Ultrasonic Contrast Medium Research Articles

A review of ultrasound contrast media

Efforts have been made over the last five decades to create effective ultrasonic contrast media (UCM) for cardiac and noncardiac applications. The initial UCM was established in the 1980s, following publications from the 1960s that detailed the discovery of ultrasonic contrast enhancement using small gaseous bubbles in echocardiographic examinations. An optimal contrast agent for echography should possess the following characteristics: non-toxicity, suitability for intravenous injection, ability to traverse pulmonary, cardiac, and capillary circulations, and stability for recirculation. Definity, Optison, Sonazoid, and SonoVue are examples of current commercial contrast media. These contrast media have shown potential for various clinical reasons, both on-label and off-label. Several possible UCMs have been developed or are in progress. Advancements in comprehending the physical, chemical, and biological characteristics of microbubbles have significantly improved the visualization of tumor blood vessels, the identification of areas with reduced blood supply, and the enhanced detection of narrowed blood vessels. Innovative advances are expected to enhance future applications such as ultrasonic molecular imaging and therapeutic utilization of microbubbles.

A review of ultrasound contrast media.

Efforts have been made over the last five decades to create effective ultrasonic contrast media (UCM) for cardiac and noncardiac applications. The initial UCM was established in the 1980s, following publications from the 1960s that detailed the discovery of ultrasonic contrast enhancement using small gaseous bubbles in echocardiographic examinations. An optimal contrast agent for echography should possess the following characteristics: non-toxicity, suitability for intravenous injection, ability to traverse pulmonary, cardiac, and capillary circulations, and stability for recirculation. Definity, Optison, Sonazoid, and SonoVue are examples of current commercial contrast media. These contrast media have shown potential for various clinical reasons, both on-label and off-label. Several possible UCMs have been developed or are in progress. Advancements in comprehending the physical, chemical, and biological characteristics of microbubbles have significantly improved the visualization of tumor blood vessels, the identification of areas with reduced blood supply, and the enhanced detection of narrowed blood vessels. Innovative advances are expected to enhance future applications such as ultrasonic molecular imaging and therapeutic utilization of microbubbles.

Evaluation of contrast-enhanced ultrasound in the differential diagnosis of benign and malignant lateral cervical lymph nodes

Objective: To investigate the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of benign and malignant lateral cervical lymph nodes. Methods: One hundred and fifteen cases of suspected lymph nodes disease, 60 males, 55 females, between November 2018 and June 2019 from clinic and inpatient in Fujian Cancer Hospital were collected. Routine ultrasound and CEUS were performed in 115 cases of lateral cervical lymph nodes. All cases underwent ultrasound-guided biopsy, and were divided into two groups of benign and malignant lymph nodes according to pathological results. The differences between the two groups were analyzed and statistically analyzed. The rate and frequency were used to qualitatively describe the ultrasound performance and observed lymph node morphology between the two groups of routine ultrasound and CEUS. The sensitivity, specificity, accuracy, negative predictive value and positive predictive value were used to evaluate the efficacy of routine ultrasound and CEUS. Results: There were 37 cases of benign lymph nodes and 78 cases of malignant lymph nodes. In benign lymph nodes, 51.4% (19/37) showed uniform high enhancement, and 48.6% (18/37) showed uneven or circular enhancement with clear boundaries and no focal enhancement area. In malignant lymph nodes, 94.9% (74/78) showed uneven enhancement, and only 5.1% (4/78) showed uniform enhancement. The difference of ultrasonic contrast medium uniformities in differentiating benign from malignant was statistically significant (P<0.001). The sensitivity, accuracy, negative predictive value and positive predictive value of routine ultrasound to differentiate benign and malignant lymph nodes were 64.1%, 65.2%, 47.2%, and 66.7%, respectively, while the corresponding values of CEUS were 93.6%, 75.7%, 73.7% and 83.9%. Conclusion: CEUS may provide a valuable basis for the differential diagnosis of benign and malignant lateral cervical lymph nodes.

