颈部淋巴结病变CT灌注成像表现与血管生成状态的相关性研究
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摘要
目的
通过分析颈部不同性质淋巴结病变的CT灌注参数及TDC曲线,探讨CT灌注成像在颈部淋巴结病变定性诊断中的价值。
研究颈部不同性质淋巴结病变各项CT灌注参数与微血管密度(micro-vessel density, MVD)及血管内皮生长因子(vascular endothelial growth factor, VEGF)间的关系,评价血管生成在颈部淋巴结病变CT灌注成像中的作用。
材料及方法
收集经CT灌注、病理证实的良、恶性颈部淋巴结病变患者69例,利用DynEva软件得出感兴趣区的时间密度曲线(time density curve, TDC),根据TDC得出淋巴结的达峰时间(time to peak, TTP)和相对强化值(relative enhancement value, REV=淋巴结增强峰值-淋巴结CT平扫值)；将灌注扫描后所得图像调入Syngo Body PCT(Siemens, Germany)软件,得到灌注参数：血流量(blood flow, BF)、血容量(blood volume, BV).通透性(permeability, per)。根据病理结果将69例病变淋巴结分为良(炎性淋巴结、结核性淋巴结)、恶性(淋巴瘤、甲状腺癌转移淋巴结、其它癌转移淋巴结)两组,统计不同病变淋巴结的各灌注参数值,其中两样本应用t检验,多样本应用方差分析对良性组与恶性组的各灌注参数及TDC参数进行比较。
在病理科找出CT灌注淋巴结病变的组织蜡块及HE染色玻片,观察肿瘤病理学特征,免疫组化检测淋巴结病变组织CD34、VEGF,并以CD34单克隆抗体标记微血管,按照Weidner等的评估标准,计算淋巴结病变内着色的毛细血管和微小血.管。应用统计学方法分析淋巴结病变的CT灌注成像参数与MVD和VEGF表达的相关性。
结果
1.颈部淋巴结病变TDC曲线形态对比中,良性淋巴结病变中炎性淋巴结TDC曲线以缓升型(50.0%)及低平型(37.5%)为主；结核性淋巴结TDC曲线也以缓升型(40.0%)及低平型(40.0%)为主。恶性淋巴结病变中,甲状腺癌转移淋巴结TDC以速升速降型为主(70.6%)；其他癌(鳞癌、腺癌)转移淋巴结TDC以速升缓降型为主(65.0%);淋巴瘤TDC以低平型为主(57.1%)。
2.恶性淋巴结病变的BF、BV及Per值较良性淋巴结高,TTP值较良性淋巴结短,差异均有统计学意义(p<0.05);但REV值在良、恶性淋巴结间差异无统计学意义(p>0.05)。恶性组中,甲状腺癌转移淋巴结灌注参数具有明显的特异性,其BF值、BV值、Per值及REV值明显高于淋巴瘤及其它癌转移淋巴结,差异有统计学意义(p<0.05);但TTP值差异无统计学意义(p>0.05)；CT灌注参数对淋巴瘤与其它癌转移淋巴结间的鉴别意义不大(p>0.05)。良性淋巴结间淋巴结炎与淋巴结结核CT灌注参数均无明显差异(p>0.05)。3.颈部良、恶性淋巴结病变MVD间差异无统计学意义(p>0.05),VEGF阳性表达的程度在良、恶性淋巴结间差异有统计学意义(p<0.05)。恶性组间甲状腺癌转移淋巴结MVD均数、VEGF阳性表达的程度均高于其它癌转移淋巴结与淋巴瘤,差异有统计学意义(p<0.05)；MVD均数、VEGF阳性表达程度在淋巴瘤与其它癌转移淋巴结间差异无统计学意义(p>0.05)。良性组间,炎性淋巴结病变和结核性淋巴结病变的MVD均数、VEGF阳性表达程度间均无统计学意义(p>0.05)。
4.颈部淋巴结病变间VEGF表达与MVD数量间差异无统计学意义(P>0.05)。
5.免疫组化结果MVD含量、VEGF表达与颈部淋巴结病变五个灌注参数比较：颈部淋巴结病变良、恶性组的MVD含量、VEGF表达与REV、BF、BV成正相关关系;与TTP成负相关关系,差异均有统计学意义(P<0.05)；与Per间无相关性,差异无统计学意义(P>0.05)。炎性、结核性、甲状腺转移淋巴结、其它癌转移淋巴结、淋巴瘤的REV、BF、BV值与MVD含量、VEGF阳性表达的程度成正相关关系,与TTP成负相关关系,差异均有统计学意义(P均<0.05)：Per值与MVD、VEGF阳性表达的程度差异无统计学意义(P>0.05)。
结论
1.在TDC曲线形态对比中,良性淋巴结间TDC形态有较大重叠性,以缓升型及低平型为主；甲状腺癌转移淋巴结TDC以速升速降型为主,其他癌(鳞癌、腺癌)转移淋巴结TDC以速升缓降型为主,淋巴瘤TDC以低平型为主。TDC曲线有助于鉴别颈部淋巴结病变的良、恶性。
2.颈部恶性淋巴结病变的BF、BV及Per值较良性淋巴结高,TTP值较良性淋巴结短;REV值在良、恶性淋巴结间无明显差异。在颈部恶性淋巴结病变中,甲状腺癌转移淋巴结BF值、BV值、Per值、REV值明显高于淋巴瘤及其他癌转移淋巴结,有一定的特异性。
3. VEGF阳性表达的程度在颈部良、恶性淋巴结病变中有一定的特异性。恶性组间甲状腺癌转移淋巴结的MVD均数、VEGF阳性表达的程度均高于其它癌转移淋巴结及淋巴瘤。
4. MVD、VEGF与CT灌注参数间有密切的相关性,CT灌注扫描成像能够反映病变血管生成状态,CT灌注参数能够从不同方面显示颈部淋巴结病变组织的微循环特点。
Objective
Through researching the relationship among the CT perfusion parameter, micro-vessel density and vascular endothelial growth factor in the cervical lymphadenopathy,to evaluate the role of the angiogenesis in CT perfusion of the cervical lymphadenopathy.
