荧光光谱医学成像诊断技术研究
|
摘要
医学诊断在临床治疗中有着举足轻重的作用,现行的诊断和治疗方法也是各有利弊。人们已经证明荧光光谱诊断技术与光子学和生物学结合可以实现对肿瘤的有效诊断,不仅能诊断病变前期微小癌症灶,而且能区分良性肿瘤和恶性肿瘤。荧光光谱诊断技术具有无损伤、非介入、精度高等优点。本文以良性病变为研究对象,开展了荧光光谱医学成像诊断技术研究。
设计并建立点荧光光谱测量系统。该系统以中心波长为405nm的LED作为激发光源,CCD光谱仪作为光谱测量器件:研究牙结石、人体正常血液、患病血液、人体患病皮肤的荧光光谱;结果分析表明正常牙齿荧光光谱荧光峰为490nm波段宽带范围为440-800nm,而牙结石荧光光谱除具有正常牙齿荧光光谱外,在620-770nm波段还有特征荧光发射;人的血液的荧光光谱对激发光频率敏感,但没有特异性;正常皮肤与患病皮肤的荧光光谱有差异但差异很小。因此,认为有些诊断(如牙结石)可以通过自体荧光光谱分析达到诊断的目的;而对皮肤病或血液等的诊断,不建议利用自体荧光光谱诊断,建议利用药物荧光光谱诊断。该研究工作是荧光光谱成像诊断研究的基础。
建立面荧光光谱诊断方法和系统。利用点荧光光谱测量系统测量牙结石牙齿的荧光光谱,研究确立牙结石诊断的荧光比例法;在牙结石面荧光光谱诊断中,利用摄取的中心波长为487nm(带宽为10nm)的图像和中心波长为649nm(带宽为38nm)图像的处理(包括比值运算、伪彩色编码等),得到牙结石的伪彩色图像;通过软件程序,实现图像的去噪声,平滑,锐化等处理;结果表明从最后的图像可以清晰地看到牙结石的边界和牙结石的厚度等信息。
设计基于TMS320C6201的图像处理系统,包括硬件部分和软件部分,并能实现信息处理的要求。在芯片的选取上,确定选择DSP芯片;在设计中通过对DSP与外围电路的设计,包括MAX706X的复位功能、时钟设计、电源设计、FIFO与DSP的连接、DSP与SDRAM的连接、DSP与FLASH的连接。很好地解决了芯片内核和外围电路的电源分配的问题,详细地描述图像矩阵的传输,并建立系统开发的软件平台。
Medicinal diagnosis is crucial to clinical therapy in modern time, conventional diagnosis and therapy technique alse each has his strong point and has his demerit, People have demonstrate that fluorescence spectrum diagnose technique integrate photon into biology can diagnose some cancers effetely, We adopt fluorescence spectrum diagnostic make diagnose pathological changes prophase turn into possibility , The technique can distinguish carcinoid with malignancy, The technique which is non-contact amd have some merits which conventional approachs have not possessed, it has been becoming a burgeoning and promising approach. During the experiment, This article research on carcinoid develop fluorescence spectrum diagnostic technique , This study make for the expend of fluorescence spectrum diagnostic technique, It is meaning and valuable for medical laser application.
We design and establish the system of point diagnosis .The system consist of LED with the midwavelengh 405nm as to be excited lamp-house and CCD monochromator as to be measure apparatus. We diagnose and find their fluorescence spectrum of calculus、blood、unhealthy blood、pathological cutis , The result exhibit that the wave crest of normal teeth is 490nm and its waveband is 440-490nm,but the fluorescence spectrum of calculus have another 620-770nm characteristic waveband.The fluorescence spectrum of human blood is sensitive to exited optical frequency, but the fluorescence spectrum doesn’t have character, The difference between normal cutis and pathological cutis is faint ,So we advise that we do not apply the diagnostic technique to cutis and blood, We suggest we adopt drug fluorescence spectrum. The study prove intact fundamental principle for fluorescence spectrum.
