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  1. NTU Theses and Dissertations Repository
  2. 電機資訊學院
  3. 生醫電子與資訊學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91132
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor曾宇鳳zh_TW
dc.contributor.advisorYufeng Jane Tsengen
dc.contributor.author姚柏仰zh_TW
dc.contributor.authorPo-Yang Yaoen
dc.date.accessioned2023-11-13T16:09:37Z-
dc.date.available2023-11-14-
dc.date.copyright2023-11-13-
dc.date.issued2023-
dc.date.submitted2023-10-04-
dc.identifier.citation1. Norris, J.L. and R.M. Caprioli, Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research. Chemical reviews, 2013. 113(4): p. 2309-2342.

2. Laskin, J. and I. Lanekoff, Ambient mass spectrometry imaging using direct liquid extraction techniques. Analytical chemistry, 2016. 88(1): p. 52-73.

3. Tamura, K., et al., Discovery of lipid biomarkers correlated with disease progression in clear cell renal cell carcinoma using desorption electrospray ionization imaging mass spectrometry. Oncotarget, 2019. 10(18): p. 1688.

4. Neumann, E.K., et al., Spatial metabolomics of the human kidney using MALDI trapped ion mobility imaging mass spectrometry. Analytical Chemistry, 2020. 92(19): p. 13084-13091.

5. Andersson, M., et al., Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction. Nature methods, 2008. 5(1): p. 101-108.

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8. Drake, R.R., et al., Defining the human kidney N‐glycome in normal and cancer tissues using MALDI imaging mass spectrometry. Journal of mass spectrometry, 2020. 55(4): p. e4490.

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52. Zhuo, C., et al., Lipidomics of the brain, retina, and biofluids: from the biological landscape to potential clinical application in schizophrenia. Translational Psychiatry, 2020. 10(1): p. 391.

53. Wood, P.L., Targeted lipidomics and metabolomics evaluations of cortical neuronal stress in schizophrenia. Schizophrenia Research, 2019. 212: p. 107-112.

54. Taha, A.Y., et al., Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients. Journal of psychiatric research, 2013. 47(5): p. 636-643.

55. Schmitt, A., et al., Altered thalamic membrane phospholipids in schizophrenia: a postmortem study. Biological psychiatry, 2004. 56(1): p. 41-45.

56. McNamara, R.K., et al., Abnormalities in the fatty acid composition of the postmortem orbitofrontal cortex of schizophrenic patients: gender differences and partial normalization with antipsychotic medications. Schizophrenia research, 2007. 91(1-3): p. 37-50.

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58. Wood, P.L., et al., Lipidomics reveals dysfunctional glycosynapses in schizophrenia and the G72/G30 transgenic mouse. Schizophrenia research, 2014. 159(2-3): p. 365-369.

59. Ghosh, S., R.A. Dyer, and C.L. Beasley, Evidence for altered cell membrane lipid composition in postmortem prefrontal white matter in bipolar disorder and schizophrenia. Journal of Psychiatric Research, 2017. 95: p. 135-142.

60. Matsumoto, J., et al., Decreased 16: 0/20: 4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia. Scientific reports, 2017. 7(1): p. 45050.

61. Esaki, K., et al., Evidence for altered metabolism of sphingosine-1-phosphate in the corpus callosum of patients with schizophrenia. Schizophrenia bulletin, 2020. 46(5): p. 1172-1181.

62. Shimamoto-Mitsuyama, C., et al., Lipid pathology of the corpus callosum in schizophrenia and the potential role of abnormal gene regulatory networks with reduced microglial marker expression. Cerebral Cortex, 2021. 31(1): p. 448-462.

63. Sano, F., et al., Associations between prefrontal PI (16: 0/20: 4) lipid, TNC mRNA, and APOA1 protein in schizophrenia: A trans-omics analysis in post-mortem brain. Frontiers in Psychiatry, 2023. 14: p. 1145437.

64. Pei, J.-C., et al., Therapeutic potential and underlying mechanism of sarcosine (N-methylglycine) in N-methyl-D-aspartate (NMDA) receptor hypofunction models of schizophrenia. Journal of Psychopharmacology, 2019. 33(10): p. 1288-1302.

65. Deininger, S.-O., et al., Normalization in MALDI-TOF imaging datasets of proteins: practical considerations. Analytical and bioanalytical chemistry, 2011. 401: p. 167-181.

