<p> Prostate cancer is among the most prevalent and deadly of malignancies in both the United States and worldwide. Ongoing diagnostic challenges in prostate cancer include differentiating low-risk and high-risk tumors, and monitoring responses to therapy in patients with aggressive disease. Prostate cancer metabolism is characterized by a shift to aerobic glycolysis with lactate production and efflux, as well as increased tricarboxylic acid cycle activity, which has led to the investigation and development of metabolic imaging strategies such as hyperpolarized 13C MRI. However, it is nontrivial to study human prostate cancer metabolism in vivo, and the capability to better characterize tumor metabolism from a variety of disease states would be valuable for metabolic imaging biomarker development. This dissertation focuses on developing ex vivo strategies to measure metabolism in benign and malignant living human prostate tissue. First, because prostate tissue heterogeneity can impact metabolic measurements, we present the engineering of a 600 MHz radiofrequency (RF) microcoil to assess the heterogeneity of freshly acquired human prostate biopsies using microscale diffusion-weighted imaging (DWI). Next, we demonstrate the capability of micro-DWI to determine the biopsy percentage of glandular tissue, setting the stage for establishing the percentage and grade of cancer using this approach. After this, we develop a protocol for nuclear magnetic resonance (NMR) quantification of lactate production and efflux and glutamate fractional enrichment in freshly acquired living human prostate biopsies cultured with [1,6-13C2]glucose. In this study we demonstrate a significantly higher lactate efflux rate coming from low-grade prostate cancer versus benign biopsies in an early-stage patient population. This sets the stage for studies of metabolic fluxes and steady-state metabolite levels in biopsies from patients with aggressive disease before and after non-surgical therapy. Finally, due to recent interest in the potential role of Myc amplification and glutaminolysis upregulation in treatment insensitive castrate-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC), we present metabolic labeling results from a study of primary human prostate tissue slice cultures (TSCs) obtained at surgery and cultured with either [1,6-13C2]glucose or [3-13C]glutamine. Our results are consistent with prior thinking on the role of glucose and glutamine metabolism in treatment-na&iuml;ve prostate cancer.</p><p>

Quantitative Magnetic Resonance has become more and more accepted for clinical trial in many fields. This technique not only can generate qMRI maps (such as T1/T2/PD) but also can be used for further postprocessing including segmentation of brain and characterization of different brain tissue. Another main application of qMRI is to measure the volume of the brain tissue such as the deep Grey Matter (dGM). The deep grey matter serves as the brain's "relay station" which receives and sends inputs between the cortical brain regions. An abnormal volume of the dGM is associated with certain diseases such as Fetal Alcohol Spectrum Disorders (FASD). The goal of this study is to investigate the effect of age on the volume change of the dGM using qMRI. Thirteen patients (mean age= 26.7 years old and age range from 0.5 to 72.5 years old) underwent imaging at a 1.5T MR scanner. Axial images of the entire brain were acquired with the mixed Turbo Spin-echo (mixed -TSE) pulse sequence. The acquired mixed-TSE images were transferred in DICOM format image for further analysis using the MathCAD 2001i software (Mathsoft, Cambridge, MA). Quantitative T1 and T2-weighted MR images were generated. The image data sets were further segmented using the dual-space clustering segmentation. Then volume of the dGM matter was calculated using a pixel counting algorithm and the spectrum of the T1/T2/PD distribution were also generated. Afterwards, the dGM volume of each patient was calculated and plotted on scatter plot. The mean volume of the dGM, standard deviation, and range were also calculated. The result shows that volume of the dGM is 47.5 ±5.3ml (N=13) which is consistent with former studies. The polynomial tendency line generated based on scatter plot shows that the volume of the dGM gradually increases with age at early age and reaches the maximum volume around the age of 20, and then it starts to decrease gradually in adulthood and drops much faster in elderly age. This result may help scientists to understand more about the aging of the brain and it can also be used to compare with the results from former studies using different techniques.

No description available.

