Showing papers in "Ultrasound in Medicine and Biology in 2001"

Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound.

Abstract: The purpose of this study was to investigate the pathologic changes of extracorporeal ablation of human malignant tumors with high-intensity focused ultrasound (HIFU). HIFU treatment was performed in the 164 patients with liver cancer, breast cancer, malignant bone tumor, soft tissue sarcoma and other malignant tumors at focal peak intensities from 5000 W x cm(-2) to 20,000 W x cm(-2), with operating frequencies of 0.8 to 3.2 MHz. To explore the pathologic impact of extracorporeal HIFU, 30 patients with malignant carcinoma underwent surgical removal after HIFU treatment. Pathologic findings showed that the treated tissues demonstrated homogeneous coagulative necrosis with an irreversible tumor cell death and severe damage to tumor blood vessels at the level of microsvasculature within the HIFU-targeted region. Thermolesions to intervening tissue were never observed. The treated region had a sharp border comprising only several cell layers between the treated and untreated areas. The repair of lesions had the processes of necrotic tissue absorption and granulation tissue replacement. It is concluded that extracorporeal treatment of human solid malignancies with HIFU could be safe, effective and feasible. As a noninvasive therapy, HIFU would be used clinically to treat patients with solid malignancies.

Measurements of bubble-enhanced heating from focused, MHz-frequency ultrasound in a tissue-mimicking material.

Abstract: Time-resolved measurements of the temperature field in an agar-based tissue-mimicking phantom insonated with a large aperture 1-MHz focused acoustic transducer are reported. The acoustic pressure amplitude and insonation duration were varied. Above a critical threshold acoustic pressure, a large increase in the temperature rise during insonation was observed. Evidence for the hypothesis that cavitation bubble activity in the focal zone is the cause of enhanced heating is presented and discussed. Mechanisms for bubble-assisted heating are presented and modeled, and quantitative estimates for the thermal power generated by viscous dissipation and bubble acoustic radiation are given.

Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging

Abstract: High-intensity focused ultrasound (HIFU) and conventional B-mode ultrasound (US) imaging were synchronized to develop a system for real-time visualization of HIFU treatment. The system was tested in vivo in pig liver. The HIFU application resulted in the appearance of a hyperechoic spot at the focus that faded gradually after cessation of HIFU exposure. The duration of HIFU exposure needed for a hyperechoic spot to appear, was inversely related to the HIFU intensity. The threshold intensity required to produce a hyperechoic spot in liver in < 1 s was 970 W/cm(2), in situ. At this HIFU dose, no immediate cellular damage was observed, providing a potential for pretreatment targeting. The real-time visualization method was used in hemostasis of actively bleeding internal pelvic vessels, allowing targeting and monitoring of successful treatment. Real-time US imaging may provide a useful tool for image-guided HIFU therapy.

Can natural strain and strain rate quantify regional myocardial deformation? A study in healthy subjects

Abstract: Strain rate (SR) and strain (epsilon) have been proposed as new ultrasound (US) indices for quantifying regional wall deformation, and can be measured from color Doppler myocardial data by determining the local spatial velocity gradient. The aim of this study was to define normal regional SR/epsilon values for both radial and longitudinal myocardial deformation. SR/epsilon profiles were obtained from 40 healthy volunteers. For radial deformation, posterior left ventricular (LV) wall SR/epsilon were calculated. For longitudinal, they were determined for basal, mid- and apical segments of the 1. septum; 2. lateral, 3. posterior and 4. anterior LV walls and for the 5. right ventricular (RV) lateral wall. SR/epsilon values describing radial deformation were higher than the corresponding SR/epsilon values obtained for longitudinal deformation. Longitudinal SR/epsilon were homogeneous throughout the septum and all LV walls. This was in contrast to the normal base-apex velocity gradient. The RV segmental SR/epsilon values were higher than those obtained from the corresponding LV wall and inhomogeneous (higher in the apical segments). SR/epsilon imaging appears to be a robust technique for quantifying regional myocardial deformation.

