Dynamic Contrast-enhanced Ultrasound Research Articles

Subtype prediction of intrahepatic cholangiocarcinoma using dynamic contrast-enhanced ultrasound

ObjectiveThe study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC).MethodsThis study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated.ResultsIn the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort.ConclusionsPreoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC.Critical relevance statementDCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes.Key PointsPreoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making.Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype.DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.Graphical

Can 3D Multiparametric Ultrasound Imaging Predict Prostate Biopsy Outcome?

ObjectivesTo assess the value of 3D multiparametric ultrasound imaging, combining hemodynamic and tissue stiffness quantifications by machine learning, for the prediction of prostate biopsy outcomes. MethodsAfter signing informed consent, 54 biopsy-naïve patients underwent a 3D dynamic contrast-enhanced ultrasound (DCE-US) recording, a multi-plane 2D shear-wave elastography (SWE) scan with manual sweeping from base to apex of the prostate, and received 12-core systematic biopsies (SBx). 3D maps of 18 hemodynamic parameters were extracted from the 3D DCE-US quantification and a 3D SWE elasticity map was reconstructed based on the multi-plane 2D SWE acquisitions. Subsequently, all the 3D maps were segmented and subdivided into 12 regions corresponding to the SBx locations. Per region, the set of 19 computed parameters was further extended by derivation of eight radiomic features per parameter. Based on this feature set, a multiparametric ultrasound approach was implemented using five different classifiers together with a sequential floating forward selection method and hyperparameter tuning. The classification accuracy with respect to the biopsy reference was assessed by a group-k-fold cross-validation procedure, and the performance was evaluated by the Area Under the Receiver Operating Characteristics Curve (AUC). ResultsOf the 54 patients, 20 were found with clinically significant prostate cancer (csPCa) based on SBx. The 18 hemodynamic parameters showed mean AUC values varying from 0.63 to 0.75, and SWE elasticity showed an AUC of 0.66. The multiparametric approach using radiomic features derived from hemodynamic parameters only produced an AUC of 0.81, while the combination of hemodynamic and tissue-stiffness quantifications yielded a significantly improved AUC of 0.85 for csPCa detection (p-value < 0.05) using the Gradient Boosting classifier. ConclusionsOur results suggest 3D multiparametric ultrasound imaging combining hemodynamic and tissue-stiffness features to represent a promising diagnostic tool for biopsy outcome prediction, aiding in csPCa localization.

Dynamic Contrast-Enhanced Ultrasonography Combined With LR-M Classification Criteria for Differentiating Malignant Liver Nodules at High Risk for Hepatocellular Carcinoma

ObjectiveWe aimed to investigate the value of quantitative parameters derived from dynamic contrast-enhanced ultrasonography (DCE-US) and a combination of these quantitative parameters with the LR-M classification criteria in distinguishing hepatocellular carcinoma (HCC) nodules and non-HCC malignancies. MethodsHCC and non-HCC malignant nodules were grouped using pathologic results, and each nodule was classified using CEUS LI-RADS 2017. Quantitative CEUS analysis of each nodule was performed using VueBox, and quantitative parameters were compared between the HCC and non-HCC groups. The diagnostic efficacy of the LR-5 category for HCC was analyzed using the LR-M classification criteria along with time-related quantitative parameters. ResultsOf the 190 malignant liver nodules, 137 and 53 were HCCs and non-HCC malignancies, respectively. The median values of quantitative parameters RT (rise time), TTP (time to peak), mTTl (mean transit time local), and FT (fall time) in the non-HCC malignant group were lower than those in the HCC group, with p < 0.05. There was a statistically significant difference in WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve), and WoR (wash-out rate) values between HCC and non-HCC malignant groups, with p < 0.05. Using LR-M washout time <60 s and FT ≤21.2 s as the new diagnostic standard, the LR-5 category showed a sensitivity of 83.9%, specificity of 96.2%, and positive predictive value of 98.3% for HCC diagnosis. ConclusionDCE-US can facilitate the distinction of HCCs and non-HCC malignancies. Non-HCC malignancies present with earlier peak enhancement and more rapid and marked washout than HCC nodules. The combination of the LR-M classification criteria and FT ≤21.2 s can significantly improve the diagnostic sensitivity of the LR-5 category for HCC.

