高血压引起组织重构的病理图像分析研究
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摘要
高血压是一种常见的心血管疾病,在高血压的病理研究中,由于高血压导致的靶器官组织和细胞结构的改变一直是人们关注的热点。对高血压病理图像进行研究,通过数字图像的处理与分析技术获取靶器官病变程度,对于高血压疾病的发生与发展,高血压药物扭转靶器官组织细胞结构改变的能力,有着非常重要的意义。
高血压损伤的靶器官以心、脑、肾为主。在这三个器官中损害的主要表现血管重构、心肌细胞肥大与组织胶原增多而导致的纤维化。衡量不同类型的病变程度,所用到的图像与处理方法并不相同。研究合适的图像分析算法,针对不同高血压病理图像建立更科学与全面的病理成像与分析方法,是本研究的目的。完成的主要工作有:对高血压引发的血管重构形态学特征的图像分析方法进行了研究; 对检测心肌胶原的正交偏光成像中消光现象在图像分析中的影响进行修正; 对心肌细胞肥大程度的图像检测方法进行了研究; 利用在上述研究中建立的分析方法和一些经典图像分析方法对心房肽在高血压心、肾组织病变中的作用从形态学的角度给予评价。
在血管重构的图像分析中,重点是分割出血管腔与血管壁。由于HE染色血管图像的特殊性,基于传统图像分割方法的色彩特征聚类和区域增长等方法均不能获得一个较为完善的分割结果。这里采用对经典的活动轮廓算法进行改进,然后用于对彩色HE染色血管图像的分割。改进后的方法组要是利用彩色图像中的HIS三种梯度值中最大者来取代原活动轮廓
Hypertension is a kind of common disease of cardiovascular system. In the research field of pathology about hypertension, the structure changing of tissues and cells in target organ always get much attention and is also the base of hypertension. With the development of technology in computer and digital image processing, the computer analysis of pathology image of hypertension become useful in research of pathogenesis and medicine of hypertension. But the usual image analysis soft is limited and inconvenienced in special image analysis.
The main target organs damaged by hypertension are heart, brain and kidney. In these three organs the damage lead to vascular remodel, hypertrophy of cardiac muscle cells, collagens hyperplasia and fiberosis of tissues. To evaluate the pathological changing degree of different organs and tissues, it need different image analysis methods, including different image segment algorithm, measurement index, even different imaging method. So the object of this article is that find suitable image analysis methods for main pathological changes of hypertension. The following works were finished: The image segment and measurement methods of vascular remodeling in hypertension; The modification of analysis methods of collagens hyperplasia in cardiac muscle; The
measurement and evaluation methods of hypertrophy of cardiac myofibers. The key in image analysis of vascular remodeling is the segment of vascular cavitys and walls. Here traditional image segment methods including color thresholds and region growing methods were tried to segment vascular but the result were not satisfactory due to the complexity of HE stained image of vascular. The active contour model was also adopted to segment vascular. To apply this method in color image, the definition gradient energy and image energy were adjusted. The segment of vascular wall was difficult. In some condition because the vascular tissue connect with the outside chorion, there is no clear boundary. The segment method based on dilation of mathematics was designed to over come it. Although people have bring forward many image segment methods, but segment by hand is needed in many time. After segment of vascular, some index including the area of vascular cavity, the area of vascular wall, the radius of cavity, the radius of wall, and thickness et al, were measured. An important symptom of remodeling of cardiac muscle is collagens hyperplasia. A technique based on picro-siriusred polarization and image analysis was investigated for evolution of collagens remodeling in myocardium of hypertension. The conventional picro-siriusred polarization method is easy to be affected by extinction phenomena, which will decrease the precision of measurement. A correction that adopt the means of 2 image gotten by spacing 45owere brought forward here, corresponding theory explain was also given. The correction will offer more exact data of collagens and collagens types. Another important symptom of remodeling of cardiac muscle is hypertrophy of cardiac muscle cells, is also the size of cardiac myofibrils become larger than normal. There always is a hard work to measure the size of
so many cardiac myofibrils in cardiac muscle images. A method designed by analysis of gray data of cardiac myofibrils image. To decrease effect of image noise, some filters are adopted. The result shown this method can be used to evaluate the degree of hypertrophy of cardiac muscle cells. Atrial natriuretic peptide(ANP) has diuretic, natriuretic, vasodilatory, and aldosterone-inhibitory effects, and can reduce arterial blood pressure. But ANP is a poor drug due to the susceptibility of ANP to enzymatic attack in the gut and the circulation with a resulting short half time. A technique based on release of the human atrial natriuretic peptide (hANP) from plasmid hANP cDNA transfected Chinese hamster ovary (CHO) cells encapsulated in polycaprolactone (PCL)-capsules was investigated for a potential therapeutic approach to hypertension. The morphological changes,histological changes were investigated post-implantation of PCL-capsules in 2K1C hypertensive rats by these image analysis methods developed in this article. This result demonstrated that the usefulness of encapsulated hANP gene transfected cells as a new tool for hANP gene delivery in studying renovascular hypertension and it is also good for improve pathology damage caused by hypertension.
