Early response evaluation of doxorubicin-nanoparticle-microbubble therapy in orthotopic hepatocellular carcinoma rat model using contrast-enhanced ultrasound and intravoxel incoherent motion-diffusion MRI

Purpose@#This study aimed to apply doxorubicin-loaded nanoparticle microbubble (Dox-NP-MB) therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) and investigate the utility of contrast-enhanced ultrasound (CEUS) and intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) for response evaluation. @*Methods@#Twenty-eight N1S1 HCC model rats were treated with either Dox-NP-MB (group [G] 1, n=8), doxorubicin (Dox) alone (G2, n=7), nanoparticle microbubbles alone (G3, n=7), or saline (G4, control, n=6) on days 0 and 7, and were sacrificed on day 11. IVIM-DWI and CEUS were performed before each treatment and before euthanasia. Efficacy was estimated by the percentage of tumor volume growth inhibition compared with control. Toxicity was assessed by body weight changes and blood tests. Post-treatment changes in IVIM-DWI and CEUS parameters were analyzed. @*Results@#Tumor volume growth was inhibited by 48.4% and 90.2% in G1 and G2 compared to G4, respectively. Compared to G2, G1 had a significantly lower degree of body weight change (median, 91.0% [interquartile range, 88.5%-97.0%] vs. 88.0% [82.5%-88.8%], P<0.05) and leukopenia (1.75×103 cells/μL [1.53-2.77] vs. 1.20×103 cells/μL [0.89-1.51], P<0.05). After the first treatment, an increase in peak enhancement, wash-in rate, and wash-in perfusion index on CEUS was observed in G3 and G4 but suppressed in G1 and G2; the apparent diffusion coefficients, true diffusion coefficients, and perfusion fractions significantly increased in G1 and G2 compared to baseline (P<0.05). @*Conclusion@#Dox-NP-MB showed reduced Dox toxicity. Early changes in some CEUS and IVIM-DWI parameters correlated with the therapeutic response.

Diagnostic criteria of perfluorobutane-enhanced ultrasonography for diagnosing hepatocellular carcinoma in high-risk individuals: how is late washout determined?

Purpose@#The aim of this study was to investigate the optimal washout criteria of perfluorobutane-enhanced ultrasonography (PFB-US) for the diagnosis of hepatocellular carcinoma (HCC) in high-risk individuals. @*Methods@#Participants at risk of HCC with treatment-naïve solid hepatic observations (≥1 cm) who underwent PFB-US from March 2019 to September 2020 were prospectively recruited. Arterial phase hyperenhancement (APHE), washout time, and washout degree were evaluated. The diagnosis of HCC was made by non-rim APHE with late and mild washout. The per-lesion diagnostic performance for diagnosing HCC using different cutoffs for late washout (50, 55, 60, 65, and 70 seconds postcontrast) and the different time windows for determining washout (until 2, 3, 4, 5, 6, 7, 8, 9, and 10 minutes postcontrast) were compared using the McNemar test. @*Results@#In total, 101 participants with 113 observations (mean size, 33.5±2.8 mm; HCCs [n=82], non-HCC malignancies [n=16], benign [n=15]) were evaluated. Non-rim APHE was observed in 86.6% (71/82) of HCCs. As the cutoff time for late washout increased, the specificity increased to 100% (95% confidence interval [CI], 88.8% to 100%) at the 60-second cutoff with 62.2% sensitivity (95% CI, 50.8% to 72.7%). When the time window for determining washout became wider, the sensitivity and accuracy increased until 6 minutes, with 100% specificity at all times. @*Conclusion@#Determining washout within 6 minutes after contrast injection with a 60-second cutoff for late washout showed the highest sensitivity without losing specificity for diagnosing HCC using PFB-US in individuals at high risk.

