Wash-in Area Under The Curve Research Articles

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.

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.

P482 Diagnostic accuracy of contrast-enhanced ultrasound for fibrotic strictures of Crohn’s disease: a systematic review and meta-analysis of individual participant data

Abstract Background Crohn's disease (CD) often leads to the development of intestinal strictures, requiring effective differentiation between inflammatory and fibrotic for the optimal treatment strategies. Despite recent advances in drug development targeting fibrosis, current evaluation methods remain insufficient. Contrast-enhanced ultrasound (CEUS) is a promising modality for assessing vascularity and inflammation, yet its accuracy in fibrosis detection needs more validation. Methods A systematic review and meta-analysis were conducted using IPD to determine the diagnostic accuracy of CEUS in identifying intestinal fibrosis in CD. Our search included databases such as MEDLINE, EMBASE, and Web of Science up until March 23, 2023. Inclusion criteria required a confirmed diagnosis of CD and studies that evaluated the accuracy of CEUS parameters, including total area under the curve (AUC), wash-in AUC, wash-out AUC, peak enhancement, wash-in perfusion index, wash-in rate, wash-out rate, rise time, fall time, and mean transit time related to fibrosis in CD (Figure 1 (A)). The quality of included studies was assessed using the QUADAS-2 tool, with each study mandatorily using surgical specimen pathology as a reference standard in at least one instance. Results Our qualitative synthesis included eight studies encompassing 306 patients. These studies were generally assessed to have a high risk of bias. It is important to note that while peak enhancement and AUC were frequently examined across studies, neither parameter had established absolute cutoff values for the diagnosis of fibrosis. From the three studies where IPD was available, detailed data from 80 patients were included in the meta-analysis (colon n=11 and small bowel n= 69). Among them, 54 underwent surgical intervention with fibrosis being confirmed in 31. The highest diagnostic accuracy was observed for total AUC and wash-in AUC, with pooled sensitivity and specificity for predicting fibrosis at 0.86 (95% CI, 0.59–0.97) and 0.25 (95% CI, 0.03–0.76), respectively (Figure 1 (B)). Conclusion This meta-analysis with IPD pioneers the exclusive evaluation of CEUS for fibrotic strictures in CD. It reveals a significant risk of bias in the primary research and a notable absence of consensus on the CEUS parameters' threshold values for distinguishing fibrosis from inflammation. The observed low specificity highlights the need for innovative strategies in future research, such as integrating CEUS with techniques like elastography, to enhance the precision of fibrosis detection in CD. PROSPERO 2020 CRD42020214472. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020214472

Renal elasticity and perfusion changes on ultrasonography in an early-stage diabetic rat model.

Renal hemodynamic changes in early diabetes occur before the onset of significant structural abnormalities or clinical manifestations, and timely detection of these changes has clinical significance. This study aimed to evaluate renal elasticity and perfusion changes in an early-stage diabetic rat model by shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS), and to explore the potential correlations between renal elasticity and perfusion parameters. A total of 18 male Sprague-Dawley rats were randomly divided into three groups: a control group (group 1, n=6), a diabetic group (group 2, n=6), and a diabetic group receiving drug therapy (group 3, n=6). An intraperitoneal injection of streptozotocin (STZ) for 2 days combined with a high-fat diet (HFD) was used as the early-stage diabetic rat model. The diabetic rats in group 3 were treated with canagliflozin and losartan for 6 weeks, whereas the rats in groups 1 and 2 were given equal amounts of purified water. Renal stiffness on SWE and perfusion parameters on CEUS were measured and compared among the three groups, then the rats were sacrificed, and serum, urine, and renal histopathology were evaluated to confirm the development of early diabetes. The early-stage diabetic rats without significant pathological changes exhibited bigger kidneys and higher blood glucose (all P<0.05). Among the CEUS parameters, peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in perfusion index (WiPI), wash-out AUC (WoAUC), wash-in and wash-out AUC (WiWoAUC), rise time (RT), and time to peak (TTP) of diabetic rats in group 2 were significantly increased (all P<0.05), and the hyperperfusion ameliorated significantly after drug treatment. The renal elasticity measured by SWE varied in accordance with certain perfusion parameters, and was strongly positively correlated with WiAUC (r=0.701, P<0.001), WoAUC (r=0.647, P<0.001), and WiWoAUC (r=0.655, P<0.001), and moderately positively correlated with PE (r=0.539, P=0.001), WiPI (r=0.555, P<0.001), RT (r=0.425, P=0.010), and TTP (r=0.439, P=0.007). Renal elasticity and perfusion changes in the early stage of diabetes, and renal elasticity was positively associated with delayed and increased perfusion.

