Harmonic US Research Articles

Harmonic Scalpel® treatment of haemorrhoidectomy versus Milligan–Morgan's method

Haemorrhoidal disease develops slowly. In comparison to electrocautery, surgical intervention with the Harmonic Scalpel® shear is a revolutionary approach for ablation of symptomatic fourth and third degree haemorrhoids. In contrast to electrocautery, Harmonic Scalpel® causes less discomfort because of its restricted lateral thermal injury during tissue dissection. The purpose of this study was to observe how effective Harmonic Scalpel® is at reducing postoperative problems after a haemorrhoidectomy. A harmonic US scalpel device was utilized to do the hemorrhoidectomy in group A, while a monopolar electrocautery device was employed in group B, which included 82 individuals. In this study, postoperative pain was more statistically significant in the Harmonic haemorridectomy group A than in group B haemorridectomy, in keeping with a pain numerical analogue scale of 1 to 10. The postoperative pain in group A was statistically significant on the 1st, 2nd, 4th, 7th, 14th, and 28th days of follow up, p<0.001. Time off work and patient satisfaction were statistically significant in the harmonic group, 2.50±0.066 compared to the surgery group, 3.56±0.070 (p<0.05). Healing of postoperative ulcers was statistically significant in the harmonic group (2.640.062 vs. 4.120.062 in surgery) (p<0.037).

Efficacy of Harmonic US and LigaSure in Surgical Treatment of 3rd and 4th Degree Internal Hemorrhoids versus Conventional Hemorrhoidectomy

Efficacy of Harmonic US and LigaSure in Surgical Treatment of 3rd and 4th Degree Internal Hemorrhoids versus Conventional Hemorrhoidectomy

Difference-Frequency Ultrasound Imaging With Non-Linear Contrast.

Conventional ultrasound imaging is based on the scattering of sound from inhomogeneities in the density and the speed of sound and is often used in medicine to resolve pathologic compared to normal tissue. Here we demonstrate a difference-frequency ultrasound (dfUS) imaging method that is based on the interaction of two sound pulses that propagate non-collinearly and intersect in space and time. The dfUS signal arises primarily from the second-order non-linear coefficient, a contrast mechanism that differs from linear and harmonic US imaging. The distinct contrast mechanism allows dfUS to image anatomic features that are not identifiable in conventional US images of salmon and pig kidney tissue. Further, dfUS produces enhanced contrast of glioblastoma tumor implanted in the mouse brain, revealing its potential for improving medical diagnosis. Progress towards a real-time system is discussed.

Small hepatocellular carcinomas: ultrasonography guided percutaneous radiofrequency ablation

Current guidelines advocate percutaneous radiofrequency (RF) ablation as a standard treatment of early stage hepatocellular carcinoma (HCC) for up to three tumors ≤3 cm in diameter. The local efficacy evaluated with short-term radiological examination may be overrated, whereas that assessed by histopathological measure might be underestimated. Long-term clinical follow-up studies guarantee the effectiveness of RF ablation for small HCC, which is now almost comparable in benefits to surgical resection. US is the most common guiding modality for percutaneous RF ablation for small HCC. However, the technical feasibility is often limited due to poor conspicuity of the index tumor on US. Implementation of artificial ascites, contrast-enhanced harmonic US, and fusion imaging of US with CT/MR can be helpful to enhance the technical feasibility of US-guided RF ablation of small HCC.

Preserving enhancement in freeze-dried contrast agent ST68: Examination of excipients

The perfluorcarbon (perfluorobutane) ultrasound contrast agent ST68, composed of sonicated mixtures of non-ionic surfactants, is stable in solution for only a few weeks at 4 °C. Freeze-drying critically diminished ST68's ability to reflect ultrasound (its echogenicity). A method of incorporating specific lyoprotectants before lyophilization was investigated. Reintroduction of perfluorobutane to the protected freeze-dried sample, followed by reconstituting with water preserved echogenicity. Glucose, trehalose, sucrose, and mannitol were tested at 100 mM and in vitro echogenicity data was collected from samples with dose concentrations of 50–300 μl/l. Glucose was found to be the best lyoprotectant providing an average ( n = 3) maximum peak enhancement of 23.2 ± 1.2 dB in vitro, measured at 5 MHz, 684 kPa, and a pulse repetition frequency (PRF) of 100 Hz ( p < 0.05 over freeze-dried ST68 control) and 20.8 ± 0.8 dB in vivo in New Zealand white rabbits at 5 MHz and a PRF of 6.7 kHz. Pulse inversion harmonic US images of a rabbit kidney, pre- and post-contrast injection (0.1 ml/kg), showed excellent enhancement and clear vascular delineation, similar to that of the original agent. For the first time this contrast agent can be successfully freeze-dried yielding a longer self-life without the need for refrigeration.

