| Cancer is a malignant tumor formed by abnormal proliferation and poor differentiation of immature cells in the human body.It is often named by its initial organ or cell type.Cervical cancer(CC),which originated from the cervix,is the second leading cause of cancer related death among women in developing countries including China.The incidence rate of this disease has gradually improved with the promotion and popularization of screening technology in recent years,and the incidence of CC tends to be younger.Human papillomavirus(HPV)infection is a high-risk factor for CC,especially subtypes 16 and 18.Other risk factors include low income,sexual life disorder,immunosuppression and smoking.The clinical stage and some pathological features of the tumor(such as degree of differentiation,lymphovascular space invasion,perineural invasion,depth of matrix infiltration,lymph node status,etc.)are closely related to its treatment and prognosis.At present,many imaging methods have been used in the diagnosis and prognosis of CC.Compared with other imaging examinations such as ultrasound(US),computed tomography(CT),magnetic resonance imaging(MRI)technology has unique advantages in safety,imaging mode and soft tissue resolution.It can accurately display the morphology,size,boundary,parametrial infiltration and surrounding organ invasion of the lesion,which is not only of great value in the early diagnosis of CC,but also useful for the formulation of treatment plan and prognosis evaluation.The International Federation of gynecology and Obstetrics(FIGO)suggested that MRI should be used as the main imaging examination method for the staging and efficacy detection of CC.The traditional MRI imaging sequence mainly focuses on morphological research,which has some limitations.The functional imaging technology developed since the 1990s realizes the quantitative or semi quantitative analysis of biological tissue information from the cellular or molecular level.Diffusion weighted imaging(DWI)is a quantitative imaging technique that reflects the diffusion movement of water molecules in living tissues.It quantitatively analyzes the diffusion movement of water molecules in diseased tissues by measuring the apparent diffusion coefficient(ADC).At present,DWI has been widely used in the study of clinical staging and pathological characteristics of CC.Compared with the traditional DWI sequence,readout segmentation of long variable echo trains-diffusion weighted imaging(RESOLVE-DWI)has the advantages of high image resolution,good display of anatomical details,less artifacts and low distortion.It has been widely used in the research of head,neck and body tumors.T1 mapping and T2 mapping are novel quantitative MRI techniques developed in recent years to evaluate the characteristics of tissue abnormalities.T1 mapping quantitatively analyzes the biological histological characteristics by measuring the longitudinal relaxation time(T1 value)of the image.The scanning sequence includes T1 mapping before and after enhancement.It has the advantages of simple operation and short scanning time.T1 mapping was mostly used to evaluate myocardial lesions(such as myocarditis,myocardial fibrosis and myocardial amyloid),as well as liver fibrosis,chronic pancreatitis and other diseases in past years.T2 mapping quantitatively reflects the tissue water content by measuring the transverse relaxation time(T2 value)of the image,which has high stability and repeatability.In the past,T2 mapping was mostly used to evaluate articular cartilage lesions(such as knee injury and intervertebral disc degeneration).In recent years,T1 mapping and T2 mapping have been gradually applied to the study of body tumors.Therefore,this subject mainly used T1 mapping,T2 mapping and RESOLVEDWI scanning sequence.Firstly,through the collection of serological data and MRI quantitative imaging data of newly diagnosed patients with CC,the clinical characteristics of CC(stage,serological index)were analyzed from the above three technical levels;secondly,by collecting the histopathological data of patients,the pathological characteristics of CC(such as tissue type,degree of differentiation,lymphovascular space invasion,perineural invasion,matrix infiltration depth and lymph node status)were effectively evaluated from different technical levels;finally,all patients with CC were followed up for 6 months to 3 years in order to analyze the