Greenleaf, James F.

Arterial stiffness is recognized as a highly clinically relevant and independent prognostic biomarker of cardiovascular disease. Arterial dispersion ultrasound vibrometry (ADUV) uses acoustic radiation force to generate propagating waves in the arterial wall and measures the wave motion to estimate arterial mechanical properties from fitting phase velocity dispersion curves to a waveguide model. ADUV measurements were made with a Verasonics V1 system with a L7-4 linear array transducer in 63 human subjects (27 male/36 female) from ages 50–88 years old. We made measurements at 10 time points within the cardiac cycle, termed cardiac stages. We estimated the phase velocity (median of cp from 400-600 Hz) and G determined from matching the dispersion curves with those from a waveguide model incorporating the artery diameter and wall thickness. Within the same study visit, we measured the intima-media thickness and diameter changes through the cardiac cycle with a General Electric Logiq E9 or E10 scanner. We also tonometry to determine the carotid-femoral pulse wave velocity. We report here comparisons of median phase velocity, cp, and inverted shear modulus, G, at different stages of the cardiac cycle with clinical metrics of arterial stiffness.

Abstract Objective. Measuring waves induced with acoustic radiation force (ARF) in arteries has been studied over the last decade. To date, it remains a challenge to quantitatively assess the local arterial biomechanical properties. The cylindrical shape and waveguide behavior of waves propagating in the arterial wall pose complexities to determining the mechanical properties of the artery. Approach . In this paper, an artery-mimicking tube in water is examined utilizing three-dimensional measurements. The cross-section of the tube is measured while a transducer is translated over 41 different positions along the length of the tube. Motion in the radial direction is calculated using two components of motion which are measured from the two orthogonal views of the cross-section. This enables more accurate estimation of motion along the circumference of tube. Main results . The results provide more information to categorize the motion in tube wall into two types of responses: a transient response and a steady state response. The transient response is caused by ARF application and the waves travel along the length of the tube for a relatively short period of time. This corresponds to the axial and circumferential propagating waves. The two circumferential waves travel along the circumference of tube in CW (clockwise) and CCW (counter-clockwise) direction and result in a standing wave. By using a directional filter, the two waves were successfully separated, and their propagation was more clearly visualized. As a steady state response, a circumferential mode is generated showing a symmetric motion (i.e. the proximal and distal walls move in the opposite direction) following the transient response. Significance. This study provides a more comprehensive understanding of the waves produced in an artery-mimicking tube with ARF application, which will provide opportunities for improving measurement of arterial mechanical properties.

Shear Wave Elastography (SWE) has been used to estimate arterial stiffness, an important biomarker for early cardiovascular diseases. In arterial SWE, the carotid artery is excited with acoustic radiation force and the observed wave propagation characteristics are used to estimate the arterial stiffness. We present an efficient guided wave inversion procedure, where the elastic modulus of the arterial wall is estimated by matching wave dispersion from experiments and simulation. Central to the proposed approach is an efficient forward model that computes the dispersion relation for the incompressible, immersed cylindrical tube; the model achieves high efficiency by combining semi-analytical finite element methods, selective reduced integration, and perfectly matched discrete layers. We utilize this forward model in an optimization framework to develop a streamlined methodology to estimate the modulus of the arterial wall. In this talk, we present the formulation of the method as well as validation using phantom experiments on 10 rubber tubes (VytaFlex-10), followed by preliminary work on inverting for the viscoelastic modulus.

Abstract Arterial stiffness is found to be an early indicator of many cardiovascular diseases. Among various techniques, shear wave elastography has emerged as a promising tool for estimating local arterial stiffness through the observed dispersion of guided waves. In this paper, we develop efficient models for the computational simulation of guided wave dispersion in arterial walls. The models are capable of considering fluid-loaded tubes, immersed in fluid or embedded in a solid, which are encountered in in vitro/ex vivo , and in vivo experiments. The proposed methods are based on judiciously combining Fourier transformation and finite element discretization, leading to a significant reduction in computational cost while fully capturing complex 3D wave propagation. The developed methods are implemented in open-source code, and verified by comparing them with significantly more expensive, fully 3D finite element models. We also validate the models using the shear wave elastography of tissue-mimicking phantoms. The computational efficiency of the developed methods indicates the possibility of being able to estimate arterial stiffness in real time, which would be beneficial in clinical settings.

Computed tomography (CT) using acoustic waves was invented at about the same time as MRI. The method of computing attenuation from projections was a direct analog of the x-ray CT approach. However, the method of computing speed from the time of flight of the acoustic ray was a larger logical jump. The field started with straight ray, earliest arrival time methods and has matured to what can be termed the full wave equation inversion method. The extension from two dimensions to three, although essential in the body, did not find a practical solution until very recently. The inverse problem represented by this field has found the attention of many investigators over the years. Practical medical implementations continue being investigated by several investigators more than 30 years after the first invention of the method. Acoustic tomography has been applied in nonmedical areas including oceanography, seismic, and solar sciences. Time awaits its success in medicine.

