| BACKGROUNDHigh intensity focused ultrasound (HIFU)has been under development for the noninvasive destruction of deep-seated tumors since the ultrasound energy can be focused to ablate tissues without damage to the overlaying or surrounding tissues. However HIFU has not been widely used in the clinical setting because it is difficult to determine the relative success or failure of the treatment.Magnetic resonance imaging (MRI) has been proposed for guiding and monitoring thermal surgery. MRI has high soft-tissue contrast and provides high-resolution images for the pre-treatment target definition and post-treatment lesion evaluation. It has been shown that there is a good correlation between the MRI images and the histology lesion sizes induced in muscle. MRI also has temperature sensitivity and provides temperature images for the ultrasound beam localization in the tissue during the sub-threshold test sonication.MRI thermometry can also be utilized to evaluate the thermal dose induced by the ultrasound beam during HIFU sonication. The thermal dose, which depends on a cumulative relationship between the temperature elevation and the duration of the exposure, provides a reasonable prediction of the size of a coagulated tissue volume. The purpose of this study was to investigate whether the equivalent thermal dose calculation based on the T-Map of MRI can be utilized for the thermal dose of the ultrasound beam in vivo.OBJECTIVE1. Calculated the threshold thermal dosage of coagulation at a 200W-10s sonication delivered in fresh beef liver tissue in vitro and rabbit thigh muscular tissue in vivo separately, used the result as a reference threshold thermal dosage, and calculated the boundary of the coagulated tissue at varying power and exposure time sonication, the calculated dimension was comparable with dimension on the histological slides. Discussing relationships of the equivalent thermal dose with tissue damage during HIFU treatment.2. Calculated the boundary of the coagulated tissue at varying power and exposure time sonication for different reference threshold temperature, and the calculated dimension of the coagulated tissue was comparable with dimension on the histological slides. Discussing relationships of temperature with tissue damage during HIFU treatment.MATERIALS AND METHODS 1. Experiment in vitro1.1 Experiment Equipment: MR imaging guided HIFU (MRIgHIFU) system which was developed by Chongqing Haifu (HIFU) Technology Co., Ltd. and Siemens together. The parameters of therapeutic transducer were: frequency-1.0MHz, focal length-150mm.1.2 Materials: Fresh beef liver tissue which had been cut into 10 cm×8 cm×6 cm size and immersed in the normal saline, back-up after 30 minutes conventional degassing.1.3 Methods: Sonications were delivered in tissue at a fixed depth of 20 mm at varying powers (150W, 200W, 250W) and times (5s, 10s, 15s). Twelve dots each group. MRI T-Map was obtained during the sonications to estimate the temperature and the thermal dosage of each voxel in the target region. The thermal dosage of each voxel was compared with the reference threshold thermal dosage to calculate the boundary and area of the coagulated tissue. Time sampling interval of MRI T-Map was 1 second, and temperature values were showed in different colors (blue: 30℃-37℃, green: 37℃-45℃, yellow: 45℃-55℃, red: 55℃-100℃). After the exposure, scan T1, T2, and PD sequences first, and then calculated the boundary of the coagulated tissue at varying power and exposure time sonication for different reference threshold temperature. The coagulation on the histological slides was comparable with calculated dimension of the coagulated tissue based on equivalent thermal dose and different reference threshold temperature, and the difference between them can be obtained. SPSS12.0 and Excel statistical software were used for the statistical analysis.2. Experiment in vivoExperiment Equipment: The same with experiment in vitro.Materials: New Zealand white rabbits.Methods: Sonications were delivered in rabbit thigh muscular tissue at 200W, 10s. Other operations were similar to experiment in vitro, and the only difference was colors representing different temperature values (blue: 45℃-50℃, green: 50℃-55℃, yellow: 55℃-60℃, red: 60℃-100℃).RESULTS1. The temperature of focus went up expeditiously during a sonication delivered in fresh beef liver tissue,and descended to the foundational temperature fleetly at the end of exposure. And the equivalent thermal dose reached its peak value seconds after the exposure, meanwhile a decrease of temperature had already begun.2. Area of target tissue where the temperature was higher than 55℃got lager during a sonication delivered in fresh beef liver tissue, and peaked at the end of exposure, then became smaller after the sonication; Calculated dimension of the coagulated tissue based on thermal dose also got lager during the sonication, and kept on growing over a period of time after the exposure. 3. 100 percent macroscopic damages were made at varying power and exposure time sonication delivered in fresh beef liver tissue, 108 dots in 9 groups. The coagulation area was hoar, augmented significantly with increase of exposure power and time, and the boundary was clear. Calculated dimension of the coagulated tissue based on thermal dose also got lager with increase of exposure power and time.4. The result of calculating the threshold thermal dosage of coagulation at a 200W-10s sonication delivered in fresh beef liver tissue in vitro was 59.6min, and there was no statistical significance between the calculated dimension of the coagulated tissue based on this reference threshold thermal dosage and the calculated dimension of the anatomical coagulated area. And there was no statistical significance between the calculated dimension of the coagulated tissue and the anatomical coagulation area when reference threshold temperature was 52℃in 7 groups of 9, but only 1 group of 9 when reference threshold temperature was 56℃. And when reference threshold temperature was 56℃,all the calculated dimension of the coagulated tissue were smaller than the anatomical coagulation area.5. In experiment of 200W-10s sonication delivered in normal rabbit leg muscular tissues by dot in vivo, there was no statistical significance between the calculated dimension of the coagulated tissue and the anatomical coagulation area when reference threshold thermal dosage was 136.5min, and when reference threshold temperature was 56℃. When reference threshold thermal dosage changed from 59.6min to 240min, the calculated dimension of the coagulated tissue varied with it from 29.9±5.8mm2 to 20.7±4.4mm2, and when reference threshold temperature changed from 52℃to 60℃, the calculated dimension of the coagulated tissue varied from 33.7±10.2mm2 to 12.3±7.4mm2.CONCLUSION1. The temperature-map (T-Map) collected during MRI guided HIFU treatment clearly reflected temperature changes in targete area, and the decrease of temperature after exposure was still useful to the calculus of thermal dosage.2. The equivalent thermal dose calculation based on the T-map of MRI correlated well with the tissue damage, and the results of experiments in vitro and in vivo were different, 59.6min in vitro, 133.8min in vivo. The difference resulted from animal body fluid cycle took away part of focal area heat and impacted the accumulation of thermal dose.3. Temperature was an important index to determine whether the tissue was damaged or not, however, to accurately determine the coagulation area, impact of time needed to be considered.
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