Contrast-enhanced Ultrasound Technique Research Articles

Contrast-enhanced endoscopic ultrasound.

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) introduced guidelines on the use of contrast-enhanced ultrasound (CEUS) in 2004. This EFSUMB-document focused mainly on liver applications. However, new applications extending beyond the liver were developed thereafter. Increased interest in recent years in CEUS technique and in the application of CEUS in novel fields like endoscopic ultrasound (EUS) has revolutionized indications and applications. As a result, the EFSUMB initiated a new update of the guidelines in 2011 to include this additional knowledge. Some of the contrast-enhanced EUS (CE-EUS) indications are established, whereas others are preliminary; these latter indications are categorized as emergent CEUS applications since the available evidence is insufficient for general recommendation. This article focuses on the use of CE-EUS in various clinical settings. The reader will get an overview of current indications and possible applications of CE-EUS. This involves the introduction of different contrast studies including color Doppler techniques (known as contrast-enhanced high mechanical index endosonography or CEHMI-EUS) as well as more modern high-resolution contrast-enhanced techniques (known as contrast-enhanced low mechanical index endosonography or CELMI EUS).

A New Technique for Assessing Renal Transplant Perfusion Preoperatively Using Contrast-Enhanced Ultrasound (CEUS) and Three-Dimensional Ultrasound (3DUS) – A Porcine Model Pilot Study

This pilot study aims to assess the viability of using contrast-enhanced ultrasound (CEUS) in renal grafts while they are on hypothermic perfusion machines prior to transplantation. We assessed the vascularity and renal perfusion of machine-perfused porcine kidneys (Maastricht category II) using CEUS. Five kidneys were placed on hypothermic machine perfusion for up to 24 hours after retrieval. The kidneys were then scanned with a low MI contrast-specific preset and a bolus of 0.5 ml of Sonovue contrast agent was administered. Contrast-specific ultrasound images of the kidney were acquired in 2D and 3D. The five kidneys demonstrated variable flow rates on the perfusion machine (10 - 37 ml/min at 30 mmHg). The CEUS technique demonstrated good perfusion and flow patterns, similar to those seen in vivo, in four kidneys. One kidney had patent arteries up to the interlobar region but no contrast filling in the cortex or medulla. Small perfusion defects were seen in two of the perfused kidneys. CEUS appears to be a viable technique for assessing global perfusion and small defects within kidneys prior to transplantation. The flow patterns seen in vitro appear to correspond to those seen in vivo. Further work is required to evaluate the relevance of the flow dynamics measured.

Kontrastverstärkter Ultraschall der Skelettmuskulatur

Functional imaging can increase the role of imaging in muscular diseases, as alterations of muscle morphology alone are non-specific for a particular disease. A good example for these functional imaging techniques is to use contrast-enhanced ultrasound (CEUS) to visualize and quantify in vivo (patho-) physiological information about the skeletal muscle microcirculation. Perfusion, i.e. the blood flow per tissue unit including capillary flow, is an important functional parameter. Pathological changes of skeletal muscle perfusion can be found in various clinical conditions, such as degenerative or inflammatory myopathy or peripheral arterial disease (PAD). This article reviews the theoretical basics of functional radiological techniques for assessing skeletal muscle perfusion and focuses on applications of microvascular imaging by CEUS which has improved the diagnosis of these muscular disorders. For evaluation of myositis, CEUS is more efficient in the diagnostic work-up than routine b-mode ultrasound because CEUS can detect inflammation-induced muscular hyperperfusion in acute myositis. This has already been demonstrated by high-mechanical index techniques using a first generation ultrasound contrast agent. Low-mechanical index CEUS techniques that require the use of a second generation contrast agent allow real-time quantification of muscular microcirculation at rest and during exercise. Using this CEUS method, the influence of different exercise intensities on the microcirculation of the exercising muscle becomes detectable. Moreover, the arterial perfusion reserve in PAD can be adequately examined using low-mechanical index CEUS. Initial findings have shown that the arterial perfusion reserve in patients suffering from PAD is reduced in comparison to healthy volunteers. In conclusion, modern CEUS techniques can offer deeper insights in muscular (patho-) physiology than just illustrating unspecific myopathic manifestations using conventional diagnostic imaging, such as edematous or lipomatous changes, hypertrophy or atrophy.