We establish the method and the system of image diagnosis. We get the fluorescence spectrum of calculus which is suited for ratio disposal . During the experiment ,we adopt the system imaging diagnosis to diagnose the teeth with calculus as a typical case . We take the image of midwavelength 487nm and the image of midwavelength 649nm ,Then we deal with them according to exclusive arithmetic. We gain perfect image and append artificial color to perfect image as to embody the extent of calculus bestrew ,Meanwhile, We get rid of noise in nonlinear median filter and get perfect result by flat and sharp and so on。
According to intact theory, We design the system of image disposal base on TMS320C6201 Digital Signal Processing,We combine the hardware system to the software system。We dissertate the principle of digital signal processing , choose all kind of import indispensable chip , design the configuration of DSP and periphery circuit including the function of MAX706X’s reposition、the design of time、the design of electrical source、the connect between FIFO and DSP、the connect between DSP and SDRAM、the connect between DSP and FLASH、and so on. During the course We resolve the distribute of electrical source between kernel and periphery circuit,We describe the transmission of image matrix, solve the problem of pivotal segment and system。We analyze all various fluorescence in order to take some requisite medicinal information。
设计并建立点荧光光谱测量系统。该系统以中心波长为405nm的LED作为激发光源,CCD光谱仪作为光谱测量器件:研究牙结石、人体正常血液、患病血液、人体患病皮肤的荧光光谱;结果分析表明正常牙齿荧光光谱荧光峰为490nm波段宽带范围为440-800nm,而牙结石荧光光谱除具有正常牙齿荧光光谱外,在620-770nm波段还有特征荧光发射;人的血液的荧光光谱对激发光频率敏感,但没有特异性;正常皮肤与患病皮肤的荧光光谱有差异但差异很小。因此,认为有些诊断(如牙结石)可以通过自体荧光光谱分析达到诊断的目的;而对皮肤病或血液等的诊断,不建议利用自体荧光光谱诊断,建议利用药物荧光光谱诊断。该研究工作是荧光光谱成像诊断研究的基础。
建立面荧光光谱诊断方法和系统。利用点荧光光谱测量系统测量牙结石牙齿的荧光光谱,研究确立牙结石诊断的荧光比例法;在牙结石面荧光光谱诊断中,利用摄取的中心波长为487nm(带宽为10nm)的图像和中心波长为649nm(带宽为38nm)图像的处理(包括比值运算、伪彩色编码等),得到牙结石的伪彩色图像;通过软件程序,实现图像的去噪声,平滑,锐化等处理;结果表明从最后的图像可以清晰地看到牙结石的边界和牙结石的厚度等信息。
设计基于TMS320C6201的图像处理系统,包括硬件部分和软件部分,并能实现信息处理的要求。在芯片的选取上,确定选择DSP芯片;在设计中通过对DSP与外围电路的设计,包括MAX706X的复位功能、时钟设计、电源设计、FIFO与DSP的连接、DSP与SDRAM的连接、DSP与FLASH的连接。很好地解决了芯片内核和外围电路的电源分配的问题,详细地描述图像矩阵的传输,并建立系统开发的软件平台。
Medicinal diagnosis is crucial to clinical therapy in modern time, conventional diagnosis and therapy technique alse each has his strong point and has his demerit, People have demonstrate that fluorescence spectrum diagnose technique integrate photon into biology can diagnose some cancers effetely, We adopt fluorescence spectrum diagnostic make diagnose pathological changes prophase turn into possibility , The technique can distinguish carcinoid with malignancy, The technique which is non-contact amd have some merits which conventional approachs have not possessed, it has been becoming a burgeoning and promising approach. During the experiment, This article research on carcinoid develop fluorescence spectrum diagnostic technique , This study make for the expend of fluorescence spectrum diagnostic technique, It is meaning and valuable for medical laser application.
We design and establish the system of point diagnosis .The system consist of LED with the midwavelengh 405nm as to be excited lamp-house and CCD monochromator as to be measure apparatus. We diagnose and find their fluorescence spectrum of calculus、blood、unhealthy blood、pathological cutis , The result exhibit that the wave crest of normal teeth is 490nm and its waveband is 440-490nm,but the fluorescence spectrum of calculus have another 620-770nm characteristic waveband.The fluorescence spectrum of human blood is sensitive to exited optical frequency, but the fluorescence spectrum doesn’t have character, The difference between normal cutis and pathological cutis is faint ,So we advise that we do not apply the diagnostic technique to cutis and blood, We suggest we adopt drug fluorescence spectrum. The study prove intact fundamental principle for fluorescence spectrum.
