Showing papers in "Ultrasound in Medicine and Biology in 2003"

Transient elastography: a new noninvasive method for assessment of hepatic fibrosis

Abstract: Chronic hepatitis is accompanied by progressive deposit of hepatic fibrosis, which may lead to cirrhosis. Evaluation of liver fibrosis is, thus, of great clinical interest and, up to now, has been assessed with liver biopsy. This work aims to evaluate a new noninvasive device to quantify liver fibrosis: the shear elasticity probe or fibroscan. This device is based on one-dimensional (1-D) transient elastography, a technique that uses both ultrasound (US) (5 MHz) and low-frequency (50 Hz) elastic waves, whose propagation velocity is directly related to elasticity. The intra- and interoperator reproducibility of the technique, as well as its ability to quantify liver fibrosis, were evaluated in 106 patients with chronic hepatitis C. Liver elasticity measurements were reproducible (standardized coefficient of variation: 3%), operator-independent and well correlated (partial correlation coefficient = 0.71, p /= F2) and with cirrhosis ( = F4), respectively. The Fibroscan is a noninvasive, painless, rapid and objective method to quantify liver fibrosis.

Shear-wave generation using acoustic radiation force: in vivo and ex vivo results.

Abstract: Acoustic radiation force impulse (ARFI) imaging involves the mechanical excitation of tissue using localized, impulsive radiation force. This results in shear-wave propagation away from the region of excitation. Using a single diagnostic transducer on a modified commercial ultrasound (US) scanner with conventional beam-forming architecture, repeated excitations with multiple look directions facilitate imaging shear-wave propagation. Direct inversion methods are then applied to estimate the associated Young's modulus. Shear-wave images are generated in tissue-mimicking phantoms, ex vivo human breast tissue and in vivo in the human abdomen. Mean Young's modulus values of between 3.8 and 5.6 kPa, 11.7 kPa and 14.0 kPa were estimated for fat, fibroadenoma and skin, respectively. Reasonable agreement is demonstrated between structures in matched B-mode and reconstructed modulus images. Although the relatively small magnitude of the displacement data presents some challenges, the reconstructions suggest the clinical feasibility of radiation force induced shear-wave imaging.

In vivo real-time freehand palpation imaging

Abstract: Previous experience with laboratory fixtures and off-line processing of elasticity data showed that problems occurring in data acquisition often resulted in poor elasticity image quality. A system for real-time estimation and display of tissue elastic properties using a clinical ultrasonic imaging system has been developed. A brief description of that system and the initial clinical tests of that system are reported. Experience with real-time freehand elasticity imaging shows that images with high contrast-to-noise ratios are consistently obtained. Images of breast lesions were acquired with freehand palpation using standard linear-array ultrasound (US) transducers. Results in volunteer patients show that high-quality elasticity images are easily obtained from in vivo breast studies. The key element to successful scanning is real-time visual feedback of B-mode and strain images that guide the patient positioning and compression direction. Results show that individual images of axial strain in tissues can be quite misleading, and that a "movie loop" of side-by-side B-mode and strain images provides significantly more information. Our preliminary data suggest that the strain image sequences for various breast pathologies are unique. For example, strain images of fibroadenomas lose contrast with increasing precompression, but those of invasive ductal carcinoma have high negative contrast (dark relative to "normal" tissue) for a wide range of precompression. In addition, a comparison of the lesion area measured in B-mode vs. strain images, for a representative image from the sequence, appears to be a sensitive criterion for separating invasive ductal carcinoma from cyst and fibroadenoma.

In vivo breast tumor detection using transient elastography.

Abstract: This paper presents first in vivo experiments for breast tumor detection using transient elastography. This technique has been developed for detection and quantitative mapping of hard lesions in soft tissues. It consists in following the propagation inside soft tissues of very low-frequency shear waves ( 60 Hz) generated by a vibrating system located at the body surface. Because transient shear waves propagate through the medium in less than 0.1 s, the shear propagation imaging is performed with an ultrafast echographic scanner able to reach frame rates up to 6000 Hz. The local shear wave speed is directly linked to the local shear Young's modulus of the medium. The shear elasticity map of the medium can then be computed using an inversion algorithm. In vivo experiments were conducted on 15 women who had palpable breast lesions. For clinical adaptability reasons, shear waves were generated by the surface of the ultrasound (US) imaging transducer itself, which was linked to a mechanical vibrator. Our preliminary in vivo results demonstrate the clinical applicability of the transient elastography technique for breast lesion detection. (E-mail: michael.tanter@espci.fr) © 2003 World Federation for Ultrasound in Medicine & Biology.

Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles

Abstract: The aim of this study was to assess the relative efficacy and mechanism of gene transfection by ultrasound (US) destruction of plasmid-bearing microbubbles. Luciferase reporter plasmid was charge-coupled to cationic lipid microbubbles. Rat hindlimb skeletal muscle was exposed to intermittent high-power US during dose-adjusted intra-arterial (IA) or IV administration of plasmid-bearing microbubbles via the carotid artery or jugular vein, respectively. At 4 days, luciferase activity in US-exposed skeletal muscle was 200-fold greater with IA than with IV administration of plasmid-bearing microbubbles, and was similar to transfection achieved by IM injection of plasmid (positive control). No transfection occurred with US and IA injection of plasmid alone. Intravital microscopy of the cremaster muscle in mice following administration of microbubbles and US exposure demonstrated perivascular deposition of fluorescent plasmid, the extent of which was twofold greater for IA compared to IV injection. Electron microscopy demonstrated a greater extent of myocellular microporations in US-exposed muscle after IA injection of microbubbles. We conclude that muscle transfection by US destruction of plasmid-bearing cationic microbubbles is amplified by IA, rather than IV, injection of microbubbles due to greater extravascular deposition of plasmid and to greater extent of myocellular microporation.

Visualisation of HIFU lesions using elastography of the human prostate in vivo: preliminary results.

Abstract: An imaging system was developed for prostate elastography in vivo using a transrectal ultrasound (US) probe to guide high-intensity focused US (HIFU) therapy of prostate cancer. Uniform compression was applied using a balloon, while a sector image was acquired. Strain was calculated from the gradient of the displacements obtained from the ultrasonic signal using the cross-correlation technique. Elastograms were acquired on a total of 31 patients undergoing HIFU therapy for localised prostate cancer. For two patients, only part of the prostate was treated and posttherapy magnetic resonance imaging (MRI) confirmed the size and position of the HIFU lesions seen in the elastograms as low strain areas, with a strain contrast ratio between 1.6 and 3.2. The whole prostate was treated for the next 29 patients. After treatment, the whole prostate appeared to be stiff in the elastograms and a 40% to 60% (mean 50%) decrease in average strain was observed when compared to strains measured before HIFU application. Tumours identified by biopsies and sonograms could occasionally be seen in the preoperative elastograms. Decorrelation effects occurred mainly because of low sonographic signal-to-noise ratio (SNR) and of out-of-plane motion induced by respiration.

Assessment of the acoustic properties of common tissue-mimicking test phantoms.

Abstract: Ultrasound (US) test phantoms incorporating tissue-mimicking materials (TMMs) play an important role in the quality control (QC) and performance testing of US equipment. Three commercially available TMMs (Zerdine from CIRS Inc.; condensed-milk-based gel from Gammex RMI; urethane-rubber-based from ATS Labs) and a noncommercial agar-based TMM, were investigated. Acoustic properties were measured over the frequency range 2.25 to 15 MHz at a range of ambient temperatures (10 to 35 degrees C). The acoustic velocity of the TMMs remained relatively constant with increasing frequency. Only the agar-based TMM had a linear increase of attenuation with frequency, with the other materials exhibiting nonlinear responses to varying degrees (f(1.08) to f(1.83)). The acoustic velocity and attenuation coefficient of all the TMMs varied with temperature, with the urethane-rubber TMM showing the greatest variation of +/- 1.2% for acoustic velocity and +/- 12% for attenuation coefficient. The data obtained in this study highlight the importance of greater knowledge of the acoustic behavior of TMMs to variations in both frequency and temperature, to ensure that accurate and precise measurements are obtained during QC and performance testing.

Carotid artery wall motion estimated from B-mode ultrasound using region tracking and block matching.

Abstract: The motion of the carotid atheromatous plaque relative to the adjacent wall may be related to the risk of cerebral events. A quantitative method for motion estimation was applied to analyse arterial wall movement from sequences of 2-D B-mode ultrasound (US) images. Image speckle patterns were tracked between successive frames using the correlation coefficient as the matching criterion. The size of the selected region-of-interest (ROI) was shown to affect the motion analysis results; an optimal size of 3.2 x 2.5 mm(2) was suggested for tracking a region at the wall-lumen interface and of 6.3 x 2.5 mm(2) for one within the tissue. The results showed expected cyclical motion in the radial direction and some axial movement of the arterial wall. The method can be used to study further the axial motion of the carotid artery wall and plaque and, thus, provide useful insight into the mechanisms of atherosclerosis.

