中药对动物实验性乳腺增生病抑制作用的病理学计算机辅助定量分析的研究
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摘要
本文介绍了我们建立的一套即适用于临床病理科又能用于科研病理分析的病理图像计算机辅助分析系统。该系统集医用显微镜、视频图像采集卡、计算机系统于一体，实现了从病理图像记录、采集、预处理到特征参数测量、结果分析、报告生成、打印等一系列功能。
系统针对显微病理图像的特点，结合临床应用和医学科研工作的需求，重点建立了一系列适合医学应用的彩色图像处理方法和特征参数测量方法。这些方法包括图像的移动、缩放、亮度／对比度调整、图像编辑以及感兴趣区域长度、面积、数量等特征参数的测量分析功能。
我们根据乳腺增生病的医学机制，利用苯甲酸雌二醇腹腔注射建立了乳腺增生病小鼠动物模型，并以生理盐水为对照、以医院名老中医的处方(高、中、低剂量)、乳癖消为阳性药物，测量了各实验组乳腺小叶数、乳腺腺泡数、腺泡腔直径和面积，定量的表征与分析了中药治疗乳腺增生病的效果。可以肯定，这些特征参数的提取和分析将为后续的中药复方疗效分析打下良好的基础
We developed the pathologic image compute-aided analysis system which was the same with the clinical pathologic department and pathologic analysis of scientific research. The system Is composed of an medical microscopy, a video image sampling card, a computer system and software what we developed specially for this system. Further more, it provides many powerful functions including pathologic image recording, image sampling, image processing, parameter measurement, result analysis, report creating, report printing and so on.
According to the characters of microscopic pathologic image and requirement of clinic and medical scientific research, we implemented various kinds of ootor image processing and parameter measuring approaches, including image movement and adjustment, brightness/contrast adjustment, image edit and length, acreage, amount measurement of RO1.
Depending on the medical theory of hyperplasia of breast, we found the chmice model of hyperplasia of breast using of Estradtol Benzoate. control of saline water, recipe of famous herbalist doctoKhigh, middle, low dosage) . Ruplxiao Plan are investigated. The amount of mammary lobule and acinus, diameter and acreage of acinus are measured. The results show the system valuable to evaluate the efficacy of Chinese medicine and serve as the basis to explore the effects of Chinese medicine.
系统针对显微病理图像的特点，结合临床应用和医学科研工作的需求，重点建立了一系列适合医学应用的彩色图像处理方法和特征参数测量方法。这些方法包括图像的移动、缩放、亮度／对比度调整、图像编辑以及感兴趣区域长度、面积、数量等特征参数的测量分析功能。
我们根据乳腺增生病的医学机制，利用苯甲酸雌二醇腹腔注射建立了乳腺增生病小鼠动物模型，并以生理盐水为对照、以医院名老中医的处方(高、中、低剂量)、乳癖消为阳性药物，测量了各实验组乳腺小叶数、乳腺腺泡数、腺泡腔直径和面积，定量的表征与分析了中药治疗乳腺增生病的效果。可以肯定，这些特征参数的提取和分析将为后续的中药复方疗效分析打下良好的基础
We developed the pathologic image compute-aided analysis system which was the same with the clinical pathologic department and pathologic analysis of scientific research. The system Is composed of an medical microscopy, a video image sampling card, a computer system and software what we developed specially for this system. Further more, it provides many powerful functions including pathologic image recording, image sampling, image processing, parameter measurement, result analysis, report creating, report printing and so on.
According to the characters of microscopic pathologic image and requirement of clinic and medical scientific research, we implemented various kinds of ootor image processing and parameter measuring approaches, including image movement and adjustment, brightness/contrast adjustment, image edit and length, acreage, amount measurement of RO1.
Depending on the medical theory of hyperplasia of breast, we found the chmice model of hyperplasia of breast using of Estradtol Benzoate. control of saline water, recipe of famous herbalist doctoKhigh, middle, low dosage) . Ruplxiao Plan are investigated. The amount of mammary lobule and acinus, diameter and acreage of acinus are measured. The results show the system valuable to evaluate the efficacy of Chinese medicine and serve as the basis to explore the effects of Chinese medicine.