Abstract 1501: Evaluation of tumor vascularity in colorectal cancer using contrast enhanced ultrasonograpy in comparison with microvessel density

Abstract Background : The relationship between tumor vascularity and malignant potential in colorectal cancer a(CRC) is reported by many authors. Therefore, to assess the tumor vascularity before surgical treatment is thought to be one of very important factors in CRC patients. Contrast enhanced ultrasonography (CEUS) can visualize the tumor vascularity vividly. We aim to determine the reliability of CEUS for the assessment of vascularity of CRC and to analyze the relationship between tumor vascularity and clinicopathological characteristics. In addition, to find the clinical application, we assessed the efficacy of chemotherapy in unresectable advanced CRC patients by CEUS. Methods : 56 patients undergoing surgical resection of CRC were studied. An ultrasound system (GE health care, LOGIC 7) is used and visualized the colo-rectal tumor using a 4.5MHZ probe. The 2nd generated ultrasonic contrast medium (Belfulbuttan, Sonazoid) is injected intravenously. Approximately 20 s after injection, microbubbles were obtained to enhance the B-mode image. Using the tumor image showing the strongest vascularity, region of interest were determined to measure mean echo intensity in the tumor. Their images were analyzed with NIH image program (developed by the US National Institutes of health) and calculated tumor vascularity as Vascular Index (VI). The clinicopathological features are based on the TNM classification from UICC. Using surgical specimens, tumor vascularity was assessed by immunohistochemistry as microvessel density in order to do statistical analysis for the correlation between VI, clinicopathologic features and microvessel density. Results : CEUS could visualize the tumor vascularity in all patients. In advanced CRC patients, we observed that the tumor invaded into other organ, such as prostate gland, small intestine and so on. The VI correlated significantly with depth of tumor invasion, liver metastasis and microvessel density. Furthermore, in patients with abundant vascularity in tumor before treatment, chemotherapy led to the reduction of VI prior to the radiographically visible difference in tumor size. Conclusion : CEUS can evaluate the tumor vascularity non-invasively and is very useful for the evaluation of their pathological diagnosis and the efficacy of chemotherapy in CRC. Citation Format: Takaomi Okawa, Hiromi Nogami, Munenori Takaoka. Evaluation of tumor vascularity in colorectal cancer using contrast enhanced ultrasonograpy in comparison with microvessel density. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1501. doi:10.1158/1538-7445.AM2015-1501

The role of contrast-enhanced harmonic endoscopic ultrasonography in the diagnosis of pancreatic cancer

Objective To evaluate the diagnostic accuracy of contrast-enhanced harmonic EUS (CH-EUS)for pancreatic cancer.Methods Patients with pancreatic occupying lesion underwent CH-EUS with ultrasonic contrast medium Sonovue.Pathological diagnoses by EUS-FNA or surgery and the follow-up results were made as the final diagnosis to evaluate the accuracy of CH-EUS for pancreatic cancer.Character-istics of CH-EUS in different pancreatic tumors were analysed.Results A total of 76 patients were en-rolled,with an average age of 53. 1 ±14. 2.Thirty-five were finally diagnosed as having pancreatic cancer, 21 local mass-type pancreatitis,10 pancreatic neuroendocrine tumor,6 cystadenoma,4 intraductal papillary mucinous neoplasm.Tumor diameter was 3. 4 ±1. 4 cm and there were 18 less than 2 cm.The sensitivity and specificity,positive and negative predictive value of CH-EUS for pancreatic cancer was 97. 1%, 92. 9%,91. 7% and 97. 5% respectively.The sensitivity was 100% combined with FNA.Conclusion CH-EUS is safe,convenient for pancreatic cancer with high accuracy and can be used as an additional diag-nostic method to EUS-FNA. Key words: Pancreatic neoplasms ; Endosonography ; Diagnosis ; Contrast enhanced harmonic ;

