| Gastric cancer is a common malignant tumor with poor prognosis in the world and a serious threat to health of human being.The incidence of gastric cancer in China is high.The numbers of disease cases and death cases account for about 50% of the world.The disease burden of gastric cancer is serious.With the development of CT technology,multi-slice spiral computed tomography(MDCT)has become an important tool and been widely used in preoperative staging,curative effect evaluation and postoperative follow-up of gastric cancer.But TNM staging and curative effect evaluation are determined mainly through observing the morphological changes,such as the thickness of gastric wall,the density of perigastric adipose tissue and the size of lymph nodes by traditional CT,which has limitations and subjectivity and causes many problems in clinical application.At present,functional imaging techniques attract more and more attentions of academia.Dual source computed tomography(DSCT)has two sets of perpendicular tubes and detectors.The two tubes can emit X-rays with different energy at the same time and then the X-rays are attenuated by human bodies and collected by the corresponding detector.So we can get two sets of data with different energy,which is named as dual energy imaging.Different material has different X-ray absorption characteristic and the same material has different attenuation value under different energy X-ray.According to this principle,dual energy imaging can separate specific materials through dual energy(DE)post-processing software and produce a variety of base material images,which can realize the quantitative measurement of specific materials.Iodine is the main element of the CT contrast agents and the most common indicator of material separation,extraction and quantitative measurement.The “Liver virtual non-contrast”(Liver VNC)mode of DE software can extraction iodine from the organization and produce virtual non-contrast(VNC)image and Iodine map at the same time.The former can replace the conventional non-contrast scan in order to reduce the radiation dose and the latter can evaluate the enhancement degree and reflect the blood supply of tissue.Both of them have good clinical application prospect and have been applied in the diagnosis and curative effect evaluation of lesions in solid organs,such as lung,liver,kidney,prostate,etc.So far,systematic studies about the application of this technology in stomach have not been seen and the related literatures are rare.Therefore,this study will from the following five parts to discuss the feasibility of applying DSCT dual energy imaging in the stomach and the application value of iodine measurement technique in preoperative staging,predicting prognosis and evaluating the curative effect after neoadjuvant chemotherapy(NAC).The first part: Feasibility study of DSCT dual energy scan in stomachThe second part: The application of iodine concentration measurement by dual energy scan in evaluating tumor angiogenesis and predicting prognosis of patients with advanced gastric adenocarcinomaThe third part: The application of quantitative measurement of iodine concentration of perigastric adipose tissue adjacent to gastric cancer by dual-energy scan for preoperative diagnosis of serosal invasionThe fourth part: The application of iodine concentration in perigastric adipose tissue by dual-energy scan for diagnosis of serosal invasion of advanced gastric cancer before and after neoadjuvant chemotherapyThe fifth part: The application of iodine concentration measurement by dual energy scan in evaluating tumor response of advanced gastric cancer to neoadjuvant chemotherapy Part One Feasibility study of DSCT dual energy scan in stomach(?)The image quality of virtual non-contrast and the radiation safety of dual energy scanningObjective: To evaluate the image quality of virtual non-contrast(VNC)and its capability to display primary tumors of gastric cancer and perigastric adipose tissues and to evaluate the radiation safety of dual energy scanning by dual-source CT(DSCT).Methods: 48 patients with gastric cancer undergoing preoperative DSCT and surgery were enrolled.The image quality of true non-contrast(TNC)and VNC was compared through subjective scoring and objective measurement of image noise.The TNC values and VNC values of primary tumor of gastric cancer and perigastric adipose tissue were