predictive value of T1 mapping,T2 mapping and RESOLVE-DWI in the recurrence of CC after treatment.We hope to find the application value of MRI quantitative imaging technology in the diagnosis and recurrence prediction of CC through this research,in order to provide theoretical support for the rational treatment and prognosis improvement of CC.Part Ⅰ The application of quantitative MRI in clinical features of cervical cancerBackground and Purpose1.To compare the diagnostic value of T1 mapping,T2 mapping and RESOLVEDWI in differentiating clinical stage of cervical cancer(CC);2.To clarify the correlation between the quantitative parameters of T1 mapping,T2 mapping,RESOLVE-DWI and the expression level of squamous carcinoma-associated antigen(SCC-Ag)in serum of patients with CC.Materials and Methods1.Collection of patients with CC:a total of 107 patients with CC confirmed by surgery pathology or cervical biopsy in the First Affiliated Hospital of Zhengzhou University from May 2018 to April 2021 were collected,including 75 cases in the low-stage group(stage ⅠB～ⅡA)and 32 cases in the high-stage group(stage ⅡB～ⅣB);2.Collection of serum samples:107 serum samples from the above CC patients were collected;3.All patients with CC underwent routine MRI,T1 mapping before and after enhancement,T2 mapping and RESOLVE-DWI;4.The longitudinal relaxation time before enhancement(T1pre),longitudinal relaxation time after enhancement(T1post),T1 reduction rate after enhancement(δ T1%),transverse relaxation time(T2)and ADC values were measured and calculated on T1 mapping,T2 mapping and ADC pseudo-color images automatically generated by Siemens post-processing workstation;5.The expression of SCC-Ag in serum samples of patients with CC was detected by enzyme-linked immunosorbent assay;6.SPSS 17.0 software was used for data statistics and analysis.All data were expressed as the means±standard error of the mean and tested for normality test.The parameter values conforming to the normal distribution were compared between groups by independent sample t-test,the receiver operating characteristic(ROC)curve was constructed by medcalc 19.0 software,the diagnostic performances of each parameter were evaluated,and the area under the curve(AUC)was compared by Delong test.Spearman correlation was used to analyze the correlation between parameters and clinical stage and serum SCC-Ag expression level.P<0.05 was statistically significant.Results1.Differences of quantitative parameters of T1 mapping,T2 mapping and RESOLVE-DWI in different clinical stages of CC.① There were significant differences in T2 value and ADC value between low-stage group and high-stage group(P<0.05);The AUC of ROC curve of T2 and ADC in differentiating low-stage group and high-stage group were 0.840 and 0.687 respectively,and the diagnostic efficiency of T2 was better than ADC(Z=2.237,P=0.025);②Taking T2=84.40 ms as the optimal threshold,the sensitivity and specificity were 76.01%and 87.52%respectively,the youden index was 0.635,and 95%confidence interval was 0.756～0.904;taking ADC=0.69×10-3mm2/s as the best threshold,the sensitivity and specificity were 76.03%and 59.41%respectively,the youden index was 0.354,and the 95%confidence interval was 0.590～0.773.2.Spearman correlation analysis showed that T2 value was negatively correlated with clinical stage of CC(r=-0.539,P<0.05),and ADC value was negatively correlated with clinical stage of CC(r=-0.296,P<0.05);ADC value was negatively correlated with serum SCC-Ag expression in patients with CC(r=-0.423,P<0.001).ConclusionsBoth T2 and ADC values are helpful parameter to evaluate the clinical stage of CC,while the diagnostic efficiency of T2 value is better than ADC value;ADC value is significantly correlated with the expression level of serum SCC-Ag in patients with CC.Part II The diagnostic value of quantitative MRI in pathological features of cervical cancerBackground and PurposeTo investigate the diagnostic value of T1 mapping,T2 mapping and RESOLVEDWI in the pathological classification,degree of differentiation,lymphovascular space invasion(LVSI),perineural invasion(PNI),depth of stromal invasion and lymph node metastasis of cervical cancer(CC).Materials and Methods1.Collection of patients with CC:a total of 107 patients with CC confirmed by surgery pathology or cervical biopsy in the First Affiliated Hospital of Zhengzhou University from May 2018 to April 2021 were