Biological effects of ultrasound: Development of safety guidelines. Part II: General review

Abstract: In the 1920s, the availability of piezoelectric materials and electronic devices made it possible to produce ultrasound (US) in water at high amplitudes, so that it could be detected after propagation through large distances. Laboratory experiments with this new mechanical form of radiation showed that it was capable of producing an astonishing variety of physical, chemical and biologic effects. In this review, the early findings on bioeffects are discussed, especially those from experiments done in the first few decades, as well as the concepts employed in explaining them. Some recent findings are discussed also, noting how the old and the new are related. In the first few decades, bioeffects research was motivated partly by curiosity, and partly by the wish to increase the effectiveness and ensure the safety of therapeutic US. Beginning in the 1970s, the motivation has come also from the need for safety guidelines relevant to diagnostic US. Instrumentation was developed for measuring acoustic pressure in the fields of pulsed and focused US employed, and standards were established for specifying the fields of commercial equipment. Critical levels of US quantities were determined from laboratory experiments, together with biophysical analysis, for bioeffects produced by thermal and nonthermal mechanisms. These are the basis for safety advice and guidelines recommended or being considered by national, international, professional and governmental organizations.

Assessing spectral algorithms to predict atherosclerotic plaque composition with normalized and raw intravascular ultrasound data

Abstract: Spectral analysis of backscattered intravascular ultrasound (IVUS) data has demonstrated the ability to characterize plaque. We compared the ability of spectral parameters (e.g., slope, midband fit and y-intercept), computed via classic Fourier transform (CPSD), Welch power spectrum (WPSD) and autoregressive (MPSD) models, to classify plaque composition. Data were collected ex vivo from 32 human left anterior descending coronary arteries. Regions-of-interest (ROIs), selected from histology, comprised 64 collagen-rich, 24 fibrolipidic, 23 calcified and 37 calcified-necrotic regions. A novel quantitative method was used to correlate IVUS data with corresponding histologic sections. Periodograms of IVUS samples, identified for each ROI, were used to calculate spectral parameters. Statistical classification trees (CT) were computed with 75% of the data for plaque characterization. The remaining data were used to assess the accuracy of the CTs. The overall accuracies for normalized spectra with CPSD, WPSD and MPSD were, respectively, 84.7%, 85.6% and 81.1% (training data) and 54.1%, 64.9% and 37.8% (test data). These numbers were improved to 89.2%, 91.9% and 89.2% (training) and 62.2%, 73% and 59.5% (test) when the calcified and calcified-necrotic regions were combined for analysis. Most CTs misclassified a few fibrolipidic regions as collagen, which is histologically acceptable, and the unnormalized and normalized spectra results were similar.

Dynamics of bubble oscillation in constrained media and mechanisms of vessel rupture in SWL.

Abstract: Rupture of small blood vessels is a primary feature of the vascular injury associated with shock-wave lithotripsy (SWL) and cavitation has been implicated as a potential mechanism. To understand more precisely the underlying mechanical cause of the injury, the dynamics of SWL-induced bubble dynamics in constrained media were investigated. Silicone tubing and regenerated cellulose hollow fibers of various inner diameters (0.2 to 1.5 mm) were used to fabricate vessel phantoms, which were placed in a test chamber filled with castor oil so that cavitation outside the phantom could be suppressed. Degassed water seeded with 0.2% Albunex® contrast agent was circulated inside the vessel phantom, and intraluminal bubble dynamics during SWL were examined by high-speed shadowgraph imaging and passive cavitation detection via a 20-MHz focused transducer. It was observed that, in contrast to the typical large and prolonged expansion and violent inertial collapse of SWL-induced bubbles in a free field, the expansion of the bubbles inside the vessel phantom was significantly constrained, leading to asymmetric elongation of the bubbles along the vessel axis and, presumably, much weakened collapse. The severity of the constraint is vessel-size dependent, and increases dramatically when the inner diameter of the vessel becomes smaller than 300 μm. Conversely, the rapid, large intraluminal expansion of the bubbles causes a significant dilation of the vessel wall, leading to consistent rupture of the hollow fibers (i.d. = 200 μm) after less than 20 pulses of shock wave exposure in a XL-1 lithotripter. The rupture is dose-dependent, and varies with the spatial location of the vessel phantom in the lithotripter field. Further, when the large intraluminal bubble expansion was suppressed by inversion of the lithotripter pressure waveform, rupture of the hollow fiber could be avoided even after 100 shocks. Theoretical calculation of SWL-induced bubble dynamics in blood confirms that the propensity of vascular injury due to intraluminal bubble expansion increases with the tensile pressure of the lithotripter shock wave, and with the reduction of the inner diameter of the vessel. It is suggested that selective truncation of the tensile pressure of the shock wave may reduce tissue injury without compromising the fragmentation capability of the lithotripter pulse. (E-mail: pzhong@acpub.duke.edu)

Freehand ultrasound elastography of breast lesions: clinical results.

