Harmonic Ultrasonography Research Articles

Classification of ultrasonographic images of small hepatocellular carcinoma using galactose-based contrast agent: relation between image patterns and histologic features.

The aim of this study was to establish the relation between observed ultrasonographic (US) images produced with a galactose-based contrast agent and histologic characteristics of small hepatocellular carcinomas (HCCs). A total of 64 nodules in 64 patients, 22 well differentiated and 42 moderately differentiated with a histologically proven HCC, smaller than 3.0 cm in diameter and who had undergone hepatectomy were consecutively examined by contrast-enhanced US using a galactose-based contrast agent. Perfusion images were acquired by intermittent high-intensity, harmonic power Doppler sonography using a high pulse-repetition frequency and high-pass filter setting. Perfusion images of the arterial and late phases were classified into several patterns and compared with the histologic findings obtained from resected specimens. Most of the well- and moderately differentiated resected HCCs showed hyperechoic change during the arterial phase. However, 13 (59%) of the well-differentiated HCCs showed isoechoic change and 27 (64%) of the moderately differentiated HCCs showed hypoechoic change during the late phase. The difference is statistically significant (P < 0.0001). In a comparison of microscopic portal invasion (vp) of HCCs using enhanced US patterns, both vp(-) and vp(+) groups showed a high incidence of the hypervascular pattern during the arterial phase; in contrast, during the late phase 11 (73%) of 15 vp(+) nodules showed hypoechoic change with spotty signals. This difference is statistically significant (P < 0.0001) when compared with a high incidence (52%) of signal defect in the vp(-) group. The existence of well-differentiated components associated with the periphery of moderately differentiated HCCs also correlated closely with patterns during the late phase (P < 0.01). Late-phase contrast-enhanced US images of small HCCs with a galactose-based contrast agent are useful for predicting specific histologic characteristics.

Treatment of hepatocellular carcinoma with percutaneous radiofrequency ablation: usefulness of contrast harmonic sonography for lesions poorly defined with B-mode sonography.

The purpose of this study was to assess the usefulness of contrast harmonic sonography guidance in percutaneous radiofrequency ablation of hepatocellular carcinomas that could not be adequately depicted by B-mode sonography. SUBJECTS AND METHODS. Twenty-one patients with 21 hepatocellular carcinomas prospectively underwent radiofrequency ablation treatment with contrast harmonic sonography as guidance. Twenty-five patients with 25 hepatocellular carcinomas were retrospectively selected as the historical control group under the same conditions as the study group; the control group patients were treated under B-mode sonography guidance. Twenty (95.2%) of the 21 patients were successfully treated during a single treatment session, and the remaining patient (4.8%) required two treatment sessions with contrast harmonic guidance. On the other hand, only eight (32%) of the 25 control subjects were successfully treated during a single treatment session using B-mode sonographic guidance without contrast imaging. The difference between these two groups was statistically significant (p = 0.002). Contrast harmonic sonography helps in the placement of radiofrequency ablation electrodes in hypervascular hepatocellular carcinomas that cannot be adequately depicted by B-mode sonography.

Evaluation of Lymph Node Perfusion Using Continuous Mode Harmonic Ultrasonography With a Second‐Generation Contrast Agent

To evaluate the contribution of continuous mode contrast-enhanced harmonic ultrasonography (CE-HUS) with a second-generation contrast agent to the characterization of superficial lymphadenopathies with respect to conventional ultrasonographic techniques (B-mode and power Doppler). Fifty-six lymph nodes from 45 patients were studied both by conventional techniques and by CE-HUS. The dimensions, intranodal architecture, margins, and location of vessels were evaluated. Subsequently, all the lymph nodes were examined by CE-HUS, and enhancement of echogenicity was evaluated. The diagnoses obtained by means of fine-needle aspiration cytologic examination, surgical biopsy, or both were compared with those obtained by ultrasonography. Of the lymph nodes examined, 30 were benign and 26 were malignant (18 metastases and 8 non-Hodgkin lymphomas). The study using CE-HUS showed intense homogeneous enhancement in 28 of 30 reactive lymph nodes; perfusion defects in 17, of which 15 were neoplastic and 2 were inflammatory; intense but inhomogeneous speckled enhancement in the early arterial phase in 5 cases of lymphoma; and, last, scarce or absent intranodal enhancement in 4 metastases. The specificity, sensitivity, and accuracy of conventional techniques in differentiation between benign and malignant lymph nodes were 76%, 80%, and 78% versus 93%, 92%, and 92.8% for CE-HUS. The increase in correct diagnoses was significant (P = .05) when conventional ultrasonography was tested against CE-HUS. Superficial lymph nodes can be characterized as being neoplastic or benign with a high degree of diagnostic accuracy on the basis of the perfusion characteristics evaluated by CE-HUS. This technique has been shown to afford a higher degree of accuracy than currently obtainable by any other ultrasonographic technique.

