Quantitative Contrast-enhanced Ultrasound Research Articles

Evaluation of contrast-enhanced ultrasound for predicting tumor grade in small (≤4 cm) clear cell renal cell carcinoma: Qualitative and quantitative analysis.

The study aimed to evaluate the utility of qualitative and quantitative analysis employing contrast-enhanced ultrasound (CEUS) in predicting the WHO/ISUP grade of small (≤4 cm) clear cell renal cell carcinoma (ccRCCs). Patients with small ccRCCs, confirmed by histological examination, underwent preoperative CEUS and were classified into low- (grade I/II) and high-grade (grade III/IV) groups. Qualitative and quantitative assessments of CEUS were conducted and compared between the two groups. Diagnostic performance was assessed using receiver operating characteristic curves. A total of 72 patients were diagnosed with small ccRCCs, comprising 23 individuals in the high-grade group and 49 in the low-grade group. The low-grade group exhibited a significantly greater percentage of hyper-enhancement compared to the high-grade group (79.6% VS 39.1%, P < 0.05). The low-grade group showed significantly higher relative index values for peak enhancement, wash-in area under the curve, wash-in rate, wash-in perfusion index, and wash-out rate compared to the high-grade group (all P < 0.05). The AUC values for qualitative and quantitative parameters in predicting the WHO/ISUP grade of small ccRCCs ranged from 0.676 to 0.756. Both qualitative and quantitative CEUS analysis could help to distinguish the high- from low-grade small ccRCCs.

Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial

BackgroundThe Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based chemotherapy. In a first cohort of patients with colorectal cancer liver metastases (CRLM), we showed that variations of the tumor-to-liver density (TTLD) ratio and modified size-based criteria determined using computed tomography (CT) data at the first restaging were better prognostic criteria than the RECIST. The aims of this study were to confirm the relevance of these radiological biomarkers as early predictors of the long-term clinical outcome and to assess their correlation with contrast-enhanced ultrasound (CEUS) parameters in a new patient cohort.MethodsIn this post-hoc study of the multicenter STIC-AVASTIN trial, we retrospectively reviewed CT data of patients with CRLM treated with bevacizumab-based regimens. We determined the size, density and TTLD ratio of target liver lesions at baseline and at the first restaging and also performed a morphologic evaluation according to the MD Anderson criteria. We assessed the correlation of these parameters with progression-free survival (PFS) and overall survival (OS) using the log-rank test and a Cox proportional hazard model. We also examined the association between TTLD ratio and quantitative CEUS parameters.ResultsThis analysis concerned 79 of the 137 patients included in the STIC-AVASTIN trial. PFS and OS were significantly longer in patients with tumor size reduction > 15% at first restaging, but were not correlated with TTLD ratio variations. However, PFS was longer in patients with TTLD ratio > 0.6 at baseline and first restaging than in those who did not reach this threshold. In the multivariate analysis, only baseline TTLD ratio > 0.6 was a significant survival predictor. TTLD ratio > 0.6 was associated with improved perfusion parameters.ConclusionsAlthough TTLD ratio variations did not correlate with the long-term clinical outcomes, TTLD absolute values remained a good predictor of survival at baseline and first restaging, and may reflect tumor microvascular features that might influence bevacizumab-based treatment efficiency.Trial registrationNCT00489697, registration number of the STIC-AVASTIN trial.

Qualitative and quantitative assessment of non-clear cell renal cell carcinoma using contrast-enhanced ultrasound