There is increasing interest in the use of small field of view (SFOV) portable gamma cameras in medical imaging. A novel hybrid optical-gamma camera (HGC) has been developed through a collaboration between the Universities of Leicester and Nottingham. This system offers high resolution gamma and optical imaging and shows potential for use at the patient bedside, or in the operating theatre. The aim of this thesis was to translate the HGC technology from in vitro laboratory studies to clinical use in human subjects. Pilot studies were undertaken with the HGC as part of this thesis. Furthermore, efforts have been made to transform the HGC technologies into a new medical device, known as Nebuleye. Initial physical evaluation of the pre-production prototype camera was carried out as part of the device developmental process, highlighting some aspects of the design that require further modification. A complete and rigorous testing scheme to assess the pre-production prototype camera has been developed and successfully implemented. The newly introduced tests enabled the system uniformity, system sensitivity, detector head shielding leakage, optical-gamma image alignment and optical image quality of the hybrid camera to be assessed objectively. This harmonised testing scheme allows characterisation and direct comparison of SFOV gamma cameras. In vitro and in vivo preclinical imaging was undertaken to examine the performance of the SFOV gamma cameras for experimental animal studies. The results of animal study have shown for the first time the feasibility and performance of these SFOV gamma cameras for imaging mice injected with a newly developed 111In labelled hybrid tracer. Further investigations are needed to improve the system resolution and prepare the camera system for combined gamma-near infrared fluorescence imaging in future. A systematic in vitro laboratory assessment method has been established to examine the imaging performance of the SFOV gamma camera in radioguided sentinel lymph node biopsy (SLNB) and radioactive seed localisation procedures for breast cancer surgery. Further preparatory work was undertaken to carry out a pilot clinical trial of the use of the pre-production prototype camera in sentinel node localisation procedures during breast cancer surgery. The clinical study protocol and routine quality control procedures have been established and are suitable for future use. Baseline data on the camera performance assessed using the routine quality control scheme have been obtained. Finally, the capabilities of the SFOV gamma camera were assessed. This has provided baseline data on user feedback and the imaging consequences on operator motion effects, as well as examining the detectability of a range of radionuclides, including 99mTc, 111In, 123I, 125I and 75Se. The first clinical results of the use of the HGC in clinical hybrid optical-gamma imaging in patients administered with 99mTc and 123I labelled radiopharmaceuticals have been reported. This clinical study has demonstrated the feasibility and capability of HGC in various clinical applications performed at the patient bedside, which included patients undergoing bone, thyroid, lacrimal drainage and lymphatic imaging as well as DaTscan studies. In conclusion, the work in this thesis has demonstrated the successful translation of an SFOV hybrid gamma camera for clinical use. This system would be ideally suited for use in the operating theatre for radioguided procedures such as sentinel node detection and tumour localisation. This system also offers potential for use with the new generation of hybrid fluorescent-radionuclide tracers currently under development.

Among patients presenting acutely with ischaemic stroke who are being considered for intravenous thrombolysis, prompt brain imaging is used to exclude contraindications to treatment (chiefly haemorrhagic stroke or other conditions mimicking stroke) rather than to identify which patients are more or less likely to benefit from thrombolysis. For example, it is unclear whether the presence or absence of arterial obstruction on imaging should be used to guide thrombolysis treatment decisions. In this thesis I explore methods of imaging arterial patency among patients presenting acutely with ischaemic stroke and look for associations between these early imaging findings, response to intravenous thrombolysis and functional outcome six-months after stroke onset. I primarily use data from the Third International Stroke Trial (IST-3), the largest ever randomised-controlled trial testing the use of intravenous alteplase for the acute treatment of ischaemic stroke. I begin by summarising the main features of stroke, covering techniques for imaging the brain and for imaging arterial patency, and post-stroke outcomes. Next I describe two literature reviews which I compiled to increase my understanding of the topic with particular reference to imaging arterial patency. This is followed by a summary of IST-3. Then I describe the general methods I used to address my thesis aims exploring relationships between imaging characteristics of arterial patency, treatment with intravenous alteplase and functional outcome after ischaemic stroke. Specifically, I investigated the following imaging features: - The hyperattenuating artery sign (HAS), which is a non-contrast enhanced CT finding thought to be indicative of acute arterial obstruction by thrombus or embolus - Arterial patency or obstruction as demonstrated using contrast enhanced CT and MR angiographic imaging. In addition to providing better characterisation of the HAS and a better understanding of how angiography helps to assess ischaemic stroke patients, I found that arterial obstruction (however this is identified on imaging) is associated with more severe stroke at baseline and worse functional outcome six months after stroke. I also prove that intravenous alteplase is effective in the presence of arterial obstruction, counter to a widely held concern that it may not be effective in this context. Most of my work has been published in peer reviewed journals. My work should give front line clinicians greater confidence to use intravenous alteplase for the treatment of ischaemic stroke associated with arterial obstruction on imaging, but more work is needed to better understand the implications of apparently normal arterial patency on imaging among patients with ischaemic stroke.