Abstract: We developed a freehand method for ultrasound elastography, which can be applied during a routine sonographic examination with off-line calculation of strain images (elastograms). Forty-eight patients with 53 breast lesions were examined and, after biopsy or operation, histologic reports were available for all lesions. The correlation coefficient of time delay estimates was used as a quality criterion for the subsequent calculation of elastograms. Beyond the qualitative evaluation of elastograms, we suggested a semiquantitative approach. For that purpose, the elastogram of each lesion was normalized to an overall strain of 1% (i.e., the average strain in the image was set to 1%). After normalization, we determined mean strain values inside and outside of each lesion, respectively. Defining solid lesions as benign and malignant lesions except for fibrous mastopathy, we found significant difference in strain between solid lesions and their surrounding tissue. However, that result must not be misunderstood to suggest that it was possible to distinguish benign from malignant lesions in general. Still, we address the potential of ultrasound elastography to improve the detection and localization of breast lesions as well as their differential diagnosis. Besides, we developed a freehand applicator for further studies, which guarantees a homogeneous axial compression regardless of the experience of the examiner.

The mechanisms of stone fragmentation in ESWL

Abstract: Currently, several mechanisms of kidney stone fragmentation in extracorporal shockwave lithotripsy (ESWL) are under discussion. As a new mechanism, the circumferential quasistatic compression or "squeezing" by evanescent waves in the stone has been introduced. In fragmentation experiments with self-focussing electromagnetic shock-wave generators with focal diameters comparable to or larger than the stone diameter, we observed first cleavage surfaces either parallel or perpendicular to the wave propagation direction. This is in agreement with the expectation of the "squeezing" mechanism. Because, for positive pulse pressures below 35 MPa and stones with radii of 15 mm or smaller, cleavage into only two fragments was observed, we developed a quantitative model of binary fragmentation by "quasistatic squeezing." This model predicts the ratio of the number of pulses for the fragmentation to 2-mm size and of the number of pulses required for the first cleavage into two parts. This "fragmentation-ratio" depends linearly alone on the stone radius and on the final size of the fragments. The experimental results for spherical artificial stones of 5 mm, 12 mm and 15 mm diameter at a pulse pressure of 11 MPa are in good agreement with the theoretical prediction. Thus, binary fragmentation by quasistatic squeezing in ESWL as a new efficient fragmentation mechanism is also quantitatively verified.

A freehand elastographic imaging approach for clinical breast imaging: system development and performance evaluation

Abstract: A prototype freehand elastographic imaging system has been developed for clinical breast imaging. The system consists of a fast data acquisition system, which is able to capture sequences of intermediate frequency echo frames at full frame rate from a commercial ultrasound scanner whilst the breast is deformed using hand-induced transducer motion. Two-dimensional echo tracking was used in combination with global distortion compensation and multi-compression averaging to minimise decorrelation noise incurred when stress is applied using hand-induced transducer motion. Experiments were conducted on gelatine phantoms to evaluate the quality of elastograms produced using the prototype system relative to those produced using mechanically induced transducer motion. The strain sensitivity and contrast-to-noise ratio of freehand elastograms compared favourably with elastograms produced using mechanically induced transducer motion. However, better dynamic range and signal-to-noise ratio was achieved when elastograms were created using mechanically induced transducer motion. Despite the loss in performance incurred when stress is applied using hand-induced transducer motion, it was concluded that the prototype system performed sufficiently well to warrant clinical evaluation.

Use of overpressure to assess the role of bubbles in focused ultrasound lesion shape in vitro

Abstract: Overpressure--elevated hydrostatic pressure--was used to assess the role of gas or vapor bubbles in distorting the shape and position of a high-intensity focused ultrasound (HIFU) lesion in tissue. The shift from a cigar-shaped lesion to a tadpole-shaped lesion can mean that the wrong area is treated. Overpressure minimizes bubbles and bubble activity by dissolving gas bubbles, restricting bubble oscillation and raising the boiling temperature. Therefore, comparison with and without overpressure is a tool to assess the role of bubbles. Dissolution rates, bubble dynamics and boiling temperatures were determined as functions of pressure. Experiments were made first in a low-overpressure chamber (0.7 MPa maximum) that permitted imaging by B-mode ultrasound (US). Pieces of excised beef liver (8 cm thick) were treated in the chamber with 3.5 MHz for 1 to 7 s (50% duty cycle). In situ intensities (I(SP)) were 600 to 3000 W/cm(2). B-mode US imaging detected a hyperechoic region at the HIFU treatment site. The dissipation of this hyperechoic region following HIFU cessation corresponded well with calculated bubble dissolution rates; thus, suggesting that bubbles were present. Lesion shape was then tested in a high-pressure chamber. Intensities were 1300 and 1750 W/cm(2) ( +/- 20%) at 1 MHz for 30 s. Hydrostatic pressures were 0.1 or 5.6 MPa. At 1300 W/cm(2), lesions were cigar-shaped, and no difference was observed between lesions formed with or without overpressure. At 1750 W/cm(2), lesions formed with no overpressure were tadpole-shaped, but lesions formed with high overpressure (5.6 MPa) remained cigar-shaped. Data support the hypothesis that bubbles contribute to the lesion distortion.

