Show moreIn Becker muscular dystrophy (BMD), muscle weakness progresses relatively slowly, with a highly variable rate among patients. This complicates clinical trials, as clinically relevant changes are difficult to capture within the typical duration of a trial. Therefore, predictors for disease progression are needed. We assessed if temporal increase of fat fraction (FF) in BMD follows a sigmoidal trajectory and whether fat fraction at baseline (FFbase) could therefore predict FF increase after 2 years (Delta FF). Thereafter, for two different MR-based parameters, we tested the additional predictive value to FFbase. We used 3-T Dixon data from the upper and lower leg, and multiecho spinecho MRI and 7-T P-31 MRS datasets from the lower leg, acquired in 24 BMD patients (age: 41.4 [SD 12.8] years). We assessed the pattern of increase in FF using mixed-effects modelling. Subsequently, we tested if indicators of muscle damage like standard deviation in water T-2 (stdT(2)) and the phosphodiester (PDE) over ATP ratio at baseline had additional value to FFbase for predicting Delta FF. The association between FFbase and Delta FF was described by the derivative of a sigmoid function and resulted in a peak Delta FF around 0.45 FFbase (fourth-order polynomial term: t = 3.7, p < .001). StdT(2) and PDE/ATP were not significantly associated with Delta FF if FFbase was included in the model. The relationship between FFbase and Delta FF suggests a sigmoidal trajectory of the increase in FF over time in BMD, similar to that described for Duchenne muscular dystrophy. Our results can be used to identify muscles (or patients) that are in the fast progressing stage of the disease, thereby facilitating the conduct of clinical trials. Show less
PurposeTo develop a method of suppressing the multi-resonance fat signal in diffusion-weighted imaging of skeletal muscle. This is particularly important when imaging patients with muscular... Show morePurposeTo develop a method of suppressing the multi-resonance fat signal in diffusion-weighted imaging of skeletal muscle. This is particularly important when imaging patients with muscular dystrophies, a group of diseases which cause gradual replacement of muscle tissue by fat.Theory and MethodsThe signal from the olefinic fat peak at 5.3 ppm can significantly confound diffusion-tensor imaging measurements. Dixon olefinic fat suppression (DOFS), a magnitude-based chemical-shift-based method of suppressing the olefinic peak, is proposed. It is verified in vivo by performing diffusion tensor imaging (DTI)-based quantification in the lower leg of seven healthy volunteers, and compared to two previously described fat-suppression techniques in regions with and without fat contamination.ResultsIn the region without fat contamination, DOFS produces similar results to existing techniques, whereas in muscle contaminated by subcutaneous fat signal moved due to the chemical shift artefact, it consistently showed significantly higher (P=0.018) mean diffusivity (MD). Because fat presence lowers MD, this suggests improved fat suppression.ConclusionDOFS offers superior fat suppression and enhances quantitative measurements in the muscle in the presence of fat. DOFS is an alternative to spectral olefinic fat suppression. Magn Reson Med 79:152-159, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. Show less
In this thesis we evaluated several MRI/S methods as outcome parameters to assess muscle pathology in DMD and BMD patients. We applied 3-point Dixon MRI to compare levels of fatty infiltration in... Show moreIn this thesis we evaluated several MRI/S methods as outcome parameters to assess muscle pathology in DMD and BMD patients. We applied 3-point Dixon MRI to compare levels of fatty infiltration in muscle of DMD patients with a semi-quantitative method. Dixon MRI showed to be more sensitive to subtle changes. Implementation of a multipeak model to account for multiple lipid spectrum peaks in this method allowed even more sensitive measurements. We evaluated non-contractile and contractile cross-sectional areas in leg muscles of DMD patients. Combined with strength measurements we could measure muscle quality and showed muscle hypertrophy and fatty infiltration to be two distinct processes. We explored the relation between dystrophin levels and fat in BMD patients and found no such relation, but did find a relation between strength and age in a subgroup, demonstrating the location of the mutation to be a major determinant of disease severity. Using T2 MRI as inflammatory marker in DMD/BMD patients and healthy controls we showed an increased T2 in DMD patients. Finally we investigated the muscle energy metabolism in BMD patients with MRS and showed increased PDE/ATP ratios prior to onset of fatty infiltration, consequently 31P MRS could be another potential outcome parameter. Show less