Through comparing the difference of perfusion parameter of the cervical lymph nodes diseases,to analyze the curve and parameter of CT perfusion in the benign lymphadenopathy (inflammatory lymph node, tuberculous lymph node)and malignant lymphadenopathy (lymphoma, thyroid cancer metastatic lymph nodes, other metastatic lymph nodes).to explore the application of CT perfusion imaging parameter in the qualitative diagnosis of cervical lymphadenopathy.
Materials and methods
Collected69cases of benign and malignant cervical lymph node lesions proved by CT perfusion and pathology, than obtain the regions of interest of the time density curve (time density curve, TDC)by using DynEva software,and obtain the time to peak (time to peak, TTP)of lymph nodes and the relative reinforcing value (relative enhancement value, REV=the enhancement peak of lymph node-lymph nodes CT flat and value) according to the TDC; put the image obtained after the perfusion scan into Syngo Body PCT (Siemens, Germany) software can get the perfusion parameters:blood flow (blood flow, BF), blood volume (blood volume, BV), permeability (permeability,per). According to the histopathological results the69cases of lesions of lymph nodes are divided into benign group(inflammatory lymph node,tuberculous lymph nodes)and malignant group(lymphoma, Thyroid carcinoma metastasis lymph nodes, other cancer metastasis lymph node).the statistics of the perfusion parameter values in different lesions of lymph nodes,of which two samples are analyzing by t test, and the multiple-samples are using repeated measures to compare the perfusion parameters and TDC parameters in benign and malignant groups.
Find the diseased tissue paraffin block and HE stained glass slides of the CT perfusion lymph node at the Department of pathology, to observe the pathological features of the tumor, to examine CD34and VEGF of lymph node lesions by immunohistochemical staining and to label the microvascular with CD34monoclonal antibody, according to Weidner's assessment standard [1] to calculate the coloring capillaries and tiny blood vessels within the lymph node lesions. Analyse the correlation between the CT perfusion imaging parameters of the lymph node lesions and the expression of MVD and VEGF by the statistical methods.
Result
1.In cervical lymph node lesions TDC curve form contrast, inflammatory lymph node TDC curve of benign lymphadenopathy to slow rise type (50.0%) and always turns defences inside type (37.5%) to give priority to. TCD curve of Tuberculous lymph node also to slow rise type (40.0%) and always turns defences inside type (40.0%) to give priority to. In Malignant lymphadenopathy. TCD curve of thyroid cancer metastasis lymph nodes To speed up main type dropped (70.6%). Other cancer (squamous cell carcinoma, gland cancer) transfer to speed up slow TDC lymph node down main type (65.0%); Lymphoma TDC always turns defences inside to main type (57.1%).
2.BF, BV and Per value of Malignant lymphadenopathy benign lymph node are higher than Benign lymph node, as TTP value shorter than it, differences are statistically significant (p<0.05). But REV value in the benign and malignant lymph node no difference (p>0.05). Malignant group, thyroid cancer transfer lymph node perfusion has the obvious specific parameters, the BF value, BV value, and REV value Per value significantly higher than lymphoma and other cancer metastasis lymph nodes, difference was statistically significant (p<0.05). But TTP value difference was't statistically significant (p>0.05). CT perfusion parameters means little on identification between lymphoma and other cancer metastasis lymph node (p>0.05). Benign lymph node with inflammation and lymph node tuberculosis infection CT perfusion parameters are no significant difference (p>0.05).
3.Differences between neck benign and malignant lymphadenopathy MVD has not statistically significant (p>0.05). The positive of strong in expression VEGF between the benign and malignant lymph nodes are statistically significant differences (p<0.05). Malignant thyroid cancer transfer between groups MVD lymph nodes, VEGF express positive mean differences are higher than other cancer metastasis lymph node and lymphoma, the difference was statistically significant (p<0.05). MVD mean differences, VEGF expression in lymphoma and other positive of cancer metastasis differences between the lymph node was not statistically significant (p>0.05). Between benign group, inflammatory lymphadenopathy and tuberculate of lymphadenopathy MVD mean differences, VEGF expression between positive were no statistically significant (p>0.05).
4.The difference between Cervical lymph node lesions VEGF expression and the MVD number was not statistically significant (P>0.05).
5.Results immunization groups MVD VEGF expression and content, and neck lymph nodes lesions of perfusion parameters:Good neck lymph node lesions, a vicious group of MVD VEGF expression and content, and REV, BV BF, is positively correlated.With a negative correlation between TTP, the differences are statistically significant (P<0.05);With no relevance between Per, no statistically significant difference (P>0.05).Inflammatory, tuberculosis, thyroid transfer lymph nodes, other cancer metastasis lymph nodes, lymphoma, cervical lymph node lesions in the MVD content, VEGF express strength and REV, BF, BV value are positively correlated relationship, and the TTP a negative correlation relationship, the differences are statistically significant (P<0.05); Per value and MVD, VEGF expression strength between was not statistically significant (P>0.05).
Conclusion
1.In the TDC curve shape in comparison, the TDC shape between inflammatory and tuberculous lymph node of benign lymph node has great overlaps,the main type is slow rise type and Lowland type. TDC of thyroid cancer metastasis lymph nodes always has rapid rise and falling fast, as in other cancer (squamous cell carcinoma, gland cancer) transfer lymph nodes rises rapidly and drops slow.TDC curve help in identifying benign and malignant lesions of cervical lymph node.
2. BF、BV and Per value of perfusion parameters of Neck malignant lymph nodes higher than the benign group, TTP values of less than benign lymph nodes;REV values have no differences between benign and malignant lymph nodes. In the neck malignant lymph nodes, thyroid cancer metastasis lymph node in malignant lymph nodes have certain specific perfusion parameters, the value of its BF, BV value, Per value and REV were significantly higher than the value of lymphoma and other cancer metastatic lymph node.
3.The positive of strong in expression VEGF in the neck benign and malignant lymph nodes has certain specific. MVD mean、VEGF expression of thyroid cancer metastasis lymph node higher than other cancers metastatic lymph nodes and lymphoma.
