Colour M-mode tissue Doppler imaging in healthy cats and cats with hypertrophic cardiomyopathy.

OBJECTIVES: To determine whether decreased diastolic and systolic myocardial velocity gradient between the endocardium and the epicardium exist in the left ventricle of cats with hypertrophic cardiomyopathy. METHODS: Myocardial velocity gradient and mean myocardial velocities were measured by colour M-mode tissue Doppler imaging in the left ventricular free wall of 20 normal cats and 17 cats with hypertrophic cardiomyopathy. RESULTS: The peak myocardial velocity gradient (sec(-1)) during the first (E1) (5.71+/-1.75 versus 11.38+/-3.1, P<0.001) and second phase (E2) (3.09+/-1.53 versus 7.02+/-3.1, P=0.005) of early diastole and also the maximum early diastolic myocardial velocity gradient (Emax) (6.12+/-2.1 versus 10.76+/-3.2, P<0.001) were reduced in cats with hypertrophic cardiomyopathy compared with normal cats. Peak myocardial velocity gradient during early systole (Se) was lower in affected cats than in normal cats (6.26+/-2.08 versus 8.67+/-2.83, P=0.006). Affected cats had a lower peak mean myocardial velocities (mm/s) during the two isovolumic periods (IVRb and IVCb) compared with normal cats (2.97+/-6.76 versus 12.74+/-5.5 and 22.28+/-9.96 versus 38.65+/-10.1, P<0.001, respectively). CLINICAL SIGNIFICANCE: This study shows that hypertrophic cardiomyopathy cats have decreased myocardial velocity gradient during both diastole and systole and also altered myocardial motion during the two isovolumic periods. Myocardial velocity gradients recorded by colour M-mode tissue Doppler imaging can discriminate between the healthy and diseased myocardium.

Design and characterisation of a wall motion phantom.

Arterial wall motion is an essential feature of a healthy cardiovascular system and it is known that wall motion is affected by age and disease. In recent years, methods have been developed for measurement of wall motion with the intention of providing diagnostically useful information. An issue with all of these techniques is the accuracy and variability of both wall motion and derived quantities such as elasticity, which requires the development of suitable test tools. In this paper, a vessel wall phantom is described for use in ultrasound studies of wall motion. The vessel was made from polyvinyl alcohol (PVA) subjected to a freeze-thaw process to form a cryogel (PVA-C). The elastic modulus, acoustic velocity and attenuation coefficient varied from 57 kPa, 1543 m s(-1) and 0.18 dB cm(-1) MHz(-1) for one freeze-thaw cycle to 330 kPa, 1583 m s(-1) and 0.42 dB cm(-1) MHz(-1) for 10 freeze-thaw cycles. Wall motion was effected by the use of pulsatile flow produced from a gear pump. The use of a downstream flow resistor removed gross distortions in the wall motion waveform, possibly by removal of reflected pressure waves. However, a low amplitude 20 Hz oscillation remained, which is unphysiologic and thought to be caused by the vibration of the distended PVA-C vessel.

Nanointerrogation of ultrasonic contrast agent microbubbles using atomic force microscopy.

Predicting the acoustic response of an encapsulated microbubble to ultrasound requires an accurate assessment of the mechanical properties of the microbubble shell. Atomic force microscopy (AFM) provides an unprecedented spatial and force resolution of the order of Angstroms and subnanonewtons, respectively. It is introduced here as a means to interrogate microbubbles manufactured for ultrasonic imaging. The advantage of AFM over scanning electron microscopy (SEM) is that the microbubbles need not be subjected to a low temperature or low-pressure environment. The microbubbles were interrogated in a liquid environment, which could potentially be a simulated physiological environment. AFM was used in tapping mode imaging to reveal topographical detail of biSphere microbubbles. Because microbubbles are large objects compared with the overall size of usual AFM tips, a convolution between the AFM tip and the microbubble was typical of the acquired topographies. However, a part of the top half of the bubble was imaged with nanometer resolution, and roughness measurements are reported. Force-distance curves were captured using contact mode AFM. The range of stiffness or effective spring constant of biSphere was found to be between 1 and 6 N m(-1). In conclusion, the AFM is proposed here for the first time as a tool to image the surface of bubbles at the nanometer range in liquid and to perform reproducible measurements on the mechanical properties of individual microbubbles.

Manufacture and acoustical characterisation of a high-frequency contrast agent for targeting applications.