高血压损伤的靶器官以心、脑、肾为主。在这三个器官中损害的主要表现血管重构、心肌细胞肥大与组织胶原增多而导致的纤维化。衡量不同类型的病变程度,所用到的图像与处理方法并不相同。研究合适的图像分析算法,针对不同高血压病理图像建立更科学与全面的病理成像与分析方法,是本研究的目的。完成的主要工作有:对高血压引发的血管重构形态学特征的图像分析方法进行了研究; 对检测心肌胶原的正交偏光成像中消光现象在图像分析中的影响进行修正; 对心肌细胞肥大程度的图像检测方法进行了研究; 利用在上述研究中建立的分析方法和一些经典图像分析方法对心房肽在高血压心、肾组织病变中的作用从形态学的角度给予评价。
在血管重构的图像分析中,重点是分割出血管腔与血管壁。由于HE染色血管图像的特殊性,基于传统图像分割方法的色彩特征聚类和区域增长等方法均不能获得一个较为完善的分割结果。这里采用对经典的活动轮廓算法进行改进,然后用于对彩色HE染色血管图像的分割。改进后的方法组要是利用彩色图像中的HIS三种梯度值中最大者来取代原活动轮廓
Hypertension is a kind of common disease of cardiovascular system. In the research field of pathology about hypertension, the structure changing of tissues and cells in target organ always get much attention and is also the base of hypertension. With the development of technology in computer and digital image processing, the computer analysis of pathology image of hypertension become useful in research of pathogenesis and medicine of hypertension. But the usual image analysis soft is limited and inconvenienced in special image analysis.
The main target organs damaged by hypertension are heart, brain and kidney. In these three organs the damage lead to vascular remodel, hypertrophy of cardiac muscle cells, collagens hyperplasia and fiberosis of tissues. To evaluate the pathological changing degree of different organs and tissues, it need different image analysis methods, including different image segment algorithm, measurement index, even different imaging method. So the object of this article is that find suitable image analysis methods for main pathological changes of hypertension. The following works were finished: The image segment and measurement methods of vascular remodeling in hypertension; The modification of analysis methods of collagens hyperplasia in cardiac muscle; The
measurement and evaluation methods of hypertrophy of cardiac myofibers. The key in image analysis of vascular remodeling is the segment of vascular cavitys and walls. Here traditional image segment methods including color thresholds and region growing methods were tried to segment vascular but the result were not satisfactory due to the complexity of HE stained image of vascular. The active contour model was also adopted to segment vascular. To apply this method in color image, the definition gradient energy and image energy were adjusted. The segment of vascular wall was difficult. In some condition because the vascular tissue connect with the outside chorion, there is no clear boundary. The segment method based on dilation of mathematics was designed to over come it. Although people have bring forward many image segment methods, but segment by hand is needed in many time. After segment of vascular, some index including the area of vascular cavity, the area of vascular wall, the radius of cavity, the radius of wall, and thickness et al, were measured. An important symptom of remodeling of cardiac muscle is collagens hyperplasia. A technique based on picro-siriusred polarization and image analysis was investigated for evolution of collagens remodeling in myocardium of hypertension. The conventional picro-siriusred polarization method is easy to be affected by extinction phenomena, which will decrease the precision of measurement. A correction that adopt the means of 2 image gotten by spacing 45owere brought forward here, corresponding theory explain was also given. The correction will offer more exact data of collagens and collagens types. Another important symptom of remodeling of cardiac muscle is hypertrophy of cardiac muscle cells, is also the size of cardiac myofibrils become larger than normal. There always is a hard work to measure the size of