4.MVD, VEGF and CT perfusion between parameters are closely related, CT perfusion scan imaging can reflect lesions angiogenesis state, CT perfusion parameters can be show from different aspects of the organization that cervical lymph node lesions micro circulation characteristics.
通过分析颈部不同性质淋巴结病变的CT灌注参数及TDC曲线,探讨CT灌注成像在颈部淋巴结病变定性诊断中的价值。
研究颈部不同性质淋巴结病变各项CT灌注参数与微血管密度(micro-vessel density, MVD)及血管内皮生长因子(vascular endothelial growth factor, VEGF)间的关系,评价血管生成在颈部淋巴结病变CT灌注成像中的作用。
材料及方法
收集经CT灌注、病理证实的良、恶性颈部淋巴结病变患者69例,利用DynEva软件得出感兴趣区的时间密度曲线(time density curve, TDC),根据TDC得出淋巴结的达峰时间(time to peak, TTP)和相对强化值(relative enhancement value, REV=淋巴结增强峰值-淋巴结CT平扫值)；将灌注扫描后所得图像调入Syngo Body PCT(Siemens, Germany)软件,得到灌注参数：血流量(blood flow, BF)、血容量(blood volume, BV).通透性(permeability, per)。根据病理结果将69例病变淋巴结分为良(炎性淋巴结、结核性淋巴结)、恶性(淋巴瘤、甲状腺癌转移淋巴结、其它癌转移淋巴结)两组,统计不同病变淋巴结的各灌注参数值,其中两样本应用t检验,多样本应用方差分析对良性组与恶性组的各灌注参数及TDC参数进行比较。
在病理科找出CT灌注淋巴结病变的组织蜡块及HE染色玻片,观察肿瘤病理学特征,免疫组化检测淋巴结病变组织CD34、VEGF,并以CD34单克隆抗体标记微血管,按照Weidner等的评估标准,计算淋巴结病变内着色的毛细血管和微小血.管。应用统计学方法分析淋巴结病变的CT灌注成像参数与MVD和VEGF表达的相关性。
结果
1.颈部淋巴结病变TDC曲线形态对比中,良性淋巴结病变中炎性淋巴结TDC曲线以缓升型(50.0%)及低平型(37.5%)为主；结核性淋巴结TDC曲线也以缓升型(40.0%)及低平型(40.0%)为主。恶性淋巴结病变中,甲状腺癌转移淋巴结TDC以速升速降型为主(70.6%)；其他癌(鳞癌、腺癌)转移淋巴结TDC以速升缓降型为主(65.0%);淋巴瘤TDC以低平型为主(57.1%)。
2.恶性淋巴结病变的BF、BV及Per值较良性淋巴结高,TTP值较良性淋巴结短,差异均有统计学意义(p<0.05);但REV值在良、恶性淋巴结间差异无统计学意义(p>0.05)。恶性组中,甲状腺癌转移淋巴结灌注参数具有明显的特异性,其BF值、BV值、Per值及REV值明显高于淋巴瘤及其它癌转移淋巴结,差异有统计学意义(p<0.05);但TTP值差异无统计学意义(p>0.05)；CT灌注参数对淋巴瘤与其它癌转移淋巴结间的鉴别意义不大(p>0.05)。良性淋巴结间淋巴结炎与淋巴结结核CT灌注参数均无明显差异(p>0.05)。3.颈部良、恶性淋巴结病变MVD间差异无统计学意义(p>0.05),VEGF阳性表达的程度在良、恶性淋巴结间差异有统计学意义(p<0.05)。恶性组间甲状腺癌转移淋巴结MVD均数、VEGF阳性表达的程度均高于其它癌转移淋巴结与淋巴瘤,差异有统计学意义(p<0.05)；MVD均数、VEGF阳性表达程度在淋巴瘤与其它癌转移淋巴结间差异无统计学意义(p>0.05)。良性组间,炎性淋巴结病变和结核性淋巴结病变的MVD均数、VEGF阳性表达程度间均无统计学意义(p>0.05)。
4.颈部淋巴结病变间VEGF表达与MVD数量间差异无统计学意义(P>0.05)。
5.免疫组化结果MVD含量、VEGF表达与颈部淋巴结病变五个灌注参数比较：颈部淋巴结病变良、恶性组的MVD含量、VEGF表达与REV、BF、BV成正相关关系;与TTP成负相关关系,差异均有统计学意义(P<0.05)；与Per间无相关性,差异无统计学意义(P>0.05)。炎性、结核性、甲状腺转移淋巴结、其它癌转移淋巴结、淋巴瘤的REV、BF、BV值与MVD含量、VEGF阳性表达的程度成正相关关系,与TTP成负相关关系,差异均有统计学意义(P均<0.05)：Per值与MVD、VEGF阳性表达的程度差异无统计学意义(P>0.05)。
结论
1.在TDC曲线形态对比中,良性淋巴结间TDC形态有较大重叠性,以缓升型及低平型为主；甲状腺癌转移淋巴结TDC以速升速降型为主,其他癌(鳞癌、腺癌)转移淋巴结TDC以速升缓降型为主,淋巴瘤TDC以低平型为主。TDC曲线有助于鉴别颈部淋巴结病变的良、恶性。
2.颈部恶性淋巴结病变的BF、BV及Per值较良性淋巴结高,TTP值较良性淋巴结短;REV值在良、恶性淋巴结间无明显差异。在颈部恶性淋巴结病变中,甲状腺癌转移淋巴结BF值、BV值、Per值、REV值明显高于淋巴瘤及其他癌转移淋巴结,有一定的特异性。
3. VEGF阳性表达的程度在颈部良、恶性淋巴结病变中有一定的特异性。恶性组间甲状腺癌转移淋巴结的MVD均数、VEGF阳性表达的程度均高于其它癌转移淋巴结及淋巴瘤。
4. MVD、VEGF与CT灌注参数间有密切的相关性,CT灌注扫描成像能够反映病变血管生成状态,CT灌注参数能够从不同方面显示颈部淋巴结病变组织的微循环特点。
Objective
Through researching the relationship among the CT perfusion parameter, micro-vessel density and vascular endothelial growth factor in the cervical lymphadenopathy,to evaluate the role of the angiogenesis in CT perfusion of the cervical lymphadenopathy.
