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  1. NTU Theses and Dissertations Repository
  2. 電機資訊學院
  3. 光電工程學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55250
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dc.contributor.advisor黃升龍(Sheng-Lung Huang)
dc.contributor.authorChih-Chieh Chen Linen
dc.contributor.author陳林志傑zh_TW
dc.date.accessioned2021-06-16T03:53:15Z-
dc.date.available2025-07-31
dc.date.copyright2020-08-07
dc.date.issued2020
dc.date.submitted2020-07-31
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[3] D. Cai, M. Zhu, W. M. Petroll, V. Koppaka, and D. M. Robertson, “The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium,” The America Journal of Pathology 184(10), 2662–2670 (2014).
[4] G. Bitirgen, A. Ozkagnici, R. A. Malik, and H. Kerimoglu, “Corneal nerve fiber damage precedes diabetic retinopathy in patients with Type 2 diabetes mellitus,” Diabetic Medicine 31(4), 431–438 (2014).
[5] S. L. Misra, H. M. Kersten, R. H. Roxburgh, H. V. Danesh-Meyer, and C. N. J. McGhee, “Corneal nerve microstructure in Parkinson's disease,” Journal of Clinical Neuroscience 39, 53–58 (2017).
[6] O. Levy et al., “Increased corneal sub-basal nerve density in patients with Sjögren syndrome treated with topical cyclosporine A,” Clinical and Experiment Ophthalmology 45(5), 455–463 (2017).
[7] N. Papanas and D. Ziegler, “Corneal Confocal Microscopy: A New Technique for Early Detection of Diabetic Neuropathy,” Current Diabetes Reports 13, 488–499 (2013).
[8] R. Malik, “CCMetrics: Cornea nerve fiber quantification.” [Online]. Available: https://www.click2go.umip.com/i/s_w/Biomedical_Software/ccmetrics.html.
[9] T. Tervo, J. Holopainen, and C. Belmonte, “Confocal microscopy of corneal nerves: A limited but still useful technique to evaluate peripheral neuropathies,” JAMA Ophthalmology 134(9), 990–991 (2016).
[10] E. Auksorius et al., “In vivo imaging of the human cornea with high-speed and high-resolution Fourier-domain full-field optical coherence tomography,” Biomedical Optics Express 11(5), 2849 (2020).
[11] W. Drexler and J. G. Fujimoto, “Optical Coherence Tomography: Technology and Applications,” 2nd Edition, Springer Inc., (2015)
[12] Wolfram MathWorld, “Wiener-Khinchin Theorem.” [Online]. Available: https://mathworld.wolfram.com/Wiener-KhinchinTheorem.html.
[13] P. F. Moulton, “Spectroscopic and laser characteristics of Ti:Al2O3,” Journal of the Optical Society of America B 3(1), 125 (1986).
[14] 王世昌, “玻璃纖衣摻鈦藍寶石晶體光纖之發展與應用,” 國立臺灣大學博士論文, (2016).
[15] S. L. Huang, “Crystal Photonics class note,” 國立臺灣大學, (2018).
[16] 陳昱彤, “全域式光學同調斷層掃描術用於動物眼睛模型之特性分析,” 國立臺灣大學碩士論文, (2018).
[17] E. Hecht, “Optics,” 5th Edition, Pearson Inc., (2016).
[18] S. Patel, J. Marshall, and F. W. Fitzke, “Refractive index of the human corneal epithelium and stroma,” Journal of Refractive Surgery 11(2), 100–105 (1995).
[19] A. J. Hertsenberg and J. L. Funderburgh, “Stem cells in the cornea,” Progress in Molecular Biology and Translational Science 134, 25–41 (2015).
[20] Dr. Urano, “Diabetes and Optic Atrophy.” [Online]. Available: https://wolframsyndrome.dom.wustl.edu/diabetes-and-optic-atrophy/.
[21] T. G. Rowsey and D. Karamichos, “The role of lipids in corneal diseases and dystrophies: a systematic review,” Clinical and Translational Medicine 6(1), 1–13 (2017).
