Scatterer size estimation using the center frequency assessed from ultrasound time domain data.

Scatterer size estimation is useful when characterizing tissue using ultrasound. In all previous studies on scatterer size, the estimations are performed in the frequency domain and are thus subjected to a trade off in time-frequency resolution. This study focused on the feasibility of estimating scatterer size in the time domain using only the ultrasound center frequency, assuming a Gaussian-shaped pulse. A model for frequency normalization was derived and the frequency-dependent attenuation was compensated. Five phantoms with well-defined sizes of spherical glass beads were made and scanned with two different linear array transducers with variable center frequencies. A strong correlation (r = 0.99, p < 10-19) between the backscattered center frequency and the product between the wave number and scatterer radius was demonstrated. On average the scatterer diameter was underestimated by 6% ± 24%. These results suggest that estimation of scatterer size is possible using only the center frequency assessed in the time domain.

Longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines.

The effects of catecholamines on longitudinal displacements and intramural shear strain of the arterial wall are unexplored. Therefore, the common carotid artery of five anaesthetized pigs was investigated using an in-house developed noninvasive ultrasonic technique. The study protocol included intravenous infusion of low-dose epinephrine (ß-adrenoceptor activation), as well as intravenous boluses of norepinephrine (α-adrenoceptor activation). Further, the effects of ß-blockade (metoprolol) were studied. There were significant positive correlations between pulse pressure and longitudinal displacement of the intima-media complex (r = 0.72; P < 0.001), as well as between pulse pressure and intramural shear strain (r = 0.48; P < 0.001). Following administration of norepinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain profoundly increased (median 190%, range 102-296%, and median 141%, range 101-182%, respectively, compared with baseline), also when given during ß-blockade (median 228%, range 133-266%, and median 158%, range 152-235%, respectively). During infusion of low-dose epinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain decreased (median 88%, range 69-122%, and median 69%, range 47-117%, respectively, compared with baseline). In conclusion, the present study shows, for the first time, that the longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Increase in longitudinal displacements seems to be strongly related to α-adrenoceptor activation. Thus metoprolol is insufficient to counteract a profound increase in longitudinal displacement and intramural shear strain following a surge of norepinephrine.

Separating overlapping click trains originating from multiple individuals in echolocation recordings.

Recordings of the acoustic activity of free-swimming groups of echolocating dolphins increase the likelihood of collecting overlapping click trains, originating from multiple individuals, in the same set of data. In order to evaluate the click properties of each individual based on such recordings it is necessary to identify which clicks originate from which animal. This paper suggests a computationally efficient strategy to separate overlapping click trains originating from multiple free-swimming bottlenose dolphins, enabling echolocation analysis at an individual level on several animals. This technique is based on sequential matching of the frequency spectra of successive clicks. The clicks are grouped together as individual click trains if the correlation coefficients between clicks are higher than a pre-set threshold level. The robustness of the algorithm is tested by adding artificially generated white Gaussian noise and comparing the results with other comparable commonly used methods based on inter-click intervals, centroid frequencies, and amplitude levels. The described method is applicable to a variety of experimental and observational contexts, e.g., those regarding echolocation development of calves, the hypothesized acoustic "etiquette" among dolphins when investigating the same object, and the possible occurrence of eavesdropping in large dolphin pods.

47-channel burst-mode recording hydrophone system enabling measurements of the dynamic echolocation behavior of free-swimming dolphins.

Detailed echolocation behavior studies on free-swimming dolphins require a measurement system that incorporates multiple hydrophones (often >16). However, the high data flow rate of previous systems has limited their usefulness since only minute long recordings have been manageable. To address this problem, this report describes a 47-channel burst-mode recording hydrophone system that enables highly resolved full beamwidth measurements on multiple free-swimming dolphins during prolonged recording periods. The system facilitates a wide range of biosonar studies since it eliminates the need to restrict the movement of animals in order to study the fine details of their sonar beams.

Feasibility of measuring acoustic streaming for improved diagnosis of rhinosinusitis.