Through comparing the difference of perfusion parameter of the cervical lymph nodes diseases,to analyze the curve and parameter of CT perfusion in the benign lymphadenopathy (inflammatory lymph node, tuberculous lymph node)and malignant lymphadenopathy (lymphoma, thyroid cancer metastatic lymph nodes, other metastatic lymph nodes).to explore the application of CT perfusion imaging parameter in the qualitative diagnosis of cervical lymphadenopathy.
Materials and methods
Collected69cases of benign and malignant cervical lymph node lesions proved by CT perfusion and pathology, than obtain the regions of interest of the time density curve (time density curve, TDC)by using DynEva software,and obtain the time to peak (time to peak, TTP)of lymph nodes and the relative reinforcing value (relative enhancement value, REV=the enhancement peak of lymph node-lymph nodes CT flat and value) according to the TDC; put the image obtained after the perfusion scan into Syngo Body PCT (Siemens, Germany) software can get the perfusion parameters:blood flow (blood flow, BF), blood volume (blood volume, BV), permeability (permeability,per). According to the histopathological results the69cases of lesions of lymph nodes are divided into benign group(inflammatory lymph node,tuberculous lymph nodes)and malignant group(lymphoma, Thyroid carcinoma metastasis lymph nodes, other cancer metastasis lymph node).the statistics of the perfusion parameter values in different lesions of lymph nodes,of which two samples are analyzing by t test, and the multiple-samples are using repeated measures to compare the perfusion parameters and TDC parameters in benign and malignant groups.
Find the diseased tissue paraffin block and HE stained glass slides of the CT perfusion lymph node at the Department of pathology, to observe the pathological features of the tumor, to examine CD34and VEGF of lymph node lesions by immunohistochemical staining and to label the microvascular with CD34monoclonal antibody, according to Weidner's assessment standard [1] to calculate the coloring capillaries and tiny blood vessels within the lymph node lesions. Analyse the correlation between the CT perfusion imaging parameters of the lymph node lesions and the expression of MVD and VEGF by the statistical methods.
Result
1.In cervical lymph node lesions TDC curve form contrast, inflammatory lymph node TDC curve of benign lymphadenopathy to slow rise type (50.0%) and always turns defences inside type (37.5%) to give priority to. TCD curve of Tuberculous lymph node also to slow rise type (40.0%) and always turns defences inside type (40.0%) to give priority to. In Malignant lymphadenopathy. TCD curve of thyroid cancer metastasis lymph nodes To speed up main type dropped (70.6%). Other cancer (squamous cell carcinoma, gland cancer) transfer to speed up slow TDC lymph node down main type (65.0%); Lymphoma TDC always turns defences inside to main type (57.1%).
2.BF, BV and Per value of Malignant lymphadenopathy benign lymph node are higher than Benign lymph node, as TTP value shorter than it, differences are statistically significant (p<0.05). But REV value in the benign and malignant lymph node no difference (p>0.05). Malignant group, thyroid cancer transfer lymph node perfusion has the obvious specific parameters, the BF value, BV value, and REV value Per value significantly higher than lymphoma and other cancer metastasis lymph nodes, difference was statistically significant (p<0.05). But TTP value difference was't statistically significant (p>0.05). CT perfusion parameters means little on identification between lymphoma and other cancer metastasis lymph node (p>0.05). Benign lymph node with inflammation and lymph node tuberculosis infection CT perfusion parameters are no significant difference (p>0.05).
3.Differences between neck benign and malignant lymphadenopathy MVD has not statistically significant (p>0.05). The positive of strong in expression VEGF between the benign and malignant lymph nodes are statistically significant differences (p<0.05). Malignant thyroid cancer transfer between groups MVD lymph nodes, VEGF express positive mean differences are higher than other cancer metastasis lymph node and lymphoma, the difference was statistically significant (p<0.05). MVD mean differences, VEGF expression in lymphoma and other positive of cancer metastasis differences between the lymph node was not statistically significant (p>0.05). Between benign group, inflammatory lymphadenopathy and tuberculate of lymphadenopathy MVD mean differences, VEGF expression between positive were no statistically significant (p>0.05).
4.The difference between Cervical lymph node lesions VEGF expression and the MVD number was not statistically significant (P>0.05).
5.Results immunization groups MVD VEGF expression and content, and neck lymph nodes lesions of perfusion parameters:Good neck lymph node lesions, a vicious group of MVD VEGF expression and content, and REV, BV BF, is positively correlated.With a negative correlation between TTP, the differences are statistically significant (P<0.05);With no relevance between Per, no statistically significant difference (P>0.05).Inflammatory, tuberculosis, thyroid transfer lymph nodes, other cancer metastasis lymph nodes, lymphoma, cervical lymph node lesions in the MVD content, VEGF express strength and REV, BF, BV value are positively correlated relationship, and the TTP a negative correlation relationship, the differences are statistically significant (P<0.05); Per value and MVD, VEGF expression strength between was not statistically significant (P>0.05).
Conclusion
1.In the TDC curve shape in comparison, the TDC shape between inflammatory and tuberculous lymph node of benign lymph node has great overlaps,the main type is slow rise type and Lowland type. TDC of thyroid cancer metastasis lymph nodes always has rapid rise and falling fast, as in other cancer (squamous cell carcinoma, gland cancer) transfer lymph nodes rises rapidly and drops slow.TDC curve help in identifying benign and malignant lesions of cervical lymph node.
2. BF、BV and Per value of perfusion parameters of Neck malignant lymph nodes higher than the benign group, TTP values of less than benign lymph nodes;REV values have no differences between benign and malignant lymph nodes. In the neck malignant lymph nodes, thyroid cancer metastasis lymph node in malignant lymph nodes have certain specific perfusion parameters, the value of its BF, BV value, Per value and REV were significantly higher than the value of lymphoma and other cancer metastatic lymph node.
3.The positive of strong in expression VEGF in the neck benign and malignant lymph nodes has certain specific. MVD mean、VEGF expression of thyroid cancer metastasis lymph node higher than other cancers metastatic lymph nodes and lymphoma.
