Showing papers in "Ultrasound in Medicine and Biology in 2005"

A review of calibration techniques for freehand 3-D ultrasound systems.

Abstract: Three-dimensional (3-D) ultrasound (US) is an emerging new technology with numerous clinical applications. Ultrasound probe calibration is an obligatory step to build 3-D volumes from 2-D images acquired in a freehand US system. The role of calibration is to find the mathematical transformation that converts the 2-D coordinates of pixels in the US image into 3-D coordinates in the frame of reference of a position sensor attached to the US probe. This article is a comprehensive review of what has been published in the field of US probe calibration for 3-D US. The article covers the topics of tracking technologies, US image acquisition, phantom design, speed of sound issues, feature extraction, least-squares minimization, temporal calibration, calibration evaluation techniques and phantom comparisons. The calibration phantoms and methods have also been classified in tables to give a better overview of the existing methods.

MRI-guided targeted blood-brain barrier disruption with focused ultrasound: Histological findings in rabbits

Abstract: Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at targeted locations. The purpose of this study was to test the safety of this method by searching for ischemia and apoptosis in areas with BBB disruption induced by pulsed ultrasound in the presence of preformed gas bubbles and by looking for delayed effects up to one month after sonication. Pulsed ultrasound exposures (sonications) were performed in the brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI) (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration = 20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound contrast agent (Optison®, GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using haematoxylin and eosin staining for general histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and TUNEL staining for apoptosis. The main effects observed were tiny regions of extravasated red blood cells scattered around the sonicated locations, indicating affected capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or apoptotic regions were detected that would indicate a compromised blood supply was induced by the sonications. No delayed effects were observed either by MRI or histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic or apoptotic death to neurons. These findings indicate that this method is safe for targeted drug delivery, at least when compared with the currently available invasive methods.

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

Abstract: 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.

Gel phantom for use in high-intensity focused ultrasound dosimetry

Abstract: An optically transparent phantom was developed for use in high-intensity focused ultrasound (US), or HIFU, dosimetry studies. The phantom is composed of polyacrylamide hydrogel, embedded with bovine serum albumin (BSA) that becomes optically opaque when denatured. Acoustic and optical properties of the phantom were characterized as a function of BSA concentration and temperature. The speed of sound (1544 m/s) and acoustic impedance (1.6 MRayls) were similar to the values in soft tissue. The attenuation coefficient was approximately 8 times lower than that of soft tissues (0.02 Np/cm/MHz for 9% BSA). The nonlinear (B/A) coefficient was similar to the value in water. HIFU lesions were readily seen during formation in the phantom. In US B-mode images, the HIFU lesions were observed as hyperechoic regions only if the cavitation activity was present. The phantom can be used for fast characterization and calibration of US-image guided HIFU devices before animal or clinical studies.

Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo.

Abstract: Previous in vivo studies have demonstrated that microvessel hemorrhages and alterations of endothelial permeability can be produced in tissues containing microbubble-based ultrasound contrast agents when those tissues are exposed to MHz-frequency pulsed ultrasound of sufficient pressure amplitudes. The general hypothesis guiding this research was that acoustic ( viz. , inertial) cavitation, rather than thermal insult, is the dominant mechanism by which such effects arise. We report the results of testing five specific hypotheses in an in vivo rabbit auricular blood vessel model: (1) acoustic cavitation nucleated by microbubble contrast agent can damage the endothelia of veins at relatively low spatial-peak temporal-average intensities, (2) such damage will be proportional to the peak negative pressure amplitude of the insonifying pulses, (3) damage will be confined largely to the intimal surface, with sparing of perivascular tissues, (4) greater damage will occur to the endothelial cells on the side of the vessel distal to the source transducer than on the proximal side and (5) ultrasound/contrast agent-induced endothelial damage can be inherently thrombogenic, or can aid sclerotherapeutic thrombogenesis through the application of otherwise subtherapeutic doses of thrombogenic drugs. Auricular vessels were exposed to 1-MHz focused ultrasound of variable peak pressure amplitude using low duty factor, fixed pulse parameters, with or without infusion of a shelled microbubble contrast agent. Extravasation of Evans blue dye and erythrocytes was assessed at the macroscopic level. Endothelial damage was assessed via scanning electron microscopy (SEM) image analysis. The hypotheses were supported by the data. We discuss potential therapeutic applications of vessel occlusion, e.g. , occlusion of at-risk gastric varices. (E-mail: jooha@u.washington.edu )

High-speed optical observations of contrast agent destruction.