Study on the Characteristics of Contrast-Enhanced Ultrasound and Its Utility in Assessing the Microvessel Density in Ovarian Tumors or Tumor-Like Lesions

Angiogenesis is a critical factor in tumor growth and metastasis, and microvessel density (MVD) was an important parameter for assessing vessels in tumors. However, radiologic assessment of tumor vascularity is not yet well established. In our study, we aimed at investigating the efficacy of contrast-enhanced ultrasonography (CEUS) in exploring the vascularity of the ovarian tumors or tumor-like lesions to assess the relationship between the parameters of the peak intensity (PI) and area under curve (AUC) on CEUS and MVD in ovarian masses. Compared to the contrast-enhanced ultrasound technique, conventional ultrasound shows limitation in differentiating benign and malignant ovarian tumors. The former is promising in improving the sensitivity of detecting small vessels and blood flow in ovarian tumors. Our results showed clear differences in enhancement patterns between benign and malignant ovary tumors or tumor-like lesions. The PI and AUC in the malignant tumors were significantly higher than those in the benign tumors or tumor-like lesions (p=0.001 and =0.01, respectively). The MVD was 43.1 ± 20.4 in the benign tumors or tumor-like lesions and was 65.3 ± 22.3 in the malignant ones (p= 0.01). In both the benign and malignant groups, the PI and AUC were correlated significantly with the MVD (r=0.595, p = 0.001; r =0.533, p = 0.003, respectively). The PI and AUC in CEUS can reflect the MVD in ovarin tumors. The PI and AUC of the ovarian masses in the contrast transvaginal sonography show significant correlation with the angiogenesis and may help in assessing tumor vascularity in ovarian masses.

CONTRAST-ENHANCED ULTRASOUND OF THE FELINE KIDNEY

Contrast-enhanced ultrasound offers a noninvasive means of subjectively and quantitatively evaluating renal perfusion in cats with renal disease, or in renal transplant patients. In this study, we characterized the pattern of ultrasonographic contrast enhancement in 16 normal feline kidneys in eight cats using contrast-enhanced power Doppler and contrast-enhanced harmonic ultrasound techniques. Mean time to peak contrast enhancement for the whole kidney was longer using contrast-enhanced harmonic ultrasound (16.8s, SD 4.7s) than contrast-enhanced power Doppler ultrasound (12.2s, SD 1.8s). The time to peak enhancement for the cortex alone in contrast-enhanced harmonic ultrasound was 13s (SD 3.2s), and for the renal medulla was 25.5s (SD 8.7s). The half time for washout of contrast agent was 39s (SD 14.5s) for contrast-enhanced harmonic ultrasound. The pattern of contrast enhancement in these normal feline kidneys can be used as normal reference values for the evaluation of clinical patients. Contrast-enhanced harmonic ultrasound may allow the differentiation between cortical and medullary perfusion patterns.

Non-invasive contrast enhanced ultrasound for quantitative assessment of tumor microcirculation. Contrast mixed mode examination vs. only contrast enhanced ultrasound examination

To evaluate the different ultrasound techniques for quantification of contrast enhanced ultrasound (CEUS) in an experimental rat prostate carcinoma model. Prostate carcinoma (MLLB-2) cells were subcutaneously injected into the right flank of male rat (Charles River, Sulzfeld, Germany, 180 to 220 g body weight). Following 18 days of subcutaneous tumor growth 9 rats underwent CEUS examination. Real time CEUS was performed after a bolus injection of SonoVue (0.2 ml, Bracco, Italy) via the lateral tail vein using a high end ultrasound system (Siemens Sequoia 512®/Acuson, Mountain View) with an 15 Mhz probe. Two different CEUS techniques, pure contrast (pc) and contrast with background (cbg) examination, were analyzed (CPS-software). Exported signal intensity (SI)-time curves and the normalized area under the curve (AUC) for the active tumor tissue, whole tumor and necrosis were compared. The mean normalized AUC for the active tumor tissue and the whole tumor was 0.84 and 0.5 in the pure contrast examination group and 0.49 and 0.3 for the contrast examination with background signal. Therefore the signal intensity of the pc group was in every examination significant higher than of the cbg group (p < 0.02). The advantage of using the additional background information is to detect the anatomic landmarks in the solid tumor model in comparison to the pure contrast enhanced ultrasound examination. The complete extension of the tumor is much easier to detect with the cbg technique due to orientation of the anatomic landmarks. As the signal intensity of the pc group is always significant higher we recommend this technique for quantification of contrast enhanced ultrasound, especially for the follow up of tumor microcirculation.

Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy

The field of regenerative medicine and its applications for cardiovascular diseases continues to grow rapidly, fuelled by the increasing numbers of symptomatic patients who are not candidates for conventional revascularization procedures and remain refractory to maximal medical therapy. Therapeutic angiogenesis, initially in the form of the administration of growth factor protein or gene therapy and, more recently, in the form of adult progenitor cell therapy, has emerged as a promising new method of treatment for patients with ischaemic heart disease and peripheral arterial disease. There is a growing interest in non-invasive imaging techniques to evaluate the response to angiogenic gene-and cell-based therapies. Contrast-enhanced ultrasound (CEU) techniques using site-specific microbubbles have recently been developed for the molecular imaging of the vascular phenotype that characterizes angiogenesis. These methods have now been modified to allow the imaging of progenitor cell engraftment into neovessels. These molecular imaging techniques using contrast ultrasound and targeted microbubbles have the potential to further characterize the angiogenic response, aid in the optimization of gene- and cell-based strategies of therapeutic neovascularization, and ultimately serve to monitor the therapeutic effects in patients enrolled in clinical trials of regenerative therapies. This review will focus specifically on CEU molecular imaging techniques for the evaluation of angiogenesis and cell therapies in cardiovascular diseases, including: (i) an overview of the techniques and results of pre-clinical studies; (ii) a comparison of CEU molecular imaging techniques with other available molecular imaging modalities; and (iii) a discussion of the future role of CEU molecular imaging in the field of regenerative medicine.

Contrast-Tuned Imaging and Second-Generation Contrast Agent SonoVue: A New Ultrasound Approach to Evaluation of Tubal Patency

Study Objective To determine whether transvaginal hysterosalpingo-contrast sonography (HyCoSy) with a new dedicated contrast-enhanced ultrasound technique, can contribute to accurate diagnosis of tubal occlusion. Design Prospective observational study (Canadian Task Force classification II-2). Setting University hospital. Patients Two-hundred twelve patients with primary or secondary infertility. Interventions All patients underwent transvaginal HyCoSy. If the tubes showed no evidence of patency after injection of air-saline solution, a solution with sulphur hexafluoride bubbles (SonoVue) was injected into the uterine cavity and tubes while contrast-tuned imaging (CnTI) was applied. Patients with tubal occlusion underwent laparoscopic chromoperturbation. Measurements and Main Results Of the 212 patients who underwent tubal insufflation with air-saline solution, 52 demonstrated tubal occlusion, bilateral in 21 patients and unilateral in 31 patients, for a total of 73 suspected occluded tubes. At the HyCoSy test with SonoVue and CnTI, only 47 tubes seemed to be occluded, and in the other 26 tubes, passage of SonoVue was observed. HyCoSy with Sono Vue demonstrated high concordance for tubal obstruction with the laparoscopic dye test (94%). Conclusions HyCoSy with SonoVue and CnTi is a low acoustic pressure technique in which bubbles are not immediately destroyed and can be detected for several minutes. This enables the signal sent to the equipment to be filtered from the echoes emanating from other tissues. Therefore, excluding the fundamental image, the bubbles are clearly observed, with no visualization of pelvic tissues and organs. This allows easier evaluation of tubal patency, provides a more accurate assessment of tubal occlusion, and enables better visualization of the tubal course.