Quantitative time intensity curve analysis of contrast-enhanced ultrasound (CEUS) examinations for the assessment of focal liver lesions.

Contrast enhanced ultrasound (CEUS) is well-established for the characterization of focal liver lesions (FLLs). By using intravenous ultrasound contrast agents, followed by specific low mechanical index examinations, CEUS enables a high spatial and temporal resolution as well as a dynamic assessment of macro- and microvascularization down to the capillaries. Nevertheless, CEUS has the disadvantage of being examiner-dependent, so quantitative analysis of time-intensity curves in dynamic CEUS (D-CEUS) could provide further information. The aim of this article is to provide a general review of the current literature regarding the usefulness of D-CEUS in the assessment of FLLs.

Application of dynamic contrast enhanced ultrasound analysis in predicting early response to systemic therapy of intrahepatic cholangiocarcinoma

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.

Application of Dynamic Contrast-Enhanced Ultrasound in Evaluation the Activity of Crohn's Disease.

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.

Motion correction of 3D dynamic contrast-enhanced ultrasound imaging without anatomical B-Mode images: Pilot evaluation in eight patients.

Dynamic contrast-enhanced ultrasound (DCE-US) is highly susceptible to motion artifacts arising from patient movement, respiration, and operator handling and experience. Motion artifacts can be especially problematic in the context of perfusion quantification. In conventional 2D DCE-US, motion correction (MC) algorithms take advantage of accompanying side-by-side anatomical B-Mode images that contain time-stable features. However, current commercial models of 3D DCE-US do not provide side-by-side B-Mode images, which makes MC challenging. This work introduces a novel MC algorithm for 3D DCE-US and assesses its efficacy when handling clinical data sets. In brief, the algorithm uses a pyramidal approach whereby short temporal windows consisting of three consecutive frames are created to perform local registrations, which are then registered to a master reference derived from a weighted average of all frames. We applied the algorithm to imaging studies from eight patients with metastatic lesions in the liver and assessed improvements in original versus motion corrected 3D DCE-US cine using: (i) frame-to-frame volumetric overlap of segmented lesions, (ii) normalized correlation coefficient (NCC) between frames (similarity analysis), and (iii) sum of squared errors (SSE), root-mean-squared error (RMSE), and r-squared (R2 ) quality-of-fit from fitted time-intensity curves (TIC) extracted from a segmented lesion. We noted improvements in frame-to-frame lesion overlap across all patients, from 68%±13% without correction to 83%±3% with MC (p=0.023). Frame-to-frame similarity as assessed by NCC also improved on two different sets of time points from 0.694±0.057 (original cine) to 0.862±0.049 (corresponding MC cine) and 0.723±0.066 to 0.886±0.036 (p ≤ 0.001 for both). TIC analysis displayed a significant decrease in RMSE (p=0.018) and a significant increase in R2 goodness-of-fit (p=0.029) for the patient cohort. Overall, results suggest decreases in 3D DCE-US motion after applying the proposed algorithm.

Dynamic Contrast-Enhanced Ultrasound in the Prediction of Advanced Hepatocellular Carcinoma Response to Systemic and Locoregional Therapies

Dynamic Contrast-Enhanced Ultrasound in the Prediction of Advanced Hepatocellular Carcinoma Response to Systemic and Locoregional Therapies

P363 Multimodal dynamic ultrasound approach as predictor of response in patients with Crohn’s disease treated with ustekinumab

