<p dir="ltr">Investigating the deformation and failure of human cortical bone under altered hydration contributes to the understanding of bone fracture. Further, studying the impact of hydration on bone deformation can lead to developing fracture prevention strategies that will enhance the lives of the aging population. In addition, characterization of cortical bone water modulation effects on biomechanical behavior helps us understand how bone dynamically changes due to aging, health conditions, and therapeutic interventions.</p><p dir="ltr">The concepts in this thesis are demonstrated on bone specimens of a 75-year-old male human subject. To investigate the potential role of water in bone as modulated by selective estrogen receptor modulators, we used magnetic resonance imaging to characterize bound water in human samples. The behavior of human cortical bone under mechanical loading protocols was tested to analyze the bone failure surface. Bone microstructure, microdamage, and fractures were observed from progressive bending experiments. Earlier evidence suggests that treating human cortical bone with Raloxifene (RAL) toughens bone but does not affect strength.</p><p dir="ltr">Questions remain about how RAL treatment affects bone biomechanics with the consideration of size effects. In this research, experiments were conducted on samples mimicking the thickness of cortical bone. Smaller thickness samples investigated in prior work were also considered, and intrinsic strength and tissue damage were introduced. Additionally, ultra-short echo-time magnetic resonance images were employed to observe 3D spatial information of bound and free water in the bone.</p><p dir="ltr">This research seeks to combine methods in bone biology and the mechanics of materials to solve problems of bone fragility. Linear strength concepts do not distinguish between treatments. However, treatment effects are detected with a nonlinear approach. Furthermore, this study provides valuable insights into quantifying bound water content within in-vitro specimen samples. These findings pave the way for further research into continued advancements addressing skeletal health challenges.</p>

Segmented analysis of subcortical structures within the nonhuman primate can potentially have a profound impact on studying the relationship between volumetric characteristics and alcohol dependencies. Image segmentations have been widely used in quantifying structural information. There are a variety of methods in which users can extract desired structures from a medical image; ranging from manual segmentations to fully-automated segmentations and 2-D to 3-D. The implications of this possibility can have tremendous applicability to medical research and diagnosis. The primary goal of my thesis is to investigate different implementation methodologies for segmenting subcortical structures such as the hippocampus and striatum and then apply that knowledge towards the development of an approach to segment these two structures from a group of alcohol-dependent Rhesus Macaque monkeys. Using the Level Set Deformable Model (LSDM) with a priori structural information, a series of T1-weighted MR images of Rhesus Macaque hippocampi and striatum were segmented in an effort to compare the structural hippocampal and striatal volumes between early and late stages of alcohol dependency. The results suggest that the volumes of both subcortical structures are affected negatively by alcoholism. Volume deficits of as much as 5% for the hippocampus and 8% for the caudate were found. / Master of Science

Significant advancements have been made within the field of regenerative medicine over the last few decades with the goal of creating biological substitutes to mimic tissue for research and wound healing purposes. Simply put, regenerative medicine works by understanding and then manipulating the processes by which cells communicate and proliferate for healing purposes. Before valuable progress can be made in regenerative medicine, smaller steps need to be taken first, like understanding the biomaterials that are used within regenerative medicine research. Biomaterials, which are materials that interact with cells and perform a function, are used to mimic the native extracellular matrix of cell scaffolding in regenerative medicine research. Numerous types of biomaterials exist, and it is important to choose the most appropriate material for the goal at hand. Therefore, biomaterials need to be characterized before useful research with the materials can be done. An important aspect of biomaterials that can be characterized is fluid flow through the biomaterials. This is important because adequate transport of oxygen, nutrients, waste, and soluble factors are required for cell proliferation and survival.[1] Biomaterials can be characterized based on their chemical, physical, and mechanical characteristics via many different characterization methods that are discussed in this paper. The overall goal of this research is to characterize the fluid flow metrics through Micro-porous Annealed Particle (MAP) hydrogels and others using Dynamic Contrast Enhanced – Magnetic Resonance Imaging (DCE-MRI) and computational analysis of the images via MATLAB. The analysis was utilized to analyze the fluid flow through several different biomaterial types, allowing for observational comparison between biomaterial groups. Overall, this method for characterizing fluid flow through biomaterials shows promise for future use and further understanding of biomaterials' roles in regenerative medicine. / Master of Science / Regenerative medicine encompasses the use of scientific knowledge and tools to determine novel methods for generating functioning tissues and organs. Commonly, biomaterials are used to assist in this process. Biomaterials frequently function as a solid structure that houses cells and encourages cell growth, eventually leading to tissue formation. Many different types of biomaterials exist, so it is important to determine the most suitable biomaterial for each project to improve efficiency and experiment outcomes. Biomaterial properties, like stiffness or flexibility, can be determined through various scientific testing methods. An important property of biomaterials is the fluid flow through the biomaterials. Cells housed inside biomaterials require oxygen and nutrients to grow, so it is important that fluids carrying these molecules can flow through biomaterials to provide support for the cells. This paper utilizes a computational analysis method to analyze Magnetic Resonance Imaging (MRI) images of fluid flow through biomaterials. The analysis provides information on fluid flow metrics through the biomaterials, like fluid flow velocity and direction. This analysis provides a new method for understanding biomaterial properties and provides the analysis for several different biomaterials.

