請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86528
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 朱士維(Shi-Wei Chu) | |
dc.contributor.advisor | 朱士維(Shi-Wei Chu | swchu@phys.ntu.edu.tw | ), | |
dc.contributor.author | Po-Yuan Wang | en |
dc.contributor.author | 汪伯元 | zh_TW |
dc.date.accessioned | 2023-03-20T00:01:14Z | - |
dc.date.copyright | 2022-09-30 | |
dc.date.issued | 2022 | |
dc.date.submitted | 2022-09-27 | |
dc.identifier.citation | [1] C. Seife, “So much more to know,” Science, vol. 309, no. 5731, pp. 78–102, Jul. 2005. [2] M. Glickstein, “Golgi and Cajal: The neuron doctrine and the 100th anniversary of the 1906 Nobel Prize,” Curr. Biol., vol. 16, no. 5, pp. R147–51, Mar. 2006. [3] M. F. Bear, B. W. Connors, and M. A. Paradiso, Neuroscience: Exploring the Brain. Lippincott Williams & Wilkins, 1996. [4] D. Schubert, R. Kötter, H. J. Luhmann, and J. F. Staiger, “Morphology, electrophysiology and functional input connectivity of pyramidal neurons characterizes a genuine layer va in the primary somatosensory cortex,” Cereb. Cortex, vol. 16, no. 2, pp. 223–236, Feb. 2006. [5] F. Li et al., “The connectome of the adult Drosophila mushroom body provides insights into function,” Elife, vol. 9, Dec. 2020. [6] Z. Zhang, L. Cong, L. Bai, and K. Wang, “Light-field microscopy for fast volumetric brain imaging,” J. Neurosci. Methods, vol. 352, p. 109083, Mar. 2021. [7] N. J. Butcher, A. B. Friedrich, Z. Lu, H. Tanimoto, and I. A. Meinertzhagen, “Different classes of input and output neurons reveal new features in microglomeruli of the adult Drosophila mushroom body calyx,” J. Comp. Neurol., vol. 520, no. 10, pp. 2185–2201, Jul. 2012. [8] S. Weisenburger and A. Vaziri, “A Guide to Emerging Technologies for Large-Scale and Whole-Brain Optical Imaging of Neuronal Activity,” Annu. Rev. Neurosci., vol. 41, pp. 431–452, Jul. 2018. [9] M. Uecker, S. Zhang, D. Voit, A. Karaus, K.-D. Merboldt, and J. Frahm, “Real-time MRI at a resolution of 20 ms,” NMR in Biomedicine, vol. 23, no. 8. pp. 986–994, 2010. [10] K. Uğurbil et al., “Pushing spatial and temporal resolution for functional and diffusion MRI in the Human Connectome Project,” Neuroimage, vol. 80, pp. 80–104, Oct. 2013. [11] N. M. Gage and B. Baars, “Fundamentals of Cognitive Neuroscience: A Beginner’s Guide.” Academic Press, 2018. [12] N. Ji, J. Freeman, and S. L. Smith, “Technologies for imaging neural activity in large volumes,” Nat. Neurosci., vol. 19, no. 9, pp. 1154–1164, Aug. 2016. [13] S. F. Cogan, “Neural stimulation and recording electrodes,” Annu. Rev. Biomed. Eng., vol. 10, pp. 275–309, 2008. [14] B. A. Wilt, L. D. Burns, E. T. W. Ho, K. K. Ghosh, E. A. Mukamel, and M. J. Schnitzer, “Advances in Light Microscopy for Neuroscience,” Annual Review of Neuroscience, vol. 32, no. 1. pp. 435–506, 2009. [15] S.