QUANTITATIVE ELASTICITY IMAGING AND SOFT TISSUE CHARACTERIZATION USING TAGGED MAGNETIC RESONANCE IMAGING

Ph.DDOCTOR OF PHILOSOPH

Early characterisation of neurodegeneration with high-resolution magnetic resonance elastography

This thesis contributes to recent interest within medical imaging regarding the development and clinical application of magnetic resonance elastography (MRE) to the human brain. MRE is a non-invasive phase-contrast MRI technique for measurement of brain mechanical properties in vivo, shown to reflect the composition and organisation of the complex tissue microstructure. MRE is a promising imaging biomarker for the early characterisation of neurodegeneration due to its exquisite sensitivity to variation among healthy and pathological tissue. Neurodegenerative diseases are debilitating conditions of the human nervous system for which there is currently no cure. Novel biomarkers are required to improve early detection, differential diagnosis and monitoring of disease progression, and could also ultimately improve our understanding of the pathophysiological mechanisms underlying degenerative processes. This thesis begins with a theoretical background of brain MRE and a description of the experimental considerations. A systematic review of the literature is then performed to summarise brain MRE quantitative measurements in healthy participants and to determine the success of MRE to characterise neurological disorders. This review further identified the most promising acquisition and analysis methods within the field. As such, subsequent visits to three brain MRE research centres, within the USA and Germany, enabled the acquisition of exemplar phantom and brain data to assist in discussions to refine an experimental protocol for installation at the Edinburgh Imaging Facility, QMRI (EIF-QMRI). Through collaborations with world-leading brain MRE centres, two high-resolution - yet fundamentally different - MRE pipelines were installed at the EIF-QMRI. Several optimisations were implemented to improve MRE image quality, while the clinical utility of MRE was enhanced by the novel development of a Graphical User Interface (GUI) for the optimised and automatic MRE-toanatomical coregistration and generation of MRE derived output measures. The first experimental study was performed in 6 young and 6 older healthy adults to compare the results from the two MRE pipelines to investigate test-retest agreement of the whole brain and a brain structure of interest: the hippocampal formation. The MRE protocol shown to possess superior reproducibility was subsequently applied in a second experimental study of 12 young and 12 older cognitively healthy adults. Results include finding that the MRE imaging procedure is very well tolerated across the recruited population. Novel findings include significantly softer brains in older adults both across the global cerebrum and in the majority of subcortical grey matter structures including the pallidum, putamen, caudate, and thalamus. Changes in tissue stiffness likely reflect an alteration to the strength in the composition of the tissue network. All MRE effects persist after correcting for brain structure volume suggesting changes in volume alone were not reflective of the detected MRE age differences. Interestingly, no age-related differences to tissue stiffness were found for the amygdala or hippocampus. As for brain viscosity, no group differences were detected for either the brain globally or subcortical structures, suggesting a preservation of the organisation of the tissue network in older age. The third experiment performed in this thesis finds a direct structure-function relationship in older adults between hippocampal viscosity and episodic memory as measured with verbal-paired recall. The source of this association was located to the left hippocampus, thus complementing previous literature suggesting unilateral hippocampal specialisation. Additionally, a more significant relationship was found between left hippocampal viscosity and memory after a new procedure was developed to remove voxels containing cerebrospinal fluid from the MRE analysis. Collectively, these results support the transition of brain MRE into a clinically useful neuroimaging modality that could, in particular, be used in the early characterisation of memory specific disorders such as amnestic Mild Cognitive Impairment and Alzheimer’s disease

Mesopelagic flesh shear viscosity estimation from in situ broadband backscattering measurements by a viscous–elastic model inversion

