Cadence Contrast Pulse Sequencing Research Articles

Modulating Nonlinear Acoustic Response of Phospholipid-Coated Microbubbles with pH for Ultrasound Imaging.

Activatable microbubble contrast agents for contrast-enhanced ultrasound have a potential role for measuring physiologic and pathologic states in deep tissues, including tumor acidosis. In this study, we describe a novel observation of increased harmonic oscillation of phosphatidylcholine microbubbles (PC-MBs) in response to lower ambient pH using a clinical ultrasound scanner. MB echogenicity and nonlinear echoes were monitored at neutral and acidic pH using B-mode and Cadence contrast pulse sequencing (CPS), a harmonic imaging technique at 7.0 and 1.5 MHz. A 3-fold increase in harmonic signal intensity was observed when the pH of PC-MB suspensions was decreased from 7.4 to 5.5 to mimic normal and pathophysiological levels that can be encountered in vivo. This pH-mediated activation is tunable based on the chemical structure and length of phospholipids composing the MB shell. It is also reliant on the presence of phosphate groups, as the use of lipids without phosphate instead of phospholipids completely abrogated this phenomenon. The increased harmonic signal likely is the result of increased MB oscillation caused by a decrease of the interfacial tension induced at a lower pH, altering the lipid conformation. While relative signal changes are interpreted clinically as mostly related to blood flow, pH effects could be significant contributors, particularly when imaging tumors. While our observation can be used clinically, it requires further research to isolate the effect of pH from other variables. These findings could pave the way toward for the development of new smart ultrasound contrast agents that expand the clinical utility of contrast-enhanced ultrasound.

Microbubbles Cloaked with Hydrogels as Activatable Ultrasound Contrast Agents.

Microbubbles (MBs) are optimal ultrasound contrast agents because their unique acoustic response allows for exquisite sensitivity in vivo. This unique response is derived from MBs' elasticity that allows them to oscillate differently from surrounding tissues. While the main use of MBs in the clinic is for cardiac and perfusion imaging, imparting MBs with bioresponsive properties would expand their use to detect pathophysiologic changes. This can be achieved by damping MBs' oscillations to silence their signal and rescuing it when they encounter the biomarker of interest to improve detection and specificity of diseases such as deep vein thrombosis (DVT). Here, we demonstrate that conjugating perfluorobutane-filled MBs with hyaluronic acid (HA) and cross-linking HA with biodegradable linkers eliminates harmonic signal because of increased MB stiffness and decreased oscillation. In this proof-of-concept study, we used a reversible pH-sensitive cross-linker to establish and validate this targeted and activatable pH-sensitive MB (pH-MB) platform. Conjugation of HA to MBs and targeting of pH-MBs to CD44-positive cells were validated. Harmonic signal loss due to stiffening of pH-MBs' shell was confirmed using a clinical ultrasound scanner equipped with Cadence contrast pulse sequencing. pH-MBs imaged before and after acidification increased harmonic signal fivefold. Because the cleavage of the cross-linker we used is reversible, harmonic signal was silenced again when the acidic suspension was neutralized, confirming that harmonic signal is dependent on the cross-linked HA. The rate of rise and the magnitude of harmonic signal increase could be manipulated by varying the phospholipid composition and the number of HA cross-linkers, indicating that the platform can be tuned to the desired response needed. In this study, we established the feasibility of using targeted and activatable MBs and plan to apply this platform to aid in the diagnosis and management of patients with DVT and potentially other conditions.