-H. Huang et al., “Optical volumetric brain imaging: speed, depth, and resolution enhancement,” J. Phys. D Appl. Phys., vol. 54, no. 32, p. 323002, Jun. 2021. [16] F. A. C. Azevedo et al., “Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain,” The Journal of Comparative Neurology, vol. 513, no. 5. pp. 532–541, 2009. [17] H. Lv et al., “Resting-State Functional MRI: Everything That Nonexperts Have Always Wanted to Know,” AJNR Am. J. Neuroradiol., vol. 39, no. 8, pp. 1390–1399, Aug. 2018. [18] L. Squire, D. Berg, F. E. Bloom, S. du Lac, A. Ghosh, and N. C. Spitzer, Fundamental Neuroscience. Academic Press, 2013. [19] F. K. Janiak et al., “Non-telecentric two-photon microscopy for 3D random access mesoscale imaging,” Nat. Commun., vol. 13, no. 1, p. 544, Jan. 2022. [20] Z. Zheng et al., “A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster,” Cell, vol. 174, no. 3, pp. 730–743.e22, Jul. 2018. [21] H. J. Bellen, C. Tong, and H. Tsuda, “100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future,” Nat. Rev. Neurosci., vol. 11, no. 7, pp. 514–522, Jul. 2010. [22] A.-S. Chiang et al., “Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution,” Curr. Biol., vol. 21, no. 1, pp. 1–11, Jan. 2011. [23] Z. Mirzoyan, M. Sollazzo, M. Allocca, A. M. Valenza, D. Grifoni, and P. Bellosta, “Drosophila melanogaster: A Model Organism to Study Cancer,” Frontiers in Genetics, vol. 10. 2019. [24] U. B. Pandey and C. D. Nichols, “Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery,” Pharmacol. Rev., vol. 63, no. 2, pp. 411–436, Jun. 2011. [25] K. Rein, M. Zöckler, M. T. Mader, C. Grübel, and M. Heisenberg, “The Drosophila Standard Brain,” Curr. Biol., vol. 12, no. 3, pp. 227–231, Feb. 2002. [26] J. C. Tuthill, “Lessons from a compartmental model of a Drosophila neuron,” J. Neurosci., vol. 29, no. 39, pp. 12033–12034, Sep. 2009. [27] Y.-H. Tsai, “Millisecond-scale Volumetric Imaging Microscopy for Drosophila Brain Study,” 2020. [28] Y. Zhou, “Physics 1922 – 1941: Including Presentation Speeches and Laureates’ Biographies.” Elsevier, 2013. [29] R. Homma et al., “Wide-field and two-photon imaging of brain activity with voltage- and calcium-sensitive dyes,” Philos. Trans. R. Soc. Lond. B Biol. Sci., vol. 364, no. 1529, pp. 2453–2467, Sep. 2009. [30] C. Li, L. Gao, Y. Liu, and L. V. Wang, “Optical sectioning by wide-field photobleaching imprinting microscopy,” Appl. Phys. Lett., vol. 103, no. 18, p. 183703, Oct. 2013. [31] J. Pawley, Handbook of Biological Confocal Microscopy. Springer Science & Business Media, 2010. [32] W. Denk, J. H. Strickler, and W. W. Webb, “Two-Photon Laser Scanning Fluorescence Microscopy,” Science, vol. 248, no. 4951. pp. 73–76, 1990. [33] G. Sancataldo, L. Silvestri, A. L. A. Mascaro, L. Sacconi, and F. S. Pavone, “Advanced fluorescence microscopy for in vivo imaging of neuronal activity,” Optica, vol. 6, no. 6. p. 758, 2019. [34] R. K. P. Benninger and D. W. Piston, “Two‐Photon Excitation Microscopy for the Study of Living Cells and Tissues,” Current Protocols in Cell Biology, vol. 59, no. 1. 2013. [35] A. H. J. Kim, H. Suleiman, and A. S. Shaw, “New approaches in renal microscopy: volumetric imaging and superresolution microscopy,” Curr. Opin. Nephrol. Hypertens., vol. 25, no. 3, pp. 159–167, May 2016. [36] F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods, vol. 2, no. 12, pp. 932–940, Nov. 2005. [37] D. A. Benaron et al., “Noninvasive functional imaging of human brain using light,” J. Cereb. Blood Flow Metab., vol. 20, no. 3, pp. 469–477, Mar. 2000. [38] G. Y. Fan, H. Fujisaki, A. Miyawaki, R.