Study Of Correlation Of MSCT Perfusion, Tumor Angiogenesis And Hypoxia In Nasopharyngeal Carcinoma

PARTâ… The Correlation Of MSCT Perfusion Parameters WithAngiogenesis In VX2 TumorObjectiveTo 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 methods8 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.ResultsThe 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^stday 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. ConclusionMSCT 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. PARTâ…¡The Relationship Among MSCT Perfusion Parameters,Angiogenesis And Hypoxia In The VX2 Tumor ModelObjectiveTo 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 methods8 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 usingχ² test, with significance assigned at the 5% level.ResultsThe 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(χ²=1.49, P=0.22). There were no significance difference of VEGF staging(χ²=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.ConclusionHIF-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. PARTâ…¢The Correlation Between MSCT Perfusion Parametersand Tumor Angiogenesis in Nasopharyngeal CarcinomaObjectiveTo 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 methods62 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.ResultsIn 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.ConclusionIt 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. PARTâ…£The Study of Correlation in MSCT Perfusion arametersand hypoxia, angiogenesis in Nasopharyngeal CarcinomaObjectiveTo 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 methods35 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 byχ² test, with significance assigned at the 5% level.ResultsMean 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(χ²=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(χ²=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(χ²=9.70, P=0.01).HIF-1αand VEGF were correlated positively with MVD of NPC(r=0.62, r=0.78, P＜0.05).ConclusionIt 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. PARTâ…¤The Study Of Relationship Of Radiation Therapy withMSCT Perfusion Parameters, Hypoxia and Angiogenesis InNasopharyngeal CarcinomaObjectiveTo 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 methods35 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 byχ² test. The perfusion data of NPCin different time were analyzed by ANOVA and mean SNK, with significance assigned atthe 5 % level.ResultsMean 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(χ²=6.00, P＜0.05), VEGF positiveexpress in two group were 92%(23/25) and 80%(8/10), their distribution had no significantdifference(χ²=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).ConclusionThere 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.