We establish the method and the system of image diagnosis. We get the fluorescence spectrum of calculus which is suited for ratio disposal . During the experiment ,we adopt the system imaging diagnosis to diagnose the teeth with calculus as a typical case . We take the image of midwavelength 487nm and the image of midwavelength 649nm ,Then we deal with them according to exclusive arithmetic. We gain perfect image and append artificial color to perfect image as to embody the extent of calculus bestrew ,Meanwhile, We get rid of noise in nonlinear median filter and get perfect result by flat and sharp and so on。
According to intact theory, We design the system of image disposal base on TMS320C6201 Digital Signal Processing,We combine the hardware system to the software system。We dissertate the principle of digital signal processing , choose all kind of import indispensable chip , design the configuration of DSP and periphery circuit including the function of MAX706X’s reposition、the design of time、the design of electrical source、the connect between FIFO and DSP、the connect between DSP and SDRAM、the connect between DSP and FLASH、and so on. During the course We resolve the distribute of electrical source between kernel and periphery circuit,We describe the transmission of image matrix, solve the problem of pivotal segment and system。We analyze all various fluorescence in order to take some requisite medicinal information。
引文
1 N.R.Paras原著.张琛主编.何赛灵译.生物光子学导论.浙江大学出版社,2006:162~166
2 Alfano.R.R, Tata.D.B, Cordero.J. Laser Induced Fluorescence Spectroscopy from Native Cancero us and Normal Tissue. IEEE Journal of Quantum Electronics. Qe-20,1984, (12):1507-1511
3 Pinheiro.A,Low-Leve.I. Laser Therapy is an Important Tool to Treat Disorders in the Maxillofacial Region. J Clinical Laser Med&Surg. 1998, 1622(4): 3226
4 M.R.Hambin, T.Hasan. Advances in Photodynamic Theory. Optics and Photo- nics News. 1996, 7(7):18–21
5 Sanderson, D.R,Fontana, R.S,Lipson, R.L.and Baldes,E.J. Haematoporphyrin as a diagnostic tool apreliminary report of newt echniques. Cancer. 1972, (30):1368-1372
6 Cotese,D.A,Kinsey,J.H,Woolner,L.B,Payne,W.S.Sanderson. Clinical application of a new endoscopic technique for detection of in situ bronchial carcinoma,Mayo Clin.Proc.1979, (11):516-520
7 Andersson.P.S, Montan,S and Svanberg. S. Multi-spectral system for medical fluorescence imaging,IEEE J.Quant.Electr. 1987, (23):1798-1805
8 R.R.Alfano, G.C.Tang, Asima, Pradan. Laser Spectra from Human Normal and Tumor Lung and Breast Tissues. Optical Science and Engineering Serises.American Institute of Physics.1988, (9):665-670
9杨远龙,叶衍铭,李郁芬等.恶性肿瘤特征自体的来源以及在诊断中的应用.复旦大学学报.1986, 25(1):9096
10 Yakshe.P.N, Bonner.R.F, Patterson.P. Laser-Induced Fluorescence Spectroscopy. Am JGastroentereolo. 1989,( 84):199
11 K.Sbanberg, E.Kjellen, J.Ankerst. Fluorescence Studies of Hematoporphyrin Derivative in Normal and Malignant Rat Tissue.Cancer Research. 1990,(46):3803-3808
12 A.E.Profio, S.S.Xie. Autofluorescence of Tumor and Lung Tissue Versus Excitation Wavelength.China Laser Medince. 1992,(20),18-22
13 Baraga.J. J, Taroni. P, Park.Y.D, An.K.Maestri, Tong.L.L, Rava,.R,P, Kittrell,.C,Dasari,R.R. and Feld.M.S. Ultraviolet laser induced fluorescence of human aorta. Spectrochim.Acta. 1989, (45A): 95-99
14 Chance.B, Cohen.P, Jobsis.F and Schoener.B. Intracellular oxidation reduction states in vivo. Science. 1962, (137): 499-508
15 Chance,B.and Schoener,B. Fluorometric studies of flavin component of respiratory chain, in Flavins and flavoproteins ed.Slater, pp.510-519 (Elservier publishing Comp, New York,USA,1966)
16 Romer T. J, Finamaueice.M, Coshren.R. M, et al. laser-induced fluorescence microscopy of normal colon and dysphasis in colonic adenomas: implications for spectroscopic diagnosis. Am J Gastroemterol. 1995, (90):8187
17 M.A.Biel. Photodynamic Therapy and the Treatment of Head and Neck, Neopl -asia.Laryngoscope. 1998, (108):59–68
18 Poon,W.S, Schomacker.K.T, Deutsch.T.F.and Martuza.R.L. Laser-induced fluorescence: experimental intraperative delineation of tumor resection margins.J.Neurosurg. 1992, (76):679-686
19 D.Hallewin, M.A.Baert and Vanherzeele. H.Fluorescence imaging of bladder cancer. Acta Urol.Belg. 1994, (62):49-52
20 Doiron.D.R, Profio.E, Vincent.R.G. and Dougherty.T.J. Fluorescence bronchoscopy for detection of lung cancer. Chest.1979, (76): 27-32
21朱箐.激光医学.上海科学技术出版社,2003: 45-48
22 K.Svanberg, S.Svanberg. Photodynamic Therapy utilizing Interstitial Light Delivery Combined with Spectroscopic Methods. Department of Physics Lund Institute of Technology.2005,40-42
23 Barbara W. Chwiror, Stanislaw Chwirot. Ultraviolet Laser-induced Fluorescence of Human Stomach Tissue:Detection of Caner Tissue by Imaging Techniques. Lasers in Surgery and Medicine 1997, (21):149-158