-K. Tsay, R. Y. Tsien, and M. H. Ellisman, “Video-rate scanning two-photon excitation fluorescence microscopy and ratio imaging with cameleons,” Biophys. J., vol. 76, no. 5, pp. 2412–2420, May 1999. [39] K. H. Kim, C. Buehler, and P. T. So, “High-speed, two-photon scanning microscope,” Appl. Opt., vol. 38, no. 28, pp. 6004–6009, Oct. 1999. [40] B. R. Masters, P. T. C. So, and W. W. Mantulin, “Handbook of Biomedical Nonlinear Optical Microscopy,” Journal of Biomedical Optics, vol. 14, no. 1. p. 019901, 2009. [41] J. Bewersdorf, R. Pick, and S. W. Hell, “Multifocal multiphoton microscopy,” Opt. Lett., vol. 23, no. 9, pp. 655–657, 1998. [42] Buist, Buist, Muller, Squier, and Brakenhoff, “Real time two-photon absorption microscopy using multi point excitation,” Journal of Microscopy, vol. 192, no. 2. pp. 217–226, 1998. [43] V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM Microscopy: Scanless Two-Photon Imaging and Photostimulation with Spatial Light Modulators,” Front. Neural Circuits, vol. 2, p. 5, Dec. 2008. [44] J. P. Parry, R. J. Beck, J. D. Shephard, and D. P. Hand, “Application of a liquid crystal spatial light modulator to laser marking,” Appl. Opt., vol. 50, no. 12, pp. 1779–1785, Apr. 2011. [45] L. Sacconi, E. Froner, R. Antolini, M. R. Taghizadeh, A. Choudhury, and F. S. Pavone, “Multiphoton multifocal microscopy exploiting a diffractive optical element,” Opt. Lett., vol. 28, no. 20, pp. 1918–1920, Oct. 2003. [46] B. O. Watson, V. Nikolenko, R. Araya, D. S. Peterka, A. Woodruff, and R. Yuste, “Two-photon microscopy with diffractive optical elements and spatial light modulators,” Front. Neurosci., vol. 4, Sep. 2010. [47] G. Thériault, Y. De Koninck, and N. McCarthy, “Extended depth of field microscopy for rapid volumetric two-photon imaging,” Opt. Express, vol. 21, no. 8, pp. 10095–10104, Apr. 2013. [48] J. Demas et al., “High-Speed, Cortex-Wide Volumetric Recording of Neuroactivity at Cellular Resolution using Light Beads Microscopy,” bioRxiv, p. 2021.02.21.432164, Feb. 22, 2021. [49] R. Lu et al., “Rapid mesoscale volumetric imaging of neural activity with synaptic resolution,” Nat. Methods, vol. 17, no. 3, pp. 291–294, Mar. 2020. [50] G. Thériault, M. Cottet, A. Castonguay, N. McCarthy, and Y. De Koninck, “Extended two-photon microscopy in live samples with Bessel beams: steadier focus, faster volume scans, and simpler stereoscopic imaging,” Front. Cell. Neurosci., vol. 8, p. 139, May 2014. [51] T. Chakraborty et al., “Converting lateral scanning into axial focusing to speed up three-dimensional microscopy,” Light Sci Appl, vol. 9, p. 165, Sep. 2020. [52] J. Jiang et al., “Fast 3-D temporal focusing microscopy using an electrically tunable lens,” Opt. Express, vol. 23, no. 19, pp. 24362–24368, Sep. 2015. [53] M. E. J. Sheffield and D. A. Dombeck, “Calcium transient prevalence across the dendritic arbour predicts place field properties,” Nature, vol. 517, no. 7533, pp. 200–204, Jan. 2015. [54] B. N. Ozbay et al., “Three dimensional two-photon brain imaging in freely moving mice using a miniature fiber