引文
1．钱礼，《外科病症的诊断思路与处理程序》，浙江科学技术出版社，1994．12
2．曹月敏，王国佩主编，《乳腺外科学》，河北科学技术出版社，1991．12
3．陈忠年，沈铭昌，《实用外科病理学》，上海医科大学出版社，1997．7
4．余英林，《数字图像处理与模式识别》，华南理工大学出版社，1990．10
蒋越峰，《乳腺X线图像计算机辅助诊断算法研究》，浙江大学生物医学工程专业硕士学位论文，2001．6
5．应剑锋，《乳腺X线钼靶图像计算机管理和辅助分析系统》，浙江大学生物医学工程专业硕士学位论文，2000．6
6．施新猷，《现代实验动物学》，人民军医出版社，2000．9
7．刘振安，苏仕花，《C语言图形设计》，1995．4
8．林增源等，“112例乳腺增生病的病例分型及治疗”，《实用外科杂志》，第11期，1986
9．邹强，“乳腺纤维性囊肿病的治疗”，《国外医学(外科学分册)》，第2期，1991
10．鲍依稀，“医用显微图像处理的研究现状及展望”，《国外医学临床生物化学与检验学分册》，第20卷，第4期，1999
11．侯文声等，“一种基于CA6300卡的病理切片图像处理系统”，《微机发展》，第5期，1998
12．阚秀等，“计算机病理图像分析技术的应用”，《诊断病理学杂志》，第5卷，第3期，1998
13．沈健等，“计算机显微数码摄像及其应用”，《汕头大学医学院学报》，第10卷，增刊，1997
14．张桂珍，“计算机图像处理系统在病理学教学及临床诊断中的应用”，《白求恩医科大学学报》，第26卷，第2期，2000
15．唐新，“乳腺增生病病理分类与中医证型相关性研究”，《上海市天山中医医院》，第4期，1999
16．王雅如等，“克乳痛治疗实验性乳腺增生病的病理观察”，《南京中医药大学学报(自然科学版)》，第16卷，第2期，2000
17．康丕顺等，“乳宁合剂治疗乳腺增生病的药效观察”，《中国新药杂志》，，第8卷，第11期，1999
18．张茂慧等，“乳痛糖浆抑制小白鼠乳腺小增生病理组织学观察研究”，《新疆医学》，第31卷，第1期，2001
19．刘官成等，“卵巢健全小鼠乳腺小叶增生模型建立及Tamoxifen疗效”，《海军医专学报》，第21卷，第1期，1999
20．高瞻，“乳腺小叶增生症从肝肾论治浅识”，《中医药研究》，第16卷，第2期，2000
21．匡志鹏等，“块结消胶囊治疗乳腺增生病的实验和临床应用研究”，《广西中医学院学报》，第18卷，第1期，2001
22．修贺明等，“针刺对小白鼠实验性乳腺增生症抑制作用的病理形态定量研究”，《中国针灸》，第9期，1997
23. 《INSTRCTIONS OF JVC COLOUR VIDEO CAMERA TK-C1380》, VICTOR COMPANY OF JAPAN, 1996
24. 《INSTRCTIONS OF OLYMPUS SYSTEM MICROSCOPE BX40》, OLYMPUS OPTICAL CO.,LTD, 1997
25． Davis JE. Major Ambulatory surgery of the general surgical patient: management of breast disease and hermias of the abdominal wall. Surg Clin North Amer 1987; 64(4) :733
26． Ottesen GL,Christense IJ,Larsen JK,etal,DNA plodrty analysis in breast carcinoma[j],Anal Quant Cytol Histol,Vol.19,1997
27． Bacus JW,Bacus JV,A method of correcting DNA plodity messurements in tissue sectiom[J],Med Pathol,Vol.7,1994
28． Yaegashi H,Takahashi T,The she,seveity,and the distribution of bronchiolar obstruction in lungs with chronic obstructive pulmonarg disease. Arch pathol Lab Med,Vol.118
29． Hance GA,Umbaugh SE,Moss RH,et al. Unsupervised color image segmentation[J],IEEE Engineering In Medicine And Biology,??1(2) ,1996
30． Thiran JP,Macq B,Mological feature extract for the classification of digital images of cancerous tissues,IEEE Trans On Biomedical Engineering,??43(10) ,1996
31． Xu J. Image analysis and its applications[M],Singapore,World Scientifics,1992
32． Du C. Very delayed infraction after mild focal cerebral ischemia,a roal for apotosis? [J],J Cereb Blood Flow Metab,Vol.16,1996
33． Sieracki ME,Reichenbach SE,Webb KL,Evaluation of Automated Threshold Selection Methods for Accurately Sizing Microscope Fluorescent Cells by Image Analysis[J],Applied and Environmental Microbiology,?55 (11) ,1989
34． Urata H,Nishimura H,Granren D,Angiotensin I coverting enzymeindepent pathways of angiorensin I formation in human tissue and cardiovascular disease[J],Vol. 5,1996
35． Henderson BE,Ross R,Benstein L,Estrogens as a Cause of Human Cancer: The Richard and Hinds Rosenthal,foundation award lecture[J],Vol. 48,1998
