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[Harmonic imaging].

Microbubbles undergoing resonant oscillation in a diagnostic ultrasound field can be induced to exhibit nonlinear motion. The ultrasound signals emitted by such microbubbles contain strong harmonics at twice the frequency of the transmitted ultrasound beam. Second harmonic imaging improves tissue-agent contrast. The usefulness of second harmonic imaging was evaluated in vivo experiments. The hepatic parenchyma was clearly enhanced in dogs. Second harmonic imaging can be expected to expand the capabilities of diagnostic ultrasound systems in visualizing tissue perfusion.

Animals↗

[Myocardial contrast echocardiography from peripheral venous injection: the potential for detection of myocardial perfusion abnormality].

Myocardial contrast echocardiography is a useful method for clinical evaluation of myocardial perfusion abnormality in ischemic heart disease. However, this method has a limitation in selection of patients because it is necessary to inject the contrast agent directly into the coronary artery in a catheterization room to obtain the image of myocardial opacification. Recently several echo contrast agents that have the potential for myocardial opacification after intravenous injection have been developed. These agents consist of perfluorocarbon gas filled-microbubble coated by a stabilizing surfactant. It's persistence is longer in air filled-microbubble such as Albunex. Safety of contrast agent and highly efficacy for myocardial opacification, no significant changes in parameters of cardiopulmonary function and hemodynamics are reported both in animal and human studies. In future contrast myocardial echocardiography with intravenous injection offers the potential for reliable and noninvasive assessment of perfusion in myocardial infarction before and after therapeutic interventions.

Animals↗

[Transcatheter arterial embolization of hepatocellular carcinoma using CO2-US].

Enhanced ultrasonography under the injection of microbubbles of carbon dioxide into the hepatic artery (CO2-US) contributed to the treatment of hepatocellular carcinoma in the selection of indication of transcatheter arterial embolization (TAE). Judging from the accumulation of the lipiodol after TAE with the combination of lipiodol, TAE was thought to be effective in the tumor which was enhanced by CO2 microbubbles more strongly and the enhancement was prolonged more longer compared to the surrounding parenchyma, even the tumor had no tumor staining on the hepatic angiography. In none of the tumor which had no enhancement, TAE was effective. In most of the tumor with isoenhancement compared with surrounding parenchyma TAE was not effective.

Carbon Dioxide↗

[Clinical assessment of contrast-enhanced ultrasonography for the diagnosis of gall bladder diseases].

We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) with intra-arterial injection of CO2 microbubbles in 37 cases of gall bladder diseases. CEUS clearly visualized arterial flow and vascularity in every lesions without debris and gave us the precise information of vascular structure for the differential diagnosis of gall bladder tumors. For example, highly bifurcated tumor vessels and strong enhancement was observed in gall bladder cancer and we could detect relatively strong enhancement along the lumen with lack of enhancement of Rokitansky-Aschoff sinus in localized-type adenomyomatosis. Though CEUS is now an invasive modality, it will enable us to understand the non-invasive modality such as color doppler imaging with intra-venous administration of microbubbles in the future.

Carbon Dioxide↗

[Application of CO2 enhanced ultrasound for two-stage operation of hepatic tumors].

The feasibility of CO2 enhanced ultrasound (CO2-EUS) was evaluated in two-stage operation patients with hepatic tumors. CO2-EUS was carried out in nine patients with indwelling catheter within hepatic artery for two-stage operation of liver cancer. CO2 microbubbles mixing by 5 ml of 5% NaHCO3 and 2.5 ml of 5% Vitamine C were injected into the indwelling catheter. The computed sonography of ACUSON 128XP/10 with a 3.5 MHz convex transducer was used for this study. The enhanced parenchyma of the liver obtained by CO2-EUS and the lasting time of enhancement was about 8 minutes. The hepatic tumors, after chemotherapeutic treatment via indwelling catheter, were variously enhanced by CO2 microbubbles. The enhanced sonogram of the tumors took the forms of hypoechoic, ring-like, or spotty enhanced pattern lasting for more than 30 minutes. The margin of the enhanced tumors was very clear in CO2-EUS. CO2-EUS detected five more lesions (size 1-3 cm) besides 9 lesions by conventional ultrasound. CO2-EUS was extremely useful in evaluating curative effects of tumor, increasing detection rates of small tumor, and improving thoroughness of two-stage operation.

Carbon Dioxide↗

Non-invasive opening of BBB by focused ultrasound.