The use of cross-correlation analysis between high-frequency ultrasound images to measure longitudinal median nerve movement

Abstract: Impaired nerve movement can lead to nerve injury (e.g., carpal tunnel syndrome). A noninvasive method to measure nerve movement in longitudinal section would enable an extensive analysis of nerve entrapment syndromes. A method has been developed using cross-correlation between successive high-frequency ultrasound (US) images to measure longitudinal movement of nerve and muscle. Control "phantom" experiments demonstrated the accuracy and reliability of this method at velocities of 1-10 mm/s. Increasing the frame interval between the compared frames enabled the accurate calculation of slower velocities. The correlation algorithm successfully measured relative movement when the US transducer was moved 1-3 mm over the surface of the forearm. Median nerve movement was repeatedly measured in the forearm during 30 degrees passive wrist extension in three subjects (range 2.63-4.12 mm) and index finger extension in seven subjects (range 1.59-4.48 mm). Median nerve movement values were consistent with those from cadaver studies.

Poroelastography: imaging the poroelastic properties of tissues

Abstract: In the field of elastography, biological tissues are conveniently assumed to be purely elastic solids. However, several tissues, including brain, cartilage and edematous soft tissues, have long been known to be poroelastic. The objective of this study is to show the feasibility of imaging the poroelastic properties of tissue-like materials. A poroelastic material is a material saturated with fluid that flows relative to a deforming solid matrix. In this paper, we describe a method for estimating the poroelastic attributes of tissues. It has been analytically shown that during stress relaxation of a poroelastic material (i.e., sustained application of a constant applied strain over time), the lateral-to-axial strain ratio decreases exponentially with time toward the Poisson's ratio of the solid matrix. The time constant of this variation depends on the elastic modulus of the solid matrix, its permeability and its dimension along the direction of fluid flow. Recently, we described an elastographic method that can be used to map axial and lateral tissue strains. In this study, we use the same method in a stress relaxation case to measure the time-dependent lateral-to-axial strain ratio in poroelastic materials. The resulting time-sequenced images (poroelastograms) depict the spatial distribution of the fluid within the solid at each time instant, and help to differentiate poroelastic materials of distinct Poisson's ratios and permeabilities of the solid matrix. Results are shown from finite-element simulations.

Construction and geometric stability of physiological flow rate wall-less stenosis phantoms.

Abstract: Wall-less flow phantoms are preferred for ultrasound (US) because tissue-mimicking material (TMM) with good acoustical properties can be made and cast to form anatomical models. The construction and geometrical stability of wall-less TMM flow phantoms is described using a novel method of sealing to prevent leakage of the blood-mimicking fluid (BMF). Wall-less stenosis flow models were constructed using a robust agar-based TMM and sealed using reticulated foam at the inlet and outlet tubes. There was no BMF leakage at the highest flow rate of 2.8 L/min in 0%, 35% and 57% diameter reduction stenoses models. Failure of the 75% stenosis model, due to TMM fracture, occurred at maximum flow rate of 2 L/min (mean velocity 10 m/s within the stenosis). No change of stenosis geometry was measured over 4 days. The construction is simple and effective and extends the possibility for high flow rate studies using robust TMM wall-less phantoms.

Stepwise logistic regression analysis of tumor contour features for breast ultrasound diagnosis.

Abstract: To assist the ultrasound (US) differential diagnosis of solid breast tumors by using stepwise logistic regression (SLR) analysis of tumor contour features, we retrospectively reviewed 111 medical records of digitized US images of breast pathologies. They were pathologically proved benign breast tumors from 40 patients (i.e., 40 fibroadenomas) and malignant breast tumors from 71 patients (i.e., 71 infiltrative ductal carcinomas). Radiologists, before analysis by the computer-aided diagnosis (CAD) system, segmented the tumors manually. The contour features were calculated by measuring the radial length of tumor boundaries. The features selection process was accomplished using a stepwise analysis procedure. Then, an SLR model with contour features was used to classify tumors as benign or malignant. In this experiment, cases were sampled with "leave-one-out" test methods to evaluate the SLR performance using a receiver operating characteristic (ROC) curve. The accuracy of our SLR model with contour features for classifying malignancies was 91.0% (101 of 111 tumors), the sensitivity was 97.2% (69 of 71), the specificity was 80.0% (32 of 40), the positive predictive value was 89.6% (69 of 77), and the negative predictive value was 94.1% (32 of 34). The CAD system using SLR can differentiate solid breast nodules with relatively high accuracy and its high negative predictive value could potentially help inexperienced operators to avoid misdiagnoses. Because the SLR model is trainable, it could be optimized if a larger set of tumor images were supplied.