measured and compared.The VNC values of perigastric adipose tissue were compared between serosal involvement group and non-serosal involvement group.The radiation dose of conventional scanning and dual energy scanning were calcuated and compared.Results:1.The subjective scores of TNC and VNC of arterial phase and venous phase were 4.85±0.36,4.77±0.47 and 4.81±0.45.The differences among them were significant(?2=10.56,P<0.05).But the scores of VNC of arterial phase and venous phase were all above the critical value of 3.The image quality of VNC could meet the diagnostic requirement.2.The image noises of TNC and VNC of arterial phase and venous phase were 6.73±0.41,5.66±0.37 and 5.65±0.34.The differences among them were significant(?2=86.79,P<0.05).The image noises of VNC of arterial phase and venous phase were lower than that of TNC.3.There was statistical difference between TNC values and VNC values of primary tumor of gastric cancer and perigastric adipose tissue(P<0.05),but the absolute values of the differences were all under13 HU.4.The difference of VNC values between serosal involvement group and non-serosal involvement group was significant(P<0.05).5.The differences of effective dose(ED)among conventional scanning and dual energy scanning of arterial phase and venous phase were significant(?2=28.21,P<0.05).The difference of ED between conventional scanning and dual energy scanning of arterial phase was significant(Z=-4.06,P<0.05).The difference between conventional scanning and dual energy scanning of venous phase was also significant(Z=-3.50,P<0.05).The ED of dual energy scanning was lower than that of conventional scanning.Summaries:1.The image quality of VNC of gastric cancer can meet the diagnostic requirement.2.TNC values and VNC values of primary tumor of gastric cancer and perigastric adipose tissue are similar.VNC can display the difference of CT attenuation value of perigastric adipose tissue between serosal involvement group and non-serosal involvement group.3.The ED of dual energy scanning was lower than that of conventional scanning.VNC has the proficiency to replace conventional non-contrastscanning,which would reduce 1/3 radiation dose.(?)Feasibility study on quantitative measurement of iodine in the simulation model of “gastral cavity-gastric wall-perigastric adipose tissue”Objective: To evaluate the feasibility of quantitative measurement of iodine in the simulation models of “gastral cavity-gastric wall-perigastric adipose tissue” by dual energy scanning.Methods: The simulation models of “gastral cavity-gastric wall-perigastric adipose tissue” were made to simulate stomachs and their background environment.The simulation “gastric walls” were filled by iodine solutions with different concentrations of 0mg/ml(normal saline),0.1mg/ml,0.2mg/ml,0.5mg/ml,1.0mg/ml,2.0mg/ml,5.0mg/ml and 10mg/ml.After dual energy scanning by DSCT,the CT attenuation values of simulation “gastric walls” were measured in the fusion images and their iodine concentrations were measured in the Iodine maps,respectively.The correlation of CT attenuation values and true iodine concentration and the correlation of measured iodine concentration values and true iodine concentration were compared.The abilities of CT attenuation value and measured iodine concentration value to distinguish iodine concentration were evaluated.Results:1.The CT attenuation values of the eight simulation “gastric walls” were 42.98 HU,41.94 HU,43.96 HU,42.29 HU,62.22 HU,79.66 HU,168.34 HU and 274.51 HU.They had correlation with true iodine concentration(r=0.887,P<0.05).From 0 mg/ml to 0.5 mg/ml,the differences of CT attenuation values among them were not statistically significant(P>0.05).When the differences of iodine concentration were 0.5 mg/ml or higher,the differences of CT attenuation values were statistically significant(P<0.05).2.The measured iodine concentration values of the eight simulation “gastric walls” were 0.15mg/ml,0.40mg/ml,0.46mg/ml,0.86mg/ml,1.43mg/ml,2.35mg/ml,6.16mg/ml and 10.75mg/ml.The values had correlation with true iodine concentration(r=0.961,P<0.05).From 0 mg/ml to 0.2 mg/ml,the differences of measured iodine concentration values among them were not statistically significant(P>0.05).When the differences of iodine concentration were 0.3 mg/ml or higher,the differences of measured iodine concentration values were statistically