Quantitative Assessment Of Percutaneous Radio-frequency Ablation Of Hepatic Metastases With Contrast-enhanced Ultrasonography

PREFACEHepatic metastases were one of clinical occurrences in malignant tumor with the high incidence rate of 30%～50%. Consequently, from the clinician's standpoint treatment of hepatic metastases would be very beneficial for clinical management.It was important to perform post-procedural assessment after radio frequency ablation (RFA) for hepatic metastases because of the high recurrence. Enhanced computed tomography and magnetic resonance imaging were the routine methods to assessing the therapy of intervention. However, they weren't convenient to be used to assess the treatment effect of RFA in real time, such as absence of residual tumor or not. RFA was guided by ultrasonography, as a result, Contrast-enhanced US had advantage in assessing the treatment in real time, quantitatively analyzing micro-vascular perfusion in tumor and distinguishing residual foci from ablated lesions. PURPOSETo investigate the usefulness of contrast-enhanced dynamic perfusion sonography in patients with hepatic metastases and evaluate the treatment efficacy of RFA quantitatively by time intensity curve (TIC) educed by contrast tune image (CnTI) together with US contrast agents (SonoVue).MATERIALS AND METHODS1. PatientsFrom October 2002 to May 2006, Twenty-five patients with hepatic metastases underwent RFA guided by sonography in our department (mean age, 56 years, age range, 38-79 years; female 10, male 15). Primary tumors as follows: pimeloma (8 patients), pancreatic carcinoma (4 patients), gastric carcinoma (4 patients), carcinoma of gallbladder (2 patients), mesenchymal tumor of gastrointestinal tract (2 patients), mammary cancer (2 patients), lung cancer (1 patient), esophageal carcinoma (1 patient), and one with unknown origin. Thirty-two hepatic metastases of twenty-five patients were quantitatively analyzed by contrast-enhanced imaging.2. Contrast agent and instrumentsContrast-enhanced US was performed by using Technos DU8 (Esaote Biomedica, Genoa, Italy). The US contrast agent SonoVue was used in all studies. A total of 2.4ml of SonoVue was injected quickly in bolus. As long as the process of contrast-enhanced US, CnTI was used. RFA was performed by using cooled-tip radio frequency lesion generator.3. Methods of contrast ultrasonography(1) Before RFA therapy: While beginning the real-time ultrasound contrast tuned image, the output of power was adjusted to low mechanical index status (0.05～0.11). Each time, one or two tumors in the same slice were selected as main objects for observation to dynamic perfusion during the first 60 seconds since injection. Then scanning of liver was performed to detect tumor on the portal venous and delayed phase.(2) After RFA therapy: Contrast-enhanced US scan of the same tumor were performed to assess treatment efficacy and detect residual unablated tumor or recurrence 30 minutes later and one month later respectively.4. Quantitative analysis methods of contrast ultrasoundThirty-two liver metastases of the twenty patients were sorted into hyper-vascular group (A) and hypo-vascular group (B). The typical enhancement pattern of group A was a whole or enhanced in the center and then as a whole in thearterial phase. The typical enhancement pattern of group B was on the peripheral edge, the center of tumor showed absence of perfusion. The pre- and post-procedural contrast US findings were compared quantitatively by analysis of the TIC of the region of interest in the edge of the tumor and the hepatic tissue. Quantitative analysis parameters included: Initial Time(IT), Initial Intensity( II), Peak Intensity(PI), Peak Time(PT) , Accelerate Slope(AS), Accelerate Time(AT), First-minute Mean Intensity(FMI), First-minute Intensity Integral(FII). 