Background: Quantitative imaging surrogates of myelin and axonal integrity using magnetization transfer and diffusion tensor imaging may provide beneficial prognostic details on long-term post-surgical recovery in dogs with spinal cord injury (SCI) secondary to intervertebral disc herniation (IVDH). Hypothesis: Magnetization transfer ratio (MTR), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) will be significantly different in patients with a successful outcome compared to patients with an unsuccessful outcome. Animals: 61 dogs with SCI secondary to IVDH were included in the final analysis. All dogs had to undergo surgical correction for SCI secondary to IVDH and be followed out for 12 weeks. Methods: Prospective cohort study. MTR, MD, AD, RD, and FA were calculated in dogs with SCI secondary to IVDH. A Wilcoxon signed-rank test was used to compare MTR, MD, AD, RD, and FA values between patients with a successful outcome and patients with an unsuccessful outcome. Statistical significance was set at p<0.05. For quantitative imaging surrogates with a significant relationship with outcome, a receiver operator characteristic (ROC) curve analysis was performed and the sensitivity and specificity for predicting successful outcome. Results: MTR (p=0.0013) was significantly lower in patients with a successful outcome compared to patients with an unsuccessful outcome. FA (p=0.435) was not significantly between groups. MD (p=0.0006), AD (p=0.0008) and RD (p=0.0002) were significantly higher in patients with a successful outcome compared to patients with an unsuccessful outcome. ROC curves were performed for MTR, AD and RD. If MTR was ≤ 53, AD ≥ 1.7 × 10-3mm2/s or RD ≥ 0.37 × 10-3 mm2/s, this resulted in a sensitivity of 96.3% and specificity of 100 in predicting a successful outcome. Conclusion and clinical relevance: MTR, MD, AD, and RD were helpful in predicting successful outcome in canine patients with surgically treated SCI secondary to IVDH. A larger cohort is needed for further evaluation. / Master of Science / Background: Certain magnetic resonance imaging (MRI) techniques can provide information about the severity of spinal cord injury. The information obtained from these MRI techniques can be helpful in predicting prognosis in dogs with intervertebral disc disease (IVDD). Hypothesis: We hypothesized that the measurements obtained from these MRI techniques would be able to predict the patients who would be able to walk following surgery (good long-term outcome), versus the patients who did not regain the ability to walk following surgery (poor long-term outcome). Animals: 62 MRIs were performed on dogs with IVDD in our study and were followed out for 12 weeks following surgery to assess long-term outcome. Results: Of the 5 MRI techniques investigated, 4 of the techniques were found to be helpful in predicted long-term outcome. When these techniques were combined, the ability to predict long-term outcome improved. Using the combined technique, all 53 patients predicted to have a good long-term had a good long-term outcome. For patients with a poor long-term outcome, 9 were predicted to have a poor long-term outcome, but only 7 patients had a poor long-term outcome. Conclusion and clinical relevance: MRI can be helpful in predicting long-term outcome in dogs with IVDD following surgery. A larger population of dogs is needed for further evaluation.