Abstract: Ultrasound contrast agents are now available since a few years and used for diagnostic purposes. Improved diagnostic decisions have been made possible with new imaging methods that are mainly based on the nonlinear properties of gas microbubbles. Since it is well known that contrast agents are destroyed by ultrasound when the acoustic pressure exceeds a threshold, extremely low acoustic pressures were applied to achieve enhanced contrast image quality. However, destruction of contrast microbubbles is not necessarily undesirable, since it is beneficial in, for example, destruction/reperfusion imaging and recently in drug delivery. We investigate in this experimental study the destruction dynamics of a contrast agent consisting of nitrogen bubbles encapsulated in a double polymer/albumin wall shell. This is accomplished using an ultrafast camera Brandaris that operates at a frame rate of 25 MHz and records 128 frames. The measurements were performed with an ultrasound sine burst of 10 cycles at 1.7 MHz. Different acoustic pressures were applied and various microsphere sizes were examined. The results show three different zones depending on the applied pressure and bubble size: these are nondestruction zone, transient zone and destruction zone. The nondestruction zone is reached for either very small microspheres or low mechanical indices (MI) (<0.3). In the destruction zone lie either large microspheres (5 m or higher) even when irradiated at low MIs or small microspheres (< 5 m) when the MI is above 0.6. The optical observations revealed that the destruction of the microspheres is characterized by shell rupture and gas release. The release of the gas gives rise to new free microbubble that lasts for a few milliseconds and then disappears due to dissolution. In the transient zone, the microspheres are mainly compressed in the first few cycles but no expansion is induced. After intense compressions, the shell fissures and gas escapes in the last cycles of the burst or during a second burst depending on the initial size and MI. These optical recordings are important to investigate contrast bubble destruction and can help in amplifying or minimizing this process. Indeed, bubble disruption remains the basis of most current sensitive methods for detecting perfusion with contrast agents and is an essential component of perfusion quantification with microbubbles, in addition to drug delivery applications and pressure measurements.

Low-intensity pulsed ultrasound: Effects on nonunions

Abstract: To study the efficacy of low-intensity pulsed ultrasound (US), or LIPUS, of 85 treated nonunion cases with a minimum fracture age of 8 months, 67 cases met the study criteria. These were: no surgical intervention during 4 months before US treatment and radiographically ceased healing for 3 months before US. In a self-paired control study, the mean fracture age of the 67 patients was 39 +/- 6.2 months. After a daily 20-min US treatment at home for an average of 168 days, 85% (57 of 67) of the nonunion cases were clinically and radiographically healed. The study did not include any cases that were malaligned, grossly instable, actively infected or that had extensive bone loss. The results demonstrate that the specific US can effect heal rates similar to those achieved by surgical means, without the associated risks and complications, and to those achieved by electrical bone growth stimulation or by extracorporeal shock-wave therapy.

Acoustic radiation force impulse imaging of the abdomen : Demonstration of feasibility and utility

Abstract: The feasibility of utilizing acoustic radiation force impulse (ARFI) imaging to assess the mechanical properties of abdominal tissues was investigated. The thermal safety of the technique was also evaluated through the use of finite element method models. ARFI imaging was shown to be capable of imaging abdominal tissues at clinically realistic depths. Correspondence between anatomical structures in B-mode and ARFI images was observed. ARFI images showed similar tumor contrast when compared with B-mode images of ex vivo abdominal cancers. Finite element method models and in vitro measurements confirmed the thermal safety of ARFI imaging at depth. ARFI imaging is inexpensive, safe and convenient and is a promising modality for use in abdominal imaging.

Hyperecho in ultrasound images of HIFU therapy: Involvement of cavitation

Abstract: High-intensity focused ultrasound (US), or HIFU, treatment of soft tissues has been shown to result in a hyperechoic region in B-mode US images. We report on detecting cavitation in vivo in correlation with the appearance of a hyperechoic region. The US system consisted of a HIFU transducer (3.3 MHz), a broadband A-mode transducer for active and passive cavitation detection and an US-imaging probe that were all confocal and synchronized. HIFU, at in situ intensities of 220 to 1710 W/cm(2), was applied for 10 s to pig muscles in vivo. Active and passive cavitation detection results showed a strong correlation between the onset of cavitation and the appearance of a hyperechoic region. Passive cavitation detection results showed that inertial cavitation typically occurred prior (within 0.5 s) to the appearance of a hyperechoic region. The observed cavitation activity confirms that bubbles are present during the formation of a hyperechoic region at the HIFU focus.