Abstract 2196: Noninvasive description of natural tumor evolution

Abstract Background: Our goal is to investigate how quantitative parameters of Contrast Enhanced Ultrasound (CEUS) and Shear Wave Elastography (SWE) change during tumor growth and link them with morphological and histological indexes. Methods: An ectopic model of murine colorectal carcinoma (CT26) was implanted in 46 mice (BALB/c ) at Day 0. On 5 subsequent days, data were acquired from subsets of these mice (D7, n=8 ; D10, n=9 ; D14, n=10 ; D16, n=9, D17, n=10) by scanning each tumor along its major, longitudinal axis in vivo to obtain conventional B-mode, SWE (SSI, Aixplorer, SL15-4 probe) and dynamic CEUS (Sequoia 512, 7-14 MHz probe, cadence contrast pulse sequencing) data. The ellipsoidal volume of each tumor was estimated from measurements of the width and thickness of the largest plane along the longitudinal and transversal plane using B-mode display on the Aixplorer device. Quantitative maps of tissue elasticity distribution in the tumor were obtained from SWE data. Average values and standard deviation of SWE data were calculated within regions selected to outline the tumor cross section on B-mode images. CEUS was performed after a syringe-pump-controlled bolus injection in the caudal vein of 40 μL of SonoVue (Bracco Suisse, Geneva, Switzerland) in a weight-adjusted volume of 0.5 mL/kg. A lognormal model was fit to the time intensity curve inside the tumor to estimate parameters related to microvascular volume and flow. All tumors imaged on a given day were excised and marked to conserve orientation and approximate position relative to the US imaging plane. Tumors were frozen with liquid nitrogen in an Optimal Cutting Temperature compound cube and stored at -80°C. Results: Significance of correlations were evaluated using the non-parametric Spearman correlation coefficient (RS). Average SWE parameters were not significantly correlated with the CEUS parameters (p > 0.03). Standard deviation of SWE in the tumor was well correlated with tumor volume (RS = 0.65 [p<6x10^-7]). For CEUS only the Time To Peak and Latency Time correlated with tumor volume (RS = 0.62 [p<4x10^-6] and RS = -0.72 [p<2x10^-8], respectively). Correlation with histological assessment of tumor microstructure is still in the process of analysis. Conclusions: These preliminary results probe the relationship between tumor volume, functional-flow and elastic properties in tumors. Both CEUS and SWE parameters were found that correlate with tumor growth and thus, appear to be sensitive to changes occurring during tumor development. Histological analysis of tumor microstructure is underway to more fully probe this point. Lack of correlation between SWE and CEUS parameters suggests that they provide complementary information. Better understanding of the sensitivity of these non invasive parameters to tumor growth changes will contribute to their eventual integration in procedures of tumor response criteria in clinical practice. Citation Format: Jerome Griffon, Delphine Le Guillou-Buffello, Oumeima Laifa, Lori Bridal, Michele Lamuraglia. Noninvasive description of natural tumor evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2196.

Real-Time Placental Perfusion on Contrast-Enhanced Ultrasound and Parametric Imaging Analysis in Rats at Different Gestation Time and Different Portions of Placenta

ObjectivesTo quantitatively analyze placental perfusion in a rat model at different gestation time and different portions of placenta by real-time contrast-enhanced ultrasound (CEUS) and parametric imaging analysis.Materials and MethodsSixty pregnant rats at different gestation time (15 dys,17 days and 20 days) were injected intravenously with microbubbles (5×105 microbubbles /ml, 1.0 ml/kg), and cadence contrast pulse sequencing (transmission frequency of 7 MHz, mechanical index 0.18) was performed. Dynamic enhancement changes in placenta at different gestation time and different portions of placenta were measured and enhancement parameters analyzed with software. Correlation between enhancement parameters and average area densities of placenta vascular compartment was compared.ResultsThe pattern and real-time sequence of enhancement in uterus and placenta were clearly depicted by CEUS. The time-to-peak enhancement was earlier in central portion than that in peripheral portion (12.30±6.33s vs 36.26±10.65 s, p = 0.005), and peak intensity of enhancement is much higher in central portion than that in peripheral portion (30.20±2.85 dB vs 20.95±6.25 dB, p = 0.000). The peak intensity of enhancement at day 15 (27.70±4.47 dB) was lower than that at day 17 (30.20±2.85 dB, p = 0.042) and at day 20 (31.85±4.41 dB, p = 0.015) of gestation. Significant correlation between average area densities of vascular compartment and the peak intensity of enhancement was identified in placenta at different gestation time (p<0.05). The average area densities of vascular compartment was higher in central portion than that in peripheral portion and has significant correlation with peak intensity of enhancement of the two potions (p<0.01).ConclusionCEUS is feasible to depict real-time sequence and quantitative parameters of perfusion in different portion of placenta at different gestational time in a rat model.