BackgroundNon-clear cell renal cell carcinoma (nccRCC) represents a rare form of renal cell carcinoma (RCC) in the clinic. It is now understood that contrast-enhanced ultrasound (CEUS) exhibits diverse manifestations and can be prone to misdiagnosis. Therefore, summarizing the distinctive features of contrast-enhanced ultrasonography is essential for differentiation from ccRCC.ObjectiveThis study aims to evaluate the diagnostic efficacy of qualitative and quantitative CEUS in diagnosing nccRCC to enhance our understanding of this condition.MethodsWe conducted a retrospective analysis of 21 patients with confirmed nccRCC following surgery and assessed the characteristic conventional ultrasound and CEUS imaging features. The paired Wilcoxon signed-rank sum test was employed to compare differences in CEUS time-intensity curve (TIC) parameters between the lesions and the normal renal cortex.ResultsRoutine ultrasound revealed the following primary characteristics in the 21 nccRCC cases: hypoechoic appearance (10/21, 47.6%), absence of liquefaction (18/21, 66.7%), regular shape (19/21, 90.5%), clear boundaries (21/21, 100%), and absence of calcification (17/21, 81%). Color Doppler flow imaging (CDFI) indicated a low blood flow signal (only 1 case of grade III). Qualitative CEUS analysis demonstrated that nccRCC predominantly exhibited slow progression (76.1%), fast washout (57%), uniformity (61.9%), low enhancement (71.5%), and ring enhancement (61.9%). Quantitative CEUS analysis revealed that parameters such as PE, WiAUC, mTTI, WiR, WiPI, WoAUC, WiWoAUC, and WOR in the lesions were significantly lower than those in the normal renal cortex (Z=-3.980, -3.563, -2.427, -3.389, -3.980, -3.493, -3.528, -2.763, P < 0.001, < 0.001, = 0.015, = 0.001, < 0.001, < 0.001, < 0.001, = 0.006). However, there were no significant differences in RT, TTP, FT, or QOF (all P > 0.05).ConclusionnccRCC exhibits distinctive CEUS characteristics, including slow progression, fast washout, low homogeneity enhancement, and ring enhancement, which can aid in distinguishing nccRCC from ccRCC.

Contrast-enhanced ultrasound (CEUS): applications from the kidneys to the bladder.

Contrast-enhanced ultrasound (CEUS) is an advanced ultrasound (US) technique utilizing ultrasound contrast agents (UCAs) to provide detailed visualization of anatomic and vascular architecture, including the depiction of microcirculation. CEUS has been well-established in echocardiography and imaging of focal hepatic lesions and recent studies have also shown the utility of CEUS in non-hepatic applications like the urinary system. The updated guidelines by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) from 2018 describe the use of CEUS for non-hepatic applications. CEUS' excellent safety profile and spatial resolution make it a superior modality to conventional US and is often comparable and even superior to CECT in some instances. In comparison to other cross-sectional imaging modalities such as CECT or MRI, CEUS offers a safe (by virtue of non-nephrotoxic US contrast agents), accurate, cost-efficient, readily available, and a quick means of evaluation of multiple pathologies of the urinary system. CEUS also has the potential to reduce the overall economic burden on patients requiring long-term follow-up due to its low cost as compared to CT or MRI techniques. This comprehensive review focuses on the applications of CEUS in evaluating the urinary system from the kidneys to the urinary bladder. CEUS can be utilized in the kidney to evaluate complex cystic lesions, indeterminate lesions, pseudotumors (vs solid renal tumors), renal infections, and renal ischemic disorders. Additionally, CEUS has also been utilized in evaluating renal transplants. In the urinary bladder, CEUS is extremely useful in differentiating a bladder hematoma and bladder cancer when conventional US techniques show equivocal results. Quantitative parameters of time-intensity curves (TICs) of CEUS examinations have also been studied to stage and grade bladder cancers. Although promising, further research is needed to definitively stage bladder cancers and classify them as muscle-invasive or non-muscle invasive using quantitative CEUS to guide appropriate intervention. CEUS has been very effective in the classification of cystic renal lesions, however, further research is needed in differentiating benign from malignant renal masses.

