| Objective:1Analyze the time density curve （TDC） and perfusion parameterscharacteristics of rabbit VX2liver cancer model underwent the spectrum CTperfusion scan.2Analyze the monochromatic feactures,the attenuation characteristic ofspectrum curve and the iodine content after ungoiong the spectrum CT scan.3Analyze the changes in perfusion parametes and iodine content after thetreatment of endostatin of the rabbit VX2liver cancer model.4The expression of FGF2protein was detected by West-blot. And analyze thecorrelation between CT perfusion parameters and nomal iodine content (NIC).Materials and Methods:Fifty-two healthy New Zealand white rabbits, weighted2.6～2.9Kg,provided bythe experimental Ainmal Center of Henan Province. The experiment got thepermission by Zhengzhou University Ethics Committee.The rabbit VX2liver cancermodels established by planting fresh tumor tissue blocks through opening surgery. 1The protocol of anti-angiogenesis therapy1died in establishing model bacase of anesthetic accident,1model no tumorafter7and14days,2models underwent pathological examination HE stainingsecected from48succed rabbit VX2models. The46rabbits with VX2liver tumorwere randomly divided into the control group (A)and the trial group(B).From the14days after tumor transplantation group A injected saline and group B injectedendostain,at the same dose of0.3mg/kg, continuing for7days.2CT scanThe rabbits were perfomed by GE Discovery CT750HD on the7th、14thand21th（the7thafter treatment）.CT perfusion scan and spectrum scan were perfomed.The reconstructed image data were transmitted to the image processin workstation foranalyzing.①erfusion imaging were analyzed by CT perfusion functional analysis software:The aorta was selected as input artery and potal vein as input vein.The tumorarea were selecte as the first ROI and the liver parenchyma without tumor as thesecond ROI. TDC cuvres were obtained. The perfusion parameters were generatedautomaticly: blood flow BF (ml/min/100mg), blood volume BV (ml/100mg), meantransit time MTT (s), permeability of the capillary vessel surface PS (ml/min/100mg)and hepatic arterial fraction HAF. And the corresponding pseudo-color images wereobtained at the same time.②The spectral image were analyzed by GSI software: The routine CT scanimages,conventional polychromatic images(QC) at arterial phase and thereconstructed monochromatic images(Mono) were obtained. The contrast-to-noiseratio (CNR), the image noise and the lesion conspicuity scores (LCS) and the overallimage quality scores (OQS) were compared with the40keV group, optimal CNR keVgroup and the QC group. The characteristics of the spectrum curve with the tumorand the area without tumor were analyzed. The iodine content of the tumor, areawithout tumor, the abdominal aorta was measured in the iodine map. The normalizediondine concentrations (NIC) were caluculated.And compred the NIC befor and aftertreatement.3Correlational analysis of perfusion parametes and NIC with the molecular biology.The tumor tissue and the tissue without tumor were obtained wth CT guidedbiopsy punctue aftet each CT scan. The tissues were stored in liquid nitrogen in-196°.The expression of FGF2protein was detected by western-blot, with the procedure:protein preparation'SDS-PAGE'transmembrane'closed'primary antibodieshybridization'second antibodies hybridization'colored reaction.Measurd theFGF1protein expressin and analysis the correlation of CT perfusion parameters andNIC with FGF1protein.Results:1The CT manifestations and general pathologic results of the rabbit VX2livercancer model①The left lobe was larger than the right lobe of the normal rabbit liver. The liverwas showed a slight enhancement in arterial phase and the degree of enhancementwas strengthened in portal venous phase. General observation: The nomal liver waslocated in the front of the abdominal cavity.The liver was divied into four parts,thetwo lobes located in the left were larger than the right.Middle lobe was located thenarrow area between the left and right lobe.There were cauduate lobe and the mastoidantrum in the front of central lobe.The fresh rabbit liver may look like reddishbrown,weighted85～130g.Under the microscope,the liver cells arranged in neat,nuclei were quite regulat in shape,uniform in size. The structure of rabbit’s liverlobule and liver sinusoid were obvious.