4.MVD, VEGF and CT perfusion between parameters are closely related, CT perfusion scan imaging can reflect lesions angiogenesis state, CT perfusion parameters can be show from different aspects of the organization that cervical lymph node lesions micro circulation characteristics.
引文
[1]Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma [J].N Engl Med,1991,324(1):1-8.
[2]MILES K A, GRIFFITHS M R. Perfusion CT: A worthwhile enhancement[J].Br J Radil, 2003,76: 220-231.
[3]Som PM.Detection of metaslasis in cervicallymph nodes:CT and MR criteria and differential diagnosis. AJR,1992,158:961-969.
[4]Feng ST. Sun CH, Peng ZP, et al.Application of 64MDCT multislice perfusion imaging in colorectal carcinoma[J]. Zhong hua Wei Chang Wai Ke Za Zhi.,2010,13(2):137-140.
[5]Lee KC, Moon WK, Chung JW, et al. Assessment of Lymph Node Metastases by Contrast-Enhanced MR Imaging in a Head and Neck Cancer ModeI[J], Korean J Ra diol .2007, (8) :9-14.
[6]Carmelite P.VEGF as a key mediator of angiogenesis in cancer. Oncology, 2005,69 (Suppl3):4-10.
[7]杨智云,孟悛非,徐巧兰,等.颈部淋巴结病变CT灌注成像[J].临床放射学杂志,2007,26(9)：865-868.
[8]于海容,王振常,闰钟钰,等.颈部淋巴结病变的CT灌注成像研究.医学临床研究.2009,26(3)：400-403.
[9]Mattern J, Koomagi R, Volm M. Vascular endothelial growth fact or expression and angiogenesis in non-small cell lung carcinoma [J]. Int J Oncol. 1995; 6:1059-1062.
[10]Bosari S, Lee AK, Delellis RA, et al. Micro vessel quantitation and Prognosis in invasive breast carcinoma[J]. Hum Pathol,1992,23(7):755-761.
[11]CamPhausen K, Menard C. Angiogenesis inhibitors and radiotherapy of Primary tumours.[J]. ExPert OPin Biol Ther,2002,2(5):477-481.
[]2]熊正文,朱光君,李春光,等.肿瘤血管及非小细胞肺癌检测技术研究进展.中华现代医学杂志[J].2001,1(3)：12-15.
[13]Duff SE. Li C, Garland JM,et al. CD 105 is important for angiogenesis:evidence and potential application[J]. FASEB J,2003,17(9):984-992.
[14]Ji RC. Lymphatic endothelial cells, tumor lymph angiogenesis and metastasis:New insights into intratumoral and peritumoral lymphatic's [J]. Cancer Metastasis Rev, 2006, 25(4):677-694.
[15]Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases.[J]. Nature(Lond),2000, 407:249-257
[16]Nisato RE. Tille JC, Pepper MS. Lymph angiogenesis and tumor metastasis[J]. Thro mb Hae-most,2003,90(4):59.
[17]Karamysheva AF. Mechanisms of angiogenesis[J]. Biochemistry(Mose).2008,73(7):751-762.
[18]Carmeliet P. VEGF as a key mediator of angiogenesis in cancer[J]..Oncology,2005, 69(SuPP13):4-10.
[19]詹启敏.分子肿瘤学[M].北京：人民卫生出版社,2005,10：325-334.
[20]Korpanty G, Smyth E, Sullivan LA, et al. Antiangiogenic therapy in lung cancer: focus on vascular endothelial growth factor pathway [J]. Exp Biol Med (Maywood), 2010,235(1):3-9.
[21]Tammela T, Enholm B, Alitalo K, et al. The biology of vascular endothelial growth factors [J].Cardiovasc Res,2005,65(3):550-563.
[22]Achen MG, McCou BK, Stacker SA. Focus on Lymph angiogenesis in tumor metastasis [J].Cancer Cell,2005,7(2):121-127.
[23]Folkman J.Shing Y,Angiogenesis[J].Journal of Biological Chemistry, 1992,267(16): 10931-10934.
[24]Folkman J, Menler E, Abernathy C, et al.Isolation of a tumor factor responsible for angiogenesis.J ExP Med,1971,133(7):275¨288.
[25]Kaio E, Tanaka s, Kitadai y.et al.Clinical signifieance of angiogenic factor exp ression at the deepest invasive site of advanced colorectal careinoma.Oncolog,2003,64(1):61-73.
[26]Weidner N, SemP le JP, Welch WR, et al.Tumor angiogenesis and metastasis Correlation in invasive breast carcinoma.N Eng J Med,1991 324(3):1-5.
[27]Uthoff SM, Duehrow M, Sehmidt MH, et al.VEGF isoforms and mutations in human colorectal cancer.Int J Cancer 2002,101:32.
[28]Kaya M, Wada T, Kawaguehi S.et al.Inereased pre-therapeuticSerum vascular Endothelia lgrowth faetor in Patients with early Clinical replace of osteosareoma.Brr Cancer 2002,86:864.
[29]Lutgendorf SK.Johnsen EL.CooPer B.et al.Vascular endothelial Growth factor and social support in Patients with ovaria carcinoma.Cancer 2002,95:808.
[30]Baltaci S, Resorlu B, Yagci C, et al. Computerized tomography for detecting perivesical infiltration and lymph node metastasis in invasive bladder carcinoma. Urol Int 2008;81:399e402.
[31]Phongkitkarun S, Kobayashi S, Kan z, et al Quantification of angiogenesis by functional computed tomography in a madrigal model in rats .Accad Ra diol,2004,11:573-582.
[32]Volm M, Koomagi R, Mattern J.Prognostic value of Vascular endothelial growth factor and its receptor Fit-l in squamous cell lung cancer. Int J Cancer.1997,74:64-67.
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[39]周景玮,陈克敏,刘林祥,等.CT灌注技术在乳腺肿瘤研究中的应用(J).实用医技杂志,2006,13(20)：3558—3561.
[40]Zhang M, Kono M.Solid Pulmonary nodules:evaluation of blood flow pattens With dynamic CT.Radiology 1997; 205:471-478.