so many cardiac myofibrils in cardiac muscle images. A method designed by analysis of gray data of cardiac myofibrils image. To decrease effect of image noise, some filters are adopted. The result shown this method can be used to evaluate the degree of hypertrophy of cardiac muscle cells. Atrial natriuretic peptide(ANP) has diuretic, natriuretic, vasodilatory, and aldosterone-inhibitory effects, and can reduce arterial blood pressure. But ANP is a poor drug due to the susceptibility of ANP to enzymatic attack in the gut and the circulation with a resulting short half time. A technique based on release of the human atrial natriuretic peptide (hANP) from plasmid hANP cDNA transfected Chinese hamster ovary (CHO) cells encapsulated in polycaprolactone (PCL)-capsules was investigated for a potential therapeutic approach to hypertension. The morphological changes,histological changes were investigated post-implantation of PCL-capsules in 2K1C hypertensive rats by these image analysis methods developed in this article. This result demonstrated that the usefulness of encapsulated hANP gene transfected cells as a new tool for hANP gene delivery in studying renovascular hypertension and it is also good for improve pathology damage caused by hypertension.
引文
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1. Hideyuki Murakami, Katsutoshi Yayama, Ju Lie Chao, et al. Atrial natriuretic peptide gene delivery attenuates gentamycin-induced nephrotoxicity in rats. Nephrol Dial Transplant,1999,14: 1376
2. Lin KF, Chao J, Chao L. Kallikrein gene delivery attenuates hypertension and cardiac hypertrophy and enhances renal function in Goldblatt hypertensive rats. Hypertension. 1998; 31: 1104
3. Lin KF, Chao J, Chao L. Atrial natriuretic peptide gene delivery attenuates hypertension cardiac hypertropy and renal injury in salt sensive rats. Hum Gene Ther. 1998; 9: 1429
4. Ferber D. Gene therapy: Safer and virus-free? Science, 2001,294: 1638-1639
5. Chen LG, Wang ZR, Wan CM, et al. Circadian renal rhythms influenced by implanted encapsulated hANP-producing cells in Goldblatt hypertensive rats. Gene Therapy.2004; 11:1515-1522
6. Chen LG, Wang ZR, Wan CM, et al. Encapsulated transgene cells attenuate hypertansion, cardiac hypertrophyand enhance renal function in Goldblatt hypertensive rats. J Gene Med 2004; 6: 786
7. Kuei-Fu Lin, Julie Chao, Lee Chao. Human atrial natriuretic peptide gene delivery reduces blood pressure in hypertensive rats. Hypertension, 1995, 26: 847-853.
8. M.Cantin, J.Gutkowska, G.Thibault, et al. Immunocytochemical localization of atrial natriuretic facter in the heart and salivary glands. Histochemistry, 1984, 80: 113-127.
9. 陈立国 屈艺 微囊化的 ANP cDNA 转染细胞降低高血压大鼠血压,航天医学与医学工程,2003 16(1):77-78
10. Sharifi AM, Akbarloo N, Heshmatian B et al. Alterration of local ACE vascular responsivemess during development of 2K1C renovascular hypertension[J]. Pharmacol Res,2003,47(3):201-207
11. Hideyuki Murakami, Katsutoshi Yayama, Ju Lie Chao, et al. Atrial natriuretic peptide gene delivery attenuates gentamycin-induced nephrotoxicity in rats. Nephrol Dial Transplant,1999,14: 1376
12. Lin KF, Chao J, Chao L. Kallikrein gene delivery attenuates hypertension and cardiac hypertrophy and enhances renal function in Goldblatt hypertensive rats. Hypertension. 1998; 31: 1104