The aim of this study was to develop and acoustically to optimise an ultrasonic contrast agent for research imaging applications at 40 MHz. A range of liposomal dispersions were manufactured and the mean backscatter power was measured using a Boston Scientific ClearView Ultra intravascular scanner with a 40 MHz, 2.5 Fr Atlantis SR Plus catheter. The scanner had been modified to allow access to the unprocessed ultrasound data, which were digitised, and the mean backscatter power was calculated over a region-of-interest centred at 2 mm from the transducer. Mean backscatter power was normalised to the data collected from a water-air interface. The effects of sonication and rapid shaking on six liposomal samples were also studied and this indicated that both techniques significantly reduced the size of the liposomes within the dispersions. Maximum mean backscatter power was measured for sonicated liposomal dispersions with 60% by weight of phosphatidylethanolamine. Moreover, this dispersion had greater mean backscatter power than sheep blood at 40 MHz.

Pulsed tissue Doppler imaging in normal cats and cats with hypertrophic cardiomyopathy.

Myocardial motion was quantified in normal cats (n = 25) and cats with hypertrophic cardiomyopathy (HCM) (n = 23) using the pulsed tissue Doppler imaging (TDI) technique. A physiologic nonuniformity was documented in the myocardial motion of normal cats, which was detected as higher early diastolic velocities, acceleration, and deceleration in the interventricular septum compared with the left ventricular free wall (LVFW). HCM cats exhibited lower early diastolic velocities, acceleration, and deceleration and also prolonged isovolumic relaxation time compared with normal cats. These differences were detected mainly along the longitudinal axis of the heart. A cutoff value of E' in the LVFW along the longitudinal axis >7.2 cm/s discriminated normal from HCM cats with a sensitivity of 92% and a specificity of 87%. The physiologic nonuniformity of myocardial motion during diastole was lost in affected cats. Systolic impairment (decreased late-systolic velocities in most segments along the longitudinal axis and decreased early systolic acceleration in both mitral annular sites) was evident in HCM cats irrespective of the presence of left ventricular outflow tract obstruction and congestive heart failure. Postsystolic thickening was recorded in the LVFW along the longitudinal axis only in affected cats (n = 6) and was another finding indicative of systolic impairment in the HCM of this species. This study identified both diastolic and systolic impairment in cats with HCM compared with normal cats. The study also documents the normal physiologic nonhomogeneity in myocardial motion in cats and the subsequent loss of this feature in the HCM diseased state.

Ultrasonic measurement of prosthetic heart valve action.

An in-vitro study has been made of the echo patterns obtained during ultrasonic Time-Motion (T-M) scanning of commonly used prosthetic heart valves. Studies have been undertaken of Starr-Edwards, Beal, and Björk-Shilley valves. From the recorded traces information has been obtained regarding the orientations of the ultrasound beam to the central axes of the valves for which accurate measurements can be made. The orientations have been determined for which the opening and closing times of the valves can be measured to within 20 ms. Characteristics of the T-M trances have been noted which allow the angle between the direction of an ultrasound beam and a central valve axis to be reduced to less than 20 degrees. This makes the error due to angular misalignment of the beam less than --6% when the range of movement of a ball, disc, or flap is being measured. Finally a number of artefacts are considered which can arise when prosthetic valves are examined with ultrasound.

The accuracy of caridac function indices derived from ultrasonic time-position scans.

A study has been made of Time-Position ultrasonic scanning as a means of obtaining measurements related to cardiac performance. The errors involved in determining these measurements have been estimated. It has been shown that the greatest accuracy can be achieved for quantities which depend on action rather than shape, such as ejection fractions and rates of myocardial fibre shortening. Attention is drawn to the fact that the ultrasonic method, unlike angiography, in no way alters the quantities being measured.

Doppler tissue imaging: myocardial wall motion velocities in normal subjects.

With a scanner modified for Doppler tissue imaging, mean myocardial velocities (MMV) across the myocardium were measured. The aim of this study was to determine the normal range of the maximum MMV in six standardized phases of the cardiac cycle. The MMV was defined as the average value of the myocardial velocity measured along each M-mode scan line throughout the thickness of the myocardium. The maximum MMV was defined as the maximum value of the MMV during the particular cardiac phase. Simultaneous gray-scale and Doppler tissue imaging M-mode images were taken of the interventricular septum and the left ventricular posterior wall from the parasternal long-axis and short-axis views in 15 normal volunteers (aged 21 to 47 years; mean 32 +/- 6 years). Each cardiac cycle was divided into six phases: atrial contraction, isovolumetric contraction, ventricular ejection, isovolumetric relaxation, rapid ventricular filling, and diastasis. Isovolumetric contraction, isovolumetric relaxation, and diastasis were subdivided into two parts a and b because of changes in the direction of the myocardial movement. For each volunteer, the mean and standard deviation of the maximum MMV were measured for each cardiac phase averaged from 12 cardiac cycles from both long-axis and short-axis views. Finally, the mean and standard deviation were taken for each cardiac phase from 180 cardiac cycles from 15 volunteers. We have found that specific cardiac phases show significant differences in the maximum MMV between the adjoining cardiac phases and significant differences also occur between the maximum MMV measured in the interventricular septum and the left ventricular posterior wall during the same cardiac phases. These normal values provide a standard against which future Doppler tissue imaging M-mode studies of abnormal left ventricular function might be compared.

