Microscopic multifrequency MR elastography for mapping viscoelasticity in zebrafish

Purpose: The zebrafish (Danio rerio) has become an important animal model in a wide range of biomedical research disciplines. Growing awareness of the role of biomechanical properties in tumor progression and neuronal development has led to an increasing interest in the noninvasive mapping of the viscoelastic properties of zebrafish by elastography methods applicable to bulky and nontranslucent tissues. Methods: Microscopic multifrequency MR elastography is introduced for mapping shear wave speed (SWS) and loss angle (φ) as markers of stiffness and viscosity of muscle, brain, and neuroblastoma tumors in postmortem zebrafish with 60 µm in-plane resolution. Experiments were performed in a 7 Tesla MR scanner at 1, 1.2, and 1.4 kHz driving frequencies. Results: Detailed zebrafish viscoelasticity maps revealed that the midbrain region (SWS = 3.1 ± 0.7 m/s, φ = 1.2 ± 0.3 radian [rad]) was stiffer and less viscous than telencephalon (SWS = 2.6 ± 0. 5 m/s, φ = 1.4 ± 0.2 rad) and optic tectum (SWS = 2.6 ± 0.5 m/s, φ = 1.3 ± 0.4 rad), whereas the cerebellum (SWS = 2.9 ± 0.6 m/s, φ = 0.9 ± 0.4 rad) was stiffer but less viscous than both (all p < .05). Overall, brain tissue (SWS = 2.9 ± 0.4 m/s, φ = 1.2 ± 0.2 rad) had similar stiffness but lower viscosity values than muscle tissue (SWS = 2.9 ± 0.5 m/s, φ = 1.4 ± 0.2 rad), whereas neuroblastoma (SWS = 2.4 ± 0.3 m/s, φ = 0.7 ± 0.1 rad, all p < .05) was the softest and least viscous tissue. Conclusion: Microscopic multifrequency MR elastography-generated maps of zebrafish show many details of viscoelasticity and resolve tissue regions, of great interest in neuromechanical and oncological research and for which our study provides first reference values

Magnetic resonance elastography (MRE) of the human brain: technique, findings and clinical applications

Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms—at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience

Quantitative Gewebecharakterisierung mittels mechanischer Kenngrößen in präklinischen Kleintiermodellen

