Advancing intravascular ultrasonic palpation toward clinical applications.

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.

A new ultrasound contrast imaging approach based on the combination of multiple imaging pulses and a separate release burst.

A new ultrasound contrast imaging technique is described that optimally employs the rupture of the contrast agent. It is based on a combination of multiple high frequency, broadband, imaging pulses and a separate release burst. The imaging pulses are used to survey the target before and after the rupture and release of free gas bubbles. In this way, both processes (imaging and release) can be optimized separately. The presence of the contrast agent is simply detected by correlating or subtracting the signal responses of the imaging pulses. Because the time delay between the imaging pulses can be very short, the subtraction is less affected by tissue motion and can be done in real time. In vitro measurements showed that by using a release burst, the detection sensitivity increased 12 to 43 dB for different types of contrast agents. In the presence of a moving phantom, the increase in sensitivity was 22 dB. This new method is very sensitive for contrast agent detection in fundamental imaging mode and, therefore, non-linear propagation effects do not limit the maximum obtainable agent-to-tissue ratio. However, because of the inherent destruction of the contrast agent, it has to operate in an intermittent way. Through experiments, we have demonstrated the potential of the method to achieve simultaneous high sensitivity for contrast detection, i.e., high agent-to-tissue ratio, and high spatial resolution performance for different types of contrast agents.

Decorrelation characteristics of transverse blood flow along an intravascular array catheter: effects of aggregation of red blood cells.

A method to measure transverse blood flow, based on the correlation between consecutive radiofrequency (RF) signals, has been introduced. This method was validated for an intravascular (IVUS) rotating single element catheter. Currently, we are implementing the method for an IVUS array transducer catheter. The decorrelation characteristics during transverse blood flow using the IVUS array catheter were investigated using computer modeling. Before this, blood was simulated as a collection of randomly located point scatterers and, by moving this scattering medium transversely across the acoustical beam, blood flow was simulated. This paper presents a more realistic scattering media by simulating aggregates of red blood cells (RBCs) as strings of point scatterers. Three configurations of aggregates of RBCs were simulated. First, aggregates of RBCs were strings with different lengths and parallel to the catheter axis. Second, the strings were with a fixed length and angles of plus or minus 45 degrees with respect to the catheter axis. Third, the strings were with different lengths and random angles ranging from -45 degrees to + 45 degrees. The decorrelation characteristics for these configurations of aggregates of RBCs were investigated and compared with point scatterers. For the aggregates of RBCs parallel to the catheter axis, the decorrelation rate became slower when the aggregate length was increased. RBC aggregations with fixed and random lengths and angles resulted in a decorrelation rate that approaches the decorrelation pattern from point scatterers. Results suggests that the presence of aggregates of RBCs will probably not affect the measurements of transverse blood flow using a decorrelation-based method and an IVUS array catheter.

Simulation of circular array ultrasound transducers for intravascular applications.

The beam shape of a circular array transducer that is commonly used in intravascular ultrasound catheters was investigated in linear mode of operation. For this use, a simulation program which can simulate the radio frequency (rf)-response of a number of scatterers has been developed. The program is based on the impulse response method, which is implemented in the frequency domain. Due to the unusual geometry of the transducer, the far field gets peculiarly shaped for large apertures. Instead of having a far field with its maximum intensity in a single lobe on the acoustical axis, the far field splits up into a dual-lobe far field with maximum intensity in two lobes off the acoustical axis. A formula is derived that predicts the occurrence of these beam shapes.

Flow estimation using an intravascular imaging catheter.

Coronary flow assessment can be useful for determining the hemodynamic severity of a stenosis and to evaluate the outcome of interventional therapy. We developed a method for measuring the transverse flow through the imaging plane of an intravascular ultrasound (IVUS) catheter. This possibility has raised great clinical interest since it permits simultaneous assessment of vessel geometry and function with the same device. Furthermore, it should give more accurate information than combination devices because lumen diameter and velocity are determined at the same location. Flow velocity is estimated based on decorrelation estimation from sequences of radiofrequency (RF) traces acquired at nearly the same position. Signal gating yields a local estimate of the velocity. Integrating the local velocity over the lumen gives the quantitative flow. This principle has been calibrated and tested through computer modeling, in vitro experiments using a flow phantom and in vivo experiments in a porcine animal model, and validated against a Doppler element containing guide wire (Flowire) in humans. Originally the method was developed and tested for a rotating single element device. Currently the method is being developed for an array system. The great advantage of an array over the single element approach would be that the transducer has no intrinsic motion. This intrinsic motion sets a minimal threshold in the detectable velocity components. Although the principle is the same, the method needs some adaptation through the inherent different beamforming of the transducer. In this paper various aspects of the development of IVUS flow are reviewed.

