Low Acoustic Power Research Articles

Three-dimensional contrast-enhanced ultrasound of the liver: Experience of 92 cases

Three-dimensional contrast-enhanced ultrasound (3D-CEUS) is a combination of three-dimensional ultrasound (3DUS) and contrast-enhanced ultrasound (CEUS). To evaluate the feasibility of 3D-CEUS in liver imaging, investigate possible influencing factors to its image quality, and evaluate the influence of 3D-CEUS to clinical outcome, low acoustic power (mechanical index, 0.08–0.13) 3D-CEUS was carried out in 102 focal liver lesions in 92 patients by using the LOGIQ 9 ultrasound scanner and a volume transducer (frequency range, 2–5 MHz; focusing ability, 2–25 cm in depth; azimuth aperture 5.9 cm). The lesions were classified into two groups: group 1 ( n = 51) for characterization and group 2 ( n = 51) for local treatment response evaluation. The factors that influenced the image quality of 3D-CEUS were analyzed. The image quality and usefulness of 3D-CEUS between the two groups were compared by using the χ 2-test. The results showed that the lesion diameter, location, and scanning route had no significant influence on the image quality in both groups, whereas interfering factors damaged the image quality in group 1. In group 1, during arterial phase, high image quality was more frequently found in hyperenhanced and hypo- or non-enhanced lesions compared with isoenhanced lesions. In group 2, interfering factor and local treatment response had no obvious influence on the image quality. The visualization rate of high image quality was 94.1% (48/51) in group 2 vs. 72.6% (37/51) in group 1 ( P = 0.012). The investigators found that 3D-CEUS improved confidence but made no change in diagnosis in 19 (37.3%) of 51 lesions in group 1, whereas 41 (80.4%) of 51 lesions in group 2 ( P = 0.000). 3D-CEUS tends to obtain better image quality and lead to higher diagnostic confidence in the lesions for local treatment response evaluation, and perhaps is more useful in this aspect in future clinical settings.

Efficient array design for sonotherapy

New linear multi-row, multi-frequency arrays have been designed, constructed and tested as fully operational ultrasound probes to produce confocal imaging and therapeutic acoustic intensities with a standard commercial ultrasound imaging system. The triple-array probes and imaging system produce high quality B-mode images with a center row imaging array at 5.3 MHz and sufficient acoustic power with dual therapeutic arrays to produce mild hyperthermia at 1.54 MHz. The therapeutic array pair in the first probe design (termed G3) utilizes a high bandwidth and peak pressure, suitable for mechanical therapies. The second multi-array design (termed G4) has a redesigned therapeutic array pair which is optimized for a high time-averaged power output suitable for mild hyperthermia applications. The ‘thermal therapy’ design produces more than 4 W of acoustic power from the low-frequency arrays with only a 10.5 °C internal rise in temperature after 100 s of continuous use with an unmodified conventional imaging system or substantially longer operation at lower acoustic power. The low-frequency arrays in both probe designs were examined and contrasted for real power transfer efficiency with a KLM model which includes all lossy contributions in the power delivery path from system transmitters to the tissue load. Laboratory verification was successfully performed for the KLM-derived estimates of transducer parallel model acoustic resistance and dissipation resistance, which are the critical design factors for acoustic power output and undesired internal heating, respectively.

SU‐GG‐J‐133: MR Guided Focused Ultrasound (MRgFU) for Cance Therapy

Purpose: The purpose of this work was to commission and to evaluate the role of MR guided high intensity focused ultrasound (MRgHIFU) in cancer therapy in ex vivo and in vivo. Method and Materials: An InSightec ExAblate 2000 HIFU system with a 1.5T GE MR scanner (MRgHIFU) is approved by FDA for the treatment of uterus fibroids clinically and being investigated in our department for treating bone metastases, prostate and breast cancers under local IRB approval. The phased array transducer is housed in a sealed bath and connected to a motion system. The focal region is cigar shaped, about 2mm in diameter and 10mm in focal length. Extensive experiments have been carried out on phantoms and excised tissues to determine optimal ultrasound parameters including the acoustic power output, frequency and exposure duration. We also performed in vivo studies on feasibility of enhancement of drug delivery for both chemotherapy and gene therapy using an animal model. Both MR T2‐weight MR image and proton resonance frequency shift MR images were used for treatment planning and monitoring the effect of the treatment in real time. Results: Phantom studies demonstrated that MRgHIFU could provide adequate temperature elevation for tissue ablation; acoustic power >10W leading to temperature elevation (ΔT) > 7 °C. At a lower acoustic power (5 W) we could keep ΔT < 4 °C, which is adequate for drug enhancement. The results were served for animal studies. Tissue damage was achieved at predetermined region in excised tissue through MR real‐time guidance. Our preliminary results showed increased drug concentrations in MRgHIFU treated mice than the control group. Conclusion: MRgHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy including tumor ablation, enhancement of drug livery and boost treatment for hypoxic tumors in combination with radiotherapy.