Blood brain barrier (BBB) is a major barrier for delivering therapeutic agents in the brain. In this study we investigated the feasibility of open the BBB by using focused ultrasound. Rabbit brains were exposed to pulsed focused ultrasound while injecting ultrasound contrast agent containg microbubbles intravenously. The BBB opening was measured after the sonications by injecting MRI contrast agent i.v. and evaluating the local enhancement in the brain. Low ultrasound powers and pressure amplitudes were found to cause focal enhancement. Before sacrificing the animals trypan blue was also injected i.v.. After the sacrifice of the animals blue spots were found in the brain in the sonicated locations. This method may have potential for targeted delivery of macromolecules in the brain.

Animals↗

[Ultrasound contrast agents].

Ultrasound contrast agents consist of tiny gas bubbles encapsulated by a stabilising membrane or shell. When combined with recent contrast-specific ultrasound techniques, they provide substantial enhancement of vessels and solid organs. The clinical use and the diagnostic value of ultrasound contrast agents are in principle comparable to those of contrast agents for CT and MRI. They add an additional dimension of information to sonography, which results in considerable improvement of diagnostic accuracy in many cases. This paper reviews the physicochemical properties of various microbubble contrast agents, discusses non-linear bubble behaviour and contrast-specific imaging techniques. An overview of the most important radiological clinical applications in the liver, kidney and spleen is given.

Contrast Media↗

[Quantification of tissue perfusion with novel ultrasound methods].

Perfusion describes an important parameter of tissue vitality, e. g. of the myocardium, brain, or the kidney. In malign tumours, perfusion is of particular interest for characterization and prognosis. In addition, new pro- or anti-angiogenic therapies require a functional imaging which is suitable to quantify vascularity. Sonographic methods for the detection of microvascularity, particularly related smaller than those amenable to Doppler ultrasound, are reviewed. The main focus deals with the explanation of contrast-enhanced sonography using replenishment kinetics of microbubbles which provides a comprehensive quantification of tissue perfusion. Alterations of the microvascularity e. g., under anti-angiogenic therapy, can be depicted in experimental studies using this novel approach. Further clinical applications can be the quantification of the perfusion in the myocardium, the brain, or the kidney. New approaches to optimize the theoretical model to describe the replenishment, and novel technical developments are discussed.

Animals↗

Contrast-enhanced triggered harmonic sonography for assessment of periarticular hemodynamic changes in experimental arthritis.

BACKGROUND: Objective quantification is critical for assessment of functional sonography in inflammatory arthritis. To create a microbubble contrast-enhanced image of vessels that lie below the resolution of a standard US system, a technique is required that detects preferentially the contrast agent echo, rejecting that from background tissue: harmonic imaging. OBJECTIVES: To investigate the ability of contrast-enhanced triggered harmonic sonography (CETHS) to evaluate periarticular hemodynamic changes over the course of experimental arthritis and to discriminate presence and absence of arthritis based on measurement values obtained at specific time-points. MATERIALS AND METHODS: Arthritis was induced in rabbits knees by intra-articular injection of serum bovine albumin, which acted as an antigen. A total of 11 rabbits (8 with unilateral arthritis and 3 control animals) were imaged at 0, 1, 7, 14, 21 and 28 days of antigen-induced arthritis and euthanized at 28 days. A continuous infusion protocol was performed (triggering times 30.0, 20.0, 10.0, 5.0, 2.0, 1.0, and 0.5 s). Hemodynamic indices of synovial microvasculature (vascular volume, mean velocity and flow rate) were obtained and compared with clinical, laboratory, and histological surrogate markers. RESULTS: Although interval CETHS changes were noted for flow rate (P=0.007) and vascular volume (P=0.003) ratios in albumin-injected knees, no significant differences in ratios were identified over time between albumin-injected and non-injected knees for flow rate (P=0.52), vascular volume (P=0.23) and mean velocity (P=0.19). Flow rate most accurately differentiated between presence and absence of arthritis according to clinical measurements in early (day 1) arthritis, and mean velocity in mid-term arthritis (day 14; both P=0.02). CONCLUSION: Although the measurement properties of CETHS indices were poor in the evaluation of hemodynamic differences over time in albumin-injected knees compared with non-injected knees, they enabled discrimination between presence and absence of arthritis at specific time-points in different stages.

Animals↗

The use of contrast-enhanced ultrasound in the management of the cirrhotic patient and for detection of HCC.