Ultrasound-mediated cavitation thresholds of liquid perfluorocarbon droplets in vitro

Abstract: This study was undertaken to measure the ultrasound (US)-mediated cavitation threshold of microdroplets as a function of its content and US parameters (frequency, amplitude and burst length). Albumin-coated droplets were prepared with perfluoropropane, perfluorohexane or perfluoromethylcyclohexane contents. The filtered suspensions were diluted to 1:1000 (v) and compared with Optison. The formulations were injected into an acoustically transparent vessel and sonicated with a single focused transducer. The frequencies employed were 0.74, 1.1, 2.18 and 3.3 MHz and the burst length and acoustic pressure were varied. The inertial cavitation threshold for each experiment was monitored through passive acoustic detection. The formation of droplet emulsion of the perfluorocarbon increased the natural boiling point of the perfluorocarbon. However, perfluorocarbon droplets having contents with higher molecular weights and boiling points did not have detectably higher inertial cavitation thresholds and, thus, the droplets do not need to be in a superheated state to be cavitated by US bursts. Therefore, higher boiling point perfluorocarbons should be investigated for this purpose and may prove to be useful for both imaging and therapy. The inertial cavitation threshold of perfluorocarbon droplets increases with frequency, and was approximately 0.7 MPa at 0.74 MHz and 1.75 MPa at 3.3 MHz. Optison, already in a gaseous state, has the lowest cavitation threshold of all formulations studied. Results show that, for the frequencies tested, there is no dependence between inertial cavitation threshold and burst lengths between 20 and 100 ms. As a conclusion, the inertial cavitation threshold of albumin-coated microdroplets of several perfluorocarbons was determined in vitro. The results indicate that the physical properties of these droplets are such that they may be useful for localized US therapies.

Inertial cavitation dose and hemolysis produced in vitro with or without Optison.

Abstract: Gas-based contrast agents (CAs) increase ultrasound (US)-induced bioeffects, presumably via an inertial cavitation (IC) mechanism. The relationship between IC dose (ICD) (cumulated root mean squared [RMS] broadband noise amplitude; frequency domain) and 1.1-MHz US-induced hemolysis in whole human blood was explored with Optison; the hypothesis was that hemolysis would correlate with ICD. Four experimental series were conducted, with variable: 1. peak negative acoustic pressure (P-), 2. Optison concentration, 3. pulse duration and 4. total exposure duration and Optison concentration. P- thresholds for hemolysis and ICD were approximately 0.5 MPa. ICD and hemolysis were detected at Optison concentrations >/= 0.01 V%, and with pulse durations as low as four or two cycles, respectively. Hemolysis and ICD evolved as functions of time and Optison concentration; final hemolysis and ICD values depended on initial Optison concentration, but initial rates of change did not. Within series, hemolysis was significantly correlated with ICD; across series, the correlation was significant at p < 0.001.

Bioeffects caused by changes in acoustic cavitation bubble density and cell concentration: a unified explanation based on cell-to-bubble ratio and blast radius.

Abstract: Acoustic cavitation has been shown to load drugs, proteins and DNA into viable cells as a complex function of acoustic and nonacoustic parameters. To better understand and quantify this functionality, DU145 prostate cancer cell suspensions at different cell concentrations (2.5 x 10(5) to 4.0 x 10(7) cells/mL) were exposed to 500 kHz ultrasound (US) over a range of acoustic energy exposures (2 to 817 J/cm(2); peak negative pressures of 0.64 to 2.96 MPa; exposure times of 120 to 2000 ms) in the presence of different initial concentrations of Optison contrast agent bubbles (3.6 x 10(4) to 9.3 x 10(7) bubbles/mL). As determined by flow cytometry, molecular uptake of calcein and cell viability both increased with increasing cell density; viability decreased and uptake was unaffected by increasing initial contrast agent concentration. When normalized relative to the initial contrast agent concentration (e.g., cells killed per bubble), bioeffects increased with increasing cell density and decreased with increasing bubble concentration. These varying effects of contrast agent concentration and cell density were unified through an overall correlation with cell-to-bubble ratio. Additional analysis led to estimation of "blast radii" over which bubbles killed or permeabilized cells; these radii were as much as 3 to 90 times the bubble radius. Combined, these results suggest that extensive molecular uptake into cells at high viability occurs for low-energy exposure US applied at a high cell-to-bubble ratio.

Enhancement of ultrasound-induced apoptosis and cell lysis by echo-contrast agents.

Abstract: To determine the effects of echo-contrast agents (ECAs) on ultrasound (US)-induced apoptosis and cell lysis, human myelomonocytic lymphoma U937 cells in suspension were exposed to 1 MHz continuous waves US for 1 min at an intensity of 0.5, 1.0, 2.0 or 4.0 W/cm(2) with or without non-shell type ECA, Levovist (2 mg/ml), and shell type, Optison (1 microl/ml) or YM454 (1 microl/ml). Levovist minimally enhanced the US-induced apoptosis at 1.0 W/cm(2) while Optison and YM454 did at 2.0 and 4.0 W/cm(2), as detected by flow cytometry. Cell lysis was also augmented when Levovist was combined with US at 2.0 W/cm(2), and when Optison was combined with US at 2.0 and 4.0 W/cm(2). YM454 showed the highest rate of enhanced cell lysis at 1.0, 2.0 and 4.0 W/cm(2). Therefore, this study shows that Optison and YM454 are effective in augmenting the US-induced cell killing, but not Levovist. Another result indicates that cavitation plays a role in the augmented effects and that inertial cavitation appears necessary for Optison and YM454 to effect their actions. In addition, results show that the rate of apoptosis is lower in the presence of ECAs with higher free radical scavenging activity, suggesting a possible role for free radicals in apoptosis. These findings suggest that some ECAs have potential to be adjuncts in cases wherein augmented US-induced cell killing is needed, such as in cancer therapy with US.