collected,including 92 cases of squamous cell carcinoma and 15 cases of adenocarcinoma;18 cases in poorly differentiated group and 34 cases in well/moderately differentiated group of cervical squamous cell carcinoma;31 cases in LVSI-positive group and 32 cases in LVSI-negative group;10 cases in PNI-positive group and 28 cases in PNI-negative group;52 cases in the group with matrix infiltration depth>1/2 and 12 cases in the group with matrix infiltration depth ≤ 1/2;20 cases with positive lymph node metastasis and 42 cases with negative lymph node metastasis;2.All patients with CC underwent routine MRI,T1 mapping before and after enhancement,T2 mapping and RESOLVE-DWI;3.The longitudinal relaxation time before enhancement(T1pre),longitudinal relaxation time after enhancement(T1post),T1 reduction rate after enhancement(δT1%),transverse relaxation time(T2)and ADC values were measured and calculated on T1 mapping,T2 mapping and ADC pseudo-color images automatically generated by Siemens post-processing workstation;4.SPSS 17.0 software was used for data statistics and analysis.All data were expressed as the means±standard error of the mean and tested for normality test.For the parameter values conforming to the normal distribution,the quantitative parameters in different pathological characteristics of CC were compared by independent sample t-test,the receiver operating characteristic(ROC)curve was constructed by medcalc 19.0 software,and the diagnostic performances of these quantitative values on the pathological characteristics of CC were compared and analyzed by Delong test,The optimal thresholds were determined according to the youden index.P<0.05 was statistically significant.Results1.The ADC value of cervical squamous cell carcinoma was significantly higher than that of adenocarcinoma(P<0.05),and the area under the curve(AUC)of ROC curve was 0.746,taking ADC=0.70×10-3mm2/s as the best threshold to distinguish cervical squamous cell carcinoma and adenocarcinoma,the sensitivity and specificity were 68.48%and 80.00%respectively,the youden index was 0.485,and the 95%confidence interval was 0.653～0.826;2.There were significant differences in T1post,δT1%,T2 and ADC values of cervical squamous cell carcinoma with different differentiation degrees(P<0.05).The AUC of ROC curve of T1post,δT1%,T2 and ADC values in differentiating poorly differentiated and well/moderately differentiated squamous cell carcinoma were 0.931,0.935,0.770 and 0.773 respectively,and the diagnostic efficiencies of T1post and δT1%values were better than T2 and ADC values(P<0.05),there was no significant difference in diagnostic efficacy between T1post and δT1%,T2 and ADC(P>0.05);taking T1post=626.09 ms as the best threshold,the sensitivity and specificity were 94.44%and 76.47%respectively,the youden index was 0.709,and the 95%confidence interval was 0.826～0.983;taking δT1%=52%as the best threshold,the sensitivity and specificity were 88.89%and 88.24%respectively,the youden index was 0.771,and the 95%confidence interval was 0.830～0.984;taking T2=83.60 ms as the best threshold,the sensitivity and specificity were 77.78%and 70.59%respectively,the youden index was 0.484,and the 95%confidence interval was 0.632～0.875;taking ADC=0.72×10-3mm2/s as the best threshold,the sensitivity and specificity are 77.78%and 67.65%respectively,the youden index is 0.454,and the 95%confidence interval is 0.636～0.877;3.The T2 values of LVSI and PNI positive group were lower than those of LVSI and PNI negative group,and the difference was statistically significant(P<0.05).The AUC of ROC curve predicted by T2 value was 0.910 and 0.761,respectively;taking T2=84.00 ms as the best threshold for predicting LVSI,the sensitivity and specificity were 77.42%and 90.62%respectively,the youden index was 0.680,and the 95%confidence interval was 0.811～0.968;taking T2=78.93 ms as the best threshold for predicting PNI,the sensitivity and specificity were 80.00%and 78.57%respectively,the youden index was 0.586,and the 95%confidence interval was 0.595～0.884;the values of T2 and ADC in the group with matrix infiltration depth>1/2 were lower than those in the group with matrix infiltration depth ≤1/2,and the difference was statistically significant(P<0.05).The AUC of ROC curve for T2 and ADC values to distinguish the depth of matrix infiltration were 0.893 and 0.716 respectively,and their diagnostic efficiency was the