Abstract Background Early prediction of the response to biological drugs in Inflammatory Bowel Diseases (IBD) is of utmost importance to allow prompt optimization of therapeutic strategies. Ustekinumab (UST) is nowadays a milestone in the treatment of Crohn’s disease (CD), but potential markers predicting its long-term efficacy are still lacking. Multimodal ultrasound (US), encompassing B-mode US, color-Doppler and contrast-enhanced US (CEUS), is a promising non-invasive technique, providing complementary information to endoscopy, due to its ability to both assess transmural healing and quantify changes in bowel microvascularization over time. The main objective of this study was to evaluate the role of multimodal US in predicting endoscopic response to UST in patients with CD. The secondary aim was to develop an US score that allows an early detection of treatment response. Methods We conducted a prospective monocentric study in the IBD outpatient clinic of Policlinico Agostino Gemelli in Rome, enrolling consecutive patients with moderate to severe ileal CD, who were scheduled to begin UST therapy as per clinical practice. Demographic, clinical and laboratory data were collected. Clinical activity was defined according to Harvey-Bradshaw Index. A complete US evaluation including B mode, Doppler, dynamic CEUS and elastography was perfomed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each US parameter and their variations from baseline were correlated with endoscopic response (SES-CD reduction of at least 50% from baseline) and mucosal healing (SES-CD &amp;lt; 3) after 1 year. Results A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. Median values of US parameters at the various time points were significantly different in the group who achieved endoscopic response from non reponders’ group (Figure 1). The univariate analysis showed that the percentage changes between T3 and T0 of bowel wall thickness, Limberg score (LS), mean signal intensity, rise time, wash-in rate (WiR), C reactive protein and Harvey-Bradshaw Index were associated with long-term therapeutic outcome (table 1). At the multivariate logistic regression analysis, three independent predictors of endoscopic response were selected: male sex, ∆%LS, and ∆%WiR. Based on the above parameters, we developed an US score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91). Conclusion Multimodal ultrasound provides early predictors of the long-term therapeutic outcome in patients with CD treated with UST.

Innovative Experimental Ultrasound and US-Related Techniques Using the Murine Model in Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a cancer with one of the highest mortality rates in the world. Several studies have been conductedusing preclinical experiments in mice to find new therapeutic strategies. Experimental ultrasound, in expert hands, is a safe, multifaceted, and relatively not-expensive device that helps researchers in several ways. In this systematic review, we propose a summary of the applications of ultrasonography in a preclinical mouse model of PDAC. Eighty-eight studies met our inclusion criteria. The included studies could be divided into seven main topics: ultrasound in pancreatic cancer diagnosis and progression (n: 21); dynamic contrast-enhanced ultrasound (DCE-US) (n: 5); microbubble ultra-sound-mediated drug delivery; focused ultrasound (n: 23); sonodynamic therapy (SDT) (n: 7); harmonic motion elastography (HME) and shear wave elastography (SWE) (n: 6); ultrasound-guided procedures (n: 9). In six cases, the articles fit into two or more sections. In conclusion, ultrasound can be a really useful, eclectic, and ductile tool in different diagnostic areas, not only regarding diagnosis but also in therapy, pharmacological and interventional treatment, and follow-up. All these multiple possibilities of use certainly represent a good starting point for the effective and wide use of murine ultrasonography in the study and comprehensive evaluation of pancreatic cancer.

Intratumoral perfusion may affect microwave ablation area of hepatocellular carcinoma

Objectives We aimed to evaluate the effect of intratumoral perfusion on microwave ablation (MWA) area in hepatocellular carcinoma (HCC). Methods Patients who underwent curative MWA for HCC between October 2013 and May 2015 were enrolled. Three days before MWA, contrast-enhanced ultrasound (CEUS) was performed to illustrate the perfusion characteristics of the target lesion. Using the Sonoliver quantification software, time-intensity curves of dynamic CEUS were obtained, and quantitative parameters were extracted. Two microwave antennae were inserted into the center of the tumor and MWA was performed with a continuous power output of 50 W for 5 min. A second CEUS was performed to measure the size of the ablated region. Thereafter, an additional MWA procedure was performed until complete ablation with a 5–10-mm safety margin was achieved. Results A total of 38 patients who underwent curative MWA for 39 HCC nodules were enrolled. The mean age was 57 years (34–80 years), and the median maximum diameter of the HCC was 3.4 cm (interquartile range, 2–6.8 cm). Time-intensity curves were obtained and the area under the curve (AUC) was selected as a parameter for intratumoral perfusion. The AUC was inversely and linearly correlated with the size of the MWA area, including long- and short-axis diameters and ablation volume. A 1,000-dB·s change in the AUC produced an average change of 1.17 ± 0.44 mm, 0.725 ± 0.355 mm, and 2.4995 ± 0.6575 cm³ in the long- and short-axis diameters and ablation volume, respectively. Conclusions The intratumoral perfusion of HCC was inversely correlated with MWA area size.