②Rabbit VX2liver cancer model: CT scan showed a round lowdensity,enhanced scan showed ring enhancement in the arterial phase, the anuularwall was thick.The tumor was showed relatively low density in portal venousphase.The central liquefaction nerosis was enlarged with the tumor growth. Generalobservation: The tumors were round, offwhite,complete capsule,with liquefactionnecrosis in the center section.Under low magnification,tumor cells were distributedlike nest with many new capillaries in the tumor interstitium.Under highmagnification,the size of the tumor cells increased with irregular shape,variancesizes.The nuclei were irregular and hyperchromatic.Unnomal goblet cells were seen.2The CT perfusion results of rabbit VX2liver cancer model ①BF, BV, PS, HAF of the tumor area were above the area without tumor, thetumor region MTT were far below the area without tumor liver tissue. Statisticalanalyzes were performed statistically significant (p <0.05).②from7thto14th,with tumor growth,CT parameters BF, BV, HAF of tumortissue showed an increasing trend, MTT, PS showed a decreased trend, which, thedifference of BF, MTT, PS was statistically significant (p <0.05), while the differenceof BV, HAF was not statistically significant (p>0.05).The liver tissues without tumorfrom7thto14th, CT parameters of perfusion of the tumor were not statisticallysignificant (p>0.05).③After endostatin Endostar treatment, the treatment group BF, BV, PS, HAFwere lower than the control group, MTT higher than the contol group, BF wasstatistically significant (P <0.05), the remaining parameter were not statisticallysignificant (p>0.05).④There wascorrelation between BF and FGF2protein,r=0.932and the otherparameters has no correlation with FGF2protein,through correlation analysis.3The spectral CT results①Image evaluation of three groups:OP group CNR(2.63±1.59) lower than40keV(2.81±1.74),with no obvious statistically significant.Higher than the QC group(1.95±1.55)with statistically significant (p <0.05);d40keV group and QC groups wasstatistically significant (p <0.05). Image noise,OP group(7.89±1.35) lower than40keV group (9.12±1.28) and higher than the QC group (6.67±1.36) withstatistically significant (p <0.05). LCS: OP group (3.86±0.68) and40keV group(3.77±0.57) had no obvious statistically significant (p>0.05), both the two groupswere higher than the QC group (3.29±0.49) whit statistical significance (p <0.05).The overall quality score (OQS):OP group (3.85±0.58) higher than40keV group(3.10±0.25) and QC group (3.38±0.55).The differences were statisticallysignificant (p <0.05).②Specrtal curve analysis:Calculate the slope of the curve with the formulaas:Kx=(HU40keV-HUXkeV)/(X-40), Kx corresponding slope, HU40keVon behalf ofthe CT values of40keV, HUXkeVrepresented different CT values of each singleenergy points.The slope was greater of tumor tissue than the distance liver tissue without tumor, with statistically significant (p <0.05).③The NIC of the tumor tissue both on the7thand the14thwere higher than theliver tissue without tumor, with statistically significant (p <0.05).After the endostatinEndostar treatment,the NIC of the trail group were less than the control group, withstatistically significant (p <0.05).And there was correlation between NIC and FGF2protein,r=0.975.Conclusions:1The method of laparotomic route for establishing rabbit VX2liver cancermodel had the advatages of ideal tumor growth rate within a short time,and the tumorwere formal with low transfer rate.The pathological and biological behavior of rabbitVX2liver tumor model were similar to HCC.So the model can be widely used forbasic imaging and hemodynamics studies.2CT perfusion and spectral scan, the dynamics of the liver tumors can beprovided by CT perfusion parameters and NIC, which can reflec the tumor’sdynamics.3FGF2protein was higher expression in tumor tissue,which can reflect thetumor blood supply.In clinical, FGF1can provide the blood supply information of thetumor,which can provide anothet indicator for observing tumor formation andtreatment effect.4The endostain Endosar showed obvious antiangiogenic effects, CT perfusionand spectrum scan can bu used to evaluate the tumor angiogenesis and the effect ofthe anti-angiogenesis therapy. The noninvasive technique was worthy of further usingin clinical for the diagnosis and curative effec of primary hepatocellular carcinoma. |
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