Noninvasive detection of intimal xanthoma using combined ultrasound, strain rate and photoacoustic imaging

Background and motivation

The structure, composition and mechanics of carotid artery are good indicators of early progressive atherosclerotic lesions. The combination of three imaging modalities (ultrasound, strain rate and photoacoustic imaging) which could provide corroborative information about the named arterial properties could enhance the characterization of intimal xanthoma.

Methods

The experiments were performed using a New Zealand white rabbit model of atherosclerosis. The aorta excised from an atherosclerotic rabbit was scanned ex vivo using the three imaging techniques: (1) ultrasound imaging of the longitudinal section: standard ultrasound B-mode (74 Hz frame rate); (2) strain rate imaging: the artery was flushed with blood and a 1.5 Hz physiologic pulsation was induced, while the ultrasound data were recorded at higher frame rate (296 Hz); (3) photoacoustic imaging: the artery was irradiated with nanosecond pulsed laser light of low fluence in the 1210-1230 nm wavelength range and the photoacoustic data was recorded at 10 Hz frame rate. Post processing algorithms based on cross-correlation and optical absorption variation were implemented to derive strain rate and spectroscopic photoacoustic images, respectively.

Results

Based on the spatio-temporal variation in displacement of different regions within the arterial wall, strain rate imaging reveals differences in tissue mechanical properties. Additionally, spectroscopic photoacoustic imaging can spatially resolve the optical absorption properties of arterial tissue and identify the location of lipid pools.

Conclusions

The study demonstrates that ultrasound, strain rate and photoacoustic imaging can be used to simultaneously evaluate the structure, the mechanics and the composition of atherosclerotic lesions to improve the assessment of plaque vulnerability.     

A novel ultrasound instrument for investigation of arterial mechanics

The study of arterial mechanics concerns functional characteristics depending on wall elasticity and flow profile. Wall elasticity can be investigated through the estimation of parameters like the arterial distensibility, which is of high clinical interest because of its known correlation not only with the advanced atherosclerotic disease, but also with aging and major risk factors for cardiovascular disease. The flow velocity profile is also clinically relevant, because it modulates endothelial function and can be responsible for the development and distribution of atherosclerotic plaques. A clinically relevant variable extracted from the blood velocity profile is the wall shear rate (WSR), which represents the spatial velocity gradient near the vessel wall. This paper describes an integrated ultrasound system, capable of detecting both the velocity profile and the wall movements in human arteries. It basically consists of a PC add-on board including a single high-speed digital signal processor. This is dedicated to the analysis of echo-signals backscattered from 128 range cells located along the axis of the interrogating ultrasound (US) beam. Echoes generated from the walls (characterized by high amplitudes and low Doppler frequencies) and from red blood cells (characterized by low amplitudes and relatively high Doppler frequencies) are independently processed in real-time. Wall velocity is detected through the autocorrelation algorithm, while blood velocity is investigated through a complete spectral analysis of all signals backscattered by erythrocytes and WSR is extracted from the estimated velocity profile. Preliminary applications of the new system, including the simultaneous analysis of blood flow and arterial wall movement in healthy volunteers and in a diseased patient, are discussed, and first results are presented.     

Synthetic aperture ultrasound imaging

The paper describes the use of synthetic aperture (SA) imaging in medical ultrasound. SA imaging is a radical break with today's commercial systems, where the image is acquired sequentially one image line at a time. This puts a strict limit on the frame rate and the possibility of acquiring a sufficient amount of data for high precision flow estimation. These constrictions can be lifted by employing SA imaging. Here data is acquired simultaneously from all directions over a number of emissions, and the full image can be reconstructed from this data. The paper demonstrates the many benefits of SA imaging. Due to the complete data set, it is possible to have both dynamic transmit and receive focusing to improve contrast and resolution. It is also possible to improve penetration depth by employing codes during ultrasound transmission. Data sets for vector flow imaging can be acquired using short imaging sequences, whereby both the correct velocity magnitude and angle can be estimated. A number of examples of both phantom and in vivo SA images will be presented measured by the experimental ultrasound scanner RASMUS to demonstrate the many benefits of SA imaging.     

Ultrasound enhanced thrombolysis in acute arterial ischemia

In vitro and animal studies have shown that thrombolysis with intravenous tissue plasminogen activator (tPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Moreover, intravenous gaseous microspheres with ultrasound have been shown to be a potential alternative to fibrinolytic agents to recanalize discrete peripheral thrombotic arterial occlusions or acute arteriovenous graft thromboses. Small phase I-II randomized and non-randomized clinical trials have shown promising results concerning the potential applications of ultrasound-enhanced thrombolysis in the setting of acute cerebral ischemia. CLOTBUST was an international four-center phase II trial, which demonstrated that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments tPA-induced arterial recanalization (sustained complete recanalization rates: 38% vs. 13%) with a non-significant trend toward an increased rate of clinical recovery from stroke, as compared with placebo. The rates of symptomatic intracerebral hemorrhage (sICH) were similar in the active and placebo group (4.8% vs. 4.8%). Smaller single-center clinical trials using transcranial color-coded sonography (TCCD) reported recanalization rates ranging from 27% to 64% and sICH rates of 0-18%. A separate clinical trial evaluating the safety and efficacy of therapeutic low-frequency ultrasound was discontinued because of a concerning sICH rate of 36% in the active group. To further enhance the ability of tPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Moreover, potential enhancement of intra-arterial tPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter) in ongoing phase II-III clinical trials. Intravenous platelet-targeted microbubbles with low-frequency ultrasound are currently investigated as a rapid noninvasive technique to identify thrombosed intracranial and peripheral vessels. Multi-national dose escalation studies of microspheres and the development of an operator independent ultrasound device are underway.     