Beam calibration without a phantom for creating a 3-D freehand ultrasound system.

Abstract: To create a freehand three-dimensional (3-D) ultrasound (US) system for image-guided surgical procedures, an US beam calibration process must be performed. The calibration method presented in this work does not use a phantom to define in 3-D space the pixel locations in the beam. Rather, the described method is based on the spatial relationship between an optically tracked pointer and a similarly tracked US transducer. The pointer tip was placed into the US beam, and US images, physical coordinates of the pointer and the transducer location were simultaneously recorded. US image coordinates of the pointer were mapped to the physical points using two different registration methods. Two sensitivity studies were performed to determine the location and number of points needed to calibrate the beam accurately. Results showed that the beam is most efficiently calibrated with approximately 20 points collected from throughout the beam. This method of beam calibration proved to be highly accurate, yielding registration errors of approximately 0.4 mm.

A fast calibration method for 3-D tracking of ultrasound images using a spatial localizer

Abstract: We have developed a fast calibration method for computing the position and orientation of 2-D ultrasound (US) images in 3-D space where a position sensor is mounted on the US probe. This calibration is required in the fields of 3-D ultrasound and registration of ultrasound with other imaging modalities. Most of the existing calibration methods require a complex and tedious experimental procedure. Our method is simple and it is based on a custom-built phantom. Thirty N-fiducials (markers in the shape of the letter “N”) embedded in the phantom provide the basis for our calibration procedure. We calibrated a 3.5-MHz sector phased-array probe with a magnetic position sensor, and we studied the accuracy and precision of our method. A typical calibration procedure requires approximately 2 min. We conclude that we can achieve accurate and precise calibration using a single US image, provided that a large number (approximately ten) of N-fiducials are captured within the US image, enabling a representative sampling of the imaging plane. (E-mail: ykim@u.washington.edu)

Transcranial ultrasound-improved thrombolysis: diagnostic vs. therapeutic ultrasound

Abstract: Success of stroke treatment with rt-PA depends on rapid vessel recanalization. Enzymatic thrombolysis may be enhanced by additional transcranial application of ultrasound (US). We investigated this novel technique using a 185-kHz probe and compared it to standard diagnostic US. In vitro studies were performed in a continuous pressure tubing system. Clots were placed in a postmortem skull and treated with rt-PA together with or without transtemporal 185-kHz US insonation (2W/cm2) and in comparison to 1-MHz diagnostic US (0.5 W/cm2). Recanalization time was significantly (p

The effect of therapeutic ultrasound on repair of the achilles tendon (tendo calcaneus) of the rat

Abstract: The purpose of this study was to evaluate the effects of therapeutic ultrasound (US) on the healing process in the Achilles tendon (Tendo calcaneus) of Wistar rats after tenotomy. Sonication was performed at a frequency of 1 MHz, an intensity of 0.5 W/cm(2) (SATA), for 5 min, over a period of 14 consecutive days in two modalities (n = 15); in both continuous and pulsed modes. The control group was divided into tenotomized, mock-sonicated and nontenotomized tendons (n = 15). On the 15th postoperative day, the tendons were removed and analyzed by using the polarized light microscopy, with the purpose of detecting and measuring the organization of collagen fibers through birefringence. The results showed a high birefringence for the tendons treated using the pulsed mode (p < 0.001), revealing the best organization and aggregation of collagen bundles. Sonication in the continuous mode induced a decrease (p = 0.047) in the ability to quicken the healing process. These findings suggest that US therapy is beneficial in the early healing process of tendons when the pulsed mode is used.

Assessment of the spatial homogeneity of artery dimension parameters with high frame rate 2-D B-mode.