No noninvasive methods exist currently with the capability of distinguishing between various stages of a sinus infection. We studied a method based on induced acoustic streaming in the accumulated fluid within the maxillary sinuses. The hypothesis was that acoustic streaming will not be induced at clinically acceptable intensity levels in infectious mucous fluid because of its high viscosity, whereas detected acoustic streaming is a strong indication that the sinus content is a noninfectious serous fluid. As a model, an anthropomorphic sinus phantom with bovine cortical bone to mimic the bone surrounding the maxillary sinus was constructed. Milk (1.5% fat content) was used as model fluid. From fluid and bone attenuation measurements, an ultrasound frequency of about 5 MHz was estimated to produce the highest acoustic streaming in the sinus phantom. Simulations of the acoustic streaming in a sealed cavity also showed that the width of the ultrasound beam should be about half the size of the cavity to optimize the streaming velocity. With a 4.9-MHz continuous-wave transducer operating at a spatial peak temporal average intensity (I(spta)) of 640 mW/cm(2), an acoustic streaming velocity of 0.19 cm/s was generated and detected in the sinus phantom.

An echolocation visualization and interface system for dolphin research.

The present study describes the development and testing of a tool for dolphin research. This tool was able to visualize the dolphin echolocation signals as well as function as an acoustically operated "touch screen." The system consisted of a matrix of hydrophones attached to a semitransparent screen, which was lowered in front of an underwater acrylic panel in a dolphin pool. When a dolphin aimed its sonar beam at the screen, the hydrophones measured the received sound pressure levels. These hydrophone signals were then transferred to a computer where they were translated into a video image that corresponds to the dynamic sound pressure variations in the sonar beam and the location of the beam axis. There was a continuous projection of the image back onto the hydrophone matrix screen, giving the dolphin an immediate visual feedback to its sonar output. The system offers a whole new experimental methodology in dolphin research and since it is software-based, many different kinds of scientific questions can be addressed. The results were promising and motivate further development of the system and studies of sonar and cognitive abilities of dolphins.

Low-energy ultrasound exposure of the streptokinase molecule may enhance but also attenuate its fibrinolytic properties.

INTRODUCTION: This study explores the mechanisms of ultrasound-enhanced fibrinolysis by investigating the effects of pre-exposure to pulsed high-frequency, low-energy ultrasound on the fibrinolytic properties of streptokinase. MATERIALS AND METHODS: Fibrinolytic activity was measured as haemoglobin release from blood clots. The fibrinolytic effects of streptokinase and ultrasound separately and in combination were studied by evaluating cumulative percentages of haemoglobin release following 1 h of exposure using two clots, one for intervention and the other concomitantly as control. In particular, the effects of exposure to ultrasound on clot-free streptokinase solution were compared to those of concomitant exposures of streptokinase solution with clot. The exposures were made at a frequency of 1 MHz (10% duty cycle) and at three intensity levels (0.5, 1.0 and 4.0 W/cm2 intensity I(SATA)). RESULTS: Increased fibrinolysis (31.2%, P=0.028) was observed after concomitant ultrasound exposure of clot and streptokinase solution at 0.5 W/cm2 intensity. Compared to unexposed streptokinase solution, the lytic effect following exposure of streptokinase solution to ultrasound was significantly increased (32.7%, P=0.002). This enhancement effect disappeared at intensity 1 W/cm2, whilst further increase to 4.0 W/cm2 inhibited the lytic effect of streptokinase, both during concomitant exposure (-25.2%, P=0.028) and after pre-exposure of streptokinase solution to ultrasound (-25.4%, P=0.002). CONCLUSION: The fibrinolytic property of streptokinase is modulated by exposure to pulsed ultrasound of frequency 1 MHz, being enhanced at low intensity and inhibited at high intensity.

Direct action on the molecule is one of several mechanisms by which ultrasound enhances the fibrinolytic effects of reteplase.

Enhanced fibrinolytic reperfusion therapy may improve the outcome in embolic stroke, where ultrasound exposure has been shown to be one option. We recently verified that the fibrinolytic properties of streptokinase were modulated following ultrasound exposure of the molecule. We have now explored this possibility following ultrasound exposure of the reteplase molecule. The effects on clot lysis of reteplase and ultrasound both separately and in combination were studied by evaluating cumulated release of haemoglobin from whole blood clots following 1 h of exposure. Specifically, we investigated how clot lysis was modulated following pulsed 1 MHz ultrasound pre-exposure of the reteplase solution at intensities ranging between 0.125 and 4 W/cm2 spatial-average temporal-average intensity (SATA) and the effects of reteplase following 1 h of pre-exposure of clots to ultrasound at high intensity (4 W/cm2SATA). Significant enhancement of clot lysis during concomitant reteplase and pulsed ultrasound exposure were observed in two intensity ranges: 0.125-0.25 and 2-4 W/cm2SATA. Pre-exposing reteplase solution to ultrasound significantly increased clot lysis only in the lower intensity range. At high ranges, pre-exposure of clots to ultrasound was followed by an increased fibrinolytic action of reteplase. Pre-exposing reteplase solution to low-intensity ultrasound induced changes in the reteplase molecule that enhanced its fibrinolytic effects. Although this effect disappeared at moderately higher ultrasound intensity, the pre-exposure of clots to ultrasound of higher intensity induced increased fibrinolytic effects of reteplase solution.