The biomechanical properties of the brain play an important role in vital functioning and disease development. Over the last decade, cerebral magnetic resonance elastography (MRE) has emerged as a valuable imaging technique, revealing important characteristics of tissue biomechanics in disease and health. However, state-of-the-art mouse brain MRE is limited by time-consuming multi-shot acquisition techniques and noise-sensitive single-frequency image reconstruction methods. Therefore, the purpose of this PhD project was the development of multifrequency mouse brain MRE based on a single-shot acquisition technique and noise-robust tomoelastography post-processing for high-resolution stiffness mapping. The feasibility of the method was demonstrated using three in vivo studies. In the first study, shear wave speed (SWS) as a surrogate of stiffness in different areas of the brain was measured. In the second study, the effect of body temperature on biophysical parameters of murine brain tissue was investigated in the normothermic to hypothermic range. Tomoelastography was combined with arterial spin labelling and diffusion-weighted imaging in order to determine the relationship between tissue stiffness, perfusion and diffusion. In the third study, mechanical brain alterations were continuously monitored during the critical phase of death in a mouse model of hypoxia. In ten animals, we quantified regional dependent SWS of 2.9 ± 0.2 m/s, 4.9 ± 0.5 m/s, 4.8 ± 0.8 m/s and 3.5 ± 0.3 m/s for the corpus callosum, hippocampus, diencephalon and cortex. In a group of six animals, we found that SWS decreased from hypothermia (28 ± 0.5 °C) to normothermia (38 ± 0.5 °C) by 6.2%, 10.1% and 7.4% in the whole brain, cortex and hippocampus, respectively. These SWS decreases were correlated with changes in water diffusion (30% increase) and blood perfusion (60% to 90% increase). Furthermore, in fourteen animals, brain death led to a 6% increase of SWS in the whole brain and 9% in the hippocampus when compared to in vivo values. Our novel multifrequency MRE method with tomoelastography processing provides mouse brain stiffness maps within shorter scan times and with greater detail resolution than a conventional MRE. Short scan times, in the order of only 40 seconds, open new horizons for continuous stiffness monitoring during different pathological processes in vivo. Clinical relevant biophysical processes in the brain, such as hypothermia and hypoxia, and the critical phase of brain death were monitored and investigated for the first time. The results show that stiffness varies across sub-regions in the murine brain, is inversely correlated with water diffusion and blood perfusion, and increases in hypoxia towards brain death. The new method contributes to the growing understanding of mechanical signatures of brain tissues and is potentially of great value for future studies of in vivo brain mechanical properties in health and disease.Die biomechanischen Eigenschaften von zerebralem Gewebe beeinflussen zahlreiche physiologische Prozesse im Gehirn. Die zerebrale Magnetresonanz-Elastographie (MRE) erwies sich dabei innerhalb des letzten Jahrzehnts als wertvolles nicht-invasives Bildgebungsverfahren und offenbarte wichtige biomechanische Merkmale im gesunden als auch kranken Gewebe. Die moderne MRE des Maushirns ist jedoch durch zeitaufwändige Multi-Shot-Bildaufnahemetechniken und rauschempfindliche monofrequente Bildrekonstruktionsmethoden begrenzt. Das Ziel dieser Promotion war die Entwicklung eines hochauflösenden Elastographie-Verfahrens mittels multifrequenter Maushirn-MRE auf der Grundlage von Einzelbildaufnahmetechniken und anschließender Tomoelastographie-Postprozessierung zur Minderung der Rauschempfindlichkeit. Die Durchführbarkeit der Methode wurde mit drei in-vivo-Studien nachgewiesen. In der ersten Studie wurden verschiedene Bereiche des Gehirns bezüglich der Scherwellengeschwindigkeit (SWS) als Surrogat der Steifigkeit vermessen. Die zweite Studie untersuchte den Einfluss der Körpertemperatur auf biophysikalische Parameter des murinen Hirngewebes im normothermen bis hypothermen Bereich. Die Tomoelastographie wurde mit arterieller Spin-Markierung und diffusionsgewichteter Bildgebung kombiniert, um mögliche Zusammenhänge zwischen Gewebesteifigkeit, Perfusion und Diffusion zu analysieren. Im Rahmen der dritten Studie wurden anhand eines hypoxischen Mausmodells die biomechanischen Veränderungen des Gehirns während der kritischen Phase des Todes kontinuierlich aufgenommen und überwacht. Für zehn Tiere wurden lokale SWS von 2,9 ± 0,2 m/s für das Corpus callosum, 4,9 ± 0,5 m/s für den Hippocampus, 4,8 ± 0,8 m/s für das Zwischenhirn und 3,5 ± 0,3 m/s für den Cortex cerebri quantifiziert. Anhand von sechs vermessenen Tieren konnte im gesamten Gehirn, Kortex und Hippocampus eine Abnahme der SWS von Hypo- (28 ± 0.5 °C) zu Normothermie (38 ± 0.5 °C) jeweils um 6,2%, 10,1% bzw. 7,4% festgestellt werden. Diese Abnahme der SWS korrelierte mit Veränderungen der Wasserdiffusion (30% Zunahme) und der Perfusion (60% bis 90% Zunahme). Darüber hinaus führte der Hirntod bei vierzehn Tieren zu einem Anstieg der SWS um 6% im gesamten Gehirn und 9% im Hippocampus gegenüber den in-vivo-Werten. Das implementierte neuartige Multifrequenz-MRE-Verfahren liefert innerhalb stark verkürzter Messzeiten Steifigkeitskarten vom Maushirn mit größerer Detailauflösung als bisherige MRE Methoden. Erstmals konnten somit klinisch relevante biophysikalische Prozesse im Gehirn wie die Hypothermie, die Hypoxie und die kritische Phase des Hirntodes beobachtet und untersucht werden. Die Ergebnisse zeigen, dass die Steifigkeit in den verschiedenen Subregionen des Gehirns der Maus variiert, mit der Wasserdiffusion und der Perfusion invers korreliert und durch Hypoxie im Rahmen des Hirntodes zunimmt. Die neuen Entwicklungen tragen zum wachsenden Verständnis der biomechanischen Eigenschaften des Hirngewebes bei

K-space data processing for Magnetic Resonance Elastography (MRE)