Current status of vesicoureteral reflux diagnosis.

In children, diagnostic imaging for vesicoureteral reflux (VUR) encompasses both radiologic and sonographic modalities. The former comprises voiding cystourethrography (VCUG), the most widespread method for examination for reflux, and radionuclide cystography (RNC). In RNC the radiation exposure is significantly less than in VCUG with continuous fluoroscopy, but the anatomic details depicted are much inferior. With the introduction of pulsed fluoroscopy, the radiation exposure of VCUG has been markedly curtailed. VCUG is the first imaging choice for the urethra. The sonographic diagnosis of VUR with the intravesical administration of an ultrasound (US) contrast agent-voiding urosonography (VUS)-is being used increasingly in the routine diagnostic imaging work-up of reflux. Various sonographic reflux examination methods had been tried in the past. The real breakthrough came with the availability of stabilized US contrast media. Further impetus came with the introduction of harmonic US imaging. The recent release of a second generation US contrast medium promises to make a further positive impact on VUS. The diagnostic accuracy of contrast-enhanced VUS has been found to be comparable to radiologic methods. VUS is primarily performed in follow-up studies and as the primary reflux examination modality in girls.

Percutaneous Radiofrequency Ablation Guided by Contrast-Enhanced Harmonic Sonography with Artificial Pleural Effusion for Hepatocellular Carcinoma in the Hepatic Dome

Percutaneous Radiofrequency Ablation Guided by Contrast-Enhanced Harmonic Sonography with Artificial Pleural Effusion for Hepatocellular Carcinoma in the Hepatic Dome

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.

Evaluation of hepatic focal nodular hyperplasia with contrast-enhanced gray scale harmonic sonography: initial experience.

To assess the potential of contrast-enhanced gray scale harmonic sonography in the evaluation of the typical vascular and enhancement patterns of hepatic focal nodular hyperplasia. Thirteen patients with 13 lesions of hepatic focal nodular hyperplasia underwent contrast-enhanced gray scale harmonic sonography. After the injection of a microbubble contrast agent (SH U 508A), gray scale harmonic sonographic studies using a Coded Harmonic Angio technique were performed with a combination of a period of continuous scanning to assess the vascular pattern (vascular imaging) and interval delay scanning to determine the sequential enhancement pattern (acoustic emission imaging). Each imaging pattern was categorized and analyzed by consensus of 2 experienced radiologists. In 12 (92%) of 13 lesions, vascular imaging during the arterial phase showed central arteries of a spoked wheel pattern, whereas the remaining lesion had stippled vascularity. On acoustic emission imaging, 11 (85%) of 13 lesions were hyperechoic during the early phase, and the remaining 2 (15%) were isoechoic compared with surrounding parenchyma. Ten (77%) of 13 lesions remained either hyperechoic (5 of 13) or isoechoic (5 of 13) during the delay phase, whereas the remaining 3 lesions (23%) were hypoechoic. Contrast-enhanced gray scale harmonic sonography showed the typical vascularity of a spoked wheel pattern during the vascular phase and persistent enhancement on serial acoustic emission imaging in most cases of hepatic focal nodular hyperplasia, and thereby it can be a promising technique in noninvasive diagnosis of this entity.

Radiofrequency ablation of liver cancer: early evaluation of therapeutic response with contrast-enhanced ultrasonography.

The early assessment of the therapeutic response after percutaneous radiofrequency (RF) ablation is important, in order to correctly decide whether further treatment is necessary. The residual unablated tumor is usually depicted on contrast-enhanced multiphase helical computed tomography (CT) as a focal enhancing structure during the arterial and portal venous phases. Contrast-enhanced color Doppler and power Doppler ultrasonography (US) have also been used to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic technology which has recently been introduced, allows for the detection of residual tumors after ablation, without any of the blooming or motion artifacts usually seen on contrast-enhanced color or power Doppler US. Based on our experience and reports in the literature, we consider that contrast-enhanced gray-scale harmonic US constitutes a reliable alternative to contrast-enhanced multiphase CT for the early evaluation of the therapeutic response to RF ablation for liver cancer. This technique was also useful in targeting any residual unablated tumors encountered during additional ablation.