Breast Cancer in Women: Evaluation of Benign and Malignant Axillary Lymph Nodes with Contrast-Enhanced Ultrasound

We assessed the value of contrast-enhanced US for differentiating between benign and malignant axillary lymph nodes in breast cancer. A total of 120 axillary lymph nodes in 92 patients with breast cancer were studied. All patients underwent grayscale US examination, unenhanced and enhanced color and power Doppler US, and enhanced grayscale harmonic US examination. The mean size of the 120 axillary lymph nodes was 1.5 cm (range 0.5 - 3.4 cm). Of all 120 axillary lymph nodes studied, 80 (67 %) were malignant and 40 (33 %) were benign according to pathological examination. The total number of vessels in baseline US did not increase between benign and malignant lymph nodes (3.3 +/- 2.2 vs. 5.4 +/- 4.0; p > 0.05). The total number of peripheral vessels was 0.5 +/- 0.8 for benign lymph nodes vs. 2.0 +/- 1.7 for malignant lymph nodes (p > 0.05). Enhanced US studies showed enhancement in both benign and malignant lymph nodes after contrast administration with a significantly higher degree of enhancement in malignant lymph nodes (p < 0.01). The total number of vessels was significantly higher in malignant lymph nodes after contrast administration (17.3 +/- 8.0 vs. 8.2 +/- 5.1, p < 0.01). Malignant lymph nodes demonstrated longer contrast enhancement duration compared to benign lymph nodes. This preliminary data shows that contrast-enhanced US can differentiate between benign and malignant lymph nodes in breast cancer.

Characterization of benign and malignant solid breast masses in harmonic 3D power Doppler imaging

Purpose The authors assessed the characteristics of benign and malignant solid breast tumors in harmonic three-dimensional (3D) power Doppler imaging and proposed decision models to classify benign and malignant breast tumors. Materials and methods A total of 86 malignant and 97 benign harmonic 3D power Doppler US images were analyzed. All the harmonic 3D power Doppler images were obtained using a Voluson730 US system (GE, Zipf, Austria) equipped with a RSP 6–12 transducer and tissue harmonic imaging modalities. Imaging analysis was performed using the Virtual Organ Computer-aided Analysis (VOCAL)-imaging program. Histogram indices, the vascularization index (VI), flow index (FI) and vascularization-flow index (VFI), were calculated for the intra-tumor and for shells with an outside thickness of 3 mm surrounding the breast tumors. The receiver operating characteristic (ROC) curves were calculated to estimate the diagnostic performances. Results The results revealed that the choice of decision model comprised the parameters of patient age, intra-tumor VI, and tumor volume to classify benign and malignant breast tumors. The area under the ROC curve (Az) was 0.910, accuracy was 81.4%, and sensitivity and specificity were 81.4% and 81.4%, respectively. The parameter intra-tumor VI was the choice for all of the histogram indices in differentiating between malignant and benign lesions. Conclusion The decision model, which was composed of patient age, tumor volume and intra-tumor VI, and a cut-off value for intra-tumor VI at the upper end of patient age and tumor volume, was recommended in clinical application.

Échographie des tendons de la coiffe en mode harmonique : les clivages sont-ils enfin visibles ?

For some, cleavage tears remain a pitfall of sonography (US). The purpose of this study is to demonstrate the visibility of intratendinous tears of the supraspinatus and infraspinatus tendons and describe their imaging features on tissue harmonic US. Prospective study of 52 patients with suspected cuff pathology who underwent US prior to CT-arthrography, CT-bursography or MR arthrography. The US examinations were performed using 7-15 MHz transducers with tissue harmonic mode (pulse subtraction). An intratendinous tear was suggested by the presence of a hypoechoic intratendinous line, extending from a partial or full thickness tear. Results from US were correlated to contrast material enhanced CT or MR findings. Ten cases of cleavage tears were detected on US compared to 18 on arthrographic examinations. False negative results occurred in poor US candidates (n=4), excessively retracted tendons (n=2) or postsurgical cuffs (n=2). Sensitivity was 55% and specificity was 94%, with PPV of 83% and NPV of 80% for the detection of intratendinous tear. The accuracy of US was lower for intratendinous tear associated with full thickness tears (5/11) compared to intratendinous tears associated with partial thickness tears (5/6). We demonstrate that cleavage tears are now visible on US using high-frequency transducers and tissue harmonic mode. However, the sensitivity remains too low, especially in patients with full thickness tear, postsurgical patients and patients that are poor candidates to US.

