Title:
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Magnetic resonance elastography studies of the musculoskeletal system
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Manual palpation is a clinical methodology to determine tissue mechanical properties, such as viscoelasticity (i.e. stiffness and viscosity), which is a primary indicator of the development of tissue pathology. Advancing medical imaging technology means it is now possible to reliably non-invasively measure tissue stiffness in-vivo through the use of Magnetic Resonance Elastography (MRE). Muscle pathology is traditionally assessed in the clinic through measurement of muscle morphology and function (e.g. Maximum Voluntary Contraction [MVC]). However, MRE has been shown to be an effective method to study muscle pathology and may offer novel biomechanical insight into, for example, muscle engagement, injury and recovery, which cannot be obtained through conventional testing. The aim of this thesis is to perform a series of exploratory investigations to determine the precision, sensitivity and reliability of the muscle MRE technique for studying the relationships between muscle mechanical properties and morphology. This is especially relevant to the clinical application of the technique which is investigated in two pilot studies. Specific interests are to investigate whether muscle MRE offers reliable insight regarding muscle ageing, injury and loading and has potential clinical application such as in monitoring recovery after time in Critical Care and the effects of Total Knee Replacement (TKR) in patients with osteoarthritis of the knee. This thesis begins with a review of musculoskeletal biomechanics, Magnetic Resonance Imaging (MRI) and MRE research to date. A limited number of clinical musculoskeletal elastography research studies were identified and which motivated several investigations conducted in this thesis. A musculoskeletal MRE analysis pipeline was developed to accurately acquire and analyse MRE data and consists of image co-registration, quantification of muscle mechanical (i.e. stiffness) and morphological properties (i.e. muscle cross-sectional area and a shape measure referred to as circularity), which may be related to clinical measures and relevant functional indices such as MVC. The pipeline includes quality control procedures to detect image artefacts and provides results which can be potentially reliably compared with those of other research groups. The first two investigations to be reported concern the study of changes in the mechanical properties of muscles that have occurred passively. In particular, the effects of ageing are studied together with the effect of time spent in Critical Care and subsequent rehabilitation. The effect of ageing was primarily evident in the quadriceps muscle group which decreased significantly in cross-sectional area and significantly increased in stiffness. The effects produced by immobilisation were also predominantly in the quadriceps but here a significant decrease in muscle cross-sectional area was associated with a decrease in muscle stiffness. The next three exploratory studies all involve an intervention or manipulation in terms of an eccentric exercise protocol which produces muscle injury as well as muscle loading. The former was based on a re-analysis of previously published work with the aim of determining whether there was a significant difference in muscle stiffness in subjects in whom injury was shown to be associated with muscle oedema on T2-weighted MR images. Here the new pixel-wise analysis of the data showed that although the two groups of subjects performed a similar workload, subjects who developed oedema may have used a different combination of muscles to perform the task, and especially may have additionally recruited medial muscles rather than efficiently co-contracting the quadriceps and hamstrings. A loading study revealed a significant relationship between the stiffness and shape (i.e. circularity) of especially rectus femoris and first steps were taken to investigate whether this relationship may show insight into the recovery of patients following TKR surgery. Taken together these exploratory investigations demonstrate the precision, sensitivity and viability of the muscle MRE technique and its promise for potential clinical application.
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