Diastolic dysfunction is the impaired ability of the left ventricle (LV) to passively fill during diastole and maintain its stroke volume at physiologic filling pressures and is associated with impaired relaxation and reduced compliance of LV. Knowledge of the quantitative values of the myocardial viscoelastic properties would improve the clinician’s ability to evaluate diastolic dysfunction in patients. To gain better understanding of the viscoelastic properties of the LV as a function of geometry, we studied Lamb wave propagation in different directions in excised porcine free-wall myocardium. The phantom consisting of a dissected porcine LV free-wall embedded in gelatin was fixed in a water tank. A mechanical shaker was used for harmonic excitation over a range of 40–500 Hz and a 7.5 MHz ultrasound transducer was used for motion measurements. Motion amplitude and phase at different depths of the sample were analyzed to obtain dispersion curves in four orthogonal directions. The data were fitted to the Lamb wave equations and shear elasticity and viscosity coefficients were estimated. The values of μ1 and μ2 were 13.75 ± 0.96 and 5.86 ± 0.75 Pa s. Our results suggest that the viscoelastic characteristics of the porcine LV free-wall in orthogonal directions were similar.

Increased stiffness of arteries has recently gained acceptance as an independent risk factor for cardiovascular and many other diseases. Pulse wave velocity (PWV) is widely used for estimating the stiffness of an artery. However, PWV is an average indicator of artery stiffness between the two measuring points, and therefore does not identify local stiffness. In addition, the thickness of the artery is needed to calculate artery elastic modulus. We have discovered that there is a series of ring resonant frequency in arteries that can be used for estimating local arterial elastic modulus. These resonances can be excited by remote palpation with selectively placed ultrasonic radiation force. Experiments on ring resonance were carried out on an excised artery as well as a rubber tube. This family of resonances occurs at relatively low frequency, around 356 Hz for the artery. Estimation of the Young’s modulus is 135 kPa by the ring frequency 356 Hz without the requirement of the arterial thickness. The estimated modulus is very consistent with the other ring resonant frequency measurements. The theory of ring resonance is developed and verified with the rubber tube experiments.

Vibro-acoustography is an imaging modality that uses ultrasound as the source of energy to explore objects at two ends of the spectrum. Employing two ultrasound beams at slightly different frequencies, this technique produces a highly localized radiation stress field that vibrates the object at the difference frequency. In response, the object produces a secondary acoustic field. This sound, which contains information about the dynamics of the object at the low difference frequency as well as objects characteristics at the ultrasound range, is used to produce an image of the object. This combination makes vibro-acoustography a unique tool to study biological tissues at low and high frequencies simultaneously. Utility of this method has already been demonstrated for a wide range of applications in vitro. In vivo applications of vibro-acoustography have been demonstrated in a recent study on human breast. It has been shown that this technique can produce high quality in vivo images at ultrasound intensities within the recommended FDA limits. Vibro-acoustography may also be used for imaging solids, such as metallic implants. This paper describes recent achievements in vibro-acoustography as well as possible future role of this technology in medicine. [This abstract includes materials patented by MF and JFG.]

Arterial wall stiffness can be associated with various diseases. The stiffness of an artery can be assessed by measurement of the pulse wave velocity (PWV). PWV is directly related to the Youngs modulus by the well-known Moens–Korteweg equation. Usually, PWV is estimated using the foot-to-foot method. However, the foot of the pressure wave is not very clear due to reflected waves. Also, the pressure wave is normally at a low frequency, hence, the time resolution is low. PWV is an average indicator of artery stiffness between the two measuring points, therefore it is not easy to identify local stiffness. We propose producing a very short pulse wave in the arterial wall using ultrasound radiation force and measuring its propagation speed along the artery by laser. The temporal resolution of this method is in the range of microseconds, which allows PWV to be measured accurately over a few millimeters. Experiments were carried out on a silicone tube in gelatin. PWV was measured by two scanning methods: (1) fixed source and scanning detector, (2) scanning source and fixed detector. Results: PWV was measured at 2 mm/40 μs by both methods. The Doppler technique was also tested which is potentially suitable for clinical applications.

A coupled vibration model, which takes into account the elastic arterial wall, the interior blood, and exterior tissue, is presented. The arterial wall is considered as a cylindrical elastic shell and is modeled with the thick shell theory due to the large thickness-to-radius ratios. Both the blood and the tissue are considered as ideal fluids and are modeled with acoustic wave theory. A newly developed method, the wave propagation approach, is extended for the coupled vibration of arterial walls. The theoretic model is evaluated against those available in the literature. The experiments were carried out on a silicone rubber tube in a water tank with an ultrasound stimulated system. This system uses the radiation force of ultrasound to vibrate the tube at low frequency and records the resulting response by a laser vibrometer. Both the excitation and measurement are remote and noncontact. The measured fundamental frequency is in good agreement with the theoretical prediction.