Right Ventricular (RV) dysfunction is a common cause of heart failure in patients with congenital heart defects and often leads to impaired functional capacity and premature death. 3D cardiac magnetic resonance imaging (CMR)-based RV/LV combination models with fluid-structure interactions have been introduced to perform mechanical analysis and optimize RV remodeling surgery. Obtaining accurate RV/LV morphology is a very important step in the model-constructing process. A semi-automatic segmentation process was introduced in this project to obtain RV/LV/Valve geometry from patient-specific 3D CMR images. A total of 420 contour results were obtained from one patient CMRI data using QMASS software package at Department of Cardiology of Children¡¯s hospital. The digital contour data were automatically acquired using a self-developed program written in MATLAB. 3D visualizations of the RV/LV combination model at different phases throughout the cardiac cycle were presented and RV/LV volume curves were given showing the volume variation based on digital contour data under MATLAB environment. For the patient considered, the RV stoke volume (SV) is 190.8 ml (normal value is 60-136 ml) and ejection fraction is 43.5% (normal value is 47%-63%). In future work, the surgical, CMR imaging and computational modeling will be integrated together to optimize patch design and RV volume reduction surgery procedures to maximize recovery of RV cardiac function.

Magnetic Resonance Imaging (MRI) is a widely used soft tissue imaging technique that has gained considerable success because of its sensitivity to several tissue parameters. However, commercially available whole-body imaging systems with large encircling radio frequency (RF) and gradient coils are less efficient when the goal is to obtain detailed, high-resolution images with high specificity and sensitivity from localized regions of the body such as the female breast. This research addresses these problems by proposing a new design in RF coil development for breast cancer screening in a conventional 1.5T MRI system. The new design provides two resonant receiving modes that operate in a quadrature configuration, and a region of interest (ROI) that closely conforms to the shape of the female breast. We adopted an optimum design strategy that combined the analytic Biot-Savart intergral equation with the Method of Moment formulation in the development of electromagnetic models and simulation tools. These models were used to analyze the magnetic field distribution and the spatial field coverage, as well as the magnetic field uniformity in the ROI. Results from our analysis were employed in the construction of a highly scalable prototype. The validation of our design strategy is confirmed by comparisons with the commercial Ansoft HFSS v8.5 finite element package.

