The Study On Efficacy And Safety Of High Intensity Focused Ultrasound Ablating Uterine Fibroid With Hyperintense On T2-Weighted Mrimaging

High intensity focused ultrasound（HIFU）ablation is safe and feasible,non-surgical, small wound, early recovery, organ-preserving techniques forthe treatment of uterine fibroids.It is widely used for treatment of uterinefibroids. HIFU can create a coagulative necrosis region by hightemperature effect produced by a tightly and precisely focused,high-intensity ultrasound beam, without harming tissues outside of thefocus.With the increasing use of HIFU in treating uterine fibroids, there aresome differences of opinions in the HIFU ablating uterine fibroids withhyperintense on T2-weighted MR imaging(MRI-T2WI) among researchers.Some people think that it is difficult to ablate and even is invalid, but othersdisagreed with that and they believed hyperintense fibroids only consumedmore sonication energy than isointense fibroids and hypointense fibroids,there are not differences of therapeutic effect.The objective of this study is to investigate the safety and efficiency of HIFU ablating uterine fibroids with hyperintense on MRI-T2WI by meansof investigating associated cases of large samples, from a technicalstandpoint. The study is to explore the role of MRI-T2WI and dynamiccontrast-enhanced MRI for predicting the difficulties during HIFU ablatinghyperintense fibroids; to analyze affecting factors of sonication energyduring HIFU ablating hyperintense fibroids by building an dosimetrymodel, to evaluate efficacy of the second HIFU by HIFU ablating recurringhyperintense fibroids which are difficult to treat by the first HIFU, toexplore biological characteristics of hyper-intense fibroids and itsinfluence on HIFU ablating by researching the isolated uterine fibroid. Wewant to provide a basis for indications and optimal treatment of HIFUablating hyperintense fibroids.Purpose1. To evaluate the safety and efficiency of HIFU ablating uterine fibroidswith hyper-intense on MRI-T2WI from a technical standpoint.2. To study the role of MRI-T2WI and dynamic contrast-enhanced MRI forpredicting the results of HIFU ablating hyperintense fibroids.3. To build a dosimetry model of HIFU ablating hyperintense fibroids andanalyze affecting factors of sonication energy.4. To explore the effect of the second HIFU by HIFU ablating recurringhyperintense fibroids.5. To explore biological characteristics of hyperintense fibroids and its influence on HIFU ablating.Materials and methodsPart one1. ObjectiveFrom Octomber2010to January2013,491patients diagnosed withuterine fibroids and scheduled for HIFU were enrolled in the1st AffiliatedHospital of Chongqing Medical University,402patients were inaccordance with the inclusive criteria;131patients with hyperintenseuterine fibroids on MRI-T2WI.2. EquipmentsJC HIFU tumour therapeutic system produced by ChongqingHaifu(HIFU) Tech Co. Ltd; Magnetic resonance imaging system produced byGermany Siemens.3. Methods(1) Pretreatment magnetic resonance image evaluation: The plain andenhanced MRI scanning were performed before HIFU ablating in allpatients to evaluate the size, number and position of the uterus and fibroids,and signal intensity of fibroid on MRI-T2WI. All the images were readand measured by three experienced radiologists.Uterine fibroids were classified as three types on pretreatmentT2-weighted MRI:1) hypointense, signal intensity like skeletal muscle;2)isointense, signal intensity is lower than myometrium but higher than thatof skeletal muscle;3) hyperintense, signal intensity is the same as or higher than myometrium.Hyperintense fibroids were subjectively classified as three groups:3.1)hetero-geneous hyperintense fibroids were defined as barred (>5mm) orlamellar high signal intensity approximately or equal to endometrium, orbarred (>5mm) or lamellar low signal intensity like skeletal muscle insidethe fibroid;3.2) slightly homogenous hyperintense fibroids were defined asuniformly distributed high signal intensity equal to or slightly higher thanmyometrium;3.3) markedly homogenous hyperintense fibroids were thatof uniformly distributed high signal intensity which was markedly higherthan myometrium and approximately equal to endometrium.Uterine fibroids were classified as slight enhancement, irregularenhancement and regular enhancement relative to myometrium on the basisof dynamic contrast-enhanced MRI during the60seconds after theinjection of gadolinium:1) Slight enhancement is that the enhancementdegree was lower than that of myometrium;2) Regular enhance-ment isdefined as that of the distribution of enhanced signal is regular and theenhance-ement degree is the same as or higher than that of myometrium;3)Irregular enhance-ment is that the distribution of enhanced signal isirregular and slightly enhanced signal is interspersed among enhancedsignal.