Analysis of correlation between dynamic contrast-enhanced ultrasound and angiogenesis activity of renal cell carcinoma

The dynamic assessment of disease activity during the follow-up of patients with Crohn's disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. In the retrospective study, patients diagnosed with CD in our hospital were included. All the diagnoses were confirmed by clinical symptoms and ileocolonoscopical results. All patients underwent intestinal ultrasound and contrast-enhanced ultrasound (CEUS) examinations within 1 week of the ileocolonoscopy examinations. Acuson Sequoia (Siemens Healthineers, Mountain View, CA, USA) and Resona R9 Elite (Mindray Medical Systems, China) with curved array and Line array transducers were used. The CEUS examination was performed with SonoVue (Bracco SpA, Milan, Italy). DCE-US analysis was performed by UltraOffice (version: 0.3-2010, Mindray Medical Systems, China) software. Two regions of interest (ROIs) were set in the anterior section of the infected bowel wall and its surrounding normal bowel wall 2 cm distant from the inflamed area. Time-intensity curves (TICs) were generated and quantitative perfusion parameters were obtained after curve fittings. The Simple Endoscopic Score for Crohn's disease (SES-CD) was regarded as the reference standard to evaluate the activity of CD. The receiver operating characteristic curve (ROC) analyses were used to determine the diagnostic efficiency of DCE-US quantitative parameters. From March 2023 to November 2023, 52 CD patients were included. According to SES-CD score, all patients were divided into active group with the SES-CD score > 5 (n = 39) and inactive group SES-CD score < 5 (n = 13). Most of the active CD patients showed bowel wall thickness (BWT) > 4.2 mm (97.4%, 38/39) or mesenteric fat hypertrophy (MFH) on intestinal ultrasound (US) scan (69.2%, 27/39). Color Doppler signal of the bowel wall mostly showed spotty or short striped blood flow signal in active CD patients (56.4%, 22/39). According to CEUS enhancement patterns, most active CD patients showed a complete hyperenhancement of the entire intestinal wall (61.5%, 24/39). The TICs of active CD showed an earlier enhancement, higher peak intensity, and faster decline. Among all CEUS quantitative parameters, amplitude-derived parameters peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), and wash-out rate (WoR) were significantly higher in active CD than in inactive CD (p < 0.05). The combined AUROC of intestinal ultrasound features and DCE-US quantitative perfusion parameters in the diagnosis of active CD was 0.987, with 97.4% sensitivity, 100% specificity, and 98.1% accuracy. DCE-US with quantitative perfusion parameters is a potential useful noninvasive imaging method to evaluate the activity of Crohn's disease.

To explore the value of dynamic contrast enhanced ultrasound (DCE-US) in preoperative differential diagnosis of focal-type autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC). From May 2016 to March 2020, patients with biopsy and histopathologically confirmed focal-type AIP (n = 9) were retrospectively included. All patients received contrast enhanced ultrasound (CEUS) examinations one week before surgery/biopsy. Dynamic analysis was performed by VueBox® software (Bracco, Italy). Eighteen cases of resection and histopathologically proved PDAC lesions were also included as control group. B mode ultrasound (BMUS) features, CEUS enhancement patterns, time intensity curves (TICs) and CEUS quantitative parameters were obtained and compared between AIP and PDAC lesions. After injection of ultrasound contrast agents, most focal-type AIP lesions displayed hyper-enhancement (2/9, 22.2%) or iso-enhancement (6/9, 66.7%) during arterial phase of CEUS, while most of PDAC lesions showed hypo-enhancement (88.9%) (P < 0.01). During late phase, most of AIP lesions showed iso-enhancement (8/9, 88.9%), while most of PDAC lesions showed hypo-enhancement (94.4%) (P < 0.001). Compared with PDAC lesions, TICs of AIP lesions showed delayed and higher enhancement. Among all CEUS perfusion parameters, ratio of PE (peak enhancement), WiAUC (wash-in area under the curve), WiR (wash-in rate), WiPI (wash-in perfusion index, WiPI = WiAUC/ rise time), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve) and WoR (wash-out rate) between pancreatic lesion and surrounding normal pancreatic tissue were significantly higher in AIP lesions than PDAC lesions (P < 0.05). DCE-US with quantitative analysis has the potential to make preoperative differential diagnosis between focal-type AIP and PDAC non-invasively.

