Contrast-enhanced Harmonic Imaging Research Articles

Utility of endoscopic ultrasound-guided hepatic abscess drainage with contrast-enhanced harmonic imaging.

Utility of endoscopic ultrasound-guided hepatic abscess drainage with contrast-enhanced harmonic imaging.

Practical approach to linear endoscopic ultrasound examination of the gallbladder

The gallbladder (GB) is a susceptible organ, prone to various pathologies that can be identified using different imaging techniques. Transabdominal ultrasound (TUS) is typically the initial diagnostic method due to its numerous well-established advantages. However, in cases of uncertainty or when a definitive diagnosis cannot be established, computed tomography (CT) or magnetic resonance imaging may be employed to provide more detailed information. Nevertheless, CT scans may sometimes offer inadequate spatial resolution, which can limit the differentiation of GB lesions, particularly when smaller yet clinically relevant abnormalities are involved. Conversely, endoscopic ultrasound (EUS) provides higher frequency compared to TUS, superior spatial resolution, and the option for contrast-enhanced harmonic imaging, enabling a more comprehensive examination. Thus, EUS can serve as a supplementary tool when conventional imaging methods are insufficient. This review will describe the standard EUS examination of the GB, focusing on its endosonographic characteristics in various GB pathologies.

The usefulness of endoscopic ultrasound in the diagnosis of gallbladder lesions.

Gallbladder tumors are neoplastic lesions; however, it can be difficult to distinguish between benign and malignant gall bladder tumors before surgery, although endoscopic ultrasound (EUS) is useful for differentiation. Fundamental B mode EUS (FB-EUS) and contrast-enhanced harmonic EUS (CH-EUS) are reported to be useful for the diagnosis of gallbladder tumor because they allow evaluation of polypoid lesion and gallbladder wall thickening. Scoring systems based on FB-EUS imaging are available for the diagnosis of malignant gallbladder polypoid lesions. The characteristic findings of malignant gallbladder polypoid lesions on CH-EUS include the presence of irregular intratumoral vessels and perfusion defects. The characteristic findings of malignant gallbladder wall thickening on FB-EUS include wall thickening >12 mm, hypoechoic internal echogenicity, inhomogeneous internal echo pattern, and disrupted wall layer, whereas CH-EUS findings include hypovascular enhancement and inhomogeneous contrast distribution pattern. In addition, FB-EUS and CH-EUS are useful for evaluating the stage of gallbladder carcinoma because they allow the evaluation of the depth of invasion of the gallbladder wall. It is usually difficult to obtain pathological evidence from gallbladder tumors before surgery and chemotherapy, even though the histological diagnosis is necessary for determining treatment policy. EUS-guided fine needle aspiration (EUS-FNA) is useful for obtaining pathological samples from gallbladder tumors before surgery and chemotherapy. The accuracy rate of EUS-FNA for gallbladder tumor is as high as 90%, but complications such as bile leakage and needle track seeding can be a problem, although it was reported that contrast-enhanced harmonic imaging is useful for avoiding them.

EUS-guided hepaticogastrostomy with contrast-enhanced harmonic imaging (with video).

EUS-guided hepaticogastrostomy with contrast-enhanced harmonic imaging (with video).

Role of CH-EUS as guidance for EUS-biliary drainage malignant obstruction.

