Dan Adam

Fluctuations in T-wave morphology and susceptibility to ventricular fibrillation

Susceptibility of the ventricles to fibrillation has been related to the degree of spatial inhomogeneity in the repolarization process. We studied the pattern of beat-to-beat fluctuations in ventricular repolarization processes in order to determine whether a relationship also exists between the temporal variability of ventricular repolarization and susceptibility to ventricular fibrillation. We used the morphology of the T-wave recorded in surface and epicardial leads as a measure of the ventricular repolarization process. The Ventricular Fibrillation Threshold (VFT) was used as the standard measure of cardiac susceptibility to fibrillation. In dog experiments, T-wave morphologic indices were computed on 1,024 sequential beats. Histogram, autocorrelation and power spectrum analyses were performed on the sequence of T-wave morphologic indices. A series of 27 experiments were performed on 20 dogs in which VFT was reduced by several different interventions--hypothermia, tachycardia and coronary artery ligation. For all three interventions we observed the same characteristic change in the pattern of T-wave morphology fluctuations. In particular, we found that as the VFT was reduced, a pattern of T-wave alternans developed. This pattern was generally not detectable by visual inspection of the ECG. It was, on the other hand, easily quantified in terms of a T-wave alternans index (TWAI) which we computed from the power spectrum of the T-wave fluctuations. In 26 of the 27 experiments, measured VFT decreased (p less than .001); in 20 of these experiments the TWAI computed from the surface ECG increased (decreased) when VFT decreased (increased) (p less than .01). In 17 experiments epicardial electrograms were recorded. In 16 of these experiments VFT decreased (p less than .001). In 16 of these 17 experiments TWAI computed from the epicardial ECG increased (decreased) when the VFT decreased (increased) (p less than .001). We conclude that statistical analysis of fluctuations in ECG complex morphology may provide a sensitive probe of ventricular vulnerability to fibrillation.

Contrast-Enhanced Ultrasound Imaging of the Vasa Vasorum: From Early Atherosclerosis to the Identification of Unstable Plaques

Proliferation of the adventitial vasa vasorum (VV) is inherently linked with early atherosclerotic plaque development and vulnerability. Recently, direct visualization of arterial VV and intraplaque neovascularization has emerged as a new surrogate marker for the early detection of atherosclerotic disease. This clinical review focuses on contrast-enhanced ultrasound (CEUS) as a noninvasive application for identifying and quantifying carotid and coronary artery VV and intraplaque neovascularization. These novel approaches could potentially impact the clinicians ability to identify individuals with premature cardiovascular disease who are at high risk. Once clinically validated, the uses of CEUS may provide a method to noninvasively monitor therapeutic interventions. In the future, the therapeutic use of CEUS may include ultrasound-directed, site-specific therapies using microbubbles as vehicles for drug and gene delivery systems. The combined applications for diagnosis and therapy provide unique opportunities for clinicians to image and direct therapy for individuals with vulnerable lesions.

Circumferential and Longitudinal Strain in 3 Myocardial Layers in Normal Subjects and in Patients with Regional Left Ventricular Dysfunction

BACKGROUND The left ventricle is not homogenous and is composed of 3 myocardial layers. Until recently, magnetic resonance imaging has been the only noninvasive technique for detailed evaluation of the left ventricular (LV) wall. The aim of this study was to analyze strain in 3 myocardial layers using speckle-tracking echocardiography. METHODS Twenty normal subjects and 21 patients with LV dysfunction underwent echocardiography. Short-axis (for circumferential) and apical (for longitudinal strain) views were analyzed using modified speckle-tracking software enabling the analysis of strain in 3 myocardial layers. RESULTS In normal subjects, longitudinal and circumferential strain was highest in the endocardium and lowest in the epicardium. Longitudinal endocardial and mid layer strain was highest in the apex and lowest in the base. Epicardial longitudinal strain was homogenous over the left ventricle. Circumferential 3-layer strain was highest in the apex and lowest in the base. In patients with LV dysfunction, strain was lower, with late diastolic or double peak. CONCLUSIONS Three-layer analysis of circumferential and longitudinal strain using speckle-tracking imaging can be performed on a clinical basis and may become an important method for the assessment of real-time, quantitative global and regional LV function.