Value of contrast-enhanced ultrasonography in assessing peripheral zone prostate cancer aggressiveness

Objective To determine whether cadence contrast pulse sequencing (CPS) harmonic ultrasonography can be used to predict aggressiveness of peripheral zone prostate cancer.Methods CPS harmonic ultrasonography was performed in 62 biopsy-proved prostate cancer patients.Time intensity curves were reconstructed for biopsy-proved or radical prostatectomy histopathology proved prostate cancer lesions.The characteristics of the curves were described using hemodynamic parameters including arrival time (AT),time-to peak (TTP) and peak intensity (PI).The differences of hemodynamic parameters between different Gleason score and pathologic stage were analyzed.Results Prostate biopsy revealed 156 peripheral zone prostate cancer lesions among 62 patients,including 40 low grade lesions and 116 high grade lesions.In comparison with low-grade lesions,the contrast agents arrived and distributed earlier in highgrade lesions (P =0.005,0.023).In addition to lower AT and TTP,high-grade tumors had higher PI than low-grade tumors (P =0.008).Among 21 patients underwent radical prostatectomy,histopathology documented 14 low grade tumors and 17 high grade tumors,significant differences of hemodynamic parameters were found between these two groups (P ＜0.05).Furthermore,prostate cancer lesions with extra capsular extension also had high PI than those confined in the gland (P =0.000).Conclusions Contrast-enhanced ultrasound and hemodynamic parameters might be helpful in predicting aggressiveness of prostate cancer. Key words: Endosongraphy; Microbubbles ; Prostatic neoplasms

Value of enhanced transrectal ultrasound targeted biopsy for prostate cancer diagnosis: a retrospective data analysis

To evaluate enhanced transrectal ultrasound (E-TRUS) techniques including real-time sonoelastography (RTE) and contrast-enhanced transrectal ultrasound (CE-TRUS) for prostate cancer (PCa) detection in men with elevated prostate-specific antigen (PSA) serum levels. A total of 133 men with elevated PSA serum levels (≥1.25ng/mL) showed PCa suspicious lesions on E-TRUS. RTE was done to assess tissue elasticity, and hard areas of the peripheral zone were considered suspicious for malignancy. CE-TRUS was done with cadence contrast pulse sequencing (CPS) technique to assess tumor neoangiogenesis, which were defined as areas with increased and rapid contrast enhancement in the peripheral zone and were considered suspicious for malignancy. All patients underwent an E-TRUS-targeted biopsy of the prostate into the suspected lesions. PCa detection rates for E-TRUS were analyzed. PCa detection rate of E-TRUS-targeted biopsy was 59.4% (79/133) using a median of 5 cores per patient and a median of 3 cores per lesion. RTE showed a per patient detection rate of 56.5% (70/124) and CE-TRUS of 74.2% (69/93). The subgroup analysis demonstrated the highest detection rates in prostate volumes<40mL (72.2%) and in men older than 70years (87%). The combined use of CE-TRUS and RTE is feasible and allows for targeted biopsy and may improve PCa detection.

UP-01.177 Renal Mass Qualitative Enhancement Using Cadence Contrast Pulse Sequencing Technology

Renal tumors development depends on local angiogenesis. Contrast enhanced ultrasound exam is developing as an important instrument when it comes to small tumors diagnosis and their vascularization assessment and allows for a reliable, noninvasive evaluation, providing real-time information on lesion vascularity. The purpose of this study was to evaluate the diagnostic efficacy of cadence contrast pulse sequencing technology (CPS) in differentiating solid renal parenchymal lesions (SRPLs) with a maximum diameter of 5cm.