66. Alexandrov, T., et al., METASPACE: A community-populated knowledge base of spatial metabolomes in health and disease. BioRxiv, 2019: p. 539478.

67. Palmer, A., et al., FDR-controlled metabolite annotation for high-resolution imaging mass spectrometry. Nature methods, 2017. 14(1): p. 57-60.

68. Wishart, D.S., et al., HMDB 4.0: the human metabolome database for 2018. Nucleic acids research, 2018. 46(D1): p. D608-D617.

69. Wadie, B., et al., METASPACE-ML: Metabolite annotation for imaging mass spectrometry using machine learning. bioRxiv, 2023: p. 2023.05. 29.542736.

70. Ovchinnikova, K., et al., OffsampleAI: artificial intelligence approach to recognize off-sample mass spectrometry images. BMC bioinformatics, 2020. 21(1): p. 1-11.

71. Smets, T., et al., Evaluation of distance metrics and spatial autocorrelation in uniform manifold approximation and projection applied to mass spectrometry imaging data. Analytical chemistry, 2019. 91(9): p. 5706-5714.

72. Fonville, J.M., et al., Hyperspectral visualization of mass spectrometry imaging data. Analytical chemistry, 2013. 85(3): p. 1415-1423.

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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91132-
dc.description.abstract質譜成像是一種具有空間解析能力的分析技術,能提供不同分子的空間分佈情況,以便識別出空間模式、梯度或局部分子變化。質譜影像可以與其他的成像模式結合,如顯微鏡、螢光成像或磁共振成像,以獲取互補的信息,使研究人員能夠對樣本有更全面、完整的觀察。然而,傳統的二維質譜成像無法提供樣本在z軸上的詳細訊息,這使得分析和解釋複雜的三維結構變得具有挑戰性。三維質譜成像具有提升深度剖析能力並實現對給定樣本特定分子體積的定量分析潛力。它能夠評估組織內代謝物濃度的空間變化。三維質譜影像的研究持續增加,表明對探索質譜影像三維特性的興趣正在上升。
思覺失調症是一種影響人們思維、情感和行為的精神疾病。其中一個思覺失調症的假說是NMDA(N-甲基-D-天冬氨酸)受體的功能不足,這導致思覺失調症的臨床症狀。越來越多的新證據表明脂質代謝與思覺失調症之間可能存在著關聯。我們提供一個以思覺失調症鼠腦為例的三維質譜成像重建流程。透過該流程,可以將實驗所得不同深度的二維質譜影像重組成三維質譜影像,從而了解分子在三維空間中的分佈。透過比較思覺失調和正常小鼠海馬迴、紋狀體和內側前額葉皮層中的脂質強度,我們發現這三個腦區中的特定脂質在兩組樣本間存在顯著差異。
zh_TW
dc.description.abstractMass spectrometry imaging (MSI) is a spatially resolved analytical technique that provides spatial distributions of different molecules, allowing for the identification of spatial patterns, gradients, or localized molecular changes. MSI can be combined with various imaging modalities, including microscopy, fluorescence imaging, and magnetic resonance imaging (MRI), to obtain complementary information, which enables researchers to have a more comprehensive and intact view of the sample. However, traditional 2D MSI does not provide detailed information along the z-axis of the sample. This makes it challenging to analyze and interpret complex 3D structures. Three-dimensional (3D) MSI has the potential to enhance depth profiling capabilities and allow for quantitative analysis of the volume. It enables the assessment of spatial variations in metabolite concentrations throughout a tissue volume. Research on 3D MSI is increasing, indicating a rising interest in exploring the 3D aspects of MSI.
Schizophrenia is a psychiatric disorder characterized by cognitive, emotional, and behavioral disturbances. One of the hypotheses of schizophrenia is the hypofunction of NMDA (N-methyl-D-aspartate) receptors, which leads to the clinical symptoms of schizophrenia. An increasing body of emerging evidence indicates a potential association between lipid metabolism and schizophrenia. We provided a three-dimensional mass spectrometry imaging reconstruction protocol using schizophrenic mouse brains as an example. With this protocol, the 2D MSI data acquired at different depths can be reconstructed into a 3D MSI, allowing us to understand the spatial distribution of molecules in a 3D space. By comparing the lipid intensities in the hippocampus, striatum, and medial prefrontal cortex (mPFC) between schizophrenia and wild-type mice, we identified specific lipids in these three brain regions that showed significant differences between the two groups.