The use of the Verasonics ultrasound system to measure shear wave velocities in CIRS phantoms

The shear wave velocity is measured in calibrated polymeric CIRS phantoms containing various spheres of two diameters located at different depths. The measurements are performed at the Verasonics ultrasound system using the method of the shear wave elasticity imaging.     

Material property estimation for tubes and arteries using ultrasound radiation force and analysis of propagating modes

Arterial elasticity has been proposed as an independent predictor of cardiovascular diseases and mortality. Identification of the different propagating modes in thin shells can be used to characterize the elastic properties. Ultrasound radiation force was used to generate local mechanical waves in the wall of a urethane tube or an excised pig carotid artery. The waves were tracked using pulse-echo ultrasound. A modal analysis using two-dimensional discrete fast Fourier transform was performed on the time-space signal. This allowed the visualization of different modes of propagation and characterization of dispersion curves for both structures. The urethane tube/artery was mounted in a metallic frame, embedded in tissue-mimicking gelatin, cannulated, and pressurized over a range of 10-100 mmHg. The k-space and the dispersion curves of the urethane tube showed one mode of propagation, with no effect of transmural pressure. Fitting of a Lamb wave model estimated Young's modulus in the urethane tube around 560 kPa. Young's modulus of the artery ranged from 72 to 134 kPa at 10 and 100 mmHg, respectively. The changes observed in the artery dispersion curves suggest that this methodology of exciting mechanical waves and characterizing the modes of propagation has potential for studying arterial elasticity.     

Elasticity reconstruction for ultrasound elastography using a radial compression: an inverse approach

To reduce the inherent mechanical artifacts in the strain images, many groups have investigated solutions to the inverse problem in elastography. However, in prostate elastography or intravascular elastography where the compression direction is radial, the inverse problem has not been studied thoroughly. In this paper, an iterative approach is proposed to reconstruct tissue elasticity for ultrasound elastography using a radial compression. The method is based upon the stress-strain relations in the polar coordinates. Computer simulations in an intravascular model are performed to illustrate the feasibility of this method in reducing the mechanical artifacts of the strain images. The reconstructed elasticity error and the contrast-transfer efficiency (CTE) as a function of the iteration number show that the inverse approach converges with a few iterations.     

Comparative study on electroosmosis modulated flow of MHD viscoelastic fluid in the presence of modified Darcy’s law

Magnetic field plays an important role in numerous fields such as biological, chemical, mechanical and medical research. In clinical and medical research the high field magnets are extremely important to create 3D images of anatomical and diagnostic importance from nuclear magnetic resonance signals. In view of these applications, the purpose of present work is to explore the impact of an external magnetic field on the viscoelastic fluid flow in the existence of electroosmosis, porous medium and slip boundary conditions. The governing equation is modified under the suitable dimensionless quantities. The resulting non-dimensional differential equation is evaluated by analytical as well as numerical (finite difference and cubic B-spline) methods. The convergence analysis is also presented for the numerical methods. The variations of sundry parameters on velocity, volume flow rate and skin friction are presented through graphical representations. The current analysis depicts that, the higher velocities are noticed in viscoelastic fluid as compared with Newtonian fluid. The velocity enhances with rising of slip and Darcy parameters. Volume flow rate rises with the slip and viscoelastic parameters. Skin friction is a decreasing function of zeta potential, Darcy number and Hall current parameter. The limiting solutions can be captured for the Newtonian fluid model by setting the viscoelastic parameter to zero.     

Tissue velocity imaging of coronary artery by rotating-type intravascular ultrasound

Intravascular ultrasound (IVUS) provides not only the dimensions of coronary artery but the information of tissue components. In catheterization laboratory, soft and hard plaques are classified by visual inspection of echo intensity. So-called soft plaque contains lipid core or thrombus and it is believed to be more vulnerable than a hard plaque. However, it is not simple to analyze the echo signals quantitatively. When we look at a reflection signal, the intensity is affected by the distance of the object, the medium between transducer and objects and the fluctuation caused by rotation of IVUS probe. The time of flight is also affected by the sound speed of the medium and Doppler shift caused by tissue motion but usually those can be neglected. Thus, the analysis of RF signal in time domain can be more quantitative than intensity of RF signal. In the present study, a novel imaging technique called "intravascular tissue velocity imaging" was developed for searching a vulnerable plaque. Radio-frequency (RF) signal from a clinically used IVUS apparatus was digitized at 500 MSa/s and stored in a workstation. First, non-uniform rotation was corrected by maximizing the correlation coefficient of circumferential RF signal distribution in two consecutive frames. Then, the correlation and displacement were calculated by analyzing the radial difference of RF signal. Tissue velocity was determined by the displacement and the frame rate. The correlation image of normal and atherosclerotic coronary arteries clearly showed the internal and external borders of arterial wall. Soft plaque with low echo area in the intima showed high velocity while the calcified lesion showed the very low tissue velocity. This technique provides important information on tissue character of coronary artery.