Miniaturized ultrasound arrays for interstitial ablation and imaging

Abstract: A potential alternative to extracorporeal, noninvasive HIFU therapy is minimally invasive intense ultrasound ablation that can be performed laparoscopically or percutaneously. An approach to minimally invasive ablation of soft tissue using miniaturized linear ultrasound arrays is presented here. Recently developed 32-element arrays with aperture 2.3 × 49 mm, therapy frequency 3.1 MHz, pulse-echo bandwidths >42% and surface acoustic energy density >80 W/cm 2 , are described. These arrays are integrated into a probe assembly, including a coupling balloon and piercing tip, suitable for interstitial ablation. An integrated electronic control system allows therapy planning and automated treatment guided by real-time interstitial B-scan imaging. Image quality, challenging because of limited probe dimensions and channel count, is aided by signal processing techniques that improve image definition and contrast, resulting in image quality comparable to typical transabdominal ultrasound imaging. Ablation results from ex vivo and in vivo experiments on mammalian liver tissue show that this approach is capable of ablation rates and volumes relevant to clinical applications of soft tissue ablation such as treatment of liver cancer. (E-mail: i.makin@guidedtherapy.com )

Early gene response to low-intensity pulsed ultrasound in rat osteoblastic cells.

Abstract: The aim of the current research was to quantify the changes in gene expression in rat bone marrow derived stromal cells (BMSC) to low intensity pulsed ultrasound (LIPUS) during early time points after the ultrasound application. LIPUS at 1.5 MHz, 30 mW/cm(2) was applied to BMSC for a single 20 min treatment. Real-time PCR was carried out to quantify the expression of early response genes and bone differentiation marker genes 0.5, 1, 3, 6 and 12 h after the end of the LIPUS treatment. Compared with the controls, LIPUS treatment resulted in elevated transient expression of early response genes (c-jun, c-myc, COX-2, Egr-1, TSC-22) as well as the bone differentiation marker genes, osteonectin and osteopontin, at 3 h. This induction of early response genes as well as extracellular matrix genes associated with cell proliferation and differentiation may represent the effect of LIPUS to cells of osteoblastic lineage.

Bone microstructure and elastic tissue properties are reflected in QUS axial transmission measurements.

Abstract: Accurate clinical interpretation of the sound velocity derived from axial transmission devices requires a detailed understanding of the propagation phenomena involved and of the bone factors that have an impact on measurements. In the low megahertz range, ultrasonic propagation in cortical bone depends on anisotropic elastic tissue properties, porosity and the cortical geometry (e.g., thickness). We investigated 10 human radius samples from a previous biaxial transmission study using a 50-MHz scanning acoustic microscope (SAM) and synchrotron radiation microcomputed tomography. The relationships between low-frequency axial transmission sound speed at 1 and 2 MHz, structural properties (cortical width Ct.Wi, porosity, Haversian canal density and material properties (acoustic impedance, mineral density) on site-matched cross-sections were investigated. Significant linear multivariate regression models (1 MHz: R 2 0.84, p < 10 4 , root-mean-square error (RMSE) 38 m/s, 2 MHz: R 2 0.65, p < 10 4 , RMSE 48 m/s) were found for the combination of Ct.Wi with porosity and impedance. A new model was derived that accounts for the nonlinear dispersion relation with Ct.Wi and predicts axial transmission velocities measured at different ultrasonic frequencies (R 2 0.69, p < 10 4 , RMSE 52 m/s). (E-mail: kay.raum@medizin.uni-halle.de) © 2005 World Federation for Ultrasound in Medicine & Biology.

Monitoring structural changes in cells with high-frequency ultrasound signal statistics.