The work in this thesis falls into three sections: (i). the development and application of a computer simulation of the MRI experiment based on the Bloch Equations incorporating all flow and motion effects that would be expected in the body, (ii). a theoretical analysis of factors affecting the efficacy of perfusion and diffusion imaging techniques and (iii). the proposal and evaluation of a new technique for the MRI measurement of perfusion. The simulation provided a powerful analytical tool used in the theoretical work of this thesis. The modularity of the design will enable simple development for future applications. The purpose of the theoretical analysis was to resolve many of the controversial issues arising from the various diffusion and perfusion imaging techniques including: the applicability of the various techniques in different in-vivo systems, the effects of motion artifacts, noise and eddy currents. Some conclusions of great significance were arrived at specifically the importance chosing a flow measurement technique appropriate to the tissue and flow type and the severe effects of motion artifacts in IVIM and phase display imaging. From this analysis a new perfusion imaging technique was derived which was implemented and evaluated in a perfusion phantom and in the calf muscle. Very good results were achieved in the phantom studies, and the results from the calf muscle were promising. On a clinical MRI system the technique could prove very useful.

An important goal of single photon emission tomography (SPECT) is the determination of absolute regional radionuclide concentration as a function of time. Quantitative and qualitative studies of SPECT with regard to clinical application is the object of this work. Three basic approaches for image reconstruction and factors which affect the choice of a reconstruction algorithm have been reviewed, discussed and the reconstruction techniques, GRADY and CBP evaluated, based on computer modelling. A sophisticated package of computational subroutines, RECLBL, for image reconstruction and for generation of phantoms, which was fully implemented on PRIME was used throughout this study. Two different systems, a rotating gamma-camera and a prototype scanning-rig have been used to carry out tomography experiments with different phantoms in emission and transmission mode. Performance assessment and reproducibility of the gamma-camera was tested prior to the experimental work. SPECT studies are generally hampered for a number of reasons, the most severe being attenuation and scattering. The effect of scattered photons on image quality was discussed, three distinct techniques were utilised to correct the images and results were compared. Determination of the depth of the source, Am-241 and Tc-99m in the attenuating media, water and TEMEX by analysing the spectroscopic data base on the SPR and spatial resolution was studied, results revealed that both techniques had the same range of depth sensitivity. A method of simultaneous emission and transmission tomography was developed to correct the images for attenuation. The reproducibility of the technique was examined. Results showed that the technique is able to present a promising and a practical approach to more accurate quantitative SPECT imaging. A procedure to evaluate images, under certain conditions has been defined, its properties were evaluated using computer modelling as well as real data. Usefulness of the odd sampling technique to improve image quality has been investigated and is recommended.