The non-invasive cardiovascular imaging modalities, cardiovascular magnetic resonance (CMR) and multi-detector computer tomography (MDCT) are playing an increasing role in both clinical and research settings. CMR is a unique imaging modality due to unsurpassed contrast between soft tissue structures that is non-invasive, does not use ionising radiation and is able to provide high-resolution information about cardiac anatomy, function, flow, perfusion, viability and metabolism. It has provided the gold standard in imaging in congenital heart disease. Recent advances in this technology have led to images of high spatial and temporal resolution that has made the characterisation of atheroma possible. While currently spatial resolution still limits its ability to characterise atheroma in native human coronary arteries in living patients, CMR imaging of the coronary arteries has future potential with further technological and sequence advances. MDCT has been used in clinical settings to measure of the amount of calcification in the coronary arteries with “coronary artery calcium scoring” of the coronary tree a surrogate marker of atherosclerosis. MDCT has also become the gold standard for angiographic imaging in most arterial beds such as the carotid and peripheral vascular systems. In the coronary arteries in particular, there have been major advances in the accuracy of coronary MDCT angiography, particularly with regards to its negative predictive value, although excessive calcification and blooming artefacts still limit the diagnostic accuracy of the technique for assessing stenotic severity. In this thesis, our aims were to address some specific novel areas advancing the utility of these imaging modalities in two major areas of interest, namely congenital heart disease and atheroma imaging. Our first step was to validate the accuracy and reproducibility of CMR, the main imaging modality we utilised. To achieve this, we assessed MR imaging of cardiac volumes and function in a normal adult Australian population with a specific focus on the reproducibility of the technique. In confirming that this technique in our hands is both accurate and reproducible, we would then be in a position to be able to confidently use this technique in our future chapters. However, more than this, we sought to establish some normal ranges for left and right atrial and ventricular parameters in our local population. This would be crucial background information for us to be able to make comparisons with future studies in patients with congenital heart disease. Having established our technique and reference ranges, we would then explore the two specific issues in the ensuing two chapters using CMR in one area of congenital heart disease, atrial septal defect. Atrial septal defect is the most common congenital heart defect first diagnosed in adults. The traditional method of assessment of these patients and for suitability for ASD closure involves semiinvasive investigation with transoesophageal echocardiography (TOE) for measurement of the defect size and atrial septal margins. MRI assessment of patients prior to percutaneous device closure compared to TOE assessment would provide information on the accuracy of TOE assessment and provide information of the utility of cardiac MRI as an alternative to TOE for the work-up of these patients prior to ASD closure. In our third original research chapter, we utilised CMR to understand the effects of percutaneous ASD closure on cardiac chamber volumes. We achieved this by assessing with cardiac MRI pre-closure and post-closure atrial and ventricular cardiac volumes. Longstanding right heart dilatation in the setting of an ASD may lead to complications including right heart failure, pulmonary hypertension and arrhythmia. Closure of the ASD should reduce right heart volumes by removing left-to-right shunting and lead to normalisation of ventricular volumes. The assessment of atrial volume changes with ASD closure may be important in furthering our understanding in its contribution to arrhythmia. Having assessed the ability of CMR to assess both the ASD dimensions, and therefore suitability for percutaneous closure, as well as the effects of ASD closure on cardiac chamber size, we look in the final two original research chapters to move to another area of research development with these highresolution imaging technologies, atherosclerosis imaging. Two particular areas we wished to focus on included the potential of high-resolution MR imaging to monitor effects of HDL infusion on atherosclerosis, and secondly to explore mechanisms behind limitations in MDCT imaging of atherosclerosis, specifically calcification and blooming artifacts. For assessing the effects of HDL infusion on atherosclerosis, we utilised a cholesterol-fed rabbit model of atherosclerosis. The abdominal aorta of the rabbit is comparable in size to the human coronary artery. Previous work with the rabbit model of atherosclerosis and magnetic resonance imaging of the aortic wall has shown that it can provide information about atherosclerotic composition as well as provide serial data of the arterial wall. While high intensity lipid-lowering with statins remains the first line management of at risk individuals, modest manipulations of serum HDL levels are associated with a significant impact on cardiovascular risk. Thus, we assessed the effect of HDL infusion and atorvastatin in a rabbit model of using MRI aortic atherosclerosis as the endpoint. In our fifth and final original research chapter, we assessed the accuracy of quantification of atherosclerotic calcification with MDCT in the carotid arteries of patients undergoing carotid endarterectomy, and sought to identify algorithms or techniques that may improve quantification of calcification. This would potentially lead to an improvement in the ability of MDCT techniques to quantify stenotic severity in coronary arteries that were calcified. To achieve these we utilised MDCT in vivo and in comparison with carotid endarterectomy specimen micro-CT. Importantly, as part of this study, we undertook a thorough assessment of reproducibility of these techniques. Thus, in summary, we have been able to confirm the accuracy and reproducibility of CMR and MDCT in the areas of a specific congenital defect (ASD) and atherosclerosis imaging, and utilised these techniques to advance our understanding of these disease states. This thesis identifies strengths and weaknesses of these techniques that will allow us to more appropriately use them for future purposes in cardiovascular disease. Future work directly stemming from this thesis has already begun, and now looks to address issues of whether CMR and MDCT may provide complimentary information about atherosclerotic lesions that may benefit outcomes in certain conditions. Specifically the work in this thesis has led to studies commencing in carotid atherosclerosis and saphenous vein graft atherosclerosis and using these imaging techniques to potentially predict adverse future outcomes. / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2008