Abstract: We investigate the use of signal envelope statistics to monitor and quantify structural changes during cell death using an in vitro cell model. Using a f/2.35 transducer (center frequency 20 MHz), ultrasound backscatter data were obtained from pellets of acute myeloid leukemia cells treated with a DNA-intercolating chemotherapy drug, as well as from pellets formed with mixtures of treated and untreated cells. Simulations of signals from pellets of mixtures of cells were generated as a summation of point scatterers. The signal envelope statistics were examined by fitting the Rayleigh and generalized gamma distributions. The fit parameters of the generalized gamma distribution showed sensitivity to structural changes in the cells. The scale parameter showed a 200% increase (p<0.05) between untreated and cells treated for 24 h. The shape parameter showed a 50% increase (p<0.05) over 24 h. Experimental results showed reasonable agreement with simulations. The results indicate that high-frequency ultrasound signal statistics can be used to monitor structural changes within a very low percentage of treated cells in a population, raising the possibility of using this technique in vivo.

Comparison of three ultrasonic axial transmission methods for bone assessment.

Abstract: This study compared three approaches to bone assessment using ultrasonic axial transmission. In 41 fresh human radii, velocity of the first arriving signal was measured with a commercial device (Sunlight Omnisense ™ ) operating at 1.25 MHz, a prototype based on 1-MHz bidirectional axial transmission and a low-frequency (200 kHz) prototype, also measuring the velocity of a slower wave. Cortical and trabecular bone mineral density, cortical thickness and cross-sectional area were determined by peripheral quantitative computed tomography. Significant but modest correlation between velocities reflects differences in the nature of the propagating waves and methodological differences. Of the higher frequency devices, bidirectional measurements provided stronger correlations with bone properties than did conventional measurements. High-frequency devices were less sensitive to cortical thickness than was the low-frequency device, because higher frequency waves interrogate thinner cortical layers. The results suggest that different axial transmission approaches reflect different bone properties. Therefore, a multifrequency technique might be useful in probing different bone properties. (E-mail: marie.muller@lip.bhdc.jussieu.fr )

Effectiveness of lipid microbubbles and ultrasound in declotting thrombosis

Abstract: The objectives of this study were to determine the effectiveness of lipid-encapsulated microbubbles and ultrasound (US) in recanalizing arteriovenous graft thrombi and the effect that tissue attenuation has on the success rate A total of 55 thrombotic occlusions were created in four canines The thrombosed grafts were randomly treated with two different 1-MHz US intensities, low (04 to 06 W/cm2) and high (10 W/cm2) Intragraft microbubbles were compared with intragraft saline and with the same dose of microbubbles given IV IV microbubbles were also given both in the presence and absence of a tissue-mimicking phantom High-intensity US (10 W/cm2) with intragraft microbubbles produced significantly higher patency and flow scores than did US with saline (p < 001) US with IV microbubbles had higher success rates in recanalizing thrombosed grafts than did US alone at all intensities Attenuation reduced the rate at which successful recanalization occurred at both low and high intensities US and microbubbles are capable of recanalizing acute arteriovenous graft thromboses Higher intensities may be needed in the presence of tissue attenuation

Segmentation of real-time three-dimensional ultrasound for quantification of ventricular function: a clinical study on right and left ventricles.

Abstract: Among screening modalities, echocardiography is the fastest, least expensive and least invasive method for imaging the heart. A new generation of three-dimensional (3-D) ultrasound (US) technology has been developed with real-time 3-D (RT3-D) matrix phased-array transducers. These transducers allow interactive 3-D visualization of cardiac anatomy and fast ventricular volume estimation without tomographic interpolation as required with earlier 3-D US acquisition systems. However, real-time acquisition speed is performed at the cost of decreasing spatial resolution, leading to echocardiographic data with poor definition of anatomical structures and high levels of speckle noise. The poor quality of the US signal has limited the acceptance of RT3-D US technology in clinical practice, despite the wealth of information acquired by this system, far greater than with any other existing echocardiography screening modality. We present, in this work, a clinical study for segmentation of right and left ventricular volumes using RT3-D US. A preprocessing of the volumetric data sets was performed using spatiotemporal brushlet denoising, as presented in previous articles Two deformable-model segmentation methods were implemented in 2-D using a parametric formulation and in 3-D using an implicit formulation with a level set implementation for extraction of endocardial surfaces on denoised RT3-D US data. A complete and rigorous validation of the segmentation methods was carried out for quantification of left and right ventricular volumes and ejection fraction, including comparison of measurements with cardiac magnetic resonance imaging as the reference. Results for volume and ejection fraction measurements report good performance of quantification of cardiac function on RT3-D data compared with magnetic resonance imaging with better performance of semiautomatic segmentation methods than with manual tracing on the US data. ( laine@columbia.edu )