[41]顾爱华.CT和MR肝脏灌注成像技术及其临床应用.国际放射医学核医学杂志,2006；30(3)：188
[42]Goh V, Padhani AR, Rasheed S. Functional imaging of colorectal cancer angiogenesis [J]. Lancet Oncology, 2007,8 (3):245-255.
[43]Pollard R. Quantitative evaluation of perfusion and permeability of peripheral tumors using contrast-enhanced computed tomography [J]. Invest Radiol 2004, 39:340-349.
[44]Li Y. Peripheral lung carcinoma:Correlation of angiogenesis and first2pass perfusion parameters of 642detector row CT[J]. Lung Cancer, 2008,61 (1):44 - 53.
[45]Ma SH, Le H B, Jia BH, et al Peripheral pulmonary nodules:Re-lationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression [J]. Bm c Cancer,2008, 8:186.
[46]Goh V. Colorectal turn or vascularity quantitative assessment with multidetector CT-Do turn or perfusion measurements reflects angiogenesis [J]. Radiology, 2008,249(2):510-517.
[47]D, Assignies G. Pancreatic endocrine tumors:tumor blood flow assessed with perfusion CT reflects angiogenesis and correlates with prognostic factors[J]. Radiology, 2009, 250(2):407-416.
[48]Dugdae PE, Miles KA, Bunce I,et al. CT Measurement of perfusion and permeability with in lymphoma masses and its ability to assess grade. activity and chemotherapeutic response. J C A T,1999, 23(4):540-547.
[49]Liu Y, Bellomi M, Gatti G, et al. Accuracy of computer tomography Perfusion in assessing metastatic involvement of enlarged axillary lymph nodes in patients with breast cancer [J]. Breast Cancer Res,2007. 9:R40.
[50]生晶、郝强,等.胰周淋巴结转移瘤的多层CT灌注成像研究[J].中华胰腺病杂志2008,8(4)：217-219.
[51]生晶,田建明,毕永明,等.CT灌注成像对颈部淋巴结病变的鉴别诊断和疗效评价[M].中国医学影像技术,2005,21(6)：856-858.
[52]Bisdas S, Baghi M, Smolarz A, Pihno NC, Lehnert T, Knecht R,Mack MG, Vogl TJ, Tuerkay S, Koh TS:Quantitative measurements of perfusion and permeability of or pharyngeal and oral cavity cancer, recurrent disease, and associated lymph nodes using first-pass contrast-enhanced computed tomography studies[J]. Invest Radiol 2007,42:1 72-1 79.
[53]梁颖,罗德红,吴宁.颈部恶性淋巴结的多层螺旋CT灌注研究[J].中华放射学杂志2004年11月第38卷第11期.
[54]杨智云.颈部淋巴结病变CT灌注成像[J].中华医学会第十三届全国放射学大会.
[55]杨智云,孟悛非,徐巧兰,等.颈部淋巴结病变CT灌注成像[J].临末放射学杂志,2007,26(9)：865-868.
[56]于海容,王振常,闰钟钰,等.颈部淋巴结病变的CT灌注成像研究.医学临床研究,2009,26(3)：400-403.
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[58]生晶,田建明,邢伟,等.MSCT灌注成像对淋巴结转移瘤的鉴别诊断和疗效评价的临床研究.实用放射学杂志,2005,21：747-749.
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[67]生晶,田建明,毕永明,等.CT灌注成像对颈部淋巴结病变的鉴别诊断和疗效评价.中国医学影像技术.2005,21(6)：856-858.
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[71]K A. Miles. Turn our angiogenesis and its relation to contrast enhancement on computed tomography: a review. European Journal of Radiology, 1999, 30(1):198.
[I]Fukumura D, Jain RK. Imaging angiogenesis and the microenvironment [J]. APM IS,2008,116: 695-715.
[2]Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma [J]. N Engl J Med,1991,324(1):1-8.
[3]Obermair A, Wanner C, Bilgi S, SPeiser P, Kaider A, Reinthaller A, et al. Tumor angiogenesis in stage IB cervieal cancer :correlation of micro vessel density with survival. Am j Obstet Gynecol, 1998; 178:314-319
[4]Bosari S, Lee AK, Delellis RA, et al. Micro vessel quantitation and Prognosis in invasive breast carcinoma. Hum Pathol,1992,23(7):755-761.
[5]CamPhausen K, Menard C. Angiogenesis inhibitors and radiotherapy of Primary tumours. ExPert OPin Biol Ther,2002,2(5):477¨481.
16]熊正文,朱光君,李春光,等.肿瘤血管及非小细胞肺癌检测技术研究进展.中华现代医学杂志2001,1(3)：12—15.
[7]Duff SE, Li C, Garland JM,et al. CD105 is important for angiogenesis:evidence and potential application[J]. FASEB J,2003.17(9):984-992.
[8]Ji RC. Lymphatic endothelial cells, tumor lymph angiogenesis and metastasis:New insights into intratumoral and peritumoral lymphatic's [J]. Cancer Metastasis Rev, 2006, 25(4):677-694.
[9]Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature(Lond),2000,407:249-257
[10]Nisato RE, Tille JC, Pepper MS. Lymph angiogenesis and tumor metastasis[J]. Thromb Haemost.2003.90(4):59.
[11]Karamysheva AF. Mechanisms of angiogenesis. Biochemistry(Mose).2008,73(7):751-762.
[12]Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology,2005,69(SuPP13):4-10.
[13]詹启敏.分子肿瘤学[M].北京：人民卫生出版社,2005,10：325-334.
[14]Korpanty G, Smyth E. Sullivan LA. et al. Antiangiogenic therapy in lung cancer: focus on vascular endothelial growth factor pathway [J]. Exp Biol Med (Maywood),2010,235(1):3-9.
[15]Tammela T, Enholm B, Alitalo K, et al. The biology of vascular endothelial growth factors .Cardiovasc Res,2005,65(3):55O-563.
[16]Achen MG, McCou BK, Stacker SA. Focus on Lymph angiogenesis in tumor metastasis .Cancer Cell,2005,7(2):121-127.