Harmonic US imaging of appendicitis in children

Harmonic imaging (HI), a relatively new ultrasound modality, was initially reported to be of use only in obese adult patients. HI increases the contrast and spatial resolution resulting in artefact-free images, and has been shown in adults to significantly improve abdominal sonography. Regarding its application in paediatric patients, just a handful reports exist and these do not encompass its use in intestinal sonography. To compare the sonomorphological image quality of HI and fundamental imaging (FI, conventional grey-scale imaging) in the diagnosis of histologically confirmed appendicitis in children. For this prospective comparative study, 50 children (male/female 25/25; mean age 9.9 years) suspected of having appendicitis were recruited. In all patients US examination of the appendix and periappendiceal region was performed preoperatively and appendectomy carried out. The final diagnosis was based on histological examination of the appendix. Both FI and HI were used in the US examination (tissue harmonic imaging, THI; Sonoline Elegra, Siemens; 7.5 MHz linear transducer). A detailed comparison of the images from FI and HI was performed using a scoring system. The parameters compared included delineation of the appendiceal contour, wall, mucosa, contents of the appendix and surrounding tissues. Furthermore, periappendiceal findings such as mesenteric echogenicity, free fluid, lymph nodes and adjacent bowel wall thickening were compared. In 43 children (86%) acute appendicitis was histologically confirmed. The inflamed appendix could be depicted in the HI and FI modes in 93% and 86%, respectively. HI was found to be significantly better for the depiction of the outer contour, wall, mucosa and contents of the appendix (P<0.01). This was also true for the demonstration of free fluid, mesenteric lymph nodes, adjacent bowel walls and mesenteric echogenicity. HI should be the preferred modality for scanning the right lower abdomen in suspected acute appendicitis. The diagnosis of acute appendicitis can then be more definitely ascertained.

Contrast Enhanced Ultrasound for Radio Frequency Ablation of Canine Prostates: Initial Results

We determined the feasibility of contrast enhanced ultrasound for radio frequency ablation of the entire prostate as a method of minimally invasive treatment for prostate cancer in a canine model. Approval of the Institutional Animal Use and Care committee was obtained. Initially 5 dogs (group 1) were tested using variable power (5 to 30 W), time (4 to 12 minutes), bolus (0.01 to 0.04 ml/kg) and infusion (3 to 11 ml per minute at 0.015 microl/kg) injections of an ultrasound contrast agent with conventional grayscale power Doppler and pulse inversion harmonic imaging to establish optimal parameters. Subsequently 4 dogs (group 2) underwent entire prostate ablation using parameters based on group 1. The size of the thermal lesions and residual viable tissue was measured with ImageJ software (National Institutes of Health, Bethesda, Maryland) on ultrasound and pathological study. Linear regression and Student's t test were used for statistical analysis. A bolus of 0.04 ml/kg, an infusion of 11 ml per minute at 0.015 microl/kg and the contrast enhanced pulse inversion harmonic imaging mode were ranked best for guiding ablation. Thermal lesion volume was proportional to ablation power and time. There was no significant difference in measured thermal lesion size in group 1 between ultrasound and pathological findings (mean +/- SD 1.51 +/- 0.74 and 1.46 +/- 0.74 cm3, p = 0.56) or in residual viable tissue in group 2 (0.43 +/- 0.043 and 0.41 +/- 0.291 cm3, p = 0.21). The average volume of prostate ablation achieved in group 2 was 96.3%. Contrast enhanced pulse inversion harmonic imaging is able to guide, monitor and control radio frequency ablation of the entire prostate.

Usefulness and limitatin of contrast-enhanced power Doppler EUS for diagnosis of pancreatic diseases