Physical enviroment of 2-D animal cell aggregates formed in a short pathlength ultrasound standing wave trap

Abstract: 2-D mammalian cell aggregates can be formed and levitated in a 1.5 MHz single half wavelength ultrasound standing wave trap. The physical environment of cells in such a trap has been examined. Attention was paid to parameters such as temperature, acoustic streaming, cavitation and intercellular forces. The extent to which these factors might be intrusive to a neural cell aggregate levitated in the trap was evaluated. Neural cells were exposed to ultrasound at a pressure amplitude of 0.54 MPa for 30 s; a small aggregate had been formed at the center of the trap. The pressure amplitude was then decreased to 0.27 MPa for 2 min, at which level the aggregation process continued at a slower rate. The pressure amplitude was then decreased to 0.06 MPa for 1 h. Temperature measurements that were conducted in situ with a 200 μm thermocouple over a 30 min period showed that the maximum temperature rise was less than 0.5 K. Acoustic streaming was measured by the particle image velocimetry method (PIV). It was shown that the hydrodynamic stress imposed on cells by acoustic streaming is less than that imposed by gentle preparative centrifugation procedures. Acoustic spectrum analysis showed that cavitation activity does not occur in the cell suspensions sonicated at the above pressures. White noise was detected only at a pressure amplitude of 1.96 MPa. Finally, it was shown that the attractive acoustic force between ultrasonically agglomerated cells is small compared with the normal attractive van der Waals force that operates at close cell surface separations. It is concluded that the standing wave trap operates only to concentrate cells locally, as in tissue, and does not modify the in vitro expression of surface receptor interactions. E-mail. coakley@cf.ac.uk

Elastography for the follow-up of high-intensity focused ultrasound prostate cancer treatment: initial comparison with mri

Abstract: We previously developed an ultrasonic elastography imaging system that may provide a simple and cost-effective solution to monitor high-intensity focused ultrasound (HIFU) treatments. The objective of this clinical study was to evaluate the reliability of our system in assessing the volume of HIFU lesions in the prostate, using a comparison with magnetic resonance imaging (MRI). Elastograms were obtained in 20 patients after HIFU treatment for prostate cancer and gadolinium-enhanced T1- and T2-weighted MRI was performed. Lesion boundaries were manually outlined and the volume was calculated. A statistically significant correlation of rho = 0.62 (p = 0.022) was found between elastographic and MRI measurements of lesion volume, with elastographic measurements that generally underestimated the volume measured in MRI. Some basic physics (hypoechoic areas) and instrumentation (frame rate and band width) issues that were detrimental to image quality in vivo are reported, along with propositions to improve the technique. Because of these issues and, although good correspondence between elastographic and MRI measurements was found in some patients, elastographic measurements were unable to predict MRI measurements in a single individual. Nevertheless, the results confirmed the potential of elastography for monitoring HIFU treatment of the prostate. Further investigation will be conducted using better suited ultrasound equipment and performing real-time elastogram calculations.

Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction.

Abstract: Gas-filled microbubbles have become an important tool as ultrasonic contrast agents. We have previously shown that ultrasound-targeted microbubble destruction (UTMD) can direct plasmids to the heart. The aim of this study was to evaluate UTMD for protein delivery. Six different groups of rats received 1 μg of luciferase protein with varying protocols: (1) luciferase-loaded microbubbles and ultrasound; (2) luciferase only; (3) luciferase and ultrasound; (4) luciferase-loaded microbubbles; (5) unloaded microbubbles incubated with luciferase and ultrasound; (6) unloaded microbubbles with ultrasound followed by luciferase. Relative luminescence units per mg protein per s were determined in hearts and control organs. The rats that received ultrasound and luciferase-loaded bubbles showed a six-fold higher cardiac luciferase uptake compared with control groups that did not include bubbles. None of the other groups significantly augmented cardiac luciferase activity. We conclude that ultrasound-targeted microbubble destruction can substantially and noninvasively augment organ-specific delivery of proteins. (Email: ralph.shohet@utsouthwestern.edu )

Monitoring the formation of thermal lesions with heat-induced echo-strain imaging: a feasibility study.