Feasibility of second‐generation ultrasound contrast media in the detection of active sacroiliitis

To determine whether a recently available contrast-enhanced ultrasound (CEUS) technique using second-generation microbubbles allows for the detection of active sacroiliitis, and to measure CEUS enhancement depth at the dorsocaudal part of the sacroiliac (SI) joints in healthy volunteers compared with patients with sacroiliitis. Forty-two consecutive patients (84 SI joints) presenting with a clinical diagnosis of sacroiliitis in 50 SI joints and 21 controls (42 SI joints) were investigated by CEUS using a standardized low mechanical index ultrasound protocol. Detected vascularity was used to retrospectively measure the enhancement depth in the dorsocaudal part of the SI joints. CEUS detected enhancement in all clinically active SI joints, showing an enhancement depth into the dorsal SI joint cleft of 18.5 mm (range 16-22.1), which was significantly higher compared with both inactive joints of patients (3.6 mm, range 0-12; P < 0.001) and healthy controls (3.1 mm, range 0-7.8; P < 0.001). All inactive joints were correctly classified based on a lack of deep enhancement in patients with sacroiliitis and controls (42 of 42, 100% sensitivity, 100% specificity; Cohen's kappa = 1). CEUS allowed the differentiation of active sacroiliitis from inactive SI joints, and proved to be a feasible method for the detection of vascularity in clinically active sacroiliitis by showing deep contrast enhancement into the SI joints not detectable in inactive joints of patients or controls. If this technique might add information to the earlier detection of sacroiliitis, it should be addressed in further studies.

Lymphosonographic sentinel node biopsy of the supraglottis in a swine model

To test the feasibility of a novel contrast-enhanced ultrasound (CEUS) technique, or lymphosonography, for sentinel node biopsy (SNB) of the supraglottis in a porcine model. In this prospective, nonrandomized animal study, blue dye and ultrasound contrast agent were injected into the supraglottis in seven 50-kg Yorkshire swine. Transcutaneous CEUS was used to identify real-time lymphatic flow of contrast through lymph channels (LC) to the sentinel lymph node (SLN). SNB was carried out, visually identifying a blue node, with the assistance of intraoperative CEUS. Bilateral modified radical neck dissections were performed to search for any residual contrast-positive or blue SLNs. In each case, at least one SLN was identified by preoperative CEUS. A total of 12 nodes were identified on preoperative CEUS, and 11 of 12 nodes were stained with blue dye (91.7%). No residual blue or contrast-positive nodes were identified on neck dissection. Lymphosonographic SNB of the supraglottis in a porcine model is technically feasible, and yields results comparable to traditional blue dye-guided techniques. No "shine-through" effect or nonsequential nodal enhancement occurred. This technique holds promise for sentinel node biopsy and allows a novel method for in vivo investigation of the lymphatic system.

Myocardial perfusion imaging with contrast echocardiography

Advances in myocardial perfusion imaging have firmly established the use of noninvasive techniques capable of providing useful information over a broad range of diagnostic and therapeutic cardiovascular problems. Evaluating regional myocardial perfusion abnormalities is a cornerstone for the diagnosis of coronary artery disease, risk assessment in those with known disease, and determination of myocardial viability. The clinical use of myocardial perfusion imaging and the current limitations of existing techniques continue to promote the development of new technologies capable of assessing microvascular and capillary perfusion abnormalities on a global myocardial level. Myocardial contrast echocardiography is an emerging technique capable of rapidly assessing myocardial perfusion at the capillary level in many different clinical settings. This article focuses on myocardial contrast-enhanced ultrasound perfusion techniques, emphasizing the unique information this modality provides compared with other noninvasive perfusion imaging techniques.

Focal liver lesions: contrast-enhanced ultrasound

Contrast-enhanced ultrasound (CEUS) represents a significant breakthrough in sonography and it is being increasingly used for the evaluation of focal liver lesions (FLLs). The unique feature of CEUS of non-invasively assessing in real-time liver perfusion throughout the vascular phase has led to a dramatic improvement in diagnostic accuracy of US in either detection or characterization of FLLs, as well as in the guidance and evaluation of response of therapeutic procedures. Currently, CEUS is included as a part of the suggested diagnostic work-up of FLLs, resulting in a better patient management and cost-effective therapy delivering. After a brief description of the basis of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs, among hepatic pseudolesions, will be described and discussed on the basis of our experience and literature data. At the same time, the most recent concepts and the use of CEUS in different clinical settings will be presented.