To explore the potential added value of dynamic contrast enhanced ultrasound (DCE-US) using VueBox® software for the diagnosis of small solid thyroid nodules (≤1.0 cm). This prospective study was approved by the institutional review board and it was performed at two hospitals from January 2020 to October 2020. B mode ultrasound and contrast enhanced ultrasound (CEUS) images were obtained for 79 small solid thyroid nodules (≤1.0 cm) confirmed by ultrasound-guided fine needle aspiration cytology results in 79 consecutive patients (55 women and 24 men, median age: 41 years). The CEUS time-intensity curves (TICs) of thyroid nodules and surrounding parenchyma were created by VueBox® software (Bracco, Italy). The CEUS quantitative parameters were obtained after curve fitting. The diagnostic performance of CEUS and DCE-US was evaluated and compared. The weighted kappa statistic (κ) was performed to assess the interobserver agreement and consistency between the diagnosis of CEUS and DCE-US. Among the 79 thyroid nodules, 56 (70.9 %) were malignant and 23 (29.1 %) were benign lesions. Hypoenhancement during the arterial phase of CEUS was associated with malignancy (P < 0.001), with an AUC of 0.705 (sensitivity 71.4 %, specificity 69.6 %). Among all CEUS quantitative parameters, the peak enhancement (PE), wash-in rate (WiR), and wash-out rate (WoR) of DCE-US in malignancies were significantly lower than those in benign nodules (P = 0.049, P = 0.046, and P = 0.020, respectively). The area under the receiver operating characteristic curves (AUCs) of PE, WiR, and WoR were 0.642 (sensitivity 65.2 %, specificity 67.9 %), 0.643 (sensitivity 43.5 %, specificity 91.1 %), and 0.667 (sensitivity 69.6 %, specificity 69.6 %) in differentiation between benign and malignant small solid thyroid nodules (≤1.0 cm), respectively. Comparing the quantitative parameters of DCE-US between small solid thyroid nodules and surrounding normal thyroid parenchyma, the PE, WiAUC, WiR, wash-in perfusion index (WiPI), WoAUC, WiWoAUC, and WoR of the nodules were significantly lower than those of normal thyroid tissue (P = 0.008, P < 0.001, P = 0.037, P = 0.009, P = 0.003, P = 0.002, P = 0.049, respectively). A total of 16 (20.3 %) nodules showed isoenhancement during the arterial phase of CEUS, while the median PE ratio of surrounding tissue and thyroid nodules was 1.70 (IQR: 1.33-1.89). VueBox® is a helpful tool for the evaluation of dynamic microvascularization of thyroid nodules, and DCE-US using VueBox® perfusion analysis could provide added values for differential diagnosis of small solid thyroid nodules (≤1.0 cm).

ObjectiveTo evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) analysis in early prediction of tumor response to systemic treatment in patients with intrahepatic cholangiocarcinoma (ICC). Patients & MethodsIn this retrospective study, patients diagnosed with ICC by core needle biopsy and histopathological results were included. All patients were diagnosed as advanced stages (stage III/IV) by the 8th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM staging system. Liver contrast-enhanced ultrasound (CEUS) examination, DCE-US analysis, CT/MRI, and blood tests were performed in all patients before and 2 months after systemic treatment. CEUS procedure was performed using an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, Germany) equipped with a 5C1 MHz convex array transducer. Time-intensity curves (TIC) and quantitative parameters were created with VueBox software. According to one-year results of the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) based on CT/MRI, patients were divided into the responder group (RG) and the non-responder group (NRG). Before and 2 months after systemic therapy, the DCE-US perfusion parameters was compared using the paired-sample t test and the Wilcoxon test. ResultsFrom September 2020 to December 2021, a total of 24 patients diagnosed with advanced ICC were included (11 males, 13 females, mean age 59.4 ± 1.8 years). According to the one year of m-RECIST results, 17 cases (70.8 %) were classified as non-responders by the final m-RECIST criteria, while 7 cases (19.2 %) were responders. Comparing before and 2 months after therapy, the RG took longer time to reach peak intensity, and the peak intensity of TIC was lower. While the TICs of NRG revealed faster enhancement after therapy. Among all DCE-US quantitative parameters, PE (peak enhancement), WiR (wash-in rate), WiPI (wash-in perfusion index) and WoR (wash-out rate) reduced significantly following 2 months of systemic therapy in RG (P < 0.05). Comparing to RG, PE and WiPI decreased slightly 2 months after therapy in NRG (P < 0.05). ConclusionsThe DCE-US analysis with quantitative parameters has the potential value to make early and quantitative evaluation of treatment response to systemic therapy in ICC patients.