Quantifying Diaphragm Blood Flow With Contrast-Enhanced Ultrasound in Humans

Despite the known interplay between blood flow and function, to our knowledge, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound to quantify relative diaphragm blood flow (Q˙DIA) in humans and assessed the technique's efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that: (1) Q˙DIA would linearly increase with pressure generation, and (2) that there would be good test-retest reliability and interanalyzer reproducibility. Can we validate what is, to our knowledge, the first minimally invasive method to measure relative diaphragm blood flow in humans? Quantitative contrast-enhanced ultrasound of the costal diaphragm was performed in healthy participants (10 male participants, 6 female participants; mean age 28 ± 5 years; BMI 22.8 ± 2.0kg/m) during unloaded breathing and three stages of loaded breathing on two separate days. Gastric and esophageal balloon catheters measured transdiaphragmatic pressure. Ultrasonography was performed during a constant-rate IV infusion of lipid-stabilized microbubbles following each stage. Ultrasound images were acquired after a destruction-replenishment sequence and diaphragm specific time-intensity data were used to determine Q˙DIA by two individuals. Transdiaphragmatic pressure for unloaded and each loading stage were 15.2 ± 0.8, 26.1 ± 0.8, 34.6 ± 0.8, and 40.0 ± 0.8 percentage of the maximum, respectively. Q˙DIA increased with each stage of loading (3.1 ± 3.1, 6.9 ± 3.6, 11.0 ± 4.9, and 13.5 ± 5.4 acoustic units/s; P< .0001). The linear relationship between diaphragmatic flow and pressure was reproducible from day to day. Q˙DIA had good to excellent test-retest reliability (0.86 [0.77, 0.92]; P< .0001) and excellent interanalyzer reproducibility (0.93 [0.90, 0.95]; P< .0001) with minimal bias. Relative Q˙DIA measurements had valid physiological underpinnings, were reliable day-to-day, and were reproducible analyzer-to-analyzer. This study indicated that contrast-enhanced ultrasound is a viable, minimally invasive method for assessing costal Q˙DIA in humans and may provide a tool to monitor diaphragm hemodynamics in clinical settings.

A modified CEUS risk stratification model for adnexal masses with solid components: prospective multicenter study and risk adjustment.

To evaluate the additional advantages of integrating contrast-enhanced ultrasound (CEUS) into the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound (US) for the characterization of adnexal lesions with solid components. This prospective multicenter study recruited women suspected of having adnexal lesions with solid components between September 2021 and December 2022. All patients scheduled for surgery underwent preoperative CEUS and US examinations. The lesions were categorized according to the O-RADS US system, and quantitative CEUS indexes were recorded. Pathological results served as the reference standard. Univariable and multivariable analyses were performed to identify risk factors for malignancy in adnexal lesions with solid components. Receiver operating characteristic (ROC) curve analysis was employed to assess diagnostic performance. A total of 180 lesions in 175 women were included in the study. Among these masses, 80 were malignant and 100 were benign. Multivariable analysis revealed that serum CA-125, the presence of acoustic shadowing, and peak intensity (PI) ratio (PImass/PIuterus) of solid components on CEUS were independently associated with adnexal malignancy. The modified CEUS risk stratification model demonstrated superior diagnostic value in assessing adnexal lesions with solid components compared to O-RADS US (AUC: 0.91 vs 0.78, p < 0.001) and exhibited comparable performance to the Assessment of Different NEoplasias in the adnexa (ADNEX) model (AUC 0.91 vs 0.86, p = 0.07). Our findings underscore the potential value of CEUS as an adjunctive tool for enhancing the precision of diagnostic evaluations of O-RADS US. The promising performance of the modified CEUS risk stratification model suggests its potential to mitigate unnecessary surgeries in the characterization of adnexal lesions with solid components. • The additional value of CEUS to O-RADS US in distinguishing between benign and malignant adnexal lesions with solid components requires further evaluation. • The modified CEUS risk stratification model displayed superior diagnostic value and specificity in characterizing adnexal lesions with solid components when compared to O-RADS US. • The inclusion of CEUS demonstrated potential in reducing the need for unnecessary surgeries in the characterization of adnexal lesions with solid components.

Intraoperative contrast-enhanced ultrasound evaluates the hemodynamic change of cerebral revascularization in adult moyamoya disease: Preliminary results

PurposeThis study aimed to determine the feasibility of using intraoperative contrast-enhanced ultrasound (CEUS) to assess subcortical hemodynamic changes in moyamoya disease patients who had undergone combined revascularization. It also aimed to investigate the correlation between quantitative CEUS parameters and post-operative neural functional recovery. MethodsThis study included seventeen patients diagnosed with moyamoya disease, confirmed through cerebral angiography, who underwent combined revascularization. Intraoperative subcortical hemodynamics were assessed using CEUS before and immediately after cerebrovascular bypass. Hemodynamic parameters were calculated by analyzing the time-intensity curve generated from a defined region of interest in each CEUS video. Post-operative neurological symptoms, computed tomography records, and short-term modified Rankin Scale (mRS) scores were also recorded. ResultsDuring the post-operative follow-up, 29.4 % of the patients experienced new neurological symptoms, including epilepsy, dyskinesia, and language impairment. Overall, CEUS quantitative parameters suggested that blood supply improved after surgery. And certain hemodynamic parameters exhibited a stronger correlation with the mRS scores, with correlation coefficients ranging up to 0.73 (p < 0.01). However, no statistically significant differences were observed among the different functional groups. The advanced parameter of wash-out intensity (δ WOI), which signifies the rate of change at the point when blood flow is completely washed out, demonstrated a significant difference between two functional groups (p = 0.02) and exhibited a correlation with mRS scores (correlation coefficients: 0.55, p = 0.02). ConclusionsThis preliminary study suggests that quantitative intraoperative CEUS can measure subcortical hemodynamic changes. It provides a novel non-invasive method that may predict the short-term post-operative neural functional recovery of combined revascularization in moyamoya disease patients.