Endoscopic ultrasound (EUS)-guided biliary drainage is the usual method of choice for patients with biliary obstructions difficult to treat by endoscopic retrograde cholangiopancreatography. In some patients, however, the bile duct is difficult to detect during EUS-guided biliary drainage. Contrast-enhanced harmonic endoscopic ultrasound has reportedly been useful for interventional EUS procedures. This study describes five patients who underwent EUS-guided biliary drainage with contrast-enhanced harmonic imaging between April 2017 and March 2020 for malignant biliary obstruction due to bile duct cancer. The procedure was performed through an intrahepatic bile duct approach in three patients and through an extrahepatic bile duct approach in the other two. Although fundamental B-mode EUS was unable to detect the target intrahepatic bile duct because the duct was filled with debris, contrast-enhanced harmonic imaging was able to detect the bile duct by clarifying its border with the hepatic parenchyma. Similarly, in patients who underwent extrahepatic bile duct approach, fundamental B-mode EUS could not distinguish between debris and tumor, whereas contrast-enhanced harmonic EUS was able to differentiate between them. The procedure was technically and clinically successful in all five patients. One patient experienced bleeding as an adverse event. In conclusion, EUS-guided biliary drainage with contrast-enhanced harmonic imaging is useful in detecting the fluid space in bile ducts filled with debris or filled with debris and tumor invasion.

Endoscopic ultrasound‐guided fine needle aspiration with contrast‐enhanced harmonic imaging for diagnosis of gallbladder tumor (with video)

Highlight Endoscopic ultrasound-guided fine needle aspiration with contrast-enhanced harmonic imaging is useful for accurately and safely obtaining tissue from a gallbladder tumor. Tamura and colleagues demonstrate how contrast-enhanced harmonic endoscopic ultrasound facilitates puncturing the gallbladder tumor while avoiding fluid spaces as it demarcates the borderline between the tumor and fluid spaces.

Characterizing Breast Lesions Using Quantitative Parametric 3D Subharmonic Imaging: A Multicenter Study

Breast cancer is the leading type of cancer among women. Visualization and characterization of breast lesions based on vascularity kinetics was evaluated using three-dimensional (3D) contrast-enhanced ultrasound imaging in a clinical study. Breast lesions (n = 219) were imaged using power Doppler imaging (PDI), 3D contrast-enhanced harmonic imaging (HI), and 3D contrast-enhanced subharmonic imaging (SHI) with a modified Logiq 9 ultrasound scanner using a 4D10L transducer. Quantitative metrics of vascularity derived from 3D parametric volumes (based on contrast perfusion; PER and area under the curve; AUC) were generated by off-line processing of contrast wash-in and wash-out. Diagnostic accuracy of these quantitative vascular parameters was assessed with biopsy results as the reference standard. Vascularity was observed with PDI in 93 lesions (69 benign and 24 malignant), 3D HI in 8 lesions (5 benign and 3 malignant), and 3D SHI in 83 lesions (58 benign and 25 malignant). Diagnostic accuracy for vascular heterogeneity, PER, and AUC ranged from 0.52 to 0.75, while the best logistical regression model (vascular heterogeneity ratio, central PER, and central AUC) reached 0.90. 3D SHI successfully detects contrast agent flow in breast lesions and characterization of these lesions based on quantitative measures of vascular heterogeneity and 3D parametric volumes is promising.

Contrast-enhanced Harmonic EUS Imaging of Pancreatic Mucinous Cystadenocarcinoma.

Contrast-enhanced Harmonic EUS Imaging of Pancreatic Mucinous Cystadenocarcinoma.

Contrast-enhanced harmonic endoscopic ultrasonography for pancreatobiliary diseases.

The combination of second-generation ultrasound contrast agents and an endoscopic ultrasonography (EUS) system with a broad-band transducer has allowed contrast-enhanced harmonic imaging in the field of EUS. In contrast-enhanced harmonic EUS (CH-EUS), diffuse homogeneous enhancement is obtained in normal parenchyma of the pancreas. The bile duct and pancreatic duct are depicted as non-enhanced ductal structures with strong contrast in comparison to the surrounding parenchyma. CH-EUS identifies pancreatic adenocarcinomas as solid lesions exhibiting hypo-enhancement with a sensitivity and specificity of 88-96% and 88-94%, respectively. In particular, 80-100% of false-negative cases in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are correctly classified by CH-EUS, suggesting CH-EUS complements EUS-FNA. Moreover, CH-EUS improves depiction of some subtle lesions in conventional EUS, thus facilitating EUS-FNA. For quantitative perfusion analysis, a time-intensity curve (TIC) for the region of interest can be generated during CH-EUS. The maximum intensity gain and the echo intensity reduction rate from the peak at 1 min obtained by TIC can be used for differentiation of pancreatic adenocarcinoma from other tumors. CH-EUS is also useful for differentiation of invasive intraductal papillary mucinous neoplasms (IPMN) from non-invasive IPMN, identification of malignant lesions in the gallbladder, and T- and N-staging of pancreatobiliary tumors.