MP-03.21 Prostate Cancer Detection Using Cadence Contrast Pulse Sequencing Technology for Targeted Biopsies

MP-03.21 Prostate Cancer Detection Using Cadence Contrast Pulse Sequencing Technology for Targeted Biopsies

An automatic respiratory gating method for the improvement of microcirculation evaluation: application to contrast-enhanced ultrasound studies of focal liver lesions

Contrast-enhanced ultrasound (CEUS), with the recent development of both contrast-specific imaging modalities and microbubble-based contrast agents, allows noninvasive quantification of microcirculation in vivo. Nevertheless, functional parameters obtained by modeling contrast uptake kinetics could be impaired by respiratory motion. Accordingly, we developed an automatic respiratory gating method and tested it on 35 CEUS hepatic datasets with focal lesions. Each dataset included fundamental mode and cadence contrast pulse sequencing (CPS) mode sequences acquired simultaneously. The developed method consisted in (1) the estimation of the respiratory kinetics as a linear combination of the first components provided by a principal components analysis constrained by a prior knowledge on the respiratory rate in the frequency domain, (2) the automated generation of two respiratory-gated subsequences from the CPS mode sequence by detecting end-of-inspiration and end-of-expiration phases from the respiratory kinetics. The fundamental mode enabled a more reliable estimation of the respiratory kinetics than the CPS mode. The k-means algorithm was applied on both the original CPS mode sequences and the respiratory-gated subsequences resulting in clustering maps and associated mean kinetics. Our respiratory gating process allowed better superimposition of manually drawn lesion contours on k-means clustering maps as well as substantial improvement of the quality of contrast uptake kinetics. While the quality of maps and kinetics was satisfactory in only 11/35 datasets before gating, it was satisfactory in 34/35 datasets after gating. Moreover, noise amplitude estimated within the delineated lesions was reduced from 62 ± 21 to 40 ± 10 (p < 0.01) after gating. These findings were supported by the low residual horizontal (0.44 ± 0.29 mm) and vertical (0.15 ± 0.16 mm) shifts found during manual motion correction of each respiratory-gated subsequence. The developed technique could be used as a basis for accurate quantification of perfusion parameters for the evaluation and follow-up of patients under antiangiogenic therapies.

Contrast-Enhanced Diagnostic Ultrasound Causes Renal Tissue Damage in a Porcine Model

Glomerular capillary hemorrhage (GCH) has been reported and confirmed as a consequence of contrast-enhanced diagnostic ultrasound (CEDUS) imaging of rat kidney. This study assessed renal tissue injury in the larger porcine model. The right kidneys of anesthetized pigs were imaged in 8 groups of 4 pigs. A Vingmed System Five ultrasound machine (General Electric Co, Cincinnati, OH) was used at 1.5 MHz in the B-mode to intermittently scan the kidney at 4-second intervals. An Acuson Sequoia 512 machine (Siemens Medical Solutions, Mountain View, CA) was used in the 1.5-MHz Cadence contrast pulse sequencing mode with intermittent agent clearance bursts at 4-second intervals. Kidneys were scanned transabdominally or after laparotomy through a saline standoff. The second machine's probe was placed in contact with the kidney for 1 group. A perflutren lipid microsphere contrast agent (Definity; Lantheus Medical Imaging, Inc, North Billerica, MA) was infused at 4 μL/kg/min (diluted 33:1 in saline) for 4 minutes during scanning. Blood-filled urinary tubules were evident on the kidney surface for all groups except the group with the probe in contact with the kidney. Glomerular capillary hemorrhage was found by histologic processing in 31.7% ± 9.8% (mean ± SD) of glomeruli in the center of the scan plane for 1.7-MPa transabdominal scanning and 1.5% ± 2.9% of glomeruli in sham samples (P < .05). In addition, hematuria was detected after scanning, and tubular obstruction occurred in some nephrons. Renal tissue damage was induced by CEDUS in the porcine model. This result, together with previous studies in rats, support a hypothesis that GCH would occur in humans from similar CEDUS exposure.