(2) Ultrasound ablation: The operation was completed by qualifiedphysician. When patients had multiple uterine fibroids, only one dominant fibroid was treated.(3) Main Outcome Measures: treatment time, sonication watt, sonicationtime, sonication energy, therapeutic intensity, ablation efficiency, EEF, painscore.(4) Posttreatment magnetic resonance image evaluation: The plain andenhanced MRI scanning was performed in a month after HIFU ablating inall patients to evaluate the size of the uterus and fibroids, Non-perfusedvolume (NPV).4. Statistical methodsStatistical analysis was performed by using SPSS17.0software.Part two1. ObjectiveFrom Octomber2010to January2013,128patients with hyperintenseuterine fibroids on MRI-T2WI who scheduled for HIFU were enrolled inthe1st Affiliated Hospital of Chongqing Medical University.2. EquipmentsEquipment is the same as that of the first part research.3. Methods(1) Pretreatment magnetic resonance image evaluation:The size, numberand position of the uterus and fibroids, signal intensity of fibroid onMRI-T2WI and dynamic contrast-enhanced MR imaging，the distance fromfibroid ventral side to skin and fibroid dorsal side to sacral, abdominal wallthickness, hyperintense signal type of fibroids, enhancement type of fibroids are recorded. All the images were read and measured by threeexperienced radiologists.Uterine fibroids were classified as hypointense, isointense andhyperintense on pretreatment T2-weighted MRI isointense. Classificationcriterias is the same as that of the first part research.Uterine fibroids were classified as slight enhancement, irregularenhancement and regular enhancement relative to myometrium on the basisof dynamic contrast-enhanced MRI. Classification criterias is the same asthat of the first part research.(2) Ultrasound ablation: The proceses is the same as that of the first partresearch.(3) Main Outcome Measures: Main outcome measures are the same asthat of the first part research.(4) Posttreatment magnetic resonance image evaluation: Parameters arethe same as that of the first part research.4. Statistical methodsStatistical analysis was performed by using SPSS17.0software.Part three1. ObjectiveFrom October2010to January2013,15patients with hyperintenseuterine fibroids who undergone double HIFU were enrolled in the1stAffiliated Hospital of Chongqing Medical University. 2. EquipmentsEquipment is the same as that of the first part research.3. Methods(1) Pretreatment magnetic resonance image evaluation: The size, NPV,NPV ratio of fibroids are recorded by plain and enhanced MRI scanningbefore and after1st HIFU treatment.(2) Ultrasound ablation: The proceses is the same as that of the first partresearch.(3) Main Outcome Measures: Main outcome measures are the same as thatof the first part research.(4) Posttreatment magnetic resonance image evaluation: Parameters are thesame as that of the first part research.4. Statistical methodsStatistical analysis was performed by using SPSS17.0software.Part four1. ObjectiveFrom April2012to December2012,35patients who undergonemyomectomy or hysterectomy, a total of39isolated fibroid specimens areenrolled in the1st Affiliated Hospital of Chongqing Medical University.2. EquipmentsParaffin section machine is produced by Chang yuan experimental setupfactory in Beijing; Light microscope is produced by Japanese OlympusCompany. Other equipment is the same as that of the first part research. 3. Methods(1) Pretreatment magnetic resonance image evaluation: Measurement isthe same as that of the first part research.(2) Main Outcome Measures: The density of fibroids is measured bymass and volume method, the moisture content of fibroids is measured bydrying method, the organization structure of fibroids is observed by HE andporosities red staining, the expression of PR and ER is observed byimmunohistochemical staining.