significant(P<0.05).Summaries:1.Measured iodine concentration values of dual energy scanning can more accurately reflect the ture iodine concentration and identify more subtle iodine concentration difference than CT attenuation values.2.The measurement of iodine concentration by dual energy scanning is not affected by the thickness of gastric wall and the background environment,this technology can be used in the study of stomach.Part Two The application of iodine concentration measurement by dual energy scan in evaluating tumor angiogenesis and predicting prognosis of patients with advanced gastric adenocarcinomaObjective: To explore the application value of iodine concentration measurement by dual energy scan in evaluating tumor angiogenesis and predicting prognosis of patients with advanced gastric adenocarcinoma.Methods: A retrospective study encompassing ninety-seven patients with advanced gastric adenocarcinoma admitted to the Fourth Hospital of Hebei Medical University from January 2015 to December 2015.The patients were imaged preoperatively with dual-energy scan and then underwent operation.All the follow-up data was received via telephone by the end of February 2018.The standardized iodine concentration(SIC)of the primary tumor of advanced gastric adenocarcinoma was measured.The correlations between SIC and patients' clinical and pathology features,the number of MVD,the expression level of VEGF and patients' survival were analyzed.The Kaplan–Meier test was employed to evaluate the patients' disease free survival(DFS)and overall survival(OS).COX regression model was adopted to improve the multiple factors analysis.Results:1.The SIC of primary tumor of advanced gastric adenocarcinoma had no relationship with patients' gender,age,tumor morphology,tumor size and differentiation degree.2.The SIC of primary tumor of advanced gastric adenocarcinoma had relationship with Lauren classification.The mean values of SIC of diffuse type,intestinal type and mixed type were 0.81±0.23,0.54±0.17 and 0.54±0.18,respectively.The differences of SIC among the three types were statistically significant(F=18.717,P<0.001).The mean value of SIC of diffuse type was higher than that of intestinal type.3.The SIC of primary tumor of advanced gastric adenocarcinoma had relationship with invasion deepth,lymph node metastasis and pathological TNM staging.The mean values of SIC of non-T4 group and T4 group were 0.52±0.20 and 0.66±0.23,respectively.The difference between the two groups was statistically significant(t=-2.728,P=0.008).The mean values of SIC of N0 group and N1-3 group were 0.53±0.17 and 0.64±0.24,respectively.The difference between the two groups was statistically significant(t=-2.084,P=0.040).The mean values of SIC of non-III staging group and III staging group were 0.50±0.17 and 0.68±0.23,respectively.The difference between the two groups was statistically significant(t=-4.135,P<0.001).4.The SIC of primary tumor of advanced gastric adenocarcinoma had relationship with the expression of VEGF.The mean value of SIC of VEGF negative expression group was 0.48±0.16 and that of positive expression group was 0.69±0.22.The difference between the two groups was statistically significant(t=-4.684,P<0.001).5.The SIC of primary tumor of advanced gastric adenocarcinoma is positively correlated with the number of MVD(r=0.4881,P<0.05).The mean number of MVD of 97 patients was 114.10±17.51,the mean value of SIC of low MVD group and high MVD group were 0.55±0.19 and 0.67±0.24.The difference between the two groups was statistically significant(t=-2.802,P<0.05).6.The patients were followed up with a median of 31 months after operation.37 patients with local recurrence or distant metastasis were observed and DFS was 61.86%(60/97).There were 28 dead cases and OS was 71.13%(69/97).The mean value of SIC of recurrence or metastasis group was 0.72±0.27 and that of non-recurrence or non-metastasis group was0.55±0.16.The difference between the two groups was statistically significant(t=3.791,P<0.001).The mean value of SIC of 97 patients was 0.62±0.23.According to the mean value,patients were divided into low SIC group and high low group.The DFS of the two groups were(27.96±7.95)months and(22.45±10.50)months.The difference between them was statistically significant(?2=11.920,P=0.001).The OS of the two groups were(29.14±6.53)months and(25.85±9.25)months.The difference