Involviert in Netzwerke für das episodische Gedächtnis sowie als Bestandteil des Hypothalamus und des limbischen Systems stellen sich die im Zwischenhirn gelegenen Mamillarkörper als Zielstruktur im Kontext affektiver Störungen dar. Bislang waren die Mamillarkörper diesbezüglich lediglich in einer postmortem durchgeführten Studie Gegenstand der Forschung; es liegen keine Untersuchungen mit Hilfe der 7 Tesla-Magnetresonanztomografie vor. Um diese neuen Möglichkeiten der in vivo-Volumetrie im Submillimeterbereich auszuschöpfen, wurde auf Grundlage einer farbkodierten Darstellung ein detaillierter Algorithmus entwickelt, der sich als Hauptergebnis der vorliegenden Arbeit als hoch reliabel erwies. In der vorliegenden Pilotstudie wurde darüber hinaus das Mamillarkörper-Volumen von 14 Patientinnen und Patienten mit einer Bipolaren Störung und 20 gesunden Kontrollpersonen anhand von hochaufgelösten T1-gewichteten MRT-Bildern bestimmt. Ein signifikanter Unterschied zwischen den beiden Gruppen konnte nicht nachgewiesen werden, ebenso kein Unterschied zwischen den Geschlechtern. Es konnte gezeigt werden, dass das Volumen der Mamillarkörper signifikant invers mit dem Alter der ProbandInnen korreliert. Des Weiteren wurde eine signifikante positive Korrelation mit dem Gesamthirnvolumen der ProbandInnen festgestellt. Krankheitsschwere und Episodenzahl hingegen hatten keinen Einfluss auf das Mamillarkörper-Volumen. Die Ergebnisse dieser Pilotstudie sollten anhand einer größeren Stichprobe überprüft werden.

Dosimetry is a vital component of treatment planning in radiation therapy. Methods of radiation dosimetry currently include the use of: ionization chambers, thermoluminescent dosimeters (TLDs), solid-state detectors and radiographic film. However, these methods are inherently either 1D or 2D and their use involves the perturbation of the radiation beam. Although the dose distribution within tissues following radiation therapy treatments can be modeled using computerized treatment planning systems, a need exists for a dosimeter that can accurately measure dose distributions directly and produce 3D dose maps. Some radiation therapy and brachytherapy treatments require mapping the dose distributions in high-resolution (typically < 1 mm). A dosimetry technique that is capable of producing high resolution 3D dose maps of the absorbed dose distribution within tissues is required. Gel dosimetry is inherently a 3D integrating dosimeter that offers high spatial resolution, precision and accuracy. Polymer gel dosimetry is founded on the basis that monomers dissolved in the gel matrix polymerize due to the presence of free radicals produced by the radiolysis of water molecules. The amount of polymerization that occurs within a polymer gel dosimeter can be correlated to the absorbed dose. The gel matrix maintains the spatial integrity of the polymers and hence a dose distribution can be determined by imaging the irradiated polymer gel dosimeter using an imaging modality such as MRI, x-ray computed tomography (CT), ultrasound, optical CT or vibrational spectroscopy. Polymer gel dosimeters, however, suffer from oxygen contamination. Oxygen inhibits the polymerization reaction and hence polymer gel dosimeters must be manufactured, irradiated and scanned in hypoxic environments. Normoxic polymer gel dosimeters incorporate an anti-oxidant into the formulation that binds the oxygen present in the gel and allows the dosimeter to be made under normal atmospheric conditions. The first part of this study was to provide a comprehensive investigation into various formulations of polymer and normoxic polymer gel dosimeters. Several parameters were used to characterize and assess the performance of each formulation of polymer gel dosimeter including: spatial resolution and stability, temporal stability of the R2-dose response, optimal R2-dose response for changes in concentration of constituents and the effects of oxygen infiltration. This work enabled optimal formulations to be determined that would provide greater dose sensitivity. Further work was done to investigate the chemical kinetics that take place within normoxic polymer gel dosimeters from manufacture to post-irradiation. This study explored the functions that each of the constituent chemicals plays in a polymer gel dosimeter. Although normoxic polymer gel dosimeters exhibit very similar characteristics to polyacrylamide polymer gel dosimeters, one important difference between them was found to be a decrease in R2-dose sensitivity over time in the normoxic polymer gel dosimeter compared to an increase in the polyacrylamide polymer gel dosimeters. From an investigation into the function of anti-oxidants in normoxic polymer gel dosimeters, alternatives were proposed. Several alternative anti-oxidants were explored in this study that found that whilst some were reasonably effective, tetrakis (hydroxymethyl) phosphonium chloride (THPC) had the highest reaction rate. THPC was found not only to be an aggressive scavenger of oxygen, but also to increase the dose sensitivity of the gel. Hence, a formulation of normoxic polymer gel dosimeter was proposed, called MAGAT, that comprised: methacrylic acid, gelatin, hydroquinone and THPC. This formulation was examined in a similar fashion to the studies of the other formulations of polymer and normoxic polymer gel dosiemeters. The gel was found to exhibit spatial and temporal stability and an optimal formulation was proposed based on the R2-dose response. Applications