Contrast-enhanced endoscopic ultrasonography.

Contrast agents are increasingly being used to characterize the vasculature in an organ of interest, to better delineate benign from malignant pathology and to aid in staging and directing therapeutic procedures. We review the mechanisms of action of first, second and third generation contrast agents and their use in various endoscopic procedures in the gastrointestinal tract. Various applications of contrast-enhanced endoscopic ultrasonography include differentiating benign from malignant mediastinal lymphadenopathy, assessment of depth of invasion of esophageal, gastric and gall bladder cancers and visualization of the portal venous system and esophageal varices. In addition, contrast agents can be used to differentiate pancreatic lesions. The use of color Doppler further increases the ability to diagnose and differentiate various pancreatic malignancies. The sensitivity of power Doppler sonography to depict tumor neovascularization can be increased by contrast agents. Contrast-enhanced harmonic imaging is a useful aid in identifying the tumor vasculature and studying pancreatic microperfusion. In the future, these techniques could potentially be used to quantify tumor perfusion, to assess and monitor the efficacy of antiangiogenic agents, to assist targeted drug delivery and allow molecular imaging.

Contrast-enhanced harmonic EUS with novel ultrasonographic contrast (Sonazoid) in the preoperative T-staging for pancreaticobiliary malignancies

Objective. Sonazoid is a new second-generation microbubble contrast for ultrasonography. In this pilot study, the diagnostic role of contrast-enhanced harmonic imaging endoscopic ultrasonography (CH-EUS) with Sonazoid was prospectively evaluated in preoperative T-staging of pancreaticobiliary malignancies. Patients and methods. Patients with suspected pancreaticobiliary malignancies underwent CH-EUS by a single examiner. After the lesions were observed carefully with conventional harmonic imaging EUS (H-EUS), CH-EUS was performed with intravenous injection of Sonazoid. A reviewer who was blinded reviewed the recordings of H-EUS and CH-EUS and assessed the T-staging. The accuracy of H-EUS and CH-EUS for T-staging was compared to the results of surgical histopathology in patients who underwent surgery. Result. Twenty-six patients underwent surgical resection and could be included in the study. The final diagnosis were pancreatic cancer in 11, bile duct cancer in 7, gallbladder cancer in 4 and ampullary cancer in 4. The overall accuracy of H-EUS and CH-EUS for T-staging were 69.2 (18/26) and 92.4% (24/26), respectively (p < 0.05). There were disagreement in six cases between H-EUS and CH-EUS. CH-EUS staged correctly in all of these six cases, whereas H-EUS misdiagnosed the depth of invasion in one case of gallbladder cancer and one case of ampullary cancer, and invasion of portal vein in two cases of pancreatic cancer and two cases of bile duct cancer. Conclusion. The depth of invasion of biliary cancer and vascular invasion of pancreatic and biliary cancer could be demonstrated more clearly with CH-EUS compared to H-EUS. CH-EUS has the potential to improve the diagnostic accuracy of preoperative T-staging of pancreaticobiliary malignancies.