Vascular tissue characterisation with IVUS elastography.

Knowledge about the mechanical properties of the vessel wall and plaque is important for guiding intravascular interventional procedures and detection of plaque vulnerability. Rupture of atherosclerotic plaques is associated with acute myocardial infarction and unstable angina pectoris. In a plaque with a lipid core, the stress due to the arterial pulsation will be concentrated in the cap and a thin cap may be unable to bear this stress. In this study, the potential of intravascular elastography to characterise fibrous, fibro-fatty and fatty tissue based on their mechanical properties was investigated. Using a custom-made set-up, intravascular echograms and elastograms of excised human femoral arteries were determined. High frequency r.f. data (30 MHz) were acquired using an intravascular catheter. The tissue was compressed using intravascular pressures of 80 and 100 mmHg. The cross-sections of interest were marked with a needle for matching with histology. Using cross-correlation estimation of gated echosignals, elastograms (images of the local strain) were determined. After the intravascular experiments, the specimens were fixed in formaldehyde and processed for paraffin embedding. Sections were stained with picrosirius red and alpha-actin to counterstain collagen and smooth muscle cells (SMC), respectively. Results of vessel cross-sections with fibrous and fatty plaque regions will be presented. The elastograms of these specimens show that the strain in fatty tissue is higher than the strain in fibrous material. In conclusion, these in vitro experiments on human femoral arteries indicate the potential of intravascular elastography to characterise different plaque components.

Intraluminal ultrasonic palpation: assessment of local and cross-sectional tissue stiffness.

Many intravascular therapeutic techniques for the treatment of significant atherosclerotic lesions are mechanical in nature: examples are angioplasty, stenting and atherectomy. The selection of the most adequate treatment would be advantageously aided by knowledge of the mechanical properties of the lesion and surrounding tissues. Based on the success of intravascular ultrasound (IVUS) in accurately depicting the morphology of atheromatous lesions, ultrasonic tissue characterisation has been proposed as a tool to determine the composition of atheroma. We describe the addition of local compliance information to the IVUS image in the form of a colour-coded line congruent with the lumen perimeter. The technique involves analysis of echo signals obtained at two or more states of incremental intravascular pressure. Using vessel phantoms and specimens, we demonstrate the utility of intravascular compliance imaging. The palpograms are able to identify lesions of different elasticity independently of the echogenicity contrast, because the information provided by the elastograms is generally independent of that obtained from the IVUS image. Thus, the palpogram can complement the characterisation of lesion from the IVUS image. We also describe cross-sectional measures of elasticity that are based on the elastogram. Finally, natural extensions of intravascular palpation to other endoluminal ultrasound applications are proposed.

Decorrelation characteristics of transverse blood flow along an intravascular array catheter.

In recent years, a new method to measure transverse blood flow based on the decorrelation of radio frequency (RF) signals has been introduced. In this paper, we investigated the decorrelation characteristics of transverse blood flow measurement using an intravascular ultrasound (IVUS) array catheter by means of computer modeling. Blood was simulated as a collection of randomly located point scatterers. Moving this scattering medium transversally across the acoustical beam represented flow. First-order statistics were evaluated, and the signal-to-noise ratio from the signals was measured. The correlation coefficient method was used to present the results. The decorrelation patterns for RF and for RF-envelope signals were studied. The decorrelation patterns from the RF signals were in good agreement with those obtained from theoretical beam profiles. This agreement suggests that the decorrelation properties of an IVUS array catheter for measuring quantitative transverse blood flow can be assessed by measuring the ultrasound beam. A line of point scatterers, moved transversally across the acoustical beam (line spread function), can determine this decorrelation behaviour.

Influence of catheter position on estimated strain in intravascular elastography.