Abstract: To elicit vessel wall inhomogeneities in diameter and distension along an arterial segment, a 2-D vessel wall-tracking system based on fast B-mode has been developed. The frame rate of a 7.5-MHz linear-array transducer (length 36 mm) is enhanced by increasing the pulse-repetition frequency to 10 kHz, decreasing the number of echo lines per frame from 128 to 64, or increasing the interspacing between echo lines with a factor of two or four. Dedicated software has been developed to extract for each echo-line the end-diastolic diameter from the B-mode image and the 2-D distension waveform from the underlying radiofrequency (RF) information. The method is validated in tubes with various focal lesion sizes. Straight segments of presumably homogeneous common carotid arteries have also been tested. The temporal and spatial SD of diameter or distension reveals inhomogeneities in time or space (i.e., inhomogeneities in artery characteristics). The method can be implemented in echo systems supporting high frame rates and real-time processing of radiofrequency data.

Power spectral strain estimators in elastography

Abstract: Elastography can produce quality strain images in vitro and in vivo. Standard elastography uses a coherent cross-correlation technique to estimate tissue displacement and tissue strain using a subsequent gradient operator. While coherent estimation methods generally have the advantage of being highly accurate and precise, even relatively small undesired motions are likely to cause enough signal decorrelation to produce significant degradation of the elastogram. For elastography to become more universally practical in such applications as hand-held, intravascular and abdominal imaging, the limitations associated with coherent strain estimation methods that require tissue and system stability, must be overcome. In this paper, we propose the use of a spectral shift method that uses a centroid shift estimate (Fig. 5) to measure local strain directly. Furthermore, we also show theoretically that a spectral bandwidth method can also provide a direct strain estimation. We demonstrate that strain estimation using the spectral shift technique is moderately less precise but far more robust than the cross-correlation method. A theoretical analysis as well as simulations and experimental results are used to illustrate the properties associated with this method.

Activation, aggregation and adhesion of platelets exposed to high-intensity focused ultrasound.

Abstract: Using platelet-rich plasma, we investigated the effect of 1.1-MHz continuous wave high-intensity focused ultrasound (HIFU) on platelet activation, aggregation and adhesion to a collagen-coated surface. Platelets were exposed for durations of 10-500 s at spatial average intensities of up to 4860 W/cm(2). To avoid heating effects, the average temperature in the HIFU tank was maintained at 33.8 +/- 4.0 degrees C during platelet experiments. Flow cytometry, laser aggregometry, environmental scanning electron microscopy and passive cavitation detection were used to observe and to quantify platelet activation, aggregation, adhesion to a collagen-coated surface and associated cavitation. It was determined that HIFU can activate platelets, stimulate them to aggregate and promote their adherence to a collagen-coated surface. In principle, HIFU can stimulate primary, or platelet-related, hemostasis. Cavitation was monitored by a passive cavitation detector during aggregation trials and was quantified to provide a relative measure of the amount of cavitation that occurred in each aggregation trial. Regression analysis shows a weak correlation (r(2) = 0.11) between aggregation and ultrasound intensity, but a substantial correlation (r(2) = 0.76) between aggregation and cavitation occurrence.

Feasibility of the flash-replenishment concept in renal tissue: which parameters affect the assessment of the contrast replenishment?

Abstract: The purpose of the study was to evaluate whether power pulse inversion (PPI) and pulse inversion (PI) techniques allow the measurement of indices of microcirculatory flow in real-time at low emission power using contrast microbubbles. PPI and PI imaging were performed in a kidney perfusion model during continuous infusion of Definity (0.12 mL/min). At steady state of tissue enhancement, contrast was destroyed by emission of echo bursts at high emission power (MI = 1.3). Consecutively, contrast replenishment was assessed at low emission power (MI = 0.09) in real-time imaging modes (PPI: 12 Hz; PI: 25 Hz). Regions-of-interest (ROI) of variable sizes were placed in the renal cortex and bigger arteries to compare replenishment of macro- and microcirculation. Nonlinear curve fitting was performed using the mathematical model y=s+A(1-e(-betat)), with A as the parameter describing blood volume and beta as a parameter describing the speed of microbubble contrast replenishment. Replenishment curves could be visually appreciated and quantitatively analyzed in all renal segments. A was significantly higher in bigger arteries compared to renal cortex (p < 0.001). beta was found to be significantly higher in the arteries as compared to the cortex (p < 0.001). The SD of beta diminishes with increasing size of the ROI. The acquisition of replenishment curves following ultrasound (US)-induced destruction of contrast microbubbles is feasible at low power using PPI and PI. Assessment of replenishment kinetics allows the differentiation between macro- and microcirculation. Size and position of the ROI have an important impact on the generation of replenishment curves in both imaging modalities, which has to be taken into account.