OR32-04 The Usefulness Of The Contrast-enhanced Ultrasound (CEUS) In Evaluating The Risk Of Malignancy In Thyroid Nodules

Abstract Disclosure: A. Zylka: None. K. Dobruch-Sobczak: None. M. Jedrzejczyk: None. H. Piotrzkowska-Wroblewska: None. P. Goralski: None. J. Galczynski: None. E. Bakula-Zalewska: None. M. Dedecjus: None. Objectives Ultrasonography (US) is a primary method used in the evaluation of the thyroid nodules, but there is no single feature predicting malignancy preoperatively with high accuracy. Contrast-enhanced ultrasound (CEUS) provides information about the vascular perfusion and hemodynamics in the thyroid nodules. Therefore, the aim of this paper was to evaluate the usefulness of CEUS in the differential diagnosis of thyroid nodules. Methods Between the years 2021 and 2022, 182 adult patients (149 women and 33 men, aged 18-85) underwent CEUS of a thyroid nodule classified after fine-needle aspiration biopsy with II-VI Bethesda category. During CEUS examination 1.5 ml of SonoVue contrast has been injected and followed by analysing of qualitative CEUS enhancement patterns. All patients subsequently underwent thyroid operation and histopathologic results were used to confirm or exclude the risk of malignancy. Analysis of the visual CEUS enhancement patterns was performed by two experienced specialists in thyroid ultrasonography. Fifteen CEUS qualitative parameters of nodules were estimated and compared with normal thyroid parenchyma including: ring enhancement; low-, iso- and high enhancement; homo- or heterogenous enhancement; slow, fast or equal wash-in and wash-out and centripetal, centrifugal or diffuse enhancement. The statistical analysis of the obtained results was performed using the logistic regression. First sensitivity, specificity and AUC were calculated only for CEUS qualitative features. Then the model was extended using the results based on US B-mode imaging which involved three suspicious features: irregular margins, microcalcifications and marked hypoechogenicity. Results Histopathologic results included 61 benign thyroid nodules (in 51 women and 10 men) and 121 thyroid carcinomas (in 99 women and 22 men). The analysis has pointed five CEUS parameters statistically significant in differential diagnosis between benign and malignant thyroid nodules: low, homogenous and centrifugal enhancement, ring enhancement and slow-wash-out of the contrast. The model, using the above parameters evaluated the risk of malignancy of thyroid nodules with sensitivity of 85.12% and specificity of 45.90% with 0.75 AUC. Including the B-mode features, the sensitivity, specificity and AUC were 85.95%, 62.30% and 0.86, respectively. Conclusions Preliminary results indicate that CEUS is an useful tool in the evaluation of the risk of malignancy in thyroid nodules. The combination of the qualitative enhancement parameters and US B-mode sonographic features increases the usefulness of the method in differential diagnosis between benign and malignant nodules. However, further multicenter studies should be performed in order to standardize qualitative and quantitative CEUS features. Presentation: Sunday, June 18, 2023

Quantitative evaluation of colorectal tumour vasculature using contrast-enhanced ultrasound: Correlation with angiogenesis and prognostic significance.

