鼻咽癌MSCT灌注与血管生成、缺氧状态的关系研究
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摘要
第一部分VX2肿瘤MSCT灌注值与微血管的关系
目的
研究VX2肿瘤生长过程中微血管生成情况，以及肿瘤微血管密度与MSCT灌注值之间的变化关系。
材料和方法
8只腿部肌肉种植VX2肿瘤的新西兰大白兔，分别于肿瘤生长第7、14、21、28天行MSCT灌注扫描，兔耳缘静脉注射碘对比剂(碘海醇300mgI／ml)6ml，流率0．6ml／s，注射同时行定层MSCT扫描，扫描条件4×5mm，旋转时间0．75s，间隔时间1．5s，持续时间至注射后45s，扫描图像输送入Function分析软件中，自动生成灌注图，手绘ROI区分别测量肿瘤及正常肌肉组织内血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标。于第7、14、21、28天行CT灌注扫描后分别处死瘤兔2只，取出肿瘤组织行免疫组化CD34单克隆抗体染色，进行微血管密度(Micro-vessel density，MVD)计数。不同时间段灌注值比较行方差分析SNK均数比较，各项MSCT各灌注指标与MVD计数之间行Pearson相关分析。P值小于0．05定为统计学显著性差异阈值。
结果
肿瘤生长大小分别为14．1±2．9mm、27．7±4．5mm、39．5±8．3mm、52．5±7．8mm，第7天MSCT灌注值BF为135．10±13．08ml／100g／min，其余灌注参数分别为PEI73．11±5．25HU，TTP18．57±1．38，BV45．0±2．53ml／100g，至第28天，相应灌注值为BF46．05±7．55ml／100g／min、PEI70．25±6．25HU、TTP35．90±1．90s、BV51．63±4．77ml／100g，第7、14天的CT灌注值与第21、28天灌注值中的BF和TTP存在显著性差异，四次灌注中的BV和PEI没有统计学显著性差异。第7、14、21、28天肿瘤标本MVD计数分别为36．5±2．12，41．5±4．94，38．0±4．24，46．5±2．12。CT灌注值中的BV与MVD存在相关性(r=0．71，P=0．02)，PEI与MVD存在弱相关(r=0．68，P=0．06)，BF、TTP与MVD之间没有显著性差异(r=0．59，r=0．15，P＞0．05)。
结论
VX2兔肿瘤模型中，随肿瘤生长，其灌注值BF在早期较高，随肿瘤生长灌注值BF下降，早期MSCT灌注值与肿瘤生长后期灌注值有明显差异。在肿瘤多层CT灌注成像的灌注值中BV值和PEI值与VX2肿瘤血管生成存在相关关系，MSCT灌注成像可以反映VX2肿瘤微血管生成特征，以及肿瘤在不同生长时期的微血管变化情况。
第二部分VX2肿瘤MSCT灌注值与缺氧状态、血管生成的关系
目的
研究VX2肿瘤乏氧状态与微血管生成情况的相互影响，探讨MSCT灌注值与VX2肿瘤乏氧状态、微血管生成之间的关系。
材料和方法
8只腿部肌肉种植VX2肿瘤的新西兰大白兔，分别于肿瘤生长第7、14、21、28天行MSCT灌注扫描，兔耳缘静脉注射碘对比剂(碘海醇300mgI／ml)6ml，流率0．6ml／s，注射同时行定层MSCT扫描，扫描条件4×5mm，旋转时间0．75s，间隔时间1．5s，持续时间至注射后45s，扫描图像于Function分析软件中，分别测量肿瘤及正常肌肉组织内血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标。于肿瘤种植后第7、14、21、28天行CT灌注扫描后分别处死瘤兔2只，肿瘤组织行HIF-1α、VEGF免疫组化染色，根据肿瘤细胞着色深度和阳性细胞百分比统计HIF-1α、VEGF表达等级。不同时间段HIF-1α、VEGF表达等级分布分别进行x~2检验，HIF-1α、VEGF表达等级之间行x~2检验，HIF-1α、VEGF与CT灌注值、MVD之间行Spearman等级相关分析。
结果
肿瘤第7、14、21、28天HIF-1α等级由低到高再降低，但其变化没有统计学显著性差异(x~2=1．49，P=0．22)，第7、14、21、28天VEGF分布无显著性差异x~2=0．27，P=0．60，HIF-1α、VEGF之间等级分布也没有显著性差异：不同时间段CT灌注BF值与HIF-1α表达存在相关性(r=0．87，P＜0．05)，不同时间段CT灌注值中PEI值和BV值与VEGF之间存在相关性(r=0．75，P=0．03；r=0．77，P=0．02)。MVD计数与HIF-1α和VEGF均没有明显相关关系。
结论
HIF-1α在VX2肿瘤血管生成调控和肿瘤生长中有着重要作用，VEGF的上调是肿瘤早期缺氧调控的重要途径，也存在其它途径参与。CT灌注值不仅与肿瘤内部微血管密度有关，部分灌注值能够反映肿瘤缺氧状态及其内部血管生成调节的过程，VX2肿瘤血流灌注与肿瘤缺氧状态和血管生成之间存在依存关系。
第三部分鼻咽癌MSCT灌注成像与其微血管生成关系的研究
目的
研究鼻咽癌MSCT灌注值与肿瘤微血管密度(MVD)、肿瘤分期的关系，探讨MSCT灌注成像对鼻咽癌微血管生成评价的价值。
材料和方法
经活检病理证实的鼻咽癌62例，静脉注射50ml对比剂后行CT灌注扫描，动态图像经function CT软件处理，自动生成灌注图像，手绘感兴趣区分别测量鼻咽癌肿瘤部位的血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标，其中35例鼻咽癌活检组织行免疫组化CD34单抗染色后，Weidner方法计数微血管密度(Micro-vessel density，MVD)。各组灌注值比较行方差分析及均数SNK比较，CT灌注值与MVD之间行Pearson相关分析，CT灌注值、MVD与肿瘤分期之间行Spearman等级相关分析，P值小于0．05定为统计学有显著性意义。
结果
35例鼻咽癌肿瘤CT灌注值BF为51．65±3．25ml／100g／min，其余各参数分别为PEI28．65±1．52HU，TTP30．68±2．01s，BV12．49±1．07ml／100g，PEI和BV与鼻咽癌分期相关(r=0．46，r=0．53，P＜0．05)，BF和BV与鼻咽癌独立T分期相关(r=0．37，r=0．42，P＜0．05)，其余指标与独立的T分期和N分期无明显相关性；35例鼻咽癌MVD为41．29±14．79，与BF、PEI、TTP、BV均存在相关性，MVD与肿瘤TNM分期存在相关性，但与独立的T分期和N分期无明显相关性。
结论
鼻咽癌具有特征的CT灌注表现，肿瘤灌注值明显高于周围组织，多层CT灌注成像的灌注值可以反映鼻咽癌微血管密度特征，灌注值高低与微血管密度存在相关关系，CT灌注中的PEI和BV值与肿瘤血管生成及鼻咽癌的TNM分期均存在一定的相关性。