such as IVBT require high-resolution dosimetry. Combined with high-resolution MRI, polymer gel dosimetry has potential as a high-resolution 3D integrated dosimeter. Thus, the second component of this study was to commission a micro-imaging MR spectrometer for use with normoxic polymer gel dosimeters and investigate artifacts related to imaging in high-resolutions. Using high-resolution MRI requires high gradient strengths that, combined with the Brownian motion of water molecules, was found to produce an attenuation of the MR signal and hence lead to a variation in the measured R2. The variation in measured R2 was found to be dependent on both the timing and amplitude of pulses in the pulse sequence used during scanning. Software was designed and coded that could accurately determine the amount of variation in measured R2 based on the pulse sequence applied to a phantom. Using this software, it is possible to correct for differences between scans using different imaging parameters or pulse sequences. A normoxic polymer gel dosimeter was irradiated using typical brachytherapy delivery and the resulting dose distributions compared with dose points predicted by the computerized treatment planning system.The R2-dose response was determined and used to convert the R2 maps of the phantoms to dose maps. The phantoms and calibration vials were imaged with an in-plane resolution of 0.1055 mm/pixel and a slice thickness of 2 mm. With such a relatively large slice thickness compared to the in-plane resolution, partial volume effects were significant, especially in the region immediately adjacent the source where high dose gradients typically exist. Estimates of the partial volume effects at various distances within the phantom were determined using a mathematical model based on dose points from the treatment planning system. The normalized and adjusted dose profiles showed very good agreement with the dose points predicted by the treatment planning system.

The retina is a thin layer of tissue lining the back of the eye and is primarily responsible for sight in vertebrates. The neural retina has a distinct layered structure with three dense nuclear layers, separated by plexiform layers comprising of axons and dendrites, and a layer of photoreceptor segments. The retinal and choroidal vasculatures nourish the retina from either side, with an avascular layer comprised largely of photoreceptor cells. Diseases that directly affect the neural retina like retinal degeneration as well as those of vascular origin like diabetic retinopathy can lead to partial or total blindness. Early detection of these diseases can potentially pave the way for a timely intervention and improve patient prognosis. Current techniques of retinal imaging rely mainly on optical techniques, which have limited depth resolution and depend mainly on the clarity of visual pathway. Magnetic resonance imaging is a versatile tool that has long been used for anatomical and functional imaging in humans and animals, and can potentially be used for retinal imaging without the limitations of optical methods. The work reported in this thesis involves the development of high resolution magnetic resonance imaging techniques for anatomical and functional imaging of the retina in rats. The rats were anesthetized using isoflurane, mechanically ventilated and paralyzed using pancuronium bromide to reduce eye motion during retinal MRI. The retina was imaged using a small, single-turn surface coil placed directly over the eye. The several physiological parameters, like rectal temperature, fraction of inspired oxygen, end-tidal CO2, were continuously monitored in all rats. MRI parameters like T1, T2, and the apparent diffusion coefficient of water molecules were determined from the rat retina at high spatial resolution and found to be similar to those obtained from the brain at the same field strength. High-resolution MRI of the retina detected the three layers in wild-type rats, which were identified as the retinal vasculature, the avascular layer and the choroidal vasculature. Anatomical MRI performed 24 hours post intravitreal injection of MnCl2, an MRI contrast agent, revealed seven distinct layers within the retina. These layers were identified as the various nuclear and plexiform layers, the photoreceptor segment layer and the choroidal vasculature using Mn54Cl2 emulsion autoradiography. Blood-oxygenlevel dependent (BOLD) functional MRI (fMRI) revealed layer-specific vascular responses to hyperoxic and hypercapnic challenges. Relative blood volume of the retina calculated by using microcrystalline iron oxide nano-colloid, an intravascular contrast agent, revealed high blood-volume in the choroidal vasculature. Fractional changes to blood volume during systemic challenges revealed a higher degree of autoregulation in the retinal vasculature compared to the choroidal vasculature, corroborating the BOLD fMRI data. Finally, the retinal MRI techniques developed were applied to detect structural and vascular changes in a rat model of retinal dystrophy. We conclude that retinal MRI is a powerful investigative tool to resolve layer-specific structure and function in the retina and to probe for changes in retinal diseases. We expect the anatomical and functional retinal MRI techniques developed herein to contribute towards the early detection of diseases and longitudinal evaluation of treatment options without interference from overlying tissue or opacity of the visual pathway.