5. Statistic AnalysisAll statistics were carried out in computer with SPSS10.0 software. A probability value < 0.05 was considered as statistically significant. RESULTS1. Forty-three tumors were detected on enhanced computed tomography (CT), fifty on routine US, and sixty-five on contrast-enhanced US. The TIC of 32 tumors were quantitatively analyzed, of which there were eighteen in hyper-vascular group (group A) and fourteen in hypo-vascular group (group B). Primary tumors of hyper-vascular group (group A) included pancreatic carcinoma, gastric carcinoma, and carcinoma of gallbladder, mesenchymal tumor of gastrointestinal tract, mammary cancer, esophageal carcinoma, and unknown origin. Primary tumors of group B included pimeloma and lung cancer. The contrast-enhanced characterization of group A was fast-in and fast-out as a whole, which manifested fast-in on the arterial phase and then fast-out. Both the contrast perfusion and fade-away of tumor were faster than liver tissue. The contrast-enhanced characterization of group B was fast-in and slow-out on the edge of tumor, which manifested fast-in on the arterial phase and then slow-out. There was no significant difference between the quantitative analysis parameters of two groups (P>0.05).2. We quantitatively analyzed the ablated position of tumors compared with the pre- and post-procedural liver parenchyma, the position of pre-ablated tumors and residual tumor. The results revealed that the parameters of PI, FMI, and FII of the ablated tumors were obviously less than the other groups (P＜0.05).3. Seven residual foci were found in 32 hepatic metastases after therapy, whichshowed the rate of complete ablation was 78.1% (25/32). One case was detected recurrence foci around necrosis one year later after RFA by contrast-enhance US, however, there were no clue on contrast-enhanced US and enhanced CT during the period. The others couldn't endure several ablations at the same time because of the size of tumor (maximum diameter larger than 6cm). Thirty minutes later after RFA the contrast US of the residual tumor manifested fast-in on the arterial phase and fast-out in hyper-vascular group unlike hypo-vascular group of slow-out. Quantitative analysis of the residual foci demonstrated that the parameters of PT and AT were obviously less than that of the liver parenchyma after ablation(P< 0.05). There were no significant difference between the indexes of the residual foci and the pre-procedural tumor (P>0.05).4. The pre-procedural analysis of TIC demonstrated that the parameter of AS of the hepatic metastases was obviously less than that of liver parenchyma (P<0.01).5. The use of enhanced CT/MRI offered a diagnostic standard of residual foci beyond 3 months follow-up after ablation. Of all seven residual foci, six residual tumors were detected by contrast-enhanced US at 30minutes after RFA. Of all 25 completely ablated lesions, 24 lesions were correctly diagnosed by contrast-enhanced US. Thus, the sensitivity of contrast-enhanced US at 30minutes after RFA in detection of residual tumor was 85.7%, specificity was 96%, and accuracy was 93.8%.6. Tumor tissue being replaced by fibrosis was no longer detected in the necrosis of post-ablation; the cells of residual tumor developed in the fibrosis. Contrast-enhanced US, obtained after RFA, showed no micro-vascular perfusion in necrosis whereas micro-vascular perfusion in the residual tumor. There was no perfusion enhancement in necrosis in follow-up.CONCLUSION1. Quantitative analysis of contrast-enhanced US can reflect the minute difference of micro-vascular perfusion among the hepatic metastases, the hepatic parenchyma, zone of coagulation necrosis, and the residual tumor.2. Harmonic imaging of contrast-enhanced US combining with quantitative analysis, which differentiates the small tumor and actual size together with the bloodsupplement of tumor, can characterize the hepatic metastases before RFA and afford treatment plans of RFA.3. Harmonic imaging of contrast-enhanced US combining with quantitative analysis can depict residual tumor immediately after RFA, consequently reduce the local recurrence.4. The sensitivity, specificity and accuracy of the contrast-enhanced US in the detection of residual tumor, 30minutes after RFA, were 85.7%, 96%, 93.8%, respectively.5. The TIC of contrast-enhanced US can reveal the dynamic process of blood perfusion of the hepatic metastases. Combined with intensity indexes, it plays an important role in evaluating curative efficiency and recurrence in post-procedural and follow-up.6. The immediate contrast-enhanced US is credible and effective to detect residual tumor after RFA of hepatic metastases, and it could take place of short term enhanced CT after ablation.