The Induced Rat Hepatocarcinoma Evolution DSCT Whole-liver Perfusion Study

[Objective]two aspects are involved in the study.First,optimize the dual-source CT rats’ scan parameters through the study of scan parameters, the dose of contrast agent and the flow rate of injection, providing right conditions for the liver CTPI.Second,with the help of the study of induced liver cancer in rats, investigate liver fibrosis in different periods, early cirrhosis,hepatocellular nodules and liver hemodynamic’s changes in pathological conditions, as well as the variation of the perfusion parameters, providing basis for the diagnosis of lesions of CTPI in different stages.[Material and methods]Part112clean and healthy male SD rats were selected and scan them with dual-source CT when intraperitoneal anesthesia was committed.Plain scan:set the current to300mAs,keep other condition unchanged,and change the tube voltage for120、100、80、70KV,then scan the same rat,when done,evaluate the image’s mean CT value, noise, SNR,CNR and image quality score. Perfusion scan:the liver with plain scan, the whole liver perfusion scan with the Body VPCT plan, dilute the contrast agent-Iopromide injection of370mg/ml by three times,then conduct tail vein injection with high-pressure syringe when scanning.Using different dose of contrast agent (1ml、2ml) and injection flow rate(0.1ml/s,0.2ml/s,0.3ml/s,0.4ml/s),every two be combined, perfusion imaging is conducted to each rat for8times under different conditions,the interval of which should be more than24h, other perfusion parameters remaining the same.After importing the original date to the workstation through the PACS,open the perfusion software of VPCT Body,enter the perfusion data,then sketch the region of interest through Motion correction、 segmentation、 Vessels、 Liver Rols, finally, ALP, PVP, HPI, and every other region of interest was generated automatically.Part2Select160clean and healthy male SD rats,and divide them into two groups randomly.As the experiment group, group A has130rats, group B30,as a comparison.Then continue to divide the rats with the standard of pathological results:Liver fibrosis,named group A1, Early cirrhosis, named group A2, liver cancer,named group A3,Hepatocyte nodules,named group A4.To the experiment group,the rats were gavaged with0.2%DEN with the standard of0.2ml/mg, once a week, for the rest time, they drink0.02%DEN on their own. The same method is adopted to the comparison group,what different was that pure water was used for gavaging and drinking.8weeks later.stop the gavage and the experiment group changed to pure water for drinking.From the8th week on,change the rats amount of experiment group to5,the comparison group2,then do plain scan and whole liver perfusion scan to them.Set the main scan parameters as follows:tube voltage70KV, tube current300mAs, scan time3.91s, delay5s,rotation time0.5s,slice3.Omm, SAFIRE3reconstruction,FOV80mm.Contrast agent1ml (Iopromide injection of370mg/ml),flow rate of injection0.2ml/s.Open the perfusion software of VPCT Body in MMWP workstation,process and analyse blood volume,blood volume,arterial liver perfusion,portal venous perfusion,hepatic perfusion index and so on.According to the maximum slope method,produce the perfusion pseudo-color,and observe the situation of the liver perfusion.[Results]Part11、 A total of10SD rats were scanned by plain CT and perfusion,but two SD rats were anesthetized death,then the average CT value, noise, SNR, CNR and graphics quality rating of each image were measured under different kV.The liver perfusion parameters were measured successfully under different contrast dose and injection flow rate.2、 The tube current was fixed to300mAs,with the decline of kV CT value had no significant difference,but image SD gradually rosed; SNR decreased by degrees,CNR side was mildly elevated,which was contrary to conventional understanding.3、 We got low ALP and PVP when the contrast dose was lml and injection flow rate was0.1ml/s;when flow rate increased to0.2ml/s, the ALP and PVP showed a upward trend; when flow rate increased from0.2ml/s to0.4ml/S PVP increased slightly, there is no statistically significant difference. When the ratio of dose was2ml,as the flow rate increased,ALP did not change much.While PVP first increased with the increase of velocity, and peaked at flow rate of0.3mL/s,then began to decline at0.4ml/s.Part21、 The experimental group SD rats130,31died of revulsant toxicity before CT scan (7swallowed by the similar),2died of straying into the trachea when gavage.Only3were scanned by pain CT due to the rat tail artery puncture failure, success of CT plain and the whole liver perfusion94.2、 Pathological detection:liver fibrosis31(S1-7, S2-7, S3-9, S4-8); early cirrhosis28; nodules of liver cells11, including RN-8,DN-2; HCC57(including cholangiocarcinoma-3and mixed cancer-2in52HCC). Others:four animals had bloody ascites,three had double lung metastasis,2had liver and lung abscess,3had abdominal wall hernia. The detection of CT perfusion to hepatocyte nodules and