Superb microvascular imaging technology of ultrasound examinations for the evaluation of tumor vascularity in hepatic hemangiomas

Purpose@#This study aimed to investigate and categorize the diverse features of hepatic hemangiomas on superb microvascular imaging (SMI) in a relatively large prospective study. @*Methods@#In this prospective study, 70 patients with 92 hepatic hemangiomas were consecutively enrolled. All nodules were radiologically confirmed with the typical imaging features of hepatic hemangiomas on dynamic computed tomography (CT) or magnetic resonance imaging (MRI). Using SMI, all lesions were evaluated and categorized into subgroups according to the flow pattern on SMI. Differences in the frequencies of SMI patterns according to lesion size and enhancement patterns on dynamic CT or MRI were also compared. @*Results@#In 67.4% (62/92) of hemangiomas, tumor vascularity was detected using SMI, while 32.6% (30/92) did not show any signal on the SMI examination, and the absence of an SMI signal was not shown in rapidly enhancing hemangiomas (0% [0/30] vs. 100% [30/30], P=0.002) and was more frequent in lesions <2 cm than in lesions ≥2 cm (44.0% [22/50] vs. 2.7% [8/42], P=0.011). In hepatic hemangiomas in which vascularity was detected (n=62), the strip rim pattern was the most common SMI pattern of hepatic hemangiomas (48.4%, 30/62), followed by the nodular rim pattern involving spotty dot-like engorged vessels (37.1%, 23/62). @*Conclusion@#The evaluation of the inner vascularity of hepatic hemangiomas with SMI was feasible for most hemangiomas, especially in larger (≥2 cm) or rapidly enhancing hemangiomas. The most frequent SMI patterns of hepatic hemangiomas were the strip rim pattern and nodular rim pattern.

Role of Contrast-Enhanced Ultrasound as a Second-Line Diagnostic Modality in Noninvasive Diagnostic Algorithms for Hepatocellular Carcinoma

Objective@#To investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) and its role as a second-line imaging modality after gadoxetate-enhanced MRI (Gd-EOB-MRI) in the diagnosis of hepatocellular carcinoma (HCC) among at risk observations. @*Materials and Methods@#We prospectively enrolled participants at risk of HCC with treatment-naïve solid hepatic observations (≥ 1 cm) of Liver Imaging Reporting and Data System (LR)-3/4/5/M during surveillance and performed Gd-EOB-MRI. A total of one hundred and three participants with 103 hepatic observations (mean size, 28.2 ± 24.5 mm; HCCs [n = 79], non-HCC malignancies [n = 15], benign [n = 9]; diagnosed by pathology [n = 57], or noninvasive method [n = 46]) were included in this study. The participants underwent CEUS with sulfur hexafluoride. Arterial phase hyperenhancement (APHE) and washout on Gd-EOB-MRI and CEUS were evaluated. The distinctive washout in CEUS was defined as mild washout 60 seconds after contrast injection. The diagnostic ability of Gd-EOB-MRI and of CEUS as a second-line modality for HCC were determined according to the European Association for the Study of the Liver (EASL) and the Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) guidelines. The diagnostic abilities of both imaging modalities were compared using the McNemar’s test. @*Results@#The sensitivity of CEUS (60.8%) was lower than that of Gd-EOB-MRI (72.2%, p = 0.06 by EASL; 86.1%, p < 0.01 by KLCA-NCC); however, the specificity was 100%. By performing CEUS on the inconclusive observations in Gd-EOB-MRI, HCCs without APHE (n = 10) or washout (n = 12) on Gd-EOB-MRI further presented APHE (80.0%, 8/10) or distinctive washout (66.7%, 8/12) on CEUS, and more HCCs were diagnosed than with Gd-EOB-MRI alone (sensitivity: 72.2% vs. 83.5% by EASL, p < 0.01; 86.1% vs. 91.1% by KCLA-NCC, p = 0.04). There were no false-positive cases for HCC on CEUS. @*Conclusion@#The addition of CEUS to Gd-EOB-MRI as a second-line diagnostic modality increases the frequency of HCC diagnosis without changing the specificities.