coupled microscope with active axial-scanning,” Sci. Rep., vol. 8, no. 1, p. 8108, May 2018. [55] L. Kong et al., “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods, vol. 12, no. 8, pp. 759–762, Aug. 2015. [56] S. Piazza, P. Bianchini, C. Sheppard, A. Diaspro, and M. Duocastella, “Enhanced volumetric imaging in 2-photon microscopy via acoustic lens beam shaping,” J. Biophotonics, vol. 11, no. 2, Feb. 2018. [57] He, Chunjing, et al. “Three-dimensional topographic and multi-elemental mapping by unilateral-shift-subtracting confocal controlled LIBS microscopy,” Spectrochim. Acta Part B At. Spectrosc., vol. 188, p. 106340, Feb. 2022. [58] H. Oku, K. Hashimoto, and M. Ishikawa, “Variable-focus lens with 1-kHz bandwidth,” Opt. Express, vol. 12, no. 10, pp. 2138–2149, May 2004. [59] M. Göppert-Mayer, “Über Elementarakte mit zwei Quantensprüngen,” Annalen der Physik, vol. 401, no. 3. pp. 273–294, 1931. [60] P. T. C. So, “Two-photon Fluorescence Light Microscopy,” eLS. 2001. [61] W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol., vol. 21, no. 11, pp. 1369–1377, Nov. 2003. [62] V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods, vol. 7, no. 8, pp. 603–614, Aug. 2010. [63] E. McLeod and C. B. Arnold, “Optical analysis of time-averaged multiscale Bessel beams generated by a tunable acoustic gradient index of refraction lens,” Appl. Opt., vol. 47, no. 20, pp. 3609–3618, Jul. 2008. [64] K.-J. Hsu, K.-Y. Li, Y.-Y. Lin, A.-S. Chiang, and S.-W. Chu, “Optimizing depth-of-field extension in optical sectioning microscopy techniques using a fast focus-tunable lens,” Opt. Express, vol. 25, no. 14, pp. 16783–16794, Jul. 2017. [65] M. Duocastella, B. Sun, and C. B. Arnold, “Simultaneous imaging of multiple focal planes for three-dimensional microscopy using ultra-high-speed adaptive optics,” J. Biomed. Opt., vol. 17, no. 5, p. 050505, May 2012. [66] A. Mermillod-Blondin, E. McLeod, and C. B. Arnold, “High-speed varifocal imaging with a tunable acoustic gradient index of refraction lens,” Opt. Lett., vol. 33, no. 18, pp. 2146–2148, Sep. 2008. [67] T.-W. Chen et al., “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature, vol. 499, no. 7458, pp. 295–300, Jul. 2013. [68] T. Knöpfel and C. Song, “Optical voltage imaging in neurons: moving from technology development to practical tool,” Nat. Rev. Neurosci., vol. 20, no. 12, pp. 719–727, Dec. 2019. [69] H. Dana et al., “High-performance calcium sensors for imaging activity in neuronal populations and microcompartments,” Nat. Methods, vol. 16, no. 7, pp. 649–657, Jul. 2019. [70] H.-Y. Chen, “Enhance Optical Penetration Depth in Drosophila Brain - Minimizing Aberration/scattering from Trachea by Liquid Filling Method,” 2022. [71] J. W. Cha et al., “Reassignment of scattered emission photons in multifocal multiphoton microscopy,” Sci. Rep., vol. 4, p. 5153, Jun. 2014. [72] K. Charan, B. Li, M. Wang, C. P. Lin, and C. Xu, “Fiber-based tunable repetition rate source for deep tissue two-photon fluorescence microscopy,” Biomed. Opt. Express, vol. 9, no. 5, pp. 2304–2311, May 2018. [73] J. L. R. Rubenstein and P. Rakic, “Neural Circuit Development and Function in the Healthy and Diseased Brain: Comprehensive Developmental Neuroscience,” Academic Press, vol. 3, 2013. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86528 | - |