same(Z=1.421,P=0.155),taking T2=90.54 ms as the optimal threshold,the sensitivity and specificity were 82.69%and 83.33%respectively,the youden index was 0.660,and the 95%confidence interval was 0.790～0.956,taking ADC=0.80×10-3mm2/s as the best threshold,the sensitivity and specificity were 80.77%and 66.67%respectively,the youden index was 0.474,and the 95%confidence interval was 0.589～0.821.There was no significant difference between the lymph node metastasis positive group and the negative group(P>0.05).ConclusionsThe quantitative parameters of T1 mapping,T2 mapping and RESOLVE-DWI could have different diagnostic values in the evaluation of histopathological features of cervical cancer.Part Ⅲ The value of quantitative MRI in predicting recurrence of cervical cancer after treatmentBackground and PurposeTo investigate the value of T1 mapping,T2 mapping and RESOLVE-DWI in predicting the recurrence of cervical cancer(CC)after treatment.Materials and Methods1.Collection of CC patients:a total of 107 patients with CC confirmed by surgery pathology or cervical biopsy in the First Affiliated Hospital of Zhengzhou University from May 2018 to April 2021 were collected,including 77 cases in the operation group(13 cases in the recurrence group and 64 cases in the non recurrence group)and 30 cases in the non operation group(10 cases in the recurrence group and 20 cases in the non recurrence group);2.Patients with CC after surgery or concurrent chemoradiotherapy were followed up for 6 months to 3 years;3.All patients with CC underwent routine MRI,T1 mapping before and after enhancement,T2 mapping and RESOLVE-DWI;4.The longitudinal relaxation time before enhancement(T1pre),longitudinal relaxation time after enhancement(T1post),T1 reduction rate after enhancement(δ T1%),transverse relaxation time(T2)and ADC values were measured and calculated on T1 mapping,T2 mapping and ADC pseudo-color images automatically generated by Siemens post-processing workstation;5.SPSS 17.0 software was used for data statistics and analysis.All data were expressed as the means±standard error of the mean and tested for normality test.The parameter values conforming to the normal distribution were compared between groups by independent sample t-test method.The receiver operating characteristic(ROC)curve was constructed by medcalc 19.0 software to evaluate the prediction performances of relevant parameters on the recurrence of CC after treatment,and the optimal thresholds were determined according to the youden index.Logistic regression analysis was used to analyze the factors influencing the recurrence of CC patients after treatment.P<0.05 was statistically significant.Results1.Among 107 patients with CC,23 cases recurred after treatment,the total recurrence rate of 21.5%.13 cases recurred in the operation group(n=77),the recurrence rate of 16.9%;10 cases recurred in the non operation group(n=30),the recurrence rate of 33.3%;2.The quantitative parameters of T1 mapping,T2 mapping and RESOLVE-DWI were used to predict the difference between recurrent group and non recurrent group after surgery of CC.① There was significant difference in T1pre value between recurrent group and non recurrent group(P<0.05);② The area under the curve(AUC)of ROC curve for predicting postoperative recurrence of CC by T1pre value was 0.742,taking T1pre=1480.19 ms as the best threshold,the sensitivity and specificity were 76.92%and 70.31%respectively,the youden index was 0.472,and the 95%confidence interval was 0.630～0.825;3.The difference of T1 mapping,T2 mapping and RESOLVE-DWI quantitative parameters in predicting the recurrence group and non recurrence group after non-surgical treatment of CC.① There was significant difference in T1pre value between recurrent group and non recurrent group in non-surgical group(P<0.05);②The AUC of ROC curve for predicting the recurrence of CC after non-surgical treatment with T1pre value was 0.780,taking T1pre=1494.00 ms as the best threshold,the sensitivity and specificity were 80.00%and 75.00%respectively,the youden index was 0.550 and the 95%confidence interval was 0.592～0.910.4.Logistic regression analysis showed that T1pre value was a predictor of recurrence in patients with CC after treatment.ConclusionsThe T1pre value of T1 mapping imaging before treatment is of significance for predicting the recurrence of CC after treatment. |
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