Two-Dimensional-Shear Wave Elastography with a Propagation Map: Prospective Evaluation of Liver Fibrosis Using Histopathology as the Reference Standard

Objective@#The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by twodimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. @*Materials and Methods@#We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value.The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. @*Results@#Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. @*Conclusion@#The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

Prognostic Value of Tumor Regression Grade on MR in Rectal Cancer: A Large-Scale, Single-Center Experience

Objective@#To determine the prognostic value of MRI-based tumor regression grading (mrTRG) in rectal cancer compared withpathological tumor regression grading (pTRG), and to assess the effect of diffusion-weighted imaging (DWI) on interobserveragreement for evaluating mrTRG. @*Materials and Methods@#Between 2007 and 2016, we retrospectively enrolled 321 patients (male:female = 208:113; meanage, 60.2 years) with rectal cancer who underwent both pre-chemoradiotherapy (CRT) and post-CRT MRI. Two radiologistsindependently determined mrTRG using a 5-point grading system with and without DWI in a one-month interval. Two pathologistsgraded pTRG using a 5-point grading system in consensus. Kaplan-Meier estimation and Cox-proportional hazard models wereused for survival analysis. Cohen’s kappa analysis was used to determine interobserver agreement. @*Results@#According to mrTRG on MRI with DWI, there were 6 mrTRG 1, 48 mrTRG 2, 109 mrTRG 3, 152 mrTRG 4, and 6 mrTRG 5.By pTRG, there were 7 pTRG 1, 59 pTRG 2, 180 pTRG 3, 73 pTRG 4, and 2 pTRG 5. A 5-year overall survival (OS) was significantlydifferent according to the 5-point grading mrTRG (p= 0.024) and pTRG (p= 0.038). The 5-year disease-free survival (DFS)was significantly different among the five mrTRG groups (p= 0.039), but not among the five pTRG groups (p= 0.072). OSand DFS were significantly different according to post-CRT MR variables: extramural venous invasion after CRT (hazard ratio= 2.259 for OS, hazard ratio = 5.011 for DFS) and extramesorectal lymph node (hazard ratio = 2.610 for DFS). For mrTRG, kvalue between the two radiologists was 0.309 (fair agreement) without DWI and slightly improved to 0.376 with DWI. @*Conclusion@#mrTRG may predict OS and DFS comparably or even better compared to pTRG. The addition of DWI on T2-weightedMRI may improve interobserver agreement on mrTRG.

Non-invasive monitoring of hepatic steatosis via acoustic structure quantification of ultrasonography with MR spectroscopy as the reference standard

Purpose@#The purpose of this study was to prospectively evaluate whether monitoring hepatic steatosis by ultrasonography with acoustic structure quantification (ASQ) is feasible, using magnetic resonance spectroscopy (MRS) as the reference standard. @*Methods@#Thirty-six patients with suspected fatty liver disease underwent both untrasonography with ASQ and MRS on the same day. After a mean follow-up period of 11.4±2.5 months, follow-up ultrasonography with ASQ and MRS were performed on 27 patients to evaluate whether hepatic steatosis had improved. The focal disturbance (FD) ratio, as calculated using ASQ, and the hepatic fat fraction (HFF), estimated by MRS, were obtained at both initial and follow-up examinations. Pearson correlation coefficients were calculated to assess the correlations between ordinal values. @*Results@#The FD ratio showed a strong, negative linear correlation with the HFF after logarithmic transformation of both variables from the initial examinations of 36 patients (ρ=-0.888, P<0.001) and the follow-up examinations of 27 patients (ρ=-0.920, P<0.001). There was also a significant, negative linear correlation between the change in the logarithm of the FD ratio and the change in the logarithm of the HFF by MRS over the follow-up period (ρ=-0.645, P<0.001). In 16 patients with an increased FD ratio on follow-up, the HFF on follow-up MRS significantly decreased, and high-density lipoprotein levels significantly increased, whereas low-density lipoprotein levels tended to decrease. @*Conclusion@#The FD ratio was significantly correlated with the HFF at both the initial and follow-up examinations, and there was also a significant correlation between changes in the FD ratio and changes in the HFF over the follow-up period.