36． Yebo Wang,et,An Image Segmentation Algorithm for Color Image,Proceedings of IEEE-EMBS Asia-Pacific Conference on Biomedical Engineering,2000
37． TAN Eng Chong,et,Area Calculation of Medical Image on Screen,Proceedings of IEEE-EMBS Asia-Pacific Conference on Biomedical Engineering,2000
38． TX Gao,et,Detection of Breast Cancer Using Near Infrared light-Experiments and Initial Clinical Results,Proceedings of IEEE-EMBS Asia-Pacific Conference on Biomedical Engineering,2000
39． Ruiz A,Almenar S,Callaghan RC,Llombart-Bosch A,Benign,preinvasive and invasive ductal breast lesions. A comparative study with quantitative techniques: morphometry,image-and flow cytometry,Pathol Res Pract,195(11) ,1999
40． Anderson NH,Hamilton PW,Bartels PH,Thompson D,Montironi R,Sloan JM,Computerized scene segmentation for the discrimination of architectural features in ductal proliferative lesions of the breast,J Pathol,181(4) ,1997
41． Fhzgibbons PL,Atypical lobular hyperplasia of the breast: a study of pathologists' responses in the College of American Pathologists Performance Improvement Program in Surgical Pathology,Arch Pathol Lab Med,124(3) ,2000
42． Wray BE,Lai-Goldman M,The design and use of a computer-based digital image acquisition,management,and communications system for conferencing in pathology,Arch Anat Cytol Pathol,43(4) ,1995
43． Tekmal RR,Kirma N,Gill K,Fonder K,Aromatase overexpression and breast hyperplasia,an in vivo model-continued overexpression of aromatase is sufficient to maintain hyperplasia without circulating estrogens,and aromatase inhibitors abrogate these preneoplastic changes in mammary glands,Endocr Relat Cancer,6(2) ,1999
44． De Boer,WI Hiemstra,et,Image analysis and quantification in lung tissue,Clinical & Experimental Allergy,Vol.31 Issue 3,2001
45． Zalevsky,Zeev; Mendlovic,David; Mendlovic,Sonia,Hybrid electrical/optical low-cost advanced image processing system for pathology diagnostic,Proceedings of SPIE-The International Society for Optical Engineering,3603O,1999,
46． Datta,Anritava; Rodenacker,Karsten,Knowledge acquisition tool in analytical pathology based on multi-media relationed database,Computer Methods and Programs in Biomedicine,44(2) ,1994,
47． Zinzindohoue P,Use of texture concept and parametric imaging concept for biomedical image segmentation,Optik (Stuttgart),103(1) ,1996,
48． Wetzel,Arthur W,Computational aspects of pathology image classification and retrieval,Journal of Supercomputing,11(3) ,1997．
49． Gan X,Schilders SP,Image enhancement through turbid media under a microscope by use of polarization gating methods,Journal of the Optical Society of America A(Opticsand image science),16(9) ,1999,
50． Li,Zhiyang; Li,Xianfang; Liu,Wu,Restoration of collection mode scanning near-field optical microscope image,Proceedings of SPIE-The International Society for Optical Engineering,36070,1999,