Ultrasound is a vital tool for the diagnosis and management of colorectal cancer (CRC). Contrast-enhanced ultrasound (CEUS) is a non-invasive, safe, and cost-effective method for evaluating tumour blood vessels, that play a crucial role in tumour growth and progression. To explore CEUS's role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis. This study prospectively enrolled 100 patients with CRC confirmed by histopathology. All patients received preoperative CEUS examinations. Quantitative parameters, such as peak intensity (PI), time to peak (TTP), and area under the curve (AUC), were derived from time-intensity curve (TIC) analysis. Tumour tissue samples were obtained during surgery and examined immunohistochemically to assess the expression of angiogenesis markers, including vascular endothelial growth factor (VEGF) and microvessel density (MVD). The correlation between CEUS parameters, angiogenesis markers, and clinicopathological features was evaluated using appropriate statistical tests. Quantitative CEUS parameters (PI, TTP, and AUC) showed significant correlations with VEGF expression (P < 0.001) and MVD (P < 0.001), indicating a strong link between tumour blood vessels and angiogenesis. Increased PI, reduced TTP, and expanded AUC values were significantly related to higher tumour stage (P < 0.001), lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). Furthermore, these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis (P < 0.001). CEUS has a high potential in guiding treatment planning and predicting patient outcomes. However, more comprehensive, multicentre studies are required to validate the clinical utility of CEUS in CRC management.

A novel quantitative approach to evaluate femoral head perfusion by contrast-enhanced ultrasound: A pilot study in infants with developmental dysplasia of the hip.

Avascular necrosis (AVN) is a major morbidity that can occur after surgical reduction of a hip with developmental dysplasia. Early detection of changes in femoral head perfusion during surgery may help detect a hip at risk for AVN and guide intraoperative management. Contrast-enhanced ultrasound (CEUS) can be employed for visualization of femoral head perfusion. In this study we evaluate a quantitative CEUS technique to assess femoral head perfusion pre- and post-surgical reduction. CEUS images were obtained following a bolus injection of an ultrasound contrast agent, prior to and again following surgical reduction and casting. An image processing technique called delta projection was used to quantify hip perfusion, measuring peak enhancement (PE) and perfusion index (PI). We analyzed CEUS images of the hips of eight patients, including seven females, whose ages ranged from 4 months to 1 year. In five hips, perfusion increased following surgery, with a mean pre-surgery PE of 6.7 ±2.5(± SE) and PI of 10.5 ±6.3; and a post-reduction PE of 13.1±6.1 (p=0.07) and PI of 14.2 ±6.2 (p=0.008). The change in contrast visualization was observed to be greater within the central aspect of the cartilaginous femoral epiphysis. The proposed technique can quantify pre- and post-surgical perfusion changes on CEUS images in patients with developmental dysplasia. This quantitative technique may provide a more objective and accurate assessment of changes in femoral head perfusion that may have the potential to be indicative of the risk of developing AVN.

Quantitative analysis using intraoperative contrast-enhanced ultrasound in adult-type diffuse gliomas with isocitrate dehydrogenase mutations: association between hemodynamics and molecular features.

The relationship between contrast-enhanced ultrasound (CEUS) hemodynamics and the molecular biomarkers of adult-type diffuse gliomas, particularly isocitrate dehydrogenase (IDH), remains unclear. This study was conducted to provide a comprehensive description of the vascularization of adult-type diffuse gliomas using quantitative indicators. Additionally, it was designed to identify any variables with the potential to intraoperatively predict IDH mutation status. This prospective study enrolled patients with adult-type diffuse gliomas between November 2021 and September 2022. Intraoperative CEUS was performed, and CEUS videos were recorded for 90-second periods. Hemodynamic parameters, including the peak enhancement (PE) difference, were calculated based on the time-intensity curve of the region of interest. A differential analysis was performed on the CEUS parameters with respect to molecular biomarkers and grades. Receiver operating characteristic curves for various parameters were analyzed to evaluate the ability of those parameters to predict IDH mutation status. Sixty patients with adult-type diffuse gliomas were evaluated. All hemodynamic parameters, apart from rising time, demonstrated significant differences between IDH-mutant and IDH-wildtype adult-type diffuse gliomas. The PE difference emerged as the optimal indicator for differentiating between IDH-wildtype and IDH-mutant gliomas, with an area under the curve of 0.958 (95% confidence interval, 0.406 to 0.785). Additionally, the hemodynamic parameters revealed significant differences across both grades and types of adult-type diffuse gliomas. Hemodynamic parameters can be used intraoperatively to effectively distinguish between IDHwildtype and IDH-mutant adult-type diffuse gliomas. Additionally, quantitative CEUS equips neurosurgeons with dynamic perfusion information for various types and grades of adult-type diffuse gliomas.

