Quo vadis medical ultrasound?

The last three decades of development in diagnostic ultrasound imaging and technology are briefly reviewed and the impact of the crucial link between the two apparently independent research efforts, which eventually facilitated implementation of harmonic imaging modality is explored. These two efforts included the experiments with piezoelectric PVDF polymer material and studies of the interaction between ultrasound energy and biological tissue. Harmonic imaging and its subsequent improvements revolutionized the diagnostic power of clinical ultrasound and brought along images of unparalleled resolution, close to that of magnetic resonance imaging (MRI) quality. The nonlinear propagation effects and their implications for both diagnostic and therapeutic applications of ultrasound are also briefly addressed. In diagnostic applications, the impact of these effects on image resolution and tissue characterization is reviewed; in therapeutic applications, the influence of nonlinear propagation effects on highly localized tissue ablation and cauterization is examined. Next, the most likely developments and future trends in clinical ultrasound technology, including 3D and 4D imaging, distant palpation, image enhancement using contrast agents, monitoring, and merger of diagnostic and therapeutic applications by e.g. introducing ultrasonically controlled targeted drug delivery are reviewed. Finally, a possible competition from other imaging modalities is discussed.     

Design and experiment of 256-element ultrasound phased array for noninvasive focused ultrasound surgery

A 256-element phased array high intensity focused ultrasound system has been designed and constructed in our laboratory. The 256-element spherical-section ultrasound phased array made from piezocomposite material operates at 1.1 MHz with 11-cm radius of curvature, 14-cm outer diameter, and 3.4-cm diameter central hole for mounting diagnostic ultrasound imaging probe. First, the explicit sound field calculation approach for the spherical-section phased array and the genetic optimal algorithm are briefly introduced as the optimal focus pattern control methods. Then, the design guidelines of 256-element spherical-section focused ultrasound phased array and 256-channel driver system are given. The results of single on and off axial focus, multiple on and off axial foci, half sub-array focus pattern provide further evidence for the 3D focus steering and sub-array mode for avoiding obstacles in focused ultrasound surgery. The multi-foci pattern can enlarge the treatment volume to 22 times larger than that of a single focus in one sonication. Finally, in vitro and transparent tissue-mimicking phantom experiment results confirm the ability of 256-element spherical-section phased array system to induce thermal lesions for noninvasive ultrasound surgery.     

横观各向同性材料中激光超声谱有限元数值模拟

研究了横观各向同性材料中激光超声波的传播特征.基于谱有限元方法,建立了横观各向同性材料中激光超声的数值模型.利用谱有限元方法模拟脉冲激光作用于材料上产生超声波及其传播的过程.讨论了横观各向同性薄板的各向异性及各向同性平面内超声波的传播特征,并分析了材料厚度的变化对产生超声波模态的影响.     

Acoustic cavitation produced by microsecond pulses of ultrasound: a discussion of some selected results.

Because of its extensive utilization in clinical practice, and because the subjects examined are often fragile and sensitive to trauma, the safety of diagnostic ultrasound has always been of concern. Of the various mechanisms through which ultrasound could act in a manner deleterious to a patient, acoustic cavitation, should it occur, appears to possess significant potential for biological damage. This paper reviews several recent reports of progress by our two groups and demonstrates the conditions under which cavitation has been observed by microsecond pulses of ultrasound. Although these results give no indications that diagnostic ultrasound may pose a true risk to a patient, they do indicate that in vivo cavitation may occur under certain conditions.     

A digital image analysis method for diagnostic ultrasound calibration

Acoustic test objects are commonly used for quality assurance testing of diagnostic ultrasound machines. However, the accompanying calibration protocols rely heavily on the judgment of the sonographer, are dependent on machine settings and are semi-quantitative. In the current study, two unique test objects and protocols were designed to quantitatively determine diagnostic ultrasound parameters, namely axial resolution and geometric uniformity, and lateral resolution and geometric uniformity of the ultrasound field. The effect of focal zone, signal gain, and distance from the ultrasound probe on these parameters was assessed. The investigation was performed using a typical low-frequency diagnostic unit equipped with a 7.5 MHz linear pulse–echo probe. Results underline the need to ensure that sensitivity of routine testing regimes is adequate for the measurements to be made. This study is a preliminary part of a larger project developing an ultrasound technique to be used as an engineering design tool in a non-clinical industrial setting for quality assurance testing of total knee replacements immersed in water.     