Hepatocellular carcinoma (HCC) is the leading cause of death in liver cirrhosis. Ultrasound (US) is widely accepted as the screening imaging modality of choice for HCC in patients with a history of chronic liver disease. However, the US characteristics of HCCs are non-specific and thus, other imaging techniques or biopsy are usually necessary to characterize focal liver lesions (FLL) and confirm malignancy. Blood flow to HCC is mainly arterial, making dynamic CT and MRI the most commonly used techniques to detect the characteristic arterial hypervascularization. Recently, the development of second-generation US contrast agents and microbubble-specific software has changed the role of US in real-time evaluation of the macro and microvascularization of FLLs. With this technology, the accuracy of US in the diagnosis of HCC and its differentiation from other FLLs such as regenerating nodules has improved dramatically. In addition, contrast-enhanced ultrasound may also be a useful tool in the staging of HCC and in the evaluation of percutaneous treatment.

Aged↗

Detection and characterisation of liver metastases.

Modern liver imaging of cancer patients requires an imaging modality that is not only highly sensitive in detecting lesions but also provides reliable characterisation of lesions and thus allows differentiation of metastases from frequently found benign lesions. Conventional ultrasound (US) has a relatively poor sensitivity and specificity for imaging liver metastases and US used to be inferior to CT and MRI mainly due to a lack of contrast agents. This has changed with the advent of microbubble contrast agents for US. The use of recent contrast agents such as SonoVue (Bracco, Italy) combined with low mechanical index contrast-specific imaging techniques such as Contrast Pulse Sequencing provides dynamic real time imaging of focal liver lesions in the arterial, portal venous and delayed phase. This improves lesion detection and characterisation. To investigate the benefit of SonoVue for detecting liver metastases we studied 40 cancer patients with liver lesions on reference imaging (CT or MRI), 37 of them had metastases. The mean number of reference confirmed metastases per patient increased from 1.85+/-1.79 on conventional ultrasound to 2.73+/-2.50 post SonoVue (p < 0.05). CEUS showed more individual metastases than baseline in 12 (34%) patients. Using CT or MRI as the reference, the mean sensitivity to individual metastases increased from 69% on baseline US to 90% post contrast (p < 0.0005). The role of SonoVue in characterisation of focal liver lesions was evaluated in 63 patients. One lesion was studied per patient. Based on standardised dynamic enhancement criteria for each lesion type, the number of correctly diagnosed lesions improved from 41 (65%) on baseline US to 58 (92%) post contrast (p < 0.001). On CEUS all 27 metastases were correctly diagnosed, while baseline US misinterpreted 2 of these. The number of correctly diagnosed benign lesions (n = 28) increased from 12 (43%) on baseline to 25 (89%) post SonoVue. In conclusion, detection and characterisation of focal liver lesions by US are markedly improved by the use of SonoVue. Contrast agents add a new dimension to sonography allowing it to rival CT and MRI, especially for lesion characterisation.

Carcinoma, Hepatocellular↗

Monitoring RF ablation.

The addition of contrast-enhanced ultrasound to monitor the extent of interstitial ablation has simplified this procedure. Newer agents such as SonoVue used with microbubble-specific software (CPS) allow continuous real-time scanning at low MIs so that, if residual perfused tumour is found, complete evaluation of the extent of tissue ablation can be carried out immediately after the procedure in the same treatment session. In the initial 18-month period after the introduction of these agents, partial necrosis occurred in 5.1% of treated lesions compared to the previous rate of 16.1%, and this improved to 3.8% in the following 2 years. The method is cost-effective because it reduces the need for repeated treatment sessions under general anaesthesia. The same method is helpful in treatment planning and follow-up.

Anesthesia, General↗

An investigation of the physical forces leading to thrombosis disruption by cavitation.

Ultrasound therapy has proven to be an efficient and safe modality for the treatment of acute arterial occlusions, and the use of therapeutic ultrasound for the treatment of thrombosis and vascular diseases holds great promise in overcoming the limitations of other available therapies. Still, there exists little published work that covers the different phenomena that take place in a thorough and comprehensive way. In this paper, we endeavor to address the subject by reviewing work on the physical properties of ultrasound propagation in the blood arteries as it relates to the cavitation of microbubbles, and we compare the impact of the different forces at work for clot disruption. Our conclusion is that the most important effect of ultrasound in the treatment of thrombotic disorders is the liquid-jet impact forces that result from strong bubble collapses in the vicinity of solid boundaries.