Aims: Our purpose is to assess usefulness of contrast-enhanced power Doppler EUS (CE-EUS) for depiction and differential diagnosis of pancreatic tumors, as compared with contrast-enhanced harmonic US (CE-US) and contrast-enhanced CT (CE-CT). Subjects and methods: Consecutive 119 patients with suspicious pancreatic tumors received CE-CT, CE-EUS and CE-US. Coded phase-inversion harmonic mode (GE Logiq 9) which depicts signals from bubbles in fine vessels was used for CE-US. Power Doppler mode was used for CE-EUS (OLYMPUS GF-UC240P-AL5). Levovist was employed as the ultrasound contrast agent for CE-US and CE-EUS. CE-CT was imaged 30 and 60 seconds after the injection of contrast media. Sensitivities in depicting tumors and in differetiating ductal carcinomas from the other tumors were compared between the 3 modalities. Results: When hypovascular nodules relative to their surrounding tissue were defined as ductal carcinomas, the sensitivity on CE-EUS (69%) was significantly lower than those on CE-CT (82%) and CE-US (88%). However, values for sensitivity in depicting small pancreatic tumors of 2cm or less on CE-US (91%) and EUS (95%) were significantly higher than that on CE-CT (56%). Concerning to those small tumors, the values for sensitivity in differentiating ductal carcinomas from the other tumors were 40%, 73% and 67% on CE-CT, CE-US and CE-EUS, respectively. EUS depicted 7 of 9 ductal carcinomas that CE-CT failed to depict, 5 of which were hypovascular on CE-EUS. Conclusion: Although CE-EUS has limitation in differentiating pancreatic tumors due to artifact such as blooming and overpainting, it may be useful for differential diagnosis of small nodules of the pancreas which the other modalities failed to depict. The invention of the technology of contrast-enhanced harmonic EUS would further improve the abilities in depicting and differentiating small tumors.

1089: Treatment response and treatment guidance of hepatocellular carcinoma: Value of contrast-enhanced harmonic US and RVS

Introduction: In 1999, an ultrasound contrast agent was introduced in Japan to the clinical practice of hepatology, especially to the diagnosis and treatment of hepatocellular carcinoma (HCC). Drastic change in the strategies both in the diagnosis and treatment of HCC has been achieved both by contrast agent and the associated innovation of ultrasound technologies. In this lecture, the present status of the new strategy brought by advances of US technologies in the diagnosis, evaluation of treatment response and treatment guidance will be presented. Role of harmonic imaging in the differential diagnosis of hepatic tumors. On contrast harmonic US, typical hemodynamic pattern of HCC, is demonstrated as abundant tumor vessels supplying from the periphery to the center of the tumor and dense tumor parenchymal stain with fast washout in high sensitivity and specificity. Characteristic hemodynamic pattern of metastases is peripheral tumor vessels with rim parenchymal stain in the vascular phase followed by perfusion defect in postvascular phase. Hemangiomas show hypovascular in the early arterial phase with gradual spotty or cotton-wool pooling lasting up to late vascular phase, which is only detected by the long interval-delay scanning. Dysplastic nodules are demonstrated as no early arterial supply with isovascularity in late vascular phase. Focal nodular hyperplasias are demonstrated as spoke-wheel pattern of blood vessels accompanied by dense stain at interval-delay scanning. Pure Arterial Phase Imaging. In 2005, a breakthrough technology, pure arterial phase imaging, which can depict only arterial accumulated MIP images, was developed by the advancement of raw data store technique and accumulation technique. By using these techniques, whether blood supply in the tumor is arterial or portal origin can be clearly depicted, which is not possible by CT or MRI. This is an innovative technique to differentiate premalignant lesion from overt HCC. Application of harmonic imaging to the treatment of HCC evaluation of treatment responses. Harmonic US is extremely useful in the evaluation of posttreatment response of HCC after Lipiodol TAE. Harmonic US can extract only the blood flow echoes created by destruction of microbubbles, whilst echoes from tissue are effectively cancelled. This mode makes it possible to clearly depict residual blood flow in tumors after RFA or PEI therapy. Real-time needle insertion guidance for local treatment of HCC. The capability of harmonic US for depicting residual cancer cells in HCCs after treatment facilitates a correct guidance for the insertion of a needle on US monitoring, which cannot be achieved by any other imaging modalities including CT or MRI. Real-time virtual sonography. Recently, concurrent real-time imaging of MDCT and US is easily obtained, which is called as real-time virtual sonography. This technique extremely facilitates the treatment guidance for HCC. Conclusion. The newly introduced sonographic technique is drastically changing the diagnostic and therapeutic strategy of HCC, resulting in an eventual improvement in the prognosis of HCC patients.

2289: Focal nodular hyperplasia indeterminate at multiphase helical CT: Diagnostic performance of contrast-enhanced harmonic US in differentiating from hepatocellular carcinoma and adenoma

2289: Focal nodular hyperplasia indeterminate at multiphase helical CT: Diagnostic performance of contrast-enhanced harmonic US in differentiating from hepatocellular carcinoma and adenoma

3018: Characterization of hepatic hemangioma: The superiority of real-time compound US and pulse inversion harmonic US to conventional US

3018: Characterization of hepatic hemangioma: The superiority of real-time compound US and pulse inversion harmonic US to conventional US

3581: Clinical application of renal perfusion image using harmonic US with microbubble contrast agent