Dynamic contrast-enhanced ultrasound (D-CEUS) to predict biological behaviour in pancreatic cancer: monocentric study preliminary results

Dynamic contrast-enhanced ultrasound (D-CEUS) to predict biological behaviour in pancreatic cancer: monocentric study preliminary results

Dynamic contrast-enhanced ultrasonography with sonazoid predicts microvascular invasion in early-stage hepatocellular carcinoma.

Microvascular invasion (MVI) is an independent risk factor for the early recurrence and poor survival of hepatocellular carcinoma (HCC). This study aims to investigate the potential clinical value of dynamic contrast-enhanced ultrasound (DCE-ultrasound)-Sonazoid in pre-operatively assessing MVI in HCC. This single centre prospective study included 140 patients with histopathologically confirmed single HCC lesions. Patients were classified according to the post-operative pathological information presence of MVI: MVI+ group (n = 32) and MVI- group (n = 108). All patients underwent DCE-ultrasound within 1 week before surgery. The quantitative perfusion parameters of HCC lesions, margins of HCC lesions, and distal liver parenchyma were obtained and analyzed. Clinicopathological (serum alpha-fetoprotein, Des-gamma-carboxyprothrombin, and pathological grade) and grayscale imaging features (tumor size) were significantly different between the MVI+ and MVI- groups (p < 0.05). Further quantitative analysis showed that when comparing the MVI+ and MVI- groups, half-decrease time and wash-out rate of HCC lesions and peak enhancement in the arterial phase of difference between the margin area of HCC and distal liver parenchyma were significantly different (p = 0.045, p = 0.035, and p = 0.023, respectively). Combining the above three quantitative parameters, the accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value were 69.3% (97/140), 37.8% (17/45), 84.3% (80/95), 53.1% (17/32), 74.1% (80/108), respectively. DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions. DCE-ultrasound with quantitative perfusion analysis has the potential to predict MVI in HCC lesions.

EFSUMB Technical Review - Update 2023: Dynamic Contrast-Enhanced Ultrasound (DCE-CEUS) for the Quantification of Tumor Perfusion.

Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.

Joint Segmentation and Differential Diagnosis of Thyroid Nodule in Contrast-Enhanced Ultrasound Images.

Microvascular perfusion can be observed in real time with contrast-enhanced ultrasound (CEUS), which is a novel ultrasound technology for visualizing the dynamic patterns of parenchymal perfusion. Automatic lesion segmentation and differential diagnosis of malignant and benign based on CEUS are crucial but challenging tasks for computer-aided diagnosis of thyroid nodule. To tackle these two formidable challenges concurrently, we provide Trans-CEUS, a spatial-temporal transformer-based CEUS analysis model to finish the joint learning of these two challenging tasks. Specifically, the dynamic swin-transformer encoder and multi-level feature collaborative learning are combined into U-net for achieving accurate segmentation of lesions with ambiguous boundary from CEUS. In addition, variant transformer-based global spatial-temporal fusion is proposed to obtain long-distance enhancement perfusion of dynamic CEUS for promoting differential diagnosis. Empirical results of clinical data showed that our Trans-CEUS model achieved not only a good lesion segmentation result with a high Dice similarity coefficient of 82.41%, but also superior diagnostic accuracy of 86.59%. Conclusion & significance: This research is novel since it is the first to incorporate the transformer into CEUS analysis, and it shows promising results on dynamic CEUS datasets for both segmentation and diagnosis tasks of the thyroid nodule.