第四部分鼻咽癌缺氧状态、血管生成和CT灌注之间的关系
目的
研究鼻咽癌缺氧状态、血管生成与CT灌注之间的关系，探讨多层CT灌注成像作为鼻咽癌缺氧状态及血管生成评估手段的可行性。
材料和方法
经活检病理证实的鼻咽癌62例中，具备完整资料的35例鼻咽癌活检标本行免疫组化HIF-1α和VEGF单抗染色，按阳性细胞着色程度和阳性细胞百分比评定HIF-1α和VEGF表达等级，35例患者均于放疗前一周内行CT灌注检查，静脉注射50ml对比剂后行CT灌注扫描，动态系列图像经function CT软件处理，自动生成各值灌注图像，手绘ROI区测量鼻咽癌肿瘤部位的血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标。CT灌注值、HIF-1α、VEGF、MVD之问行Spearman等级相关分析，HIF-1α和VEGF分级与肿瘤分期之间行双向有序行列表x~2检验。
结果
鼻咽癌肿瘤CT灌注值BF、PEI、TTP、BV分别为51．65±3．25ml／100g／min、28．65±1．52HU、30．68±2．01s、12．49±1．07ml／100g，35例鼻咽癌中HIF-1α阳性染色27例(77．14％)，其表达等级与肿瘤分期之间没有显著性差异(x~2=2．91，P=0．08)，与CT灌注中BF值存在负相关(r=-0．54，P＜0．05)，与BV值弱相关(r=0．42，P=0．07)；VEGF阳性表达31例(88．57％)，表达等级与肿瘤分期之间有显著性差异(x~2=4．10，P=0．04)，VEGF与CT灌注中PEI值存在相关性(r=0．57，P＜0．05)。HIF-1α和VEGF表达等级之间有显著关系(x~2=9．70，P＜0．05)，HIF-1α和VEGF与MVD之间均存在相关关系(r=0．62，r=0．78 P＜0．05)。
结论
鼻咽癌HIF-1α和VEGF阳性表达率较高，而且两者表达存在依从关系，HIF-1α表达虽然与肿瘤分期没有显著性关系，但HIF-1α与肿瘤灌注值BF及BV之间、及MVD之间存在相关性；VEGF与肿瘤分期和肿瘤微血管生成均存在联系，并与CT灌注中的PEI存在相关，CT灌注成像中BF、BV、PEI能够部分反映鼻咽癌的乏氧状态和血管生成的部分特征，对于HIF-1α和VEGF的血管调控尚待进一步研究。
第五部分鼻咽癌MSCT灌注、血管生成及缺氧状态与放疗的关系
目的
研究鼻咽癌MSCT灌注、缺氧状态及血管生成与肿瘤放疗后短期肿瘤消退的关系，评价MSCT灌注通过缺氧状态及血管生成评估鼻咽癌放疗敏感性的可行性。
材料和方法
从62例鼻咽癌中，选取临床病理及影像资料完整的鼻咽癌35例，35例鼻咽癌活检标本行免疫组化HIF-1α和VEGF单抗染色，按阳性细胞着色程度和阳性细胞百分比评定HIF-1α和VEGF表达等级。35例患者均于放疗前、放疗中(34cGy～38cGy)、放疗结束后行MSCT灌注检查，静脉注射50ml对比剂后行CT灌注扫描，动态图像经function CT软件处理，自动生成灌注图像，并测量每次鼻咽癌肿瘤部位的血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标。测量肿瘤长径计算每例鼻咽癌放疗中、放疗结束时的肿瘤消退率，并按照肿瘤消退率将35例鼻咽癌分为放疗敏感组(Gs)和放疗不敏感组(Gns)，对两组的CT灌注值、MVD分别进行组间t检验，两组HIF-1α和VEGF表达等级行x~2检验。对两组放疗前后BF、PEI、TTP和BV值分别进行方差分析和SNK均数比较，了解放疗前后灌注值变化情况。
结果
35例鼻咽癌放疗中及放疗结束后总体肿瘤消退率为0．41±0．20和0．54±0．24，消退在0．11-1．0之间，放疗中及放疗结束后消退率的比较两次复查消退率并无显著性差异，其中敏感组消退率为0．50±0．17和0．67±0．16，不敏感组消退率为0．19±0．05和0．24±0．03，两组间消退率比较存在显著性差异(t=5．66，t=8．11，P＜0．01)，敏感组(Gs)初始CT灌注值BF为57．04±18．39ml／100g／min，其余各参数分别为PEI27．72±9．46HU，TTP27．32±8．57s，BV13．14±5．77ml／100g；不敏感组初始灌注值分别为BF38．20±14．62ml／100g／min，PEI24．00±7．49HU，TTP 39．10±15．24s，BV10．89±7．64ml／100g，两组间初始BF值、TTP值之间有显著性差异(F=8．23，F=8．48，P＜0．01)，但两组之间的PEI和BV没有显著性差异。比较两组放疗前后灌注值的比较发现，敏感组放疗后BF、PEI和BV均有下降，TTP上升，均具有统计学差异，其中BF值和PEI值在放疗中即有明显下降(F=50．59，F=4．85，P＜0．01)；而在不敏感组，仅有BF值在放疗后下降(F=9．64，P＜0．01)，PEI、TTP和BV改变均无显著性差异。敏感组及不敏感组HIF-1α表达阳性率分别为76％(19／25)和80％(8／10)，其等级分布在两组中有显著性差异(x~2=6．00，P＜0．05)，VEGF表达阳性率分别为92％(23／25)和80％(8／10)，其等级分布在两组中没有显著性差异(x~2=2．01，P=0．16)。敏感组及不敏感组MVD分别为46．6±13．25和35．0±15．8，两组间MVD比较具有显著性差异(F=4．90，P＜0．05)。
结论
鼻咽癌放疗敏感性与CT灌注值、HIF-1α表达等级、MVD之间有着明显的相关性，与VEGF表达等级无明显相关，CT灌注中高灌注的肿瘤，HIF-1α表达等级低，MVD高，对放疗敏感性高，反之CT灌注低的肿瘤，MVD低，HIF-1α表达等级高，对放疗有一定的抵抗。对放疗敏感的鼻咽癌在放疗中即可发现BF及PEI值明显下降，放疗后灌注值改变不明显的鼻咽癌常提示肿瘤消退不满意，对放疗不敏感。CT灌注成像能够部分反映鼻咽癌的乏氧状态和血管生成，可通过CT灌注值高低和放疗中灌注值的变化对鼻咽癌放疗敏感性作出评估。
PARTⅠThe Correlation Of MSCT Perfusion Parameters WithAngiogenesis In VX2 Tumor
Objective
To study angiogenesis of VX2 soft-tissue tumor in the rabbit, and analysis thecorrelation of MSCT perfusion parameters and micro-vessel density(MVD) during theprocess of tumor growth.