Contrast-enhanced ultrasound features of adrenal lesions in dogs.

The contrast-enhanced ultrasound (CEUS) features of adrenal lesions are poorly reported in veterinary literature. Qualitative and quantitative B-mode ultrasound and CEUS features of 186 benign (adenoma) and malignant (adenocarcinoma and pheochromocytoma) adrenal lesions were evaluated. Adenocarcinomas (n=72) and pheochromocytomas (n=32) had mixed echogenicity with B-mode, and a non-homogeneous aspect with a diffused or peripheral enhancement pattern, hypoperfused areas, intralesional microcirculation and non-homogeneous wash-out with CEUS. Adenomas (n=82) had mixed echogenicity, isoechogenicity or hypoechogenicity with B-mode, and a homogeneous or non-homogeneous aspect with a diffused enhancement pattern, hypoperfused areas, intralesional microcirculation and homogeneous wash-out with CEUS. With CEUS, a non-homogeneous aspect and the presence of hypoperfused areas and intralesional microcirculation can be used to distinguishbetween malignant (adenocarcinoma and pheochromocytoma) and benign (adenoma) adrenal lesions. Lesions were characterised only by means of cytology. CEUS examination is a valuable tool for distinction between benign and malignant adrenal lesions and can potentially differentiate pheochromocytomas from adenocarcinomas and adenomas. However, cytology and histology are necessary to obtain the final diagnosis.

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.

Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. SWE allowed differentiation between benign PGT (Warthin's Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs.

Contrast-Enhanced Ultrasound in the Differentiation between the Most Common Benign Parotid Gland Tumors: A Systematic Review and Meta-Analysis.

Recently, contrast-enhanced ultrasound (CEUS) has become a promising tool in distinguishing benign from malignant parotid gland tumors. However, its usefulness in differentiating various benign parotid tumors has not been determined so far. This study aimed to systematically review the literature to determine the utility of CEUS in the preoperative differentiation between pleomorphic adenomas (PAs) and Warthin's tumors (WTs) of the parotid gland. PubMed, Embase, and Cochrane were searched for English-language articles published until 21 July 2022. Fifteen studies were included. On CEUS examination, a significantly greater percentage of PAs displayed heterogeneous enhancement texture compared to WTs. Contrarily, the enhanced lesion size, the enhancement margin, and the presence of the enhancement rim did not differ significantly between the entities. Significantly longer normalized mean transit time (nMTT) and time to peak (TTP) were observed in PAs. Contrarily, the mean values of area under the curve (AUC) and time from peak to one half (TPH) were significantly higher for WTs. Due to the considerable overlap among the qualitative CEUS characteristics of PAs and WTs, the reproducible, investigator-independent quantitative CEUS measurements have a greater potential to distinguish PAs from WTs, which might influence the selection of an appropriate management strategy.

Ovarian contrast-enhanced ultrasonography and Doppler fluxometry in bitches during the postovulatory estrus and corpora lutea formation

The aim of the present study was to evaluate the vascularization features of canine ovaries during the follicular phase and the formation of the corpora lutea by using Doppler ultrasonography and Contrast-Enhanced Ultrasound (CEUS). Eight healthy bitches were enrolled in the study and were evaluated at five different timepoints (T1 – T5) of the estrous cycle established by vaginal cytology and serum progesterone concentration. Ultrasonographic examinations were performed by a single operator using the ACUSON S2000/SIEMENS machine equipped with a linear multifrequency transducer (9.0 MHz). Color-coded Doppler evaluation of the ovarian parenchyma was performed to investigate the aspects of the signal detection throughout the different timepoints. Pulsed-wave Doppler of the intraovarian arteries was performed to evaluate spectral waveform and doppler velocimetric parameters of Systolic Peak Velocity (SPV cm/s), End Diastolic Velocity (EDV cm/s), Resistivity Index (RI) and Pulsatility Index (PI). CEUS evaluation of the ovaries was performed using a vascular contrast agent (SonoVue®, Bracco, Sao Paulo, Brazil) and the CADENCE™ Contrast Pulse Sequencing (CPS, Siemens) software, in order to perform both qualitative and quantitative analysis. Perfusion parameters of pixel number, peak intensity (PPI in %), time to peak intensity (TTP in s), mean transit time (MTT in s) and area under the curve (AUC in %). Colour-coded Doppler evaluation demonstrated an increase in signal detection as cycle progressed, with blood flow initially detected with few coloured pixels and mainly at the ventral surface of the ovaries. Further on, the number of coloured pixels increased and spreading to the central region, resulting in a circular-like pattern around the corpora hemorrhagica. The spectral waveform was consistent at all timepoints. SPV (cm/s) and EDV (cm/s) presented a numeric trend and a slight statistical difference at all timepoints, whereas no difference was found for RI and PI. CEUS evaluation demonstrated an increase in pixel intensity across all the timepoints. Quantitative CEUS analysis revealed a statistical difference in PPI (%), MTT (s) and AUC (%) at T5. CEUS evaluation of the ovaries was feasible and demonstrated a marked increase in perfusion parameters in the late postovulatory period, demonstrating its applicability in the assessment of canine corpora lutea development.

