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