To investigate the clinical value of dynamic contrast enhanced ultrasound (D-CEUS) in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). In this retrospective study, 16 patients with surgery and histopathologically proved HCC lesions were included. Patients were classified according to the presence of MVI: MVI positive group (n = 6) and MVI negative group (n = 10). Contrast enhanced ultrasound (CEUS) examinations were performed within a week before surgery. Dynamic analysis was performed by VueBox® software (Bracco, Italy). Three regions of interests (ROIs) were set in the center of HCC lesions, at the margin of HCC lesions and in the surrounding liver parenchyma accordingly. Time intensity curves (TICs) were generated and quantitative perfusion parameters including WiR (wash-in rate), WoR (wash-out rate), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiPi (wash-in perfusion index) were obtained and analyzed. All of HCC lesions showed arterial hyperenhancement (100 %) and at the late phase as hypoenhancement (75%) in CEUS. Among all CEUS quantitative parameters, the WiAUC and WoAUC were higher in MVI positive group than in MVI negative group in the center HCC lesions (P < 0.05), WiAUC, WoAUC and WiPI were higher in MVI positive group than in MVI negative group at the margin of HCC lesions. WiR and WoR were significant higher in MVI positive group. D-CEUS with quantitative perfusion analysis has potential clinical value in predicting the existence of MVI in HCC lesions.

Diagnostic and Prognostic Molecular Markers in Renal Cell Carcinoma

To evaluate the feasibility of dynamic contrast enhanced ultrasound (DCE-US) in predicting treatment response of high-intensity focused ultrasound (HIFU) in patients with locally advanced pancreatic cancer (LAPC) lesions. In this prospective study, 10 patients with pathologically confirmed LAPC lesions (7 men, 3 women; average age, 61.13±5.80 years) were prospectively enrolled. All patients received HIFU treatment with peak intensity at 12000 W/cm2. Contrast enhanced ultrasound (CEUS) was performed with an ACUSON Oxana 2 ultrasound equipment and a 6 C-1 transducer (1-6 Hz). A dose of 2.4 ml SonoVue was injected for each examination. Time intensity curves (TICs) were generated and quantitative analyses were performed by SonoLiver software. B mode ultrasound (BMUS) features, CEUS enhancement patterns, TICs, CEUS quantitative parameters and serum carcinoma antigen 19-9 (CA19-9) levels were compared before and 4 weeks after HIFU treatment. Statistical analyses were performed with SPSS Version 20.0 and GraphPad Prism 5. While comparing before and after HIFU, no significant difference was obtained on mean size of lesion, BMUS or CEUS features. After HIFU treatment, TICs showed decreased and delayed enhancement. Among all CEUS quantitative parameters, significant decrease could be found in maximum intensity (MI) (60.66±23.95% vs 41.31±26.74%) and mean transit time (mTT) (76.66±47.61 s vs 38.42±28.35 s). CA19-9 level decreased significantly after HIFU (2747.92±4237.41 U/ml vs 715.08±1773.90 U/ml) (P = 0.05). DCE-US combining with quantitative analysis might be a useful imaging method for early treatment response evaluation of HIFU in LAPC lesions.

Added value of dynamic contrast-enhanced ultrasound analysis for differential diagnosis of small (≤ 20 mm) solid pancreatic lesions

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly defined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in difficult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an efficient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

Improved Detection of Hepatic Metastases with Contrast-enhanced Low Mechanical-index Pulse Inversion Ultrasonography During the Liver-specific Phase of Sonazoid: Observer Performance Study with JAFROC Analysis

Applications of Dynamic Contrast-Enhanced Ultrasound in Differential Diagnosis of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma in Non-cirrhotic Liver.