Contrast-Enhanced Ultrasound and Conventional Ultrasound Characteristics of Breast Cancer With Different Molecular Subtypes

BackgroundIdentifying molecular subtypes of breast cancer (BC) is of great significance in selecting optimal treatment strategy. Different molecular subtypes of BC have various vascular distribution characteristics. Contrast-enhanced ultrasound (CEUS) can dynamically display the microcirculation of tumor. This study intends to explore the conventional ultrasound and CEUS characteristics of different molecular subtypes of BC. MethodsDuring this prospective study, 86 patients with BC who were divided into Luminal A (LA), Luminal B (LB), HER2 over-expression (H2), and triple-negative (TN). The CEUS qualitative and quantitative characteristics of BC with different molecular subtypes was explored, as well as the conventional ultrasound features. In addition, the diagnostic efficiency of CEUS quantitative parameters in differentiating molecular subtypes of BC was analyzed. ResultsOur study found that the Adler grade differed significantly among 4 molecular subtypes (P < .05). The enhancement speed, enhancement degree and size after enhancement of 4 molecular subtypes were statistically different (P < .05). The wash in slope (WIS), peak intensity (PI), and wash-in area under the curve (WiAUC) differed significantly among 4 subtypes (P < .05). The diagnostic efficiency of PI was better for detecting LA and H2 subtype with the areas under the receiver operating characteristic curve was 0.778 and 0.734, respectively. ConclusionDifferent molecular subtypes of BC have different CEUS and conventional ultrasound characteristics. CEUS can provide valuable imaging basis for precise clinical diagnosis and individualized therapy of BC with different molecular subtypes.

Effects of exercise and cold-water exposure on microvascular muscle perfusion.

Microvascular blood flow (MBF) and its intramuscular regulation are of importance for physiological responsiveness and adaptation. The quantifiable in-vivo monitoring of MBF after cycling or systemic cold-water exposure may reveal new insights into capillary regulatory mechanisms. This study aimed to assess the role of exercise and cold therapy on MBF by using contrast-enhanced ultrasound (CEUS). Twenty healthy athletes were recruited and randomly assigned to an intervention (IG) or a control group (CG). MBF was quantified in superficial (rectus femoris, RF) and deep muscle layers (vastus intermedius, VI). Representative perfusion parameters (peak enhancement (PE) and wash-in area under the curve (WiAUC)) were measured after a standardized measurement protocol for both groups at resting conditions (t0) and after cycling (20 min., 70% Watt max, t1) for both groups, after cold-water immersion exposure for IG (15 min., 12°C) or after precisely 15 minutes of rest for CG (t2) and for both groups after 60 minutes of follow-up (t3). At t1, MBF in VI increased significantly compared to resting conditions in both groups in VI (p= 0.02). After the cold-water exposure (t2), there were no statistically significant changes in perfusion parameters as well as after 60 minutes of follow-up (t3) (p = 0.14). Cycling leads to an upregulation of MBF. However, cold exposure does not change the MBF. The implementation of CEUS during different physiological demands may provide deeper insight into intramuscular perfusion regulation and regenerative processes.

Prediction of renal recovery following sepsis-associated acute kidney injury requiring renal replacement therapy using contrast-enhanced ultrasonography.