W1049 Quantification of Microvascular Activation in Ileal Crohn's Disease By Software Elaboration Data Applied to CEUS: Correlation with Biological Activity Indexes

PURPOSE Microvascular activation and angiogenesis induced by inflammation in ileal loops affected by Crohn's disease (CD) can be demonstrated by contrast-enhanced wideband harmonic imaging ultrasound (CEUS) with second-generation intravascular contrast media (blood-pool). Aim of the present perspective study was to evaluate if Time To Peak (TTP), Maximum Peak Intensity (MPI) and Slope (Coefficient of the wash-in slope) (β ) are able to predict and quantify inflammatory activity in ileal CD. METHOD AND MATERIALS The study was performed by means of digital US scanner Philips iU22 with dedicated software for low-mechanical-index studies and a 4 to 8 MHz linear-array probe. Fifthy-four transabdominal US examinations with second generation contrast agent (SonoVue® i.v. 4,8 ml) were performed. After informed consent, between 2005 and 2007, fifthy-four consecutive patients (M38, F16, age range 18-69 years; mean 35) affected by ileal CD without colonrectal disease or with inactive colonic disease, were studied by CEUS. According to Montreal classification 16 patients had inflammatory, 17 stricturing and 21 penetrating disease The US data obtained after SV administration allow to draw up time-intensity curves through software-assisted HDI-QLab and to obtain following parameters: time to peak (TTP), maximum peak intensity (MPI) coefficient of the wash-in slope (β ). Through ROC curve analysis, quantitative data were correlated with Biological Activity as Gold Standard, that is the positivity of at least 3 beetweenCDAI, laboratory parameters, endoscopy, radiology. RESULTS In distinguish active disease, TTP (seconds) with a cut-off >8.1 showed sensitivity 97.2% specificity 77.7% (p=0.0001, AUC 0.86); MPI (Db), cut-off >24, sensitivity 97.2%, specificity 83.3% (p=0.0001, AUC 0.927); Slope (Db/sec), cut-off >4.5, sensitivity 86.1%, specificity 83.3%, (p=0.0001, AUC 0.891). CONCLUSION This study demonstrates that TTP, MPI and Slope are able to predict and quantify inflammatory activity in ileal CD. Quantitative CEUS and definite cut-off could improve the reliability of conventional US to detect active bowel wall inflammation in CD. Quantitative data could objectivate the response to the therapies. CEUS could be used in the follow-up because of lack of radiation exposure.

Acoustic fingerprints of dye-labeled protein submicrosphere photoacoustic contrast agents

Dye-labeled protein microspheres, submicron in size and capable of producing thermoelastically generated ultrasound in response to laser stimulation, are presented as contrast agents for photoacoustic imaging. Incident laser energy absorbed by fluorescein isothiocyanate (FITC)-labeled elastin submicrospheres results in thermoelastically generated sound production. Plotted A-line graphs reveal a distinctive morphology and a greater than two orders of magnitude increase in signal amplitude subsequent to converting FITC elastin into submicrospheres (despite a four orders of magnitude decrease in concentration). Evidence of nonlinearity and enhancement of ultrasound backscatter indicate a potential use in contrast-enhanced harmonic imaging. Photoacoustic and ultrasound imaging of FITC-elastin submicrospheres in a water-filled phantom vessel shows enhanced contrast at low concentration and clear delineation of the phantom vessel wall.

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma.

The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

M1116 Contrast-Enhanced Wideband Harmonic Imaging Ultrasound and Contrast Media “Blood-Pool”: Quantitative Measurement of Inflammatory Activity in Crohn's Disease Using Parametric Imaging

M1116 Contrast-Enhanced Wideband Harmonic Imaging Ultrasound and Contrast Media “Blood-Pool”: Quantitative Measurement of Inflammatory Activity in Crohn's Disease Using Parametric Imaging

Contrast-enhanced wideband harmonic imaging ultrasound (SonoVue®): A new technique for quantifying bowel wall vascularity in Crohn's disease