2．曹月敏，王国佩主编，《乳腺外科学》，河北科学技术出版社，1991．12
3．陈忠年，沈铭昌，《实用外科病理学》，上海医科大学出版社，1997．7
4．余英林，《数字图像处理与模式识别》，华南理工大学出版社，1990．10
蒋越峰，《乳腺X线图像计算机辅助诊断算法研究》，浙江大学生物医学工程专业硕士学位论文，2001．6
5．应剑锋，《乳腺X线钼靶图像计算机管理和辅助分析系统》，浙江大学生物医学工程专业硕士学位论文，2000．6
6．施新猷，《现代实验动物学》，人民军医出版社，2000．9
7．刘振安，苏仕花，《C语言图形设计》，1995．4
8．林增源等，“112例乳腺增生病的病例分型及治疗”，《实用外科杂志》，第11期，1986
9．邹强，“乳腺纤维性囊肿病的治疗”，《国外医学(外科学分册)》，第2期，1991
10．鲍依稀，“医用显微图像处理的研究现状及展望”，《国外医学临床生物化学与检验学分册》，第20卷，第4期，1999
11．侯文声等，“一种基于CA6300卡的病理切片图像处理系统”，《微机发展》，第5期，1998
12．阚秀等，“计算机病理图像分析技术的应用”，《诊断病理学杂志》，第5卷，第3期，1998
13．沈健等，“计算机显微数码摄像及其应用”，《汕头大学医学院学报》，第10卷，增刊，1997
14．张桂珍，“计算机图像处理系统在病理学教学及临床诊断中的应用”，《白求恩医科大学学报》，第26卷，第2期，2000
15．唐新，“乳腺增生病病理分类与中医证型相关性研究”，《上海市天山中医医院》，第4期，1999
16．王雅如等，“克乳痛治疗实验性乳腺增生病的病理观察”，《南京中医药大学学报(自然科学版)》，第16卷，第2期，2000
17．康丕顺等，“乳宁合剂治疗乳腺增生病的药效观察”，《中国新药杂志》，，第8卷，第11期，1999
18．张茂慧等，“乳痛糖浆抑制小白鼠乳腺小增生病理组织学观察研究”，《新疆医学》，第31卷，第1期，2001
19．刘官成等，“卵巢健全小鼠乳腺小叶增生模型建立及Tamoxifen疗效”，《海军医专学报》，第21卷，第1期，1999
20．高瞻，“乳腺小叶增生症从肝肾论治浅识”，《中医药研究》，第16卷，第2期，2000
21．匡志鹏等，“块结消胶囊治疗乳腺增生病的实验和临床应用研究”，《广西中医学院学报》，第18卷，第1期，2001
22．修贺明等，“针刺对小白鼠实验性乳腺增生症抑制作用的病理形态定量研究”，《中国针灸》，第9期，1997
23. 《INSTRCTIONS OF JVC COLOUR VIDEO CAMERA TK-C1380》, VICTOR COMPANY OF JAPAN, 1996
24. 《INSTRCTIONS OF OLYMPUS SYSTEM MICROSCOPE BX40》, OLYMPUS OPTICAL CO.,LTD, 1997
25． Davis JE. Major Ambulatory surgery of the general surgical patient: management of breast disease and hermias of the abdominal wall. Surg Clin North Amer 1987; 64(4) :733
26． Ottesen GL,Christense IJ,Larsen JK,etal,DNA plodrty analysis in breast carcinoma[j],Anal Quant Cytol Histol,Vol.19,1997
27． Bacus JW,Bacus JV,A method of correcting DNA plodity messurements in tissue sectiom[J],Med Pathol,Vol.7,1994
28． Yaegashi H,Takahashi T,The she,seveity,and the distribution of bronchiolar obstruction in lungs with chronic obstructive pulmonarg disease. Arch pathol Lab Med,Vol.118
29． Hance GA,Umbaugh SE,Moss RH,et al. Unsupervised color image segmentation[J],IEEE Engineering In Medicine And Biology,??1(2) ,1996
30． Thiran JP,Macq B,Mological feature extract for the classification of digital images of cancerous tissues,IEEE Trans On Biomedical Engineering,??43(10) ,1996
31． Xu J. Image analysis and its applications[M],Singapore,World Scientifics,1992
32． Du C. Very delayed infraction after mild focal cerebral ischemia,a roal for apotosis? [J],J Cereb Blood Flow Metab,Vol.16,1996
33． Sieracki ME,Reichenbach SE,Webb KL,Evaluation of Automated Threshold Selection Methods for Accurately Sizing Microscope Fluorescent Cells by Image Analysis[J],Applied and Environmental Microbiology,?55 (11) ,1989
34． Urata H,Nishimura H,Granren D,Angiotensin I coverting enzymeindepent pathways of angiorensin I formation in human tissue and cardiovascular disease[J],Vol. 5,1996
35． Henderson BE,Ross R,Benstein L,Estrogens as a Cause of Human Cancer: The Richard and Hinds Rosenthal,foundation award lecture[J],Vol. 48,1998