Sources of error in maximum velocity estimation using linear phased-array Doppler systems with steady flow.

Abstract: Using linear-array Doppler ultrasound (US) transducers, the measured maximum velocity may be in error and lead to incorrect clinical diagnosis. This study investigates the existence and cause of maximum velocity estimation errors for steady flow of a blood-mimicking fluid in a tissue-mimicking phantom. A specially designed system was used that enabled fine control of flow rate, transducer positioning and transducer angle relative to the flow phantom. Doppler machine settings (transducer aperture size, focal depth, beam-steering, gain) were varied to investigate a wide range of clinical applications. To estimate the maximum velocity, a new signal-to-noise ratio (SNR) independent method was developed to calculate the maximum frequency from an ensemble averaged Doppler power spectrum. This enabled the impact of each factor on the total Doppler error to be determined. When using the new maximum frequency estimator, it was found that the effect of transducer focal depth, intratransducer, intramachine, intermachine (that was tested) and beam-steering did not significantly contribute to maximum velocity estimation errors. Instead, it was the dependence of the maximum velocity on the Doppler angle that made, by far, the greatest contribution to the estimation error. Because our maximum frequency estimator took into account the effect of intrinsic spectral broadening, the degree of overestimation error was not as great as that previously published. Thus, the effects of Doppler angle and intrinsic spectral broadening are the chief sources of Doppler US error and should be the focus of future efforts to improve the accuracy.

Advancing intravascular ultrasonic palpation toward clinical applications.

Abstract: This paper describes the first reported attempt to develop a real-time intravascular ultrasonic palpation system. We also report on our first experience in the catherization laboratory with this new elastographic imaging technique. The prototype system was based on commercially available intravascular ultrasound (US) scanner that was equipped with a 20-MHz array catheter. Digital beam-formed radiofrequency (RF) echo data (i.e., 12 bits, 100 Hz) was captured at full frame rate from the scanner and transferred to personal computer (PC) memory using a fast data-acquisition system. Composite palpograms were created by applying a one-dimensional (1-D) echo tracking technique in combination with global motion compensation and multiframe averaging to several pairs of RF echo frames that were obtained in the diastolic phase of the cardiac cycle. The quality of palpograms was assessed by conducting experiments on vessel phantoms and on patients. The results demonstrated that robust and consistent palpograms could be generated in almost real-time using the proposed system. Good correlation was observed between low strain values and regions of calcification as identified from the intravascular US (IVUS) sonograms. Although the clinical results are clearly preliminary, it was concluded that the prototype system performed sufficiently well to warrant further and more in-depth clinical investigation.

High-frequency ultrasonic attenuation and backscatter coefficients of in vivo normal human dermis and subcutaneous fat

Abstract: In vivo attenuation and backscatter coefficients of normal human forearm dermis and subcutaneous fat were determined in the ranges 14 to 50 MHz and 14 to 34 MHz, respectively. Data were collected using three different transducers to ensure that results were independent of the measurement system. Attenuation coefficient was obtained by computing spectral slopes vs. depth, with the transducers axially translated to minimize diffraction effects. Backscatter coefficient was obtained by compensating recorded backscatter spectra for system-dependent effects and, additionally, for one transducer using the reference phantom technique. Good agreement was seen between the computed attenuation and backscatter results from the different transducers/methods. The attenuation coefficient of the forearm dermis was well described by a linear dependence with a slope that ranged between 0.08 to 0.39 (median = 0.21) dB mm(-1) MHz(-1). The backscatter coefficient of the dermis was generally in the range 10(-3) to 10(-1) Sr(-1) mm(-1) and showed an increasing trend with frequency. No significant differences in attenuation coefficient slope between the forearm dermis and fat were noted. Within the range of 14 to 34 MHz, the ratio of integrated (average) backscatter of dermis to that of fat ranged from 1.03 to 87.1 (median = 6.45), indicating significantly higher backscatter for dermis than for fat. Data were also recorded at the fingertip where the attenuation coefficient slope of the dermis was seen to be higher than that at the forearm.

Lysis and sonoporation of epidermoid and phagocytic monolayer cells by diagnostic ultrasound activation of contrast agent gas bodies.