Carotid Plaque Vulnerability: Quantification of Neovascularization on Contrast-Enhanced Ultrasound With Histopathologic Correlation

OBJECTIVE The purpose of this research is to develop a computerized method to quantify carotid plaque neovascularization on contrast-enhanced ultrasound images and to compare the results with the histopathologic analysis of the plaque. SUBJECTS AND METHODS Twenty-seven patients (age range, 48-84 years; mean [± SD] age, 68.4 ± 9.72 years) were recruited before endarterectomy. Contrast-enhanced ultrasound examination of the carotid artery was performed by applying low mechanical index and harmonics with pulse inversion. An algorithm was developed that implemented several image processing methods to automatically quantify neovascularization and reconstruct the vascular tree in the atheromatous plaque. Neovascularization and the number of inflammatory cells seen on histopathologic analysis of the plaque after endarterectomy were compared with neovascularization determined by the computerized method. The mean (± SD) ratios of the ultrasound and histopathologic measurements were calculated. RESULTS In five patients, heavy calcification of the plaque prevented visualization of plaque texture. Intraplaque neovascularization on contrast-enhanced ultrasound images was significant in 19 patients and low in three patients. The ratio of the neovascularization area to the total plaque area on contrast-enhanced ultrasound images was well correlated with the same histopathologic ratio (R(2) = 0.7905) and with the number of inflammatory cells present in the plaque (R(2) = 0.6109). The histopathologic ratio and the number of intraplaque inflammatory cells also were well correlated (R(2) = 0.7034). CONCLUSION The newly developed method allowed quantification of the intraplaque neovascularization as a feature of vulnerability in the carotid plaque and proved to be highly correlated with histopathologic results.

Semiautomated Border Tracking of Cine Echocardiographic Ventnrcular Images

Two-dimensional ultrasound sector scans of the left ventricle (LV) are commonly used to diagnose cardiac mechanical function. Present quantification procedures of wall motion by this technique entail inaccuracies, mainly due to relatively poor image quality and the absence of a definition of the relative position of the probe and the heart. The poor quality dictates subjective determination of the myocardial edges, while the absence of a position vector increases the errors in the calculations of wall displacement, LV blood volume, and ejection fraction. An improved procedure is proposed here for automatic myocardial border tracking (AMBT) of the endocardial and epicardial edges in a sequence of video images. The procedure includes nonlinear filtering of whole images, debiasing of gray levels, and location-dependent contrast stretching. The AMBT algorithm is based upon tracking movement of a small number of predefined set of points, which are manually defined on the two myocardial borders. Information from one image is used, by utilizing predetermined statistical criteria to iteratively search and detect the border points on the next one. Border contours are reconstructed by Spline interpolation of the border points. The AMBT procedure is tested by comparing processed sequences of cine echocardiographic scan images to manual tracings by an objective observer and to results from previously published data.

A new method of spatial compounding imaging

A new method of spatial compound imaging is presented that improves image quality without the usual requirement to decrease the frame rate. The new method of imaging utilizes three transducers for data acquisition. The transducer located at the center of the transducer system is a phased array probe that acts as both transmitter and receiver. The other transducers are unfocused pistons that act only as receivers. Envelope data acquired by each transducer are combined to form a final image with improved quality (speckle contrast, target detectability and lateral resolution). It is shown that the improvement in speckle contrast depends on the correlation between individual images acquired by the transducers. The effective aperture approach is used for analytic estimation of the correlation between images in order to optimize the lateral separation between transducers. Using simulations, several compounding strategies have been performed to find the strategy that maximizes image quality. The central frequency of 2.5 MHz is used in simulations. Quantitative analysis of simulated B-mode images shows that the new method of imaging efficiently improves visibility, detectability, and lateral resolution of low contrast regions. The image frame rate is preserved because multiple scans are not required for the spatial compounding.

Blind deconvolution of ultrasound sequences using nonparametric local polynomial estimates of the pulse

The problem of reconstructing the reflectivity of a biological tissue is examined by means of blind deconvolution of the echo ultrasound signals. It is shown that the quality of the reconstruction procedure can be significantly improved when initially the ultrasonic pulse is accurately estimated. A new approach to the estimation of the ultrasound pulse echo sequences is proposed, using local polynomial approximation, which is closely related to the wavelet transform theory. This approach can be viewed as a modification of homomorphic deconvolution, by using bases different from the Fourier basis of the space of square-integrable functions L/sup 2/. The bases used here are the orthogonal compactly supported wavelet bases. It is shown that the locality of the estimate can be extremely useful in number of cases of practical interest, resulting in estimates with smaller root-mean squared (rms) errors, as compared with estimates employing the Fourier basis. This approach is applied to ultrasound signals, for estimation of the ultrasound pulse log-spectrum from the log-spectrum of radio-frequency (RF) sequences. It is shown, conceptually and experimentally, that the proposed approach can provide robust and rapidly computed estimates of the ultrasound pulses from the RF-sequences, as obtained in the process of tissue scanning. The pulse phase was recovered using the minimum-phase assumption, which was found to hold for the transducers in use. The obtained pulse estimates are used for the deconvolution of the RF-sequences, which result in stable estimates of the tissue reflectivity function, fairly independent of the properties of the imaging system. Simulated data, data obtained from several phantoms and from in vitro experiments have been processed and the results seem to be quite promising.