Magnetic resonance imaging (MRI) is a very versatile imaging modality which can be used to acquire several different types of images. Some examples include anatomical images, images showing local brain activation and images depicting different types of pathologies. Brain activation is detected by means of functional magnetic resonance imaging (fMRI). This is useful e.g. in planning of neurosurgical procedures and in neurological research. To find the activated regions, a sequence of images of the brain is collected while a patient or subject alters between resting and performing a task. The variations in image intensity over time are then compared to a model of the variations expected to be found in active parts of the brain. Locations with high correlation between the intensity variations and the model are considered to be activated by the task. Since the images are very noisy, spatial filtering is needed before the activation can be detected. If adaptive filtering is used, i.e. if the filter at each location is adapted to the local neighborhood, very good detection performance can be obtained. This thesis presents two methods for adaptive spatial filtering of fMRI data. One of these is a modification of a previously proposed method, which at each position maximizes the similarity between the filter response and the model. A novel feature of the presented method is rotational invariance, i.e. equal sensitivity to activated regions in different orientations. The other method is based on bilateral filtering. At each position, this method averages pixels which are located in the same type of brain tissue and have similar intensity variation over time. A method for robust correlation estimation is also presented. This method automatically detects local bursts of noise in a signal and disregards the corresponding signal segments when the correlation is estimated. Hence, the correlation estimate is not affected by the noise bursts. This method is useful not only in analysis of fMRI data, but also in other applications where correlation is used to determine the similarity between signals. Finally, a method for correcting artifacts in complex MR images is presented. Complex images are used e.g. in the Dixon technique for separate imaging of water and fat. The phase of these images is often affected by artifacts and therefore need correction before the actual water and fat images can be calculated. The presented method for phase correction is based on an image integration technique known as the inverse gradient. The method is shown to provide good results even when applied to images with severe artifacts.

During cardiac ischemia, intracellular calcium (Ca²⁺) overload occurs which can result in cell death. MRI T₁ shortening contrast agent manganese (Mn²⁺) acts as a surrogate marker for Ca²⁺. Cardiac T₁-mapping manganese-enhanced MRI (MEMRI) techniques were applied to study the efflux of Mn²⁺ from both healthy mice and mice post-myocardial infarction (MI) surgery. Temporal changes in the myocardial relaxation rate, ∆R₁, post-MnCl₂ infusion were shown to be linearly correlated to the absolute Mn content. The relative importance of individual efflux mechanisms in healthy mice was investigated by inhibiting the sodium-calcium exchanger (NCX) with SEA0400, following infusion of MnCl₂, with SEA0400 reducing the rate of Mn²⁺ efflux. Regional alterations in Mn²⁺ uptake and efflux were also studied post-myocardial infarction, allowing for the identification of potentially salvageable myocardium in the peri-infarcted zone surrounding the necrosed tissue. Application of pharmacokinetic models to in vivo and elemental analysis data from both the healthy and MI mice groups suggested that the NCX was more active in Mn²⁺ efflux than for Ca²⁺ and that there was an increase in Mn²⁺ uptake due to the disease condition, consistent with Ca²⁺ overloading. Studying Mn²⁺ efflux using these protocols could provide a pre-clinical model for examining alterations in relative Ca²⁺ fluxes and to potentially monitor disease progression.

Imaging guidance may allow minimally invasive alternatives to open surgical exposure and help reduce procedure risk and morbidity. The inherent vascular and soft-tissue contrast of MRI make it an appealing imaging modality to guide cardiovascular interventional procedures. Advances in real-time MRI have made MRI-guided procedures a realistic possibility. The MR environment, however, introduces additional challenges to the development of compatible, conspicuous and safe devices. The overall goal of this work was to enable selected MRI-guided cardiovascular interventional procedures with clearly visible MR devices. In the first part of this work, we developed actively visualized devices for three distinct MRI-guided interventional procedures and techniques to assess their signal performance. We then investigated factors influencing complex device safety in the MR environment and evaluated a technique to better determine and monitor potential device heating. This input contributed to the development of a system to further improve device safety with continual device monitoring and dynamic scanner feedback control. In the final part of this work, we demonstrated the utility of MRI guidance and actively visualized devices to enable traditional and complex cardiovascular access. Together these provide important elements to bring MRI-guided cardiovascular interventional procedures closer to clinical implementation.