Unusual Benign Focal Liver Lesions

This presentation aims to provide an overview of the manifestations of some unusual benign focal liver lesions (FLLs) on low-acoustic power contrast-enhanced sonography (CES) with a sulfur hexafluoride contrast agent. The patients were selected retrospectively from 2209 cases with FLLs who had undergone CES examinations for characterization during the past 3 years. The pathologic examinations proved that they were intrahepatic biliary cystadenoma (n = 1), angiomyolipoma (AML; n = 4), lipoma (n = 1), biliary epithelial dysplasia (n = 1), a fungal inflammatory mass (n = 1), tuberculoma (n = 2), an inflammatory pseudotumor (n = 7), sarcoidosis (n = 1), solitary necrotic nodules (n = 2), peliosis hepatis (n = 2), and focal fibrosis after surgery (n = 4). Contrast-enhanced sonography was beneficial in leading to a diagnosis of benignity for some lesions showing hyperenhancement during the arterial phase and sustained enhancement during the portal or late phase, such as liver AML and lipoma. The benign nature of other lesions showing no enhancement during all phases, such as solitary necrotic nodules and focal fibrosis, was also suggestible. On the other hand, for those lesions showing hyperenhancement, isoenhancement, or hypoenhancement during the arterial phase and hypoenhancement during the late phase, including intrahepatic biliary cystadenoma, biliary epithelial dysplasia, infected liver diseases, the inflammatory pseudotumor, sarcoidosis, and peliosis hepatis, the differential diagnosis between benignity and malignancy was difficult, and pathologic tests were mandatory. The CES features of unusual benign FLLs may enrich knowledge when performing CES examinations for characterization and may provide clues for a specific diagnosis of an individual lesion such as liver AML.

Evidence for a Plasma Core during Multibubble Sonoluminescence in Sulfuric Acid

Multibubble sonoluminescence arises from the cavitation of bubbles owing to high-intensity ultrasonic irradiation of liquids. The spectrum of multibubble sonoluminescence in concentrated sulfuric acid sparged with Ar, at relatively low acoustic power, consists of a broad continuum extending into the UV with SO and Ar emission lines on top of this continuum. The observation of the Ar lines indicates that an optically opaque plasma is probably generated inside the bubble during cavitation. There are three distinct light-emitting morphologies for multibubble sonoluminescence from an ultrasonic horn; as the acoustic intensity is increased, the emission changes from filamentous, to bulbous, to cone shaped, and it is only from the filamentous emission that strong atomic and molecular emissions are observed.

Quantification of hepatic parenchymal blood flow by contrast ultrasonography with flash-replenishment imaging

Flash-replenishment (FR) utilizes destruction of microbubbles in the scan volume by high-power ultrasound and enables to observe reperfusion at a low acoustic power. In this paper, we introduced theoretic equation between probability density function (PDF) of the transit time in the scan volume and time intensity curve (TIC) measured by FR method. From the equations, it was explained that the mean transit time (MTT) through the scan volume was calculated from the plateau level and tangent of the initial slope. Animal experiments were also performed to measure TIC in the parenchymal region of the liver using FR method. From the result of the TIC, the variant of the PDF for the transit time was found to be small and the average MTT was 11.1 s. Hepatic blood flow by an ultrasonic transit time flowmeter was also measured in the same experiment, and adequate correlation was obtained from between the two methods. The results suggested that the FR method, which is a noninvasive measurement, can predict the blood flow of the liver. (E-mail: moriyasu@tokyo-med.ac.jp)

Contrast Enhanced Ultrasonography for Focal Liver Lesions Characterization: Clinical Perspective

Gray-scale and color Doppler ultrasonography have limited accuracy in characterization of focal liver lesions because a significant overlapping exists between the echo pattern and vascularity of benign and malignant lesions. Several clinical studies have demonstrated that characterization of focal liver lesions that are indeterminate at conventional ultrasonography could be improved using microbubble contrast agents with contrast specific modes. In particular, latest generation ultrasound contrast agents allow evaluation of lesion vascularity in real time using low acoustic power contrast specific modes with the resolution afforded with gray-scale imaging. In this review article the enhancement pattern of different types of benign and malignant focal liver lesions using low acoustic power contrast specific modes is described, and the current role of contrast enhanced ultrasonography in liver lesion characterization is discussed. Keywords: Liver neoplasms, diagnosis, ultrasound (US), microbubble contrast agents