[22] A. O. Eghrari, S. A. Riazuddin, and J. D. Gottsch, “Overview of the cornea: structure, function, and development,” Progress in Molecular Biology and Translational Science 134, 7–23 (2015).
[23] Y. T. Chen et al., “En face and cross-sectional corneal tomograms using sub-micron spatial resolution optical coherence tomography,” Scientific Reports 8(1), 1–10 (2018).
[24] “角膜的生理學.” [Online]. Available: http://doctor.get.com.tw/m/Journal/detail.aspx?no=407039.
[25] D. W. DelMonte and T. Kim, “Anatomy and physiology of the cornea,” Journal of Cataract Refractive Surgery 37(3), 588–598 (2011).
[26] S. Hayashi, T. Osawa, and K. Tohyama, “Comparative observations on corneas, with special reference to Bowman’s layer and Descemet’s membrane in mammals and amphibians,” Journal of Morphology 254(3), 247–258 (2002).
[27] “Anatomy and physiology of cornea.” [Online]. Available: https://www.slideshare.net/Lhacha/anatomy-and-physiology-of-cornea.
[28] J. Chen et al., “Descemet’s membrane supports corneal endothelial cell regeneration in rabbits,” Scientific Reports 7(1), 1–13 (2017).
[29] “Sub-basal Nerve Plexus.” [Online]. Available:
https://aibolita.com/eye-diseases/38894-subbasal-nerve-plexus.html.
[30] S. Patel and L. Tutchenko, “The refractive index of the human cornea: A review,” Contact Lens Anterior Eye 42(5), 575–580 (2019).
[31] “Scale Model of Human Eye.” [Online]. Available:
http://hyperphysics.phy-astr.gsu.edu/hbase/vision/eyescal2.html.
[32] J. O. Hjortdal, “Regional elastic performance of the human cornea,” Journal of Biomechanics 29(7), 931–942 (1996).
[33] M. Brines et al., “Corneal nerve fiber size adds utility to the diagnosis and assessment of therapeutic response in patients with small fiber neuropathy,” Scientific Reports 8(1), 1–11 (2018).
[34] R. Malik, “ACCMetrics: Corneal nerve fiber analyser.” [Online]. Available: https://www.click2go.umip.com/i/s_w/Biomedical_Software/accmetrics_v2.html.
[35] “國家實驗動物中心:FVB/NJNarl 小鼠.” [Online]. Available: http://www.nlac.org.tw/p3_animal2_detail.asp?cid=1 nid=6 ppage=0 type=1
[36] 李泔泓, “實驗動物操作之相關技術介紹.” [Online]. Available: https://www.narlabs.org.tw/
[37] S. C. G. Tseng, S. Y. Chen, Y. C. Shen, W. L. Chen, and F. R. Hu, “Critical appraisal of ex vivo expansion of human limbal epithelial stem cells,” Current Molecular Medicine 10(9), 841–850 (2010).
[38] M. Reichard et al., “Age-related changes in murine corneal nerves,” Current Eye Research 41(8), 1021–1028 (2016).
[39] T. Panagiotis, “Animal Models in Eye Research,” 1st Edition, Elsevier Inc., (2008).
[40] D. Wu et al., “Evaluation the change of corneal epithelium thickness after pterygium excision with conjunctival autograft transplantation by fourier domain optical coherence tomography,” 中華眼科雜誌50(11), 833–838 (2014).
[41] H. F. Li, W. M. Petroll, T. Møller-Pedersen, J. K. Maurer, H. D. Cavanagh, and J. V. Jester, “Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing (CMTF),” Current Eye Research 16(3), 214–221 (1997).
[42] L. A. Deinema, A. J. Vingrys, H. R. Chinnery, and L. E. Downie, “Optical coherence tomography reveals changes to corneal reflectivity and thickness in individuals with tear hyperosmolarity,” Translational Vision Science Technology 6(3), 6 (2017).
[43] “臺灣國家眼庫.” [Online]. Available: https://nebt.org.tw/.