24王振亚.自体荧光和肿瘤的光谱诊断研究进展.光电子技术与信息. 1999,12(1):3-8
25 W .illem, M.Star. Light dosimetry in vivo. Phys. Med. Bio. 1997, (42):763-787.
26 Li W, Chen.W.G..Tissue's autofluorescence spectroscopy disgnosis technology. Applied Laser. 1995, 15:(1):46
27陈亚娟,李家泽,余小敏.激光诱导自体荧光成像法(LIFI)诊断肺癌.光学技术. 2004,30(4):2-6
28李步洪,谢树森,林棋榕.激光诱导荧光在肿瘤诊断中的应用.福建师范大学报.1998,14(2) :107-111
29 Haishan Zeng Alan Weiss, Richard Cline. Real-time endoscopic fluorescence imaging for early cancer detection in the gastrointestional tract. Bioimaging. 1998,(6):151-165
30 Haishan.Zeng. A Computerized Autoflourescence and Diffuse Reflectance Spectroanalyser for in vivo Skin Studies .Phys Med Biol.1993,38:231-240
31 Haishan Zeng. Novel Microspectrophotometer and its Biomedical Applications Optical Engineering. 1993: 32(8):1809-1813
32 N. Ramanujam, M. F. Mitchell,A. Mahadevan-Jansen, S. Thomsen.Cervical Precancer Detection Using a Multivariate Statistical Algorithm Based on Laser Induced Fluorescence Spectra at Multi-ple Excitation Wavelengths. Photochem. Photohiol. 1996, 64: 720-735
33 Kevin.T. Ultraviolet laser-induced fluorescence of colonic polys Gastroenter- ology. 1992; 102:1155-1160
34 V. Dinh, Panjehpour M, et al. In vivo cancer diagnosis of.the esophagus using differential normalized fluorescence indices. Lasers Surg Med. 1995;16(1): 41-47
35 I.Georgakoudi,B. C. Jacobson, J. Dam, et al. Fluorescence, Refectance, and Light-Scattering Spectroscopy for Evaluating Dysplasia in Patients With Barretts Esophagus, Gastroenterology .2001,120:1620-1629
36 G. Bottiroli, A. C. Croce, D. Locatelli,R. Nano, E. G iombe 11 i,A. Messina, E. Benericetti. Brain Tissue Autofluorescence:an Aid for Intra-operative Delin-eation of Tumor Resection Margins. Cancer Detect. Prevent. 1998,22(4):330-339
37 F. Koenig, F. J. McGovern, H. Enquist, R. Larne, T. F. Deutsch, K. T.Schomacker, Autofluorescence Guided Biopsy for the Early Diagnosis of Bladder Carcinoma. J. Urol.,1998,159(6):1871-1875
38 M. L. Harries, S. Lam, C. MacAulay, J. A. Qu, B. Palcic. Diagnostic Imaging of the Larynx: Autofluorescence of Laryngeal Tumors Using the Helium Cadmium Laser. J. Laryngol. Otol. 1995, 109:108-110
39 K. Izuishi,H. Tajiri,M. Ryu et al. Detection of Bile Duct Cancer by Autofluorescence Cholangioscopy: a Pilot Study. Hepato Gas-troenterolo iv.1999,46(26):804-807
40 Rava,R.P, Richards-Kortum, R.,Fitzmaurice, M.Cothren, R.Petras, R. Sivak, M., Lecin. H. and Feld. M.S.Early detection of dysplasia in colon and bladder tissue using laser induced fluorescence, in Optical Methods for Tumor Treatment and Early Diagnosis: Mechansims and Techniques,ed,Dougherty,T.J., Proc.SPIE vol. 1991,(1426):68-78
41 Andersson-Engels.S. and Wilson.B.C. In vivo fluorescence in clinical oncology:Fundamental and practical issues. J. Cell Pharmacal. 1992, (3):48-61
42 Benson.R.C, Meyer, R.A, Zaruba. M.E. and McKhann, G.M, Cellular autofluorescence-is ti due to flavins? . J.Histochem.Cytochem, 1979,(27):44-48
43 Nirmala.Ramanujam. Fluorescence Spectroscopy In Vivo. Biomedical Spectroscopy.1999, (1):1-37
44 Haishan Zeng,Alan Weiss,Richard.Real-time endoscopic fluorescence imaging for early cancer detection in the gastrointestinal tract. Bioimaging. 1998, (6):151-165