横观各向同性材料中激光超声谱有限元数值模拟

研究了横观各向同性材料中激光超声波的传播特征．基于谱有限元方法,建立了横观各向同性材料中激光超声的数值模型．利用谱有限元方法模拟脉冲激光作用于材料上产生超声波及其传播的过程．讨论了横观各向同性薄板的各向异性及各向同性平面内超声波的传播特征,并分析了材料厚度的变化对产生超声波模态的影响．     

Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro

Light scattering was used to measure the radial pulsations of individual ultrasound contrast microbubbles subjected to pulsed ultrasound. Highly diluted Optison or Sonazoid microbubbles were injected into either a water bath or an aqueous solution containing small quantities of xanthan gum. Individual microbubbles were insonified by ultrasound pulses from either a commercial diagnostic ultrasound machine or a single element transducer. The instantaneous response curves of the microbubbles were measured. Linear and nonlinear microbubble oscillations were observed. Good agreement was obtained by fitting a bubble dynamics model to the data. The pulse-to-pulse evolution of individual microbubbles was investigated, the results of which suggest that the shell can be semipermeable, and possibly weaken with subsequent pulses. There is a high potential that light scattering can be used to optimize diagnostic ultrasound techniques, understand microbubble evolution, and obtain specific information about shell parameters.     

Lack of increase in cell transformation frequency of C3H cells after exposure to pulsed ultrasound

Liebeskind et al. reported that ultrasound from a diagnostic ultrasound unit caused an increase in cell transformation of in vitro C3H cells. The objective of this study was to attempt verification of this result, using the same cell line and a similar ultrasound exposure regimen. Four experiments were undertaken, each involving an ultrasound, X-ray (positive control) and sham exposure regimen. There was no increase in cell transformation frequency with the ultrasound exposure, but a small and statistically significant increase with the X-ray regimen.     

Optimal design and experimental investigation of surfactant encapsulated microbubbles

The diagnostic capabilities of ultrasound imaging can be improved with contrast-specific nonlinear imaging modalities such as harmonic and subharmonic imaging. The nonlinear response of an encapsulated microbubble in an acoustic field is strongly influenced by the shell viscoelastic properties that are determined by the shell composition and thickness. In this paper, the subharmonic performance of a surfactant encapsulated microbubble was optimized by choosing the appropriate composition of shell material with the aid of theoretical model. To study the effects of viscoelastic properties of microbubble shell materials on the nonlinear scattered response of microbubbles, a theoretical model-modified Herring equation for the oscillation of encapsulated microbubbles in the ultrasound field was employed. Based on this model, a computer aided design system was developed to optimize and analyze the acoustic properties, particularly subharmonic responses, of microbubbles under different shell parameters. Furthermore, surfactant encapsulated microbubbles with different viscoelastic properties were prepared by changing the shell composition. Their shell viscoelastic behavior was measured indirectly as dilational modulus of monolayer film formed with surfactant molecular. Moreover, in vitro quantitative acoustic properties measurements of these microbubbles were carried out to evaluate their subharmonic performance. Both of the theoretical simulation and acoustic measurement showed that the surfactant encapsulated microbubbles with good subharmonic properties could be designed and prepared by adjusting the shell material composition with the guide of the computer aided design system.     

Preparation and in vitro evaluation of an ultrasound-triggered drug delivery system: 10-hydroxycamptothecin loaded PLA microbubbles

10-Hydroxycamptothecin (HCPT) loaded PLA microbubbles, used as an ultrasound-triggered drug delivery system, were fabricated by a double emulsion-solvent evaporation method. The obtained microbubbles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and confocal laser scanning microscope (CLSM). In addition, the effect of diagnostic ultrasound exposure on BEL-7402 cells combined with HCPT-loaded PLA microbubbles was evaluated using cytotoxicity assay, CLSM and flow cytometry (FCM). It was found that the HCPT-loaded PLA microbubbles showed smooth surface and spherical shape, and the drug was amorphously dispersed within the shell and the drug loading content reached up to 1.69%. Nearly 20% of HCPT was released upon exposure to diagnostic ultrasound at frequency of 3.5 MHz for 10 min. Moreover, HCPT fluorescence in the cells treated only with the HCPT-loaded PLA microbubbles was discernible, but less intense, while those treated with the microbubbles in conjunction with ultrasound exposure was evident and intense, indicating an increased cellular uptake of HCPT by ultrasound exposure. Cytotoxicity test on BEL-7402 cells indicated that the HCPT-loaded PLA microbubbles combined with ultrasound exposure were more cytotoxic than the microbubbles alone. The results suggest that the combination of drug loaded PLA microbubbles and diagnostic ultrasound exposure exhibit an effective intracellular drug uptake by tumor cells, indicating their great potential for antitumor therapy.     