Assessment of Ischemia-Induced Microvascular Remodeling Using Contrast-Enhanced Ultrasound Vascular Anatomic Mapping

Our aim was to apply novel contrast-enhanced ultrasound (CEU) techniques to characterize remodeling in different vascular compartments during ischemia-mediated angiogenesis. Hind limb ischemia was produced by ligation of an external iliac artery in 60 rats, half of which were treated with intramuscular fibroblast growth factor (FGF)-2 (5 microg). The proximal adductor muscles of the ischemic and control hind limb were studied immediately after ligation and at days 4, 7, or 14. Low-power maximum intensity projection imaging was performed to assess large intramuscular vessels to the fourth branch order. CEU data were analyzed to measure capillary perfusion and functional noncapillary microvascular blood volume. Resting capillary perfusion was reduced by 30% after arterial ligation and recovered earlier in FGF-2-treated versus nontreated rats (day 4 vs. 14). Changes in perfusion were temporally related to expansion of noncapillary microvascular blood volume on CEU, which was associated with an arteriogenic response on histology. Expansion of and organization (fractal distribution) of large collateral vessels occurred gradually over 2 weeks and was slightly more rapid with FGF-2 treatment. We conclude that CEU can separately assess collateral development, more distal arteriogenesis, and secondary changes in capillary perfusion that occur differentially with ischemia and growth factor therapy.

Quantitative evaluation of muscle perfusion with CEUS and with MR

Functional imaging might increase the role of imaging in muscular diseases, since alterations of muscle morphology alone are not specific for a particular disease. Perfusion, i.e., the blood flow per tissue and time unit including capillary flow, is an important functional parameter. Pathological changes of skeletal muscle perfusion can be found in various clinical conditions, such as degenerative or inflammatory myopathies or peripheral arterial occlusive disease. This article reviews the theoretical basics of functional radiological techniques for assessing skeletal muscle perfusion and focuses on contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) techniques. Also, the applications of microvascular imaging, such as in detection of myositis and for discriminating myositis from other myopathies or evaluating peripheral arterial occlusive disease, are presented, and possible clinical indications are discussed. In conclusion, dedicated MR and CEUS methods are now available that visualize and quantify (patho-)physiologic information about microcirculation within skeletal muscles in vivo and hence establish a useful diagnostic tool for muscular diseases.

Characterization of focal liver lesions using an innovative contrast-enhanced ultrasound technique

To evaluate the clinical performance of an innovative contrast-enhanced ultrasound (CEUS) technique in characterization of focal liver lesions (FLL). CEUS was performed in 505 patients with FLLs. A sulfur hexafluoride-filled microbubble ultrasound contrast agent and a continuous real-time imaging technique of contrast pulse sequencing were used. The observation items included initial nodule enhancement time, enhancement level and pattern, and dynamic evolution of enhancement along with the CEUS phases. There were similar findings for both malignant and benign FLLs in initial enhancement time and enhancement level on CEUS. The dynamic evolution of enhancement along with enhancement phase was the most significant parameter for characterization of FLLs. Most malignant lesions showed enhancement at arterial phase and hypo-enhancing at late phase, whereas the benign lesions presented enhancement at arterial phase and persistent hyper- or iso-enhancing until late phase. Using these characteristics as a diagnostic criteria, the sensitivity, specificity, positive predicative value, negative predicative value and accuracy of CEUS in identifying malignant FLLs were 95.7% (313/327), 86.0% (153/178), 92.6% (313/338), 91.6% (153/167) and 92.3% (466/505), respectively. Characterization of FLLs by using the innovative CEUS technique is recommendable due to its safety, facility and high accuracy.

Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review

BackgroundFurther investigation of confirmed UTI in children aims to prevent renal scarring and future complications.MethodsWe conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age.Results73 studies were included. Many studies had methodological limitations or were poorly reported.Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring.Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation.ConclusionThere is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required.