between them was statistically significant(?2=12.907,P<0.001).7.Invasion deepth,lymph node metastasis,p TNM staging and SIC were identified as the independent risk factors affecting DFS of patients with advanced gastric adenocarcinoma.The relative risks of them to DFS prognosis were 0.195?0.379?6.623 and 2.802,respectively.8.Invasion deepth,p TNM staging and SIC were identified as the independent risk factors affecting OS of patients with advanced gastric adenocarcinoma.The relative risks of them to OS prognosis were 0.281,7.225 and 2.835,respectively.Summaries:1.The SIC of primary tumor of advanced gastric adenocarcinoma has no relationship with patients' gender,age,tumor morphology,tumor size and differentiation degree.2.The SIC of primary tumor of advanced gastric adenocarcinoma has relationship with Lauren classification.The SIC of diffuse type is higher than that of intestinal type.3.The SIC of primary tumor of advanced gastric adenocarcinoma has relationship with invasion deepth,lymph node metastasis and pathological TNM staging.4.The SIC of primary tumor of advanced gastric adenocarcinoma has relationship with the expression of VEGF.The SICof VEGF positive expression group is higher than that of negative expression group.5.The SIC of primary tumor of advanced gastric adenocarcinoma is positively correlated with the number of MVD.The SIC of high MVD group is higher than that of low MVD group.6.The SIC of recurrence or metastasis group is higher than that of non-recurrence or non-metastasis group.DFS and OS of paitients with high SIC are shorter than those of paitients with low SIC.7.Invasion deepth,lymph node metastasis,p TNM staging and SIC are identified as the independent risk factors affecting DFS of patients with advanced gastric adenocarcinoma.8.Invasion deepth,p TNM staging and SIC are identified as the independent risk factors affecting OS of patients with advanced gastric adenocarcinoma.Part Three The application of quantitative measurement of iodine concentration of perigastric adipose tissue adjacent to gastric cancer by dual energy scan for preoperative diagnosis of serosal invasionObjective: To investigate the application value of quantitative measurement of iodine concentration(IC)of perigastric adipose tissue adjacent to gastric cancer by dual energy scan for preoperative diagnosis of serosal invasion.Methods: Fifty-four patients with gastric cancers were enrolled.Patients were imaged preoperatively with dual energy scan and the IC of perigastric adipose tissue adjacent to gastric cancer was calculated from arterial phase(AP)and venous phase(VP)images.The histologic analysis of resected specimens was used as a ‘gold standard' reference for diagnosis of serosal invasion.Receiver operating characteristic(ROC)curve analysis was employed to assess the utility of IC of perigastric adipose tissue adjacent to gastric cancer for identifying serosal invasion.Results:1.Postoperative histology revealed that 32 patients had serosal invasion,and 22 did not.There were no significant differences between group with serosal invasion and group without serosal invasion in terms of age,gender and location of the gastric cancer(P > 0.05),but there was significant difference in the pathologic type(P<0.05).2.The accuracy,sensitivity and specificity of conventional CT for identifying serosal invasion were 68.5%(37/54),82.6% and 58.1%,respectively.3.The IC of perigastric adipose tissue adjacent to gastric cancer tumor was significantly higher in group with serosal invasion than that in group without serosal invasion(AP: 0.60±0.34 vs.0.09±0.19 mg/ml,P<0.05;VP: 0.83±0.41 vs.0.27±0.21 mg/ml,P<0.05).4.At an IC threshold of 0.25 mg/ml for AP images,the area under the ROC curve(AUC)was 0.89 and the accuracy,sensitivity and specificity for diagnosis of serosal invasion were 85.2%,84.4% and 86.4%.At an IC threshold of 0.45 mg/ml for VP images,the AUC was 0.90 and the accuracy,sensitivity and specificity for diagnosis of serosal invasion were 87.0%,87.5% and 86.4%.Summaries:1.The IC of perigastric adipose tissue adjacent to gastric cancer is significantly higher in group with serosal invasion than that in group without serosal invasion.2.The quantitative measurement of iodine of perigastric adipose tissue adjacent to gastric cancer could provide more accurate evidences for diagnosis of serosal invasion and could represent a novel and accurate