Pislaru, Cristina

Abstract Diastolic dysfunction causes close to half of congestive heart failures and is associated with increased stiffness in left-ventricular myocardium. A clinical tool capable of measuring viscoelasticity of the myocardium could be beneficial in clinical settings. We used Lamb wave Dispersion Ultrasound Vibrometry (LDUV) for assessing the feasibility of making in vivo non-invasive measurements of myocardial elasticity and viscosity in pigs. In vivo open-chest measurements of myocardial elasticity and viscosity obtained using a Fourier space based analysis of Lamb wave dispersion are reported. The approach was used to perform ECG-gated transthoracic in vivo measurements of group velocity, elasticity and viscosity throughout a single heart cycle. Group velocity, elasticity and viscosity in the frequency range 50–500 Hz increased from diastole to systole, consistent with contraction and relaxation of the myocardium. Systolic group velocity, elasticity and viscosity were 5.0 m s −1 , 19.1 kPa, 6.8 Pa · s, respectively. In diastole, the measured group velocity, elasticity and viscosity were 1.5 m s −1 , 5.1 kPa and 3.2 Pa · s, respectively.

We have proposed generating a bending wave in the arterial wall using ultrasound radiation force and measuring the wave velocity along the arterial wall [Zhang et al., IEEE Trans. Ultrason. Ferroelectr. Freq. Control 52, 642–652 (2005)]. Here, we report the results of in vivo studies on pigs. The pig was anesthetized, and a micromanometer tip catheter was inserted into the femoral artery to measure luminal pressure. A water bath was created on the animal’s groin to allow unimpeded access of the ultrasound beams to the femoral artery. The femoral artery was first located using a 13-MHz linear-array transducer. Then, a vibro-acoustography image was obtained to ensure precise positioning of the excitation force relative to the artery. The artery was excited by the force transducer and the resulting vibration of the arterial wall was measured by a sensing Doppler transceiver. Measured wave velocity was 3.1 m/s at 300 Hz. With this new method wave velocity over a distance of 5 mm, and therefore stiffness of arteries, can be measured locally and non-invasively. Measurement time is short in a few tens of milliseconds, which allows pressure dependence and pharmacological effect on the wall properties to be measured at different cardiac times.

Ultrasound (US) enhancement of plasmid-based gene transfer is an emerging technique. Our hypothesis was that two contrast agents (Optison and PESDA), and two US exposure modalities (dedicated continuous wave system and diagnostic scanner) may have different effects. Luciferase plasmid with or without contrast agent was added to vascular smooth muscle cells and endothelial cells, followed by US exposure. Luciferase activity was measured 24 h later. US exposure consistently induced higher transfection rates than all controls. PESDA was superior to Optison in both cell lines. In vitro, continuous wave and diagnostic US were not significantly different. In vivo, Lux and PESDA were injected into skeletal muscles of rats (IM or intra-arterial) followed or not by US exposure. In separate animals, adenovirus encoding for luciferase was injected IM and was not followed by US exposure. Gene transfer efficacy was 8–10 fold higher with US and PESDA than with plasmid alone, but 2 fold lower than with adenovirus. However, as opposed to adenovirus, US-enhanced plasmid gene transfer was highly localized to the injected muscle, with no expression at distal sites. Our results support the hypothesis that contrast agents and exposure modalities are not equivalent with regard to gene transfer efficacy.

The cardiovascular diseases such as atherosclerosis, coronary artery disease, hypertension and diastolic dysfunction have been associated with arterial stiffening and decreased ventricular compliance. Noninvasive techniques capable of quantifying elasticity and viscosity of cardiovascular tissues could facilitate early diagnosis and improve treatment. Here, we present a technique that uses focused ultrasound radiation force to excite mechanical waves in the tissue of interest and pulse echo to track the tissue deformation. Analysis of tissue deformation as a function of time using Fourier transforms allows calculation of the phase wave velocity dispersion (change of velocity as a function of frequency) of various modes of deformation. Continuum mechanics equations governing the motion of a viscoelastic plate and a tube are used to model the myocardial wall and arteries, respectively. Dispersion equations are derived for the two geometries and fit to the measured velocity dispersion to estimate tissue elasticity and viscosity. ECG-gated in vivo measurements of porcine myocardial and arterial elasticity and viscosity through a heart cycle are reported. The results show that both elasticity and viscosity increase during systole and decrease during diastole in the myocardium and arteries, consistent with underlying physiology.

Pulse wave velocity (PWV) is widely used for estimating the stiffness of an artery. PWV is measured by the time of travel of the “foot” of the pressure wave over a known distance. This technique has a low time resolution and is an average measurement of artery stiffness between the two measuring positions. In this paper an arterial wave is generated non-invasively in the vessel wall by the radiation force of ultrasound. The wave velocity in the vessel is measured non-invasively by ultrasound with high time resolution over a short distance of a few millimeters.

Background— In this study we evaluate the diastolic deformation of ischemic/reperfused myocardium and relate this deformation to tissue elastic properties. Methods and Results— Farm pigs were subjected to left anterior descending coronary artery occlusion followed by reperfusion to create either stunning (n=12) or transmural myocardial infarction (n=12). Ultrasound-derived radial strain rates (SR) and strain were measured in the ischemic and remote walls. Myocardial stiffness was estimated from diastolic pressure–wall thickness relationship obtained from preload alterations. At reperfusion, end-systolic strain (ε sys ) was significantly reduced in both stunned and infarcted walls compared with their remote walls (3±3% versus 26±2% and 1±0% versus 33±5%, respectively; P <0.0001) or baseline values. Diastolic passive deformation (ε A ) and rates of deformation during early (E SR ) and late (A SR ) diastole were comparable between stunned and remote walls (ε A : 7.3±1.6% versus 7.9±1.9%; E SR : −2.7±0.4 s −1 versus −2.6±0.5 s −1 ; A SR : −1.8±0.2 s −1 versus −1.9±0.3 s −1 ; P =NS for all) but were of significantly lower magnitude in infarcted walls versus remote walls (ε A : 1.1±0.2% versus 11.4±1.9%; E SR : −0.3±0.1 s −1 versus −2.4±0.4 s −1 ; A SR : −0.3±0.1 s −1 versus −2.5±0.4 s −1 ; P <0.0001 for all). Stiffness coefficient of exponential diastolic pressure–wall thickness relation was higher for infarcted ( P <0.05) but not for stunned walls ( P =NS) compared with their remote walls. Conclusions— Early after postischemic reperfusion and in the presence of severely reduced systolic deformation, diastolic passive deformation (and rates of deformation) can distinguish stiff, noncompliant, transmurally infarcted myocardial walls from those more compliant walls containing viable but stunned myocardium.