Localized harmonic motion imaging: theory, simulations and experiments.

Abstract: Several techniques have been developed in an effort to estimate mechanical properties of tissues. These techniques typically estimate static or harmonic motion resulting from an externally or internally applied mechanical stimulus. In this paper, we discuss the advantages of utilizing a new technique that performs radiofrequency (RF) signal tracking to estimate the localized oscillatory motion resulting from the harmonic radiation force produced by two focused ultrasound (US) transducer elements with overlapping beams oscillating at distinct frequencies. Finite-element and Monte-Carlo simulations were performed to characterize the range of oscillatory displacements produced by a harmonic radiation force. In the experimental verification, three transducers were used: two single-element focused transducers and one lead zirconate-titanate (PZT) composite 16-element probe. Four agar gels were utilized to determine the effect of stiffness on the motion amplitude. Estimates of the displacement relative to the initial position (i.e., at the onset of the application of the radiation force) were obtained during the application of the radiation force that oscillated at frequencies ranging between 200 Hz and 800 Hz. In the simulations, the estimated oscillatory displacement spanned from −800 to 600 μm and the frequencies of excitation could easily be estimated from the temporal variation of the displacement. In addition, a frequency upshift (on the order of tens of Hz) was estimated with stiffness increase. Furthermore, an exponential decrease of the displacement amplitude with stiffness was observed at all frequencies investigated. An M-mode version to depict both the spatial and temporal variations of the locally induced displacement was used. In experiments with gels of different stiffness, the resulting amplitude of the harmonic displacement estimated oscillated at the same frequencies and ranged from −300 to 250 μm. An exponential decrease of the displacement amplitude with the gel stiffness was also observed. In tissue experiments, the results showed that the method is feasible in tissues and that focused US surgery (FUS) ablation can be detected. These preliminary results demonstrate the feasibility of imaging localized harmonic motion as induced by an oscillatory US radiation force. Due to the highly localized and harmonic nature of the estimated response, this technique may be proven to be highly suitable for simple and accurate estimation of the elastic modulus variation in tissues due to disease. (E-mail: elisak@bwh.harvard.edu)

A Newtonian rheological model for the interface of microbubble contrast agents.

Abstract: A quantitative model of the dynamics of an encapsulated microbubble contrast agent will be a valuable tool in contrast ultrasound (US). Such a model must have predictive ability for widely varying frequencies and pressure amplitudes. We have developed a new model for contrast agents, and successfully investigated its applicability for a wide range of operating parameters. The encapsulation is modeled as a complex interface of an infinitesimal thickness. A Newtonian rheology with surface viscosities and interfacial tension is assumed for the interface, and a modified Rayleigh–Plesset equation is derived. The rheological parameters (surface tension and surface dilatational viscosity) for a number of contrast agents (Albunex®, Optison® and Quantison®) are determined by matching the linearized model dynamics with experimentally obtained attenuation data. The model behavior for Optison® (surface tension 0.9 N/m and surface dilatational viscosity 0.08 msP) was investigated in detail. Specifically, we have carried out a detailed interrogation of the model, fitted in the linear regime, for its nonlinear prediction. In contrast to existing models, the new model is found to capture the characteristic subharmonic emission of Optison® observed by Shi et al. (1999) . A detailed parametric study of the bubble behavior was executed using the ratio of scattering to attenuation (STAR). It shows that the encapsulation drastically reduces the influence of resonance frequency on scattering cross-section, suggesting possible means of improvement in imaging at off-resonant frequencies. The predictive capability of the present model indicates that it can be used for characterizing different agents and designing new ones. (E-mail: sarkar@me.udel.edu)

Radiation-force technique to monitor lesions during ultrasonic therapy

Abstract: This report describes a monitoring technique for high-intensity focused ultrasound (US), or HIFU, lesions, including protein-denaturing lesions (PDLs) and those made for noninvasive cardiac therapy and tumor treatment in the eye, liver and other organs. Designed to sense the increased stiffness of a HIFU lesion, this technique uniquely utilizes the radiation force of the therapeutic US beam as an elastographic push to detect relative stiffness changes. Feasibility was demonstrated with computer simulations (treating acoustically induced displacements, concomitant heating, and US displacement-estimation algorithms) and pilot in vitro experimental studies, which agree qualitatively in differentiating HIFU lesions from normal tissue. Detectable motion can be induced by a single 5 ms push with temperatures well below those needed to form a lesion. Conversely, because the characteristic heat diffusion time is much longer than the characteristic relaxation time following a push, properly timed multiple therapy pulses will form lesions while providing precise control during therapy. (E-mail: muratore@rrinyc.org) © 2003 World Federation for Ultrasound in Medicine & Biology.