Materials and methods
8 rabbits were implanted with VX2 tumor tissue in proximal thighs. MSCT perfusionscan were performed on those rabbits with Mx8000 Quad CT in the 7,14,21,28 days afterimplant respectively. The functional maps were produced automatically and perfusionparameters including blood flow(BF), peak enhancement index(PEI), time to peak(TTP)and blood volume(BV) were calculated by the workstation. The perfusion values weremeasured by the manually defined ROI within tumor. 2 rabbits were sacrificed every 7 daysafter CT perfusion, and the resected specimens were staining by CD34 for quantification ofMVD. The perfusion parameters and MVD of different phase were analyzed by ANOVA;MSCT perfusion parameters were correlated with MVD by Pearson correlation analysis,with significance assigned at the 5% level.
Results
The tumor diameters of 7~(th), 14~(th), 21~(st), 28~(th) day were 14.1mm, 27.7mm, 39.5mm and52.5mm. The values of BF, PEI, TTP and BV in 7~(th) day were 135.10±13.08ml/100g/min,73.11±5.25HU, TTP 18.57±1.38s and 45.0±2.53ml/100g, and which were 46.05±7.55ml/100g/min, 70.25±6.25HU, 35.90±1.90s and 51.63±4.77ml/100g in 28~(th) day respectively.The BF and TTP values of 7~(th) day and 14~(th) day have significant difference with those in 21~(st)day and 28~(th) day. The MVD counting of 7~(th), 14~(th), 21~(st), 28~(th) day were 36.5±2.12, 41.5±4.94,38.0±4.24, 46.5±2.12. BV (r=0.71, P=0.02)and PEI(r=0.68, P=0.06) were correlatedpositively with MVD, but BF (r=0.59, P＞0.05) and TTP (r=0.15, P＞0.05) did not.
Conclusion
MSCT perfusion was an accurate and relatively simple functional imaging techniqueto give a quantitative assessment of blood perfusion of soft-tissue tumors. Tumor BV andPEI correlate positively with MVD and may reflect the character and change ofmicro-vessel of tumor in different stages.
PARTⅡThe Relationship Among MSCT Perfusion Parameters,Angiogenesis And Hypoxia In The VX2 Tumor Model
Objective
To study the relationship of angiogenesis, hypoxia and MSCT perfusion parameters ofVX2 soft-tissue tumor in the rabbit model, and to analysis the influence by hypoxia,angiogenesis and blood flow during the process of tumor growth.
Materials and methods
8 rabbits were implanted with VX2 tumor tissue in proximal thighs. MSCT perfusionscan were performed on those rabbits with Mx8000 Quad CT in the 7,14,21,28 days afterimplant respectively. The 45s-perfusion CT examination was underwent and perfusionmaps were produced automatically. Blood flow(BF), peak enhancement index(PEI), time topeak(TTP) and blood volume(BV) were measured by the manually defined ROI withintumor. 2 rabbits were sacrificed every 7 days after CT perfusion, and the resectedspecimens were stained immunohistochemically to identified HIF-1αand VEGF forassessment of their stage. The perfusion parameters and stage of HIF-1αand VEGF wereanalyzed using Spearmen rank correlation, the distribution of HIF-1αand VEGF staginganalyzed usingχ~2 test, with significance assigned at the 5% level.
Results
The HIF-1αstaging of 7~(th), 14~(th), 21~(st), 28~(th) day increase gradually with time and thenfollowing decrease. The HIF-1αstaging of vary time have no significance difference(χ~2=1.49, P=0.22). There were no significance difference of VEGF staging(χ~2=0.27, P=0.60). There were no significant associations between HIF-1αand VEGF. Significantcorrelation were observed between BF with HIF-1α(r=0.87, P＜0.05), PEI and BV werecorrelated positively with VEGF(r=0.75, P=0.03; r=0.77, P=0.02). There were nosignificant associations between MVD and HIF-1αor VEGF.
Conclusion
HIF-1αis an important factor in the regulation of angiogenesis and tumor growth in VX2 soft-tissue tumor, up-regulating of VEGF is the major path in hypoxia modulation,other pathway exist too. Blood perfusion values correlate positively with HIF-1αandVEGF and they may reflect the regulation of hypoxia and micro-vessel partially in tumor. Ithave correlation among the blood perfusion, hypoxia and angiogenesis in VX2 tumor.
PARTⅢThe Correlation Between MSCT Perfusion Parametersand Tumor Angiogenesis in Nasopharyngeal Carcinoma
Objective
To explore the correlation of MSCT perfusion parameters and biologic character innasopharyngeal carcinoma (NPC), To investigate the clinical utility of MSCT perfusion fornasopharyngeal carcinoma.
Materials and methods
62 NPC patients were underwent MSCT perfusion imaging of nasopharynx withMx8000 Quad CT. The perfusion data of tumors and nasopharyngeal wall such as bloodflow(BF), peak enhancement index(PEI), time to peak(TTP) and blood volume (BV)weremeasured. MVD was counted by CD34 staining of biopsy tissues using Weidner's methodin 35 cases of NPC. The perfusion values in different stages were analyzed with ANOVAand means SNK. The correlation of MSCT perfusion parameters with MVD was analysedusing Pearson correlation analysis, perfusion parameters and MVD were correlated withMVD by Spearman rank correlation analysis, with significance assigned at the 5% level.
Results
In 35 cases of NPC, BF, PEI, TTP and BV of NPC lesion were 51.65±3.25ml/min/100g, 28.65±1.52HU, 30.68±2.01s, 12.49±1.07 ml/100g respectively, PEI andBV in NPC were correlated positively with its clinical stage(r=0.46, r=0.53, P＜0.05), BFand BV were correlated positively with T stage of NPC(r=0.37, r=0.42, P＜0.05), otherperfusion values have no correlation with T stage or N stage. The value of MVD in 35 casesNPC group was 41.29±14.79, which was correlated with BF, PEI, TTP and BV values ofMSCT perfusion. MVD was correlated positively with TNM stage of NPC, but have nocorrelation with T stage or N stage.
