Application Of Multimodal MRI In The Diagnosis Of Endometrial Carcinoma

BackgroundEndometrial carcinoma(EC)is an endometrium-derived malignant neoplasm originated from the endometrial glands;the incidence of EC is only secondary to that of breast cancer,lung cancer and colon cancer in America and Europe,and is the most frequently diagnosed malignant tumor of reproductive system in women.EC is the second most common cancer followed with cervical cancer in China;however,its incidence keeps increasing annually which has been one of the most serious concerns for the health of women.The prognosis of EC is closely associated with the its stage and grade;the more advanced stage,the more unfavorable therapeutic effect and prognosis.Five-year survival rates for stage I,II,III and IV were 81%-91%,67%-77%,32%-60%,and 5%-20%,respectively,indicating clearly that early diagnosis and accurate grading of EC are the key to improve the survival rate of patients,which requests a higher standard bar for early diagnosis and accurate grading of EC.Multiple imaging approaches are currently available for preoperative diagnosis(detection,location,qualitative and quantitative measurements),staging,grading of EC,such as segment diagnostic curettage,hysteroscopy,transvaginal ultrasound,CT,and PET;however,they have their own specific limitations.Therefore,a novel detection method for EC to improve preoperative diagnosis,staging and grading is urgently needed.MRI possess the feature of comprehensively displaying the anatomical structure and signal characteristics of the uterus and its surrounding tissues,benefited from its variety parameters,multiple imaging sequences,multi-dimensional imaging and high tissue resolution.So that MRI not only could precisely locate the position of EC and accurately diagnose,but also clearly display the depth and extent of invasion as well as the lymph node metastasis,which is very informative for staging and provides the reliable evidences for the connection between the tumor invasion and histological classification and differentiation.All of these are the decisive information for operation mode selection and postoperative evaluation,and very helpful to improve the survival rates of patients.The most value of MRI is the early diagnosis(stage I and II),and the difficulties of early diagnosis are the detection for tiny lesions confined to the endometrium and the judgment on the superficial muscle invasion,cervical invasion,lymph node early metastasis.The single-mode MRI for EC diagnosis and staging was investigated firstly by us in accordance to latest FIGO staging criteria.Our research findings in combination with global literatures indicated that blade artifact corrected T2 WI with fat suppression by conventional MRI scanning is helpful for determination of whether the junctional zone being broken through by tumor,though lack of the functional information.The hemodynamic characteristics of living tissues could be reflected by time-signal intensity curve and semi-quantitative parameters(including BF,BV,MTT and PS)acquired from MR dynamic enhancement(DCE-MRI)FLASH-3D-VIBE-FS technology.It was found that in combination of DCE-MRI and T2 WI could improve the diagnosis accuracy of depth of muscular invasion up to 92%.However,it was less than satisfactory on the early diagnosis and lymph node metastasis determination.Diffusion-weighted imaging(DWI)can detect the lesions related to the movement of water molecules before morphological alterations,and quantify the movement of water molecules by apparent diffusion coefficient(ADC)values,so as to reflect the capillary perfusion and diffusion characteristics.The main value of DWI is to detect the lesion which could be easily missed by the conventional imaging sequences,by which DWI could further improve the accuracy of diagnosis and detection rate of lymph node metastasis.However,ADC value cannot differentiate the benign and malignant lymph nodes.MRS is a novel imaging technology,utilizing1H-MRS imaging to quantitative analyze choline(3.2ppm),unsaturated fatty acid(2.0ppm),triglycerides-CH2(1.3ppm)and-CH3(0.9ppm),in order to reveal the mechanism of pathophysiological changes of EC at molecular metabolism level.Yet the acquired information is limited by these singlemode imaging technologies,which is helpful to investigate the morphology or specific abnormal function of tumor,but the biological complexity of EC could not be fully revealed.The multimodal MRI combines the properties of anatomy,functionality and image for the comprehensive analysis,and has become the hot topic in the current iconographical filed.The reliability,stability and fault-tolerant ability of multimodal MRI have been greatly improved,which efficiently assists clinicians to make accurate diagnosis based on the comprehensive information of lesion tissues or organs,and eventually to design more reasonable therapeutic strategy and achieve more satisfactory treatment effect.However,it remains to be further explored to comprehensively utilize multimodal MRI,meanwhile to avoid the drawbacks of different modal images,and obtain the complete anatomical and functional information of disease.Up to date,there is lack of published study of multimodal MRI on the EC;therefore,the tentative plan was proposed by us to combine structural and functional MRI as multimodal imaging technology,in order to explore the fundamental basis of pathophysiological alteration and functional abnormality of EC,which would be a solid basis for subsequent research.On the basis of previous single-modal research,the current study focused on multimodal MRI of EC included the following major contents: based on the structural information related MRI imaging,creatively utilizing the blade artifact corrected T2 WI with fat suppression technology,in combination with multimodal MRI technology such as DWI,1H-MRS,and DCE-FLASH-3D-VIBE to investigate the feasibility of multimodal MRI for early diagnosing the muscle invasion and cervical involvement of EC;to evaluate the application value of FLASH-3D dynamic enhanced MRI technology for diagnosis of EC;to evaluate the accuracy of multimodal MRI for EC staging as guidance for preoperative surgical mode selection and postoperative prognosis prediction.In the current