[44] 施承宏, “全域式光學同調斷層掃描術用於角膜神經影像分析,” 國立臺灣大學碩士論文, (2019).
[45] C. M. Bishop, “Pattern recognition and machine learning,” Springer, (2006).
[46] Personal communication with Professor I-Ping Tu.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55250-
dc.description.abstract在眼角膜的檢測當中,建構高解析度的三維影像,可以提供臨床醫師更多的診斷資訊,對疾病做精準的判斷。例如:角膜各層結構之形貌與厚度。除此之外,角膜富含感覺神經,許多的系統性與眼表面疾病,皆與角膜亞基底神經之形貌變化有關。目前文獻上也報導了許多與角膜神經相關的疾病,例如:帕金森氏症、糖尿病與乾眼症。因此精確定量角膜亞基底神經形貌,就有機會對疾病進行早期的診斷。
在本研究當中,使用高空間解析度之全域式光學同調斷層掃描,其具有等向性及微米等級解析度之特性,能夠展示角膜各橫平面、縱平面與三維立體影像。除此之外,本系統還具有大面積掃描的能力,能夠藉由拼接的方式組合多個視域之大面積影像。
藉由檢體小鼠與兔子實驗,證實本系統具有細胞等級的成像能力,且能夠對角膜亞基底神經做定量的分析。在兔子的實驗當中,我們發現了許多影響神經量化的複雜形貌,例如:K結構與基底上皮細胞邊界。而小鼠角膜神經形貌定量結果為:主幹神經密度136.93 ± 19.18 mm-2;分枝神經密度731.00 ± 186.19 mm-2;分枝神經連接點密度608.01 ± 116.99 mm-2;角膜亞基底神經密度61.46 ± 1.78 mm/mm2;神經寬度1.08 ± 0.32 µm;扭曲度0.0681 ± 0.0132;平均分枝點4.57 ± 1.41;分枝主幹比5.53 ± 2.04;K line平均值為 Grade 1;短神經15 ± 3.5根;平行性0.7500 ± 0.0475;單一影像中之平行性標準差0.30 ± 0.02。
利用全域式光學同調斷層掃描,可清楚地拍攝出小鼠角膜亞基底神經細微的結構,並同時得到角膜之縱平面影像。接著透過自行編寫的神經分析軟體TCCMetrics,精確的將神經形貌定量為十二項量化參數。結合以上兩者技術,在臨床上有望促進疾病早期之診斷。
zh_TW
dc.description.abstractIn cornea examination, high-resolution three-dimensional images can provide clinicians with more diagnostic information, such as corneal thickness and cellular morphology. In addition, the cornea is a densely innervated tissue with sensory nerve fibers. Both ocular surface and systemic diseases are associated with corneal nerves. Therefore, accurate quantification can help in disease diagnosis at earlier stages.
In this study, we use high spatial-resolution full-field optical coherence tomography (FF-OCT) with isotropic cellular resolution as an examination instrument. This technique can provide images from reconstructed three-dimensional information and a large field of view by stitching tomograms side by side.
We validated the imaging ability with ex vivo mice and rabbit, and quantified the corneal sub-basal nerve morphology by twelve parameters. The quantitative results of ex vivo mice are as follows: NFD, 136.93 ± 19.18 mm-2; BND, 731.00 ± 186.19 mm-2; BNCD, 608.01 ± 116.99 mm-2; NFL, 61.46 ± 1.78 mm/mm2; NFW, 1.08 ± 0.32 µm; TC, 0.068 ± 0.013; BNCM, 4.57 ± 1.41; BMR, 5.53 ± 2.04; average K line grading, Grade 1; numbers of short nerve fiber, 15 ± 3.5; parallelism, 0.75 ± 0.05; and standard deviation of single-image parallelism, 0.3 ± 0.02.