dc.description.abstract | 為了了解大腦的機制,腦神經影像技術在一個多世紀以來經歷了許多突破性的發展,然而我們對大腦的了解依然有限。迄今為止仍然沒有理想的影像技術能夠同時在整個大腦中實現足夠高的時空間解析度。為了達成這項目標,此研究裡我們以果蠅作為我們的模式生物,因為其極小的大腦體積,且具有相對完整的神經結構性圖譜。為了取得活體果蠅全腦功能性影像,我們需要達到以下需求:(I)非侵入性觀測;(II)微米尺度的空間解析度以分辨單一神經元;(III)~一百微米的穿透深度以進行果蠅腦中的深組織影像;(IV)毫秒等級時間解析度的體積影像以觀察三維空間中的功能性影像。 由於雙光子光學顯微鏡的眾多優點,其經常被用於大腦功能性研究,例如其非侵入性及微米尺度的空間解析度,光學切片能力亦適合進行深組織影像,達成了需求(I~III)。然而,大部分雙光子顯微鏡透過掃描整個樣本以獲得三維影像,限制了其影像速度。在此研究中我們分別在橫向及軸向加快成像速度以達成高速三維影像。在橫向上,我們利用繞射分光元件將單道光分成32道光,並使用32通道的光電倍增管提高其影像速度。在軸向上,我們使用可調式聲波梯度折射率透鏡達成焦點在此軸上的高速掃描。透過這結合這兩項技術,我們實現了時間解析度為兩毫秒的體積影像,即達成需求(IV)。 此研究使用鈣離子螢光蛋白(GCaMP7f)標記的果蠅腦進行活體觀測,透過觀察自發活動,發現了果蠅腦內蕈狀體中不同亞區的瞬時反應。通過進一步以電擊刺激果蠅,我們在頻域中觀察到週期性活動。證明了此系統能夠觀察活體果蠅腦的功能性影像。然而,在我們系統中還有一個需要被解決的問題:資料擷取過程中的數據遺失。可能的原因為軟體的過度負載,造成中央處理器的低處理效率。在未來更換較高效能的中央處理器後,期望我們所建立的高速多焦點多光子體積顯微鏡,能夠對於未來建立果蠅大腦的功能性神經連接圖譜有所幫助。 | zh_TW |
dc.description.abstract | Brain is an important organ that plays a necessary role in our emotions, thought, memory, and almost every process that regulates our body. In order to understand the mechanism of the brain, numerous studies have progressed for more than a century. However, our understanding of the brain is still limited. The reason is that no ideal imaging tool nowadays has the capability to simultaneously achieve micrometer and millisecond spatiotemporal resolution in the whole brain. To achieve this requirement, we select Drosophila to be our sample because of its small brain size and the nearly-complete structural connectome. In order to accomplish in vivo whole Drosophila brain functional imaging, we need to reach the following requirements: (I) noninvasive method, (II) micrometer spatial resolution to distinguish neurons, (III) ~100 μm penetration depth for Drosophila deep tissue imaging, (IV) millisecond temporal resolution volumetric imaging for 3D functional dynamics. Two-photon microscopy (2PM) is often used for in vivo brain study because of its noninvasive characteristic, ~μm scale spatial resolution and optical sectioning that offers remarkable penetration depth, achieving the requirements (I - III), respectively. However, the imaging speed is limited since 2PM typically requires raster scanning through the whole sample. Here we increase the speed on the lateral axis via multifocal imaging formed by a diffractive optical element (DOE) and a multichannel PMT. The axial speed is enhanced by a tunable acoustic gradient-index (TAG) lens, which scans the focus on the axial axis with an ~100 kHz. Through combining these two optical elements, we are able to achieve volumetric imaging with ~2 ms temporal resolution, which accomplishes the last requirement (IV). In this study, we apply our system on the GCaMP7f-labeled Drosophila brains for in vivo imaging. With spontaneous activities, we discover the distinct transient response in different subcompartments in the mushroom body. We further stimulate the Drosophila via electric shock, and observe periodic activities in the frequency domain. However, one challenge remains is the data lost during imaging, which is caused by the software-induced low CPU processing efficiency. With replacing a high-performance CPU to overcome this difficulty in the future, our high-speed multifocal multiphoton volumetric microscope paves the way toward establishing functional connectome in Drosophila brain. | en |