Contrast-enhanced ultrasound features of focal pancreatic lesions in cats.

A large overlap in the ultrasound (US) features of focal pancreatic lesions (FPLs) in cats is reported. Furthermore, only a small number of studies describing the contrast-enhanced ultrasound (CEUS) features of FPLs in cats have been conducted today. The aim of this study is to describe the B-mode US and CEUS features of FPLs in cats. Ninety-eight cats cytologically diagnosed with FPL were included. The lesions were classified as adenocarcinoma (n = 40), lymphoma (n = 11), nodular hyperplasia (n = 17), other benign lesion (OBL) (n = 20), cyst (n = 4) or other malignant lesion (OML) (n = 6). Several qualitative and quantitative B-mode and CEUS features were described in each case. OMLs and cysts were not included in the statistical analysis. A decision tree to classify the lesions based on their B-mode and CEUS features was developed. The overall accuracy of the cross-validation of the decision tree was 0.74 (95% CI: 0.63–0.83). The developed decision tree had a very high sensitivity and specificity for nodular hyperplasia (1 and 0.94, respectively) as well as good sensitivity and specificity for both adenocarcinomas (0.85 and 0.77, respectively) and OBLs also (0.70 and 0.93, respectively). The algorithm was unable to detect any specific feature for classifying lymphomas, and almost all the lymphomas were classified as adenocarcinomas. The combination between CEUS and B-mode US is very accurate in the classification of some FPLs, especially nodular hyperplasia and adenocarcinomas. Cytopathology and or histopathology is still a fundamental step FPL diagnostic workflow.

Contrast-enhanced ultrasound for the evaluation of symptomatic and asymptomatic carotid plaques: A systematic review and meta-analysis.

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality for the assessment of plaque vulnerability. We aimed to systematically review and meta-analyze the ability of CEUS parameters to differentiate between symptomatic and asymptomatic carotid plaques and to assess its reproducibility. PubMed, EMBASE, and Cochrane Library databaseswere searched for studies that potentiallyevaluated carotid plaques using CEUS. From the initial 2870 searches, 11 relevant publications comprising a total of 821 carotid plaques were reviewed. Data on CEUS parameters including quantitative and semi-quantitative parameters were extracted and analyzed. The overall analysis showed significantly higher CEUS parameters in symptomatic carotid plaques compared to asymptomatic carotid plaques (standardised mean difference (SMD) .95, 95% confidence interval (CI) .56-1.27, p<.01). Intra and inter-observer reproducibility of quantitative CEUS parameters were excellent (intra-observer, r=.95, 95% CI .87-1; inter-observer, r=.93, 95% CI .80-.1). Semi-quantitative CEUS parameters showed good intra-observer reliability and moderate inter-observer reliability (intra-observer, r=.77, 95% CI .64-.89; inter-observer, r=.75, 95% CI .61-.89). Heterogeneity among studies compared CEUS parameters in symptomatic and asymptomatic plaques and studies assessed inter-observer reproducibility, and significant biases in studies assessing CEUS reproducibility were present. CEUS is a useful vascular imaging method to differentiate between symptomatic and asymptomatic carotid plaques with moderate to excellent reproducibility. Quantitative CEUS analysis appeared to be more sensitive and reliable in assessing carotid plaques than semi-quantitative parameters. Further longitudinal prospective trials evaluating carotid plaque in asymptomatic population using CEUS to determine plaque characteristics that can become symptomatic are required.