Acute Relapses of Crohn's Disease On Follow-up: Can Contrast Enhanced Harmonic Sonography Differentiate Inflammatory vs. Fibro-Stenosing Forms? Busto Arsizio Hospital, Busto Arsizio, Italy.

Literature Reviews: SELECTED ABSTRACTS FROM THE OFFICIAL PROCEEDINGS OF THE 10TH CONGRESS OF THE WORLD FEDERATION FOR ULTRASOUND IN MEDICINE AND BIOLOGY: Obstetric Ultrasound: Abdominal Ultrasound: Contrast Agents

Early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma: utility of gray scale harmonic ultrasonography with a microbubble contrast agent.

To evaluate the utility of gray scale harmonic ultrasonography with a microbubble contrast agent in the early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma. Seventy-five patients with 81 nodular hepatocellular carcinomas (1.3-4.8 cm) treated with percutaneous radio frequency ablation were evaluated with contrast-enhanced gray scale harmonic ultrasonography after intravenous bolus injection of a galactose-based microbubble contrast agent. The vascularity within the ablation zones was evaluated with a continuous scan for 3 to 5 seconds between 15 and 30 seconds after initiation of contrast agent injection. To evaluate the perfusion of the ablation zones, intermittent stimulated acoustic emission imaging was performed with a rapid sweeping technique from the end of the continuous scan. All patients underwent follow-up 3-phase helical computed tomography at 1 month after radio frequency ablation and were followed for at least 1 year. The results of contrast-enhanced ultrasonography were compared with those of follow-up computed tomography in terms of the presence or absence of residual unablated tumors. In 10 (12%) of the 81 treated hepatocellular carcinomas, contrast-enhanced ultrasonography showed either nodular or crescentic enhancing foci at the margins of ablation zones, suggesting residual unablated tumors. Contrast-enhanced computed tomography obtained 1 month after radio frequency ablation confirmed the residual unablated tumors in the same 10 lesions. Diagnostic agreement between 1-month follow-up computed tomography and contrast-enhanced ultrasonography was achieved in all 81 cases (100%). Contrast-enhanced gray scale harmonic ultrasonography can be a reliable alternative to contrast-enhanced computed tomography in the early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma.

Differential diagnosis of hepatic tumors by using contrast enhancement patterns at US.

To assess the accuracy of pattern-based classification of contrast material-enhanced wideband harmonic gray-scale ultrasonographic (US) images in the differential diagnosis of hepatic tumors. A total of 183 hepatic lesions in 183 patients were studied; lesions included 116 hepatocellular carcinomas, 42 liver metastases, and 25 liver hemangiomas. After injection of a galactose-palmitic acid contrast agent, lesions were scanned with contrast-enhanced wideband harmonic gray-scale US in the arterial, portal venous, and late venous phases. The enhancement patterns were classified, and multiple logistic regression analysis was used to identify diagnostic patterns that enabled differentiation between hepatic tumors. Five enhancement patterns were found to be significant in predicting different hepatic tumors. In hepatocellular carcinomas, the presence of intratumoral vessels in the arterial phase and homogeneous or heterogeneous enhancement in the portal phase were the most typical patterns. In metastases, the absence of intratumoral vessels in the arterial phase and ring enhancement or a perfusion defect in the portal phase were the most typical patterns. In hemangiomas, the absence of intratumoral vessels in the arterial phase and peripheral nodular enhancement in the portal phase were the most typical patterns. The sensitivity, specificity, and accuracy of diagnosis based on combinations of enhancement patterns were, respectively, 94.8%, 94.0%, and 94.5% for hepatocellular carcinoma; 90.5%, 94.3%, and 93.4% for metastasis; and 88.0%, 99.4%, and 97.8% for hemangioma. Contrast-enhanced wideband harmonic gray-scale US is a useful tool for differentiating among the hepatic tumors studied.

