| Uterine fibroids are the most common benign tumors in women with childbearing age.In China,the incidence is about 20~50%.High intensity focused ultrasound(HIFU)is a noninvasive treatment technique.However,for some special types of fibroids(deeper position,hypervascularity,celluar,etc.),the treatment may be inefficient and time-consuming,which may lead to a lot of serious complications.How to improve efficiency of treatment,shorten the ablated time,reduce the incidence of adverse reactions and ensure the security? This issues of HIFU still need be addressed in the ablation of uterine fibroids.In this study,the clinical comparative study was applied to explored the safety and efficacy of micro-bubble contrast agent(Sono Vue)enhancing treatment effects of HIFU for uterine fibroids.Then,a variety of functional MRI techniques(diffusion weighted imaging(DWI),T1 Mapping and T2 Mapping)was used to predict the difficulty of ablation and evaluate the effectiveness for the enhancing treatment effects of HIFU after administration of Sono Vue;and the multi-modal methods were applied to provide the information about the pathologic features of various types of uterine fibroids before and after ablation.Ultimately,various multi-modal radiological methods were ensured safer and more effective of the enhancing treatment effects of HIFU after administration of Sono Vue and used to guide the clinical treatment.Objectives: To assess the feasibility,safety and efficacy of the enhancing treatment effects of HIFU after administration of Sono Vue;to predict the difficulty of ablation and evaluate the effectiveness for the enhancing treatment effects of HIFU after administration of Sono Vue by the use of functional MRI(such as DWI and ADC,T1 Mapping and T2 mapping)to find more convenient and intuitive classification with the help of functional MRI.Finally,the aim is to improve the accuracy,clinical efficacy and efficiency of HIFU in the treatment of uterine fibroids and to provide fully evidence for the clinical application and promotion in the future.Methods:(1)232 patients were divided into two treatment groups according to the order of treatment time: HIFU ablation group(group A)and HIFU + microbubble contrast agent ablation group(group B).Two groups were treated by JC-200 focused ultrasound tumor treatment system.During the treatment,the pain degree visual analogue scale was used to evaluate the response to the patients and recorded the major adverse events after administration of Sono Vue.After the treatment,various dose-related parameters(release energy,irradiation time,treatment time,irradiation power,treatment intensity and ablation efficiency)and dosimetric parameter(energy efficiency factor,EEF)were recorded for both groups,and the complications and adverse events were evaluated.The cases were scanned by MRI before and after ablation in order to localize and evaluate the ablation effects.Whether were the fibroids filled with magnetic resonance contrast agent,which was defined as necrosis.(2)There were 156 patients with symptomatic uterine fibroids.Followed the traditional method,all fibroids were subdivided into 5 groups according to the signal intensity of T2 WI image.DWI images were obtained before and after ablation,and the DWI and ADC values were measured on the post-processing station.Qualitative and quantitative analysis were worked,respectively.Firstly,the characteristics of DWI images before and after ablation were observed for 5 groups of uterine fibroids.Then,the values of DWI and ADC of 5 groups before and after ablation were compared with those of normal myometrium.Finally,the values of the dose-related parameters of 5 groups of uterine fibroids were recorded and compared with each other.The correlation between the ADC values and the difficulty of ablation of uterine fibroids was studied.(3)Before and after ablation,5 groups of uterine fibroids were scanned by T1 Mapping,T1 Mapping functional images were obtained and T1 signal values were measured.T1 values of 5 groups of fibroids were compared with those of myometrium;T1 values of each group before and after the treatment were compared,respectively.Finally,the correlation between T1 values and the difficulty of ablation for uterine fibroids was investigated based on the above qualitative and quantitative data.(4)Before and after ablation,5 groups of uterine fibroids were scanned by T2 Mapping,functional images were obtained and T2 signal values were measured.The functional images of uterine fibroids before and after ablation were qualitatively and quantitatively assessed.Qualitative assessment: T2 pseudo-color maps before and after the ablation were compared and observed the signal changes.And then,the fibroids were classified according to those maps.Quantitative assessment: Firstly,T2 values of 5 groups of fibroids were compared with those of myometrium;T2 values of each group before and after the treatment were compared,respectively.Finally,based on the T2 pseudocolor maps and T2 values,the nature of uterine fibroids and the changes after ablation were analyzed from the microscopic pathology.Results:(1)The irradiation time,irradiation power and irradiation intensity of group B(HIFU+Sono Vue)were lower than those of group A(HIFU alone group).The ablation efficiency of group B was higher than that of group A(P < 0.05).For the group B,time of the appearance of the stable hyperechogenicity was shorter than that of group A,the difference was statistically significant(P < 0.05).The incidence rate of adverse reactions in pain,skin burning and radiating pain of lower limb was lower in group B than in group A,and there was significant difference between the two groups.The visual analogue scores were 3.1±0.9 and 3.5±0.8,respectively,and the highest scores were no more than 5 points.There was no significant difference between the two groups.For B group,no complications such as first-degree burn and sacrococcygeal pain was found.