High-definition freehand 3-D ultrasound

Abstract: This paper describes a high-definition freehand 3-D ultrasound (US) system, with accuracy surpassing that of previously documented systems 3-D point location accuracy within a US data set can be achieved to within 05 mm Such accuracy is possible through a series of novel system-design and calibration techniques The accuracy is quantified using a purpose-built tissue-mimicking phantom, designed to create realistic clinical conditions without compromising the accuracy of the measurement procedure The paper includes a thorough discussion of the various ways of measuring system accuracy and their relative merits; and compares, in this context, all recently documented freehand 3-D US systems

Within-subject variability of flow-mediated vasodilation of the brachial artery in healthy men and women: implications for experimental studies

Abstract: Flow-mediated vasodilation (FMD) of the brachial artery is used as a marker of cardiovascular disease risk. It is defined as the percentage dilation from the baseline diameter in response to a provoked increase in blood flow. The within-subject variability, crucial in the design of trials with FMD as an endpoint, appears to vary widely between studies. We assessed the analytical and within-subject variability of FMD in healthy subjects and estimated the number of subjects needed to detect various treatment effects in intervention trials and observational studies. FMD was assessed with B-mode high-resolution ultrasound (US). A total of 13 volunteers were measured on six occasions, after they had fasted overnight. Within-subject variability was assessed from all six scans per subject. Analytical variation or reading variation was assessed by reading one scan of each subject twice by one observer. The mean (±SD) FMD was 5.60 ± 2.15 FMD% of the baseline diameter. The within-subject SD was 2.8 FMD%, resulting in a coefficient of variation (CV) of 2.8/5.6 × 100% = 50.3%. The CVs for the baseline and maximum diameter were much smaller: 4.8% (SD 0.193 mm at a mean of 4.060 mm) for the baseline and 5.2% (SD 0.222 mm at a mean of 4.285 mm) for the maximum. The CV for reading variation was 34%. The number of subjects needed to detect a treatment difference of 2 FMD% with a probability of 0.05 and a power of 0.80 would be 31 in a crossover design and 62 per group in a parallel design for comparison of group changes. We conclude that the within-subject variability of FMD is large, about 50% of the mean response. This includes biologic and reading variation. Repeated measurements and repeated readings of recorded measurements are recommended to reduce variability.

The effects of pulsed low-intensity ultrasound on chondrocyte viability, proliferation, gene expression and matrix production.

Abstract: This study was designed to examine the effects of pulsed low-intensity ultrasound (PLIUS) on chondrocyte viability, proliferation, matrix production and gene expression. Chondrocytes were isolated from the distal part of the sternum of 16-day-old chick embryos and cultured in alginate beads. PLIUS at 2 mW/cm(2) (group PLIUS(2)) and 30 mW/cm(2) (group PLIUS(30)) was applied to chondrocytes for a single 20-min treatment. A control group was treated without PLIUS. The viability of chondrocytes was not affected by exposure to PLIUS. PLIUS influenced chondrocyte proliferation in an intensity-dependent manner. By day 7 after application of PLIUS, the gene expression and synthesis of aggrecan was the same as in the controls. At this same time point, the expression and synthesis of type II collagen was not different between the controls and PLIUS(30), but was increased in PLIUS(2). PLIUS was shown to inhibit the expression of type X collagen. This inhibition of chondrocyte hypertrophy may prove to be significant in the management of cartilage degeneration.

Muscle ultrasound analysis: normal values and differentiation between myopathies and neuropathies

Abstract: In this study, 145 healthy adults (20 to 94 years old, 69 women) were examined using ultrasound (US) imaging to obtain reference values of muscle parameters that were previously not available. We measured biceps and quadriceps sizes and subcutaneous fat thickness. To quantify muscle aspect, we defined and calculated the muscle aspect parameters muscle density, inhomogeneity and white-area index by digital image analysis. All muscle aspect parameters were found to increase with age, which may be due to age-related muscle replacement by fatty tissue and collagen. Other age-, weight- and gender-dependencies are also discussed. The complete set of muscle parameters was used to differentiate between typical myopathies and neuropathies in a group of 32 patients (24 to 79 years old, 18 women). We were successful in almost completely separating the two types of disorders based on abnormality of muscle aspect parameters alone. These preliminary results show that this set of normal muscle parameters can be used to help diagnose neuromuscular disorders. It will also facilitate follow-up in disease progression and therapy.

The pulse length-dependence of inertial cavitation dose and hemolysis.