[17]Goh V. Padhani AR, Rasheed S. Functional imaging of colorectal cancer angiogenesis [J]. Lancet Oncology, 2007, 8 (3):245-255.
[18]Pollard R. Quantitative evaluation of perfusion and permeability of peripheral tumors using contrast-enhanced computed tomography [J]. Invest Radiol 2004, 39:340-349.
[19]Li Y. Peripheral lung carcinoma:Correlation of angiogenesis and first2pass perfusion parameters of 642detector row CT[J]. Lung Cancer, 2008, 61 (1):44-53.
[20]Ma SH, Le H B, Jia BH, et al Peripheral pulmonary nodules:Re-lationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression [J]. Bm c Cancer.2008. 8: 186.
[21]Goh V. Colorectal turn or vascularity quantitative assessment with multidetector CT-Do turn or perfusion measurements reflects angiogenesis [J]. Radiology, 2008,249(2):510-517.
[22]D'Assignies G. Pancreatic endocrine tumors:tumor blood flow assessed with perfusion CT reflects angiogenesis and correlates with prognostic factors[J]. Radiology,2009,250(2):407-416.
[1]Fukumura D, Jain RK. Imaging angiogenesis and the microenvironment [J]. APM IS,2008.116: 695-715.
[2]Weidner N, Semple JP. Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma [J]. N Engl J Med,1991,324(1):1-8.
[3]Obermair A, Wanner C, Bilgi S. SPeiser P, Kaider A, Reinthaller A, et al. Tumor angiogenesis in stage IB cervieal cancer :cation of micro vessel density with survival. Am [J]. Obstet Gynecol, 1998;178:314-319
[4]Bosari S, Lee AK, Delellis RA, et al. Micro vessel quantitation and Prognosis in invasive breast carcinoma[J]. Hum Pathol,1992,23(7):755¨761.
[5]CamPhausen K, Menard C. Angiogenesis inhibitors and radiotherapy of Primary tumours.[J]. ExPert OPin Biol Ther,2002,2(5):477-481.
[6]熊正文,朱光君,李春光,等.肿瘤血管及非小细胞肺癌检测技术研究进展.中华现代医学杂志[J].2001,1(3)：12-15.
[7]Duff SE, Li C, Garland JM .et al. CD105 is important for angiogenesis:evidence and potential application[J]. FASEB J.2003,17(9):984-992.
[8]Ji RC. Lymphatic endothelial cells, tumor lymph angiogenesis and metastasis:New insights into intratumoral and peritumoral lymphatic's [J]. Cancer Metastasis Rev, 2006.25(4):677-694.
[9]Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases.[J]. Nature(Lond),2000,407:249-257
[10]Nisato RE, Tille JC. Pepper MS. Lymph angiogenesis and tumor metastasis[J]. Thro mb Hae-most,2003,90(4):59.
[11]Karamysheva AF. Mechanisms of angiogenesis[J]. Biochemistry(Mose).2008,73(7):751-762.
[12]Carmeliet P. VEGF as a key mediator of angiogenesis in cancer[J]..Oncology,2005 69(SuPP13):4-10.
[13]詹启敏.分子肿瘤学[M].北京：人民卫生出版社,2005,10：325-334.
[14]Korpanty G, Smyth E, Sullivan LA, et al. Antiangiogenic therapy in lung cancer:focus on vascular endothelial growth factor pathway [J]. Exp Biol Med (Maywood),2010,235(1):3-9.
[15]Tammela T, Enholm B, Alitalo K, et al. The biology of vascular endothelial growth factors [J].Cardiovasc Res,2005,65(3):550-563.
[16]Achen MG, MeCou BK, Stacker SA. Focus on Lymph angiogenesis in tumor metastasis [J].Cancer Cell,2005,7(2):121-127.
[17]周景玮,陈克敏,刘林祥,等.CT灌注技术在乳腺肿瘤研究中的应用[J].实用医技杂志,2006,13(20)：3558—3561.
[18]MILESKA, HAYBALLMP, DIXON AK. Co lour perfusion imaging:a new application of computed tomography[J]. Lancet,1991,337:643-645.
[19]顾爱华.CT和MR肝脏灌注成像技术及其临床应用.国际放射医学核医学杂志[J],2006；30(3)：188
[20]Goh V. Padhani AR, Rasheed S. Functional imaging of colorectal cancer angiogenesis [J]. Lancet Oncology,2007,8 (3):245-255.
[21]Pollard R. Quantitative evaluation of perfusion and permeability of peripheral tumors using contrast-enhanced computed tomography [J]. Invest Radiol 2004.39: 340-349.
[22]Li Y. Peripheral lung carcinoma:Correlation of angiogenesis and first2pass perfusion parameters of 642detector row CT[J]. Lung Cancer,2008,61 (1):44-53.
[23]Ma SH, Le H B, Jia BH, et al Peripheral pulmonary nodules:Re-lationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression [J]. Bm c Cancer,2008,8: 186.
[24]Goh V. Colorectal tum or vascularity quantitative assessment with multidetector CT-Do turn or perfusion measurements reflects angiogenesis [J]. Radiology,2008,249(2):510-517.
[25]D'Assignies G. Pancreatic endoerine tumors:tumor blood flow assessed with perfusion CT reflects angiogenesis and correlates with prognostic factors[J]. Radiology.2009,250(2):407-416.
[26]Dugdae PE, Miles KA, Bunce I,et al. CT Measurement of perfusion and permeability with in lymphoma masses and its ability to assess grade[J]. activity and chemotherapeutic response. JCAT,I 999,23(4):540-547.
[27]Liu Y, Bellomi M, Gatti G, et al. Accuracy of computer tomography Perfusion in assessing metastatic involvement of enlarged axillary lymph nodes in patients with breast cancer [J]. Breast Cancer Res,2007,9:R40
[28]生晶、郝强.胰周淋巴结转移瘤的多层CT灌注成像研究(J].中华胰腺病杂志2008,8(4)：217—219
[29]生晶,田建明,毕永明,等.CT灌注成像对颈部淋巴结病变的鉴别诊断和疗效评价.中国医学影像技术[J].,2005,21(6)：856-858.