International audienceObject: Magnetic Resonance Elastography (MRE) requires substantial data processing based on phase image reconstruction, wave enhancement and inverse problem solving. The objective of this study is to propose a new, fast MRE method based on MR raw data processing, particularly adapted to applications requiring fast MRE measurement or high elastogram update rate.Material and Methods: The proposed method allows measuring tissue elasticity directly from raw data without prior phase image reconstruction and without phase unwrapping. Experimental feasibility is assessed both in a gelatin phantom and in the liver of a porcine model in vivo. Elastograms are reconstructed with the raw MRE method and compared to those obtained using conventional MRE. In a third experiment, changes in elasticity are monitored in real-time in a gelatin phantom during its solidification by using both conventional MRE and raw MRE.Results: The raw MRE method shows promising results by providing similar elasticity values to the ones obtained with conventional MRE methods while decreasing the number of processing steps and circumventing the delicate step of phase unwrapping. Limitations of the proposed method are the influence of the magnitude on the elastogram and the requirement for a minimum number of phase offsets.Conclusion: This study demonstrates the feasibility of directly reconstructing elastograms from raw data

Entwicklung der multifrequenten Magnetresonanz-Elastographie zur Quantifizierung der biophysikalischen Eigenschaften von menschlichem Hirngewebe

Magnetic resonance elastography (MRE) is an emerging technique for the quantitative imaging of the biophysical properties of soft tissues in humans. Following its successful clinical application in detecting and characterizing liver fibrosis, the scientific community is investigating the use of viscoelasticity as a biomarker for neurological diseases. Clinical implementation requires a thorough understanding of brain tissue mechanics in conjunction with innovative techniques in new research areas. Therefore, three in vivo studies were conducted to analyze the inherent stiffness dispersion of brain tissue over a wide frequency range, to investigate real-time MRE in monitoring the viscoelastic response of brain tissue during the Valsalva maneuver (VM), and to study mechanical alterations of small lesions in multiple sclerosis (MS). Ultra-low frequency MRE with profile-based wave analysis was developed in 14 healthy subjects to determine large-scale brain stiffness, from pulsation-induced shear waves (1 Hz) to ultra-low frequencies (5 – 10 Hz) to the conventional range (20 – 40 Hz). Furthermore, multifrequency real-time MRE with a frame rate of 5.4 Hz was introduced to analyze stiffness and fluidity changes in response to respiratory challenges and cerebral autoregulation in 17 healthy subjects. 2D and 3D wavenumber-based stiffness reconstruction of the brain was established for conventional MRE in 12 MS patients. MS lesions were analyzed in terms of mechanical contrast with surrounding tissue in relation to white matter (WM) heterogeneity. We found superviscous properties of brain tissue at large scales with a strong stiffness dispersion and a relatively high model-based viscosity of η = 6.6 ± 0.3 Pa∙s. The brain’s viscoelasticity was affected by perfusion changes during VM, which was associated with an increase in brain stiffness of 6.7% ± 4.1% (p<.001), whereas fluidity decreased by -2.1 ± 1.4% (p<.001). In the diseased brain, the analysis of 147 MS lesions revealed 46% of lesions to be softer and 54% of lesions to be stiffer than surrounding tissue. However, due to the heterogeneity of WM stiffness, the results provide no significant evidence for a systematic pattern of mechanical variations in MS. Nevertheless, the results may explain, for the first time, the gap between static ex vivo and dynamic in vivo methods. Fluidity-induced dispersion provides rich information on the structure of tissue compartments. Moreover, viscoelasticity is affected by perfusion during cerebral autoregulation and thus may be sensitive to intracranial pressure modulation. The overall heterogeneity of stiffness obscures changes in MS lesions, and MS may not exhibit sclerosis as a mechanical signature. In summary, this thesis contributes to the field of human brain MRE by presenting new methods developed in studies conducted in new research areas using state-of-the-art technology. The results advance clinical applications and open exciting possibilities for future in vivo studies of human brain tissue.Die Magnetresonanz-Elastographie (MRE) ist ein Verfahren zur quantitativen Darstellung der viskoelastischen Eigenschaften von Weichgewebe. Nach der erfolgreichen klinischen Anwendung in der Leberdiagnostik wird versucht, Viskoelastizität als Biomarker für neurologische Krankheiten zu nutzen. Hierzu bedarf es einer genauen Analyse der Gewebemechanik und innovativen Anwendungsgebieten. Daher, wurden drei Studien durchgeführt, um die Steifigkeitsdispersion von Hirngewebe zu analysieren, das viskoelastische Verhalten während des Valsalva Manövers (VM) abzubilden, und die mechanischen Veränderungen in Läsionen bei Multipler Sklerose (MS) zu untersuchen. Niedrigfrequenz-MRE mit profilbasierter Wellenanalyse wurde in 14 Probanden entwickelt, um die Steifigkeit des Gesamthirns von pulsationsinduzierten Scherwellen (1 Hz) über ultraniedrige Frequenzen (5 – 10 Hz) bis hin zum konventionellen Bereich (20 – 40 Hz) zu bestimmen. Außerdem wurde die multifrequente Echtzeit-MRE mit einer Bildfrequenz von 6.4 Hz eingeführt, um die viskoelastische Antwort des Gehirns auf respiratorische Herausforderungen bei 17 gesunden Probanden zu untersuchen. Neue 2D- und 3D-Wellenzahl-basierte Steifigkeitsrekonstruktionen für das Gehirn wurden in 12 MS Patienten und konventioneller MRE entwickelt. Die Steifigkeitsänderungen in MS-Läsionen wurden mit umliegender weißer Substanz und dessen Heterogenität verglichen. Wir fanden superviskose Eigenschaften des Hirngewebes mit einer starken Dispersion und relativ hohen, modellbasierten Viskosität von η = 6,6 ± 0,3 Pa∙s. Die mechanischen Gewebeeigenschaften wurden durch Perfusionsänderungen während VM beeinflusst und die Hirnsteifigkeit erhöhte sich um 6,7 ± 4,1% (p<.001) wobei sich die Fluidität um -2,1 ± 1,4% (p<.001) verringerte. Die Analyse von 147 MS-Läsionen ergab, dass 54% bzw. 46% der Läsionen steifer bzw. weicher sind als das umgebende Gewebe. Aufgrund der Heterogenität der WM-Steifigkeit konnte jedoch kein Hinweis auf ein systematisches Muster mechanischer Veränderungen in MS-Läsionen gefunden werden. Die Ergebnisse können zum ersten Mal die Lücke zwischen statischen ex vivo und dynamischen in vivo Methoden erklären. Die fluiditätsinduzierte Dispersion liefert interessante Informationen über die zugrundeliegende Gewebestruktur. Darüber hinaus wird die Viskoelastizität durch die Perfusion während der zerebralen Autoregulation beeinflusst und kann daher empfindlich auf intrakranielle Druckschwankungen reagieren. Die allgemeine Heterogenität der Steifigkeit überschattet die Veränderungen in MS-Läsionen, und somit ist Sklerose möglicherweise kein prominentes Merkmal von MS. Zusammenfassend lässt sich festhalten, dass diese Dissertation einen Beitrag zum Gebiet der MRE leistet, indem neue Methoden und Anwendungen in neuen Forschungsgebieten mit modernster Technologie dargestellt werden. Hierdurch wird die klinische Translation gefördert und spannende Möglichkeiten für zukünftige Studien eröffnet