Conclusion
It had characteristic manifest in NPC perfusion image. NPC have highly perfusionthan normal tissue. The MSCT perfusion values can reflect the character of micro-vessel ofNPC and clinical stage. PEI and BV have positively correlation with angiogenesis and clinical stage of nasopharyngeal carcinoma.
PARTⅣThe Study of Correlation in MSCT Perfusion arametersand hypoxia, angiogenesis in Nasopharyngeal Carcinoma
Objective
To explore the correlation of MSCT perfusion parameters and hypoxia, angiogenesisin nasopharyngeal carcinoma (NPC), To investigate the value of clinical utility to predicthypoxia or angiogenesis by MSCT perfusion for nasopharyngeal carcinoma.
Materials and methods
35 NPC patients which have complete image and tissue specimens, were underwentMSCT perfusion imaging of nasopharynx with Mx8000 Quad CT. The perfusion data oftumors such as blood flow(BF)、peak enhancement index(PEI)、time to peak(TTP) andblood volume (BV)were calculated. The biopsy specimens were staining by HIF-1αandVEGF. The correlation of MSCT perfusion parameters, HIF-1α, VEGF and MVD wereanalysed using Spearman rank correlation analysis, the relationship in HIF-1α, VEGF andclinical stage were analyzed byχ~2 test, with significance assigned at the 5% level.
Results
Mean BF、PEI、TTP and BV of NPC lesion were 51.65±3.25 ml/min/100g,28.65±1.52HU, 30.68±2.01s, 12.49±1.07ml/100g respectively. In 35 cases of NPC,HIF-1αexpress positively in 27 cases(77.14%), HIF-1αexpress ranks had no correlationwith clinical stage of NPC(χ~2=2.91, P=0.08), but had correlations with BF (r=-0.54,P＜0.05) and BV(r=0.42, P=0.07). VEGF express positively in 31 cases(88.57%), VEGFexpression ranks had significant correlation with clinical stage of NPC(χ~2=4.10, P＜0.05),and its ranks had correlations with PEI of tumor perfusion(r=0.57, P＜0.05). Theexpression ranks of HIF-1αand VEGF had significant correlation(χ~2=9.70, P=0.01).HIF-1αand VEGF were correlated positively with MVD of NPC(r=0.62, r=0.78, P＜0.05).
Conclusion
It have highly positive express of HIF-1αand VEGF in NPC specimen, and their express rank have positive correlation. Though the express of HIF-1αhave no correlationwith clinical stage, it have positive correlation with BF, BV in MSCT perfusion and MVDof specimen. The VEGF express correlate positively with clinical stage, angiogenesis andPEI in MSCT perfusion. The BF, BV and PEI of MSCT perfusion can reflect partially thecharacter of angiogenesis and hypoxia of NPC. However, the regulation of hypoxia, bloodflow and microvessel angiogenesis in NPC still need to be explore further.
PARTⅤThe Study Of Relationship Of Radiation Therapy withMSCT Perfusion Parameters, Hypoxia and Angiogenesis InNasopharyngeal Carcinoma
Objective
To study the relationship of tumor regression with its MSCT perfusion parameters,hypoxia and angiogenesis in nasopharyngeal carcinoma (NPC), To evaluate the feasibilityof MSCT perfusion to predict radiosensitivity, hypoxia and angiogenesis fornasopharyngeal carcinoma.
Materials and methods
35 NPC patients, which have complete image and tissue specimen, were underwentMSCT perfusion examination of nasopharynx with Mx8000 Quad CT three times, whichwere before radiation therapy, within radiation therapy(34cGy～38cGy) and radiationtherapy ending respectively. The perfusion data of tumors such as blood flow(BF), peakenhancement index(PEI), time to peak(TTP) and blood volume (BV)were measured inperfusion maps. The tumor regression rate were calculated through the diameters of tumorbefore and after radiotherapy.35 cases of NPC was divided into radiosensitivity group andnon-radiosensitivity group. MSCT perfusion parameters and MVD of two group wereanalyzed by t-test. The express ranks were analyzed byχ~2 test. The perfusion data of NPCin different time were analyzed by ANOVA and mean SNK, with significance assigned atthe 5 % level.
Results
Mean tumor regression rate in 35 cases was 0.41±0.20 and 0.54±0.24 in processingand ending of radiotherapy respectively, tumor regression rate in radiosensitivity group was0.50±0.17 and 0.67±0.16,those in non-radiosensitivity group was 0.19±0.05 and 0.24±0.03,significant difference was exist in tumor regression rate in two group(t=5.66, t=8.11,P＜0.01). The preliminary BF value in radiosensitivity group was 57.04±18.39ml/100g/min,its PEI, TTP, BV values were 27.72±9.46 HU, 27.32±8.57s, 13.14±5.77ml/100grespectively. The preliminary BF value in non-radiosensitivity group was 38.20±14.62 ml/100g/min, its PEI, TTP, BV values were 24.00±7.49HU, 39.10±15.24, 10.89±7.64ml/100g respectively. The preliminary BF value and TTP value between two groups hadsignificant difference(F=8.23, F=8.48, P＜0.01), no significant difference exist in PEI andBV value. In radiosensitivity group, BF, PEI and BV values decreased, TTP value increasedwith radiotherapy, BF and PEI markly decreased within radiation therapy(34cGy～38cGy)(F=50.59, F=4.85, P＜0.01); but in non-radiosensitivity group, only BF value decreasedin the ending of radiation therapy(F=9.64, P＜0.01), the change of PEI、TTP and BV hadno significant difference. HIF-1αpositive express in two group were 76%(19/25)and80%(8/10), their distribution had significant difference(χ~2=6.00, P＜0.05), VEGF positiveexpress in two group were 92%(23/25) and 80%(8/10), their distribution had no significantdifference(χ~2=2.01, P=0.16), MVD in two group were 46.6±13.25 and 35.0±15.8, MVD intwo group had significant difference(F=4.90, P＜0.05).
Conclusion
There were positive correlation among radiosensitivity with blood perfusion,HIF-1αand MVD of NPC, but VEGF express did not. The high CT perfusion valuetumors were radiosensitivity, and had highly MVD value and lowly HIF-1αexpress;otherwise, lowly CT perfusion tumors had lowly MVD value and high HIF-1αexpress,they appeared to radiation resistance. BF and PEI values can be decreased significant after34-38cGy dose in the radiosensitivity NPC, in contrast, if CT perfusion values didn'tchange early with radiation therapy, those NPC may be nonradiosensitivity and poorlyprognosis. CT perfusion can reflect hypoxia and angiogenesis of NPC, and may predict theradiosensitivity of NPC by the perfusion parameters and their early changes withradiotherapy.