In elastography, an erroneous strain estimate is obtained when the radial strain and the probing ultrasound beam are not properly aligned: the "strain projection artifact". In practice, an angle between the strain and the ultrasound beam will be present in most of the cases due to inhomogeneities or nonuniform compression. In this study, a theoretical function describing the strain projection artifact is derived as a function of the angle between the radial strain and the ultrasound beam. Two main factors for an angle between strain and ultrasound beam in intravascular elastographic experiments are eccentricity and tilt of the transducer. The theoretical functions describing these errors are corroborated with strain estimates from an experiment with a circular, homogeneous gel-based vessel phantom. Comparison between the theoretical functions and the experimental results reveals that the strain projection artifact is well described by the theoretical findings. As a result, the experimental data can be corrected for this artifact. The corrected elastograms reveal that correct strain estimates are obtained when the eccentricity of the intravascular catheter is less than 63%. An "off-the-wall" device may be required to advance intravascular elastography to in vivo implementation.

Echo decorrelation from displacement gradients in elasticity and velocity estimation.

Several ultrasonic techniques for the estimation of blood velocity, tissue motion and elasticity are based on the estimation of displacement through echo time-delay analysis. A common assumption is that tissue displacement is constant within a short observation time used for time delay estimation (TDE). The precision of TDE is mainly limited by noise sources corrupting the echo signals. In addition to electronic and quantization noise, a substantial source of TDE error is the decorrelation of echo signals because of displacement gradients within the observation time. The authors present a theoretical model that describes the mean changes of the crosscorrelation function as a function of observation time and displacement gradient. The gradient is assumed to be small and uniform within the observation time; the decorrelation introduced by the lateral and elevational displacement components is assumed to be small compared with the decorrelation caused by the axial component. The decorrelation model predicts that the expected value of the crosscorrelation function is a low-pass filtered version of the autocorrelation function (i.e., the crosscorrelation obtained without gradients). The filter is a function of the axial gradient and the observation time. This theoretical finding is corroborated experimentally. Limitations imposed by decorrelation in displacement estimation and potential uses of decorrelation in medical ultrasound are discussed.

Intravascular ultrasound elastography.

Intravascular Ultrasound Blastography. The response of a tissue to mechanical excitation is a function of its mechanical properties. Excitation can be dynamic or quasistatic in nature. The response (e.g. displacement, velocity, compression) can be measured via ultrasound. This is the main principle underlying ultrasound elasticity imaging, sonoelasticity imaging, or ultrasound elastography. It is of great interest to know the local hardness of vessel wall and plaques. Intravascular elastography yields information unavailable or inconclusive if obtained from IVUS alone and thus contributes to more correct diagnosis. Potentially it can be used for therapy guidance. During the last decade several working groups used elastography in intravascular applications with varying success. In this paper we discuss the various approaches by different working groups. Focus will be on the approach of the Rotterdam group. Using a 30 MHz IVUS catheter, RF data are acquired from vessels in vitro at different intraluminal pressures. Local tissue displacement estimation by cross-correlation is followed by computation of the local strain. The resulting image supplies local information on the elastic properties of the vessel and plaque with high spatial resolution. Feasibility and usefulness are shown by means of phantom measurements. Furthermore, initial in vitro results of femoral arteries and correlation with histology are discussed. Phantom data show that the elastograms reveal information not presented by the echogram. In vitro artery data prove that in principle elastography is capable of identifying plaque composition where echography fails.

Intravascular ultrasound elastography: assessment and imaging of elastic properties of diseased arteries and vulnerable plaque.

OBJECTIVE: Intravascular elastography is concerned with methods for measuring the local elastic properties using intravascular ultrasound (IVUS). The elastic properties of the vessel wall and atheroma can be measured through the strain. Knowledge of these mechanical properties is useful for guiding interventional procedures (balloon dilatation, ablation) and detection of plaque vulnerability. METHODS: Elastograms and palpograms (images of strain) were constructed using the relative local displacements between IVUS images acquired at two levels of intravascular pressure with a 30-MHz echo catheter. These displacements were estimated from the time shift between gated radio-frequency echo signals using cross-correlation algorithms with interpolation around the peak. RESULTS: Experiments on gel-based phantoms mimicking atherosclerotic vessels demonstrated the capability of elastography to identify soft and hard plaques independently of the echogenicity contrast. In vitro experiments on human arteries have demonstrated the potential of intravascular elastography to identify different plaque types based on the mechanical properties. These plaques could not be identified using the IVUS image alone. Regions with elevated mechanical stress could also be detected. These stress concentrations are related to plaque fracture. CONCLUSION: Intravascular elastography provides information that is frequently unavailable or inconclusive from the IVUS image and therefore may assist in the diagnosis and treatment of atherosclerotic disease.

Intravascular imaging.