Inversion‐recovery MR elastography of the human brain for improved stiffness quantification near fluid–solid boundaries

Purpose: In vivo MR elastography (MRE) holds promise as a neuroimaging marker. In cerebral MRE, shear waves are introduced into the brain, which also stimulate vibrations in adjacent CSF, resulting in blurring and biased stiffness values near brain surfaces. We here propose inversion-recovery MRE (IR-MRE) to suppress CSF signal and improve stiffness quantification in brain surface areas. Methods: Inversion-recovery MRE was demonstrated in agar-based phantoms with solid-fluid interfaces and 11 healthy volunteers using 31.25-Hz harmonic vibrations. It was performed by standard single-shot, spin-echo EPI MRE following 2800-ms IR preparation. Wave fields were acquired in 10 axial slices and analyzed for shear wave speed (SWS) as a surrogate marker of tissue stiffness by wavenumber-based multicomponent inversion. Results: Phantom SWS values near fluid interfaces were 7.5 ± 3.0% higher in IR-MRE than MRE (P = .01). In the brain, IR-MRE SNR was 17% lower than in MRE, without influencing parenchymal SWS (MRE: 1.38 ± 0.02 m/s; IR-MRE: 1.39 ± 0.03 m/s; P = .18). The IR-MRE tissue-CSF interfaces appeared sharper, showing 10% higher SWS near brain surfaces (MRE: 1.01 ± 0.03 m/s; IR-MRE: 1.11 ± 0.01 m/s; P < .001) and 39% smaller ventricle sizes than MRE (P < .001). Conclusions: Our results show that brain MRE is affected by fluid oscillations that can be suppressed by IR-MRE, which improves the depiction of anatomy in stiffness maps and the quantification of stiffness values in brain surface areas. Moreover, we measured similar stiffness values in brain parenchyma with and without fluid suppression, which indicates that shear wavelengths in solid and fluid compartments are identical, consistent with the theory of biphasic poroelastic media