Ultrasonic Imaging of Tumor Angiogenesis Using Contrast Microbubbles Targeted via the Tumor-Binding Peptide Arginine-Arginine-Leucine

Endothelial cells (EC) of angiogenic tumor vasculature are characterized by altered expression of molecular markers on their surface. Numerous peptides have been identified that specifically bind tumor angiogenic endothelium, including the tripeptide arginine-arginine-leucine (RRL). We hypothesized that ultrasound contrast microbubbles (MB) targeted via linkage with RRL would specifically adhere to tumor angiogenic endothelium versus normal myocardium, and that this selective adhesion could be detected ultrasonically. Microbubbles were conjugated to cyclic peptides containing either RRL (RRL-MB) or a glycine control sequence (control-MB). As measured in a parallel plate flow chamber, in vitro adhesion of RRL-MBs was three times greater to cultured tumor-derived ECs than to normal ECs (P < 0.01), demonstrating selective binding of RRL-MBs to tumor endothelium. Mice bearing s.c. Clone C or PC3 tumors were given i.v. injections of fluorescent RRL to show in vivo localization to tumor vasculature or were ultrasonically imaged following i.v. injections of targeted contrast MBs. Ultrasound images showed strong RRL-MB contrast enhancement within the tumors but not the control tissue myocardium. Control-MBs caused minimal enhancement in either tissue. Quantitative acoustic videointensity was significantly greater for the tumors than the hearts (5 +/- 1 versus 0.5 +/- 1 intensity units; P = 0.001). These data show that ultrasound contrast MBs targeted to tumor vasculature via RRL preferentially adhere to tumor versus normal vasculature and that this selective adherence can be detected with ultrasound. Targeted microbubbles may thus offer a noninvasive contrast-enhanced ultrasound imaging technique for the functional imaging of tumor neovascularization, and may have further implications for therapeutic tumor targeting.

Signalverstärkte Lebersonographie - Charakteristika einzelner Lebertumoren und Detektionsmöglichkeiten - eine Übersichtsarbeit

Contrast-enhanced ultrasound techniques represent the most challenging efforts in recent ultrasound developments. Contrast-enhanced imaging of the liver will be reviewed with respect to the literature and our own experience. Echo-enhancing agents, also known as ultrasound contrast media, have improved the accuracy of liver ultrasound within recent years. The characterisation of focal liver lesions which is possible by flow characteristics and the improved detection of liver tumors give special importance to the contrast agents. The agents consist of air or gas bubbles coated with different shell media. These micro-bubbles act as strong reflectors to the ultrasound beam enhancing the backscatter signal up to 30 dB. There are differences between blood pool agents and agents with a liver-specific late phase. The agents remain in the vessels during the vascular phase and lead to enhancement of different structures (arterial, capillary, portal venous, and sinusoidal perfusion). This is the first real-time imaging technique of liver lesions that allows a unique analysis of tumor perfusion. Liver tumors known to be hyperperfused in the arterial phase (e. g., focal nodular hyperplasia, hepatocellular carcinoma, and hyperperfused metastases) can be detected and characterised. Hypoperfused tumours (e. g., liver metastases of the gastrointestinal tract) can be recognised in the portal venous phase as less perfused "black spots". Due to of the recently available improved ultrasound technology and affordable ultrasound systems, a reduction in the use of computed tomography (CT) and magnetic resonance imaging (MRI) may be possible, allowing these important technologies to be available for other indications (e. g., brain, thorax).

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.

Hepatocellular carcinoma in adenomatous hyperplasia: detection with contrast-enhanced US with carbon dioxide microbubbles.

Adenomatous hyperplasia (AH) of the liver is considered a precancerous lesion because hepatocellular carcinoma (HCC) has been found in nodules of AH at histologic examination. Contrast material-enhanced ultrasound (US) with intraarterial infusion of carbon dioxide microbubbles was performed in four patients with HCC in AH lesions. In all four patients, a "hyperechoic focus in an area of hypoechoic change" in relation to the adjacent liver was demonstrated, compatible with the minimal vascular change associated with neoplastic transformation and carcinoma development. Because early detection of the minute cancer foci that may develop in an AH nodule is clinically important, this contrast-enhanced US technique may be a useful tool for the detection of these associated lesions.