Abstract: Epidermoid A431 (human carcinoma) and phagocytic RAW-264.7 cells were grown as monolayers on 5-microm thick Mylar sheets by standard culture methods. The sheets formed one window of disk-shaped ultrasound (US) exposure chambers. A diagnostic US machine in spectral Doppler mode was used for exposure with a 3.5-MHz scanhead aimed upward at the chamber in a 37 degrees C water bath. Sonoporation and cell lysis were evaluated for assessment of cell membrane damage. For both epidermoid and RAW cells on the upper window with 1% Optison contrast agent, cell lysis was detectable in addition to sonoporation. The phagocytic cells tended to retain the gas bodies when incubated with contrast agent, and membrane damage occurred even for exposure on the bottom window. The effects were also seen for RAW cells incubated with 5% contrast agent for 15 min and then rinsed before exposure. Above a threshold range for lysis and sonoporation of 0.09 to 0.23 MPa, the counts of affected cells increased for both cell lines to about 20% at 0.83 MPa. These results indicate relatively low thresholds for membrane damage induced by diagnostic US activation of contrast agent gas bodies, with a potential for targeting of these effects to phagocytic cells.

Contrast-transfer efficiency for continuously varying tissue moduli: simulation and phantom validation.

Abstract: This study consisted of two parts. In the first part, the contrast-transfer efficiency (CTE) in elastography was extended to account for continuous changes of modulus distribution. It was shown that, for a finite size background, the strain contrast approaches the modulus contrast in the case of Gaussian distributions. Thus, an increase in the CTE was obtained. For a fixed background size, it was shown that the CTE increases as the SD of the Gaussian distribution increases. This property was explained by the redistribution of strain concentrations at the inclusion/background interface. In the second part of the study, the CTE was verified experimentally. Six gelatin/agar/water-based phantoms embedding inclusions with modulus contrast varying between ± 6 dB were manufactured. It was shown that the modulus at the interface inclusion/background was continuous and, in turn, resulted in an increase of the CTE as compared to the known case of a sharp boundary. The continuous inclusion/background interface was explained by the existence of an osmotic pressure gradient. (E-mail: Faouzi.Kallel@uth.tmc.edu)

Evaluation of voxel-based registration of 3-D power Doppler ultrasound and 3-D magnetic resonance angiographic images of carotid arteries.

Abstract: (Received 20 July 2000, in final form 30 March 2001) Spatial registration and fusion of ultrasound (US) images with other modalities may aid clinical interpretation. We implemented and evaluated on patient data an automated retrospective registration of magnetic resonance angiography (MRA) carotid bifurcation images with 3-D power Doppler ultrasound (PD US) and indirectly with 3-D B-mode US. Volumes were initially thresholded to reduce the uncorrelated noise signals. The registration algorithm subsequently maximized the mutual information measure between the PD US and 3-D MRA via iterative simplex search to find best rigid body transformation. We rated the performance of the algorithm visually on (n = 5) clinical MRA and 3-D PD US datasets. We also evaluated quantitatively the effect of thresholding, initial misalignment of the paired volumes and the reproducibility registration. We investigated the effect of image artefacts by simulation experiments. Preregistration misalignments of up to 5 mm in the transaxial plane, up to 10 mm along the axis of the carotids and up to 40 ° resulted in 107 of 110 successful registrations, with translational and rotational errors of 0.32 mm ± 0.3 mm and 1.6 ± 2.1°. The algorithm was not affected by missing arterial segments of up to 8 mm in length. The average registration time was 4 min. We conclude that the algorithm could be applied to 3-D US PD and MRA data for automated multimodality registration of carotid vessels without the use of fiducials.

Ultrasound-induced physiological effects and secondary metabolite (saponin) production in Panax ginseng cell cultures

Abstract: This work was aimed at the effects of ultrasound (US) on the growth and secondary metabolite biosynthesis of cultured plant cells. Suspension cultures of Panax ginseng cells were exposed to US at power density below 82 mW/cm3 for short periods of time (1-4 min) in a US bath (38.5-kHz fixed frequency and 810 W maximum peak power). Under most exposure conditions, US stimulated the biosynthesis of secondary metabolites, the ginsenoside saponins of ginseng cells, increasing the total saponin content of the cell by up to 75%. The growth and viability of ginseng cells were usually depressed immediately after the exposure to US, but recovered gradually to levels similar to those of a normal culture in a few days, with virtually no net loss of biomass yield at the end of the culture period. At some lower US doses, sonicated cultures could even reach slightly higher biomass yields than that of normal cultures. The effects of US on cell growth and secondary metabolite yield showed a significant correlation with the total US energy emitted (i.e., the product of US power and exposure time). Mechanical stress and microstreaming induced by acoustic cavitation were considered as the most possible causes of the various physiological effects of US on ginseng cells. In particular, the stimulation of secondary metabolite production by US may be a result of US-induced plant cell defense response.