45 Martin.Loning, Heyke.Diddens, Wolfgang.Kupker. Laparoscopic Fluorescence Detection of Ovarian Carcinoma Metastases Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX,American Cancer Society.2004, 10(102): 1652-1655
46 S. Aandersson-engels, A.Gustafson, J.Johansson, U.Stentam, K.Svanberg and S.Svanberg. Investigation of Possible Fluorophores in Human Atherosclerotic Plaque.Laser In The Life. Science.1992, 5(12):1~11
47 Dirk Zaak, Ronald Sroka, Michael Hoppner, Wael Khoder, Oliver Reicjh, Stefan Tritschler, Rolf Muschter, Ruth Knuchel and Alfons Hofstetter. Photodynamic Therapy by Means of 5-ALA Induced PpIX in Human Prostate Cancer Preliminary Results, Med.Laser Appl. 2003,(18):91~95
48 Claes af Klinteberg, Markus Andreasson, Ola Sandstr?m, Compact medical fluorosensor for minimally invasive tissue characterization. Review of scientific instruments.2005, (76):034303
49 Thomas G. Spiro, J. Michael Burke. Protein control of porphyrin conformation Comparison of resonace raman spectra of heme proteins with mesoporphyrin analogues. Journal of the American Chemical Society. 1976, 98(18): 5482-5489
50 Pedersen.G. D,Mccormick. N. J,Reynolds.L.O. Transport calculations forlight scattering in blood. Biophys.J. 1976, 16: 199-207
51 Reynolds.L. O, Fohnson. C.C, Ishimaru. A Diffuse reflectance from a finite blood medium: applications to the modeling of fiber optice catheters. Appl Opt. 1976, 15: 2059-2067
52杨明媚,蒋治良.兔红细胞的共振散射光谱研究.光谱学与光谱分析.2002. 22(2): 204-208
53杨哗,张镇西,蒋大宗.激光散射技术在血细胞计数及分类中的应用.激光技术.1997. 21(4):231-236
54杨哗,张镇西,蒋大宗.血细胞计数分类的弹性光散射.生物医学工程学杂志. 1997, 14(2):170-175
55 Alexandra Alimova,A.Katz,Vidyasagar Sriamoju,Yuri.Budanshy,Alexei A.Bykov. Hybrid phosphorescence and fluorescence native spectroscopy for breast cancer detection. Journal of Biomedical Optics.2007,12(1):014004
56 E.Kurihara, T.Koseki, K.Gohara, T.Nishihara, T.Ansai, T.Takehara. Detection of Subgingival Calculus and Dentine Caries by Laser Fluorescence. Journal of Periodontal Research. 2004, 39(1):59–65
57 A.Ribeiro, C.Rousseau, J.Girkin, A.Hall, R.Strang, C.J.Whitters, S.Creanor,A.S.Gomes. A Preliminary Investigation of a Spectroscopic Technique for theDiagnosis of Natural Caries Lesions. Journal of Dentistry. 2005, 33(1):73–78
58 W.Buchalla, A.M.Lennon, T.Attin. Fluorescence Spectroscopy of Dental Calculus.Journal of Dental Research. 2004, 39(5):327–332
59 H.H.Liu, P.K.Dasgupta, H.J.Zheng. High Performance Optical Absorbance Detectors Based on Low Noise Switched Integrators. Talanta. 40
60 B.C.Yang, H.Z.Tian, J.Xu, Y.F.Guan. An Integrated Light Emitting Diodeinduced Fluorescence Detector for Capillary Electrophoresis. Talanta. 2006,69:996–1000
61吕诚然,刘斌,谢红,杨国东,于小平.遥感图象处理与信息提取方法的研究.2004,(23):4
62 F.Krause,A.Braun,M.Frentzen.The possibility of detecting subgingival calculus by laser-fluorescence in vitro.Laser Med Sci.2003,(18):32-35
63何东健.图象处理和分析.第一版.西安电子科技出版社,2003:29-33
64何东健.图象处理和分析.第一版.西安电子科技出版社,2003:80-82
65 M.Alrubaiee,M.Xu,S.K.Gayen,and R.R.Alfano.Localization and cross section reconstruction of fluorescent targets in ex vivo breast tissue using independent component analysis.Applied Physics Letters.2006,(89):133902.