Comparison of contrast-enhanced harmonic ultrasonography and power Doppler ultrasonography for depicting vascularity of hepatocellular carcinoma identified by angiography-assisted CT

The sensitivity of contrast-enhanced harmonic gray scale imaging was compared with that of power Doppler sonography in depicting tumor vascularity and contrast enhancement of hepatocellular carcinoma (HCC) identified by angiography-assisted computed tomography (CT). One hundred thirty-nine classic HCC nodules (108 patients), each appearing as a high-attenuation mass on early-phase CT during hepatic arteriography and as a perfusion defect on CT during arterial portography, were evaluated. Vascular findings and contrast enhancement patterns were evaluated by contrast-enhanced harmonic gray scale imaging. Arterial pulsatile flow into each nodule was checked by power Doppler sonography. Sensitivity of each modality for depicting tumor vascularity was examined by angiography-assisted CT findings as the gold standard. The sensitivity of contrast-enhanced harmonic gray scale imaging (134/139, 96.4%) was significantly greater than that of power Doppler sonography (96/139, 69.1%) ( P<0.05). Twenty-six of twenty-seven nodules (96.3%) in the lateral segment, in which motion artifact is likely, were enhanced by contrast-enhanced harmonic gray scale imaging. Contrast-enhanced harmonic gray scale imaging is more sensitive than power Doppler sonography and is a noninvasive method that can be used as effectively as angiography-assisted CT to evaluate tumor vessels and contrast enhancement of HCC.

Renal blood flow measurement with contrast-enhanced harmonic ultrasonography: evaluation of dopamine-induced changes in renal cortical perfusion in humans.

An accessible non-invasive method for evaluating renal regional blood flow in real time is highly desirable in the clinical setting. Recent progress in ultrasonography with microbubble contrast has allowed quantification of regional blood flow in animal models. Goal ofthis study was to establish a convenient contrast--enhanced harmonic ultrasonography (CEHU) method for evaluating renal cortical blood flow in humans. We carried out intermittent second harmonic imaging in 9 healthy volunteers. Pulse interval was progressively decreased from 4 s - 0.2 s during continuous venous infusion of the microbubble contrast agent. Pulse interval versus CEHU-derived acoustic intensity plots provided microbubble velocity (MV) and fractional vascular volume (FVV) during renal cortical perfusion in humans. Low-dose dopamine infusion (2 microg/min/kg) resulted in a significant increase in MV which correlated well with the increase in total renal blood flow (RBF) determined by a conventional study of p-aminohippurate clearance (C(PAH)) (r = 0.956, p < 0.0001). Although FVV was not significantly increased, alterations in CEHU-derived renal cortical blood flow calculated by the products of MV and FVV were also correlated with alterations in total RBF (r = 0.969, p < 0.0001). Thus, low-dose dopamine infusion increases renal cortical blood flow observed in CEHU, mainly by increasing MV. The present study shows that renal cortical blood flow in humans can be measured non-invasively by CEHU and that CEHU can be used for quantitatively evaluating changes induced by a therapeutic agent such as dopamine in flow velocity and in FVV.

Harmonic US in hepatobiliary disease

Harmonic ultrasound (US) is a new sonographic imaging method that exploits the effect of nonlinear propagation on the acoustic signal as it travels through the human body or tissue. It produces sonographic images by using second harmonic signals generated by tissue itself during this nonlinear propagation of insonated acoustic energy. The resultant advantages are improved lateral resolution, reduced side lobe artifact, and increased signal-to-noise ratio. Our recent clinical studies using tissue harmonic US showed that tissue harmonic US provided significantly better image quality in both solid and cystic hepatic structures than conventional imaging, and enabled significantly improved image quality and improved diagnostic accuracy in evaluation of gallbladder disease. Harmonic US enhances the signals from contrast over those from tissue, since the contrast agent microbubbles generate far more harmonic energy than tissue does. New promising contrast-enhanced US techniques are pulse inversion harmonic, coded harmonic angio (CHA), and agent detection imaging (ADI). CHA uses codes to suppress the fundamental signal, and uses decoding techniques optimized for contrast agents, to suppress tissue signal, thus, improving sensitivity and uniquely optimizing for contrast signal visualization in dynamic flow states. ADI is a microbubble-specific mode that is designed for optimal detection of stimulated acoustic emission from a fragile agent such as Levovist, and is characterized as its high mechanical index that provides extreme sensitivity to the presence of microbubble. Our recent clinical experience of contrast-enhanced harmonic US with Levovist will be presented in various diseases of hepatobiliary system.