Can pulsed ultrasound increase tissue damage during ischemia? A study of the effects of ultrasound on infarcted and non-infarcted myocardium in anesthetized pigs.

BACKGROUND: The same mechanisms by which ultrasound enhances thrombolysis are described in connection with non-beneficial effects of ultrasound. The present safety study was therefore designed to explore effects of beneficial ultrasound characteristics on the infarcted and non-infarcted myocardium. METHODS: In an open chest porcine model (n = 17), myocardial infarction was induced by ligating a coronary diagonal branch. Pulsed ultrasound of frequency 1 MHz and intensity 0.1 W/cm2 (ISATA) was applied during one hour to both infarcted and non-infarcted myocardial tissue. These ultrasound characteristics are similar to those used in studies of ultrasound enhanced thrombolysis. Using blinded assessment technique, myocardial damage was rated according to histopathological criteria. RESULTS: Infarcted myocardium exhibited a significant increase in damage score compared to non-infarcted myocardium: 6.2 +/- 2.0 vs. 4.3 +/- 1.5 (mean +/- standard deviation), (p = 0.004). In the infarcted myocardium, ultrasound exposure yielded a further significant increase of damage scores: 8.1 +/- 1.7 vs. 6.2 +/- 2.0 (p = 0.027). CONCLUSION: Our results suggest an instantaneous additive effect on the ischemic damage in myocardial tissue when exposed to ultrasound of stated characteristics. The ultimate damage degree remains to be clarified.

Evaluation of an ultrasonic echo-tracking method for measurements of arterial wall movements in two dimensions.

The longitudinal movement of blood vessel walls has so far gained little or no attention, as it has been presumed that these movements are of a negligible magnitude. However, modern high-resolution ultrasound scanners can demonstrate that the inner layers of the arterial wall exhibit considerable movements in the longitudinal direction. This paper evaluates a new, noninvasive, echo-tracking technique, which simultaneously can track both the radial and the longitudinal movements of the arterial wall with high resolution in vivo. Initially, the method is evaluated in vitro using a specially designed ultrasound phantom, which is attached to and moved by an X-Y system, the movement of which was compared with two high-resolution triangulation lasers. The results show an inaccuracy of 2.5% full scale deflection (fsd), reproducibility of 12 microm and a resolution of 5 microm, which should be more than sufficient for in vivo studies. The ability of the method is also demonstrated in a limited in vivo study in which a preselected part of the inner vessel wall of the right common carotid artery of a healthy volunteer is tracked in two dimensions over many cardiac cycles. The results show well reproducible x-y movement loops in which the recorded radial and longitudinal movements both are of the magnitude millimetre.

Profound increase in longitudinal displacements of the porcine carotid artery wall can take place independently of wall shear stress: a continuation report.

The mechanisms underlying longitudinal displacements of the arterial wall, that is, displacements of the wall layers along the artery, and the resulting intramural shear strain remain largely unknown. We have already found that these displacements undergo profound changes in response to catecholamines. Wall shear stress, closely related to wall shear rate, represents the viscous drag exerted on the vessel wall by flowing blood. The aim of the work described here was to study possible relations between the wall shear rate and the longitudinal displacements. We investigated the carotid arteries of five anesthetized pigs in different hemodynamic situations using in-house developed non-invasive ultrasound techniques. The study protocol included administration of epinephrine, norepinephrine and ß-blockade (metoprolol). No significant correlation between longitudinal displacement of the intima-media complex and wall shear rate was found. This result suggests that one or multiple pulsatile forces other than wall shear stress are also working along arteries, strongly influencing arterial wall behavior.

Movement artefact suppression in blood perfusion measurements using a multifrequency technique.