Microcirculatory dysfunction plays a critical role in sepsis-associated acute kidney injury (S-AKI) development; however, its impact on renal recovery remains uncertain. We investigated the association between cortical microcirculatory function assessed using contrast-enhanced ultrasonography (CEUS) and renal recovery after S-AKI needing renal replacement therapy (RRT). This retrospective study included 23 patients who underwent CEUS among those who underwent acute RRT for S-AKI. In addition, we acquired data from 17 healthy individuals and 18 patients with chronic kidney disease. Renal recovery was defined as sustained independence from RRT for at least 14 days. Of the CEUS-derived parameters, rise time, time to peak, and fall time were longer in patients with S-AKI than in healthy individuals (p = 0.045, 0.01, and 0.096, respectively). Fourteen patients (60.9%) with S-AKI receiving RRT experienced renal recovery; and these patients had higher values of peak enhancement, wash-in area under the curve (AUC), wash-in perfusion index, and washout AUC than those without recovery (p = 0.03, 0.01, 0.03, and 0.046, respectively). We evaluated the receiver operating characteristic curve and found that the peak enhancement, wash-in AUC, wash-in perfusion index, and wash-out AUC of CEUS derivatives estimated the probability of renal recovery after S-AKI requiring RRT (p = 0.03, 0.01, 0.03, and 0.04, respectively). CEUS-assessed cortical microvascular perfusion may predict renal recovery following S-AKI that requires RRT. Further studies are essential to validate the clinical utility of microcirculatory parameters obtained from CEUS to estimate renal outcomes in various etiologies and severities of kidney disease.

Early Prediction of Response to Neoadjuvant Chemotherapy Using Quantitative Parameters on Automated Breast Ultrasound Combined with Contrast-Enhanced Ultrasound in Breast Cancer.

This prospective study was aimed at evaluating the role of automated breast ultrasound (ABUS) and contrast-enhanced ultrasound (CEUS) in the early prediction of treatment response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. Forty-three patients with pathologically confirmed invasive breast cancer treated with NAC were included. The standard for evaluation of response to NAC was based on surgery within 21 d of completing treatment. The patients were classified as having a pathological complete response (pCR) and a non-pCR. All patients underwent CEUS and ABUS 1 wk before receiving NAC and after two treatment cycles. The rising time (RT), time to peak (TTP), peak intensity (PI), wash-in slope (WIS) and wash-in area under the curve (Wi-AUC) were measured on the CEUS images before and after NAC. The maximum tumor diameters in the coronal and sagittal planes were measured on ABUS, and the tumor volume (V) was calculated. The difference (∆) in each parameter between the two treatment time points was compared. Binary logistic regression analysis was used to identify the predictive value of each parameter. ∆V, ∆TTP and ∆PI were independent predictors of pCR. The CEUS-ABUS model achieved the highest AUC (0.950), followed by those based on CEUS (0.918) and ABUS (0.891) alone. The CEUS-ABUS model could be used clinically to optimize the treatment of patients with breast cancer.

Diagnostic Value of Qualitative and Quantitative Contrast-Enhanced Ultrasound for Pathological Subtypes of Small Solid Renal Masses.

To assess the diagnostic value of qualitative and quantitative contrast-enhanced ultrasound (CEUS) for pathological subtypes of small solid renal masses (sSRMs). Patients with sSRMs confirmed by surgical pathology from January 2019 to November 2021 were retrospectively identified. All patients were divided into 3 groups: clear cell renal cell carcinoma (ccRCC) group, none-ccRCC group (renal cell carcinoma other than ccRCC), and angiomyolipoma (AML) group. The mass position, size, echogenicity and blood flow signals were compared. The speed of wash-in, wash-out, the degree of peak enhancement and the homogeneity at peak enhancement, the presence of pseudocapsule sign in CEUS imaging were qualitatively evaluated. Peak enhancement, wash-in area under the curve (WiAUC), rise time, time to peak, wash-in rate (WiR), wash-in perfusion index (WiPI) and tumor-to-cortex enhancement ratio of the above parameters in CEUS imaging were quantitatively evaluated. Of 105 patients, 105 sSRMs (66 ccRCC, 18 none-ccRCC, 21 AML) were enrolled in this study. No significant differences were found on location, size and echogenicity among 3 groups (all P > .05). The proportion of fast-washout and hypo-enhancement were highest in none-ccRCC group. Heterogeneous enhancement was detected in 87.88% in ccRCC group which is significantly higher than other 2 groups. Hundred percent of the AML showed no pseudocapsule sign, which is the highest among the 3 groups. Peak enhancement, WiAUC, WiR, WiPI of ccRCC group were the highest among the 3 groups. Qualitative and quantitative CEUS not only has the diagnostic value in distinguishing AML from malignant sSRMs, but also helps to differentiate the pathological subtypes of sSRMs.