Abstract: Gas-based ultrasound (US) contrast agents increase erythrocyte sonolysis, presumably via enhancing inertial cavitation (IC) activity. The amount of IC activity (IC "dose") and hemolysis generated by exposure to 1.15 MHz US were examined with different US pulse lengths, but with the same delivered acoustic energy, for Optison and Albunex. The hypotheses were that 1. at longer pulse lengths, IC would generate more bubbles that could nucleate additional IC activity; 2. if the interval between pulse pairs were short enough for the next pulse to hit derivative bubbles before their dissolution, more IC could be induced; and 3. hemolysis would be proportional to IC activity. Two types of studies were performed. In the first, bubble generation after each burst of IC activity was quantified using an active cavitation detector (ACD), for different pulse lengths (5, 10, 20, 30, 50, 100 or 200 cycles), but the same pressure level (3 MPa) and total "on" time (173.16 ms). Low concentrations of either Optison or Albunex were added into the tank with high-intensity and interrogating transducers orthogonal to each other. For pulse lengths > 100 cycles, and pulse repetition intervals < 5 ms, a "cascade" effect (explosive bubble generation) was observed. In the second, IC was measured by passive detection methods. IC dose and hemolysis were determined in whole blood samples at a pressure level (3 MPa) and interpulse interval (5 ms) that induced the "cascade" effect. Each blood sample was mixed with the same number of contrast microbubbles (Optison approximately 0.3 v/v % and Albunex approximately 0.5 v/v %), but exposed to different pulse lengths (5, 10, 20, 30, 50, 100 or 200 cycles). With Optison, up to 60% hemolysis was produced with long pulses (100 and 200 cycles), compared with < 10% with short pulses (5 and 10 cycles). Albunex generated considerably less IC activity and hemolysis. The r(2) value was 0.99 for the correlation between hemolysis and IC dose. High pulse-repetition frequency (PRF) (500 Hz) generated more hemolysis than the low PRF (200 Hz) at 3 MPa. All experimental results could be explained by the dissolution times of IC-generated bubbles.

Sonographic evaluation of the size of achilles tendon: the effect of exercise and dominance of the ankle

Abstract: This study was undertaken to measure and compare the thickness and cross-sectional area of the Achilles tendon between frequent- and infrequent-exercise subjects, and between the dominant and nondominant ankles in an asymptomatic Chinese population. Interobserver variability in the measurement of the size of Achilles tendon was also evaluated. High-resolution ultrasound (US) examination of Achilles tendons was performed in 40 healthy subjects (20 who frequently exercised, had exercise at least 3 days per week and at least 2 h per session; and 20 who infrequently exercised); their age range was 19 to 25 years. The thickness and cross-sectional area of the Achilles tendons were measured in a transverse scan at the level of medial malleolus. For each subject, the Achilles tendons were measured by five operators to evaluate the interobserver variability in the measurements. The mean thickness and cross-sectional areas of the Achilles tendon in a healthy Chinese population are 5.23 mm(2) and 56.91 mm(2)(2), respectively. The mean thickness of the Achilles tendon of frequent-exercise subjects (dominant ankle 5.43 mm, nondominant ankle 5.38 mm) was significantly greater than that of infrequent-exercise subjects (dominant ankle 5.08 mm, nondominant ankle 5.04 mm) (p 0.05). In both frequent- and infrequent-exercise subjects, there was no significant difference in the mean thickness and cross-sectional area of Achilles tendon between dominant and nondominant ankles (p > 0.05). There was a high reproducibility in the sonographic measurement of the thickness (68%) and cross-sectional area (81%) of Achilles tendons. Results suggested that exercise would cause increase in the thickness and cross-sectional area of Achilles tendon. Interobserver variability is not significant in the sonographic measurement of Achilles tendons.

Improvement in breast tumor discrimination by support vector machines and speckle-emphasis texture analysis

Abstract: Recent statistics show that breast cancer is a major cause of death among women in developed countries. Hence, finding an accurate and effective diagnostic method is very important. In this paper, we propose a high precision computer-aided diagnosis (CAD) system for sonography. We utilize a support vector machine (SVM) to classify breast tumors according to their texture information surrounding speckle pixels. We test our system with 250 pathologically-proven breast tumors including 140 benign and 110 malignant ones. Also we compare the diagnostic performances of three texture features, i.e., speckle-emphasis texture feature, nonspeckle-emphasis texture feature and conventional all pixels texture feature, applied to breast sonography using SVM. In our experiment, the accuracy of SVM with speckle information for classifying malignancies is 93.2% (233/250), the sensitivity is 95.45% (105/110), the specificity is 91.43% (128/140), the positive predictive value is 89.74% (105/117) and the negative predictive value is 96.24% (128/133). Based on the experimental results, speckle phenomenon is a useful tool to be used in computer-aided diagnosis; its performance is better than those of the other two features. Speckle phenomenon, which is considered as noise in sonography, can intrude into judgments of a physician using naked eyes but it is another story for application in a computer-aided diagnosis algorithm.