Intrahepatic Transit Time Predicts Liver Fibrosis in Patients with Chronic Hepatitis B: Quantitative Assessment with Contrast-Enhanced Ultrasonography

We investigated the use of contrast-enhanced ultrasonography (CEUS) with quantitative measurements to assess the stages of liver fibrosis in patients with chronic hepatitis B. One-hundred twenty-two patients with chronic hepatitis B were divided into three groups according to the Scheuer scoring system pathologically and according to clinical evidence: mild fibrosis (S0 and S1, n = 36); moderate fibrosis (S2 and S3, n = 24); and cirrhosis (S4 and clinically typical cirrhosis, n = 62). CEUS of hepatic vessels and parenchyma was performed using the Cadence contrast pulse sequencing technique, with an intravenous bolus injection of a contrast agent (SonoVue). Real-time CEUS imaging of the liver was recorded and analyzed offline. Contrast arrival time, baseline, and peak intensity in the hepatic artery, portal vein, right hepatic vein, and liver parenchyma were used to calculate intrahepatic transit times, hepatic artery to hepatic vein transit time (HA-HVTT) and portal vein to hepatic vein transit time (PV-HVTT), as well as increased signal intensity (ISI). The correlations between these quantitative parameters and the stages of fibrosis were analyzed using Spearman rank correlation coefficients. HA-HVTT and PV-HVTT were shortened gradually with the progression of liver fibrosis. PV-HVTT was statistically significant differences existed between the two paired groups (mild vs. moderate vs. cirrhosis groups, p < 0.001), whereas HA-HVTT was changed significantly between mild and moderate or cirrhosis groups ( p < 0.001). HA-HVTT and PV-HVTT changes were significantly correlated with liver fibrosis severity (r = −0.5930, p < 0.001; r = −0.8215, p < 0.001). Area under receiver operating characteristic curves for HA-HVTT and PV-HVTT were 0.891 ± 0.034 and 0.955 ± 0.020 at fibrosis scores ≥S2, and 0.785 ± 0.040 and 0.946 ± 0.018 at fibrosis score ≥S4, respectively. ISI values in the portal vein and liver parenchyma decreased with the severity of fibrosis. This study demonstrated that hepatic CEUS with quantitative measurements of intrahepatic transit time reflected the severity of liver fibrosis. The real-time CEUS imaging with use of software-based quantitative analysis could provide reliable information of hepatic hemodynamic changes to noninvasively assess the severity of liver fibrosis in patients with chronic hepatitis B. (E-mail: ding.hong@zs-hospital.sh.cn)

Contrast‐enhanced ultrasonography using cadence‐contrast pulse sequencing technology for targeted biopsy of the prostate

To evaluate contrast-enhanced ultrasonography (US) using cadence-contrast pulse sequencing (CPS) technology, compared with systematic biopsy for detecting prostate cancer, as grey-scale US has low sensitivity and specificity for detecting prostate cancer. In all, 44 men with suspicious prostate-specific antigen (PSA) levels and CPS findings were assessed; all had CPS-targeted and systematic biopsy. Transrectal CPS images were taken with a low mechanical index (0.14). A microbubble contrast agent (SonoVue, Bracco International BV, Amsterdam, the Netherlands) was administered as a bolus, with a maximum dose of 4.8 mL. CPS was used to assess prostatic vascularity. Areas with a rapid and increased contrast enhancement within the peripheral zone were defined as suspicious for prostate cancer. Up to five CPS targeted biopsies were taken and subsequently a 10-core systematic biopsy was taken. Cancer detection rates for the two techniques were compared. Overall, cancer was detected in 35 of 44 patients (80%), with a mean PSA level of 3.8 ng/mL. Lesions suspicious on CPS showed cancer in 35 of 44 patients (80%) and systematic biopsy detected cancer in 15 of 44 patients (34%). CPS-targeted cores were positive in 105 of 220 cores (47.7%) and in 41 of 440 systematic biopsy cores (9.3%) (P < 0.001). Lesions suspicious on CPS were false-positive in nine of 44 patients (20%). The mean Gleason score for systematic biopsy was 6.7 and for CPS-targeted biopsy 6.8 (P > 0.05). The sensitivity of CPS for detecting cancer was 100% (confidence interval, 95%). However, limitations in the series included that only CPS-positive cases were investigated, and CPS-targeted biopsy should be evaluated in a more extended biopsy scheme. Contrast-enhanced US using CPS enables excellent visualization of the microvasculature associated with prostate cancer, and can improve the detection of prostate cancer compared with systematic biopsy.