This project concerns the development of electrical impedance tomography towards the production of complex impedance images. The prime intention was to investigate the feasibility of developing suitable instrumentation; but not clinical applications. It was aimed to develop techniques for the performance evaluation of data collection systems. To achieve this it was necessary to design and develop a multi· current source type impedance tomography system, to act as a platform for the current study and for future work. The system developed is capable of producing conductivity and permittivity images. It employs microprocessor based data collection electronics, providing portability between a range of possible host computers. The development of the system included a study of constant amplitude current source circuits leading to the design and employment of a novel circuit. In order to aid system testing, a surface mount technology resistor-mesh test object was produced. This has been adopted by the EEC Concerted Action on Impedance Tomography (CAIT) programme as the first standard test object. A computer model of the phantom was produced using the industry standard ASTEC3 circuit simulation package. This development allows the theoretical performance of any system topology, at any level of detail, to be established. The imaging system has been used to produce images from test objects, as well as forearm and lung images on humans. Whilst the conductivity images produced were good, the permittivity in-vivo images were noisy, despite good permittivity images from test objects. A study of the relative merits of multiple and single stimulus type systems was carried out as a result of the discrepancies in the in-vivo and test object images. This study involved a comparison of the author's system with that of Griffiths at the University Hospital of Wales. The results showed that the multi current source type system, whilst able to reduce stray capacitance, creates other more significant errors due to circuit matching; future development in semiconductor device technology may help to overcome this difficulty. It was identified that contact impedances together with the effective capacitance between the measurement electrode pairs in four-electrode systems reduces the measurability of changes in phase. A number of benchmarking indices were developed and implemented, both for system characterisation and for practical/theoretical design comparisons.

<p> Horses are powerful animals: a galloping horse&rsquo;s forefoot hits the ground with an average of about 2,000 pounds of force. This can result in many kinds of injuries. To work with and love a horse properly, the owner needs to understand more than just grooming and feeding. Owners must understand how the horse operates, particularly the structure and workings of the horse&rsquo;s legs, to comprehend how a broken leg impairs a horse. This understanding enables the owner to work well with a veterinarian in determining the best course of treatment for an injury. </p><p> A review of the current veterinary literature and public resources showed that illustrated information regarding types of limb fractures in horses, options for repair and post-operative outcomes, that can be easily understood by the lay person, do not exist. The lack of sufficiently illustrated resources covering this topic indicates a great need for this valuable information. </p><p> The objective of this thesis is to illustrate common types of fractures, to assist owners in understanding different types of fractures, repair options, and possible outcomes of any intervention. Three cases, each with a specific type of fracture, were analyzed to develop understanding of the damage, the impact on the horse and surgical options versus the need for euthanasia. The finished product of this research was two posters, one for repair and the other for euthanasia, designed to enhance the owner&rsquo;s comprehension of the injuries.</p><p>

This thesis is the culmination of a program of research which initially began in 1995. It reflects a major professional interest in the imaging of sports injuries which developed gradually over the 10 year period between 1992 to 2001, based upon previous clinical experience and expertise in the management of musculoskeletal injuries and their anatomical and pathomechanical origins. The central theme of study relates to the use of cross-sectional imaging techniques to investigate the pathoanatomical basis for groin pain in althletes with particular reference to professional soccer players with chronic groin pain. The current thesis is based around two key postulates. Firstly, that most of the commonly diagnosed causes of groin pain in professional athletes are anatomically and functionally linked and, secondly, that modern cross-sectional imaging can demonstrate both the correct diagnosis and the underlying biomechanical causes. The program of study consists of three different but linked project themes. The first investigates the scope of the problem, i.e. the differential diagnosis and prevalence of groin pain in professional soccer players. The second investigates the precise "normal" anatomy, i.e. the gross topographical anatomy of the pubic symphysis and parasymphyseal regions as actually exists rather than the regional anatomy that appears in classical anatomical texts. The third builds upon the first two projects and, investigates the underlying pathomechanical processes using magnetic resonance imaging. The study results suggest that a unifying mechanism of injury exists which partly explains the diagnostic and therapeutic difficulties that occur in athletes with groin pain. It also demonstrates that better understanding of the true pubic symphyseal anatomy allows a more accurate diagnosis to be made and that magnetic resonance imaging can demonstrate the relevant underlying pathoanatomy. The thesis adds significantly to the body of scientific knowledge related to this important sports-related, clinical condition.