Real-time visualization and quantitation of canine gastric mucosal blood flow by contrast-enhanced ultrasonography

Objective. Contrast-enhanced ultrasonography has become a method of choice for evaluating gastric blood flow, but intermittent scanning techniques can sometimes distort the results. Low-mechanical index imaging using Definity as the injected contrast material has been advocated for real-time evaluation of microperfusion in other organs. We investigated the reliability of low-mechanical index imaging using Definity in the evaluation of gastric mucosal blood flow. Material and methods. Under general anesthesia, 10 beagle dogs weighing 9–10 kg underwent real-time harmonic imaging under low acoustic power (mechanical index = 0.2) after intravenous contrast injection using Definity (60 mg/kg). Laser Doppler flow measurement was also performed to evaluate gastric mucosal blood flow. After administration of a diclofenac sodium suppository, low-mechanical index imaging and laser Doppler flowmetry were repeated. Results. Real-time visualization of gastric mucosal blood flow was successful in all dogs undergoing low-mechanical index imaging with Definity. Quantitative assessment of gastric mucosal blood flow was successful in eight dogs. After diclofenac sodium administration, gastric mucosal blood flow measured by both laser Doppler flowmetry and contrast ultrasonography decreased in seven of eight dogs; in the other dog, gastric mucosal blood flow increased slightly. A strong positive correlation was evident between blood flow measured by laser Doppler flowmetry and low-mechanical index imaging (r=0.777, p<0.005). Conclusions. Low-mechanical index imaging with Definity is a non-invasive way to evaluate gastric mucosal blood flow in real-time, high-resolutional images, which may have additional important gastrointestinal tract applications.

Surfactant-stabilized contrast agent on the nanoscale for diagnostic ultrasound imaging

Ultrasound contrast agents (CA) are generally micron-sized stabilized gas bubbles, injected IV. However, to penetrate beyond the vasculature and accumulate in targets such as tumors, CA must be an order of magnitude smaller. We describe a method of achieving nanometer-sized, surfactant-stabilized CA by differential centrifugation. High g force was shown to destroy bubble integrity. Optimal conditions (300 rpm for 3 min) produced an agent with a mean diameter of 450 nm, which gave 25.5 dB enhancement in vitro at a dose of 10 μL/mL, with a 13 min half-life. In vivo, the CA produced excellent power Doppler and grey-scale pulse inversion harmonic images at low acoustic power when administered. In vivo dose-response curves obtained in three rabbits showed enhancement between 20 and 25 dB for dosages above 0.025 mL/kg. These results encourage further investigation of the possible diagnostic and therapeutic benefits of using nanoparticles as CA, including passive targeting and accumulation in tumors. (E-mail: wheatley@coe.drexel.edu)

Focal liver lesion characterization using low acoustic power ultrasound imaging

To determine if real-time low acoustic power imaging with SonoVue (Bracco, Italy), a sulphur hexafluoride based microbubble contrast agent, increases diagnostic performance of baseline ultrasound (US) and color Doppler US (CDUS) when used to characterize focal liver lesions.

Optimising phase and amplitude modulation schemes for imaging microbubble contrast agents at low acoustic power

A series of in vitro experiments were performed to determine the efficacy of generalised phase- and amplitude-modulated sequences for low-power nonlinear microbubble contrast imaging. The microbubble agent Definity® (Dupont, Boston, MA) was exposed to sequences in which the phase and amplitude were changed from one pulse to the next. Echoes from these pulses were combined to suppress or enhance particular linear or nonlinear components. The results show that established two-pulse pulse-inversion and amplitude-modulation approaches perform similarly, providing 14 ± 1 dB of enhancement, compared with the echoes from the linear scatterer. A two-pulse combined phase and amplitude sequence achieved an additional 4 ± 1 dB of enhancement. This improvement is due to improved preservation of second and third order harmonic signals, while maintaining the suppression of the linear signals. These results were obtained at low power, below the threshold of microbubble destruction, and are applicable to real-time perfusion imaging. (E-mail: r.eckersley@imperial.ac.uk)

Extra-low acoustic power harmonic images of the liver with perflutren: novel imaging for real-time observation of liver perfusion.