66霍宏涛.数字图像处理.第二版.北京理工大学出版社, 2002: 113-115
67霍宏涛,数字图像处理.第二版.北京理工大学出版社, 2002:90-93
68汪安民.DSP应用开发实用子程序.人民邮电出版社.2005:9-10
69李方慧,王飞,何佩琨.TMS320C6000系列DSP原理与应用.第2版.电子工业出版社.2003:4-13
70汪智,严洪,李春生.基于DMA控制的数据Ping-Pong传输.电子器件应用.2005,(4):78-79
2 Alfano.R.R, Tata.D.B, Cordero.J. Laser Induced Fluorescence Spectroscopy from Native Cancero us and Normal Tissue. IEEE Journal of Quantum Electronics. Qe-20,1984, (12):1507-1511
3 Pinheiro.A,Low-Leve.I. Laser Therapy is an Important Tool to Treat Disorders in the Maxillofacial Region. J Clinical Laser Med&Surg. 1998, 1622(4): 3226
4 M.R.Hambin, T.Hasan. Advances in Photodynamic Theory. Optics and Photo- nics News. 1996, 7(7):18–21
5 Sanderson, D.R,Fontana, R.S,Lipson, R.L.and Baldes,E.J. Haematoporphyrin as a diagnostic tool apreliminary report of newt echniques. Cancer. 1972, (30):1368-1372
6 Cotese,D.A,Kinsey,J.H,Woolner,L.B,Payne,W.S.Sanderson. Clinical application of a new endoscopic technique for detection of in situ bronchial carcinoma,Mayo Clin.Proc.1979, (11):516-520
7 Andersson.P.S, Montan,S and Svanberg. S. Multi-spectral system for medical fluorescence imaging,IEEE J.Quant.Electr. 1987, (23):1798-1805
8 R.R.Alfano, G.C.Tang, Asima, Pradan. Laser Spectra from Human Normal and Tumor Lung and Breast Tissues. Optical Science and Engineering Serises.American Institute of Physics.1988, (9):665-670
9杨远龙,叶衍铭,李郁芬等.恶性肿瘤特征自体的来源以及在诊断中的应用.复旦大学学报.1986, 25(1):9096
10 Yakshe.P.N, Bonner.R.F, Patterson.P. Laser-Induced Fluorescence Spectroscopy. Am JGastroentereolo. 1989,( 84):199
11 K.Sbanberg, E.Kjellen, J.Ankerst. Fluorescence Studies of Hematoporphyrin Derivative in Normal and Malignant Rat Tissue.Cancer Research. 1990,(46):3803-3808
12 A.E.Profio, S.S.Xie. Autofluorescence of Tumor and Lung Tissue Versus Excitation Wavelength.China Laser Medince. 1992,(20),18-22
13 Baraga.J. J, Taroni. P, Park.Y.D, An.K.Maestri, Tong.L.L, Rava,.R,P, Kittrell,.C,Dasari,R.R. and Feld.M.S. Ultraviolet laser induced fluorescence of human aorta. Spectrochim.Acta. 1989, (45A): 95-99
14 Chance.B, Cohen.P, Jobsis.F and Schoener.B. Intracellular oxidation reduction states in vivo. Science. 1962, (137): 499-508
15 Chance,B.and Schoener,B. Fluorometric studies of flavin component of respiratory chain, in Flavins and flavoproteins ed.Slater, pp.510-519 (Elservier publishing Comp, New York,USA,1966)
16 Romer T. J, Finamaueice.M, Coshren.R. M, et al. laser-induced fluorescence microscopy of normal colon and dysphasis in colonic adenomas: implications for spectroscopic diagnosis. Am J Gastroemterol. 1995, (90):8187
17 M.A.Biel. Photodynamic Therapy and the Treatment of Head and Neck, Neopl -asia.Laryngoscope. 1998, (108):59–68
18 Poon,W.S, Schomacker.K.T, Deutsch.T.F.and Martuza.R.L. Laser-induced fluorescence: experimental intraperative delineation of tumor resection margins.J.Neurosurg. 1992, (76):679-686
19 D.Hallewin, M.A.Baert and Vanherzeele. H.Fluorescence imaging of bladder cancer. Acta Urol.Belg. 1994, (62):49-52
20 Doiron.D.R, Profio.E, Vincent.R.G. and Dougherty.T.J. Fluorescence bronchoscopy for detection of lung cancer. Chest.1979, (76): 27-32
21朱箐.激光医学.上海科学技术出版社,2003: 45-48
22 K.Svanberg, S.Svanberg. Photodynamic Therapy utilizing Interstitial Light Delivery Combined with Spectroscopic Methods. Department of Physics Lund Institute of Technology.2005,40-42
23 Barbara W. Chwiror, Stanislaw Chwirot. Ultraviolet Laser-induced Fluorescence of Human Stomach Tissue:Detection of Caner Tissue by Imaging Techniques. Lasers in Surgery and Medicine 1997, (21):149-158