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

The aim of the work described here was to investigate the value of dynamic contrast enhanced ultrasound (DCE-US) and quantitative analysis in pre-operative differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) in non-cirrhotic liver. In this retrospective study, patients with histopathologically proven ICC and HCC lesions in non-cirrhotic liver were included. All patients underwent contrast-enhanced ultrasound (CEUS) examinations with an Acuson Sequoia unit (Siemens Healthineers, Mountain View, CA, USA) unit or LOGIQ E20 (GE Healthcare, Milwaukee, WI, USA) within 1 wk before surgery. SonoVue (Bracco, Milan, Italy) was used as the contrast agent. B-mode ultrasound (BMUS) features and CEUS enhancement patterns were analyzed. DCE-US analysis was performed by VueBox software (Bracco). Two regions of interest (ROIs) were set in the center of the focal liver lesions and their surrounding liver parenchyma. Time-intensity curves (TICs) were generated, and quantitative perfusion parameters were obtained and compared between the ICC and HCC groups using the Student t-test or Mann-Whitney U-test. From November 2020 to February 2022, patients with histopathologically confirmed ICC (n=30) and HCC (n=24) lesions in non-cirrhotic liver were included. During the arterial phase (AP) of CEUS, ICC lesions exhibited heterogeneous hyperenhancement (13/30, 43.3%), heterogeneous hypo-enhancement (2/30, 6.7 %) and rim-like hyperenhancement (15/30, 50.0%), whereas all HCC lesions exhibited heterogeneous hyperenhancement (24/24, 100.0%) (p < 0.05). Subsequently, most of the ICC lesions exhibited AP wash-out (83.3%, 25/30), whereas a few cases exhibited wash-out in the portal venous phase (PVP) (15.7%, 5/30). In contrast, HCC lesions exhibited AP wash-out (41.7%, 10/24), PVP wash-out (41.7%, 10/24) and a small part of late phase wash-out (16.7%, 4/24) (p < 0.05). Compared with those of HCC lesions, TICs of ICCs revealed earlier and lower enhancement during the AP, faster decline during the PVP and reduced area under the curve. The combined area under the receiver operating characteristic curve (AUROC) of all significant parameters was 0.946, with 86.7% sensitivity, 95.8% specificity and 90.7% accuracy in differential diagnosis between ICC and HCC lesions in non-cirrhotic liver, which improved the diagnostic efficacy of CEUS (58.3% sensitivity, 90.0% specificity and 75.9% accuracy). ICC and HCC lesions in non-cirrhotic liver might exhibit some overlap of CEUS features in diagnosis. DCE-US with quantitative analysis would be helpful in pre-operative differential diagnosis.

Liver Cancer Vascularity Driven by Extracellular Matrix Stiffness: Implications for Imaging Research.

Extracellular matrix stiffness represents a barrier to effective local and systemic drug delivery. Increasing stiffness disrupts newly formed vessel architecture and integrity, leading to tumor-like vasculature. The resulting vascular phenotypes are manifested through different cross-sectional imaging features. Contrast-enhanced studies can help elucidate the interplay between liver tumor stiffness and different vascular phenotypes. This study aims to correlate extracellular matrix stiffness, dynamic contrast-enhanced computed tomography, and dynamic contrast-enhancement ultrasound imaging features of 2 rat hepatocellular carcinoma tumor models. Buffalo-McA-RH7777 and Sprague Dawley (SD)-N1S1 tumor models were used to evaluate tumor stiffness by 2-dimensional shear wave elastography, along with tumor perfusion by dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography. Atomic force microscopy was used to calculate tumor stiffness at a submicron scale. Computer-aided image analyses were performed to evaluate tumor necrosis, as well as the percentage, distribution, and thickness of CD34+ blood vessels. Distinct tissue signatures between models were observed according to the distribution of the stiffness values by 2-dimensional shear wave elastography and atomic force microscopy ( P < 0.05). Higher stiffness values were attributed to SD-N1S1 tumors, also associated with a scant microvascular network ( P ≤ 0.001). Opposite results were observed in the Buffalo-McA-RH7777 model, exhibiting lower stiffness values and richer tumor vasculature with predominantly peripheral distribution ( P = 0.03). Consistent with these findings, tumor enhancement was significantly greater in the Buffalo-McA-RH7777 tumor model than in the SD-N1S1 on both dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography ( P < 0.005). A statistically significant positive correlation was observed between tumor perfusion on dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography in terms of the total area under the curve and % microvessel tumor coverage ( P < 0.05). The stiffness signatures translated into different tumor vascular phenotypes. Two-dimensional shear wave elastography and dynamic contrast-enhanced ultrasonography adequately depicted different stromal patterns, which resulted in unique imaging perfusion parameters with significantly greater contrast enhancement observed in softer tumors.