Objective. To assess the possibility of quantitative determination of bowel wall vascularity using contrast-enhanced (SonoVue®) wideband harmonic imaging ultrasound and the HDI-Lab software in patients with Crohn's disease. Material and methods. Twenty-one patients (13 F, 8 M, average age 33.8±12.7 years, range 21–60 years) with histologically confirmed Crohn's disease and bowel wall thickness ≥5 mm were recruited for the study. All ultrasound examinations were performed using a Philips HDI 5000 scanner. Bowel wall vascularity was determined at the site of maximum bowel wall thickness at baseline and at 30, 60, 90 and 120 s following application of the contrast enhancer SonoVue (1.2 ml) using the HDI-Lab software. Results. The mean length of bowel segments exhibiting increased wall thickness was 122.3 mm (range: 23–350±74.7 mm), with a mean wall thickness of 7.6±1.2 mm. Onset of echo enhancement secondary to contrast medium application was observed after an average 13.4 s (range 7–19±4.2 s). Echo intensity corresponding to maximum vascularity was measured 30 s after application of contrast medium. Maximum average contrast medium uptake was 217.5% (range 118–466±100.1%). Conclusions. It is possible to quantify bowel wall vascularity accurately in patients with Crohn's disease using contrast-enhanced pulse inversion ultrasound (low-MI).

Ultrasound detection of spontaneous hepato‐cellular carcinomas in X/myc bitransgenic mice

To evaluate trans-abdominal ultrasound for the detection of Hepatocellular carcinoma (HCC) in a bitrasgenic murine (X/myc) model using a commercially available high-frequency ultrasound unit. Sixty-one female animals were included in this study. These animals were submitted to a single ultrasound examination of the liver under general anesthesia (isoflurane), and then euthanized. Results of ultrasound were compared with necropsy and histopathology. The lesions demonstrated a fairly consistent aspect (oval- or round-shaped, well-defined hypoechoic homogeneous lesions), and lesions as small as 2 mm were identified. For detection of hepatic nodules per mouse the sensitivity was 75%, the specificity was 100% and the accuracy was 88.5%. For detection of hepatic focal lesions per lesions the overall sensitivity was 60%, the specificity was 97%, and the accuracy was 75.9%. Contrast-enhanced harmonic ultrasound imaging did not improve the identification of the lesions in our experimental conditions. High-frequency ultrasound appears to be an efficient tool allowing new possibilities to use this animal model and evaluate new therapies in longitudinal studies, which are much more powerful.

Diagnosis of vesicoureteric reflux with low-dose contrast-enhanced harmonic ultrasound imaging

Harmonic US imaging has been shown to be better than conventional US for the detection and visualisation of microbubbles in contrast-enhanced voiding urosonography (VUS). To determine the diagnostic efficacy of VUS using a reduced dose of the US contrast medium in comparison to voiding cystourethrography (VCUG). Fifty-five children (17 boys, 38 girls; mean age 4 years) were recruited. All patients underwent VUS by harmonic imaging followed by VCUG. The dose of the US contrast medium (Levovist) administered intravesically was half of the recommended dose i.e. 5% of the bladder filling volume. A total of 114 kidney-ureter (K-U) units were available for evaluation. Vesicoureteric reflux (VUR) was detected in 29 K-U units by one or both examination modalities. There was a 91.2% concordance rate between VUS and VCUG. VUR in seven and three K-U units were detected only by VUS and VCUG, respectively. Taking VCUG as the reference method, VUS had the following diagnostic results: 86.4% sensitivity, 92.4% specificity, positive and negative predictive values of 73.1 and 96.6%, respectively. Even when the dose of US contrast medium is halved, the diagnostic efficacy of harmonic VUS is comparable to VCUG. Consequently, we recommend an US contrast medium dose of 5% of the bladder filling volume for the diagnosis of VUR using contrast-enhanced harmonic VUS.