The variation of integrated backscatter in human hearts in differing ultrasonic transthoracic views.

It has been shown previously that in normal subjects the interventricular septum imaged in the long-axis view (LAX) and the left ventricular posterior wall imaged in both the LAX and the short-axis view (SAX) exhibit cyclic variation of integrated backscatter (IB) throughout the cardiac cycle, with maximum values occurring at end diastole (ED) and minimum at end systole (ES). The ability to demonstrate this cyclic variation within these myocardial regions in only two ultrasonic views has limited the potential clinical utility of an IB imaging system. To determine whether clinically useful information on the variation of IB is available from different myocardial regions in different ultrasonic views, we measured ED to ES variation of IB from the parasternal and apical views in normal subjects with a radiofrequency acquisition technique. Two independent clinical observers analyzed ED to ES variation of IB from 14 normal volunteers (mean age 32 +/- 6 years; range 21 to 45 years) in reconstructed two-dimensional ultrasonic images obtained from the parasternal LAX and SAX and apical two-chamber (2C) and four-chamber (4C) views. ED to ES variation of IB was measured from manually traced regions of interest (ROI) within the myocardium. These ROIs were chosen interactively and were located within the midposterior wall and the midanteroseptum in LAX views; within the midposterior wall, midanteroseptum, midseptum, and midlateral wall in SAX views; within the midseptum and the midlateral wall in 4C views; and within the midinferior wall and the midanterior wall 2C views. In all analyzed ROIs within the parasternal and apical views, ED to ES variation of IB was found. We have shown that the maximum magnitude of IB was at ES within the midseptum and in 10 out of 14 volunteers in the midanteroseptum measured from SAX views, the midanterior wall from 2C views, and the midlateral wall from 4C views. The rest of the ROIs analyzed exhibited the maximum value of IB cyclic variation at ED. We have confirmed that the ED to ES variation of IB is present not only when measured from the two standard parasternal views but also from the two apical views in all analyzed myocardial walls, and the minimum of this cyclic variation was not always coincident with ES nor the maximum with ED.

Color Doppler myocardial imaging: a new technique for the assessment of myocardial function.

Color Doppler myocardial imaging is a new technique that has been developed specifically to allow color Doppler imaging of myocardial wall motion rather than blood pool imaging. Such a technique has the potential to interrogate velocities, accelerations, and Doppler signal strength within the myocardial wall. Moreover, the concomitant enhancement of the myocardial Doppler signal after an intravenous injection of a transpulmonary echocardiographic contrast agent could permit the noninvasive assessment of regional myocardial perfusion. Thus this new imaging modality could be a valuable adjunct to the ultrasound assessment of myocardial ischemia.

Deconvolution in medical ultrasonics: practical considerations.

Deconvolution can, in principle, enhance the spatial resolution of specular reflectors in medical ultrasonic imaging but, in practice, the resolution improvement offered is offset by the introduction of undesirable artefacts. In this study, several problems related to deconvolution were identified and practical suggestions for minimising artefacts were made. These include: fitting a three-dimensional surface to experimentally measured beam profiles in order to take into account the depth-dependence of the point spread function (PSF); adaptive detail-preserving noise filtering as a preprocessing tool in order to improve the quality of the data and reduce the speckle enhancement artefact; a histogram modification procedure in order to overcome the problems of ringing, over- and undershooting. Processing of a large number of A-scan data obtained from tissue-mimicking phantoms and the abdomens of normal volunteers demonstrated the efficiency of these techniques in reducing artefacts. The performance of deconvolution in terms of resolution improvement was satisfactory when data from resolution test objects were processed but poor with abdominal scans. This difference in performance raises the question as to how similar the PSF in tissue is to the experimentally measured PSF in water or even a tissue-mimicking material.

A computer controlled flow phantom for generation of physiological Doppler waveforms.