目的
研究VX2肿瘤生长过程中微血管生成情况，以及肿瘤微血管密度与MSCT灌注值之间的变化关系。
材料和方法
8只腿部肌肉种植VX2肿瘤的新西兰大白兔，分别于肿瘤生长第7、14、21、28天行MSCT灌注扫描，兔耳缘静脉注射碘对比剂(碘海醇300mgI／ml)6ml，流率0．6ml／s，注射同时行定层MSCT扫描，扫描条件4×5mm，旋转时间0．75s，间隔时间1．5s，持续时间至注射后45s，扫描图像输送入Function分析软件中，自动生成灌注图，手绘ROI区分别测量肿瘤及正常肌肉组织内血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标。于第7、14、21、28天行CT灌注扫描后分别处死瘤兔2只，取出肿瘤组织行免疫组化CD34单克隆抗体染色，进行微血管密度(Micro-vessel density，MVD)计数。不同时间段灌注值比较行方差分析SNK均数比较，各项MSCT各灌注指标与MVD计数之间行Pearson相关分析。P值小于0．05定为统计学显著性差异阈值。
结果
肿瘤生长大小分别为14．1±2．9mm、27．7±4．5mm、39．5±8．3mm、52．5±7．8mm，第7天MSCT灌注值BF为135．10±13．08ml／100g／min，其余灌注参数分别为PEI73．11±5．25HU，TTP18．57±1．38，BV45．0±2．53ml／100g，至第28天，相应灌注值为BF46．05±7．55ml／100g／min、PEI70．25±6．25HU、TTP35．90±1．90s、BV51．63±4．77ml／100g，第7、14天的CT灌注值与第21、28天灌注值中的BF和TTP存在显著性差异，四次灌注中的BV和PEI没有统计学显著性差异。第7、14、21、28天肿瘤标本MVD计数分别为36．5±2．12，41．5±4．94，38．0±4．24，46．5±2．12。CT灌注值中的BV与MVD存在相关性(r=0．71，P=0．02)，PEI与MVD存在弱相关(r=0．68，P=0．06)，BF、TTP与MVD之间没有显著性差异(r=0．59，r=0．15，P＞0．05)。
结论
VX2兔肿瘤模型中，随肿瘤生长，其灌注值BF在早期较高，随肿瘤生长灌注值BF下降，早期MSCT灌注值与肿瘤生长后期灌注值有明显差异。在肿瘤多层CT灌注成像的灌注值中BV值和PEI值与VX2肿瘤血管生成存在相关关系，MSCT灌注成像可以反映VX2肿瘤微血管生成特征，以及肿瘤在不同生长时期的微血管变化情况。
第二部分VX2肿瘤MSCT灌注值与缺氧状态、血管生成的关系
目的
研究VX2肿瘤乏氧状态与微血管生成情况的相互影响，探讨MSCT灌注值与VX2肿瘤乏氧状态、微血管生成之间的关系。
材料和方法
8只腿部肌肉种植VX2肿瘤的新西兰大白兔，分别于肿瘤生长第7、14、21、28天行MSCT灌注扫描，兔耳缘静脉注射碘对比剂(碘海醇300mgI／ml)6ml，流率0．6ml／s，注射同时行定层MSCT扫描，扫描条件4×5mm，旋转时间0．75s，间隔时间1．5s，持续时间至注射后45s，扫描图像于Function分析软件中，分别测量肿瘤及正常肌肉组织内血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标。于肿瘤种植后第7、14、21、28天行CT灌注扫描后分别处死瘤兔2只，肿瘤组织行HIF-1α、VEGF免疫组化染色，根据肿瘤细胞着色深度和阳性细胞百分比统计HIF-1α、VEGF表达等级。不同时间段HIF-1α、VEGF表达等级分布分别进行x~2检验，HIF-1α、VEGF表达等级之间行x~2检验，HIF-1α、VEGF与CT灌注值、MVD之间行Spearman等级相关分析。
结果
肿瘤第7、14、21、28天HIF-1α等级由低到高再降低，但其变化没有统计学显著性差异(x~2=1．49，P=0．22)，第7、14、21、28天VEGF分布无显著性差异x~2=0．27，P=0．60，HIF-1α、VEGF之间等级分布也没有显著性差异：不同时间段CT灌注BF值与HIF-1α表达存在相关性(r=0．87，P＜0．05)，不同时间段CT灌注值中PEI值和BV值与VEGF之间存在相关性(r=0．75，P=0．03；r=0．77，P=0．02)。MVD计数与HIF-1α和VEGF均没有明显相关关系。
结论
HIF-1α在VX2肿瘤血管生成调控和肿瘤生长中有着重要作用，VEGF的上调是肿瘤早期缺氧调控的重要途径，也存在其它途径参与。CT灌注值不仅与肿瘤内部微血管密度有关，部分灌注值能够反映肿瘤缺氧状态及其内部血管生成调节的过程，VX2肿瘤血流灌注与肿瘤缺氧状态和血管生成之间存在依存关系。
第三部分鼻咽癌MSCT灌注成像与其微血管生成关系的研究
目的
研究鼻咽癌MSCT灌注值与肿瘤微血管密度(MVD)、肿瘤分期的关系，探讨MSCT灌注成像对鼻咽癌微血管生成评价的价值。
材料和方法
经活检病理证实的鼻咽癌62例，静脉注射50ml对比剂后行CT灌注扫描，动态图像经function CT软件处理，自动生成灌注图像，手绘感兴趣区分别测量鼻咽癌肿瘤部位的血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标，其中35例鼻咽癌活检组织行免疫组化CD34单抗染色后，Weidner方法计数微血管密度(Micro-vessel density，MVD)。各组灌注值比较行方差分析及均数SNK比较，CT灌注值与MVD之间行Pearson相关分析，CT灌注值、MVD与肿瘤分期之间行Spearman等级相关分析，P值小于0．05定为统计学有显著性意义。
结果
35例鼻咽癌肿瘤CT灌注值BF为51．65±3．25ml／100g／min，其余各参数分别为PEI28．65±1．52HU，TTP30．68±2．01s，BV12．49±1．07ml／100g，PEI和BV与鼻咽癌分期相关(r=0．46，r=0．53，P＜0．05)，BF和BV与鼻咽癌独立T分期相关(r=0．37，r=0．42，P＜0．05)，其余指标与独立的T分期和N分期无明显相关性；35例鼻咽癌MVD为41．29±14．79，与BF、PEI、TTP、BV均存在相关性，MVD与肿瘤TNM分期存在相关性，但与独立的T分期和N分期无明显相关性。
结论
鼻咽癌具有特征的CT灌注表现，肿瘤灌注值明显高于周围组织，多层CT灌注成像的灌注值可以反映鼻咽癌微血管密度特征，灌注值高低与微血管密度存在相关关系，CT灌注中的PEI和BV值与肿瘤血管生成及鼻咽癌的TNM分期均存在一定的相关性。
第四部分鼻咽癌缺氧状态、血管生成和CT灌注之间的关系
