| Objective The present work evaluated whether or not asuperabsorbent polymer (SAP) and ultrasound contrast agent (UCA) aloneor in combination could enhance damage efficacy of high-intensity focusedultrasound (HIFU) on hydatid cysts and explore a new combined therapyfor echinococcosis.Methods and results Firstly, HIFU of50W acoustic power and10μlUCA were used to treat protoscolices suspensions. After different HIFUexposure time, the changes of ultrasound images of protoscolices wereobserved, the temperatures of protoscolices suspensions were taken, theprotoscolices of the cysts were stained by eosin exclusion assay, and thestructures of protoscolices were observed by light microscopy. Withincrease of HIFU irradiation time, the changes of ultrasonic gray scale ofprotoscolices increased, and similar profiles of protoscolices death rate andrising temperature of protoscolices suspensions were observed as well when HIFU irradiation power was constant. It was also observed that thechanges of protoscolices mentioned above were more pronounced in thegroup treated with same dose of HIFU assisted with UCA. At a constantacoustic power of HIFU, although extending treatment time of HIFU alonecould increase the temperature of protoscolices suspension as high as thattreated with HIFU and UCA, the death rate of protoscolices irradiated byHIFU alone was less than that treated by HIFU and UCA. HIFU of50Wacoustic power, with the aid of10μl UCA and0.01g SAP alone or incombination, was used to ablate protoscolices suspensions. Echoenhancement of ultrasound image, increase of mortality rate ofprotoscolices, and serious structural damages of protoscolices wereobserved in the group of HIFU combined with UCA or SAP alone. Thestructural changes of protoscolices were also observed in the group ofHIFU irradiation aided with a combination of UCA and SAP, which wasmore obvious than that treated with HIFU just with aid of UCA or SAPalone.Secondly, One hundred and fifty fresh cysts were divided into6groups according to the diameters of cysts, and every group was receivedfollowing treatments respectively: Group A without HIFU treatment; GroupB treated with0.1μl UCA only; Group C treated with HIFU only; Group Dtreated with0.1ml UCA and HIFU; Group E treated with0.2ml UCA and HIFU. During the irradiation of HIFU, the changes of ultrasonic gray scaleof the cysts were recorded accordingly, and the instant death rates ofprotoscoleces were determined from the hydatid fluids. It wasdemonstrated that the changes of ultrasonic gray scale and the instant deathrate of protoscoleces treated with UCA and HIFU were significant thanthose in the groups treated with HIFU only, or UCA only, and the changeswere obvious in the groups treated with the increase of UCA. Then Fifteenfresh cysts were divided into3groups and every group was receivedfollowing treatments respectively: Group A (blank control) without HIFUtreatment; Group B treated with HIFU only; Group C treated with0.1mlUCA and HIFU. During the irradiation of HIFU, the changes of ultrasonicgray scale of the cysts and the macroscopic observation of cyst walls weretaken, the pathological, scanning electron microscopy and transmissionelectron microscopy of cyst walls were taken as well. It was found thatHIFU could destroy laminated layer and germinal layer of cyst walls, butthere was at a certain extent residual of germinal layer. Completedestruction or even disappearance of laminated layer and germinal layerwas observed in the cysts treated by HIFU combined with UCA. Thehydatid cysts were used for the ablation HIFU with the aid of UCA andSAP alone or in combination. The echo enhancements of ultrasound image,increases of mortality rates of protoscolices, and serious structural damages of protoscolices were observed in the cysts ablated by HIFU combined withUCA and SAP alone or in combination, and the combination of UCA andSAP revealed a best assistive effect on HIFU ablation. To evaluate whetheror not the destructive effects of HIFU (100w) on the cyst walls couldenhanced by UCA and SAP alone or in combination, the gross pathologicalobservations of ablated cysts, and observations of pathological, scanningelectron microscopy and transmission electron microscopy of ablated cystwalls were taken. It was observed that HIFU could destroy laminated layersand germinal layers of cyst walls, but there were residuals of germinallayers. Complete destructions or even disappearances of laminated layersand germinal layers were observed in the cysts ablated by HIFU combinedwith UCA and SAP alone or in combination. It was also found that thedestructive effect of HIFU aided with a combination of UCA and SAP tohydatid cysts was more effective than that of HIFU just aided with UCA orSAP alone. These results suggested that both UCA and SAP could be usedas a HIFU enhancing agent to improve the efficacy of HIFU on hydatidcysts without prolonging ablation time and increasing acoustic power ofHIFU，which could reduce the recurrence of cystic echinococcosis.Thirdly, a rabbit model with transplanted hydatid cyst was establishedby implanting a cyst isolated from infected sheep liver, and HIFU with theaid of UCA and SAP alone or in combination was used to ablate hydatid cysts in the abdominal cavities of rabbits. The results demonstrated thatHIFU had some lethal effects on hydatid cysts in vivo, namely echoenhancements of ultrasound images, increases of mortality rates ofprotoscolices, serious structural damages of protoscolices, and destructionsor even disappearance of laminated layer and germinal layer in the cystsablated by HIFU combined with UCA and SAP alone or in combination.There were no evidences of pathological changes on the rabbits’ skinsoverlying the cysts after HIFU ablation. The results suggested that therabbit model with transplanted hydatid cyst may serve as an idealexperimental animal model for HIFU-ablation trial to hydatid cyst in vivo,and the materials of UCA and SAP were proved as HIFU enhancing agentsin HIFU ablation therapy for hydatosis of the animal model, and HIFU at adosage of100W acoustic powers was a safe and feasible parameter toablate hydatid cysts in the special animal model. These results laid atheoretical foundation for improving HIFU therapy for hydatosis byinoculation of UCA and SAP into hydatid cysts.Conclusions Firstly, the killing effect of HIFU on protoscolices can beenhanced by adding UCA to the protoscolices suspensions, which resultedfrom both cavitation and thermal effects of UCA, and UCA could be usedas synergistic agent to improve efficacy of HIFU on hydatid cyst; secondly,the destructive effects of HIFU on the protoscolices isolated from hydatid cysts could be enhanced by UCA and SAP alone or in combination, and thecombination of UCA and SAP revealed a best ablation effect; thirdly, UCAcould enhance the killing efficacy of HIFU on hydatid cyst in vitro;fourthly, UCA could enhance the destructive effects of HIFU on hydatidcyst walls in vitro; fifthly, UCA and SAP might be used as a HIFUenhancing agent to improve the efficacy of HIFU ablation to hydatid cysts,which could be a possible therapeutic option for cystic echinococcosis;sixthly, the rabbit model with transplanted hydatid cyst may serve as anoptional animal model for the experiments of HIFU ablation to hydatid cystin vivo; finaly, the destructive effect of HIFU ablation on hydatid cysts inthe rabbit model could be enhanced by UCA and SAP alone or incombination, and destruction of HIFU aided with a combination of UCAand SAP to hydatid cyst was more effective than those aided with UCA orSAP alone. No pathological changes were found on the skins of rabbitsthrough which the HIFU passed. |
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