The standard way of suppressing movement artefacts in Doppler measurements is by means of a high-pass filter. This is because artefacts usually are of high amplitude, but have low frequencies. The immediate drawback is, then, that low-velocity blood flow is also filtered out. In this paper, a method to reduce movement artefacts in blood perfusion measurements is proposed, using simultaneous transmission and reception of multiple frequencies in a continuous-wave Doppler system. It is shown that Doppler signals originating from blood may be considered uncorrelated for a large enough frequency separation between channels, and tissue movements are more correlated. By subtracting perfusion estimates obtained by time-domain processing, correlated signals can be suppressed. The subtraction algorithm is shown to produce a linear perfusion estimate, but with twice the standard deviation compared to an estimate obtained by simply averaging channels. Movement artefacts in both in vitro and in vivo models are shown to be reduced by the algorithm. Imbalance between channels does, however, cause the artefacts to be only partly reduced. The problem can be alleviated by filtering the signals prior to subtraction, but this results in a nonlinear estimate, especially for large time constants in the filter. Some amount of filtering can still be desirable to suppress partly correlated artefacts, even if identical time-domain processing units are implemented, as could be done digitally.

A new non-invasive ultrasonic method for simultaneous measurements of longitudinal and radial arterial wall movements: first in vivo trial.

During recent years, the radial movement of the arterial wall has been extensively studied, and measurements of the radial movement are now an important tool in cardiovascular research for characterizing the mechanical properties of the arterial wall. In contrast, the longitudinal movement of vessels has gained little or no attention as it has been presumed that this movement is negligible. With modern high-resolution ultrasound, it can, however, be seen that the intima-media complex of the arterial wall moves not only in the radial direction, but also in the longitudinal direction during pulse-wave propagation. This paper describes a new non-invasive ultrasonic method that is able to measure simultaneously two dimensionally arterial vessel wall movements. The method is demonstrated in a limited in vivo trial. Results from the in vivo trial show that, apart from the well-known radial movement, there is a distinct longitudinal movement in the human common carotid artery with, in this case, the intima-media complex moving substantially as compared with the region of the tunica adventitia. Two-dimensional evaluation of the vessel-wall movements, taking not only the radial movement, but also the longitudinal movement into account, may provide novel information of importance in the evaluation of vessel-wall function.

Frequency dependence of speckle in continuous-wave ultrasound with implications for blood perfusion measurements.

Speckle in continuous wave (CW) Doppler has previously been found to cause large variations in detected Doppler power in blood perfusion measurements, where a large number of blood vessels are present in the sample volume. This artifact can be suppressed by using a number of simultaneously transmitted frequencies and averaging the detected signals. To optimize the strategy, statistical properties of speckle in CW ultrasound need to be known. This paper presents analysis of the frequency separation necessary to obtain independent values of the received power for CW ultrasound using a simplified mathematical model for insonation of a static, lossless, statistically homogeneous, weakly scattering medium. Specifically, the autocovariance function for received power is derived, which functionally is the square of the (deterministic) autocorrelation function of the effective sample volumes produced by the transducer pair for varying frequencies, at least if a delta correlated medium is assumed. A marginal broadening of the modeled autocovariance functions is expected for insonation of blood. The theory is applicable to any transducer aperture, but has been experimentally verified here with 5-MHz, 6.35-mm circular transducers using an agar phantom containing small, randomly dispersed glass particles. A similar experimental verification of a transducer used in multiple-frequency blood perfusion measurements shows that the model proposed in this paper is plausible for explaining the decorrelation between different channels in such a measurement.

Automatic measurements of diameter, distension and intima media thickness of the aorta in premature rabbit pups using B-mode images.

To improve cardiovascular research, there is a growing need for arterial characterization in small animals. We developed a method, ARTIC (arterial characterization) for measuring lumen diameter, distension and intima media thickness (IMT). In this study ARTIC was used to automatically characterize the aorta of premature rabbit pups. Automatic measurements were compared with manual measurements, both performed by three observers. Diameter was 769 ± 140 µm (manual) and 766 ± 142 µm (automatic), distension was 35 ± 15 µm (manual) and 40 ± 12 µm (automatic) and IMT was 84 ± 11 µm (manual) and 88 ± 8 µm (automatic) (mean ± standard deviation). The variation in the measured diameter, distension and IMT ranged from 1.1% to 26.0% (manual) and from 1.0% to 9.0% (automatic). The intra-class correlation coefficient ranged from 33.0% to 99.3% (manual) and from 76.9% to 99.6% (automatic). The evaluation revealed that it is feasible to use ARTIC on B-mode images of arteries with small dimensions, which makes it a useful tool for arterial characterization in small animals.

Different patterns of longitudinal displacement of the common carotid artery wall in healthy humans are stable over a four-month period.

