Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (p. 119-136).

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

This thesis includes a summary of some of the early developments of M.IR and NQR detection. Elementary introduction to NQR detection is also discussed. Finally the construction of a high level NQR Spectrometer operating in the regenerative mode is treated. This regenerative spectrometer, originally designed by D. Sill, M. Hayek, Y. Alon, and A. Simievic and published in Rev. Sci. Instr. 38, 11 (1967), is discussed extensively.Ball State UniversityMuncie, IN 47306

The increase of calcium in the cell can induce cellular functions such as fertilization, cell division and cell communication. Calcium (Ca2+) carries out these processes through proteins called calcium sensors. An important calcium modulator is calmodulin. Calmodulin has four possible Ca2+ binding sites that have the characteristic helix-loop-helix (EF hand) motif. When the EF hands bind to Ca2+, methionine rich hydrophobic patches are exposed allowing for CaM to interact with target proteins. However, there are proteins that can interact with CaM at low levels of Ca2+ or in the absence of Ca2+. An enzyme that is activated by CaM is nitric oxide synthase (NOS), which converts L-arginine to L-citrulline and nitric oxide (•NO), where •NO is used to carry out important cellular functions. There are three isoforms of the enzyme; endothelial, neuronal and inducible NOS. The first two isoforms are activated by Ca2+-bound CaM when there is an influx of Ca2+ and are therefore Ca2+-dependent whereas inducible NOS (iNOS) is activated and binds tightly to CaM regardless of the Ca2+ concentration and is therefore Ca2+-independent. Of particular interest is the iNOS enzyme, since no three-dimensional structures of the reductase domain or the CaM-binding region have been solved. All three isoforms of NOS exist as homodimers, where each monomer consisting of a reductase domain and an oxygenase domain separated by a CaM-binding region. The reductase domain contains binding sites for NADPH and the flavins, FAD and FMN, which facilitate electron transfer from the NADPH to the catalytic heme in the oxygenase domain of the opposite monomer. The transfer of electrons from the FAD to the heme is carried out by the FMN domain which is proposed to swing between the two docking points since the distance between the two points is too large for electron transfer. This electron transfer point is under the control of CaM, which is essential for NOS activation. This dynamic process and the direct role of CaM have yet to be observed structurally. A method to monitor dynamics structurally is through the use of nuclear magnetic resonance (NMR) spectroscopy. Therefore as the first step to determine the NMR structure of the FMN domain with the CaM-binding region, the structure of the iNOS CaM-binding region bound to CaM will be determined. The structure will allow for further characterization and identification of important interactions between the iNOS CaM-binding region and CaM which contribute to the unique properties of iNOS.

The increase of calcium in the cell can induce cellular functions such as fertilization, cell division and cell communication. Calcium (Ca2+) carries out these processes through proteins called calcium sensors. An important calcium modulator is calmodulin. Calmodulin has four possible Ca2+ binding sites that have the characteristic helix-loop-helix (EF hand) motif. When the EF hands bind to Ca2+, methionine rich hydrophobic patches are exposed allowing for CaM to interact with target proteins. However, there are proteins that can interact with CaM at low levels of Ca2+ or in the absence of Ca2+. An enzyme that is activated by CaM is nitric oxide synthase (NOS), which converts L-arginine to L-citrulline and nitric oxide (•NO), where •NO is used to carry out important cellular functions. There are three isoforms of the enzyme; endothelial, neuronal and inducible NOS. The first two isoforms are activated by Ca2+-bound CaM when there is an influx of Ca2+ and are therefore Ca2+-dependent whereas inducible NOS (iNOS) is activated and binds tightly to CaM regardless of the Ca2+ concentration and is therefore Ca2+-independent. Of particular interest is the iNOS enzyme, since no three-dimensional structures of the reductase domain or the CaM-binding region have been solved. All three isoforms of NOS exist as homodimers, where each monomer consisting of a reductase domain and an oxygenase domain separated by a CaM-binding region. The reductase domain contains binding sites for NADPH and the flavins, FAD and FMN, which facilitate electron transfer from the NADPH to the catalytic heme in the oxygenase domain of the opposite monomer. The transfer of electrons from the FAD to the heme is carried out by the FMN domain which is proposed to swing between the two docking points since the distance between the two points is too large for electron transfer. This electron transfer point is under the control of CaM, which is essential for NOS activation. This dynamic process and the direct role of CaM have yet to be observed structurally. A method to monitor dynamics structurally is through the use of nuclear magnetic resonance (NMR) spectroscopy. Therefore as the first step to determine the NMR structure of the FMN domain with the CaM-binding region, the structure of the iNOS CaM-binding region bound to CaM will be determined. The structure will allow for further characterization and identification of important interactions between the iNOS CaM-binding region and CaM which contribute to the unique properties of iNOS.