(2)Qualitative assessments of DWI images: for 5 groups of uterine fibroids,DWI functional maps before treatment showed that the signal in the ablated area was even lower(compared with the myometrium);DWI functional maps after treatment showed that the surrounding of ablation area showed high signal and the center region of ablation area showed low signal,like the target ring.Quantitative assessments of DWI: ADC values were compared among the 6 groups;the difference was statistically significant.ADC values were sorted that myometrium>slightly homogeneous hyperintense group>markedly homogenous hyperintense group>hetero-geneous hyperintense group> isointense group> hypointense group.ADC values after treatment in each group was lower than that before treatment(P<0.05).The ADC values of isointense group and hypointense group were the lowest,so the uterine fibroids of these two groups were easily ablated by HIFU and shorter time.For slightly homogeneous hyperintense group,the ADC value was highest among five groups,and there were time-comsuming,inefficient and the highest EEF.So the treatment for the fibroids of this group were the most difficult among the five groups.(3)Quantitative assessments of T1 Mapping: The T1 values of uterine fibroids in five groups were compared with myometrium.There was significant difference among six groups(P<0.05).The difference was statistically significant between T1 values of each group before and after operation(P<0.05).T1 values were sorted that myometrium>slightly homogeneous hyperintense group>markedly homogenous hyperintense group>heterogeneous hyperintense group> hypointense group> isointense group.(4)Qualitative assessments of T2 Mapping: The color of hypointense group was lighter than that of myometrium.The color of isointense group showed the combination of dark and light color but mainly light.The color of hetero-geneous hyperintense group showed the combination of dark and light color but mainly dark.The color of slightly homogeneous hyperintense group was even-distributed which was in between hypointense group and markedly homogenous hyperintense group.The color of markedly homogenous hyperintense group was even-distributed which was in between slightly homogeneous hyperintense group and hetero-geneous hyperintense group.Quantitative assessments of T2 Mapping: For isointense group,T2 values after treatment were lower than those before treatment(135.58±27.92 vs 77.67±25.84.P<0.05).For the other four groups,T2 values after treatment were higher than those before treatment.Pathological structures were deduced: ?hypointense group: fibroids with collagen fibers showed that collagen fibers were arranged in the direction of the disorder or the structure of collagen fiber was damaged or even disintegrated after the ablation,which accompanied by water molecules increased.The result showed that the internal color becomed deeper and T2 values were increased after ablation.?collagen fibers of isointense group were more than those of hypointense group and the damaged smooth muscle cells were replaced by white or translucent collagen tissue after ablation.Finally,T2 value decreased.?T2 values of hetero-geneous hyperintense group and markedly homogenous hyperintense group were higher before treatment than after treatment.We deduce that fibroids for the two groups contained other ingredients(such as mucous,cystic fluid and fat),but hyalinization and revolutionary never happen.?the uterine fibroids with rich cells for lightly homogeneous hyperintense group after ablation showed that abnormal smooth muscle cells were dehydrated and necrosis;the small blood vessels and capillaries appeared embolism and rupture;red blood cells penetrated between the muscle fibers;tumor tissue was edema;and intracellular water becomed free water.Finally,T2 value increased.Conclusions:(1)Ultrasound contrast agent(Sono Vue)can reduce the irradiation time and the time of the appearance of the stable hyperechogenicity,improve the ablation efficiency,reduce the irradiation power and treatment intensity,reduce the occurrence of side effects and adverse reactions.This therapeutic way is safe,effective and has worthwhile for the clinical application.(2)The characteristics of DWI functional images display are related to the distribution of the vessels with fibroids and the energy deposition site during ablation.The ADC values of fibroids in hypointense group and isointense group are the lowest than other groups,so the treatment of fibroids were easier and shorter time.The fibroids in the slightly homogeneous hyperintense group which were the higher ADC value,the longer time,the lowest ablated rate and the highest EEF,which was the most difficult to ablate in the five types of fibroids.(3)T1 signal values were measured by T1 mapping functional images.T1 values were sorted that myometrium>slightly homogeneous hyperintense group>markedly homogenous hyperintense group>hetero-geneous hyperintense group>hypointense group>isointense group.For the five types of uterine fibroids,the higher was T1 value and the more difficult treatment was the fibroids,and the converse is also true.T1 value was higher after treatment than before treatment.(4)T2 pseudo-color image and its value were obtained by T2 Mapping technique based on multi-echo spin echo sequence.According to T2 functional pseudo-color map,uterine fibroids were more intuitively classified.The pathological changes of different types for uterine fibroids were deduced based on T2 functional Pseudo-color images combined with T2 values.To meet the demands which was micro-pathological results based on radiological techniques.This established the foundation to develop radiology-pathology. |
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