24王振亚.自体荧光和肿瘤的光谱诊断研究进展.光电子技术与信息. 1999,12(1):3-8
25 W .illem, M.Star. Light dosimetry in vivo. Phys. Med. Bio. 1997, (42):763-787.
26 Li W, Chen.W.G..Tissue's autofluorescence spectroscopy disgnosis technology. Applied Laser. 1995, 15:(1):46
27陈亚娟,李家泽,余小敏.激光诱导自体荧光成像法(LIFI)诊断肺癌.光学技术. 2004,30(4):2-6
28李步洪,谢树森,林棋榕.激光诱导荧光在肿瘤诊断中的应用.福建师范大学报.1998,14(2) :107-111
29 Haishan Zeng Alan Weiss, Richard Cline. Real-time endoscopic fluorescence imaging for early cancer detection in the gastrointestional tract. Bioimaging. 1998,(6):151-165
30 Haishan.Zeng. A Computerized Autoflourescence and Diffuse Reflectance Spectroanalyser for in vivo Skin Studies .Phys Med Biol.1993,38:231-240
31 Haishan Zeng. Novel Microspectrophotometer and its Biomedical Applications Optical Engineering. 1993: 32(8):1809-1813
32 N. Ramanujam, M. F. Mitchell,A. Mahadevan-Jansen, S. Thomsen.Cervical Precancer Detection Using a Multivariate Statistical Algorithm Based on Laser Induced Fluorescence Spectra at Multi-ple Excitation Wavelengths. Photochem. Photohiol. 1996, 64: 720-735
33 Kevin.T. Ultraviolet laser-induced fluorescence of colonic polys Gastroenter- ology. 1992; 102:1155-1160
34 V. Dinh, Panjehpour M, et al. In vivo cancer diagnosis of.the esophagus using differential normalized fluorescence indices. Lasers Surg Med. 1995;16(1): 41-47
35 I.Georgakoudi,B. C. Jacobson, J. Dam, et al. Fluorescence, Refectance, and Light-Scattering Spectroscopy for Evaluating Dysplasia in Patients With Barretts Esophagus, Gastroenterology .2001,120:1620-1629
36 G. Bottiroli, A. C. Croce, D. Locatelli,R. Nano, E. G iombe 11 i,A. Messina, E. Benericetti. Brain Tissue Autofluorescence:an Aid for Intra-operative Delin-eation of Tumor Resection Margins. Cancer Detect. Prevent. 1998,22(4):330-339
37 F. Koenig, F. J. McGovern, H. Enquist, R. Larne, T. F. Deutsch, K. T.Schomacker, Autofluorescence Guided Biopsy for the Early Diagnosis of Bladder Carcinoma. J. Urol.,1998,159(6):1871-1875
38 M. L. Harries, S. Lam, C. MacAulay, J. A. Qu, B. Palcic. Diagnostic Imaging of the Larynx: Autofluorescence of Laryngeal Tumors Using the Helium Cadmium Laser. J. Laryngol. Otol. 1995, 109:108-110
39 K. Izuishi,H. Tajiri,M. Ryu et al. Detection of Bile Duct Cancer by Autofluorescence Cholangioscopy: a Pilot Study. Hepato Gas-troenterolo iv.1999,46(26):804-807
40 Rava,R.P, Richards-Kortum, R.,Fitzmaurice, M.Cothren, R.Petras, R. Sivak, M., Lecin. H. and Feld. M.S.Early detection of dysplasia in colon and bladder tissue using laser induced fluorescence, in Optical Methods for Tumor Treatment and Early Diagnosis: Mechansims and Techniques,ed,Dougherty,T.J., Proc.SPIE vol. 1991,(1426):68-78
41 Andersson-Engels.S. and Wilson.B.C. In vivo fluorescence in clinical oncology:Fundamental and practical issues. J. Cell Pharmacal. 1992, (3):48-61
42 Benson.R.C, Meyer, R.A, Zaruba. M.E. and McKhann, G.M, Cellular autofluorescence-is ti due to flavins? . J.Histochem.Cytochem, 1979,(27):44-48
43 Nirmala.Ramanujam. Fluorescence Spectroscopy In Vivo. Biomedical Spectroscopy.1999, (1):1-37
44 Haishan Zeng,Alan Weiss,Richard.Real-time endoscopic fluorescence imaging for early cancer detection in the gastrointestinal tract. Bioimaging. 1998, (6):151-165