image method for preoperative staging.Part Four The application of iodine concentration in perigastric adipose tissue by dual energy scan for diagnosis of serosal invasion of advanced gastric cancer before and after neoadjuvant chemotherapyObjective: To explore the application value of iodine concentration in perigastric adipose tissue(ICPAT)by dual energy scan for diagnosis of serosal invasion(SI)of advanced gastric cancer before and after neoadjuvant chemotherapy(NAC).Methods: 43 patients with c T4 advanced gastric cancer who underwent dual energy scan before and after NAC were enrolled.ICPAT was measured and the standardized ICPAT(SICPAT)was calculated.These parameters were measured again 1 month later by the same radiologist.The consistency of the two measurements was evaluated by Bland and Altman plotting.According to the postoperative pathologic results,the patients were divided into two groups: downstaging group(n=13)and non-downstaging group(n=30).ICPAT and SICPAT of pre-and post-NAC were compared in the two groups,respectively.The changes of ICPAT(?ICPAT)and SICPAT(?SICPAT)were compared between the two groups.ROC curve was used to evaluate the capability of the parameters in identifying SI after NAC.Results:1.According to postoperative pathologic results,13 patients were at non-T4 stage(downstaging group)and the other 30 patients were at T4 stage(non-downstaging group)after NAC.There was no significant difference between the two groups in terms of clinical features,such as gender,age,locations of lesions and pathologic types(P>0.05).2.Contrasted with postoperative pathologic results,the accuracy,false negative rate and false positive rate of conventional CT in identifying SI after NAC were 74.42%,43.75% and 14.81%.3.There was a significant difference of ICPAT and SICPAT before and after NAC in downstaging group(0.91±0.24 vs.0.22±0.20,Z=-3.074,P<0.05;0.20±0.04 vs.0.04±0.04,Z=-3.189,P<0.05).Both ICPAT and SICPAT dropped significantly after NAC in downstaging group.4.The difference of SICPAT before and after NAC in non-downstaging group were negligible(0.94±0.33 vs.0.79±0.18,Z=-1.644,P>0.05),while there was a significant difference of ICPAT before and after NAC in this group(0.21±0.07 vs.0.19±0.05,Z=-2.835,P<0.05).5.The difference of ICPAT and SICPAT between downstaging group and non-downstaging group varied from insignificance before NAC(0.91±0.24 vs.0.94±0.33,Z=-0.210,P>0.05;0.20±0.04 vs.0.21±0.07,Z=-0.105,P>0.05)to significance after NAC(0.22±0.20 vs.0.79±0.18,Z=-4.250,P<0.05;0.04±0.04 vs.0.19±0.05,Z=-4.444,P<0.05).6.The differences of ?SICPAT between the two groups were statistically significant(0.16±0.06 vs 0.02±0.07,Z=-3.505,P<0.05).The drop of SICPAT in downstaging group was greater than that in non-downstaging group.7.The AUC was 0.929,if ?SICPAT was equal to or greater than 0.095,the sensitivity,specificity and accuracy of SICPAT in identifying post-NAC negative SI were 92.30 %,86.70 %,and 88.37%,respectively.8.The measurement results of ?SICPAT by the two times maintained a high level of consistency.Summaries:1.SICPAT can reflect serosal status of gastric cancer more accurately than ICPAT after NAC.2.The drop of SICPAT in downstaging group is greater than that in non-downstaging group.The AUC is 0.929,if ?SICPAT is equal to or greater than 0.095,the sensitivity,specificity and accuracy of SICPAT in identifying post-NAC negative SI are 92.30 %,86.70 %,and 88.37%,respectively.3.The measurement reproducibility of ?SICPAT is high.4.SICPAT is an effective index in assessing serosal status in patients with gastric cancer post-neoadjuvant chemotherapy,with higher accuracy than conventional CT and can be employed to evaluate the effectiveness of NAC timely and decide the optimal operation time.Part Five The application of iodine concentration measurement by dual energy scan in evaluating tumor response of advanced gastric cancer to neoadjuvant chemotherapyObjective: To investigate the application value of iodine concentration(IC)measurement to evaluate the response of gastric cancer to preoperative neoadjuvant chemotherapy(NAC),and compare the abilities of various existing evaluation methods and the method of IC measurement to predict the response of gastric cancer to NAC.Methods: A total of 30 patients were enrolled who underwent dual energy scanning before and after NAC.The T staging,tumor maximal thickness(TMT),tumor