Early Assessment of Chemoradiotherapy Response for Locally Advanced Pancreatic Ductal Adenocarcinoma by Dynamic Contrast-Enhanced Ultrasound.

To evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) and quantitative parameters in early prediction of tumor response to chemoradiotherapy (CRT) in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). In this prospective study, patients with biopsy-proved and histopathologically proved LAPC who underwent regular CRT were recruited. DCE-US evaluations were performed before and four months after CRT. SonoVue-enhanced contrast-enhanced ultrasound (CEUS) was performed by an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, USA) equipped with a 5C1 MHz convex array transducer. Time-intensity curves were created by VueBox software (Bracco, Italy), and various DCE-US quantitative parameters were obtained. Taking Response Evaluation Criteria in Solid Tumors (RECIST) based on computed tomography (CT) or magnetic resonance imaging (MRI) as the gold standard, DCE-US parameters were compared between the treatment responder group (RG) and non-responder group (NRG). The correlation between the DCE-US parameters and the serum carbohydrate antigen 19-9 (CA 19-9) level was also analyzed. Finally, 21 LAPC patients (mean age 59.3 ± 7.2 years) were included. In comparing the RG (n = 18) and NRG (n = 3), no significant change could be found among the mean size of the lesions (31.2 ± 8.1 mm vs. 27.2 ± 8.3 mm, p = 0.135). In comparing the TICs between the two groups, the LAPC lesions in the RG took a longer time to reach peak enhancement and to wash out. Among all the DCE-US parameters, RT (rise time), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiWoAUC (wash-in and wash-out area under the curve) decreased significantly after CRT in the RG (p &lt; 0.05). The RT ratio, WiAUC ratio, WoAUC ratio and WiWoAUC ratio were closely correlated with the change in serum CA 19-9 level in the RG (p &lt; 0.05). DCE-US might be a potential imaging method for non-invasive follow-up for early response in LAPC patients treated by CRT.

Correlation between serum cystatin C level and renal microvascular perfusion assessed by contrast-enhanced ultrasound in patients with diabetic kidney disease

Objectives To investigate the relationship between serum cystatin C (CysC) levels and renal microvascular perfusion in patients with diabetic kidney disease (DKD). Methods A total of 57 patients with high CysC levels and 45 patients with normal CysC levels were enrolled. Data on clinical characteristics and laboratory examination results were also collected. Contrast-enhanced ultrasound (CEUS) of the kidneys was successively performed. The time-intensity curve (TIC) and related quantitative parameters of the kidneys were obtained by CEUS and the correlations between CysC and CEUS parameters were analyzed. Results Compared to the normal CysC group, the high CysC group had significantly lower wash-in area under the curve (WiAUC), wash-out area under the curve (WoAUC), and wash-in and wash-out area under the curve (WiWoAUC). In the normal CysC group, patients with Stage III chronic kidney disease (CKD) had higher AUCs than those with Stage I–II CKD (p < 0.05). In the high CysC group, patients with Stage IV–V CKD had lower wash-in AUC compared to patients with Stage I–II CKD (p = 0.023). The renal cortex microvascular perfusion parameters AUCs were positively correlated with the estimated glomerular filtration rate (GFR) (r = 0.280, 0.222, and 0.243), and CysC was inversely correlated with AUCs (r= −0.299, −0.251, and −0.273). Conclusions CEUS parameters reflected changes in renal microvascular perfusion in patients with DKD, while AUCs might be useful indicators of declining GFR in DKD patients with increased CysC.

The value of contrast-enhanced ultrasound quantitative parameters in the prognosis prediction of hepatocellular carcinoma after thermal ablation: a retrospective cohort study.

