磁振造影（Conventional magnetic resonance imaging, MRI）是一種具非侵入性的醫療方法，在臨床醫療的研究上有許多廣泛的應用。其中，由MRI所延伸的另一種技術，磁振頻譜（Proton magnetic resonance spectroscopy, MRS），可以提供更明確的損傷特徵，因此常使用幫助不同的內部病理診斷，尤其是腦部上的應用。針對腦膿瘍從其他腦部疾病中區分出來，對於臨床上的診斷和治療是非常重要的。而氨基酸、丙氨酸、乳酸鹽和醋酸鹽被認為是腦膿瘍病患腦中會出現的指標性代謝物，尤其是氨基酸。而LCModel是一款知名可靠又方便操作的後處理工具，可以提供代謝物客觀的定量和絕對濃度分析。本篇論文會利用LCModel來分析氨基酸的磁振頻譜，並進一步作辨識和濃度定量，希望對臨床上患有腦膿瘍的病患帶來更精準且快速的診斷和治療。

然而活體磁振頻譜會因為含有雜訊而造成判斷上的困難，在本篇論文中我們想要驗證LCModel在分析氨基酸代謝物的可靠性，因此我們利用LCModel分析加上不同程度的雜訊後的GAVA模擬訊號，藉此了解當雜訊到達某個程度時所造成訊雜比低落和濃度間的影響。我們的目的是希望能了解可能最佳的可靠分析方法，希望對臨床上腦膿瘍病患的診斷有所幫助。

Conventional magnetic resonance imaging (MRI) is a noninvasive and nondestructive technique and ideally suited for applications in clinical studies. In addition to the information of human anatomy provided by MRI, magnetic resonance spectroscopy (MRS) also provided a noninvasive method to investigate the metabolites in the body and is therefore regarded as a valuable method to examine tumors and disorders especially for the brain applications. To diagnose pyogenic brain abscess from other diseases is very important for clinic treatment. Cytosolic amino acids, lactate, alanine and acetate have been recognized as potential abscess markers, especially amino acids. LCModel is a well-known and reliable post-processing tool for MRS which can provide objectively quantitative of metabolite concentration. In this thesis, we would use LCModel to analyze the spectra of amino acids and further to identify and quantitate these metabolites. And we hope that the method would benefit more precisely noninvasive diagnosis and treatment of pyogenic brain abscess.

However, due to the possibly poor SNR of in vivo proton MR spectroscopy, it might be difficult to identify these metabolites. In this study, we would validate the accuracy of LCModel in the analysis of amino acids. We used GAVA-simulated resonance spectra with different level noise as our input signals and analyzed by LCModel to understand the influence of concentrations and SNR caused by different level noise. Our goal is to find an optimally reliable method to help the clinic diagnosis of abscess patients.

致謝 I
中文摘要 II
ABSTRACT III
TABLE OF CONTENTS IV
LIST OF FIGURES VI
LIST OF TABLES VIII
CHAPTER 1 INTRODUCTION 1
1.1 BACKGROUND 1
1.2 LITERATURE REVIEWS 2
1.3 MOTIVATION 3
1.4 ORGANIZATION OF THE THESIS 4
CHAPTER 2 THEORY 5
2.1 IN VIVO MR SPECTROSCOPY 5
2.2 THE METABOLITES OF HUMAN BRAIN 6
CHAPTER 3 METERIAL AND METHODS 16
3.1 GAMMA AND GAVA 16
3.2 LCMODEL 16
3.3 EXPERIMENT DESIGN 17
3.3.1 Simulated MR Spectroscopy Signal of Amino acids 18
3.3.2 Different Noise Ratio Addition 18
3.3.3 Parameters of LCModel 19
3.3.4 SNR and Difference Value Calculation 20
3.3.4.1 SNR Calculation 20
3.3.4.2 Difference Value Calculation 21
3.3.5 Application – Abscess Studies 22
3.3.5.1 Subjects 22
3.3.5.1 MR Imaging Protocol and In Vivo 1H-MR Spectroscopy 22
CHAPTER 4 RESULTS 29
4.1 SNR V.S. DIFFERENCE VALUE 29
4.2 ABSCESSES STUDIES 31
CHAPTER 5 DISCUSSION AND CONCLUSION 50
5.1 DISCUSSION 50
5.1.1 SNR v.s. Difference value 50
5.1.2 Abscesses Studies 53
5.2 CONCLUSION 55
REFERENCES 62