Contrast-Enhanced Second-Harmonic Sonography in the Detection of Pseudocapsule in Renal Cell Carcinoma

Our purpose was to assess the capacity of contrast-enhanced second-harmonic sonography to detect a pseudocapsule in renal masses compared with conventional gray-scale sonography. SUBJECTS AND METHODS. Thirty-two patients with 40 renal masses suspicious for renal cancer (mean diameter, 3.1 cm) were prospectively studied with contrast-enhanced second-harmonic sonography during IV administration of a second-generation sonographic contrast agent. The sonographic criteria for the presence of a pseudocapsule were a peritumoral hypoanechoic halo on conventional gray-scale imaging and a rim of perilesional enhancement, increasing in the tardive phase of the examination, on contrast-enhanced second-harmonic imaging. Multiphasic helical CT or dynamic MRI or both were performed in all patients. Final diagnoses of the 40 renal masses were as follows: hemorrhagic cysts, five; angiomyolipomas, four; lymphomas, four; metastasis from lung cancer, one; and renal cell carcinomas (RCCs), 26. Histologic diagnosis of RCC was surgically obtained in all patients. Nephron-sparing surgery was performed in 12 of 26 RCCs, and radical nephrectomy was performed in the remaining 14. At pathologic examination, pseudocapsule was found in 14 (53.8%) of 26 RCCs. On conventional sonography, the presence of a pseudocapsule was detected in 3 of 14 RCCs (sensitivity, 21%). Sonographic contrast-enhanced harmonic imaging revealed the presence of pseudocapsule in 12 of 14 RCCs (sensitivity, 85.7%). In the remaining 12 RCCs with either absent or extensive neoplastic infiltration of pseudocapsule seen at pathologic evaluation, pseudocapsule was not visible on either conventional or contrast-enhanced second-harmonic sonography. The pseudocapsule was not visible in any of the 14 noncancerous renal masses on either conventional or contrast-enhanced sonography. Sonographic contrast-specific imaging with a second-generation contrast agent is effective in improving the sonographic visualization of tumoral pseudocapsule. This finding could be useful both in the sonographic diagnosis and in the choice of conservative surgery for renal cell carcinoma. The potential role of second-harmonic contrast-enhanced sonography in the management of renal cell carcinoma should be investigated in larger series and compared with the findings of state-of-the-art MRI and CT.

Measurement of coronary flow velocity reserve in the posterior descending coronary artery by contrast-enhanced transthoracic doppler echocardiography

Background Although the measurement of coronary flow velocity (CFV) reserve (CFVR) in the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography has been established, its success rate in the posterior descending coronary artery (PD) is still limited. Objective This study reports the feasibility and diagnostic accuracy of measuring CFVR in the PD by transthoracic Doppler echocardiography. Methods CFVR in both the distal LAD and the PD was measured in 151 consecutive patients before coronary angiography. PD flow was investigated under the guidance of a nondirectional Doppler color flow map with harmonic imaging in the modified apical 2-chamber view. Intravenous contrast agent, Levovist, was injected to enhance the CFV envelope at baseline and during hyperemia. Results CFVR was obtained in 145 patients in the LAD and 126 patients in the PD ( P < .001). The success rate of CFVR measurement in the PD was significantly higher in the last 50 patients (88%) than it was in the first 50 patients (72%) ( P < .05). CFVR in the PD was significantly lower for patients with significant stenosis of the artery supplying the PD than it was in those without stenosis (1.58 ± 0.59 vs 2.45 ± 0.72, P < .001). CFVR in the distal LAD was 1.40 ± 0.62 in patients with significant LAD stenosis and 2.45 ± 0.80 in those without stenosis ( P < .001). If a cut-off value of CFVR < 2 was used, sensitivity, specificity, and accuracy for the diagnosis of significant (>50%) stenosis of the artery supplying the PD were 84%, 83%, and 83%, respectively, whereas for the LAD they were 91%, 75%, and 80%, respectively. Conclusions Noninvasive measurement of CFVR in the PD could be obtained in the majority of unselected patients using a nondirectional Doppler color flow map and contrast-enhanced harmonic imaging. The diagnostic accuracy of CFVR in the PD is similar to that of the LAD and, hence, has a potential clinical use.