45 Martin.Loning, Heyke.Diddens, Wolfgang.Kupker. Laparoscopic Fluorescence Detection of Ovarian Carcinoma Metastases Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX,American Cancer Society.2004, 10(102): 1652-1655
46 S. Aandersson-engels, A.Gustafson, J.Johansson, U.Stentam, K.Svanberg and S.Svanberg. Investigation of Possible Fluorophores in Human Atherosclerotic Plaque.Laser In The Life. Science.1992, 5(12):1~11
47 Dirk Zaak, Ronald Sroka, Michael Hoppner, Wael Khoder, Oliver Reicjh, Stefan Tritschler, Rolf Muschter, Ruth Knuchel and Alfons Hofstetter. Photodynamic Therapy by Means of 5-ALA Induced PpIX in Human Prostate Cancer Preliminary Results, Med.Laser Appl. 2003,(18):91~95
48 Claes af Klinteberg, Markus Andreasson, Ola Sandstr?m, Compact medical fluorosensor for minimally invasive tissue characterization. Review of scientific instruments.2005, (76):034303
49 Thomas G. Spiro, J. Michael Burke. Protein control of porphyrin conformation Comparison of resonace raman spectra of heme proteins with mesoporphyrin analogues. Journal of the American Chemical Society. 1976, 98(18): 5482-5489
50 Pedersen.G. D,Mccormick. N. J,Reynolds.L.O. Transport calculations forlight scattering in blood. Biophys.J. 1976, 16: 199-207
51 Reynolds.L. O, Fohnson. C.C, Ishimaru. A Diffuse reflectance from a finite blood medium: applications to the modeling of fiber optice catheters. Appl Opt. 1976, 15: 2059-2067
52杨明媚,蒋治良.兔红细胞的共振散射光谱研究.光谱学与光谱分析.2002. 22(2): 204-208
53杨哗,张镇西,蒋大宗.激光散射技术在血细胞计数及分类中的应用.激光技术.1997. 21(4):231-236
54杨哗,张镇西,蒋大宗.血细胞计数分类的弹性光散射.生物医学工程学杂志. 1997, 14(2):170-175
55 Alexandra Alimova,A.Katz,Vidyasagar Sriamoju,Yuri.Budanshy,Alexei A.Bykov. Hybrid phosphorescence and fluorescence native spectroscopy for breast cancer detection. Journal of Biomedical Optics.2007,12(1):014004
56 E.Kurihara, T.Koseki, K.Gohara, T.Nishihara, T.Ansai, T.Takehara. Detection of Subgingival Calculus and Dentine Caries by Laser Fluorescence. Journal of Periodontal Research. 2004, 39(1):59–65
57 A.Ribeiro, C.Rousseau, J.Girkin, A.Hall, R.Strang, C.J.Whitters, S.Creanor,A.S.Gomes. A Preliminary Investigation of a Spectroscopic Technique for theDiagnosis of Natural Caries Lesions. Journal of Dentistry. 2005, 33(1):73–78
58 W.Buchalla, A.M.Lennon, T.Attin. Fluorescence Spectroscopy of Dental Calculus.Journal of Dental Research. 2004, 39(5):327–332
59 H.H.Liu, P.K.Dasgupta, H.J.Zheng. High Performance Optical Absorbance Detectors Based on Low Noise Switched Integrators. Talanta. 40
60 B.C.Yang, H.Z.Tian, J.Xu, Y.F.Guan. An Integrated Light Emitting Diodeinduced Fluorescence Detector for Capillary Electrophoresis. Talanta. 2006,69:996–1000
61吕诚然,刘斌,谢红,杨国东,于小平.遥感图象处理与信息提取方法的研究.2004,(23):4
62 F.Krause,A.Braun,M.Frentzen.The possibility of detecting subgingival calculus by laser-fluorescence in vitro.Laser Med Sci.2003,(18):32-35
63何东健.图象处理和分析.第一版.西安电子科技出版社,2003:29-33
64何东健.图象处理和分析.第一版.西安电子科技出版社,2003:80-82
65 M.Alrubaiee,M.Xu,S.K.Gayen,and R.R.Alfano.Localization and cross section reconstruction of fluorescent targets in ex vivo breast tissue using independent component analysis.Applied Physics Letters.2006,(89):133902.
66霍宏涛.数字图像处理.第二版.北京理工大学出版社, 2002: 113-115
67霍宏涛,数字图像处理.第二版.北京理工大学出版社, 2002:90-93
68汪安民.DSP应用开发实用子程序.人民邮电出版社.2005:9-10
69李方慧,王飞,何佩琨.TMS320C6000系列DSP原理与应用.第2版.电子工业出版社.2003:4-13
70汪智,严洪,李春生.基于DMA控制的数据Ping-Pong传输.电子器件应用.2005,(4):78-79