study,the diagnostic efficiency of multimodal MRI technology for EC was objectively and accurately evaluated,in order to realize the multi-source image information fusion including the anatomical structure,functional metabolism,and molecular movement of EC,primarily establish clinical application system for early accurate diagnosis and therapeutic evaluation of EC;meanwhile,our study would provide scientific evidences for implementation of multimodal MRI imaging system and information platform characterized by the broad application,easy operation,accuracy and high efficiency.Part 1: FLASH-3D Dynamic Contrast-Enhanced Imaging in The Diagnosis of Endometrial CarcinomaObjectives1.To explore FLASH-3D dynamic enhancement technology for the preoperative staging of endometrial carcinoma.2.To evaluate the diagnostic accuracy of FLASH-3D dynamic enhancement technology for muscular invasion depth and cervical involvement assessment.3.To evaluate the diagnostic value of FLASH-3D dynamic enhancement technology for the diagnosis of endometrial carcinoma.Methods Sixty-four patients of endometrial carcinoma(EC)admitted in our hospital between July 2012 and December 2014 with complete clinical records and confirmed by histopathology study were recruited into the current study,as subjects of prospective study.The age of the patients ranged between 35 and 73 years,in average of 45.2±8.3years.On the basis of preoperative routine MRI examination,the FLASH-3D dynamic enhanced MRI scanning was performed,and the tumors were surgically removed about nine days in average after MRI examination.The MRI dynamic enhancement features of uterus all and tumors were analyzed by double-blinded method.The stages of EC,and the results of muscle invasion depth and cervical involvement determined by FLASH-3D dynamic enhancement were compared with the FIGO stage of EC acquired from the postoperative histopathology.Results In the current study,there were 46,7,4,5,and 2 patient for endometrial adenocarcinoma,serous adenocarcinoma,mucinous adenocarcinoma,clear cell carcinoma,and adenosquamous carcinoma,respectively.And they were staged as I for44 patients(28 patients of Ia and 16 patients of Ib),II for12 patients,III for five patients,and IV for three patients.The staging accuracy by the FLASH-3D(DCE-MRI)sequence was 79.7%(51/64);the sensitivity,specificity,and accuracy for muscle invasion depth determination were 82.1%,88.9%,and 85.9%,respectively;the sensitivity and accuracy for cervical involvement were 90.4% and 85.9%.Compared with postoperative histopathology,there was no significant difference(P > 0.05).Conclusion FLASH-3D dynamic enhancement technology was of significant value in the early diagnosis and preoperative staging of EC,and could significantly improve the diagnostic accuracy on muscle invasion depth of EC as guidance for clinical surgical mode selection and postoperative evaluation,which was promising to be a routine assessment on the pelvic carcinoma in woman.Part 2: The Diagnostic Value of multimodal MRI in Endometrial Carcinoma StagingBackground Multimodal MRI as the technology in combination of both structural information imaging and functional information imaging,is the frontier and hot topic of global research,though it was rarely reported in China.It combines properties of structure,functionality and image,providing the local anatomical,physiological,biochemical,and pathophysiological information of lesions.The reliability and stability of images have been greatly improved so that the clinicians could be well aware of the comprehensive information of tumor to make accurate judgment on location and characteristics of tumor,eventually to design more reasonable therapeutic strategy to achieve more satisfactory treatment effect.The technology could not only accurately determine the stage of EC,but also provide the guidance on the preoperative surgical mode selection and postoperative prognosis prediction;therefore,it was of great value to improve survival rate of ER patients.Objectives Based on the new staging criteria defined by International Federation of Gynecology and Obstetrics(FIGO)in 2009,the objective of the current study is to explore the accuracy and diagnostic value of multimodal MRI on the EC staging,in order to provide advance instruction on preoperative surgical mode selection and postoperative prognosis prediction.Methods Eighty-three patients of endometrial carcinoma(EC)admitted in the First Affiliated Hospital of Shenzhen University between June 2011 and August 2015 underwent multimodal MRI examination with complete clinical and surgery pathological records and were recruited into the current study retrospectively.The age of the patients ranged between 24 and 76 years,in average of 47.3±9.4 years,including34 premenopause and 49 postmenopause patients.The surgeries were performed around one to two weeks after MRI examination,and the lesions were staged and graded by histopathology.The staging results determined by multimodal MRI were compared with that determined by postoperative histopathology in accordance with FIGO 2009 staging criteria,by double-blind method and paired ?2test of four-fold table(Mc Nema test),to evaluate the accuracy of EC staging by multimodal MRI.Results There were 56,7,5,7,4,2,and 2 patients for endometrial adenocarcinoma,serous adenocarcinoma,mucinous adenocarcinoma,clear cell carcinoma,mixed type adenocarcinoma,adenosquamous carcinoma,and small cell carcinoma,respectively,including histopathology grading 1(G1)of 29 patients,histopathology grading 2(G2)of 21 patients,and histopathology grading 3(G3)of 33 patients.According to the FIGO2009 staging system,there were 56,17,7,and 3 patients with stage I,II,III,IV respectively.The accuracies of multimodal MRI for staging from I to IV were 91.6%(76/83),91.6%(76/83),92.8%(77/83),and 97.6%(81/83),respectively,which was highly consistent to that defined by histopathology(P>0.05).Conclusion1.FIGO new staging criteria defined in 2009 was more concise,reasonable,and practical for clinical guidance.2.The preoperative staging of EC by multimodal MRI was greatly improved according to the new staging criteria.3.Multimodal MRI was one of important imaging assessment for preoperative staging and therapeutic strategy design of EC.