Based on three-dimensional (3D) information, quantitative data such as plaque volume can be calculated. The procedure includes automatic contour detection based in image segmentation methods and greatly speeds up clinical evaluation. With the use of additional X-ray information, the true tortuous vessel geometry can be reconstructed in 3D. This allows, by numerical modelling techniques, to calculate endothelial shear stress values which in turn may indicate sites prone to stenosis. With a decorrelation technique for radio frequency (RF) echo information from sequential data in the same beam direction and integration method over the entire cross section, blood velocity can be shown colour-coded during the cardiac cycle, while even blood flow quantification seems to be possible. In vitro as well as animal experiments have shown the feasibility of the method. Intravascular imaging can be used to study the biomechanical properties of atheroma components. Local radial strain as a measure of local tissue hardness can be estimated in principle. Hard or soft plaques can be identified from the strain images independently of the echogenic contrast between plaque and vessel wall.

New developments in intravascular ultrasound imaging.

IntraVascular Ultrasound Imaging (IVUS) has already been proposed in the early days of diagnostic ultrasound. Today, it has come under further full attention as a result of minimal invasive techniques. Not only excellent intravascular two-dimensional (2D) images are presently obtained, also three-dimensional (3D) reconstructed images show their diagnostic value. Based on 3D information, quantitative data such as plaque volume can be calculated. The procedure includes automatic contour detection based on image segmentation methods and greatly speeds up clinical evaluation. With the use of additional X-ray information, the true tortuous vessel geometry can be reconstructed in 3D. This allows, by numerical modelling techniques, to calculate endothelial shear stress values, which in turn may indicate sites prone to stenosis. With a decorrelation technique for radiofrequency (RF) echo information from sequential data in the same beam direction and integration method over the entire cross section, blood velocity can be shown colour-coded during the cardiac cycle, while even blood flow quantification seems to be possible. In vitro as well as in vivo experiments have shown the feasibility of the method. Intravascular imaging can be used to study the biomechanical properties of atheroma components. Local radial strain, used as a measure of local tissue hardness, can be estimated to identify hard or soft plaques independently of the echogenicity contrast between plaque and vessel wall.

Intravascular ultrasound elastography in human arteries: initial experience in vitro.

Intravascular elastography is a new technique to obtain the local mechanical properties of the vessel wall and its pathology using intravascular ultrasound (IVUS). Knowledge of these mechanical properties may be useful for guiding interventional procedures. An experimental set-up is described for assessment of the strain data of arteries. Using a 30-MHz IVUS catheter, radio frequency data are acquired with a custom-made high-performance data acquisition system. High-resolution, local tissue displacement estimation by cross-correlation is followed by computation of local strain. An algorithm that uses a priori knowledge of the correlation coefficient function was applied to filter the obtained strain data. With this experimental set-up, intravascular elastograms containing 400 angles/revolution with a radial resolution of 200 microns can be produced. The feasibility of intravascular elastography with this experimental set-up is demonstrated using two diseased human femoral arteries. Qualitative comparison of the elastograms with the echograms and the histology demonstrates the potential of intravascular elastography to obtain mechanical information from the vessel wall and from plaque.

Blood flow assessment with intravascular ultrasound catheters: the ideal tool for simultaneous assessment of the coronary haemodynamics and vessel wall?

We present the potentials of a novel method of intracoronary flow visualization and quantification that is based on conventional intravascular ultrasound (IVUS) imaging catheters. The quantification of flow is obtained from analysis of the rate of decorrelation of digitized radiofrequency ultrasound echo signals. Flow information is superimposed on the IVUS image using a colour scale. Integration of the blood velocity components normal to the scan plane permits calculation of the volume flow. Validation using IVUS and electromagnetic (EM) flowmeter recordings were obtained in vivo from instrumented pigs. IVUS flow (IVUS(f)) compared favourably to EM flow (EM(f)): IVUS(f)=1.0 EM(f)+5.72 cc/min, r2=0.98. Clinical results for the first five patients investigated are reported. A Doppler wire was used to measure the flow in four coronary arteries and one renal artery in baseline and hyperaemia conditions. IVUS flow and derived coronary flow reserve (CFR) demonstrated a very good agreement with the data derived from the combination of quantitative angiography and velocity when measured with the Doppler wire (DOP(f)): IVUS(f)=1.01 DOP(f)-20 cc/min, r2=0.90 and IVUS(cfr)=1.03 DOP(cfr)-0.03, r2=0.93. This demonstrates that simultaneous morphological and physiological assessment of coronary or peripheral arteries with one IVUS catheter is feasible. This method should be very useful for the evaluation of intermediate coronary stenoses or the results of revascularization procedures.