Simulation of diagnostic ultrasound image pulse sequences in cavitation bioeffects research

Research on cavitational bioeffects of diagnostic ultrasound (DUS) typically involves a diagnostic scanner as the exposure source. However, this can limit the ranges of exposure parameters for experimentation. Anesthetized hairless rats were mounted in a water bath and their right kidneys were exposed to ultrasound. Amplitude modulation with Gaussian envelopes simulated the image pulse sequences (IPSs) produced by diagnostic scanning. A 10 mulkgmin IV dose of Definity((R)) contrast agent was given during 1-5 min exposures. Glomerular capillary hemorrhage was assessed by histology. A stationary exposure approximated the bioeffects induced by DUS within the beam area. However, the use of five closely spaced exposures more faithfully reproduced the total effect produced within a DUS scan plane. Single pulses delivered at 1 s intervals induced the same effect as the simulated DUS. Use of 100 ms triangle-wave modulations for ramp-up or ramp-down of the IPS gave no effect or a large effect, respectively. Finally, an air-backed transducer simulating DUS without contrast agent showed a zero effect even operating at twice the present DUS guideline upper limit. Relatively simple single-element laboratory exposure systems can simulate diagnostic ultrasound exposure and allow exploration of parameter ranges beyond those available on present clinical systems.     

Effects of an implant on temperature distribution in tissue during ultrasound diathermy

The effects of an implant on temperature distribution in a tissue-mimicking hydrogel phantom during the application of therapeutic ultrasound were investigated. In vitro experiments were conducted to compare the influences of plastic and metal implants on ultrasound diathermy and to calibrate parameters in finite element simulation models. The temperature histories and characteristics of the opaque (denatured) areas in the hydrogel phantoms predicted by the numerical simulations show good correlation with those observed in the in vitro experiments. This study provides an insight into the temperature profile in the vicinity of an implant by therapeutic ultrasound heating typically used for physiotherapy. A parametric study was conducted through numerical simulations to investigate the effects of several factors, such as implant material type, ultrasound operation frequency, implant thickness and tissue thickness on the temperature distribution in the hydrogel phantom. The results indicate that the implant material type and implant thickness are the main parameters influencing the temperature distribution. In addition, once the implant material and ultrasound operation frequency are chosen, an optimal implant thickness can be obtained so as to avoid overheating injuries in tissue.     

Numerical simulation of laser-generated ultrasound in non-metallic material by the finite element method

The use of a pulsed laser for the generation of the elastic waves in non-metallic materials in the thermoelastic regime is investigated by using finite element method (FEM), taking into account not only thermal diffusion and the finite spatial and temporal shape of the laser pulse, but also optical penetration and the temperature dependence of material properties. The optimum finite element model is established based on analysis of two important parameters, meshing size and time step, and the stability of solution. Temperature distributions and temperature gradient fields in non-metallic material for different time steps are obtained, this temperature field is equivalent to a bulk force source to generate ultrasonic wave. The laser-generated ultrasound waveforms at the epicenter and surface acoustic waveforms (SAWs) are obtained and the influence of optical penetration into the material on the temperature field and the ultrasound waveforms are analyzed. The numerical results indicate that the heat penetration into non-metallic material is caused mainly by the optical penetration, and the ultrasound waveforms, especially the shape of the precursor, are strongly dependent on the optical penetration depth into non-metallic material.     

Increased heating by diagnostic ultrasound due to nonlinear propagation

The heating of tissues by the absorption of ultrasound is an important safety consideration in the use of diagnostic ultrasound. This paper shows that models of ultrasonic heating for this situation need to take account of nonlinear propagation. Measurements were made of the temperature rise in a sample of tissue-mimicking gel, caused by the application of 3.6-MHz focused ultrasonic beams for 3 min. The propagation path to the focus was in water, to mimic the situation where the fetus is scanned through the full bladder. The effect of nonlinear propagation was seen by changing the pressure amplitude of the pulse, while altering the pulsing regime to preserve a constant spatial-peak temporal-average intensity of 1 W cm-2. When nonlinear distortion was present, an enhancement in the temperature rise was observed, which correlated with the value of the shock parameter. The enhancement ratio was typically up to a factor of 3, and the maximum temperature rise observed was 2 degrees C. This enhanced heating was seen both at the surface of the tissue-mimicking gel and after propagation through 23 mm of the material. Under conditions of nonlinear propagation, the maximum heating usually occurs in the prefocal region, rather than at the focus.     