The threshold for brain damage in rabbits induced by bursts of ultrasound in the presence of an ultrasound contrast agent (optison )

Abstract: The purpose of this study was to test the hypothesis that burst ultrasound (US) in the presence of a US contrast agent using parameters similar to those used in brain blood flow measurements causes tissue damage. The brains of 10 rabbits were sonicated in 3-8 locations with 1.5-MHz, 10- micro s bursts repeated at a frequency of 1 kHz at temporal peak acoustic pressure amplitudes ranging from 2 to 12.7 MPa. The total sonication time for each location was 20 s. Before each sonication, a bolus of US contrast agent was injected IV. Contrast-enhanced magnetic resonance (MR) images were obtained after the sonications to detect local enhancement in the brain. Whole brain histological evaluation was performed, and the sections were stained with hematoxylin and eosin (H and E), TUNEL, and vanadium acid fuchsin (VAF) staining to evaluate tissue effects, including apoptosis and ischemia. Both the magnetic resonance imaging (MRI) contrast enhancement and histology findings indicated that brain tissue damage was induced at a pressure amplitude level of 6.3 MPa. The damage included vascular wall damage, hemorrhage and, eventually, necrosis. Mild vascular damage was observed localized in a few microscopic tissue volumes in about half of the sonicated locations at all pressure values tested (down to 2 MPa). However, these sonications did not induce any detectable tissue effects, including ischemia or apoptosis. As a conclusion, the study showed that the US exposure levels currently used for blood flow measurements in brain are below the threshold of blood-brain barrier opening or brain tissue damage. However, one should be aware that brain damage can be induced if the exposure level is increased.

A novel ultrasound indentation system for measuring biomechanical properties of in vivo soft tissue.

Abstract: Technologies for soft tissue analysis are advancing at a rapid place For instance, elastography, which provides soft tissue strain images, is starting to be tried in clinical practice as a tool for diagnosing cancer Soft tissue deformation modeling and analysis is also an active area of research that has application in surgery planning and treatment Typically, quantitative soft tissue analysis uses nominal values of soft tissue biomechanical properties However, in practice, soft tissue properties can vary significantly between individuals Hence, for soft tissue methodologies to reach their full potential as patient-specific techniques, there is a need to develop ways to efficiently measure soft tissue mechanical properties in vivo This paper describes a prototype real-time ultrasound (US) indentation test system developed to meet this need The system is based on the integration of a force sensor and an optical tracking system with a commercial US machine integrated with a suite of analysis methodologies In a study on a single-layer phantom, we used the system to compare various methods of estimating linear elastic properties (via a theoretical approximation, 2-D finite element analysis, 3-D finite element analysis and a standard material-testing method) In a second study on a three-layer gelatin phantom, we describe a new finite-element-based inverse solution for recovering the Young's moduli of each layer to show how the system can estimate properties of internal components of soft tissue Finally, we show how the system can be used to derive a modified quasilinear viscoelastic (QVL) model on real breast tissue

Tumor growth reduction and DNA transfer by cavitation-enhanced high-intensity focused ultrasound in vivo

Abstract: The potential application of high-intensity focused ultrasound (US), HIFU, was investigated for nonthermal gene transfer and tumor ablation. Renal carcinoma (RENCA) tumors were implanted on the hind leg of BALB/c mice and injected with a marker plasmid. Optison US contrast agent was also injected into the tumor (IT) or into the venous (IV) circulation. HIFU at 1.55 MHz was applied to the tumors with guidance from diagnostic US images. One test of transfection was also performed with lithotripter shock waves. In one set of exposures, tumor volume was followed for 4 days and a beta-galactosidase marker plasmid was used for localization of transfected cells. A second set of exposures employed a luciferase marker plasmid for assessing overall transfection after 2 days. Use of 100-ms bursts at 8-MPa peak rarefactional pressure amplitude stopped tumor growth during the 4-day period, compared to a 2.8-fold growth in shams and yielded luciferase expression 34-fold greater than in shams. Longer bursts or higher pressure amplitudes led to decreases in tumor growth, but did not yield increases in transfection. The HIFU results were similar to those of shock waves for cavitation enhanced by IT Optison. These results should aid in optimizing the application of HIFU for nonthermal tumor treatment.

Speed of sound in normal and degenerated bovine articular cartilage.

Abstract: The unknown and variable speed of sound may impair accuracy of the acoustic measurement of cartilage properties. In this study, relationships between the speed of sound and cartilage composition, mechanical properties and degenerative state were studied in bovine knee and ankle cartilage (n = 62). Further, the effect of speed variation on the determination of cartilage thickness and stiffness with ultrasound (US) indentation was numerically simulated. The speed of sound was significantly (n = 32, p < 0.05) dependent on the cartilage water content (r = -0.800), uronic acid content (per wet weight, r = 0.886) and hydroxyproline content (per wet weight, r = 0.887, n = 28), Young's modulus at equilibrium (r = 0.740), dynamic modulus (r = 0.905), and degenerative state (i.e., Mankin score) (r = -0.727). In addition to cartilage composition, mechanical and acoustic properties varied significantly between different anatomical locations. In US indentation, cartilage is indented with a US transducer. Deformation and thickness of tissue are calculated using a predefined speed of sound and used in determination of dynamic modulus. Based on the simulations, use of the mean speed of sound of 1627 m/s (whole material) induced a maximum error of 7.8% on cartilage thickness and of 6.2% on cartilage dynamic modulus, as determined with the US indentation technique (indenter diameter 3 mm). We believe that these errors are acceptable in clinical US indentation measurements.