The postoperative recurrence rate is the main factor affecting the prognosis of hepatocellular carcinoma (HCC) patients, this study sought to investigate the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the recurrence and the survival of HCC patients after thermal ablation. The data of 97 patients with pathologically diagnosed HCC who underwent thermal ablation were retrospectively included in this study. The patients had an average age of 46.6 years (range, 23-79 years), and 79 were male and 18 were female. CEUS follow-up was performed at 1- and 3-month after thermal ablation, then at 6-month intervals thereafter for 5 years. CEUS was performed before thermal ablation, and the results were analyzed quantitatively using CEUS perfusion software (VueBox®, Bracco, Italy). The ratios of the CEUS quantitative parameters between the HCC lesions and reference liver parenchyma were calculated. The parameters included the average contrast signal intensity (MeanLin), peak enhancement (PE), rising time (RT), fall time (FT), time to peak (TTP), mean transit time (mTT), perfusion index (PI), Wash-in Area Under the Curve (WiAUC), Wash-in Rate (WiR), Wash-in Perfusion Index (WiPI), Wash-out Area Under the Curve (WoAUC), Wash-out Rate (WoR), and WiAUC + WoAUC (WiWoAUC). The correlations between the preoperative CEUS quantitative parameter ratios, the blood laboratory indexes, postoperative recurrence, and survival were analyzed using log-rank tests and a Cox regression model. The average follow-up duration period was 79 months (range, 5-145 months). The average recurrence time after ablation was 1-127 months, and the median disease-free survival time was 21 months. The 1-, 3- and 5-year survival rates were 96.9%, 92.3%, and 80.6%, respectively. The log-rank tests showed that tumor size, prothrombin time, and WiAUC, WoAUC, and WiWoAUC ratios were predictors of survival, and aspartate aminotransferase was a predictor of recurrence. The Cox regression analysis showed that tumor size [odds ratio (OR): 6.421; 95% CI: 1.434-28.761] and alanine transaminase (OR: 0.88; 95% CI: 0.010-0.742) were predictors of a poor prognosis. CEUS quantitative parameters before thermal ablation and blood laboratory indexes provide potential clinical value for predicting the postoperative recurrence and survival of HCC patients.

Application of dynamic contrast enhanced ultrasound in distinguishing focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma.

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.

Comparison of superb microvascular imaging (SMI) quantified with ImageJ to quantified contrast-enhanced ultrasound (qCEUS) in liver metastases-a pilot study.

The aim of the study was to compare methods for the assessment of vascularisation of liver metastases (LM) between superb microvascular imaging (SMI), contrast-enhanced ultrasound, and microvascular density (MVD). SMI results were quantified as the vascularisation quotient (VQ), based on a grey-scale analysis with ImageJ image software. Those results were compared to contrast-enhanced ultrasonography (CEUS) values, calculated with VueBox®. MVD was measured with an anti-CD34 antibody. This study included 13 patients with LM. The VQ showed a strong correlation with the quantified parameters of contrast-enhanced ultrasound. The parameters of quantified contrast-enhanced ultrasound compared with quantified SMI showed the following statistical correlations: peak enhancement (PE), in arbitrary unit (a.u.) (r=0.72104, P=0.0054), PE in Decibel (dB) (r=0.65918, P=0.00141), Wash-in- Area Under the Curve (WiAUC) in a.u. (r=0.63604, P=0.00194), Wash-in Perfusion-Index (WiPI) in a.u. (r=0.73337, P=0.0043), Wash-in Perfusion-Index (WiPI) in dB (r=0.65642, P=0.0194), Wash-in-Rate (WiR) in a.u. (r=0.7304, P=0.0036) and Wash-in-Rate (WiR) in dB (r=0.82897, P=0.0005). Comparison of the two methods, SMI and contrast-enhanced ultrasound (CEUS), for quantitative assessment of vascularisation of LM showed good correlation. The contrast-independent Doppler technique SMI can qualitatively assess the vascularisation of LM.

Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging.