Studies on the foundation and development of diagnostic ultrasound

In recent years, various types of diagnostic imaging methods, such as CT, MRI, PET and Ultrasound, have been developed rapidly and become indispensable as clinical diagnostic tools. Among these imaging modalities, CT, MRI and PET all apply electromagnetic waves like radiation rays. In contrast, an ultrasound imaging method uses a completely different mechanical pressure wave: “sound”. Ultrasound has various features, including inaudible sound at very high frequencies, which allows its use in medical diagnoses. That is, ultrasound techniques can be applied in transmission, reflection and Doppler methods. Moreover, the sharp directivity of an ultrasound beam can also improve image resolution. Another big advantage of diagnostic ultrasound is that it does not harm the human body or cause any pain to patients. Given these various advantages, diagnostic ultrasound has recently been widely used in diagnosing cancer and cardiovascular disease and scanning fetuses (Fig. 1) as well as routine clinical examinations in hospitals. In this paper, I outline my almost 50-year history of diagnostic ultrasound research, particularly that performed at the early stage from 1950–56.Open in a separate windowFig. 1.The recent ultrasonic real-time imaging diagnostic instrument by electric scan system and three dimensional images of fetus.     

Design of thermistor probes for measurement of ultrasound intensity distributions

Thermistors coated with absorbing material provide small omnidirectional probes for measurement of ultrasound intensity distributions. They are simple and inexpensive to construct and can be made with dimensions less than 1 mm. The use of various glues, varnishes and resins for the ultrasound absorbing coating is considered. Heat is generated by shear viscosity in the neighbourhood of the boundary between the thermistor and coating material. The rate of temperature rise over the first one or two hundred milliseconds after the ultrasound is switched on is a reasonably linear function of intensity over the range used in physiotherapy.     

The impact of bubbles on measurement of drug release from echogenic liposomes

Echogenic liposomes (ELIP) encapsulate gas bubbles and drugs within lipid vesicles, but the mechanisms of ultrasound-mediated drug release from ELIP are not well understood. The effect of cavitation activity on drug release from ELIP was investigated in flowing solutions using two fluorescent molecules: a lipophilic drug (rosiglitazone) and a hydrophilic drug substitute (calcein). ELIP samples were exposed to pulsed Doppler ultrasound from a clinical diagnostic ultrasound scanner at pressures above and below the inertial and stable cavitation thresholds. Control samples were exposed to a surfactant, Triton X-100 (positive control), or to flow alone (negative control). Fluorescence techniques were used to detect release. Encapsulated microbubbles reduced the measured fluorescence intensity and this effect should be considered when assessing drug release from ELIP. The origin of this effect is not specific to ELIP. Release of rosiglitazone or calcein compared to the negative control was only observed with detergent treatment, but not with ultrasound exposure, despite the presence of stable and inertial cavitation activity. Release of rosiglitazone or calcein from ELIP exposed to diagnostic ultrasound was not observed, even in the presence of cavitation activity. Ultrasound-mediated drug delivery strategies with ELIP will thus rely on passage of the drug-loaded liposomes to target tissues.     

A comparison of two methods for determining ultrasonic intensity for medical transducers

The spatial and temporal average intensity (ISATA) is determined for four diagnostic ultrasound transducers by two methods: (a) direct measurements (beam profiling) with a miniature hydrophone, as described in the AIUM-NEMA standard, and (b) estimating from measurements of total power and assumptions about beam size. The latter method is frequently used by diagnostic ultrasound manufacturers when reporting output levels to users and regulatory agencies. However, due to the conventions for defining beam area, this method actually overestimates the spatial average intensity. For the four transducers tested, the estimated ISATA exceeds the measured ISATA by several hundred percent. The spatial peak, temporal average intensity (ISPTA) was also measured for the four transducers and is less than the estimated ISATA in every case.     

激光超声的原理及其在固体中的应用

激光超声是指脉冲激光所产生的脉冲超声。激光超声是较新的产生超声的方法。它的主要特色是，可以遥发遥收，这样就有可能在高温、有危险辐射等恶劣环境下以及在样品运动的生产线上进行超声检测。皮秒级和飞秒级的激光所激发的超声近来又用来研究固体中电子和声子的相互作用。文章介绍了固体中激光超声的声学性能及两种产生机理：热弹机理和电子机理。     

Therapeutic ultrasound an overview

Therapeutic ultrasound is defined as the use of ultrasound for the treatment of diseased or injured organs or bodily structures and is quite distinct from diagnostic ultrasound. There were many early attempts in the past to use ultrasound in therapy for a variety of applications and while some of these have not been pursued others have led on to clinical applications which are now used routinely. Such progress has been made possible by a number of factors including advances in transducer design, more accurate measurement and calibration of acoustic power and careful experiments to determine the precise nature of chemical processes taking place during and following the exposure of tissue to ultrasound. Major advances have been made in some fields where ultrasound is used such as physiotherapy, surgical instruments, chemotherapy, drug delivery and more recently, high intensity focused ultrasound (HIFU). The last of these has seen enormous activity leading to the formation of the International Society of Therapeutic Ultrasound and a number of very well attended regular specialist meetings. In this review some historical perspectives of therapeutic ultrasound and progress in the field since the early 1990's will be presented.