Abstract: We investigated the feasibility of using echo-strain images to visualize the extent of high-intensity ultrasound (US)-induced thermal lesions during their formation. Echo-strain, defined as the relative deformation of the backscattered ultrasonic signal, is due to tissue expansion and to changes in the speed of sound during heating. First, a theoretical framework was developed to predict the influence of these effects on the echo signal. Then, a simulation tool was developed to create simulated echo-strain images in thermal lesions. Finally, experimental echo-strain images were acquired in 10 porcine liver samples in vitro for various exposure durations and ultrasonic intensities (resulting in lesions that extended 3 to 8 mm deep from the surface). For this purpose, radiofrequency (RF) frames were acquired at 8 frames per s while heating. For each consecutive pair of RF frames, an echo-strain image was calculated using standard elastographic processing. The echo-strain images were cumulated and displayed. The experimental echo-strain images were compared with gross pathology. The (isoechoic) lesions were visible both in simulated and in experimental cumulated echo-strain images as apparent expansion areas (tensile echo-strain), whereas surrounding tissues exhibited apparent compression. The tensile echo-strain area underestimated the lesion in simulations, but was representative of the lesion in experiments. High correspondence was found between the lesion depth measured from experimental cumulative echo-strain images ( y ) and from gross pathology ( x ) (Pearson's correlation=0.90, linear regression y = x −0.1 mm, residual error=0 ± 0.9 mm). We hypothesized that significant tissue expansion made the thermal lesions highly visible in the experimental echo-strain images. In two cases, the ultrasonic intensity was too low to induce a lesion, and the corresponding experimental echo-strain images showed no visible lesion. We conclude that cumulative echo-strain images have the potential to monitor the formation of high-intensity US-induced thermal lesions. (E-mail: Souchon@lyon.inserm.fr)

Targeting vascular endothelium with avidin microbubbles

Abstract: Targeting microbubbles (MBs) to specific vascular beds enables contrast ultrasound to be used for molecular imaging. There are several methods for attaching targeting moieties to the surface of MBs. In the present study, we demonstrate that avidin (Av) can be incorporated into the shell of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) MBs (Av-PESDA-MBs) and serve as an anchor that links Av-PESDA-MBs to biotinylated monoclonal antibodies (mAbs). This novel linking strategy was used to conjugate Av-PESDA-MBs to mAbs specific for endoglin (CD105) or a control IgG. MBs targeted to CD105 specifically bound to endothelial cells, but not to fibroblasts, in vitro but Av-PESDA-MBs conjugated with the control IgG did not specifically target either cell type. We conclude that Av-PESDA-MBs represent a novel and attractive tool to conjugate MBs with biotinylated mAbs for the purposes of vascular targeting and molecular imaging.

Automated fetal head detection and measurement in ultrasound images by iterative randomized Hough transform.

Abstract: An image-processing and object-detection method was developed to automate the measurements of biparietal diameter (BPD) and head circumference (HC) in ultrasound fetal images. The heads in 214 of 217 images were detected by an iterative randomized Hough transform. A head was assumed to have an elliptical shape with parameters progressively estimated by the iterative randomized Hough transform. No user input or size range of the head was required. The detection and measurement took 1.6 s on a personal computer. The interrun variations of the algorithm were small at 0.84% for BPD and 2.08% for HC. The differences between the automatic measurements and sonographers' manual measurements were 0.12% for BPD and -0.52% for HC. The 95% limits of agreement were -3.34%, 3.58% for BPD and -5.50%, 4.45% for HC. The results demonstrated that the automatic measurements were consistent and accurate. This method provides a valuable tool for fetal examinations.

Investigation of intensity thresholds for ultrasound tissue erosion.

Abstract: — Our previous studies have shown that short intense pulses delivered at certain pulse repetition frequencies (PRF) can achieve localized, clean erosion in soft tissue. In this paper, the intensity thresholds for ultrasound induced erosion and the effects of pulse intensity on erosion characterized by axial erosion rate, perforation area and volume erosion rate were investigated on in vitro porcine atrial wall tissue. Ultrasound pulses with a 3-cycle pulse duration and a 20-kHz PRF were delivered by a 788-kHz single element focused transducer. I SPPA values of 1000 to 9000 W/cm 2 were tested. Results show the following: (1) the estimated intensity threshold for generating erosion was at I SPPA of 3220 W/cm 2 ; (2) the axial erosion rate increased with higher intensity at I SPPA ≤ 5000 W/cm 2 , while decreased with higher intensity at I SPPA ≥ 5000 W/cm 2 ; and (3) the perforation area and the volume erosion rate increased with higher intensity.