Blood Coagulation↗

New perspectives for the use of contrast-enhanced liver ultrasound in clinical practice.

The introduction of second-generation microbubble ultrasound contrast agents and the development of contrast specific ultrasound techniques have improved the ability of contrast enhanced ultrasound in detecting and characterising liver lesions, offering new perspectives for its exploitation in clinical hepatology. Indeed, several studies have demonstrated a high diagnostic accuracy in focal lesion characterisation (85-96%) in patients either with or without underlying chronic liver disease. This review article describes the basic principles of contrast enhanced ultrasound, defines the different vascular features of benign and malignant liver lesions, and assesses its clinical impact in different clinical scenarios, according to the guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology, contrast enhanced ultrasound enables the characterisation of focal liver lesions, regardless of the presence or absence of underlying chronic liver disease. Contrast enhanced ultrasound is also useful in staging and follow-up of cancer patients and in monitoring local ablative treatment. Contrast enhanced ultrasound is expected to be considerably increased and replace many computed tomography and magnetic resonance imaging examinations in near future, according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. Therefore, it is necessary to take measures in order to meet the demand for an increasing number of these procedures.

Contrast Media↗

Noninvasive vessel-selective perfusion imaging with intravenous myocardial contrast echocardiography.

BACKGROUND: Intravenous myocardial contrast echocardiography (MCE) cannot identify each perfusion area of coronary vessels separately. However, by destroying microbubbles passing through a specific vessel using high-power ultrasound during intravenous MCE, vessel-selective perfusion imaging (VSPI) may be feasible. METHODS: In 10 open-chest dogs, intermittent short-axis images were obtained during contrast agent infusion using an ultrasound system. For VSPI, a probe coupled to another ultrasound machine was placed on the proximal left circumflex coronary artery (LCx). High-power ultrasound pulses were transmitted to destroy bubbles passing through the LCx. A negative contrast area on VSPI was considered to represent the perfusion area of the LCx (LCx-VSPI). A negative contrast area on conventional MCE during LCx occlusion and a region without staining by Evans blue dye were used as gold standards for defining the LCx perfusion area. LCx-VSPI was compared with a negative contrast area on conventional MCE during LCx occlusion and a region without staining by Evans blue dye. RESULTS: Despite lack of LCx occlusion, high-power destructive pulses produced a definite area of negative contrast on the LCx region. Decreased power of ultrasound pulses resulted in disappearance of the negative contrast area. An excellent relationship was demonstrated between both LCx-VSPI and a negative contrast area on conventional MCE during LCx occlusion (r = 0.93, P <.0001), and LCx-VSPI and a region without staining by Evans blue dye (r = 0.92, P =.0002). CONCLUSION: VSPI during intravenous MCE may be feasible for noninvasive assessment of perfusion areas associated with specific vessels.

Animals↗

Corrected quantification method to determine myocardial blood flow using real-time myocardial contrast echocardiography.

BACKGROUND: The quantitative assessment of myocardial blood flow using real-time myocardial contrast echocardiography is based on a replenishment of bubble density after bubble destruction by high-power ultrasound exposure (burst). However, all microbubbles in the myocardial vessels are not necessarily completely destroyed, which results in unreliable data of the replenishment curve analysis. OBJECTIVE: The aim of this study was to propose a corrected equation for the replenishment curve analysis based on the hypothesis in which the initial intensity just after burst should be equivalent to the baseline intensity before contrast infusion, and to examine whether the regional difference of myocardial perfusion parameters could be minimized by the use of corrected equation of replenishment curve. METHODS: Myocardial opacification of the left ventricular short-axis view was observed using low mechanical index during infusion of Definity in open-chest dogs. Bubble destruction was set in two ways, either high (0 dB) or low (-11 dB) power burst. The videointensity (VI) of baseline before contrast infusion (f-value) was assumed as an initial intensity after complete bubble destruction. Changes of the VI after burst were fitted to both exponential functions: y = a (1 - e(-beta t)) + c (conventional equation) and y = a (1 - e(-beta(t - d))) + f (corrected equation). The c-value was the measured VI just after burst. The d-value was the hypothetical time of onset of the replenishment curve if all bubbles were completely destroyed. The plateau VI was defined as the A-value, which was the sum of a- and c-values or a- and f-values, respectively. The maximal difference of beta-value among myocardial regions was calculated by either equation. RESULTS: The A-value was almost identical in either equation regardless of the acoustic power of burst. The beta-value by the conventional equation was higher after the incomplete burst than that after complete burst (0.45 +/- 0.12 vs 0.54 +/- 0.16). By contrast, the beta-value calculated by the corrected equation was almost identical despite complete or incomplete bursts (0.46 +/- 0.13 vs 0.48 +/- 0.15). The maximal difference of beta-value was significantly reduced by the use of corrected equation (conventional 0.24 +/- 0.14 vs corrected 0.18 +/- 0.10). CONCLUSIONS: Variation of beta-value because of the incomplete bubble destruction can be minimized by using the corrected equation: y = a (1 - e(-beta(t - d))) + f. Further, the corrected equation can improve the regional variation of beta-value.