Dynamic Perfusion Representation and Aggregation Network for Nodule Segmentation using Contrast-enhanced US.

Dynamic contrast-enhanced ultrasound (CEUS) imaging has been widely applied in lesion detection and characterization, due to its offered real-time observation of microvascular perfusion. Accurate lesion segmentation is of great importance to the quantitative and qualitative perfusion analysis. In this paper, we propose a novel dynamic perfusion representation and aggregation network (DpRAN) for the automatic segmentation of lesions using dynamic CEUS imaging. The core challenge of this work lies in enhancement dynamics modeling of various perfusion areas. Specifically, we divide enhancement features into the two scales: short-range enhancement patterns and long-range evolution tendency. To effectively represent real-time enhancement characteristics and aggregate them in a global view, we introduce the perfusion excitation (PE) gate and cross-attention temporal aggregation (CTA) module, respectively. Different from the common temporal fusion methods, we also introduce an uncertainty estimation strategy to assist the model to locate the critical enhancement point first, in which a relatively distinguished enhancement pattern is displayed. The segmentation performance of our DpRAN method is validated on our collected CEUS datasets of thyroid nodules. We obtain the mean dice coefficient (DSC) and intersection of union (IoU) of 0.794 and 0.676, respectively. Superior performance demonstrates its efficacy to capture distinguished enhancement characteristics for lesion recognition. Code is available https://github.com/wanpeng16/DpRAN.

VueBox® perfusion analysis of dynamic contrast enhanced ultrasound provides added value in the diagnosis of small thyroid nodules.

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).

Multiparametric Dynamic Ultrasound Approach for Differential Diagnosis of Primary Liver Tumors.

A correct differentiation between hepatocellular carcinoma (HCC) and intracellular cholangiocarcinoma (ICC) is essential for clinical management and prognostic prediction. However, non-invasive differential diagnosis between HCC and ICC remains highly challenging. Dynamic contrast-enhanced ultrasound (D-CEUS) with standardized software is a valuable tool in the diagnostic approach to focal liver lesions and could improve accuracy in the evaluation of tumor perfusion. Moreover, the measurement of tissue stiffness could add more information concerning tumoral environment. To explore the diagnostic performance of multiparametric ultrasound (MP-US) in differentiating ICC from HCC. Our secondary aim was to develop an US score for distinguishing ICC and HCC. Between January 2021 and September 2022 consecutive patients with histologically confirmed HCC and ICC were enrolled in this prospective monocentric study. A complete US evaluation including B mode, D-CEUS and shear wave elastography (SWE) was performed in all patients and the corresponding features were compared between the tumor entities. For better inter-individual comparability, the blood volume-related D-CEUS parameters were analyzed as a ratio between lesions and surrounding liver parenchyma. Univariate and multivariate regression analysis was performed to select the most useful independent variables for the differential diagnosis between HCC and ICC and to establish an US score for non-invasive diagnosis. Finally, the diagnostic performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis. A total of 82 patients (mean age ± SD, 68 ± 11 years, 55 men) were enrolled, including 44 ICC and 38 HCC. No statistically significant differences in basal US features were found between HCC and ICC. Concerning D-CEUS, blood volume parameters (peak intensity, PE; area under the curve, AUC; and wash-in rate, WiR) showed significantly higher values in the HCC group, but PE was the only independent feature associated with HCC diagnosis at multivariate analysis (p = 0.02). The other two independent predictors of histological diagnosis were liver cirrhosis (p < 0.01) and SWE (p = 0.01). A score based on those variables was highly accurate for the differential diagnosis of primary liver tumors, with an area under the ROC curve of 0.836 and the optimal cut-off values of 0.81 and 0.20 to rule in or rule out ICC respectively. MP-US seems to be a useful tool for non-invasive discrimination between ICC and HCC and could prevent the need for liver biopsy at least in a subgroup of patients.