Two-Dimensional-Shear Wave Elastography with a Propagation Map: Prospective Evaluation of Liver Fibrosis Using Histopathology as the Reference Standard

Objective@#The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by twodimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. @*Materials and Methods@#We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value.The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. @*Results@#Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. @*Conclusion@#The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

Prediction of Treatment Outcome of Chemotherapy Using Perfusion Computed Tomography in Patients with Unresectable Advanced Gastric Cancer

OBJECTIVE: To evaluate whether data acquired from perfusion computed tomography (PCT) parameters can aid in the prediction of treatment outcome after palliative chemotherapy in patients with unresectable advanced gastric cancer (AGC). MATERIALS AND METHODS: Twenty-one patients with unresectable AGCs, who underwent both PCT and palliative chemotherapy, were prospectively included. Treatment response was assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (i.e., patients who achieved complete or partial response were classified as responders). The relationship between tumor response and PCT parameters was evaluated using the Mann-Whitney test and receiver operating characteristic analysis. One-year survival was estimated using the Kaplan-Meier method. RESULTS: After chemotherapy, six patients exhibited partial response and were allocated to the responder group while the remaining 15 patients were allocated to the non-responder group. Permeability surface (PS) value was shown to be significantly different between the responder and non-responder groups (51.0 mL/100 g/min vs. 23.4 mL/100 g/min, respectively; p = 0.002), whereas other PCT parameters did not demonstrate a significant difference. The area under the curve for prediction in responders was 0.911 (p = 0.004) for PS value, with a sensitivity of 100% (6/6) and specificity of 80% (12/15) at a cut-off value of 29.7 mL/100 g/min. One-year survival in nine patients with PS value > 29.7 mL/100 g/min was 66.7%, which was significantly higher than that in the 12 patients (33.3%) with PS value ≤ 29.7 mL/100 g/min (p = 0.019). CONCLUSION: Perfusion parameter data acquired from PCT demonstrated predictive value for treatment outcome after palliative chemotherapy, reflected by the significantly higher PS value in the responder group compared with the non-responder group.

Hepatocellular Carcinoma: Texture Analysis of Preoperative Computed Tomography Images Can Provide Markers of Tumor Grade and Disease-Free Survival

OBJECTIVE: To investigate the usefulness of computed tomography (CT) texture analysis (CTTA) in estimating histologic tumor grade and in predicting disease-free survival (DFS) after surgical resection in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Eighty-one patients with a single HCC who had undergone quadriphasic liver CT followed by surgical resection were enrolled. Texture analysis of tumors on preoperative CT images was performed using commercially available software. The mean, mean of positive pixels (MPP), entropy, kurtosis, skewness, and standard deviation (SD) of the pixel distribution histogram were derived with and without filtration. The texture features were then compared between groups classified according to histologic grade. Kaplan-Meier and Cox proportional hazards analyses were performed to determine the relationship between texture features and DFS. RESULTS: SD and MPP quantified from fine to coarse textures on arterial-phase CT images showed significant positive associations with the histologic grade of HCC (p < 0.05). Kaplan-Meier analysis identified most CT texture features across the different filters from fine to coarse texture scales as significant univariate markers of DFS. Cox proportional hazards analysis identified skewness on arterial-phase images (fine texture scale, spatial scaling factor [SSF] 2.0, p <001; medium texture scale, SSF 3.0, p <001), tumor size (p = 0.001), microscopic vascular invasion (p = 0.034), rim arterial enhancement (p = 0.024), and peritumoral parenchymal enhancement (p = 0.010) as independent predictors of DFS. CONCLUSION: CTTA was demonstrated to provide texture features significantly correlated with higher tumor grade as well as predictive markers of DFS after surgical resection of HCCs in addition to other valuable imaging and clinico-pathologic parameters.

Dynamic Contrast-Enhanced Ultrasound of Gastric Cancer: Correlation with Perfusion CT and Histopathology

OBJECTIVE: To assess the relationship between contrast-enhanced ultrasound (CEUS) parameters and perfusion CT (PCT) parameters of gastric cancers and their correlation with histologic features. MATERIALS AND METHODS: This prospective study was approved by our Institutional Review Board. We included 43 patients with pathologically-proven gastric cancers undergoing CEUS using SonoVue® (Bracco) and PCT on the same day. Correlation between the CEUS parameters (peak intensity [PI], area under the curve [AUC], rise time [RT] from 10% to 90% of PI, time to peak [TTPUS], and mean transit time [MTTUS]) and PCT parameters (blood flow, blood volume, TTPCT, MTTCT, and permeability surface product) of gastric cancers were analyzed using Spearman's rank correlation test. In cases of surgical resection, the CEUS and PCT parameters were compared according to histologic features using Mann-Whitney test. RESULTS: CEUS studies were of diagnostic quality in 88.4% (38/43) of patients. Among the CEUS parameters of gastric cancers, RT and TTPUS showed significant positive correlations with TTPCT (rho = 0.327 and 0.374, p = 0.045 and 0.021, respectively); PI and AUC were significantly higher in well-differentiated or moderately-differentiated tumors (n = 4) than poorly-differentiated tumors (n = 18) (p = 0.026 and 0.033, respectively), whereas MTTCT showed significant differences according to histologic types (poorly cohesive carcinoma [PCC] vs. non-PCC), T-staging (≤ T2 vs. ≥ T3), N-staging (N0 vs. N-positive), and epidermal growth factor receptor expression (≤ faint vs. ≥ moderate staining) (p values < 0.05). CONCLUSION: In patients with gastric cancers, CEUS is technically feasible for the quantification of tumor perfusion and may provide correlative and complementary information to that of PCT, which may allow prediction of histologic features.