The features of images below the extra-low mechanical index level were studied to elucidate a suitable mechanical index level for observing real-time and continuous harmonic images of rabbit livers with VX-2 tumors with the use of perflutren. Eight New Zealand White rabbits, 2 with healthy livers and 6 with VX-2 tumors, were examined by harmonic imaging (1.85 and 3.7 MHz) at a frame rate of 17 Hz under various mechanical index levels. Real-time enhanced images of the liver were observed continuously in all rabbits. Vascular images were more clearly visualized at the low mechanical index level (mechanical index, 0.18) than at any other level. However, predominant enhanced images of the whole liver were observed only at the extra-low mechanical index level (mechanical index, 0.06). In VX-2 tumors, tumor vessels were shown more clearly at a low acoustic power level than at an extra-low level. The histologically proved area of viable tumor was enhanced as a stain in the tumor nodule at an extra-low mechanical index level. Harmonic imaging under extra-low mechanical index levels with perflutren could provide real-time and continuous enhanced images of the liver, which would contribute to improvement of the diagnostic ability of contrast-enhanced sonography in liver diseases.

Safety levels for exposure of cornea and lens to very high-frequency ultrasound.

Very high-frequency (50-MHz) ultrasound is widely used for imaging the anterior segment of the eye. Our aim was to determine whether exposures to ultrasound at and above those used in diagnostic imaging systems might cause bioeffects in ocular tissues. We characterized the output parameters of a polyvinylidene difluoride transducer using a needle hydrophone. We exposed sites on the cornea or lens of rabbits for up to 30 minutes at a 10-kHz pulse repetition frequency. Tissue obtained immediately or 24 hours after exposure was examined by light microscopy. A numeric model was implemented to calculate expected temperature elevations in the cornea and lens under experimental conditions. No tissue changes were observed directly or by slit lamp. Light microscopy showed no abnormalities attributable to ultrasound exposure. Simulations showed that even long-term exposures should produce temperature elevations of less than 1 degree C in both the cornea and lens. With the use of exposure parameters 4 to 5 orders of magnitude greater than encountered in a clinical situation, no tissue changes were observed. This is consistent with the small (0.2 degrees C) temperature rises computed in simulations. The lack of biological effects is attributable to the small dimensions of the focal zone, allowing rapid dissipation of heat, and the low total acoustic power produced by the transducer.

Induction of apoptosis in human leukemic cells by ultrasonic low energy treatment

Abstract The biophysical effects of ultrasound have been frequently surveyed and its use has been proposed for some years, often in conjunction with other energy types (hyperthermia, radiation) for the treatment of cancer cells. This procedure requires long preparation, energy and the use of photosensitizers. In contrast, the technique described here, using diagnostic ultrasonic frequencies, requires a low acoustic power level and, in the absence of any chemical synergy, triggers apoptosis in leukemic cells. 2 hours after ultrasonic treatment of K562 cells, a sequence of events recognized as hallmarks of apoptosis was observed: depletion of glutathione, a drop of mitochondrial potential, translocation of phospatidylserine and, subsequently, loss of membrane integrity. These effects are not dependent on the formation of species issued from the sonolysis of the solvent medium. By using minute amounts of energy, necrosis generally associated with a high physiological stress is minimized (

Grey-scale contrast enhancement in rabbit liver with DMP115 at different acoustic power levels

The contrast enhancement effect of ultrasound (US) contrast agent DMP-115 (YM454, Definity™) in rabbit liver at two acoustic transmit power levels was studied. A total of 12 rabbits with healthy livers and 7 rabbits with VX-2 tumors were used. Grey-scale ultrasonograms in both fundamental (3.75 MHz) and harmonic (2.5/5.0 MHz) imaging modes were performed at a frame rate of 26 Hz under baseline acoustic power (MI = 0.6) or lower acoustic power (MI = 0.2). The contrast enhancement depended on the contrast agent dose and the acoustic power. The video intensity change was higher in the portal vein under the baseline acoustic power and higher in the liver parenchyma under the lower acoustic power. The contrast-enhanced US observation of the VX-2 tumor in the arterial phase correlated well with the angiographic and histopathological appearance of the tumor. In the parenchymal phase, the borderline of the tumor could be clearly delineated from the surrounding liver parenchyma. Continuous fundamental and harmonic grey-scale imaging with DMP115 has the capability of making peripheral circulation images of liver parenchyma and tumors.