To differentiate pyogenic brain abscess from other brain diseases such as necrotic glioblastomas is very important for clinic treatment. Cytosolic animo acids, lactate, alanine, succinate and acetate have been recognized as potential abscess markers. LCModel is a well-known tool to analyze the MRS data, as it provides opportunity of quantitative of metabolite concentration. Using MRS with LCModel to identify and quantitate these metabolites would benefit more precisely noninvasive diagnosis and treatment of pyogenic brain abscess. However, to differentiate the MR spectra of strongly overlapping metabolites are not easy. In this study, we validate the accuracy of LCModel on detecting these overlapping metabolites. We use some GAVA-simulated resonance spectra as our input signals and figure out the performance of LCModel analysis in different conditions. Our goal is to find an optimal analysis method to help the clinic diagnosis of abscess patients. Our result shows that the determination of basis sets is very important since the analyzed result might be different due to the improper selection of basis sets.

Phased array coils are composed of several surface coils receiving individual element signals simultaneously. Each individual surface coil provides the equivalent of the coil diameter range, and higher SNR. Therefore, combining these non-interactive phased array coils, can achieve a wide range of scan areas, uniform sensitivity and better SNR. Therefore our experiment was performed with two different coils of quadrature coil and phased array coil. Phased array MRS data were compared using various combination approaches. Data acquired by quadrature coil was regarded as a standard to verify the reliability and accuracy of metabolite concentration. The aim of our study is to do eddy current correction before and after the combination of each element coil data with LCModel analysis for quantitative comparison of metabolite concentrations. Our result shows that doing eddy current correction for each phased array coil before signal combination can achieve higher reliability and accuracy of SNR and quantitative concentrations of MR spectra in vivo.

Using Graphic Processor Unit (GPU) to process the parallel operation via Compute Unified Device Architecture (CUDA) is a new technology in recent years. In the past, the GPU has been used in parallel operation but it was not easy for programming so that it couldn¡¦t be widely used in applications. CUDA is the newly-developed environment based on C language mainly for improving the complexity in programming with CUDA. The applications of GPU with CUDA has been expending to various fields gradually due to support of IEEE floating point as well as its lower cost in hardware while comparing to the super computers. Magnetic Resonance Spectroscopy (MRS) has the feature of non-invasive to probe the concentration distributed of metabolites in vivo. It can assist doctor in clinical diagnosis. The Magnetic Resonance Spectroscopy Imaging (MRSI) is imaging by many Signal Voxel Spectroscopy (SVS) to become multi-dimension MRS image. In MRSI, it can offer more information than SVS. CUDA are applied to MR image widely such as accelerating the image reconstruction and promoting the image quality, but in MRS it is seldom for the related application. In this paper, we using the CUDA to applied in MRS, the MRSI data pre-processing, to accelerate the spatial location in MRSI. In this work, we firstly use random data with different dimensions: 1D (one-dimension), 2D and 3D to evaluate the performance of Fourier transformation by using CUDA. We also finally apply some GE 2D/3D MRSI data to see how the acceleration of using CUDA works. Our results show that the acceleration rate of Fastest Fourier Transform (FFT) with CUDA in 1D, 2D and 3D random data largely increases as the data size increases. In the experiment of 2D/3D MRSI data, we find that using CUDA for accelerating the MRSI RAW-file generating procedure would avoid the data moving times, and it is not good for CUDA 1D FFT with parallel architecture while too small data amount processing in kernel. Therefore, how to solve the relationship between MRSI data format with CUDA FFT library and how to decrease the data moving time will discuss in the study.

Conventional magnetic resonance (MR) imaging has been widely applied to clinical analysis studies due to its non-invasive property. Proton MR spectroscopy complements conventional MR imaging by enabling better lesion characterization. Thus, proton MR spectroscopy is used to assist in the differential diagnosis of intracranial pathologies. LCModel is a reliable and user-friendly post-processing tool which is used to analyse absolute concentrations in our thesis. Our phantom are solution of alanine (Ala), cytosolic amino acids (AAs), lactate (Lac), and n-acetyl aspartate (NAA) in a spherical flasks of glass. We used three basis sets with difference echo time (TE) to experiment. We also performed a retrospective study of subjects with brain abscesses referred during a span of 10 years. All subjects underwent conventional MR imaging and in vivo proton MR spectroscopy, and subjects are classified four groups according to the spectrum characteristics described in the literatures. In this thesis, phantom experiments as well as GAVA simulation are included for the basis sets comparison. Then, abscesses subjects are analyzed by LCModel using these basis sets and compared with clinical diagnosis. Our result shows that using GAVA simulation as the basis sets may provide better consistency among all metabolites and thus achieve more reliable quantification of magnetic resonance spectroscopy.

Magnetic resonance spectroscopy has been widely used in medical applications, rendering precise evaluation and diagnosis in clinics. As the development of various tools for automatic spectra analysis, providing objective quantification of metabolites, absolute concentrations has been playing an important role in clinical studies and applications as well. In this study, we investigate the reliability and accuracy of absolute concentration quantified by LCModel. Ten healthy subjects were included. We compared the resultant concentrations calculated by internal water scaling and phantom calibration, both of which are provided by LCModel. Partial volume effect was also taken into account to improve the accuracy of absolute concentrations. Automatic segmentation was applied to volume of interest in order to separate gray matter and white matter, which will facilitate the further partial volume correction and thus better accuracy of absolute quantification.