Value of Contrast-Enhanced Ultrasound using Cadence Contrast Pulse Sequencing (CPS) technology for Prostate Cancer Detection: preliminary results

We evaluated contrast-enhanced ultrasound (US) using cadence contrast pulse sequencing (CPS) technology in comparison with systematic biopsy for detection of prostate cancer (PCa).

Evaluation of focal fatty infiltration of the liver using color Doppler and contrast‐enhanced sonography

To investigate the vascular characteristics of focal fatty infiltration (FFI) in the liver using color Doppler sonography (CDUS) and contrast-enhanced sonography (CEUS). We prospectively examined 25 areas of FFI of the liver in 20 patients via conventional gray-scale sonography, CDUS, and CEUS. Cadence contrast pulse sequencing and the contrast agent SonoVue were used for CEUS examination. CEUS criteria for diagnosis of FFI were isoenhancement or hypoenhancement in the arterial phase and homogeneous isoenhancement in the portal and late phases. CDUS revealed a draining vein in 4 of 9 (44%) lesions in the hepatic hilum, whereas CEUS revealed a draining vein in 8 (89%) lesions. A vein was associated with the 2 lesions located at the edge of segment II on both CDUS and CEUS. Blood flow was seen on both CDUS and CEUS in the 2 lesions adjacent to the falciform ligament. In one patient, CDUS and CEUS revealed the mid-hepatic vein coursing between 2 FFIs. In the arterial phase of CEUS, the lesions were hypoenhancing in 44% (11/25), iso-enhancing in 44% (11/25), and hyperenhancing in 12% (3/25). In the portal phase and in the late vascular phase, all 25 lesions (100%) were iso-enhancing. Sensitivity of combined sonography and CDUS in the diagnosis of FFI was 44%, and overall accuracy was 81%. The sensitivity of CEUS in the diagnosis of FFI was 88%, and its overall accuracy was 96%. FFI in the porta hepatis is correlated with aberrant venous drainage. FFI around the falciform ligament may be related to divergence of the portal vein or unusual blood supply. In the arterial phase of CEUS, FFI lesions were iso-enhancing as often as they were hypoenhancing.

Diagnostic Efficacy of Contrast-Enhanced Ultrasonography in Solid Renal Parenchymal Lesions With Maximum Diameters of 5 cm

The purpose of this study was to evaluate the diagnostic efficacy of contrast-enhanced ultrasonography (CEUS) using a sulfur hexafluoride contrast agent and the cadence contrast pulse sequencing mode in differentiating solid renal parenchymal lesions (SRPLs) with a maximum diameter of 5 cm. Seventy-one patients with 72 SRPLs with a maximum diameter of 5 cm underwent conventional ultrasonographic and CEUS examinations in our department. The final diagnoses were 44 renal cell carcinomas (RCCs; confirmed by pathologic examination), 24 renal angiomyolipomas (4 by pathologic examination and 20 by computed tomography, magnetic resonance imaging, and follow-up studies), 1 oncocytoma (by pathologic examination), 2 hypertrophied columns of Bertin, and 1 renal abscess (both by computed tomography, magnetic resonance imaging, and follow-up studies). Three observers who were blinded to other results and the final diagnoses reviewed the conventional ultrasonographic and CEUS images. Hyperenhancement in the late phase (30-90 seconds after agent injection) was the most important finding for predicting SRPLs with a maximum diameter of 5 cm to be RCCs. With this criterion, the specificity and sensitivity for diagnosing solid RCCs (<or= 5 cm) were 96.4% and 77.3%, respectively. Heterogeneous enhancement was another valuable finding suggestive of RCCs. Most renal angiomyolipomas were homogeneously enhanced with hypoenhancement in the arterial and late phases. Hypertrophied columns of Bertin could be reliably differentiated on CEUS; however, there was an overlap of CEUS appearances between some benign lesions and hypovascular RCCs. Contrast-enhanced ultrasonography could be an effective and necessary examination for differentially diagnosing SRPLs with a maximum diameter of 5 cm.