3581: Clinical application of renal perfusion image using harmonic US with microbubble contrast agent

3256: The application of harmonic US with microbubble contrast agent in patients with benign and malignant ovarian tumors

3256: The application of harmonic US with microbubble contrast agent in patients with benign and malignant ovarian tumors

Kontrastmittelgestützte „Low-MI-Real-Time”-Sonographie zur Beurteilung der Dignität fokaler Leberläsionen

Contrast enhanced sonography using phase-inversion harmonic mode is a promising technique to detect and characterize hepatic lesions. Aim of the following study was to evaluate whether this technique can characterize liver tumors. During January and December 2004, 46 patients with a solitary liver lesion were examined. The age of the 21 women and 25 men ranged between 37 and 82 years. The tumor size was between 8 mm and 14.5 cm. First conventional B-mode sonography and color-coded sonography were performed, followed by intravenous injection of the contrast agent SonoVue and continuous sonographic examination over 5 minutes using "low MI real-time" phase-inversion mode. The examination was video taped. The enhancement was evaluated qualitatively. Of the 21 malignant lesions, 20 could be correctly diagnosed as malignant. One of the malignant lesions was classified as benign. Of the 25 benign lesions, 21 could be classified correctly as benign, however, 4 lesions (2 hemangiomas, 1 adenoma, 1 teratoma) showed no enhancement in the portal and late phase and were incorrectly classified as malignant as well. Using pulse-inversion harmonic US with SonoVue, liver lesions showing an isoechoic or hyperechoic enhancement can be classified as probably benign. Further work up is necessary in case of little or no enhancement on delayed phase imaging.

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.

Harmonic US imaging of vesicoureteric reflux in children: usefulness of a second generation US contrast agent.

Contrast-enhanced voiding urosonography (VUS) is largely accepted both for the diagnosis and follow-up of vesicoureteric reflux (VUR) in children. To evaluate the usefulness of contrast-enhanced second-harmonic VUS in the diagnosis and grading of VUR, using a second-generation contrast agent. Eighty consecutive children were prospectively studied with contrast-enhanced second-harmonic VUS. All children received a second-generation contrast medium, constituted by phospholipid-stabilized microbubbles of sulphur-hexafluoride (SonoVue, Bracco, Milan, Italy). US monitoring of the bladder, of the retrovesical space and of the kidneys was performed using, alternatively, both tissue-harmonic and contrast-harmonic modes. In those young boys where VUR was depicted at VUS, examination was completed with transperineal, sagittal urethral exploration during micturition. VUR was graded in five steps and diagnoses were compared with voiding cystourethrography (VCUG). VUR was diagnosed in 52 reno-ureteral units with VUS. In 49 of these reno-ureteral units, VCUG confirmed the presence of VUR. In comparison to VUS, sensitivity and negative predictive value of VCUG were inferior. The grade of VUR detected at VUS was higher than that detected at VCUG in three units. In no case was the grade of VUR detected at VCUG higher than the one detected at VUS. The differences between VUS and VCUG in grading VUR were statistically significant (p=0.02). Imaging of the normal posterior urethra was skilfully demonstrated with US in 15 young boys with VUR. No statistically significant differences were found between tissue-harmonic and contrast-harmonic mode (p=0.102). Contrast-enhanced second-harmonic VUS is a sensitive and easy technique for the evaluation of VUR. A second-generation US contrast medium such as SonoVue, if available, should be the first choice as the dose required for one examination is much lower and consequently significant reduction of contrast agent cost is possible.

Hepatocellular carcinoma: spectrum of contrast-enhanced gray-scale harmonic sonography findings.

Sonography (US) is the most commonly used tool in the assessment of patients with chronic liver disease. Nevertheless, small nodules can be overlooked. Moreover, even if the lesion is readily recognizable, difficulty persists in differentiating hepatocellular carcinoma (HCC) from pre-tumoral, dysplastic stages of nodule evolution. In addition, US is the main tool in guiding percutaneous ablation therapies for HCC and in evaluating patients after treatment, but changes are not specific and difficulties persist in recognizing residual tumor during and after the ablation procedure. Contrast-enhanced, gray-scale, harmonic US offers new possibilities in the imaging of liver tumors. The real-time, low-mechanical index technique employed in our institution allows a true dynamic assessment of the tumor during the various phases of contrast medium circulation. This pictorial essay focuses on typical and atypical appearances of HCC when imaged with contrast-specific, real-time US. Findings useful for lesion detection, differential diagnosis, posttreatment assessment, and follow-up especially are illustrated. The potential role of contrast-enhanced US in various clinical settings is emphasized.