hepatocellular carcinoma:CT perfusion94, all were found perfusion abnormalities.Diagnosis of retrospective analysis combined with the change of pathological findings and perfusion parameters:liver fibrosis31(S1-7, S2-7, S3-9,S4-8); early cirrhosis28.65lesions were found in35,nodules of liver cells10, HCC-55(the missed one hepatocyte nodules and two HCC were the size of sesame seeds under pathologic examination and naked eye view, close to the blood vessels and not found by CT perfusion). Others:four animals with bloody ascites, three with double lung metastasis, two with liver and lung abscess, three with abdominal wall hernia.3、 Comparison of each stage of liver fibrosis and each perfusion parameter of control group:there were no statistical difference of the ALP in each stage of liver fibrosis(p>0.05); there was statistical difference between PVP and control group,(p<0.05), the totality showed a downward trend; there were statistical difference between each group of TLP (total liver perfusion)(p<0.05), the totality showed a downward trend. Pairwise comparison shows:there was no significant difference of each perfusion parameter between mild liver fibrosis group and control group (p>0.05); the comparison of each perfusion parameter of moderate to severe liver fibrosis group and control group were statistically different except BV (p<0.05); each perfusion parameter of moderate to severe liver fibrosis except BV was significantly different (p <0.05)4、Comparison of each perfusion parameter of cirrhosis group and control group:BF, BV,PVP, TLP of the cirrhosis group totality shows a downward trend; ALP, HPI, MTT, a upward trend.5、 Each perfusion parameter of liver cancer group and control group comparison: there were statistically significant difference between each parameter of the experimental group and control group(p<0.05). Further pairwise comparison:each parameter of control group and the experimental group has difference, especially the liver tissue of the control group and the distant liver tissue of experimental group (P <0.05) Each perfusion parameter of lesion center and distant liver tissue, the edge of lesion and distant liver tissue had significant difference (p<0.05); ALP and TLP of the lesion center and edge had no significant difference, but PVP was opposite (p<0.05), so was HPI (p<0.05)6、 The comparison of group liver cancer, group hepatocellular nodules and group control:each perfusion parameter of control group and experimental group was statistically different(p<0.05).Farther pairwise comparison:parameters of liver parenchymas in control group and different positions of the experimental group were statistically different (p<0.05); each perfusion parameter of RN and DN, R.N and HCC, DN and HCC was statistically different (p<0.05).Through RN-DN-HCC we can see a gradually upward trend in BF, BV, ALP, TLP, HPI, MTT and gradually declining trend in PVP.Similar with DN, HCC had higher perfusion value,that is, HPI and MTT rose significantly,ALP increased and PVP decreased significantly. Thus increase radians of ALP,MTT and HPI may be valuable perfusion parameters to differentiate benign and malignant liver nodules. [Conclusions]Part11、 The optimization of tube current and tube voltage of new dual-source SD rat liver scan:70kV and300mAs.2、 The contrast dose and injection flow rate had influence on ALP and PVP,when the new dual-source CT liver perfusion imaging was made using slope method,while HPI was relatively stable and less affected.Considering from safety and accuracy, the amount of parity with lml and injection rate with0.2ml/s best fit for SD rats’new dual-source CT liver perfusion imaging.Part21、 CT perfusion imaging can reflect the hemodynamic changes of the evolution process of liver fibrosis-cirrhosis-liver cell nodules-liver cancer and measure the blood flow of hepatic artery and portal vein quantitatively.2、Variation trends of each stage and parameter. In the evolution process of liver fibrosis-cirrhosis of the liver-liver cells nodules-liver cancer, there exists the decrease of PVP, HPI, TLP, BV and MTT prolonging,ALP shows an upward trend, while BF decreased first and then rose,which provides a reliable basis for the dynamic review of the patients with hepatitis. For the the3、At the liver fibrosis stage, with the aggravating of liver fibrosis,PVP reached the maximum net change in value-added,suggesting that PVP had the highest titer in the diagnosis of liver fibrosis severity.CT perfusion imaging is a non-invasive, repeatable way that can provide reliable objective basis to check for the early detection of medium and heavy hepatic fibrosis and has important clinical significance.4、 During the cirrhosis period,plateau of relatively slow change of parameters appears with smaller slope for each parameter.5、 From RN to DN, and then to HCC, ALP, HPI and MTT, changes in net value-added was large compared to other parameters,suggesting the net increase in radians of ALP, HPI and MTT were quite valuable to diagnose and differentiate liver benign and malignant nodules.