Microvascular Flow Imaging of Residual or Recurrent Hepatocellular Carcinoma after Transarterial Chemoembolization: Comparison with Color/Power Doppler Imaging

OBJECTIVE: To determine the feasibility of microvascular flow imaging (MVFI) in comparison with color/power Doppler imaging (CDI/PDI) for detection of intratumoral vascularity in suspected post-transarterial chemoembolization (TACE) residual or recurrent hepatocellular carcinomas (HCCs) by using contrast-enhanced ultrasonography (CEUS) or hepatic angiography (HA) findings as the reference standard. MATERIALS AND METHODS: One hundred HCCs (mean size, 2.2 cm) in 100 patients treated with TACE were included in this prospective study. CDI, PDI, and MVFI were performed in tandem for evaluating intratumoral vascularity of the lesions by using an RS85 ultrasound scanner (Samsung Medison Co., Ltd.). Intratumoral vascularity in each technique was assessed by two radiologists in consensus by using a 5-point scale. Then, one of the two radiologists and another radiologist performed additional image review in the reverse order (MVFI-PDI-CDI) for evaluation of intra- and interobserver agreements. Results were then compared with those of either HA or CEUS as the reference. The McNemar test, logistic regression analysis, and intraclass correlation coefficient (ICC) were used. RESULTS: CEUS or HA revealed intratumoral vascularity in 87% (87/100) of the tumors. Sensitivity (79.3%, 69/87) and accuracy (80.0%, 80/100) of MVFI were significantly higher than those of CDI (sensitivity, 27.6% [24/87]; accuracy, 37.0% [37/100]) or PDI (sensitivity, 36.8% [32/87]; accuracy, 44.0% [44/100]) (all p 0.9) and good interobserver agreements (ICCs > 0.6). CONCLUSION: MVFI demonstrated significantly higher sensitivity and accuracy than did CDI and PDI for the detection of intratumoral vascularity in suspected residual or recurrent HCCs after TACE.

Quantitative Evaluation of Hepatic Steatosis Using Normalized Local Variance in a Rat Model: Comparison with Histopathology as the Reference Standard

OBJECTIVE: To evaluate the diagnostic performance of the normalized local variance (NLV) ultrasound technique in the assessment of hepatic steatosis, and to identify the factors that influence the NLV value using histopathological examination as the reference standard. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were fed a methionine-choline-deficient diet for variable periods (0, 2, 4, 6, 8, 10, or 12 days or 2, 3, or 4 weeks; four rats per group). At the end of each diet duration, magnetic resonance spectroscopy (MRS) and NLV examination were performed. Thereafter, the rats were sacrificed and their livers were histopathologically evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic capability of the NLV value in the detection of varying degrees of hepatic steatosis. Univariate and multivariate linear regressions were used to determine the factors associated with the NLV value. RESULTS: The areas under the ROC curve for the detection of mild, moderate, and severe hepatic steatosis were 0.953, 0.896, and 0.735, respectively. The NLV value showed comparable diagnostic performance to that of MRS in the detection of ≥ mild or ≥ moderate hepatic steatosis. Multivariate linear regression analysis revealed that the degree of hepatic steatosis was the only significant factor affecting the NLV value (p < 0.001). CONCLUSION: The NLV value of ultrasound demonstrated satisfactory diagnostic performance in the assessment of varying degrees of hepatic steatosis. The degree of hepatic steatosis was the only significant factor that affected the NLV value.