BackgroundUnderstanding angiogenesis in prostate cancer is essential. LNCaP prostate xenograft tumors are androgen responsive and closely mimic clinical disease. Orthotopic animal models replicate aspects of the cancer microenvironment and are more clinically relevant than subcutaneous models. Comparative studies investigating angiogenesis using contrast-enhanced ultrasound (CEUS) imaging in subcutaneous and orthotopic mouse models of prostate cancer have not been performed.MethodsTumor microcirculation and perfusion in subcutaneous and orthotopic LNCaP xenograft Balb/c athymic nude mice models were compared by investigating microbubble wash-in with CEUS.ResultsThe take rate of subcutaneous and orthotopic tumors were 58.3% and 68.2%, respectively. On CEUS, orthotopic prostate tumors enhanced more rapidly than subcutaneous tumors. Mean arrival-time (Atm) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 4.21±1.86, 1.72±0.79, and 0.73±0.12 s, respectively. Mean Atm was significantly longer for subcutaneous tumors compared to orthotopic prostate tumors or kidney (P<0.01). Mean time to peak enhancement (TtoPk) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 38.56±13.23, 12.39±7.17, and 3.74±1.41 s, respectively. Mean TtoPk were significantly shorter for orthotopic prostate tumors and kidney compared to subcutaneous tumors (P<0.01). Mean wash-in area under the curve (WiAuC) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 611.11±247.52, 1,800.57±623.11, and 1,887.51±103.68 dB, respectively. Mean AUC was significantly higher for orthotopic prostate tumors and kidney compared to subcutaneous tumors (P<0.01). Parametric imaging confirmed these findings. The density of CD31-positive vessels was significantly higher in orthotopic prostate tumors (43.98±6.14 vessels/field) compared to subcutaneous tumors (15.44±3.74 vessels/field, P<0.01).ConclusionsThese findings demonstrate that orthotopic LNCaP xenografts better recreate a pro-angiogenic microenvironment than subcutaneous LNCaP xenografts.

Potential application of dynamic contrast enhanced ultrasound in predicting microvascular invasion of hepatocellular carcinoma.

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.

Multiparametric ultrasonographic analysis of testicular tumors: a single-center experience in a collective of 49 patients

Purpose: The aim of the present retrospective single-center study is to evaluate the diagnostic performance of multiparametric ultrasonography for characterizing testicular tumors.Method: Forty-nine patients with testicular tumors, 36 of malignant vs 13 of benign entity, were included in this retrospective single-center study on whom multiparametric sonography, encompassing native B-mode, Color Doppler, contrast-enhanced ultrasound (CEUS) and elastography, was performed between 2011–2018. In 48 of 49 patients, findings from multiparametric analysis were correlated with histopathological results. The applied contrast agent for CEUS was a second-generation blood pool agent. Ultrasonography examinations were performed and interpreted by a single experienced radiologist with more than 15 years of experience (EFSUMB Level 3).Results: Multiparametric ultrasonography was successfully performed in all included patients without any adverse effects. Concomitant testicular microlithiasis, rapid arterial wash-in, elevated values for perfusion quantification – Peak Enhancement (PE), Wash-in Area Under the Curve (WiAUC) and Wash-in Perfusion Index (WiPI) – and higher shear wave velocities were significantly associated with malignancy.Conclusions: Multiparametric ultrasonography depicts a non-ionizing, directly accessible and cost-effective imaging modality that allows for the extensive characterization of testicular tumors, thereby helping to discriminate between malignant and benign entity of testicular tumors.

Color coded perfusion analysis and microcirculation imaging with contrast enhanced ultrasound (CEUS) for post-interventional success control following thermal ablative techniques of primary and secondary liver malignancies.

Evaluation of the post-interventional success following ablative techniques (radiofrequency and microwave) using a new color coded perfusion quantification software with CEUS in patients with primary and secondary liver malignancies. 75 patients (60 males, 15 females, age 24-84 years, mean 62.7 years) with 128 malignant liver lesions were included in this study. Between 01/2013 and 06/2018, the therapeutic interventional procedure in 88 lesions was MWA, in 40 lesions RFA. All patients underwent CEUS using a convex multifrequency probe (1-6 MHz) following application of 1-2.4 ml sulphur hexaflouride microbubbles, before and within 24 hours following RFA and MWA to detect residual tumor tissue. Postprocessing of the stored DICOM loops from 15 sec up to 1 min using a perfusion quantification software regarding peak enhancement (pE), time to peak (TTP), mean transit time (MTT), rise time (Ri) and Wash-in area under the curve (WiAUC) in the center of the lesion, the border area and periphery was performed. In patients treated with RFA, pE differences between center of the lesion vs. surrounding liver were found to be statistically extremely significant (p < 0.001), differences between center of the lesion and margin were also statistically significant (p < 0.01). mTT, TTP, WiAuC and Ri showed no significant difference between center, margin or surrounding liver.In patients treated with MWA, statistically significant differences (p < 0.05) were found for pE, Ri and mTT regarding the differences between center of lesion and surrounding tissue. WiAuC and TTP showed no significant differences between center, margin or surrounding liver. CEUS with perfusion imaging is a valuable supporting tool for post-interventional success control following RFA and MWA of primary and secondary liver maligancies. Focus should be placed upon pE following MWA and pE, Ri and mTT following RFA.