dc.description.provenance | Made available in DSpace on 2023-03-20T00:01:14Z (GMT). No. of bitstreams: 1 U0001-2509202221061500.pdf: 7306566 bytes, checksum: 4abb1ac98b31147c11020b03d2c0df57 (MD5) Previous issue date: 2022 | en |
dc.description.tableofcontents | 謝辭 i 摘要 ii ABSTRACT iii CONTENTS v LIST OF FIGURE vii LIST OF TABLE ix Chapter 1. Introduction: Challenges of brain study and possible solutions 1 1.1 Current status in brain study 1 1.1.1 Brain features 1 1.1.2 Challenges of common technique in brain science 4 1.1.3 Model animal: Drosophila 7 1.1.4 Challenges of in vivo Drosophila brain study 8 1.2 Comparison of brain study techniques 9 1.2.1 Optical microscopy in brain imaging 9 1.2.2 Speed limitation in two-photon microscopy 12 1.2.3 Enhancing speed in lateral axis with multifocus (DOE) 12 1.2.4 Enhancing speed in axial axis with a TAG lens 13 1.3 Aim: Functional volumetric brain imaging in Drosophila brain study 17 Chapter 2. Principle of each technique 19 2.1 Two-photon microscopy 19 2.2 Diffractive optical element (DOE) 21 2.3 TAG lens 23 2.4 High speed two-photon volumetric microscopy 27 Chapter 3. Experimental method: system design and sample preparation 28 3.1 Optical setup 28 3.2 Hardware setup 35 3.3 Experimental protocol 38 3.4 Drosophila sample: Electric shock 47 Chapter 4. Improvement of the system and solutions 49 4.1 Crosstalk in multichannel 49 4.2 Shift on galvo axis 50 4.3 Missing data causing image shift 54 Chapter 5. Biology results 59 5.1 Functional Drosophila imaging: Spontaneous 59 5.2 Functional Drosophila imaging: Electric simulation 63 Chapter 6. Conclusion and discussion 70 6.1 Increasing the emitted photon yield 70 6.2 CPU performance might cause missing data 71 6.3 Absorption of the TAG lens 72 6.4 Other applications of this system 73 REFERENCE 74 | |
dc.language.iso | en | |
dc.title | 多焦雙光子體積顯微鏡於果蠅腦之功能性影像 | zh_TW |
dc.title | Functional Volumetric Imaging of Drosophila and System Improvement of High-speed Multifocal Two-photon Microscopy | en |
dc.type | Thesis | |
dc.date.schoolyear | 110-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳順吉(Shun-Chi Wu),李夢麟(Meng-Lin Li),朱麗安(Li-An Chu) | |
dc.subject.keyword | 多焦點顯微鏡,雙光子顯微鏡,可調式聲波梯度折射率透鏡,體積成像,功能性影像, | zh_TW |
dc.subject.keyword | Multifocal microscopy,Two-photon microscopy,Tunable acoustic gradient-index lens,Volumetric imaging,Functional imaging, | en |
dc.relation.page | 81 | |
dc.identifier.doi | 10.6342/NTU202204017 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2022-09-28 | |
dc.contributor.author-college | 理學院 | zh_TW |
dc.contributor.author-dept | 物理學研究所 | zh_TW |
dc.date.embargo-lift | 2022-09-30 | - |
顯示於系所單位: | 物理學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
U0001-2509202221061500.pdf | 7.14 MB | Adobe PDF | 檢視/開啟 |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。