目的
研究鼻咽癌缺氧状态、血管生成与CT灌注之间的关系，探讨多层CT灌注成像作为鼻咽癌缺氧状态及血管生成评估手段的可行性。
材料和方法
经活检病理证实的鼻咽癌62例中，具备完整资料的35例鼻咽癌活检标本行免疫组化HIF-1α和VEGF单抗染色，按阳性细胞着色程度和阳性细胞百分比评定HIF-1α和VEGF表达等级，35例患者均于放疗前一周内行CT灌注检查，静脉注射50ml对比剂后行CT灌注扫描，动态系列图像经function CT软件处理，自动生成各值灌注图像，手绘ROI区测量鼻咽癌肿瘤部位的血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标。CT灌注值、HIF-1α、VEGF、MVD之问行Spearman等级相关分析，HIF-1α和VEGF分级与肿瘤分期之间行双向有序行列表x~2检验。
结果
鼻咽癌肿瘤CT灌注值BF、PEI、TTP、BV分别为51．65±3．25ml／100g／min、28．65±1．52HU、30．68±2．01s、12．49±1．07ml／100g，35例鼻咽癌中HIF-1α阳性染色27例(77．14％)，其表达等级与肿瘤分期之间没有显著性差异(x~2=2．91，P=0．08)，与CT灌注中BF值存在负相关(r=-0．54，P＜0．05)，与BV值弱相关(r=0．42，P=0．07)；VEGF阳性表达31例(88．57％)，表达等级与肿瘤分期之间有显著性差异(x~2=4．10，P=0．04)，VEGF与CT灌注中PEI值存在相关性(r=0．57，P＜0．05)。HIF-1α和VEGF表达等级之间有显著关系(x~2=9．70，P＜0．05)，HIF-1α和VEGF与MVD之间均存在相关关系(r=0．62，r=0．78 P＜0．05)。
结论
鼻咽癌HIF-1α和VEGF阳性表达率较高，而且两者表达存在依从关系，HIF-1α表达虽然与肿瘤分期没有显著性关系，但HIF-1α与肿瘤灌注值BF及BV之间、及MVD之间存在相关性；VEGF与肿瘤分期和肿瘤微血管生成均存在联系，并与CT灌注中的PEI存在相关，CT灌注成像中BF、BV、PEI能够部分反映鼻咽癌的乏氧状态和血管生成的部分特征，对于HIF-1α和VEGF的血管调控尚待进一步研究。
第五部分鼻咽癌MSCT灌注、血管生成及缺氧状态与放疗的关系
目的
研究鼻咽癌MSCT灌注、缺氧状态及血管生成与肿瘤放疗后短期肿瘤消退的关系，评价MSCT灌注通过缺氧状态及血管生成评估鼻咽癌放疗敏感性的可行性。
材料和方法
从62例鼻咽癌中，选取临床病理及影像资料完整的鼻咽癌35例，35例鼻咽癌活检标本行免疫组化HIF-1α和VEGF单抗染色，按阳性细胞着色程度和阳性细胞百分比评定HIF-1α和VEGF表达等级。35例患者均于放疗前、放疗中(34cGy～38cGy)、放疗结束后行MSCT灌注检查，静脉注射50ml对比剂后行CT灌注扫描，动态图像经function CT软件处理，自动生成灌注图像，并测量每次鼻咽癌肿瘤部位的血流量(BF)、最大强化指数(PEI)、峰值到达时间(TTP)及血容量(BV)作为灌注指标。测量肿瘤长径计算每例鼻咽癌放疗中、放疗结束时的肿瘤消退率，并按照肿瘤消退率将35例鼻咽癌分为放疗敏感组(Gs)和放疗不敏感组(Gns)，对两组的CT灌注值、MVD分别进行组间t检验，两组HIF-1α和VEGF表达等级行x~2检验。对两组放疗前后BF、PEI、TTP和BV值分别进行方差分析和SNK均数比较，了解放疗前后灌注值变化情况。
结果
35例鼻咽癌放疗中及放疗结束后总体肿瘤消退率为0．41±0．20和0．54±0．24，消退在0．11-1．0之间，放疗中及放疗结束后消退率的比较两次复查消退率并无显著性差异，其中敏感组消退率为0．50±0．17和0．67±0．16，不敏感组消退率为0．19±0．05和0．24±0．03，两组间消退率比较存在显著性差异(t=5．66，t=8．11，P＜0．01)，敏感组(Gs)初始CT灌注值BF为57．04±18．39ml／100g／min，其余各参数分别为PEI27．72±9．46HU，TTP27．32±8．57s，BV13．14±5．77ml／100g；不敏感组初始灌注值分别为BF38．20±14．62ml／100g／min，PEI24．00±7．49HU，TTP 39．10±15．24s，BV10．89±7．64ml／100g，两组间初始BF值、TTP值之间有显著性差异(F=8．23，F=8．48，P＜0．01)，但两组之间的PEI和BV没有显著性差异。比较两组放疗前后灌注值的比较发现，敏感组放疗后BF、PEI和BV均有下降，TTP上升，均具有统计学差异，其中BF值和PEI值在放疗中即有明显下降(F=50．59，F=4．85，P＜0．01)；而在不敏感组，仅有BF值在放疗后下降(F=9．64，P＜0．01)，PEI、TTP和BV改变均无显著性差异。敏感组及不敏感组HIF-1α表达阳性率分别为76％(19／25)和80％(8／10)，其等级分布在两组中有显著性差异(x~2=6．00，P＜0．05)，VEGF表达阳性率分别为92％(23／25)和80％(8／10)，其等级分布在两组中没有显著性差异(x~2=2．01，P=0．16)。敏感组及不敏感组MVD分别为46．6±13．25和35．0±15．8，两组间MVD比较具有显著性差异(F=4．90，P＜0．05)。
结论
鼻咽癌放疗敏感性与CT灌注值、HIF-1α表达等级、MVD之间有着明显的相关性，与VEGF表达等级无明显相关，CT灌注中高灌注的肿瘤，HIF-1α表达等级低，MVD高，对放疗敏感性高，反之CT灌注低的肿瘤，MVD低，HIF-1α表达等级高，对放疗有一定的抵抗。对放疗敏感的鼻咽癌在放疗中即可发现BF及PEI值明显下降，放疗后灌注值改变不明显的鼻咽癌常提示肿瘤消退不满意，对放疗不敏感。CT灌注成像能够部分反映鼻咽癌的乏氧状态和血管生成，可通过CT灌注值高低和放疗中灌注值的变化对鼻咽癌放疗敏感性作出评估。
PARTⅠThe Correlation Of MSCT Perfusion Parameters WithAngiogenesis In VX2 Tumor
Objective
To study angiogenesis of VX2 soft-tissue tumor in the rabbit, and analysis thecorrelation of MSCT perfusion parameters and micro-vessel density(MVD) during theprocess of tumor growth.
