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京都大学 / 新制・論文博士 / 博士(医学) / 乙第13489号 / 論医博第2257号 / 新制||医||1059(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 波多野 悦朗, 教授 羽賀 博典 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p> This thesis presents an optimal design method for MRI (Magnetic Resonance Imaging) teardrop gradient waveforms in two and three dimensions. Teardrop in two dimensions was introduced at ISMRM 2001 by Anand et al. to address the need for a high efficiency balanced k-space trajectory for real-time cardiac SSFP (Steady State Free Precession) imaging.</p> <p> We have modeled 2D and 3D teardrop gradient waveform design as nonlinear convex optimization problems with a variety of constraints including global constraints (e.g., moment nulling for motion insensitivity). Commercial optimization solvers can solve the models efficiently. The implementation of AMPL models and numerical testing results with the solver MOSEK are provided. This optimal design procedure produces physically realizable teardrop waveforms which enable real-time cardiac imaging with equipment otherwise incapable of doing it, and optimally achieves the maximum resolution and motion artifact reduction goals. The research may encompass other waveform design problems in MRI and has built a good foundation for further research in this area.</p> / Thesis / Master of Science (MSc)

In this thesis, we introduce a novel method of reconstructing fibre directions from diffusion images. By modelling the Principal Diffusion Direction PDD (the fibre direction) directly, we are able to apply regularization to the fibre direction explicitly, which was not possible before. Diffusion Tensor Imaging (DTI) is a technique which extracts information from multiple Magnetic Resonance Images about the amount and orientation of diffusion within the body. It is commonly used for brain connectivity studies, providing information about the white matter structure. Many methods have been represented in the literature for estimating diffusion tensors with and without regularization. Previous methods of regularization applied to the source images or diffusion tensors. The process of extracting PDDs therefore required two or three numerical procedures, in which regularization (including filtering) is applied in earlier steps before the PDD is extracted. Such methods require and/or impose smoothness on all components of the signal, which is inherently less efficient than using regularizing terms that penalize non-smoothness in the principal diffusion direction directly. Our model can be interpreted as a restriction of the diffusion tensor model, in which the principal eigenvalue of the diffusion tensor is a model variable and not a derived quantity. We test the model using a numerical phantom designed to test many fibre orientations in parallel, and process a set of thigh muscle diffusion-weighted images. / Thesis / Master of Science (MSc)

The liver is a multi-function organ that plays important roles in nutrient metabolism, biochemical transformations and blood detoxification. The purpose of the current work was to optimize Blood Oxygen Level Dependent (BOLD) liver functional MR imaging and analysis to allow the distinction between healthy volunteers and subjects with chronic liver disorders known to lead to fibrosis and reduced liver function (in this case, Hepatitis-C). Liver BOLD signal can be modulated by breathing 100% 0 2 or through intake of a meal. Previous results using these stimuli have been inconclusive when comparing healthy and diseased livers. In addition, liver BOLD analysis has been traditionally carried out using general linear models (GLM). Since the liver has a dual blood supply (portal and arterial derived), its resultant haemodynamic response is complex. This makes it too difficult to employ GLM approaches, as they require the prediction and modeling of a response function. We chose a model-free, or data-driven approach, called principle component analysis (PCA) to analyze liver data. Initial optimization was done by determining the time of maximal hepatic portal vein (HPV) blood flow following ingestion of a controlled meal (235 mL of Ensure Plus®). Statistically significant increases in HPV flow resulted at all measurement intervals, with the maximal postprandial change (71% increase in comparison to the baseline flow) at thirty minutes after ingestion. Implementing acquisition and analysis optimizations with our dual liver challenge model (hyperoxia cycling in pre- and postprandial states), the PCA approach was able to detect all of the diseased livers (n=6), while missing four of the healthy subjects (n=ll). The GLM technique, on the other hand, did not detect two of the patients and two of the healthy subjects. Thus, if this liver challenge is to be used as a screening tool, a model-free data analysis approach is suggested as more appropriate since it minimizes the chances of reporting false-negative results (based on this preliminary cohort). Although more false positives were detected with this method, it is of less concern seeing as these inaccuracies can be screened using simple blood tests. Promising results were obtained in this project, however, further studies using data-driven approaches such as partial least squares (PLS) are needed. / Thesis / Master of Science (MSc)

Intra-cellular sodium (23Na) concentration is directly related to cellular health. Thus, sodium magnetic resonance imaging (MRI) can provide metabolic information on tissue health that a routine clinical (proton) MRI cannot. 23Na-MRI could be a valuable tool to assist physicians in the diagnosis, prognosis, and monitoring of a variety of pathologies. However, due to factors that include quantum mechanical limitations and biological restrictions, the signal-to-noise ratio (SNR) of a sodium scan is much lower than that of a standard proton scan, which limits the practicality of 23Na-MRI in a clinical setting. This project looks to improve the viability of 23Na-MRI and focuses on an often overlooked facet of MRI development, the radio frequency (RF) coil. Fractal antennas have been used in telecommunication systems for years, and are generally exploited for their compact nature, allowing for the same performance of a larger antenna, in a smaller space. They have also been shown to be capable of a wider transmission bandwidth (BW) than a standard antenna and with MRI applications they have been shown to provide a small SNR increase in proton imaging. It is hypothesized that a surface coil with a Koch snowflake fractal geometry can provide increased SNR for a sodium MRI scan, compared to that of a standard circular geometry coil, by producing a more homogeneous magnetic field in both space and frequency. To test the hypothesis two coils, one circular and the other a Koch snowflake fractal, were simulated. The simulated magnetic fields were compared on their homogeneity and magnitude before the two coils were constructed and implemented with a variety of sodium MRI scans. B1+ maps were acquired to measure RF field homogeneity, and SNR was determined for both coil geometries. The coils were also tested for their homogeneity over varied transmit BWs by comparing images with various field of view (FOV) sizes. Finally the coils were compared for clinical viability in a test of healthy human knee imaging. The circular coil had a more homogeneous B1+ field than the fractal at depths between 10-40mm, and had a higher SNR in its produced images. The circular coil acquired more signal in vivo which provided a higher detail image, but the fractal coil's SNR was higher due to reduced noise. The fractal coil performed better over a wider BW which indicates that further research should be conducted into the applications of fractal coils in multi-nuclear MRI scans. / Thesis / Master of Applied Science (MASc)