Color Coded Perfusion Imaging with Contrast Enhanced Ultrasound (CEUS) for Post-Interventional Success Control Following Irreversible Electroporation (IRE) of Primary and Secondary Malignant Liver Lesions.

Evaluation of the post-interventional success following irreversible electroporation (IRE) using a new color coded perfusion quantification software with contrast-enhanced ultrasound (CEUS) in patients with malignant lesions of the liver. Thirty-eight patients with 68 malignant liver lesions underwent IRE. All malignant lesions were investigated with CEUS before and within 24 hours following IRE to detect residual tumor tissue. The parameters analyzed by color coded perfusion quantification software were: the peak enhancement (pE), time to peak (TTP), mean transit time (mTT), rise (Ri) and wash-in area under the curve (WiAUC). Perfusion in the center, the margins of the lesions and in the surrounding liver were evaluated using these parameters. Hepatocellular carcinoma (HCC) with complete ablation showed significantly different changes between the center and the margin of the lesions for WiAUC (p<0.05) and pE (p<0.01). Also significant differences were noted between the center of the lesions and the surrounded tissue for the same parameters (p<0.01). In the completely ablated metastatic lesions, significant differences were found between the center of the lesion and the margins (p < 0.01) and between the center of the lesion and the surrounding liver (p < 0.05) for WiAUC. mTT, TTP and Ri showed no significant changes between the center of the lesions, margin of the lesions or surrounding tissue. Also, no significant differences were found for these parameters in the different regions of interest for HCC or the metastatic lesions with partial ablation success. CEUS with perfusion imaging is a valuable supporting tool for the post-interventional evaluation of liver lesions following IRE. Focus should be placed on the peak enhancement (pE) and the wash-in area under the curve (WiAUC).

Identification of two distinct hereditary hemorrhagic telangiectasia patient subsets with different hepatic perfusion properties by combination of contrast-enhanced ultrasound (CEUS) with perfusion imaging quantification.

BackgroundHereditary hemorrhagic telangiectasia (HHT) is marked by arteriovenous fusion comprising hepatic vascular malformations (HVaMs) with the chance of bleeding.AimsWe investigated HVaMs in HHT patients by combination of contrast-enhanced ultrasound (CEUS) with perfusion imaging quantification to be able to sub-classify a high risk cohort of asymptomatic HHT patients.MethodsThe imaging characteristics on CEUS in 34 patients (aged 21–84 years; mean 58.9) with HHT were retrospectively evaluated. Real-time contrast harmonic imaging, sulfur hexafluoride-filled microbubbles and motion adjustment were utilized. Cine loops of the liver were digital stored, perfusion was quantified using a software reading DICOM data`s.ResultsHVaMs were diagnosed in 31 out of 34 patients. Significant uppermost peak enhancement (PE), wash-in area under the curve (WiAUC) and wash-in perfusion index (WiPI) were identified in the shunt region (100%), next in the hilar region (PE 32.6%; WiAUC 33.9%; WiPI 34.1%), and the lowest in the hepatic parenchyma (PE 10.2%; WiAUC 12.0%; WiPI 9.5%). The perfusion parameters in the shunt region compared to the other regions were significantly increased in one subgroup of patients. Consistent with this, the intrahepatic portal vein diameter and Buscarini grading was significantly higher, while portal vein peak velocity was significantly lower in this patient subset. By statistical analysis, we could correlate PE and WiPI to these clinical parameters, while WiAUC showed no clinical association.ConclusionsFor the first time we combined CEUS findings with motion adjustment software to quantitative determine perfusion parameters of a cohort of HHT patients. Hereby, we could identify a subset of HHT patients with two markedly increased parameter values in the shunt region compared to the hilus/hepatic parenchyma. This could contribute to sub-classify a high-risk group of HHT patients with therapeutic indication.