Asymmetric double-quantum-well phase modulator using surface acoustic waves

An AlGaAs-GaAs asymmetric double-quantum-well (DQW) optical phase modulator using surface acoustic waves is investigated theoretically. The optimization steps of the DQW structure, which so far have not been reported in detail, are discussed here. The optimized phase modulator structure is found to contain a five-period QDW active region. A surface acoustic wave induces a potential field which provides the phase modulation. Analysis of the modulation characteristics show that by using the asymmetric DQW, the large change of the induced potential at the surface and thus large modification of the quantum-well (QW) structure can be utilized. The modification of each QW structure is consistent, although this consistency is not always preserved in typical surface acoustic wave devices. Consequently, the change of refractive index in each of the five DQW's is almost identical. Besides, the change of effective refractive index is ten times larger here in comparison to a modulator with a five-period single QW as the active region and thus produces a larger phase modulation. In addition, a long wavelength and a low surface acoustic wave power required here simplify the fabrication of surface acoustic wave transducer and the acoustooptic phase modulator.

Inelastic neutron scattering on the high-frequency ultrasound in single crystals

We have observed, for the first time, inelastic neutron scattering from the phonons externally excited in single crystals. We have used ultrasonic transducers (50–200 MHz) for the excitation and neutron spin-echo spectroscopy for observing acoustic phonons. This allowed us to trace evolution of the elastic Bragg intensity I(0) and of the phonon harmonics up to the seventh order as a function of the excitation power. In contrast to the common belief, we have found that in perfect Si ultrasound does not seriously increase I(0), but an apparent increase in the Bragg intensity is entirely due to the onset of inelastic scattering. At the highest power we observed a cross-over to a chaotic phonon behavior. In deformed Si I(0) strongly decreases at a low acoustic power. The same effect could be observed in KBr and graphite crystals where the ultrasonic field made the entire mosaic blocks vibrate.

Influences of ultrasonic machine settings, transducer frequency and placement of region of interest on the measurement of integrated backscatter and cyclic variation

Integrated backscatter and its cyclic variation are potentially important parameters to discriminate normal from diseased myocardium. Cyclic variation of integrated backscatter is expected to be independent of machine settings. Backscatter images of swine hearts were taken using a two-dimensional backscatter system while acoustic power was varied at different time gain control (TGC) settings. Cyclic variation was measured in vivo with various acoustic power and TGC settings using different transducer frequencies. Three different regions were analyzed. For any given TGC setting, the relationship between acoustic power and integrated backscatter in vitro was linear only over a narrow range. In vivo, cyclic variation was present at all regions studied in both long- and short-axis views. However, lower acoustic power (<15 dB) and TGC (<20 dB), or excessive settings of acoustic power (>35 dB) and TGC (>50 dB), produced minimal cyclic variation. Appropriate acoustic power (20–35 dB) and TGC (30–50 dB) produced larger and more consistent cyclic variation at the posterior region of the left ventricle. These data indicate that each region has specific, appropriate machine settings to maximize the magnitude of cyclic variation.

The Use of Optimally Shaped Piezo-electric Film Sensors in the Active Control of Free Field Structural Radiation, Part 2: Feedback Control

Feedback control of free field structural radiation is considered. State equations are formulated with a transformation which decouples the acoustic power error criterion. Using the resultant equations, expressed in terms of “transformed mode” states, the order of the state equations can be significantly reduced at low frequencies. Two experimental implementations of feedback control strategies using shaped piezoelectric polymer film sensors to measure the transformed system states are described. The first of these is a simple analog implementation. The second implementation is in discrete time, where an adaptive algorithm for optimizing the weights of IIR filters for practical use is described. It is shown that by using the outlined control approach significant levels of low frequency acoustic power attenuation can be obtained with no control spillover and subsequent increase in higher frequency acoustic power output.

Elementary excitations and a collective mode in hcp4He

We have measured the velocity and attenuation of sound at 10, 30, and 50 MHz in solid4He at higher purity, lower density, and lower acoustic power than have been measured previously. At 10 MHz the velocity varies asT 4, as would be expected for a very high quality crystal with remarkably low dislocation density. The temperature dependence of the attenuation reveals coupling to thermally activated excitations that are consistent with vacancies measured in other work. However, in our work the activation energy is ∼0.7 K so that their concentration is sufficiently high to require Bose statistics. At 30 and 50 MHz, an unexpected, additional resonant behavior was observed. We show that the resonance is consistent with the existence of a collective mode of the vacancies and with a finite population of ground state vacancies.