Macromolecular magnetic resonance imaging (MRI) contrast agents have unique localization and contrast enhancement properties. We have designed and studied a monodisperse paramagnetic β-cyclodextrin click cluster (Gd10) decorated with Gd-containing arms and unique contrast enhancing polymers. To synthesize Gd10, a novel alkyne-functionalized diethylenetriaminetetraacetic acid chelate was created and coupled to a per-azido-β-cyclodextrin core and chelated with Gd(III) to yield the precursor macromolecule. Luminescence measurements were carried out using an analogous structure Eu(III)-containing structure and indicated that each lanthanide has an average of 1.8 water exchange sites. Gd10 yields a high relaxivity profile (6.2 mM⁻¹ s⁻¹ per Gd(III) at 9.4 T). Gd10 shows toxicity higher than clinically used contrast agents such as Magnevist&trade in vitro in cardiomyoblast cells. No acute toxicity was observed in the rats (n = 9) and contrast enhanced image analysis indicates renal processes may be involved in clearance. The contrast enhancing polymers we developed are new macromolecular beacons that allow the delivery of nucleic acids to be visualized at different biological scales. They contain repeated oligoethyleneamines, for binding and compacting nucleic acids into nanoparticles, and Gd(III)/Eu(III) chelates. The chelated lanthanides allow the visualization of the delivery vehicle via microscopy and via magnetic resonance imaging (MRI). We demonstrate that these new delivery beacons effectively bind plasmid DNA(pDNA) and protect their cargo nucleic acids from nuclease damage. The lanthanide-chelate materials have been found to efficiently deliver pDNA into cultured cells and do not exhibit toxicity. Micrographs of cultured cells exposed to the nanoparticle complexes formed with fluorescein-labeled pDNA and the europium-chelated polymers reveal effective intracellular imaging of the delivery process. MRI of bulk cells exposed to the complexes formulated with pDNA and the gadolinium-chelated structures show bright image contrast, allowing visualization of effective intracellular delivery on the tissue-scale. Because of their versatility as imaging probes, these delivery beacons posses remarkable potential for tracking and understanding nucleic acid transfer in vitro and have promise for in vivo imaging applications. In later studies the Ln-chelating polymers were co-polymerized with dimethylgalacterate which definitively increases luciferase gene expression (up 50x enhancement) and cellular uptake (up to 2x enhancement). / Ph. D.

Yes / Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention in paediatric patients. Ultrasound is generally the diagnostic imaging modality of choice, followed by CT, where paediatric appendicitis is suspected. However, high operator dependency and diagnostic restrictions related to anatomical and clinical presentation may limit consistency of application. This paper explores whether MRI is a viable alternative to ultrasound as the primary imaging modality. Method: A systematic review of the literature was undertaken. A search of Medline, Cinahl, PubMed Central and Google Scholar was undertaken supplemented by a review of reference lists, author searching and review of NICE evidence base for existing guidelines. Included studies were assessed for bias using the QUADAS-2 quality assessment tool and data were extracted systematically using a purposefully designed electronic data extraction proforma. Results: Seven studies were included in final review. The age range of participants extended from 0 to 19 years. Only one study with a patient age range of 0e14 used sedation. Sensitivity estimates from the included studies ranged from 92% to 100% while specificity ranged from 89% to 100%. A significant variation in the number and type of sequences was noted between the studies. Conclusion: MRI offers high sensitivity and specificity comparable to contrast enhanced CT and greater than ultrasound as reported in the literature. Where accessibility is not a restriction, MRI is a viable alternative to ultrasound in the assessment and diagnosis of paediatric appendicitis. Clinical practice recommendations have been provided to facilitate the translation of evidence into practice.

A study was performed to establish the appearance of normal equine laryngeal cartilages using magnetic resonance imaging. Specimens were acquired from clinically normal horses that were euthanized for reasons other than respiratory disease. Three in situ and 5 ex vivo larynges were imaged using a 0.3 Tesla system. Images were obtained in the transverse plane using T1-weighted 3D spin echo, T2-weighted 3D spin echo, T2-weighted gradient echo, short tau inversion recovery (STIR), and proton density spin echo sequences. Five ex vivo larynges were also imaged in the transverse plane using a 1.5 Tesla system, sequences included T1-weighted 3D spin echo, T2-weighted 3D turbo-spin echo, turbo inversion recovery (TIRM), and proton density spin echo sequences. A frozen gross laryngeal specimen was sliced in 5-mm transverse sections for comparison to the MR images. Excellent correlation was found between MR images and the gross transverse sections. Successful imaging was accomplished using both imaging systems; however, the 1.5 Tesla system yielded superior image resolution. The 0.3 Tesla imaging system would accommodate the intact equine head, which was not possible using the 1.5 Tesla MRI system. The internal morphology of the laryngeal cartilages was clearly identified in all imaging sequences obtained. Cartilages were found to differ in signal intensity based on the tissue composition and imaging sequences performed. MRI was determined to be a useful imaging modality for evaluating the cartilage morphology of the equine larynx. Further investigation is required to document pathologic morphology. / Master of Science