Heterogeneous multifrequency direct inversion (HMDI) for magnetic resonance elastography with application to a clinical brain exam

A new viscoelastic wave inversion method for MRE, called Heterogeneous Multifrequency Direct Inversion (HMDI), was developed which accommodates heterogeneous elasticity within a direct inversion (DI) by incorporating first-order gradients and combining results from a narrow band of multiple frequencies. The method is compared with a Helmholtz-type DI, Multifrequency Dual Elasto-Visco inversion (MDEV), both on ground-truth Finite Element Method simulations at varied noise levels and a prospective in vivo brain cohort of 48 subjects ages 18–65. In simulated data, MDEV recovered background material within 5% and HMDI within 1% of prescribed up to SNR of 20 dB. In vivo HMDI and MDEV were then combined with segmentation from SPM to create a fully automated “brain palpation” exam for both whole brain (WB), and brain white matter (WM), measuring two parameters, the complex modulus magnitude |G*| , which measures tissue “stiffness”, and the slope of |G*| values across frequencies, a measure of viscous dispersion. |G*| values for MDEV and HMDI were comparable to the literature (for a 3-frequency set centered at 50 Hz, WB means were 2.17 and 2.15 kPa respectively, and WM means were 2.47 and 2.49 kPa respectively). Both methods showed moderate correlation to age in both WB and WM, for both |G*| and |G*| slope, with Pearson’s r ≥ 0.4 in the most sensitive frequency sets. In comparison to MDEV, HMDI showed better preservation of recovered target shapes, more noise-robustness, and stabler recovery values in regions with rapid property change, however summary statistics for both methods were quite similar. By eliminating homogeneity assumptions within a fast, fully automatic, regularization-free direct inversion, HMDI appears to be a worthwhile addition to the MRE image reconstruction repertoire. In addition to supporting the literature showing decrease in brain viscoelasticity with age, our work supports a wide range of inter-individual variation in brain MRE results

Viscoelasticity Imaging of Biological Tissues and Single Cells Using Shear Wave Propagation

Changes in biomechanical properties of biological soft tissues are often associated with physiological dysfunctions. Since biological soft tissues are hydrated, viscoelasticity is likely suitable to represent its solid-like behavior using elasticity and fluid-like behavior using viscosity. Shear wave elastography is a non-invasive imaging technology invented for clinical applications that has shown promise to characterize various tissue viscoelasticity. It is based on measuring and analyzing velocities and attenuations of propagated shear waves. In this review, principles and technical developments of shear wave elastography for viscoelasticity characterization from organ to cellular levels are presented, and different imaging modalities used to track shear wave propagation are described. At a macroscopic scale, techniques for inducing shear waves using an external mechanical vibration, an acoustic radiation pressure or a Lorentz force are reviewed along with imaging approaches proposed to track shear wave propagation, namely ultrasound, magnetic resonance, optical, and photoacoustic means. Then, approaches for theoretical modeling and tracking of shear waves are detailed. Following it, some examples of applications to characterize the viscoelasticity of various organs are given. At a microscopic scale, a novel cellular shear wave elastography method using an external vibration and optical microscopy is illustrated. Finally, current limitations and future directions in shear wave elastography are presented

K-space data processing for magnetic resonance elastography (MRE)

OBJECTIVE: Magnetic resonance elastography (MRE) requires substantial data processing based on phase image reconstruction, wave enhancement, and inverse problem solving. The objective of this study is to propose a new, fast MRE method based on MR raw data processing, particularly adapted to applications requiring fast MRE measurement or high elastogram update rate. MATERIALS AND METHODS: The proposed method allows measuring tissue elasticity directly from raw data without prior phase image reconstruction and without phase unwrapping. Experimental feasibility is assessed both in a gelatin phantom and in the liver of a porcine model in vivo. Elastograms are reconstructed with the raw MRE method and compared to those obtained using conventional MRE. In a third experiment, changes in elasticity are monitored in real-time in a gelatin phantom during its solidification by using both conventional MRE and raw MRE. RESULTS: The raw MRE method shows promising results by providing similar elasticity values to the ones obtained with conventional MRE methods while decreasing the number of processing steps and circumventing the delicate step of phase unwrapping. Limitations of the proposed method are the influence of the magnitude on the elastogram and the requirement for a minimum number of phase offsets. CONCLUSION: This study demonstrates the feasibility of directly reconstructing elastograms from raw data

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