Detection of Carotid Adventitial Vasa Vasorum and Plaque Vascularization With Ultrasound Cadence Contrast Pulse Sequencing Technique and Echo-Contrast Agent

Adventitial vasa vasorum and plaque vascularization have been established as predictors of unstable atheromasic lesions in cerebro- and cardiovascular patients. Ultrasound contrast agents provide reliable information on tissue perfusion and microcirculation. We used contrast ultrasound duplex scanning to identify carotid plaque vascularization. Contrast carotid duplex scanning was performed in 23 patients with plaques of different degree of stenosis and echogenicity. Plaque vascularization was detected in the fibrous and fibro-fatty tissue and not observed in the calcific nor in the necrotic and hemorrhagic tissue. Constantly, a small vessel was observed under ulcerations. Carotid contrast ultrasound imaging appears to be an emerging technique for identifying plaque angiogenesis. Further studies are needed to clarify the role of plaque angiogenesis for assessing cerebrovascular risk and to monitor effects of therapies aimed to plaque remodelling.

Contrast ultrasound imaging: the best method to detect type II endoleak during endovascular aneurysm repair follow-up☆

Type II endoleak is the most common complication after endovascular aneurysm repair and require close surveillance. Hence, the need to validate new techniques as alternative to helical CT-scan, the reference standard. The aim of this study is to evaluate the efficacy of Cadence Contrast Pulse Sequencing ultrasound technique with second generation contrast agents in detecting endoleaks, and to compare the results with data obtained from CTA. 30 patients with endovascular stent grafts, during their regular follow-up consisting in serial CT and ultrasound exams performed at discharge, at one and six months and at one year thereafter, previous informed consent, were enrolled in a prospectic double blind study design in order to compare triphasic helical CT-scan to another adjunctive ultrasound investigation (Cadence CPS technique with Sono Vue). No more than 15 days occurred between the two examinations. In the study were evaluated only data obtained from the comparison of the two concomitant investigations, independently from the follow-up. Variables analysed were changes in the maximum diameter of the aneurysmal sac, presence and type of endoleak, if detected. In the case of disagreement between the two diagnostic tools angiography was performed. One patient dropped out because of violation of the study protocol (a stroke occurred in the time interval between the two investigations). Both exams visualised patency and proper graft placement in all the remaining patients. Aneurysmal diameters with both investigations overlapped (r(s):0.98). In 21 patients no endoleak was detected with a significant aneurysmal sac shrinkage (P<0.001). In seven patients both methods confirmed presence of endoleak. Ultrasonography detected all type of endoleaks, while CT-scan was uncertain in one. Moreover, in one patient CT-angiography showed an increased aneurysmal diameter without other evidence, while a contrast ultrasound investigation disclosed a type II low-flow endoleak, confirmed by angiography. The Cadence Contrast Pulse Sequencing with echo contrast agent is an ultrasound technique that substantially improves the ultrasound diagnostic reliability.

Standardize and Compare Contrast-enhanced Ultrasonographic Digital Images Obtained with Different Technologies: How to Overcome the Subjectivity

This study was conducted to compare digital images obtained with cadence contrast pulse sequencing (CPS) and coherent contrast imaging (CCI) technologies for contrast-enhanced ultrasonography (CEUS). A CEUS study on 17 focal liver lesions was performed using CPS and CCI technologies with a second-generation contrast media. The lesion/liver ratio and conspicuity index were then calculated and compared with Adobe Photoshop 6.0. Lesion/liver ratio and conspicuity index using CCI ranged from 1.3 to 7.1 (mean value, 3) and 19 to 127 (mean value, 58), respectively; by using CPS, we obtained results ranging from 2 to 19.1 (mean value, 8.9) and 57 to 164 (mean value, 109.2). Lesion/liver ratio and the conspicuity index for the lesions using CPS showed significantly (p < 0.0001) superior results than those obtained using CCI. The computed analysis with standardization allows an objective evaluation of digital images of CEUS. CPS technology resulted in better lesion conspicuity compared to CCI during CEUS study on focal liver lesions.