Animals↗

Contrast-enhanced ultrasonographic spoke-wheel sign in hepatic focal nodular hyperplasia.

BACKGROUND: To determine the utility of contrast-enhanced ultrasonography (CEUS) in assessing hepatic tumors with central feeding arteries found by color/power Doppler ultrasonograophy (CDUS/PDUS). METHODS: We prospectively studied 37 hepatic tumors (34 patients), with a mean size of 2.9cm and each having a central feeding artery, by CDUS/PDUS. The CEUS was performed with a galactose-based microbubble contrast agent. The detection of a spoke-wheel sign was interpreted as evidence of focal nodular hyperplasia (FNH). All patients underwent tumor biopsies or surgical resection. RESULTS: CEUS showed a central feeding artery with a spoke-wheel sign in 36 tumors, including 34 FNHs and 2 hepatocellular carcinomas. The remaining tumor was demonstrated to be FNH despite the absence of a spoke-wheel sign as detected by CEUS. The sensitivity of the spoke-wheel sign or central scar for FNH was 97.1% (34/35), 40% (14/35), 28.6% (10/35), 50% (8/16) and 0% (0/15) for CEUS, CDUS/PDUS, dynamic computed tomography (CT) or magnetic resonance imaging (MRI), hepatic angiography and liver scintigraphy, respectively. The two hepatocellular carcinomas showed scirrhous changes histologically. CONCLUSIONS: CEUS is more sensitive than CDUS/PDUS, dynamic CT, MRI, hepatic angiography and liver scintigraphy in the detection of the spoke-wheel sign or central scar in FNH. Scirrhous hepatocellular carcinoma should be included in the differential diagnosis for liver tumors with spoke-wheel sign detected by CEUS.

Adolescent↗

Mapping age-related elasticity changes in porcine lenses using bubble-based acoustic radiation force.

Bubble-based acoustic radiation force aims to measure highly localized tissue viscoelastic properties. In the current investigation, acoustic radiation force was applied to laser-induced bubbles to measure age-related changes in the spatial distribution of elastic properties within in vitro porcine lenses. A potential in vivo technique to map lens elasticity is crucial to understanding the onset of presbyopia and develop new treatment options. Bubble-based acoustic radiation force was investigated as a technique to measure the spatial elasticity distribution of the lens in its natural state without disrupting the lens capsule. Laser-induced optical breakdown (LIOB) generated microbubbles in a straight line across the equatorial plane of explanted porcine lenses with 1mm lateral spacing. Optical breakdown occurs when sufficiently high threshold fluence is attained at the focus of femtosecond pulsed lasers, inducing plasma formation and bubble generation. A two-element confocal ultrasonic transducer applied 6.5 ms acoustic radiation force-chirp bursts with the 1.5 MHz outer element while monitoring bubble position within the lens using pulse-echoes with the 7.44 MHz inner element. A cross-correlation method was used to measure bubble displacements and determine exponential time constants of the temporal responses. Maximum bubble displacements are inversely proportional to the local Young's modulus, while time constants are indicative of viscoelastic properties. The apparent spatial elasticity distributions in 41 porcine lenses, ranging from 4 months to 5 years in age, were measured using bubble-based acoustic radiation force. Bubble displacements decrease closer to the porcine lens center, suggesting that the nucleus is stiffer than the cortex. Bubble displacements decrease with increasing lens age, suggesting that porcine lenses become stiffer with age. Bubble-based acoustic radiation force may be well-suited as a potential in vivo technique to spatially map elastic properties of the lens and guide therapeutic procedures aimed at restoring accommodation.

Aging↗