Materials and methods
8 rabbits were implanted with VX2 tumor tissue in proximal thighs. MSCT perfusionscan were performed on those rabbits with Mx8000 Quad CT in the 7,14,21,28 days afterimplant respectively. The functional maps were produced automatically and perfusionparameters including blood flow(BF), peak enhancement index(PEI), time to peak(TTP)and blood volume(BV) were calculated by the workstation. The perfusion values weremeasured by the manually defined ROI within tumor. 2 rabbits were sacrificed every 7 daysafter CT perfusion, and the resected specimens were staining by CD34 for quantification ofMVD. The perfusion parameters and MVD of different phase were analyzed by ANOVA;MSCT perfusion parameters were correlated with MVD by Pearson correlation analysis,with significance assigned at the 5% level.
Results
The tumor diameters of 7~(th), 14~(th), 21~(st), 28~(th) day were 14.1mm, 27.7mm, 39.5mm and52.5mm. The values of BF, PEI, TTP and BV in 7~(th) day were 135.10±13.08ml/100g/min,73.11±5.25HU, TTP 18.57±1.38s and 45.0±2.53ml/100g, and which were 46.05±7.55ml/100g/min, 70.25±6.25HU, 35.90±1.90s and 51.63±4.77ml/100g in 28~(th) day respectively.The BF and TTP values of 7~(th) day and 14~(th) day have significant difference with those in 21~(st)day and 28~(th) day. The MVD counting of 7~(th), 14~(th), 21~(st), 28~(th) day were 36.5±2.12, 41.5±4.94,38.0±4.24, 46.5±2.12. BV (r=0.71, P=0.02)and PEI(r=0.68, P=0.06) were correlatedpositively with MVD, but BF (r=0.59, P＞0.05) and TTP (r=0.15, P＞0.05) did not.
Conclusion
MSCT perfusion was an accurate and relatively simple functional imaging techniqueto give a quantitative assessment of blood perfusion of soft-tissue tumors. Tumor BV andPEI correlate positively with MVD and may reflect the character and change ofmicro-vessel of tumor in different stages.
PARTⅡThe Relationship Among MSCT Perfusion Parameters,Angiogenesis And Hypoxia In The VX2 Tumor Model
Objective
To study the relationship of angiogenesis, hypoxia and MSCT perfusion parameters ofVX2 soft-tissue tumor in the rabbit model, and to analysis the influence by hypoxia,angiogenesis and blood flow during the process of tumor growth.
Materials and methods
8 rabbits were implanted with VX2 tumor tissue in proximal thighs. MSCT perfusionscan were performed on those rabbits with Mx8000 Quad CT in the 7,14,21,28 days afterimplant respectively. The 45s-perfusion CT examination was underwent and perfusionmaps were produced automatically. Blood flow(BF), peak enhancement index(PEI), time topeak(TTP) and blood volume(BV) were measured by the manually defined ROI withintumor. 2 rabbits were sacrificed every 7 days after CT perfusion, and the resectedspecimens were stained immunohistochemically to identified HIF-1αand VEGF forassessment of their stage. The perfusion parameters and stage of HIF-1αand VEGF wereanalyzed using Spearmen rank correlation, the distribution of HIF-1αand VEGF staginganalyzed usingχ~2 test, with significance assigned at the 5% level.
Results
The HIF-1αstaging of 7~(th), 14~(th), 21~(st), 28~(th) day increase gradually with time and thenfollowing decrease. The HIF-1αstaging of vary time have no significance difference(χ~2=1.49, P=0.22). There were no significance difference of VEGF staging(χ~2=0.27, P=0.60). There were no significant associations between HIF-1αand VEGF. Significantcorrelation were observed between BF with HIF-1α(r=0.87, P＜0.05), PEI and BV werecorrelated positively with VEGF(r=0.75, P=0.03; r=0.77, P=0.02). There were nosignificant associations between MVD and HIF-1αor VEGF.
Conclusion
HIF-1αis an important factor in the regulation of angiogenesis and tumor growth in VX2 soft-tissue tumor, up-regulating of VEGF is the major path in hypoxia modulation,other pathway exist too. Blood perfusion values correlate positively with HIF-1αandVEGF and they may reflect the regulation of hypoxia and micro-vessel partially in tumor. Ithave correlation among the blood perfusion, hypoxia and angiogenesis in VX2 tumor.
PARTⅢThe Correlation Between MSCT Perfusion Parametersand Tumor Angiogenesis in Nasopharyngeal Carcinoma
Objective
To explore the correlation of MSCT perfusion parameters and biologic character innasopharyngeal carcinoma (NPC), To investigate the clinical utility of MSCT perfusion fornasopharyngeal carcinoma.
Materials and methods
62 NPC patients were underwent MSCT perfusion imaging of nasopharynx withMx8000 Quad CT. The perfusion data of tumors and nasopharyngeal wall such as bloodflow(BF), peak enhancement index(PEI), time to peak(TTP) and blood volume (BV)weremeasured. MVD was counted by CD34 staining of biopsy tissues using Weidner's methodin 35 cases of NPC. The perfusion values in different stages were analyzed with ANOVAand means SNK. The correlation of MSCT perfusion parameters with MVD was analysedusing Pearson correlation analysis, perfusion parameters and MVD were correlated withMVD by Spearman rank correlation analysis, with significance assigned at the 5% level.
Results
In 35 cases of NPC, BF, PEI, TTP and BV of NPC lesion were 51.65±3.25ml/min/100g, 28.65±1.52HU, 30.68±2.01s, 12.49±1.07 ml/100g respectively, PEI andBV in NPC were correlated positively with its clinical stage(r=0.46, r=0.53, P＜0.05), BFand BV were correlated positively with T stage of NPC(r=0.37, r=0.42, P＜0.05), otherperfusion values have no correlation with T stage or N stage. The value of MVD in 35 casesNPC group was 41.29±14.79, which was correlated with BF, PEI, TTP and BV values ofMSCT perfusion. MVD was correlated positively with TNM stage of NPC, but have nocorrelation with T stage or N stage.