A flow phantom for the generation of physiological Doppler waveforms is described. The suspension of scattering particles is driven by a gear pump powered by a stepping motor. The speed of the stepping motor is controlled by a BBC microcomputer. The waveform shape is selected from a library of waveforms from disc. Use of the microcomputer allows the waveform shape and mean flow to be easily changed. Sephadex particles suspended in a solution of glycerol were used as artificial blood. Thin walled heat shrink tubing which had been moulded around metal rods was used. Distortions in the waveforms caused by reflections from the end of the tubing were largely removed by reducing the pipe diameter to half of its value for 30 cm from the end of the pipe. There was good agreement between the control waveforms and the Doppler waveforms over a wide range of waveform pulsatility.

A comparison of colour flow imaging algorithms.

In this paper we will present and explain coherently the two main algorithms which are currently used in commercial colour flow imaging systems, namely the frequency domain based autocorrelation algorithm and the time domain based cross correlation algorithm. The autocorrelation algorithm is a robust optimum mean frequency baseband estimator, for both high and low signal to noise ratio (SNR). Its main disadvantage is its aliasing problem. However the cross correlation algorithm does not suffer from this problem, and this has been one of the main reasons for its development. The mathematics behind these two algorithms and the general data processing steps used for their implementation will be also presented. The subject of clutter removal filtering will be discussed and valuable points will be made. A practical relevant approach on how to discriminate between wanted blood flow related estimates and unwanted false estimates due to noise will be presented. On the aliasing problem of the autocorrelation algorithm, a promising solution known as spatial tracking of estimated mean frequency does exist, which will be also introduced in detail. Towards the end of this paper other algorithms, which are currently the subject of research and have potential for development, will be discussed.

An in vitro study of a microbubble contrast agent using a clinical ultrasound imaging system.

Optimal insonation settings for contrast imaging are yet to be specified, mainly due to the lack of good understanding of the behaviour of the microbubbles. A satisfactory model that explains the behaviour of individual contrast agent scatterers has not yet been reported in the literature. An in vitro system based on a commercial scanner (ATL HDI3000) has been developed to investigate the backscatter of such agents. Suspensions of Definity were introduced in an anechoic tank. The frequency of transmitted ultrasound varied from 1 to 5 MHz, pulse period from 2 to 10 periods and peak negative acoustic pressure from 0.08 to 1.7 MPa. The backscatter at the fundamental and second harmonic frequency windows from the agent was normalized in terms of the corresponding components of backscatter from a blood mimicking fluid suspension. The agent provided a dominant resonance effect at 1.6 MHz transmit frequency. Second harmonic normalized backscatter averaged around 9 dB higher than the fundamental. The normalized fundamental backscatter intensity was linear with peak negative pressure. The second harmonic at resonance peaked at 0.5 MPa suggestive of bubble disruption above such pressure. The system proved capable of illustrating the ultrasonic behaviour of Definity in vitro, and the investigation suggested particular insonation conditions for optimal image enhancement using Definity.

Understanding the limitations of ultrasonic backscatter measurements from microbubble populations.

Despite over ten years of in vitro investigations of ultrasound contrast agents, the level of understanding of their behaviour in ultrasound fields is limited. Several problems associated with these investigations, particular to the nature of contrast agents, are discussed. Using a commercial scanner the RF normalized backscatter of two different contrast agents (Definity and Quantison) was measured at different suspension concentrations and acoustic pressures. Both contrast agents scattered ultrasound nonlinearly and the backscatter showed a dependence on acoustic pressure. In order to assess the average behaviour of the agents across the range of acoustic pressures and microbubble concentrations the experimental data were fitted to a theoretically acceptable model using nonlinear regression analysis. The analysis showed that both the backscatter and the attenuation of the Quantison suspensions displayed a higher order of dependence on acoustic pressure than the Definity suspensions. It was also discovered that Quantison microbubbles did not demonstrate uniform behaviour across the acoustic pressure range. At lower acoustic pressures the behaviour could not follow a model similar to that which predicted the behaviour at higher acoustic pressures, which was mainly due to the fact that free bubbles were released in a fashion dependent on acoustic pressure. The fact that two different populations of scatterers exist in the same suspensions makes the assessment of the behaviour of the particular agent impossible with the high concentrations that are commonly used. Very low concentration suspensions whereby single scattering events can be monitored should be more useful. In conclusion, the approach of using high microbubble concentrations in order to investigate the properties of ultrasonic contrast agents is limited in that the results of such studies cannot be used to understand the behaviour of single microbubbles.

An in vitro system for the study of ultrasound contrast agents using a commercial imaging system.