Contrast-enhanced harmonic EUS in diagnosis of pancreatic occupying lesions

Objective To evaluate the accuracy of contrast-enhanced harmonic EUS （CEH-EUS） by using a second-generation contrast medium in differential diagnosis of pancreatic occupying lesions. Methods Patients with suspected pancreatic neoplasms or chronic pancreatitis were enrolled and underwent CEH-EUS by using ultrasonic contrast medium Sonovue. Cytological and/or histological diagnoses were made by EUS-FNA and the final follow-up results. Characteristics of enhancement of the target areas, such as enhancement sequence, time features, pattern grade and venous elution degree were investigated. Results A total of 23 patients were enrolled, in which 13 were diagnosed with FNA as having pancreatic cancer, 7 with chronic pancreatitis, 2 with intraductal papillary mucinous neoplasms and 1 with microcystic serous cystadenoma. The accuracy of CEH-EUS was 95.65% , which was significantly higher than that of conventional EUS （78.2%）. Enhancement of pancreatic cancer by CEH-EUS was later than or simultaneous with the nearby tissues, with heterogeneous low enhancement or fulfillment defect areas, and early subsidence without obvious peak. Enhancement of benign pancreatic diseases was simultaneous with the surrounding tissues, with homogenous fulfillment and simultaneous subsidence. Conclusion CEH-EUS is safe, convenient and accurate in diagnosis of pancreatic occupying lesions and can be used as an additional diagnostic method to EUSFNA. Key words: Pancreatic diseases ; Endoscopic uhrasonography ; Diagnosis ; Contrast enhanced harmonic

Dynamische konstrastmittelgestützte Ultraschallkavographie bei Kavafilterpatienten

In 35 patients during 42 examinations, vena-caval blood flow was visualized by application of a new ultrasonic contrast medium (Echovist) via a dorsopedal vein. A caval filter had previously been implanted in 32 patients. In 94 out of 99 cases, application of the contrast medium allowed a diagnostically relevant enhancement of the echogenicity of the caval blood flow. In addition, the caval filters allowed altered flow geometry to be depicted in detail.

Transesophageal contrast echocardiography, open foramen ovale and aneurysm of the atrial septum. Experiences with D-galactose suspension

The advantages of transesophageal echocardiography using a D-galactose suspension rather than conventional ultrasonic contrast medium for the detection of a cardiac source of peripheral embolism was to be investigated. In 100 patients consecutively examined with transesophageal echocardiography applying a conventional ultrasonic contrast medium the examination was repeated adding a Valsalva test and using a solution of D-galactose (Echovist-300, Schering AG) as contrast medium. With conventional contrast media, 5 interatrial shunts only (2 ASD, 3 patent foramina ovalia, PFO) were detected. Completion of echocardiography with a systemic Valsalva test and use of Echovist-300 resulted in the diagnosis of another 40 PFO. In 17 of 26 patients having an atrial septal aneurysm, an interatrial shunt (1 ASD, 16 PFO) was demonstrated. The use of a solution of D-galactose as contrast medium appears to increase the sensitivity of echo-cardiography for demonstrating a cardiac source of peripheral embolism.

Evaluation of colon cancer vascularity by flash echo imaging

Objective. Tumor vascularity is strongly related to the prognoses of patients with various malignant primary tumors, including colorectal cancer. The aim of this study was to confirm the usefulness of harmonic flash echo imaging (H-FEI) for the preoperative evaluation of tumor vascularity in colorectal cancer by comparison with CD34 staining of resected specimens. Material andmethods. Seventeen patients undergoing surgical resection for advanced colorectal cancer (9 M, 8 F) were enrolled in this study. An ultrasound system transmitting ultrasound pulses at 2.3 MHz and receiving them at 4.6 MHz (second harmonic) was used for H-FEI. After intravenous injection of ultrasonic contrast medium (SHU 508A), intermittent harmonic scanning was carried out for 120 s at intervals of 4 s. On the tumor image of the strongest enhancement in each patient, 5 regions of interest were taken to decide the mean echo intensity of the tumor. Immunohistochemistry using antibodies against CD34 was carried out on resected specimens. The mean microvessel density was decided by counting microvessels on 5 fields (×400) of CD34-stained specimens. Results. The mean value of H-FEI intensity was 5.44±1.10, and the mean microvessel count with CD34 staining was 35.0±7.95. A significant positive linear correlation was observed between the intensity of H-FEI determined preoperatively and the microvessel count in CD34-stained specimens (r=0.741, p=0.0006). Conclusion. Vascularity of colon cancer can be evaluated non-invasively using H-FEI.