Using an in-house developed ultrasonic method, we have shown that there is distinct longitudinal multiphasic displacement of the human common carotid artery (CCA) wall during the cardiac cycle. Different subjects showed markedly different patterns of displacement. At present, it is not known if the pattern of displacement in an individual is stable over time. Therefore, in this study, we measured the longitudinal displacement of the right CCA in 10 healthy humans at two different occasions 4 months apart. The basic pattern of longitudinal displacement for an individual was highly stable, including intraclass correlation coefficient (ICC) of 0.88 for the ratio between the first antegrade and the retrograde displacement, and ICC of 0.76 for the magnitude of the first antegrade displacement. The stable basic pattern of displacement showed marked differences among subjects, also of the same age and gender. Further studies are needed to elucidate the underlying mechanisms, the physiologic, pathophysiologic and clinical implications of this phenomenon.

A method for arterial diameter change measurements using ultrasonic B-mode data.

Arterial diameter change is related to distending blood pressure and is used in estimation of arterial stiffness parameters. A common technique to track the arterial walls is by integration of wall velocities estimated by different methods using cross correlation or tissue Doppler. However, because of the high pulse repetition frequency and the need for separate pulsing sequences, the B-mode image quality is affected. We have previously developed a fast algorithm for direct measurement of lumen diameter using B-mode images. In this study we have improved the technique to be more robust and also implemented measurements of diameter change, maximum differential wall velocity and relative diameter change of the common carotid artery noninvasively in vivo. The influence of the lateral width of the region of interest (ROI; 1 pixel, 0.1 mm, 0.5 mm, 1 mm, 2.5 mm and 5 mm) was evaluated. Using the optimal lateral width (2.5 mm), the systematic and random differences between two consecutive measurements were 21 microm and 105 microm, respectively, for lumen diameter measurement; -7 microm and 39 microm, respectively, for lumen diameter change measurements; -0.2 mm/s and 0.9 mm/s, respectively, for maximum relative wall velocity; and -0.2 % and 0.8 %, respectively, for measurements of the relative diameter change. The coefficient of variation (CV) was 1.9%, 5.2%, 7.9% and 6.0%, respectively. The study indicates that the reproducibility is sufficient for in vivo studies when the width of the ROI is 1.0 mm or wider.

Evaluation of an algorithm for arterial lumen diameter measurements by means of ultrasound.

We have developed an algorithm for arterial luminal diameter measurement by means of ultrasound and evaluated the algorithm on agar vessel phantoms and in vivo. The algorithm utilises relative threshold detection on the inner slopes of the arterial walls before the resolution is improved by solving the equation of a straight line between the samples around the threshold value. Further, correction distances added to compensate for the underestimation when using the inner slopes were found to be 304 µm for the near wall and 415 µm for the far wall. The measured mean diameters of ten consecutive images of 3-, 6- and 9-mm phantoms were 3,006 µm (SD 4), 5,918 µm (SD 1) and 8,936 µm (SD 2), respectively. The mean differences between the images were 0.19, 0.04 and 0.37 µm, respectively. In vivo, the intra- and inter-observer variabilities were -64 µm (2SD 358) and -57 µm (2SD 366), respectively.

In vitro studies and safety assessment of Doppler ultrasound as a diagnostic tool in rhinosinusitis.

We have previously proposed the use of Doppler ultrasound to noninvasively stage a sinus infection. In this study, we first investigated the acoustic properties of nonpurulent and mucopurulent sinus secretions. The density, viscosity, speed of sound and attenuation of 18 samples of sinus fluid were examined. We then assessed the safety of the method by determining the temperature increase when ultrasound is transmitted through a bone sample of the same thickness as the anterior wall of the maxillary sinus. As a measure of the probability to generate acoustic streaming, we determined the ratio of sound attenuation over the viscosity of the sinus fluid and compared this with the value obtained from acoustic streaming measurements on a model system. The results indicated that detectable levels of acoustic streaming can be generated in serous sinus fluid, which has a low viscosity, but is very unlikely in mucopurulent secretions. The attenuation of the mucopurulent sinus fluid was 10 times higher than that of the serous cyst fluid, but the viscosity of the mucopurulent secretion was a thousand times higher than that of serous fluid. The safety experiments gave a temperature increase of the bone of <1.5°C at I(spta) of 640 mW/cm(2), below the temperature increase considered to be harmful by the World Federation for Ultrasound in Medicine and Biology.