| BACKGROUNDHigh intensity focused ultrasound (HIFU) has been an emerging noninvasive technology for clinical treatment of some tumors and non-tumor diseases and the outcomes are good. How HIFU can be used to treat is that low intensity ultrasound is focused into the body to form a high intensity target, where hyperther mi a, cavitation and mechanical effects are generated. So nonreversible damage, coagulative necrosis is formed as the temperature at the focus rise above56℃within1s.Being a noninvasive surgical tool, monitor is a key factor of the HIFU therapy. Reliable and accurate monitor tool is essential for safe and effective HIFU therapy. The main monitoring modalities are B-mode ultrasonography (US) and magnetic resonance imaging (MRI), so the HIFU therapy devices can be classified into US guided HIFU (USgHIFU) and MRI guided HIFU (MRIgHIFU). US has advantages of real-time monitoring, simplicity, low-price and easy combination with HIFU device. USgHIFU treatment devices have been used in clinic for several years. US can be used to monitor HIFU treatment is based in hyperecho in B-mode image after HIFU irradiation and it is the current clinical "gold standard’ for identifying tissue ablation. But main reason of appearance of hyperrcho in B-mode image was not clear, and the debate is cavitation bubbles and boiling bubbles.Coagulation necrosis in the tissues induced by HIFU exposure is ellipsoidal in shape. However, drop-shaped and triangle-shaped lesions can also be seen in some conditions. There were also some debates between cavitation bubbles and boiling bubbles about the cause of deformations.Thus, we investigated the reasons of hyperecho and lesion deformation in the focal region of HIFU with various irradiation parameters to generate cavitation bubbles and/or boiling bubbles. In this study, B-mode images after exposures were obtained and compared with those before HIFU, ex vivo bovine livers were sliced to get the shapes of lesions.The main mechanism of HIFU therapy is thermal. Besides, cavitation can result high-temperature, high-pressure, high-speed jet to damage surrounding tissues. Some previous studies showed that hyperecho indicated over-treatment which threatened safety of HIFU therapy. Pulsed HIFU (pHIFU) can induce non-thermal damages in tissues. So another experiment in this study was to explore whether non-thermal erosion could be formed in the focal region of HIFU, the mechanism and monitoring using B-mode were also investigated preliminarily.PURPOSE1. To study the main reason of hyperecho in B-mode image after HIFU exposure;2. To study the main reason of lesion deformation during HIFU treatment;3. To explore the feasibility of non-thermal erosion in tissue exposed to pHIFU;4. To study the mechanism of erosion and monitoring using B-mode ultrasonography preliminarily.METHODS1. Materials:Bovine livers slaughtered within6hours with fewer blood vessels and connective tissue are cut into cuboids of100min×100mm×60mm and then negative pressure degassed in the saline for30minutes.2. Experimental Setup:Model JC200HIFU tumor therapeutic system (bowl-focused, US monitoring,0.94MHz); Passive cavitation detection system:planar piezoelectric transducers (0.5MHz and5MHz center frequency), high-speed data acquisition card, Lab VIEW development platform, computer etc.; Temperature acquisition system: temperature data loggers, E-type thermocouple, computer and data reading program.3. Methods:3.1Effect of cavitation and boiling bubbles to appearance of hyperecho and lesion deformation after ex vivo tissue exposed to HIFU(1) Correct output of HIFU device;(2) HIFU point sonications were delivered in degassed bovine livers with20mm-depth, parameters were50W×10s,50W×10s,100W×10s,150W×5s,200W×2s and200W×5s;(3) During HIFU irradiations, acoustic emissions were obtained using the PCD system and then were transformed to frequency domain with a FFT program written on LabVIEW, and then amplitudes of sub-harmonics, fourth-harmonics and RMSs of broadband noise in3-7MHz were obtained;(4) During HIFU exposures, temperatures in the focal regions of HIFU were measured by the temperature acquisition system. The peak temperatures during6HIFU irradiations were statistically analyzed;(5) After20HIFU irradiations, B-mode images were recorded instantly and compared with those obtained before HIFU exposures;(6) After HIFU exposures, the livers were sliced into1-2mm and the maximum areas of coagulation necrosis were found to observe the lesion shapes.3.2Preliminary study of non-thermal erosion in ex vivo tissue exposed to pHIFU(1) Correct output of HIFU device and then set to pHIFU work mode;(2) HIFU point sonications were delivered in degassed bovine livers with follow irradiation parameters: Power (W) Duty cycle PRF (Hz) Time (s) Depth (mm)1%602%305004203%204%15(3) During HIFU irradiations, acoustic emissions were obtained using the PCD system and then were transformed to frequency domain;(4) During6HIFU irradiations, temperatures in the focal regions were measured by the temperature acquisition system and statistically analyzed;(5) After6exposures, B-mode images were obtained and compared with those before HIFU, the changes of grayscales were calculated.(6) After pHIFU exposures, the livers were sliced into1～2mm and the maximum areas of erosions were found. The specimens were hematoxylin-eosin (HE) stained.RESULTS1. Sub-harmonics were observed during all HIFU irradiations; RMSs of broadband noise increased with the powers of150W and200W; While the power is150W, RMS was small in the beginning and increased later; RMS was high but decreased during the200W-5s HIFU exposure;2. The peak temperatures in the focal regions of HIFU with parameters of50W×10s,50W×80s,100W×10s,150W×5s,200W×2s and200W×5s were62.40±6.50℃,93.61±2.46℃,67.29±2.56℃,77.84±6.96℃,75.69±5.18℃and88.10±4.06℃respectively;3. After HIFU irradiations with parameters of50W×10s,100W×10s,150Wx5s and200Wx2s, there was no hyperecho seen in the B-mode images, the lesions were ellipsoid-shaped; when parameters were200W×5s and50W×80s, hyperecho were observed, the lesions were drop-shaped and triangle-shaped respectively;4. The amplitudes of fourth-harmonics during HIFU irradiations of50W×80s and200W×5s increased, then RMS decreased when the parameter was200W×5s;5. The visible non-thermal damages in livers exposed to pHIFU were holes without solid contents;6. During the pHIFU irradiations with1%-4%duty cycles, the maximum temperatures in the focal regions were41.19±1.42℃45.73±1.92℃,53.07±2.09℃and64.13±2.56℃respectively, broadband noise were observed;7. Gray scales decreased after pHIFU irradiations with erosions formed.CONCLUSIONS1. Effects of cavitation and boiling bubbles to HIFU are different;2. Hyperecho and coagulation necrosis deformations are mainly caused by boiling bubbles;3. If fourth-harmonic relates to boiling, boiling bubbles are probably generated when the temperature in the focal region is approximately80℃;4. Temperatures in the focal region are affected by duty cycles of pHIFU, non-thermal erosions can be formed by high acoustic power, low duty cycles pHIFU exposures, cavitation may be the main injury mechanisms;5. B-mode ultrasonography has the potential to monitor pHIFU exposure, but a lot of researches will be necessary. |
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