A portable high-intensity focused ultrasound system for the pancreas with 3D electronic steering: a preclinical study in a swine model

PURPOSE: The aim of this animal study was to evaluate the safety and feasibility of a portable, ultrasonography-guided, high-intensity focused ultrasound (USg-HIFU) system to treat the pancreas. METHODS: Eight swine were included. Using a portable HIFU device (ALPIUS 900, Alpinion Medical Systems), ablations were performed on the pancreas in vivo. Different acoustic intensities were applied (1.7 kW/cm2 or 1.5 kW/cm2, n=2 [group A for a pilot study]; 1.5 kW/ cm2, n=3 [group B]; and 1.2 kW/cm2, n=3 [group C]). Magnetic resonance imaging (MRI) was performed immediately (group A) or 7 days (groups B and C) after HIFU treatment. In groups B and C, serum amylase and lipase levels were measured on days 0 and 7, and performance status was observed every day. Necropsy was performed on days 0 (group A) or 7 (groups B and C) to assess the presence of unintended injuries and to obtain pancreatic and peripancreatic tissue for histological analysis. RESULTS: Ablation was noted in the pancreas in all swine on MRI, and all pathologic specimens showed coagulation necrosis in the treated area. The mean ablation areas on MRI were 85.3±38.1 mm2, 90.7±21.2 mm2, and 54.4±30.6 mm2 in groups A, B, and C, respectively (P>0.05). No animals showed evidence of complications, except for one case of a pseudocyst in group B. CONCLUSION: This study showed that pancreas ablation using a portable USg-HIFU system may be safe and feasible, and that coagulation necrosis of the pancreas was successfully achieved with a range of acoustic intensities.

Role of CT in Differentiating Malignant Focal Splenic Lesions

OBJECTIVE: The purpose of this study was to asses the CT findings and clinical features differentiating malignant from benign focal splenic lesions. MATERIALS AND METHODS: Among 673 patients with splenectomy, we included 114 patients with pathologically confirmed focal splenic lesions (malignant = 66, benign = 48). Two radiologists retrospectively assessed CT findings including: size, number, solid component, margin, wall, calcification, contrast-enhancement, lymph node (LN) enlargement and possible malignancy. We assessed clinical features including age, sex, underlying malignancy, fever, and leukocytosis. Multivariate logistic regression analysis was performed to identify significant predictors of malignant lesion. We used receiver operating curve analysis for determination of diagnostic performance. RESULTS: Common findings of malignant lesions include enhanced, mainly solid, ill-defined margin, absence of splenomegaly, absence of the wall, absence of calcification, LN enlargement, and presence of underlying malignancy (p < 0.05). Among them, mainly solid features (odds ratio [OR], 39.098, p = 0.007), LN enlargement (OR, 6.326, p = 0.005), and presence of underlying malignancy (OR, 8.615, p = 0.001) were significant predictors of malignancy. The mean size of benign splenic lesions (5.8 ± 3.3 cm) was larger than that of malignant splenic lesions (4.0 ± 3.4 cm). Diagnostic performance of CT findings by two reviewers using receiver operating characteristic curve analysis for differentiation of malignant lesions was 0.856 and 0.893, respectively. CONCLUSION: Solid nature of the splenic mass on CT images, LN enlargement, and presence of underlying malignancy are significant predictors of malignant splenic lesion.

Alteration of MRP2 expression and the graft outcome after liver transplantation

PURPOSE: Multidrug resistance-associated protein (MRP) 2 is a glutathione conjugate in the canalicular membrane of hepatocytes. Early graft damage after liver transplantation (LT) can result in alteration of MRP2 expression. The purpose of this study was to evaluate the relationship between the pattern of MRP2 alteration and graft outcome. METHODS: Forty-one paraffin-embedded liver graft tissues obtained by protocol biopsy within 2 months after LT; these were stained using monoclonal antibodies of MRP2. We selected 15 live donor biopsy samples as a control, that showed homogenous canalicular staining for MRP2. The pattern of canalicular MRP2 staining of graft was classified into 3 types: homogenous (type C0), focal (type C1), and no (type C2,) staining of the canaliculi. RESULTS: In total, 17.1% graft tissues were type C0, 36.6% were type C1, and 46.3% were type C2. The median operation time was longer in patients with type C2 (562.6 minutes) than in patients with type C0 (393.8 minutes) (P = 0.038). The rates of posttransplant complications were higher in patients with type C2 (100%) than in patients with type C0 (42.9%) and C1 (73.3%) (P < 0.001). CONCLUSION: MRP2 expression pattern was altered in 82.9% after LT. The pattern of MRP2 alteration was associated with longer operation time and higher rates of post-LT complications.