(3) Ultrasound ablation: Isolated fibroid specimen is ablated by HIFU,gray scale of fibroid specimen during procedure is recorded by includedsoftware of HIFU system, coagulation necrosis area of fibroid specimenafter procedure is measured.4. Statistical methodsStatistical analysis was performed by using SPSS17.0software.ResultsPart one1. Ablation results: Hyperintense fibroids had significantly higher EEFthan that of hypointense/isointense fibroids, but with lower treatmentefficiency and smaller NPV ratio. Among hyperintense fibroids, slightlyhomogeneous hyperintense fibroids had the smallest NPV ratio andtreatment efficiency, but the highest EEF. No difference was observedbetween markedly homogeneous and heterogeneous hyperintense fibroidsand hypointense/isointense fibroids. Acceptability: The incidence of pain and pain scores were significantlyhigher in patients with slightly homogenous hyperintense fibroids than thatof patients with hypointense/isointense fibroids.2. Ablation results: The fibroids with regular enhancement on dynamiccontrast-enhanced MRI had the lowest NPV ratio and treatment efficiency,but the highest EEF.Acceptability: The mean pain scores of regular enhancement are higherthan that of patients with slight and irregular enhancement.3. Ablation results: Among hyperintense fibroids, the fibroids withslightly homogeneous hyperintense on T2WI and regular enhancement ondynamic contrast-enhanced MRI had the smallest NPV ratio and treatmentefficiency, but the highest EEF.Acceptability: No difference was observed in the incidence of pain andthe mean pain scores of patients with slightly homogeneous hyperintensefibroids on T2WI and regular enhancement on dynamic contrast-enhancedMRI are higher than other group.Prediction Specificity of three methods: The specificity of T2WIcombining dynamic contrast-enhanced MRI is the highest for predicting theefficacy of HIFU ablating hyperintense fibroids.Part two1. The sonication energy of HIFU ablating hyperintense fibroids isrelation to thedistance from fibroid ventral side to skin, maximum diameter of fibroid, enhancement type of fibroids and T2WI hyperintense signal typeof fibroids.2. Dosimetric models of HIFU ablating hyperintense fibroids:y=0.474*X1-0.427*X2+6.212*X3+4.914*X4[y=EEF, X1=the distance from fibroid ventral side to skin；X2=maximum diameter of fibroid；X3=enhancement type of fibroids（1=slightenhancement，2=irregular enhancement，3=regular enhancement）；X4=hyperintense signal type of fibroids（1=heterogeneous hyperintensefibroids,2=markedly homogeneous fibroids,3=slightly homogenoushyperintense fibroids）]Part threeAblation results: The second HIFU ablation of recuring slightlyhomogeneous hyperintense fibroids is no difference with1stHIFU ablationin treatment efficiency, NPV and EEF.Acceptability: There is no difference between two groups in theincidence of pain and the mean pain scores.Part four1. The density and the collagen content of slightly homogeneoushyperintense fibroid are lower than that of hypointense/isointense fibroids,but the moisture content and cell content is richer, the expression of ER andPR is higher.2. When isolated fibroid specimen is ablated by HIFU, gray scale of slightly homogeneous hyperintense fibroids during procedure is smallerthan hypointense fibroid, and real coagulation necrosis area is also smallerafter procedure.Conclusions1. From a perspective of technology success, heterogeneous hyperintensefibroids and markedly hyperintense fibroids on T2-weighted MRI, thefibroids with regular enhancement on dynamic contrast-enhanced MRI canbe considered as an indication of HIFU; the fibroids with slightlyhomogeneous hyperintense on T2WI and regular enhancement on dynamiccontrast-enhanced MRI is the hardest to ablate. MRI-T2WI combiningdynamic contrast-enhanced MRI can predict the efficacy of HIFU ablatinghyperintense fibroids.2. The distance from fibroid ventral side to skin, maximum diameter offibroid, enhancement type of fibroids and T2WI hyperintense signal type offibroids can be as a predictor of sonication energy of HIFU ablatinghyperintense fibroids.3. The second HIFU ablation can not improve therapeutic efficacy ofrecuring slightly homogeneous hyperintense fibroid after1stHIFU ablation.4. Lower density and collagen, richer moisture content and cell content,higher expression of ER and PR are reason for unsatisfactory therapeuticefficacy of HIFU ablating slightly homogeneous hyperintense fibroids.