In fisheries acoustics, target strength (TS) is a key parameter in converting acoustic measurements to biological information such as biomass. Modelling is a versatile tool to estimate TS of marine organisms. For swimbladdered fish, flesh shear viscosity is one of the required parameters to correctly calculate TS around the resonance frequency, where the target scatters most strongly. Resonance of mesopelagic swimbladdered fish can occur over a range of frequencies and can be within commonly used frequencies (e.g. 18, 38, or 70 kHz). Since there is little information on flesh shear viscosity of fish, especially for mesopelagic species, their resonance can bias the biological information extracted from acoustic measurements. Here, first, the applicability of using a spherical model to estimate resonant backscattering of a generic swimbladder is investigated. Subsequently, a viscous–elastic spherical gas backscattering model is used to estimate the flesh shear viscosity of swimbladdered mesopelagic fish (most likely Cyclothone spp., Family: Gonostomatidae) from in situ broadband backscattering measurements. Finally, the effects of flesh shear viscosity on the TS of swimbladdered mesopelagic fish at 18, 38 (a widely used channel to study mesopelagic layers), and 70 kHz are examined.publishedVersio

In silico evaluation and optimisation of magnetic resonance elastography of the liver

Objective. Magnetic resonance elastography (MRE) is widely adopted as a biomarker of liver fibrosis. However, in vivo MRE accuracy is difficult to assess. Approach. Finite element model (FEM) simulation was employed to evaluate liver MRE accuracy and inform methodological optimisation. MRE data was simulated in a 3D FEM of the human torso including the liver, and compared with spin-echo echo-planar imaging MRE acquisitions. The simulated MRE results were compared with the ground truth magnitude of the complex shear modulus (∣G*∣) for varying: (1) ground truth liver ∣G*∣; (2) simulated imaging resolution; (3) added noise; (4) data smoothing. Motion and strain-based signal-to-noise (SNR) metrics were evaluated on the simulated data as a means to select higher-quality voxels for preparation of acquired MRE summary statistics of ∣G*∣. Main results. The simulated MRE accuracy for a given ground truth ∣G*∣ was found to be a function of imaging resolution, motion-SNR and smoothing. At typical imaging resolutions, it was found that due to under-sampling of the MRE wave-field, combined with motion-related noise, the reconstructed simulated ∣G*∣ could contain errors on the scale of the difference between liver fibrosis stages, e.g. 54% error for ground truth ∣G*∣ = 1 kPa. Optimum imaging resolutions were identified for given ground truth ∣G*∣ and motion-SNR levels. Significance. This study provides important knowledge on the accuracy and optimisation of liver MRE. For example, for motion-SNR ≤ 5, to distinguish between liver ∣G*∣ of 2 and 3 kPa (i.e. early-stage liver fibrosis) it was predicted that the optimum isotropic voxel size is 4–6 mm

A biomechanical analysis of shear wave elastography in pediatric heart models

Early detection of cardiac disease in children is essential to optimize treatment and follow-up, but also to reduce its associated mortality and morbidity. Various cardiac imaging modalities are available for the cardiologist, mainly providing information on tissue morphology and structure with high temporal and/or spatial resolution. However, none of these imaging methods is able to directly measure stresses or intrinsic mechanical properties of the heart, which are potential key diagnostic markers to distinguish between normal and abnormal physiology. This thesis investigates the potential of a relatively new ultrasound-based technique, called shear wave elastography (SWE), to non-invasively measure myocardial stiffness. The technique generates an internal perturbation inside the tissue of interest, and consequently measures the propagation of the acoustically excited shear wave, of which the propagation speed is directly related to tissue stiffness. This allows SWE to identify regions with higher stiffness, which is associated with pathology. SWE has shown to be successful in detecting tumors in breast tissue and fibrosis in liver tissue, however application of SWE to the heart is more challenging due to the complex mechanical and structural properties of the heart. This thesis provides insights into the acoustically excited shear wave physics in the myocardium by using computer simulations in combination with experiments. Furthermore, these models also allow to assess the performance of currently used SWE-based material characterization algorithms

Imaging Sensors and Applications

In past decades, various sensor technologies have been used in all areas of our lives, thus improving our quality of life. In particular, imaging sensors have been widely applied in the development of various imaging approaches such as optical imaging, ultrasound imaging, X-ray imaging, and nuclear imaging, and contributed to achieve high sensitivity, miniaturization, and real-time imaging. These advanced image sensing technologies play an important role not only in the medical field but also in the industrial field. This Special Issue covers broad topics on imaging sensors and applications. The scope range of imaging sensors can be extended to novel imaging sensors and diverse imaging systems, including hardware and software advancements. Additionally, biomedical and nondestructive sensing applications are welcome