Cavitation detection during shock-wave lithotripsy.

Abstract: A system was built to detect cavitation in pig kidney during shock-wave lithotripsy (SWL) with a Dornier HM3 lithotripter. Active detection using echo on B-mode ultrasound, and passive cavitation detection using coincident signals on confocal orthogonal receivers, were used to interrogate the renal collecting system (urine) and the kidney parenchyma (tissue). Cavitation was detected in urine immediately upon shock-wave (SW) administration in urine or urine plus X-ray contrast agent but, in native tissue, cavitation required hundreds of SWs to initiate. Localization of cavitation was confirmed by fluoroscopy, sonography and by thermally marking the kidney using the passive cavitation detection receivers as high-intensity focused ultrasound sources. Cavita- tion collapse times in tissue and native urine were about the same, but less than in urine after injection of X-ray contrast agent. The finding that cavitation occurs in kidney tissue is a critical step toward determining the mechanisms of tissue injury in SWL. (E-mail: bailey@apl.washington.edu) © 2005 World Federation for Ultrasound in Medicine & Biology.

Study of sonoporation dynamics affected by ultrasound duty cycle

Abstract: Sonoporation is the ultrasound-induced membrane porosity and has been investigated as a means for intracellular drug delivery and nonviral gene transfection. The dynamic characteristics of sonoporation, such as formation, duration and resealing of the pores in the cell membrane, determine the process of intracellular uptake of molecules or agents of interest that are otherwise obstructed by the cell membrane barrier. Sonoporation dynamics is also important for postultrasound cell survival. In this study, we investigated the effects of ultrasound duty cycle on sonoporation dynamics using Xenopus oocyte as a model system. Transducer with a center frequency of 0.96 MHz was used to generate pulsed ultrasound of desired duty cycle (5%, 10% and 15%) at a pulse repetition frequency of 1 Hz and an acoustic pressure of 0.4 MPa in our experiments. Employing voltage clamp techniques, we measured the transmembrane current as the direct result of decreased membrane resistance due to pore formation induced by ultrasound application. We characterized the sonoporation dynamics from these time-resolved recordings of trans- membrane current to indicate cell membrane status, including pore formation, extension and resealing. We observed that the transmembrane current amplitude increased with increasing duty cycle, while the recovering process of membrane pores and cell survival rate decreased at higher duty cycles. (E-mail: cheri.deng@cwru.edu) © 2005 World Federation for Ultrasound in Medicine & Biology.

Transforming growth factor-β1 mediates the effects of low-intensity pulsed ultrasound in chondrocytes

Abstract: Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing, but the precise mechanism is still unknown. We used aggregate chondrocyte culture system to analyze LIPUS-induced effects on chondrocytes. First, Northern analyses revealed that LIPUS maintained higher expression levels of type II collagen and aggrecan mRNA and delayed the appearance of type X collagen mRNA expression. We also showed that DNA content was increased and that alkaline phosphatase activity was maintained low by daily treatment. Moreover, LIPUS significantly promoted transforming growth factor (TGF)-beta1 mRNA expression and the protein production at 2 h and 12 h after the treatment, respectively. Furthermore, recombinant TGF-beta1 protein mimicked the LIPUS effect and anti-TGF-beta1 neutralizing antibody reversed all these changes induced by the LIPUS treatment. These results indicate that LIPUS promotes the proliferation and retains the differentiation state of chondrocytes in the aggregate culture and that TGF-beta1 plays an important role in mediating the LIPUS effects in chondrocytes.

Quantification of carotid plaque volume measurements using 3D ultrasound imaging.

Abstract: An accurate and reliable technique used to quantify carotid plaque volume has practical importance in research and patient management. In this study, we develop and investigate a theoretical description of carotid plaque volume measurements made using three-dimensional (3D) ultrasound (US) images and compare it with experimental results. Multiple observers measured 48 3D US patient images of carotid plaque (13.2 to 544.0 mm(3)) by manual planimetry. Coefficients of variation in the measurement of plaque volume were found to decrease with increasing plaque size for both inter- (90.8 to 3.9%) and intraobserver (70.2 to 3.1%) measurements. Plaque volume measurement variability was found to increase with interslice distance (ISD), while the relative measurement accuracy remained constant for ISDs between 1.0 and 3.0 mm and then decreased. Root-mean-square (RMS) difference between our theoretical description of plaque volume measurement variance and the experimental results was 5.7%. Thus, our results support the clinical utility of measuring carotid plaque volume by manual planimetry noninvasively using 3D US.