36． Yebo Wang,et,An Image Segmentation Algorithm for Color Image,Proceedings of IEEE-EMBS Asia-Pacific Conference on Biomedical Engineering,2000
37． TAN Eng Chong,et,Area Calculation of Medical Image on Screen,Proceedings of IEEE-EMBS Asia-Pacific Conference on Biomedical Engineering,2000
38． TX Gao,et,Detection of Breast Cancer Using Near Infrared light-Experiments and Initial Clinical Results,Proceedings of IEEE-EMBS Asia-Pacific Conference on Biomedical Engineering,2000
39． Ruiz A,Almenar S,Callaghan RC,Llombart-Bosch A,Benign,preinvasive and invasive ductal breast lesions. A comparative study with quantitative techniques: morphometry,image-and flow cytometry,Pathol Res Pract,195(11) ,1999
40． Anderson NH,Hamilton PW,Bartels PH,Thompson D,Montironi R,Sloan JM,Computerized scene segmentation for the discrimination of architectural features in ductal proliferative lesions of the breast,J Pathol,181(4) ,1997
41． Fhzgibbons PL,Atypical lobular hyperplasia of the breast: a study of pathologists' responses in the College of American Pathologists Performance Improvement Program in Surgical Pathology,Arch Pathol Lab Med,124(3) ,2000
42． Wray BE,Lai-Goldman M,The design and use of a computer-based digital image acquisition,management,and communications system for conferencing in pathology,Arch Anat Cytol Pathol,43(4) ,1995
43． Tekmal RR,Kirma N,Gill K,Fonder K,Aromatase overexpression and breast hyperplasia,an in vivo model-continued overexpression of aromatase is sufficient to maintain hyperplasia without circulating estrogens,and aromatase inhibitors abrogate these preneoplastic changes in mammary glands,Endocr Relat Cancer,6(2) ,1999
44． De Boer,WI Hiemstra,et,Image analysis and quantification in lung tissue,Clinical & Experimental Allergy,Vol.31 Issue 3,2001
45． Zalevsky,Zeev; Mendlovic,David; Mendlovic,Sonia,Hybrid electrical/optical low-cost advanced image processing system for pathology diagnostic,Proceedings of SPIE-The International Society for Optical Engineering,3603O,1999,
46． Datta,Anritava; Rodenacker,Karsten,Knowledge acquisition tool in analytical pathology based on multi-media relationed database,Computer Methods and Programs in Biomedicine,44(2) ,1994,
47． Zinzindohoue P,Use of texture concept and parametric imaging concept for biomedical image segmentation,Optik (Stuttgart),103(1) ,1996,
48． Wetzel,Arthur W,Computational aspects of pathology image classification and retrieval,Journal of Supercomputing,11(3) ,1997．
49． Gan X,Schilders SP,Image enhancement through turbid media under a microscope by use of polarization gating methods,Journal of the Optical Society of America A(Opticsand image science),16(9) ,1999,
50． Li,Zhiyang; Li,Xianfang; Liu,Wu,Restoration of collection mode scanning near-field optical microscope image,Proceedings of SPIE-The International Society for Optical Engineering,36070,1999,