Effect of Levovist® on splanchnic hemodynamics in cirrhotic patients

This study was aimed to assess the effect of Levovist® on Doppler parameters of splanchnic hemodynamics. A total of 12 patients with cirrhosis and 12 healthy subjects underwent Doppler ultrasound (US) examination of the portal vein and of the hepatic, splenic and superior mesenteric arteries before, 5 to 8 and 12 to 15 min after the start of an 8-min long IV infusion of 2.5 g of Levovist®. Mean velocity and mean diameter were calculated for the portal vein. Resistance index was determined for the arteries. A significant increase of resistance index was observed in the hepatic (0.80 ± 0.07 vs. 0.71 ± 0.06; p < 0.01) and splenic arteries (0.72 ± 0.06 vs. 0.64 ± 0.06; p < 0.01) 5 to 8 min after contrast agent injection in patients with cirrhosis, but not in controls. Neither portal vein diameter nor portal flow mean velocity changed during the test in both controls and cirrhotic patients. This effect might be related to a selective trapping of microbubbles in the altered hepatic and splenic microvasculature in patients with cirrhosis rather than being artefactual. It might have implications on harmonic imaging US protocols designed to image the cirrhotic liver in the early arterial phase. (E-mail: sgaiani@med.unibo.it)

Hepatocellular carcinoma treated with radiofrequency ablation: evaluation of posttreatment response with a new contrast-enhanced harmonic sonography

Hepatocellular carcinoma treated with radiofrequency ablation: evaluation of posttreatment response with a new contrast-enhanced harmonic sonography

Contrast-enhanced harmonic sonography in the evaluation of therapeutic response to radiofrequency ablation of hepatocellular carcinoma. initial report

Contrast-enhanced harmonic sonography in the evaluation of therapeutic response to radiofrequency ablation of hepatocellular carcinoma. initial report

Splenic trauma: evaluation with contrast-specific sonography and a second-generation contrast medium: preliminary experience.

To report our experience in the assessment of splenic trauma with contrast-coded sonography and a second-generation contrast medium. From January to May 2002, 120 patients were studied with sonography for suspected splenic trauma. Twenty-five were selected for further imaging because of sonographic findings positive for splenic injury, findings positive for peritoneal fluid only, indeterminate findings, and negative findings with high clinical or laboratory suspicion. These patients underwent contrast-enhanced harmonic sonography and contrast-enhanced helical computed tomography. Among the 25 patients studied, 6 had no spleen trauma at initial and follow-up evaluation. One patient had a hypoperfused spleen without parenchymal damage, and 18 had splenic injuries; these 19 patients were considered positive. Hemoperitoneum was identified by sonography, contrast-enhanced sonography, and contrast-enhanced computed tomography in 74% of the 19 positive cases. Perisplenic clots were recognized in 58% of the cases by computed tomography and in 42% by baseline and enhanced sonography. Splenic infarctions were found in 11% of cases by contrast-enhanced sonography and computed tomography; none was found by unenhanced sonography. Parenchymal traumatic lesions were identified in 12 of 18 patients with splenic injuries by unenhanced sonography, in 17 cases by contrast-enhanced sonography, and in all 18 cases by contrast-enhanced computed tomography. A minimal splenic lesion was found in the single patient with a false-negative contrast-enhanced sonographic finding. Contrast-enhanced sonography correlated appreciably better than unenhanced sonography in detecting injuries and in estimating their extent. Findings undetectable on unenhanced sonography were also noted: splenic hypoperfusion in 11% of positive cases on both contrast-enhanced sonography and contrast-enhanced computed tomography, contrast medium pooling in 21% of cases on both contrast-enhanced sonography and computed tomography, and contrast extravasation in 11% of cases on computed tomography and 5% on contrast-enhanced sonography. Contrast-enhanced sonography is a promising tool in the assessment of splenic trauma. In institutions where sonography is used as the initial procedure, this technique may increase its effectiveness.

Specificity of contrast-enhanced harmonic sonography for characterization of solid, incidentally detected focal liver lesions

Specificity of contrast-enhanced harmonic sonography for characterization of solid, incidentally detected focal liver lesions

Acute relapses of Crohn’s disease on follow-up: can contrast enhanced harmonic sonography differentiate inflammatory vs. fibro-stenosing forms?

Acute relapses of Crohn’s disease on follow-up: can contrast enhanced harmonic sonography differentiate inflammatory vs. fibro-stenosing forms?