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dc.description.tableofcontents誌謝 i
中文摘要 ii
ABSTRACT iii
CONTENTS v
LIST OF FIGURES viii
LIST OF TABLES x
GLOSSARY xi
Chapter 1 Introduction 1
1.1 Mass Spectrometry Imaging 1
1.1.1 The Basics of MSI 1
1.1.2 Multimodal Imaging with MSI 2
1.2 Three-dimensional (3D) mass spectrometry imaging 3
1.2.1 The Symptoms of Schizophrenia 6
1.2.2 The Hypotheses of Schizophrenia 6
1.2.3 Mouse models of schizophrenia 7
1.2.4 Serine racemase-deficient (SR-/-) mice 8
1.2.5 Lipid Disturbances in Schizophrenia 9
Chapter 2 Materials and Methods 12
2.1 Experimental Procedures 12
2.1.1 Sample Preparation 12
2.1.2 DESI MSI experiment 13
2.2 MSI data Processing 13
2.2.1 On-tissue Spectra Extraction and Peak Picking 13
2.2.2 Normalization 14
2.2.3 Metabolite Annotation 14
2.3 Data Compression 15
2.3.1 Dimensionality Reduction 16
2.3.2 Hyperspectral Visualization 17
2.3.3 Image Segmentation 18
2.4 3D MSI Reconstruction and Analysis 19
2.4.1 Optical Image Processing 20
2.4.2 Consecutive Histological Images and Multimodal Image Registration 20
2.4.3 Region of interest (ROI) selection 21
2.4.4 Three-dimensional Reconstruction 22
2.4.5 Statistical Analysis 22
Chapter 3 Results and Discussion 23
3.1 Molecular Annotation of MSI Data 23
3.2 Hyperspectral visualization provides histoanatomical structure information 24
3.3 The clustering results of the four samples have similar spatial distributions 31
3.4 The results of statistical analysis indicate the significant differences in certain lipids between the SR-/- samples and WT samples 36
3.4.1 Phosphatidylinositols (PI) have significantly higher levels in the hippocampus of SR-/- mice 37
3.4.2 Phosphatidic acids (PAs) have relatively higher levels in the striatum of SR-/- mice 40
3.4.3 Multiple phosphatidylserine (PS) species show relatively higher levels in the mPFC of SR-/- mice 42
3.5 Limitations and Future Perspectives 45
3.5.1 The Limitation 45
3.5.2 The Future Perspective 45
Chapter 4 Conclusion 47
References 48
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dc.language.isoen-
dc.subject質譜影像zh_TW
dc.subject脂質zh_TW
dc.subject小鼠模型zh_TW
dc.subject失覺失調症zh_TW
dc.subject三維質譜影像zh_TW
dc.subject質譜影像zh_TW
dc.subject脂質zh_TW
dc.subject小鼠模型zh_TW
dc.subject失覺失調症zh_TW
dc.subject三維質譜影像zh_TW
dc.subjectMass spectrometry imagingen
dc.subjectlipiden
dc.subjectMass spectrometry imagingen
dc.subjectthree-dimensional mass spectrometry imagingen
dc.subjectschizophreniaen
dc.subjectmouse modelen
dc.subjectlipiden
dc.subjectmouse modelen
dc.subjectschizophreniaen
dc.subjectthree-dimensional mass spectrometry imagingen
dc.title用於增強空間分析和分子定位的三維質譜影像重建流程:以思覺失調小鼠大腦為例zh_TW
dc.title3D Mass Spectrometry Imaging Reconstruction Protocol for Enhanced Spatial Profiling and Molecular Mapping with Example Application of Schizophrenia Mouse Brainen
dc.typeThesis-
dc.date.schoolyear112-1-
dc.description.degree碩士-
dc.contributor.oralexamcommittee蕭明熙;賴文崧;張瑞峰zh_TW
dc.contributor.oralexamcommitteeMing-Shi Shiao;Wen-Sung Lai;Ruey-Feng Changen
dc.subject.keyword質譜影像,三維質譜影像,失覺失調症,小鼠模型,脂質,zh_TW
dc.subject.keywordMass spectrometry imaging,three-dimensional mass spectrometry imaging,schizophrenia,mouse model,lipid,en
dc.relation.page53-
dc.identifier.doi10.6342/NTU202304283-
dc.rights.note未授權-
dc.date.accepted2023-10-05-
dc.contributor.author-college電機資訊學院-
dc.contributor.author-dept生醫電子與資訊學研究所-
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