Study On The Biological Effect And Clinical Dosimetry Of Focused Ultrasound Ablation Of Breast Fibroadenoma

In the past two decades,focused ultrasound ablation surgery(FUAS)has been increasingly applied to the clinical treatment of breast cancer and breast fibroadenoma because of its advantages of non-invasiveness and preserving the breast cosmesis.However,with the development of clinical application,researchers found that the effectiveness and safety of FUAS in the treatment of breast lesions varied in different studies.The possible reason was that the biological focal region(BFR)of focused ultrasound transducer used in previous clinical studies was mostly with narrow ellipsoid or lancet-like shape,which was easily leaded to tissue damage in the acoustic pathway when FUAS was used in the treatment of breast tumors.ObjectivesBased on the studies of new designed focused ultrasound transducer produced by our team in the early stage,the aim of this study is to explore the BFR morphology optimization and biological effect improvement of FUAS by using this new transducer in different tissue acoustic fields,and study the clinical efficacy and clinical dosimetry influencing factors of FUAS in the treatment of breast fibroadenoma,in order to provide clinical dosimetry basis for the formulation and optimization of clinical treatment scheme of FUAS ablation of breast fibroadenoma.Materials and methods(1)Taking the traditional transducer as the control,the degassed water was used as the ideal acoustic field,the bionic phantom was used as the inorganic acoustic field,the bovine liver was used as the simple tissue acoustic field,and the bovine liver with pig skin and ribs were used as the complicated tissue acoustic field.The new transducer generated focused ultrasound with different energy,and the morphological differences of AFR and BFR between the new transducer and the traditional transducer in different acoustic fields were observed.The difference of coagulation necrosis volume and the temperature rise between the near field and the far field of the acoustic pathway were detected by thermocouple.(2)Adult lactating female goats were selected.Under general anesthesia,two kinds of transducers were used for breast sonication experiment.The animals were euthanized 7 days after sonication.After pictures of skin and acoustic channel tissue were collected,breast tissue was cut.TTC staining,H&E staining and transmission electron microscopy were performed.(3)A total of 76 patients with breast fibroadenoma diagnosed by core needle puncture and treated by FUAS were enrolled in the clinical trial,including 49 cases in the new transducer group(78 lesions)and 27 cases in the traditional transducer group(35 lesions).The baseline level,treatment information,treatment effectiveness indicators(ablation rate,EEF)and safety indicators(intra-treatment pain VAS score,adverse events)were compared.Among them,5 patients in the new transducer group underwent mastectomy within 1 week after FUAS treatment,and the ablated fibroadenoma were underwent TTC staining,H&E staining,NADH diaphorase staining and electron microscopy.(4)The basic conditions and treatment information of 78 breast fibroadenoma lesions in the new transducer group were retrospectively analyzed.The ablation rate and EEF were taken as dependent variables,and a total of 7 factors were taken as independent variables,including age,body mass index(BMI),the longest diameter of the lesion,the distance from shallow margin of fibroadenoma to the skin,the distance from deep margin of fibroadenoma to the pectoralis major muscle,the tissue type of the near field of the acoustic pathway.The correlations between independent variables and dependent variables were analyzed.Furthermore,the optimize scaling regression model was established for analyzing the influencing factors of EEF,and the dosimetry prediction model is verified.Results(1)Under the same sonication energy,the AFR shape and BFR shape of the new transducer were ellipsoid or conical,while the AFR shape and BFR shape of the traditional transducer were spindle,and there was a significant difference in the aspect ratio of AFR and BFR between them(P < 0.05).Under the same sonication energy,the volume of coagulation necrosis caused by the new transducer was significantly larger than that of the traditional transducer,and the EEF value was significantly lower than that of the traditional transducer(P < 0.05).The temperature rise of each temperature measuring point of the new transducer in the near field and the far field of the acoustic pathway was significantly lower than that of the traditional transducer(P < 0.05).(2)In animal experiments,the necrosis volume of the coagulative necrosis area of the new transducer were significantly larger,and EEF was significantly smaller than the traditional transducer(P < 0.05).When using high sonication energy,the skin on the goat mammary gland surface was intact immediately after sonication with the new transducer,while two slightly red areas appeared on the skin surface of the goat mammary gland immediately after the sonication of the traditional transducer.It was found that there were no signs of tissue damage in the acoustic pathway of the two transducers.The results of H & E staining and transmission electron microscope confirmed that the goat mammary gland target appeared typical coagulation necrosis after sonication with the new transducer.(3)The results of clinical trial showed that there was no significant difference in age,BMI and lesion length between the two groups(P >0.05).The total treatment time,treatment time per unit volume of tumor and hyperechoic scale emerging time in the new transducer group were significantly shorter than those in the traditional transducer group(P <0.05).There was no significant difference in sonication energy and ablation rate between the two groups(P > 0.05).The EEF of the new transducer group was higher than that of the traditional transducer group(P < 0.05).After ablation of breast fibroadenoma with a new transducer,TTC staining,H&E staining,NADH diaphorase staining and electron microscopy showed coagulative necrosis in the target tissue.There were no adverse events,such as fever,delayed skin injury and pectoralis major muscle injury,in both groups.The VAS score of the new transducer group was significantly lower than that of the traditional transducer group(P <0.05).(4)The independent variables significantly correlated with EEF included the length of fibroadenoma,the distance from the lesion to the skin and the type of near field tissue of acoustic pathway.The EEF prediction model was established based on the three independent variables: (?) =-0.496 × X1 + 0.287 × X2 + 0.203 × X3(variable: (?) = EEF,X1 = the length of fibroadenoma,X2 = the distance from the lesion to the skin,X3= the type of near field tissue of acoustic pathway).ConclusionIn this study,the biological effects of focused ultrasound ablation of breast tissue were comprehensively analyzed through in vitro tissue,in vivo animal experiment and clinical research.The results showed that compared with the traditional transducer,the new transducer was more effective and safer in the treatment of breast fibroadenoma.The factors influencing the clinical dosimetry of focused ultrasound ablation of breast fibroadenoma were analyzed for the first time,and a dose prediction model was established.The results showed that the length of fibroadenoma,the distance from the lesion to the skin and the type of near field tissue of acoustic pathway could be used as predictors to evaluate the dosimetry of FUAS.