Elastic and acoustic properties of vessel mimicking material for elasticity imaging.

The mechanical and acoustic properties of agar-gelatin gels, used to construct vessel mimicking phantoms for ultrasonic elasticity studies, were investigated. Gels with varying compression moduli were made using a gelatin solution (8% by weight) with a variable amount of agar (1%-3% by weight). Carborundum particles were added as scattering material. The compression modulus was determined using a dynamic mechanical analyzer. The dependence of the compression modulus and the acoustic parameters on the agar concentration, as well as on the age and the temperature of the samples, was investigated. The results show that the compression modulus is strongly influenced by these factors, while the effect on the acoustic parameters is less. Compression moduli spanning a useful range for vascular phantom construction with realistic acoustic parameters can be achieved by varying the amount of agar. Phantoms constructed from these gels are well suited to serve as a model for plaque containing vessels.

Potentials of volumetric blood-flow measurement.

Current intravascular ultrasound techniques produce real-time imaging of a vessel cross-section with a scan plane normal to blood flow. When randomly distributed blood particles travel through this ultrasound imaging plane, the received echo signals decorrelate as a function of time. The speed of such a decorrelation procedure is proportional to the flow velocity. This phenomenon provides a potential to estimate blood velocities by means of decorrelation analysis. In this paper, we present a method for measuring local blood velocity and quantifying volume flow directly from cross-sectional intravascular ultrasound data. This method is based on multiple decorrelation assessments with a sequence of radio frequency echo signals. The velocity measurement is obtained by comparing the measured decorrelation value with the prior knowledge of the beam characteristics of an intravascular ultrasound transducer. Volume flow is derived by integrating the cross-sectional area and its corresponding velocity vector over the vessel lumen. The decorrelation-based method was tested in vitro with a flow phantom. Measurements were also carried out in vivo in pig experiments to determine the usefulness of this method in clinical settings. Preliminary results of these experiments indicate that the proposed decorrelation method is able to extract cross-sectional velocity profiles and volumetric flow both in vitro and in vivo.

Intravascular elastography: principles and potentials.

Many intravascular therapeutic techniques for the treatment of significant atherosclerotic lesions are mechanical in nature: angioplasty, stenting and atherectomy. The selection of the most adequate treatment would be advantageously aided by knowledge of the mechanical properties of the lesion. Based on the success of conventional intravascular ultrasound (IVUS) imaging in accurately depicting the morphology of atheromatous lesions, ultrasonic tissue characterization has been proposed to determine the composition of atherosclerotic plaques. Elastography is an ultrasound-based imaging technique capable of producing cross-sectional elasticity images called elastograms. The technique involves analysis of echo signals obtained at two states of incremental intravascular pressure. High resolution, local tissue displacement estimation by cross-correlation is followed by computation of local strain. Strain is utilized as an indicator of the local compliance of tissue under the assumption of constant stress within the scan plane. Using vessel-mimicking phantoms, we demonstrate the feasibility of intravascular elastography experimentally. The elastograms are able to depict lesions of different elasticity independently of the echogenicity contrast, since the information provided by the elastograms is generally independent of that obtained from the conventional IVUS image. Thus, the elastogram can complement the characterization of lesions from the conventional IVUS image. Progress to in vitro and in vivo testing is expected in conjunction with ongoing improvements in the current instrumentation and processing.

Intravascular elasticity imaging using ultrasound: feasibility studies in phantoms.

A technique is described for measuring the local hardness of the vessel wall and atheroma using intravascular ultrasound. Strain images were constructed using the relative local displacements, which are estimated from the time shifts between gated echo signals acquired at two levels of intravascular pressure. Time shifts were estimated using one-dimensional correlation with bandlimited interpolation around the peak. Tissue-mimicking phantoms with typical morphology and hardness topology of some atherosclerotic vessels were constructed. Hard and soft regions could be distinguished on the strain image, independently of their contrast in echogenicity. Thus, the potential of ultrasonic hardness imaging to provide information that may be unavailable from the echogram alone was demonstrated. The strain images of the homogeneous and layered phantoms showed some artifacts that need to be corrected for, to obtain images of the modulus of elasticity. For in vitro and in vivo experiments, the spatial resolution of the technique needs to be improved. Furthermore, two-dimensional correlation techniques may be necessary in case of nonradial expansion and an off-centre catheter position.