２１世紀における神経超音波の役割―ニューロナビゲーションを例に―

Ultrasound has several advantages over CT or MRI, such as real-time data acquisition, mobility, cost-efficiency, and freedom from the risk of X-ray radiation injury and problems with the use of magnetic materials. Recent advances in ultrasonography, such as transcranial color-coded duplex imaging, broad bandwidth scanning, 3-dimensional ultrasound and ultrasonic contrast medium, have enabled the development of new methods of clinical diagnosis. The diagnostic usefulness of ultrasonography is described as a tool for neuronavigation where intraoperative findings must be displayed in real time. Ultrasonography will help surgeons to make appropriate judgements regarding surgical procedures in relation to intraoperative shift of the brain, especially in cases of cystic lesion, ventricular or multiple lesions, which tend to be responsible for large brain shifts. Ultrasound will provide anatomical findings over the course of surgery and make up for the deficits of other diagnostic tools such as MRI. Ultrasound-based neuronavigation will thus become popularized. The role of neurosonology in 21st century medicine is thus discussed by reference to neuronavigation as an example.

Preoperative Assessment of Gastric Cancer Vascularity by Flash Echo Imaging

Background: Tumor vascularity as indicated by immunohistochemical staining is a significant prognostic factor in gastric and other cancers. Non-invasive preoperative assessment of the vascularity of gastric cancers has not been possible. We aim to determine the reliability of harmonic flash echo imaging (FEI) for assessment of vascularity of gastric cancers by comparison with CD34 staining of resected specimens. Methods: Twelve patients undergoing surgical resection of advanced gastric cancer were studied. An ultrasound system transmitting ultrasound pulses at 2.3 MHz and receiving them at 4.6 MHz (second harmonic image) was used for harmonic FEI. Approximately 30 s after intravenous injection of ultrasonic contrast medium (SHU 508A, Levovist), second harmonics (4.6 MHz) emitted from microbubbles were obtained to enhance the B-mode images. Using the tumor image showing strongest enhancement in each FEI series, regions of interest were determined to measure mean echo intensity in the tumor. Immunohistochemistry using antibodies against CD34 was carried out in resected specimens. Tumor vascularity was determined by counting stained microvessels. Results: A significant positive correlation was noted between sonographic amplitude determined preoperatively by FEI analysis and number of CD34-stained microvessels in tumor specimens ( r = 0.869, P = 0.004). Conclusion: Vascularity of gastric cancers now can be evaluated non-invasively by harmonic FEI.

Enhancement of cytotoxicity of Bleomycine by shock waves : The effect of ultrasonic contrast medium

Enhancement of cytotoxicity of Bleomycine by shock waves : The effect of ultrasonic contrast medium

Microparticles as ultrasonic contrast media

Ultrasonic contrast media are provided comprising small particles with entrapped gas, where the compositions can be selected for rapid dissolution with production of microbubbles or maintaining the gas in microtubules, microchambers or microcracks, providing for echogenicity. The particles are readily formed by precipitation from a liquid, either solution or melt, of a monomeric material, followed by drying and mechanically reducing the size of the particles.