Probe calibration for freehand 3-D ultrasound.

Abstract: Ultrasound (US) probe calibration establishes the rigid body transformation between the US image and a tracking device attached to the probe. This is an important requirement for correct 3-D reconstruction of freehand US images and, thus, for accurate surgical navigation based on US. In this study, we evaluated three methods for probe calibration, based on a single-point phantom, a wire-cross phantom requiring 2-D alignment and a wire phantom for freehand scanning. The processing of acquired data is fairly common to these methods and, to a great extent, based on automated procedures. The evaluation is based on quality measures in 2-D and 3-D reconstructed data. With each of the three methods, we calibrated a linear-array probe, a phased-array sector probe and an intraoperative probe. The freehand method performed best, with a 3-D navigation accuracy of 0.6 mm for one of the probes. This indicates that clinical accuracy in the order of 1 mm may be achieved in US-based surgical navigation.

The interobserver reliability of ovarian volume measurement is improved with three-dimensional ultrasound, but dependent upon technique.

Abstract: The effect of measurement technique on the interobserver reliability of ovarian volume calculation from three-dimensional (3-D) ultrasound (US) data was investigated. Ovarian volume was calculated in 20 patients by two observers using both the "prolate ellipsoid formula" and a new 3-D rotational technique (VOCAL). There was a significant difference between observers in mean ovarian volume calculated by the prolate ellipsoid formula (31.54 mL vs. 26.54 mL: p < 0.05), which proved to be a significantly less reliable technique than 3-D rotational volume calculation with VOCAL. Image quality was significantly better (p < 0.001) and measurements were significantly more reliable (p < 0.05) in the B-plane than in the C- plane of the multiplanar display. Rotational measurement of ovarian volume from 3-D US data is significantly more reliable between observers than volume estimation from 2-D parameters using the prolate ellipsoid formula, but is dependent upon image quality, which is significantly better in the B-plane than in the C-plane.

Ultrasonic multifeature tissue characterization for prostate diagnostics.

Abstract: A new system for prostate diagnostics based on multifeature tissue characterization is proposed. Radiofrequency (RF) ultrasonic echo data are acquired during the standard transrectal ultrasound (US) imaging examination. Nine spectral, texture, first order and morphologic parameters are calculated and fed into two adaptive neuro-fuzzy inference systems (FIS) working in parallel. The outputs of the FISs are fed into a postprocessing procedure evaluating contextual information before being combined to form a malignancy map in which areas of high cancer probability are marked in red. The malignancy map is presented to the physician during the examination to improve the early detection of prostate cancer. The system has been evaluated on 100 patients undergoing radical prostatectomy. The ROC curve area using leave-one-out cross-validation over patients is A(Z) = 0.86 when distinguishing between hyperechoic and hypoechoic tumors and normal tissue and A(Z) = 0.84 when distinguishing between isoechoic tumors and healthy tissue, respectively. Tumors that are not visible in the conventional B-mode image can be located. Diagnosis of the prostate carcinoma using multifeature tissue characterization in combination with US imaging allows the detection of tumors at an early stage. Also, biopsy guidance and therapy planning can be improved.

Clinical evaluation of chirp-coded excitation in medical ultrasound

Abstract: Despite the enormous development in medical ultrasound (US) imaging over the last decades, penetration depth with satisfying image quality is often a problem in clinical practice. Coded excitation, used for years in radar techniques to increase signal-to-noise ratio (SNR), has recently been introduced in medical US scanning. In the present study, coded excitation using frequency-modulated US signals is implemented and evaluated in vivo.A total of nine male volunteers were scanned in three different abdominal locations, using both conventional pulsed and coded excitation. A modified scanner (B-K Medical model 3535) with transmitter and receiver boards developed in our group and a mechanical 4 MHz transducer were used. The system acquired coded and conventional US image frames interleaved, yielding identical acquisitions with the two techniques. Cine-loop sequences were evaluated by three experienced sonographers estimating penetration depth and scoring image quality of both conventional and coded imaging. The results showed a significant (p < 0.001) increase in penetration depth around 2 cm. Image quality was significantly (p < 0.001) better using codes at full usable depth and slightly, but also significantly (p < 0.05), better above depths, where the effect of coded excitation was noticeable to the sonographers. We conclude that the higher SNR offered by coded excitation gives improved image quality and provides increased penetration in medical US imaging. This increased SNR can, alternatively, be used to allow imaging at higher frequencies and thereby increase spatial resolution without any loss of penetration.