A new immobilisation method to arrange particles in a gel matrix by ultrasound standing waves

Abstract: Ultrasonic forces may be used to manipulate particles in suspension. For example, a standing wave ultrasound (US) field applied to a suspension moves the particles toward areas of minimal acoustic pressure, where they are orderly retained creating a predictable heterogeneous distribution. This principle of ultrasonic retention of particles or cells has been applied in numerous biotechnological applications, such as mammalian cell filtering and red blood cell sedimentation. Here, a new US-based cell immobilisation technique is described that allows manipulation and positioning of cells/particles within various nontoxic gel matrices before polymerisation. Specifically, gel immobilisation was used to directly demonstrate that the viability of yeast cells arranged by an US standing wave is maintained up to 4 days after treatment. The versatility of this immobilisation method was validated using a wide range of acoustic devices. Finally, the potential biotechnological advantages of this US-controlled particle positioning method combined with gel immobilisation/encapsulation technology are discussed. (E-mail: groeschl@iap.tuwien.ac.at )

Comparative evaluation of strain-based and model-based modulus elastography.

Abstract: Elastography based on strain imaging currently endures mechanical artefacts and limited contrast transfer efficiency. Solving the inverse elasticity problem (IEP) should obviate these difficulties; however, this approach to elastography is often fraught with problems because of the ill-posed nature of the IEP. The aim of the present study was to determine how the quality of modulus elastograms computed by solving the IEP compared with those produced using standard strain imaging methodology. Strain-based modulus elastograms (i.e., modulus elastograms computed by simply inverting strain elastograms based on the assumption of stress uniformity) and model-based modulus elastograms (i.e., modulus elastograms computed by solving the IEP) were computed from a common cohort of simulated and gelatin-based phantoms that contained inclusions of varying size and modulus contrast. The ensuing elastograms were evaluated by employing the contrast-to-noise ratio (CNRe) and the contrast transfer efficiency (CTEe) performance metrics. The results demonstrated that, at a fixed spatial resolution, the CNRe of strain-based modulus elastograms was statistically equivalent to those computed by solving the IEP. At low modulus contrast, the CTEe of both elastographic imaging approaches was comparable; however, at high modulus, the CTEe of model-based modulus elastograms was superior. (E-mail: marvin.m.doyley@dartmouth.edu) © 2005 World Federation for Ultrasound in Medicine & Biology.

Monitoring stiffness changes in lesions after radiofrequency ablation at different temperatures and durations of ablation

Abstract: The variations in the stiffness or stiffness contrast of lesions resulting from radiofrequency (RF) ablation of canine liver tissue at different temperatures and for different ablation durations at a specified temperature are analyzed. Tissue stiffness, in general, increases with temperature; however, an anomaly exists around 80 ° C, where the stiffness of the lesion is lower than that of the lesion ablated at 70 °C. On the other hand, the stiffness increases monotonically with the duration of ablation. Plots illustrating the ratio of mean strains in normal canine liver tissue to mean strains in ablated thermal lesions demonstrate the variation in the stiffness contrast of the thermal lesions. The contrast-to-noise ratio (CNRe) of the lesions, which serves as an indicator of the detectability of the lesions under the different experimental imaging conditions described above, is also presented. The results presented in this paper show that the elastographic depiction of stiffer thermal lesions is better, in terms of the CNRe parameter. An important criterion in the elastographic depiction of RF-ablated regions of tissue is the trade-off between ablation temperature and duration of ablation. Tissue necrosis can occur either by ablating tissue to high temperatures for short durations or to lower temperatures for longer durations. In this paper, we attempt to characterize the elastographic depiction of thermal lesions under these different experimental conditions. This paper provides results that may be utilized by practitioners of RF ablation to decide the ablation temperature and duration, on the basis of the strain images of normal liver tissue and ablated thermal lesions discussed in this paper. (E-mail: tvarghese@wisc.edu )