The use of FF-OCT can clearly capture the sub-basal nerve morphology in mice. By means of the self-written neural analysis software TCCMetrics, the nerve's morphology is accurately quantified through twelve parameters. The combination of these two technologies is expected to facilitate the early clinical diagnosis of a wide range of diseases.
en
dc.description.provenanceMade available in DSpace on 2021-06-16T03:53:15Z (GMT). No. of bitstreams: 1
U0001-3007202017202200.pdf: 12926211 bytes, checksum: e04efc634c2412f023e7ada596599d8b (MD5)
Previous issue date: 2020
en
dc.description.tableofcontents誌謝 I
摘要 II
Abstract III
目錄 IV
圖目錄 VI
表目錄 XIII
第一章 緒論 1
第二章 Mirau-based全域式光學同調斷層掃描術與眼睛結構介紹 3
2.1 光學同調斷層掃描(OCT)原理 3
2.2 Mirau-based 全域式光學同調斷層掃描系統 13
2.2.1 系統簡介 13
2.2.2 影像擷取與處理 22
2.2.3 高速CMOS相機之高亮度光源需求分析 26
2.2.4 系統之橫向與縱向解析度 31
2.2.5 影像訊噪比 36
2.2.5.1 移動平均處理 37
2.2.5.2 不同系統掃描速度 40
2.3 眼睛結構介紹 42
第三章 角膜亞基底神經之分析與量化方法 47
3.1 神經影像處理與量化方法 47
3.1.1 神經影像之處理方法 47
3.1.2 神經量化參數介紹 50
3.2 神經分析程式介紹與比較 57
3.2.1 CCMetrics 57
3.2.2 ACCMetrics 61
3.2.3 現有分析軟體之優劣分析 62
3.3 TCCMetrics神經量化軟體介紹 63
第四章 角膜之OCT影像量測與分析 68
4.1 Ex vivo正常FVB小鼠角膜量測與分析 68
4.1.1 Ex vivo FVB小鼠角膜樣本之製備與量測方法 68
4.1.2 小鼠角膜量測結果與影像分析 70
4.1.3 小鼠角膜大圖拼接結果與影像分析 77
4.1.4 小鼠角膜神經影像量化分析 82
4.2 Ex vivo正常紐西蘭大白兔角膜量測與分析 89
4.2.1 Ex vivo 兔子角膜樣本之製備與量測方法 89
4.2.2 兔子角膜量測結果與影像分析 90
第五章 結論與未來展望 95
5.1 結論 95
5.2 未來展望 98
參考文獻 99
附錄一 神經影像強化程式 104
附錄二 TCCMetrics角膜亞基底神經量化軟體 105
附錄三 角膜亞基底神經研究進度 116
dc.language.isozh-TW
dc.subject角膜亞基底神經zh_TW
dc.subject全域式光學同調斷層掃描zh_TW
dc.subject神經形貌量化zh_TW
dc.subject角膜zh_TW
dc.subjectCorneal sub-basal nerveen
dc.subjectQuantitative of corneal sub-basal nerveen
dc.subjectFull-field optical coherence tomographyen
dc.subjectCorneaen
dc.title利用全域式光學同調斷層掃描術與自編軟體進行角膜神經的量化分析
zh_TW
dc.titleQuantification of Corneal Nerve's Image Using TCCMetrics and Full-field Optical Coherence Tomographyen
dc.typeThesis
dc.date.schoolyear108-2
dc.description.degree碩士
dc.contributor.advisor-orcid黃升龍(0000-0001-6244-1555)
dc.contributor.oralexamcommittee陳偉勵(Wei-Li Chen),杜憶萍(I-Ping Tu),蔡佳穎(Chia-Ying Tsai)
dc.contributor.oralexamcommittee-orcid陳偉勵(0000-0002-1538-2414)
dc.subject.keyword全域式光學同調斷層掃描,角膜,角膜亞基底神經,神經形貌量化,zh_TW
dc.subject.keywordFull-field optical coherence tomography,Cornea,Corneal sub-basal nerve,Quantitative of corneal sub-basal nerve,en
dc.relation.page116
dc.identifier.doi10.6342/NTU202002120
dc.rights.note有償授權
dc.date.accepted2020-08-03
dc.contributor.author-college電機資訊學院zh_TW
dc.contributor.author-dept光電工程學研究所zh_TW
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