An in vitro system for the investigation of the behaviour of contrast microbubbles in an ultrasound field, that provides a full diagnostic range of settings, is yet to be presented in the literature. The evaluation of a good compromise of such a system is presented in this paper. It is based on (a) an HD13000 ATL scanner (Bothell, WA, USA) externally controlled by a PC and (b) on the use of well-defined reference materials. The suspensions of the reference ultrasonic scattering material are placed in an anechoic tank. The pulse length ranges from 2 to 10 cycles, the acoustic pressure from 0.08 to 1.8 MPa, the transmit frequency from 1 to 4.3 MHz, and the receive frequency from 1 to 8 MHz. The collection of 256 samples of RF data, at an offset distance from the transducer face, was performed at 20 MHz digitization rate, which corresponds to approximately 1 cm depth in water. Two particle suspensions are also presented for use as reference scatterers for contrast studies: (a) a suspension of Orgasol (ELF Atochem, Paris, France) particles (approximately 5 microm mean diameter) and (b) a suspension of Eccosphere (New Metals & Chemicals Ltd, Essex, UK) particles (approximately 50 microm mean diameter). A preliminary experiment with the contrast agent Definity (DuPont Pharmaceutical Co, Waltham, MA) showed that the above two materials are suitable for use as a reference for contrast backscatter.

A versatile test-object for the calibration of ultrasonic Doppler flow instruments.

Versatility in test-objects for ultrasonic Doppler units is desirable. The test-object described comprises a thin-walled plastic tube embedded in tissue-mimicking material. Blood is simulated using a mixture of water and glycerol with sephadex particles to act as scatterers. The test-object is suitable for use with a wide range of Doppler units which employ pulsed and continuous ultrasound in the frequency range 1 to 10 MHz. Calibration of several types of Doppler and imaging duplex systems has been performed for flow velocities up to 100 cm/s through a 10 mm tube. Above this velocity, for this tube dimension, turbulence occurs prevents the accurate measurement of flow velocity. The versatility of the test-object is further enhanced by the feasibility of manufacturing vessels of different shape and size. Slow flow through the tissue equivalent material may also be detected.

A comparison of the Doppler spectra from human blood and artificial blood used in a flow phantom.

A comparison between the Doppler signals from human blood and artificial blood used in a flow phantom is described. The artificial blood used was a suspension of Sephadex particles in a glycerol solution. The Doppler power was measured as a function of Sephadex concentration and found to peak at a concentration of about 40% by volume. The power from blood was less by a factor of 150-250 than the power from Sephadex of a similar concentration. The first and second order statistics of the Doppler spectra from Sephadex were independent of particle concentration, and were very similar to those of spectra from blood.

An investigation of simulated umbilical artery Doppler waveforms. I. The effect of three physical parameters on the maximum frequency envelope and on pulsatility index.

The effect of three physical parameters on the accuracy of estimation of the maximum frequency envelope and pulsatility index (PI) of simulated umbilical artery Doppler waveforms was investigated. The physical parameters were beam-vessel angle, the offset between the beam axis and vessel axis, and the thickness of overlying attenuating material. Waveforms were acquired using a physiological flow phantom. The maximum frequency envelope was calculated using a threshold maximum frequency follower which was adaptive to the level of background noise. A gold standard maximum frequency envelope was obtained from the ensemble averaged waveform when there was alignment of beam and vessel axis, a 50 degrees beam-vessel angle and 2 cm of attenuating material. Indices of bias, variability and accuracy of estimation of the maximum frequency envelope and PI were calculated by comparing subsequent maximum frequency envelopes with the gold standard maximum frequency envelope. Both the maximum frequency envelope and PI were estimated to a similar degree of accuracy over a wide range of physical conditions. In this study, the error in PI was less than 0.15 for beam-vessel angles less than 80 degrees, for beam-vessel axis offset distances less than 7.5 mm, at a transducer-vessel distance of 5 cm, and for attenuator thicknesses less than 4.5 cm. The percentage root-mean square error for estimation of the maximum frequency envelope was approximately 10% or less for beam-vessel angles less than 75 degrees, for beam-vessel axis offset distances less than 7.5 mm, and for attenuator thicknesses less than 4 cm.

Rapid measurement of the spatial resolution of colour flow scanners.

An acoustic grid for rapid measurement of the spatial resolution of colour velocity images is described. The grid is composed of alternate widths of acoustic window and acoustic attenuator. Attenuation is provided by the use of a layer of waterproof paper, which is wrapped in close contact with a tube of a flow phantom. The colour image consists of several closely spaced lines. When the grid line spacing is less than the spatial resolution, the colour lines cannot be separately visualised. The use of several grids of different spacing provides a measure of the spatial resolution. It is shown that the spatial resolution is dependent on the position of the focal zone.