Involviert in Netzwerke für das episodische Gedächtnis sowie als Bestandteil des Hypothalamus und des limbischen Systems stellen sich die im Zwischenhirn gelegenen Mamillarkörper als Zielstruktur im Kontext affektiver Störungen dar. Bislang waren die Mamillarkörper diesbezüglich lediglich in einer postmortem durchgeführten Studie Gegenstand der Forschung; es liegen keine Untersuchungen mit Hilfe der 7 Tesla-Magnetresonanztomografie vor. Um diese neuen Möglichkeiten der in vivo-Volumetrie im Submillimeterbereich auszuschöpfen, wurde auf Grundlage einer farbkodierten Darstellung ein detaillierter Algorithmus entwickelt, der sich als Hauptergebnis der vorliegenden Arbeit als hoch reliabel erwies. In der vorliegenden Pilotstudie wurde darüber hinaus das Mamillarkörper-Volumen von 14 Patientinnen und Patienten mit einer Bipolaren Störung und 20 gesunden Kontrollpersonen anhand von hochaufgelösten T1-gewichteten MRT-Bildern bestimmt. Ein signifikanter Unterschied zwischen den beiden Gruppen konnte nicht nachgewiesen werden, ebenso kein Unterschied zwischen den Geschlechtern. Es konnte gezeigt werden, dass das Volumen der Mamillarkörper signifikant invers mit dem Alter der ProbandInnen korreliert. Des Weiteren wurde eine signifikante positive Korrelation mit dem Gesamthirnvolumen der ProbandInnen festgestellt. Krankheitsschwere und Episodenzahl hingegen hatten keinen Einfluss auf das Mamillarkörper-Volumen. Die Ergebnisse dieser Pilotstudie sollten anhand einer größeren Stichprobe überprüft werden.

Computed Tomography (CT) is often used for building 3D biomechanical models of human anatomy. This method exposes the subject to a significant x-ray dose and provides limited soft-tissue contrast. Magnetic Resonance Imaging (MRI) is a potential alternative to CT for this application, as MRI offers significantly better soft-tissue contrast and does not expose the subject to ionizing radiation. However, MRI requires long scan times to achieve 3D images at sufficient resolution, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). These long scan times can make subject motion a problem. This thesis describes my work to reduce scan time while achieving sufficient resolution, SNR, and CNR for 3D biomechanical modeling of (1) the human larynx, and (2) the human hip. I focused on two important strategies for reducing scan time and improving SNR and CNR: the design of RF coils optimized to detect MRI signals from the anatomy of interest, and the determination of MRI relaxation properties of the tissues being imaged (allowing optimization of imaging parameters to improve CNR between tissues). Work on the larynx was done in collaboration with the Thomson group in Mechanical Engineering at BYU. To produce a high-resolution 3D image of the larynx, a 2-channel phased array was constructed. Eight different coil element designs were analyzed for use in the array, and one chosen that provided the highest Q-ratio while still meeting the mechanical constraints of the problem. The phased array was tested by imaging a pig larynx, a good substitute for the human larynx. Excellent image quality was achieved and MR relaxometry was then performed on tissues in the larynx. The work on the hip was done in collaboration with the Anderson group in orthopedics at the University of Utah, who are building models of femoral acetabular impingement (FAI). Accurate imaging of hip cartilage requires injection of fluid into the hip joint capsule while in traction. To optimize contrast, MR relaxometry measurements were performed on saline, isovue, and lidocaine solutions (all typically injected into the hip). Our analysis showed that these substances actually should not be used for MR imaging of the hip, and alternate strategies should be explored as a result.