Iodine Quantification on Spectral Detector-Based Dual-Energy CT Enterography: Correlation with Crohn's Disease Activity Index and External Validation

OBJECTIVE: To correlate CT parameters on detector-based dual-energy CT enterography (DECTE) with Crohn's disease activity index (CDAI) and externally validate quantitative CT parameters. MATERIALS AND METHODS: Thirty-nine patients with CD were retrospectively enrolled. Two radiologists reviewed DECTE images by consensus for qualitative and quantitative CT features. CT attenuation and iodine concentration for the diseased bowel were also measured. Univariate statistical tests were used to evaluate whether there was a significant difference in CTE features between remission and active groups, on the basis of the CDAI score. Pearson's correlation test and multiple linear regression analyses were used to assess the correlation between quantitative CT parameters and CDAI. For external validation, an additional 33 consecutive patients were recruited. The correlation and concordance rate were calculated between real and estimated CDAI. RESULTS: There were significant differences between remission and active groups in the bowel enhancement pattern, subjective degree of enhancement, mesenteric fat infiltration, comb sign, and obstruction (p < 0.05). Significant correlations were found between CDAI and quantitative CT parameters, including number of lesions (correlation coefficient, r = 0.573), bowel wall thickness (r = 0.477), iodine concentration (r = 0.744), and relative degree of enhancement (r = 0.541; p < 0.05). Iodine concentration remained the sole independent variable associated with CDAI in multivariate analysis (p = 0.001). The linear regression equation for CDAI (y) and iodine concentration (x) was y = 53.549x + 55.111. For validation patients, a significant correlation (r = 0.925; p < 0.001) and high concordance rate (87.9%, 29/33) were observed between real and estimated CDAIs. CONCLUSION: Iodine concentration, measured on detector-based DECTE, represents a convenient and reproducible biomarker to monitor disease activity in CD.

Prediction of Local Tumor Progression after Radiofrequency Ablation (RFA) of Hepatocellular Carcinoma by Assessment of Ablative Margin Using Pre-RFA MRI and Post-RFA CT Registration

OBJECTIVE: To evaluate the clinical impact of using registration software for ablative margin assessment on pre-radiofrequency ablation (RFA) magnetic resonance imaging (MRI) and post-RFA computed tomography (CT) compared with the conventional side-by-side MR-CT visual comparison. MATERIALS AND METHODS: In this Institutional Review Board-approved prospective study, 68 patients with 88 hepatocellulcar carcinomas (HCCs) who had undergone pre-RFA MRI were enrolled. Informed consent was obtained from all patients. Pre-RFA MRI and post-RFA CT images were analyzed to evaluate the presence of a sufficient safety margin (≥ 3 mm) in two separate sessions using either side-by-side visual comparison or non-rigid registration software. Patients with an insufficient ablative margin on either one or both methods underwent additional treatment depending on the technical feasibility and patient's condition. Then, ablative margins were re-assessed using both methods. Local tumor progression (LTP) rates were compared between the sufficient and insufficient margin groups in each method. RESULTS: The two methods showed 14.8% (13/88) discordance in estimating sufficient ablative margins. On registration software-assisted inspection, patients with insufficient ablative margins showed a significantly higher 5-year LTP rate than those with sufficient ablative margins (66.7% vs. 27.0%, p = 0.004). However, classification by visual inspection alone did not reveal a significant difference in 5-year LTP between the two groups (28.6% vs. 30.5%, p = 0.79). CONCLUSION: Registration software provided better ablative margin assessment than did visual inspection in patients with HCCs who had undergone pre-RFA MRI and post-RFA CT for prediction of LTP after RFA and may provide more precise risk stratification of those who are treated with RFA.