[30]Bisdas S, Baghi M, Smolarz A, Pihno NC, Lehnert T, Knecht R,Mack MG, Vogl TJ, Tuerkay S, Koh TS:Quantitative measurements of perfusion and permeability of or pharyngeal and oral cavity cancer, recurrent disease, and associated lymph nodes using first-pass contrast-enhanced computed tomography studies[J]. Invest Radiol 2007,42:172-179.
[31]梁颖,罗德红,吴宁.颈部恶性淋巴结的多层螺旋CT灌注研究[J].中华放射学杂志2004年11月第38卷第11期.
[2]MILES K A, GRIFFITHS M R. Perfusion CT: A worthwhile enhancement[J].Br J Radil, 2003,76: 220-231.
[3]Som PM.Detection of metaslasis in cervicallymph nodes:CT and MR criteria and differential diagnosis. AJR,1992,158:961-969.
[4]Feng ST. Sun CH, Peng ZP, et al.Application of 64MDCT multislice perfusion imaging in colorectal carcinoma[J]. Zhong hua Wei Chang Wai Ke Za Zhi.,2010,13(2):137-140.
[5]Lee KC, Moon WK, Chung JW, et al. Assessment of Lymph Node Metastases by Contrast-Enhanced MR Imaging in a Head and Neck Cancer ModeI[J], Korean J Ra diol .2007, (8) :9-14.
[6]Carmelite P.VEGF as a key mediator of angiogenesis in cancer. Oncology, 2005,69 (Suppl3):4-10.
[7]杨智云,孟悛非,徐巧兰,等.颈部淋巴结病变CT灌注成像[J].临床放射学杂志,2007,26(9)：865-868.
[8]于海容,王振常,闰钟钰,等.颈部淋巴结病变的CT灌注成像研究.医学临床研究.2009,26(3)：400-403.
[9]Mattern J, Koomagi R, Volm M. Vascular endothelial growth fact or expression and angiogenesis in non-small cell lung carcinoma [J]. Int J Oncol. 1995; 6:1059-1062.
[10]Bosari S, Lee AK, Delellis RA, et al. Micro vessel quantitation and Prognosis in invasive breast carcinoma[J]. Hum Pathol,1992,23(7):755-761.
[11]CamPhausen K, Menard C. Angiogenesis inhibitors and radiotherapy of Primary tumours.[J]. ExPert OPin Biol Ther,2002,2(5):477-481.
[]2]熊正文,朱光君,李春光,等.肿瘤血管及非小细胞肺癌检测技术研究进展.中华现代医学杂志[J].2001,1(3)：12-15.
[13]Duff SE. Li C, Garland JM,et al. CD 105 is important for angiogenesis:evidence and potential application[J]. FASEB J,2003,17(9):984-992.
[14]Ji RC. Lymphatic endothelial cells, tumor lymph angiogenesis and metastasis:New insights into intratumoral and peritumoral lymphatic's [J]. Cancer Metastasis Rev, 2006, 25(4):677-694.
[15]Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases.[J]. Nature(Lond),2000, 407:249-257
[16]Nisato RE. Tille JC, Pepper MS. Lymph angiogenesis and tumor metastasis[J]. Thro mb Hae-most,2003,90(4):59.
[17]Karamysheva AF. Mechanisms of angiogenesis[J]. Biochemistry(Mose).2008,73(7):751-762.
[18]Carmeliet P. VEGF as a key mediator of angiogenesis in cancer[J]..Oncology,2005, 69(SuPP13):4-10.
[19]詹启敏.分子肿瘤学[M].北京：人民卫生出版社,2005,10：325-334.
[20]Korpanty G, Smyth E, Sullivan LA, et al. Antiangiogenic therapy in lung cancer: focus on vascular endothelial growth factor pathway [J]. Exp Biol Med (Maywood), 2010,235(1):3-9.
[21]Tammela T, Enholm B, Alitalo K, et al. The biology of vascular endothelial growth factors [J].Cardiovasc Res,2005,65(3):550-563.
[22]Achen MG, McCou BK, Stacker SA. Focus on Lymph angiogenesis in tumor metastasis [J].Cancer Cell,2005,7(2):121-127.
[23]Folkman J.Shing Y,Angiogenesis[J].Journal of Biological Chemistry, 1992,267(16): 10931-10934.
[24]Folkman J, Menler E, Abernathy C, et al.Isolation of a tumor factor responsible for angiogenesis.J ExP Med,1971,133(7):275¨288.
[25]Kaio E, Tanaka s, Kitadai y.et al.Clinical signifieance of angiogenic factor exp ression at the deepest invasive site of advanced colorectal careinoma.Oncolog,2003,64(1):61-73.
[26]Weidner N, SemP le JP, Welch WR, et al.Tumor angiogenesis and metastasis Correlation in invasive breast carcinoma.N Eng J Med,1991 324(3):1-5.
[27]Uthoff SM, Duehrow M, Sehmidt MH, et al.VEGF isoforms and mutations in human colorectal cancer.Int J Cancer 2002,101:32.
[28]Kaya M, Wada T, Kawaguehi S.et al.Inereased pre-therapeuticSerum vascular Endothelia lgrowth faetor in Patients with early Clinical replace of osteosareoma.Brr Cancer 2002,86:864.
[29]Lutgendorf SK.Johnsen EL.CooPer B.et al.Vascular endothelial Growth factor and social support in Patients with ovaria carcinoma.Cancer 2002,95:808.
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[2]Weidner N, Semple JP. Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma [J]. N Engl J Med,1991,324(1):1-8.
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[5]CamPhausen K, Menard C. Angiogenesis inhibitors and radiotherapy of Primary tumours.[J]. ExPert OPin Biol Ther,2002,2(5):477-481.
[6]熊正文,朱光君,李春光,等.肿瘤血管及非小细胞肺癌检测技术研究进展.中华现代医学杂志[J].2001,1(3)：12-15.
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[9]Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases.[J]. Nature(Lond),2000,407:249-257
[10]Nisato RE, Tille JC. Pepper MS. Lymph angiogenesis and tumor metastasis[J]. Thro mb Hae-most,2003,90(4):59.
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