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研究生: 陳英誠
Ying-Cheng Chen
論文名稱: 由共軛焦顯微鏡影像建立果蠅標準腦架構
Framework for Creation of the Drosophila Standard Brain from Confocal Microscopy Images
指導教授: 陳永昌
Yung-Chang Chen
口試委員:
學位類別: 博士
Doctor
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2007
畢業學年度: 95
語文別: 英文
論文頁數: 84
中文關鍵詞: 共軛焦顯微鏡影像果蠅標準腦分割表面重建模型平均對位
外文關鍵詞: Confocal Microscopy Images, Drosophila Standard Brain, Segmentation, Surface Reconstruction, Model Averaging, Registration
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  • 腦部是人體機能運作最重要的中樞,由於人類腦部神經細胞個數相當驚人,由數十億個神經細胞互相連結成數兆個聯結點的神經網路,因此要瞭解人類腦部神經網路變得相當困難,在生命科學的基礎研究上,便以具有學習與記憶能力的果蠅來進行研究,幫助瞭解腦部神經網路的結構與運作情形,其不僅結構比較單純且細胞數目較少(約有十三萬個),我們對於它的相關知識也較為充足(果蠅被拿來進行基因相關研究已經超過五十年,且其全部基因組也於西元2000年三月完成定序),已經可以進行基因與腦神經網路關係的研究了。對於果蠅嗅覺、味覺、聽覺、視覺、記憶、求偶等腦神經網路之建構,與各種感官機制與神經疾病、老化之間的關連的研究,將有助於明瞭人腦的功能,並有助於研發帕金森氏症、阿茲海默症、杭廷頓跳舞症,及嗅覺、味覺喪失等跟腦部有關疾病的治療方法。
    在共軛焦顯微鏡硬體的發展與染色技術的提升下,已經能夠對果蠅腦部進行解析度精於0.1μm的掃瞄取像,不過在進行相關研究時,建立一個果蠅標準腦模型卻是必須的:在研究基因與腦部發展的關係時,使某個基因進行突變,觀察該基因與腦部的發展有何關係(可能造成某處退化或消失),需要一個標準正常腦進行比較,由於不同果蠅間擁有程度不一的變異,我們不能隨便取一個正常果蠅樣本當成標準腦,因此我們需要一個經過廣義平均的標準腦模型;另外,在建立完整神經網路的工作中,需要經過成千上萬次不同果蠅的實驗,將不同訊息傳遞的神經網路記錄下來,經過對位技術放入單一模版果蠅腦中,若以標準腦模型來作為此一模版,可減少對位時的平均扭曲,而提高對位結果的可信度。
    我們提出了一個完整的系統架構來建立果蠅標準腦,使用共軛焦顯微鏡取得個別果蠅腦部的三維切片資訊,經過影像處理加以分割、三維重建之後,可得個別果蠅腦部資訊,再將所有取樣果蠅的資訊整合並執行廣義平均,便可得到我們所要的標準腦模型。此一標準果蠅腦模型由標準腦外廓(經形狀平均後的腦外廓)及標準神經氈(經形狀平均後的神經氈)組成,求出各種神經氈在標準腦外廓中平均的方位後,將標準神經氈放置於標準腦外廓中適當的位置與角度後,我們便可得到最終的果蠅標準腦。


    To understand the human brain is a difficult task, because of its enormous number of neuron. In basic research of life science, a fruit fly, Drosophila melanogaster, with the abilities of learning and memory is chosen for research to facilitate the understanding of structures and functions of the brain. With the advent of fluorescent proteins, molecular biological techniques and the advanced confocal microscopy, it is now possible to visualize the expression of genes even in single cells. In the neurobiology of Drosophila, a standard for brain anatomy is necessary. Since there are more than thousands of genes expressed in the Drosophila brain, there is no way to observe all of them in a single tissue. A complete genetic map of the neural networks can only be achieved by warping individual gene expression images into a common coordinate system, a standard framework of the Drosophila brain.
    We propose a Drosophila brain atlas, also called the Drosophila standard brain, for serving as a common coordinate system in the neurobiology of Drosophila. It is constructed from confocal microscopy scans of individual Drosophila brains. We obtain the individual brain model by first acquiring the confocal microscopy raw images and following an image processing procedure for segmentation and 3-D reconstruction. Combining all these individual brain models and applying the general averaging procedure, we can finally generate the standard brain model. The Drosophila standard brain comprises the standard cortex (the average-shape cortex) and the standard neuropils (the average-shape neuropils). The standard neuropils are located within the standard cortex with the average positions and orientations. Compared with arbitrarily selected templates, the standard template can give smaller average disparity to the individual Drosophila brains and consequently lead to a better warping result.

    List of Figures List of Tables Chapter 1 Introduction 1.1 Motivation 1.2 Framework 1.3 Background and Related Works 1.4 Contributions 1.5 Thesis Organization Chapter 2 Segmentation of Confocal Microscopy Images 2.1 Introduction 2.2 Overview of the Algorithm 2.3 Preparation of Template 2.4 Registration of Template 2.5 Modified Snake Algorithm 2.6 Experimental Results 2.7 Summary Chapter 3 Surface Reconstruction from Sequential Parallel 2D Sections 3.1 Introduction 3.2 Overview of the Algorithm 3.3 Contour-Correspondence Analysis 3.3.1 Initialization 3.3.2 Improved correspondence-determining algorithm 3.4 Surface Tiling 3.4.1 Polygonal contour approximation 3.4.2 Tiling Triangles 3.4.3 Degenerate cases and contour interpolation 3.4.4 Branching problems 3.5 Rendering and Quantitative Analysis 3.5.1 Three-dimensional rendering 3.5.2 Surface area and volume computation 3.6 Experimental Results 3.7 Summary Chapter 4 Creation of the Drosophila Standard Cortex and Neuropils 4.1 Introduction 4.2 Overview of the Algorithm 4.3 Coarse-level Averaging 4.3.1 Non-axial structures 4.3.2 Axial structures 4.4 Fine-level Averaging 4.5 Experimental Results 4.6 Summary Chapter 5 Creation of the Drosophila Standard Brain 5.1 Introduction 5.2 Overview of the Algorithm 5.3 Registration of the Standard Neuropils 5.4 Average Position and Orientation of the Standard Neuropils 5.5 Experimental Results 5.6 Summary Chapter 6 Conclusions and Future Research 6.1 Summary and Conclusions 6.2 Suggestions for Future Research References

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