Differential Diagnosis of Focal Nodular Hyperplasia With Quantitative Parametric Analysis in Contrast-Enhanced Sonography

We investigated the potential of quantitative parametric analysis in the differential diagnosis of focal nodular hyperplasia (FNH) from other hypervascularized liver focal lesions. Eighty-five focal liver lesions (in 83 patients) were explored using contrast-enhanced ultrasound (SonoVue and Cadence Contrast Pulse Sequencing) consisting of typical FNH (n=52), hepatocellular carcinoma (n=11), hemangioma with high flow (n=8), hypervascular metastases (n=10), and hepatocellular adenoma (n=4). QontraXt software (AMID, Italy) was used here to estimate the following parameters: maximum peak value, Tr (time corresponding to time for obtaining 63% of the plateau), beta parameter corresponding to the exponential factor, and slope corresponding to the tangent value of the first phase of enhancement. These parameters were obtained from the time-intensity curves derived from the enhancement observed in 2 regions of interest corresponding, respectively, to the whole lesion and the central region only. A significant statistical difference (P<0.05) was found in the values of Tr, beta, and slope between FNH and other hypervascularized lesions on both the whole lesion and central region. Among these parameters, slope appeared as the most valuable whatever the region of interest, ie, central or whole lesion (P<0.01). Central region was more accurate in the differentiation of FNH and concordant with visual characterization. Quantitative parametric curve analysis of the different hypervascularized lesions confirms the depiction of the central artery in FNH and thus could help in differentiating this specific focal liver lesion from the others.

Diagnostic Accuracy of Contrast-Enhanced Ultrasound in Focal Lesions of the Liver Using Cadence Contrast Pulse Sequencing

The purpose of this study was to assess the accuracy of Cadence Contrast Pulse Sequencing (Siemens-Acuson, CA) method with injection of SonoVue (Bracco Imaging SpA, Italy) for the detection and characterisation of focal liver lesions in comparison with a reference modality during routine use. 138 consecutive patients (62 women, 76 men; mean age: 52 years for women and 63 years for men) corresponding to 144 examinations with 381 lesions participated in this prospective study from December 2002 to November 2003. Inclusion criteria were lesions detected by conventional US and the availability of a reference imaging examination (CT or MR imaging) within three weeks. The underlying liver lesions characterised by a reference modality (including biopsy in 29 lesions) were distributed as follows: haemangioma (n = 56), focal nodular hyperplasia (n = 27), hepatocellular carcinoma (n = 44), hepatocellular adenoma (n = 5), liver metastasis (n = 174), abscess (n = 2), cysts (n = 45), other benign lesions (n = 24) and 3 peritoneal metastases. A significant improvement was reported in the number of detected lesions between contrast-enhanced ultrasound and baseline ultrasonography (351 lesions versus 280 lesions, respectively, p < 0.01), whereas no significant difference was noted between contrast-enhanced ultrasound and reference imaging (351 versus 377 lesions, respectively). On the whole, contrast-enhanced ultrasound allowed a complete diagnosis in 96 % of the detected nodules with a significant improvement compared to conventional sonography in which the diagnosis was suspected in only 52 % out of these cases (p < 0.001). No significant difference was noted between contrast-enhanced ultrasound and the reference modality concerning characterisation of nodules. The present study clearly indicates that contrast-enhanced sonography using Sonovue and Cadence Contrast Pulse Sequencing allows real-time imaging with high accuracy and thus will be a competitive alternative to other modalities such as CT and MR imaging for liver imaging.