The Feasibility Study of Contrast-enhanced Ultrasound Using a 3 Dimension Transducer for Tumor Volume Measurement in Rabbit Hepatic VX2 Carcinoma Comparison with 2 Dimension Ultrasound and 3 Dimension Ultrasound without Contrast: Preliminary Results

BACKGROUND/AIMS: To investigate the feasibility of tumor volume measurement using contrastenhanced ultrasound (US) with 3 dimension transducer (3D CEUS) in rabbit hepatic VX2 carcinoma. METHODS: Three different tumor volume measurements, including 2D US using the equation, 4/3(π)(abc), 3D US without contrast, and 3D CEUS were performed in 35 rabbit hepatic VX2 carcinomas. With the tumor volume from computerized tomography (CT) as a reference standard, we compared difference between CT volume and each different US tumor volume. The mean difference and correlation coefficient between each US volume measurement and CT volume were analyzed. RESULTS: Tumor volume measurement using 3D CEUS and 2D US using equation showed no statistical difference compared to CT volume (0.276 cm3, 0.212 cm3, and 0.263 cm3 vs. 0.306 cm3, 0.247 cm3, 0.276 cm3, P>0.05). However, 3D CEUS provided the highest correlation coefficient with CT volume (R=0.835 and 0.720) and the highest intraclass correlation (0.973 and 0.993). 3D CEUS provided a smaller mean difference with CT volume (0.016 cm3 and 0.033 cm3) than 2D US, showing 3D CEUS's accurate measurement of tumor volume. CONCLUSIONS: Due to its highly accurate, reliable, and reproducible measurements of tumor volume, 3D CEUS may be useful for predicting the therapeutic response evaluation after treatment.

Prospective Validation of Intra- and Interobserver Reproducibility of a New Point Shear Wave Elastographic Technique for Assessing Liver Stiffness in Patients with Chronic Liver Disease

OBJECTIVE: To assess intra- and inter-observer reproducibility of a new point shear wave elastography technique (pSWE, S-Shearwave, Samsung Medison) and compare its accuracy in assessing liver stiffness (LS) with an established pSWE technique (Virtual Touch Quantification, VTQ). MATERIALS AND METHODS: Thirty-three patients were enrolled in this Institutional Review Board-approved prospective study. LS values were measured by VTQ on an Acuson S2000 system (Siemens Healthineer) and S-Shearwave on an RS-80A (Samsung Medison) in the same session, followed by two further S-Shearwave sessions for inter- and intra-observer variation at 8-hour intervals. The technical success rate (SR) and reliability of the measurements of both pSWE techniques were compared. The intra- and inter-observer reproducibility of S-Shearwave was determined by intraclass correlation coefficients (ICCs). LS values were measured by both methods of pSWE. The diagnostic performance in severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was evaluated using the receiver operating characteristics curve analysis and the Obuchowski measure with the LS values of transient elastography as the referenced standard. RESULTS: The VTQ (100%, 33/33) and S-Shearwave (96.9%, 32/33) techniques did not display a significant difference in technical SR (p = 0.63) or reliability of LS measurements (96.9%, 32/33; 93.9%, 30/32, respectively, p = 0.61). The inter- and intra-observer agreement for LS measurements using the S-Shearwave technique was excellent (ICC = 0.98 and 0.99, respectively). The mean LS values of both pSWE techniques were not significantly different and exhibited a good correlation (r = 0.78). To detect F ≥ 3 and F = 4, VTQ and S-Shearwave showed comparable diagnostic accuracy as indicated by the following outcomes: areas under receiver operating characteristics curve (AUROC) = 0.87 (95% confidence intervals [CI] 0.70–0.96), 0.89 for VTQ (95% CI 0.74–0.97), respectively; and AUROC = 0.84 (95% CI 0.67–0.94), 0.94 (95% CI 0.80–0.99) for S-Shearwave (p > 0.48), respectively. The Obuchowski measures were similarly high for S-Shearwave and VTQ (0.94 vs. 0.95). CONCLUSION: S-Shearwave shows excellent inter- and intra-observer agreement and diagnostic effectiveness comparable to VTQ in detecting LS.