References
[1] H. Poptani, et al., "Cystic intracranial mass lesions: possible role of in vivo MR spectroscopy in its differential diagnosis," Magn Reson Imaging, vol. 13, pp. 1019-29, 1995.
[2] S. W. Provencher, "Estimation of metabolite concentrations from localized in vivo proton NMR spectra," Magnetic Resonance in Medicine, vol. 30, pp. 672-679, 1993.
[3] S. H. Kim, et al., "Brain abscess and brain tumor: Discrimination with in vivo H-1 MR spectroscopy," Radiology, vol. 204, pp. 239-245, Jul 1997.
[4] P. H. Lai, et al., "Pyogenic brain abscess: Findings from in vivo 1.5-T and 11.7-T in vitro proton MR spectroscopy," American Journal of Neuroradiology, vol. 26, pp. 279-288, Feb 2005.
[5] V. P. Tikhonov and N. A. Kostromina, "Pmr study of conformational changes in leucine,isoleucine,and valine.," Theoretical and experimental chemistry, vol. 13, pp. 496-503, 1978.
[6] P. H. Lai, et al., "In vivo differentiation of aerobic brain abscesses and necrotic glioblastomas multiforme using proton MR spectroscopic imaging," American Journal of Neuroradiology, vol. 29, pp. 1511-1518, Sep 2008.
[7] D. Pal, et al., "In vivo proton MR spectroscopy evaluation of pyogenic brain abscesses: a report of 194 cases," AJNR Am J Neuroradiol, vol. 31, pp. 360-6, Feb 2010.
[8] P. J. Keller, "Basic Principles of Magnetic Resonance Imaging," Dept. of Magnetic Resonance Research, Barrow Neurological Institute, St. Joseph's Hopital and Medical Center, Phoenix, AZ,85013, pp. 5-29, Jun.1988.
[9] W. G. Proctor and F. C. Yu, "The dependence of a nuclear magnetic resonance frequency upon chemical compound," Phys Rev 77, p. 717, 1950.
[10] Robin A. de Graaf, "In vivo NMR spectroscopy : principles and techniques " John Wiley & Sons, 2007.
[11] M. Garg, et al., "Brain abscesses: etiologic categorization with in vivo proton MR spectroscopy," Radiology, vol. 230, pp. 519-27, Feb 2004.
[12] T. Higuchi, et al., "Effects of severe global ischemia on N-acetylaspartate and other metabolites in the rat brain," Magn Reson Med, vol. 37, pp. 851-7, Jun 1997.
[13] S. Brulatout, et al., "A one-dimensional (proton and phosphorus) and two-dimensional (proton) in vivo NMR spectroscopic study of reversible global cerebral ischemia," J Neurochem, vol. 66, pp. 2491-9, Jun 1996.
[14] Y. K. Govindaraju V, Maudsley AA., "Proton NMR chemical shifts and coupling constants for brain metabolites.," NMR Biomed., vol. 13, pp. 129-153, 2000.
[15] R. H. Britt, et al., "Neuropathological and Computerized Tomographic Findings in Experimental Brain-Abscess," Journal of Neurosurgery, vol. 55, pp. 590-603, 1981.
[16] A. Stahl, et al., "Lipid metabolites in the pathogenesis and treatment of neovascular eye disease," British Journal of Ophthalmology, vol. 95, pp. 1496-1501, Nov 2011.
[17] S. A. Smith, et al., "Computer-Simulations in Magnetic-Resonance - an Object-Oriented Programming Approach," Journal of Magnetic Resonance Series A, vol. 106, pp. 75-105, Jan 1994.
[18] B. J. Soher, et al., "GAVA: spectral simulation for in vivo MRS applications," J Magn Reson, vol. 185, pp. 291-9, Apr 2007.
[19] B. J. Soher, Aygula, Z.,Maudsley, A., "GAVA-Users Manual and Reference.," 2008.
[20] S. W. Provencher, "Automatic quantitation of localized in vivo 1H spectra with LCModel," NMR Biomed, vol. 14, pp. 260-4, Jun 2001.
[21] S. W. Provencher, "LCModel & LCMgui User's Manual.," 2005.
[22] L. Shu-Yi, "The Categorization of Pyogenic Brain Abscesses Using in Vivo Proton MR Spectroscopy with LCModel.," Computer Science and Engineering, National Sun Yat-sen., 2011.
[23] R. Kreis, "Issues of spectral quality in clinical 1H-magnetic resonance spectroscopy and a gallery of artifacts," NMR Biomed, vol. 17, pp. 361-81, Oct 2004.