Diagnostic Value of Quantitative Contrast-Enhanced Ultrasound in Comparison to Endoscopy in Children With Crohn's Disease.

Quantitative contrast-enhanced US (CEUS) provides objective evaluation of bowel wall perfusion and has been reported as a useful method for evaluating Crohn's disease (CD) activity in children. We tested its' diagnostic accuracy in comparison to endoscopy and evaluated its' usefulness in comparison to Pediatric Crohn's Disease Activity Index (PCDAI) and fecal Calprotectin (FC). Children with CD and thickened bowel wall on abdominal US were prospectively enrolled. Disease activity was evaluated with quantitative CEUS, PCDAI and FC and compared to a simple endoscopic score for Crohn's disease (SES-CD). Spearman's correlation and Cohen's kappa statistic between the SES-CD and other disease activity measures were performed and diagnostic accuracies calculated. 36 children 3.5-18 years old (mean age 14 years) were included. The quantitative CEUS had 78.57% sensitivity (95%CI 0.59-0.92), 100% specificity (95%CI 0.63-1.0) and 83.33% diagnostic accuracy (95% CI 0.67-0.94). The concordance remission agreement with endoscopy was substantial for quantitative CEUS and PCDAI (quantitative CEUS: κ=0.62; 95% CI 0.363-0.877; PCDAI: κ=0.615; 95% CI 0.311-0.920), but only fair for FC (κ=0.389; 95% CI 0.006-0.783). Correlation between all measures and endoscopy was moderate and statistically significant (quantitative CEUS: rs =0.535, PCDAI: rs =0.543, FC: rs =0.497). Quantitative CEUS has a potential of becoming a complementary method for evaluation of CD activity in children due to its' high specificity in comparison to endoscopy. Lower sensitivity makes it deficient as a single measure and further management should be guided by PCDAI and FC results as well.

Contrast enhanced ultrasound for characterization of suspected soft tissue vascular anomalies

BackgroundEvaluation of perfusion characteristics is the key to characterize vascular anomalies. Contrast-enhanced ultrasound (CEUS) is a radiation-free modality to evaluate this in real-time and can be coupled along with Doppler-ultrasound (US). ObjectiveTo evaluate the utility of CEUS in characterization of suspected soft-tissue vascular anomalies and compare its diagnostic accuracy with Doppler-US. Materials and methodsThis was an ethically-approved cross-sectional study, done from November 2017- November 2019, involving 93 patients (55 M/38F; mean age 23.6 ± 11.9 years) in development cohort and 128 (66 M/62F; mean age 21.4 ± 11.1 years) in validation cohort. Patients suspected to have soft-tissue vascular anomalies on clinical evaluation and US were included. Clinical features, US, Doppler, subjective and quantitative CEUS features (from time-intensity curves) were evaluated. Composite gold standard employing MRI, phlebogram, DSA or biopsy was used to make the final diagnosis. The CEUS features found to be significantly different in the development cohort were prospectively validated in the validation cohort. P-value < 0.05 was considered significant, ROC curves were drawn and threshold values obtained for the various quantitative parameters. A prospective diagnosis was suggested in the validation group along with a degree of diagnostic confidence and accuracy was calculated. ResultsThe spectrum of lesions included 77 venous malformations, 46 fibro-adipose vascular anomalies, 32 vascular tumors, 20 arteriovenous malformations and 20 lymphatic malformations. All lesions were found to have distinctive temporal and morphological subjective enhancement patterns. Quantitative parameters like rise-time, mean-transit-time, time-to-peak, peak-enhancement showed significant differences between the various groups (P value < 0.05). Addition of CEUS not only increased the diagnostic accuracy of Doppler-US from 76.5% (91/119) to 88.2% (105/119), but also the degree of diagnostic confidence in characterization of soft-tissue vascular anomalies. None of the patients showed any contrast-related adverse effects. ConclusionContrast-enhanced ultrasound is useful to characterize different types of soft-tissue vascular anomalies and increases the diagnostic accuracy and confidence over Doppler-ultrasound.