volume(TV)and tumor density(TD)before and after NAC were measured and then the responses of gastric cancer to NAC were evaluated according to T staging,Response Evaluation Criteria in Solid Tumors(RECIST 1.1)criteria,Choi's criteria and Lee SM's volume evaluation criteria.The above assessment results were compared with postoperative pathological assessment results.The IC of primary tumors of gastric cancer were measured before and after NAC and the standardized IC(SIC)were calculated.The diagnostic efficacy of the method of IC measurement was evaluated using receiver operating characteristic(ROC)curves.Results:1.According to the criteria of down-staging,the accuracy,sensitivity and specificity to evaluate the response of gastric cancer to NAC were 53.33%,31.58% and 90.91%.The positive predictive value(PPV)and negative predictive value(NPV)were 85.71% and 43.48%.2.According to RECIST 1.1 criteria,the accuracy,sensitivity and specificity to evaluate the response of gastric cancer to NAC were 63.33%,47.37%and 90.91%.The PPV and NPV were 90.00% and 50.00%.3.According to Lee SM's volume evaluation criteria,the accuracy,sensitivity and specificity to evaluate the response of gastric cancer to NAC were 60.00%,57.89%and 63.64%.The PPV and NPV were 73.33% and 46.67%.4.According to Choi's criteria,the accuracy,sensitivity and specificity to evaluate the response of gastric cancer to NAC were 80.00%,94.74%and 54.44%.The PPV and NPV were 78.26% and 85.71%.5.In terms of evaluating the curative effect,SIC of primary tumor of gastric cancer was superior to IC.The cut-off value for identifying the response of gastric cancer to NAC was a decrease rate of ?26.5% for %?SIC and the accuracy,sensitivity and specificity values were 76.67%,68.40% and 90.90%.The PPV and NPV were 92.86% and 62.50%.6.The consistencies of the assessment results of CT T staging,volume measurement and postoperative pathological assessment results were poor(k=0.183,P>0.05;k=0.200,P>0.05),The consistency of the assessment results of diameter measurement and postoperative pathological assessment results was fair(k=0.327,P<0.05).The consistencies of the assessment results of density measurement,iodine measurement and postoperative pathological assessment results were moderate(k=0.534,P<0.05;k=0.541,P<0.05).Summaries:The prediction efficacy of SIC of primary tumors of gastric cancer is better than those of morphological evaluation methods and is equal to that of density measurement.SIC is a promising convenient imaging method for evaluating the response of gastric cancer to NAC.Conclusions:1.The image quality of VNC of gastric cancer can meet the diagnostic requirement.TNC values and VNC values of primary tumor of gastric cancer and perigastric adipose tissue are similar.The ED of dual energy scanning was lower than that of conventional scanning.2.The measurement of iodine concentration by dual energy scanning is not affected by the thickness of gastric wall and the background environment,this technology can be used in the study of stomach.Measured iodine concentration values can more accurately reflect the ture iodine concentration and identify more subtle iodine concentration difference than CT attenuation values.3.The SIC of primary tumor of advanced gastric adenocarcinoma has relationship with Lauren classification,invasion deepth,lymph node metastasis,pathological TNM staging,the expression of VEGF and the number of MVD.SIC is identified as the independent risk factors affecting DFS and OS of patients with advanced gastric adenocarcinoma.4.The quantitative measurement of iodine of perigastric adipose tissue adjacent to gastric cancer could provide more accurate evidences for diagnosis of serosal invasion and could represent a novel and accurate image method for preoperative staging.5.SICPAT is an effective index in assessing serosal status in patients with gastric cancer post-neoadjuvant chemotherapy,with higher accuracy than conventional CT and can be employed to evaluate the effectiveness of NAC timely and decide the optimal operation time.6.The prediction efficacy of SIC of primary tumors of gastric cancer is better than those of morphological evaluation methods and is equal to that of density measurement.SIC is a promising convenient imaging method for evaluating the response of gastric cancer to NAC. |
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