Background Ulcerative Colitis (UC) is a chronic inflammatory disease characterized by periods of relapse and remission. While colonoscopy is currently the gold standard for assessing disease activity, its invasiveness, low patient tolerance and associated risks make it unsuitable for frequent monitoring of intestinal inflammation. Despite these challenges, a "treat-to-target" approach is crucial in the era of biological therapies. Intestinal Ultrasound (IUS) offers a non-invasive, cost-effective and well-tolerated alternative to monitor treatment response. Indeed, the Milan Ultrasound Criteria (MUC), based on B-mode and color-doppler parameters, have been recently developed to assess disease activity in UC1,2. Dynamic Contrast-Enhanced Ultrasound (D-CEUS) allows visualization of tissue microvascularization, providing objective quantitative parameters derived from time-intensity curve analysis, potentially representing a promising tool to quantify bowel inflammation. The aim of our study was to assess the role of D-CEUS in predicting 6 months clinical remission to advanced therapies (biologic and small molecules). Methods We prospectively enrolled consecutive UC patients starting a new advanced treatment for clinical practice. Patients underwent IUS, D-CEUS and clinical assessment at baseline and at 8 (T1), 16 (T2) and 24 (T3) weeks after starting treatment. According to STRIDE-II consensus3, clinical remission at T3 was defined as partial Mayo score &amp;lt;3 and no subscore &amp;lt;1. Time-intensity curves were analyzed through VueBox® software (figure 1). Patients needing surgery or treatment change before T3 were classified as "non-responders". Logistic regression analysis was performed to evaluate the predictive role of D-CEUS in achieving clinical remission at T3. Statistical significance was defined as p&amp;lt;0.05. Results 40 patients were enrolled (mean age 39±13 years, 60% males), 44.4% (n=18) of which had previously failed at least one line of advanced therapy. At T3, 50% of patients achieved clinical remission (n=20). Univariate logistic regression analyses showed that reductions of Peak Enhancement (PE) and Wash-in Perfusion Index (WiPI) at T2 were predictive of clinical remission at T3 (OR=0.99, p=0.032 and OR=0.25, p=0.036 respectively). Moreover, the percentage changes between T2 and T0 (△% T2 – T0) of PE and WiPI were associated with 6 months clinical remission (OR=0.19 p=0.019 and OR=0.26 and p=0.04, respectively). Lastly, our results confirmed the value of MUC (at T1 and T2) in predicting clinical remission at T3 (OR=0.62, p=0.03 and OR=0.73, p=0.048, respectively). Conclusion D-CEUS provides early predictors of 6 months clinical remission in UC patients treated with advanced therapies.

Significance of Thymidine Kinase Activity in Renal Cell Carcinoma

Introduction: Thymidylate synthase (TS) and thymidine kinase (TK) are the key enzymes in the de novo and salvage DNA synthetic process, respectively. Orotate phosphoribosyltransferase (OPRT) plays an important role in the de novo pathway of DNA and RNA synthesis. In contrast, dihydropyrimidine dehydrogenase (DPD) is a key enzyme involved in degradation of DNA and RNA. We examined the activities of TS, TK, OPRT and DPD in 83 renal cell carcinomas and normal kidneys and evaluated the clinical significance. Methods: TS, TK, OPRT and DPD activities in non-fixed fresh frozen renal cell carcinomas and normal kidneys were determined enzymatically by the FdUMP binding assay, the DEAE cellulose disc method, the 5-FU phosphorylation assay and the 5-FU degradation assay, respectively. Results: TS activity was 5-fold higher in renal cell carcinoma compared to normal kidney. TS activity in Stage III/IV renal cell carcinoma was 3-fold higher than that in Stage I/II renal cell carcinoma. In addition, the level of TS activity in Grade 3 renal cell carcinoma was 2-fold higher than that in Grade 1 and Grade 2 carcinomas. TK activity was approximately 4-fold higher in normal kidney compared with renal cell carcinoma. TK activity in Stage IV renal cell carcinoma was 2-fold higher than that in Stage I-III renal cell carcinoma. Furthermore, the level of TK activity in Grade 3 renal cell carcinoma was 2-fold higher than that in Grade 1 and Grade 2 carcinomas. OPRT activity was approximately 7-fold higher in renal cell carcinoma compared to normal kidney. OPRT activity in Stage III/IV renal cell carcinoma was 2-fold higher than that in Stage I/II renal cell carcinoma. The level of OPRT activity in Grade 3 renal cell carcinoma was 3-fold higher than those in Grade 1 and Grade 2 carcinomas. DPD activity was approximately 2-fold higher in normal kidney compared to renal cell carcinoma. The higher stage and grade of renal cell carcinoma was, the lower DPD activity was observed. The level of OPRT activity correlated with those of TS and TK activities. However, DPD activity was not associated with TS activity. High TS, TK, OPRT activities and low DPD activity predicted worse prognosis in patients with renal cell carcinoma.Conclusions: The present study has demonstrated that TS, TK, OPRT and DPD activities in renal cell carcinoma correlated with the stage/grade status of renal cell carcinoma. In addition, the levels of TS, TK, OPRT and DPD activities were prognostic parameters in patients with renal cell carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5572. doi:1538-7445.AM2012-5572

Contrast-Enhanced Sonography for Differential Diagnosis of Pleurisy and Focal Pleural Lesions of Unknown Cause