Conclusion
It had characteristic manifest in NPC perfusion image. NPC have highly perfusionthan normal tissue. The MSCT perfusion values can reflect the character of micro-vessel ofNPC and clinical stage. PEI and BV have positively correlation with angiogenesis and clinical stage of nasopharyngeal carcinoma.
PARTⅣThe Study of Correlation in MSCT Perfusion arametersand hypoxia, angiogenesis in Nasopharyngeal Carcinoma
Objective
To explore the correlation of MSCT perfusion parameters and hypoxia, angiogenesisin nasopharyngeal carcinoma (NPC), To investigate the value of clinical utility to predicthypoxia or angiogenesis by MSCT perfusion for nasopharyngeal carcinoma.
Materials and methods
35 NPC patients which have complete image and tissue specimens, were underwentMSCT perfusion imaging of nasopharynx with Mx8000 Quad CT. The perfusion data oftumors such as blood flow(BF)、peak enhancement index(PEI)、time to peak(TTP) andblood volume (BV)were calculated. The biopsy specimens were staining by HIF-1αandVEGF. The correlation of MSCT perfusion parameters, HIF-1α, VEGF and MVD wereanalysed using Spearman rank correlation analysis, the relationship in HIF-1α, VEGF andclinical stage were analyzed byχ~2 test, with significance assigned at the 5% level.
Results
Mean BF、PEI、TTP and BV of NPC lesion were 51.65±3.25 ml/min/100g,28.65±1.52HU, 30.68±2.01s, 12.49±1.07ml/100g respectively. In 35 cases of NPC,HIF-1αexpress positively in 27 cases(77.14%), HIF-1αexpress ranks had no correlationwith clinical stage of NPC(χ~2=2.91, P=0.08), but had correlations with BF (r=-0.54,P＜0.05) and BV(r=0.42, P=0.07). VEGF express positively in 31 cases(88.57%), VEGFexpression ranks had significant correlation with clinical stage of NPC(χ~2=4.10, P＜0.05),and its ranks had correlations with PEI of tumor perfusion(r=0.57, P＜0.05). Theexpression ranks of HIF-1αand VEGF had significant correlation(χ~2=9.70, P=0.01).HIF-1αand VEGF were correlated positively with MVD of NPC(r=0.62, r=0.78, P＜0.05).
Conclusion
It have highly positive express of HIF-1αand VEGF in NPC specimen, and their express rank have positive correlation. Though the express of HIF-1αhave no correlationwith clinical stage, it have positive correlation with BF, BV in MSCT perfusion and MVDof specimen. The VEGF express correlate positively with clinical stage, angiogenesis andPEI in MSCT perfusion. The BF, BV and PEI of MSCT perfusion can reflect partially thecharacter of angiogenesis and hypoxia of NPC. However, the regulation of hypoxia, bloodflow and microvessel angiogenesis in NPC still need to be explore further.
PARTⅤThe Study Of Relationship Of Radiation Therapy withMSCT Perfusion Parameters, Hypoxia and Angiogenesis InNasopharyngeal Carcinoma
Objective
To study the relationship of tumor regression with its MSCT perfusion parameters,hypoxia and angiogenesis in nasopharyngeal carcinoma (NPC), To evaluate the feasibilityof MSCT perfusion to predict radiosensitivity, hypoxia and angiogenesis fornasopharyngeal carcinoma.
Materials and methods
35 NPC patients, which have complete image and tissue specimen, were underwentMSCT perfusion examination of nasopharynx with Mx8000 Quad CT three times, whichwere before radiation therapy, within radiation therapy(34cGy～38cGy) and radiationtherapy ending respectively. The perfusion data of tumors such as blood flow(BF), peakenhancement index(PEI), time to peak(TTP) and blood volume (BV)were measured inperfusion maps. The tumor regression rate were calculated through the diameters of tumorbefore and after radiotherapy.35 cases of NPC was divided into radiosensitivity group andnon-radiosensitivity group. MSCT perfusion parameters and MVD of two group wereanalyzed by t-test. The express ranks were analyzed byχ~2 test. The perfusion data of NPCin different time were analyzed by ANOVA and mean SNK, with significance assigned atthe 5 % level.
Results
Mean tumor regression rate in 35 cases was 0.41±0.20 and 0.54±0.24 in processingand ending of radiotherapy respectively, tumor regression rate in radiosensitivity group was0.50±0.17 and 0.67±0.16,those in non-radiosensitivity group was 0.19±0.05 and 0.24±0.03,significant difference was exist in tumor regression rate in two group(t=5.66, t=8.11,P＜0.01). The preliminary BF value in radiosensitivity group was 57.04±18.39ml/100g/min,its PEI, TTP, BV values were 27.72±9.46 HU, 27.32±8.57s, 13.14±5.77ml/100grespectively. The preliminary BF value in non-radiosensitivity group was 38.20±14.62 ml/100g/min, its PEI, TTP, BV values were 24.00±7.49HU, 39.10±15.24, 10.89±7.64ml/100g respectively. The preliminary BF value and TTP value between two groups hadsignificant difference(F=8.23, F=8.48, P＜0.01), no significant difference exist in PEI andBV value. In radiosensitivity group, BF, PEI and BV values decreased, TTP value increasedwith radiotherapy, BF and PEI markly decreased within radiation therapy(34cGy～38cGy)(F=50.59, F=4.85, P＜0.01); but in non-radiosensitivity group, only BF value decreasedin the ending of radiation therapy(F=9.64, P＜0.01), the change of PEI、TTP and BV hadno significant difference. HIF-1αpositive express in two group were 76%(19/25)and80%(8/10), their distribution had significant difference(χ~2=6.00, P＜0.05), VEGF positiveexpress in two group were 92%(23/25) and 80%(8/10), their distribution had no significantdifference(χ~2=2.01, P=0.16), MVD in two group were 46.6±13.25 and 35.0±15.8, MVD intwo group had significant difference(F=4.90, P＜0.05).
Conclusion
There were positive correlation among radiosensitivity with blood perfusion,HIF-1αand MVD of NPC, but VEGF express did not. The high CT perfusion valuetumors were radiosensitivity, and had highly MVD value and lowly HIF-1αexpress;otherwise, lowly CT perfusion tumors had lowly MVD value and high HIF-1αexpress,they appeared to radiation resistance. BF and PEI values can be decreased significant after34-38cGy dose in the radiosensitivity NPC, in contrast, if CT perfusion values didn'tchange early with radiation therapy, those NPC may be nonradiosensitivity and poorlyprognosis. CT perfusion can reflect hypoxia and angiogenesis of NPC, and may predict theradiosensitivity of NPC by the perfusion parameters and their early changes withradiotherapy.
引文
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