Transesophageal echocardiography and contrast‐TCD in the detection of a patent foramen ovale

Patent foramen ovale (PFO) is increasingly recognized in association with cryptogenic stroke. Using transesophageal echocardiography (TEE) and transcranial Doppler sonography with ultrasonic contrast medium (contrast-TCD), we evaluated the frequency of a PFO as the fundamental condition of paradoxical embolism in 111 patients after cerebral ischemia. There was a right-left shunt in 50 patients (45%) with TEE. In 31 of 40 patients with stroke of unknown etiology, a PFO was the only detectable finding associated with cerebral ischemia. Using TEE as the "gold standard," the sensitivity of contrast-TCD was 91.3%, specificity 93.8%, and the overall accuracy 92.8%. Contrast-TCD failed to detect a right-left shunt in four patients, but there were four other patients with negative TEE and positive contrast-TCD. We conclude that contrast-TCD is a highly sensitive method for detecting a right-left shunt. Its advantages are low cost, its ability to detect single contrast-medium embolism, and control of the Valsalva maneuver by observing the decrease of cerebral blood flow. Evidence of PFO in cryptogenic stroke should prompt a search for a subclinical venous thrombosis as the embolic source.

Usefulness of an intravenous contrast medium in the characterization of high-grade internal carotid stenosis with color Doppler-assisted duplex imaging.

The remaining limitations of ultrasonographic imaging in accurately quantifying internal carotid stenosis or diagnosing internal carotid occlusion may be overcome by enhancing the echogenicity of flowing arterial blood with contrast agents. This study assessed the usefulness of the intravenous (transpulmonary) contrast medium SH U 508 A in improving the characterization and quantification of severe internal carotid stenosis. We examined 32 patients (30 had vessels with a stenosis of greater than 70% luminal narrowing and 2 had vessel occlusions) using a 7.5-MHz linear-array transducer for color Doppler-assisted duplex imaging before and after injection of the contrast medium. The SH U 508 A-induced increase in carotid blood echogenicity began 11 +/- 2 (mean +/- SD) seconds after the start of the bolus injection, peaked at 21 +/- 2 dB, and showed a half-life of 75 seconds. Quantitative vascular measurements (cross-sectional luminal area reduction and plaque length, respectively) obtained before and after contrast application were highly correlated (r > .90). Visualization of the entire length of the intrastenotic residual flow lumen, however, was significantly improved by contrast enhancement (52% versus 83%, P = .01). This pilot study on patients with extracranial carotid artery disease suggested that ultrasonic contrast media may be most useful in improving the ultrasonography-based diagnosis of internal carotid occlusion.

Nachweis der Durchgängigkeit der Tubae uterinae mit der farbkodierten Duplexsonographie in Kombination mit Ultraschallkontrastmittel

Tubal patency was studied in 17 sterile women by means of colour-coded duplex sonography (CCDS) with local injection of an ultrasonic contrast medium. The results were compared with a conventional hysterosalpingogram. CCDS demonstrated all the soft tissues and their mobility. The ultrasonic contrast medium was SH U 454 (Schering). The colour signals generated by the air bubbles makes it possible to demonstrate tubal patency on both sides. The combination of an ultrasonic contrast medium and CCDS provides a simple, rapid, accurate and safe method for demonstrating tubal patency. Tubal patency can be demonstrated in the presence of anatomical complications and requires only a small amount of contrast medium.

Moving-picture corss-sectional echocardiography in normal children

Using a parallel-scan B-mode ultrasonic system (Vidoson, Siemens) 200 children with clinically normal hearts were examined. Using a cross-section parallel to the left sternal border, rapid and easily reporducible multi-frame echocardiograms were obtained with simultaneous presentation of the aortic, pulmonary and mitral valves. Interpretation of this cross-section, with echos from the three valves, the aortic route, pulmonary artery, right and left ventricles and left atrium, was checked against post-mortem studies and in-vivo contrast studies with ultrasonic contrast medium (indocyanine-green). As the described method is not ECG-triggered, only important morphological changes are demonstrable.