Enhanced heat deposition using ultrasound contrast agent - modeling and experimental observations

Ultrasound contrast agents (UCA), created originally for visualization and diagnostic purposes, recently have been suggested as efficient enhancers of ultrasonic power deposition in tissue. The ultrasonic energy absorption by the contrast agents, considered as problematic in diagnostic imaging, might have beneficial impact in therapeutic applications such as targeted hyperthermia-based or ablation treatments. Introduction of gas microbubbles into the tissue to be treated can improve the effectiveness of current treatments by limiting the temperature rise to the treated site and minimising the damage to the surrounding healthy tissues. To this end, proper assessment of the governing parameters of energy absorption by ultrasonically induced stabilized bubbles is important for both diagnostic and therapeutic ultrasound applications. The current study was designed to predict theoretically and measure experimentally the dissipation and heating effects of encapsulated UCA in a well-controlled and calibrated environment. The ultrasonic effects of the microbubble concentration, transmitted intensity, and frequency on power dissipation and stability of the UCA have been studied. The maximal temperature elevation obtained during 300 s experiments was 21/spl deg/C, in a 10 ml volume target containing UCA, insonified by unfocused 3.2 MHz continuous wave (CW) at spatial average intensity of 1.1 W/cm/sup 2/ (182 kPa). The results also suggest that higher frequencies are more efficiently absorbed by commonly used UCA. In particular, for spatial average intensity of 1.1 W/cm/sup 2/ and concentration of 5/spl middot/10/sup 6/ microspheres/cm/sup 3/, no significant reduction of UCA absorption was noticed during the first 150 s for insonation at 3.2 MHz and the first 100 s for insonation at 1 MHz. In addition, when lower average intensity of 0.5 W/cm/sup 2/ (160 kPa) at 3.2 MHz was used, the UCA absorptivity sustained for almost 200 s. Thus, when properly activated, UCA may be suitable for localized hyperthermic therapies.

Modulation of the Arterial Coronary Blood Flow by Asynchronous Activation with Ventricular Pacing

This study aims to test the assumptions that: (1) coronary arterial flow is attenuated in an early activated region by ventricular pacing; (2) asynchronous mechanical activation caused by ventricular pacing under controlled perfusion pressure and intact coronary tone is associated with reduced coronary flow compared to atrial pacing; and (3) abolishment of vascular tone under controlled perfasion pressure diminishes the expected difference in blood flow between atrial and ventricular pacing. Blood flow velocity (BFV) in the left anterior descending (LAD) and the left circumflex arteries (CFX) and a wall thickening index were measured in 14 open‐chest dogs under normal conditions, and constant perfasion pressure. Four pacing sites were used: right atrium (RAJ, mid‐right ventricle (RVyJ, mid‐left ventricle (LVp), and left ventricular apex (Apex. Pacing modes were either sequential ventriculoatrial (VA) (protocol A, n = 7), or sequential atrioventricalar (AV) (protocol B, n = 7), with a shorter AV difference (30 msec) than normal. Residis: BFV was decreased in the LAD during HV and Apex, pacingby 9.7%‐12.9% versas LVp and by 1.6%‐14.6% versus LVp (P < 0.05). No BFV variations were observed in the CFX. Flow velocity conductance (FVC = mean blood flow velocity divided by the mean aortic pressure) was higher by 16%‐28% in the CFX for the three ventricular pacing sites versus the airial pacing, and higher by 14.1%± 6.1% only in LVp versus RAp pacing in the LAD (P < 0.05). Wall thickening index reduced during ventricular pacing in all three ventricular sites by 50%‐64% (P < 0.05) compared to atrial pacing. Under constant perfusion pressure, LAD blood flow decreased with ventricular pacing as compared to right atrial pacing; this was particularly pronounced during the diastolic phase (16.6%−45.5%, P < 0.02). Normalized oscillatory flow amplitude (OFA.J was reduced in RVy, pacing compared to RAp and LVp pacing (16.2 ± 3.5 and 21.7%± 4.1%, respectively, P < 0.03). The variations in blood flow and OFAn disappeared with adenosine‐mediated maximum vasodilatation. Summary; (1) Mean and phasic flows are reduced in the early activated LAD region by ventricular pacing (RVp, Apex. (2) Under controlled perfusion pressure and intact vascular tone, ventricular pacing compromises blood flow compared with atrial pacing. (3) This effect disappears when vascular tone is eliminated by intracoronary injection of adenosine, suggesting that the coronary autoregulation is responsible for some of the effects.

Layer-specific strain analysis by speckle tracking echocardiography reveals differences in left ventricular function between rats and humans

The rat heart is commonly used as an experimental model of the human heart in both health and disease states, assuming that heart function of rats and humans is alike. When studying a rat model, echocardiography is usually performed on sedated rats, whereas standard echocardiography on adult humans does not require any sedation. Since echocardiography results of sedated rats are usually inferred to alert humans, in the present study, we tested the hypothesis that differences in left ventricular (LV) function may be present between rats sedated by a low dose of ketamine-xylazine and alert humans. Echocardiography was applied to 110 healthy sedated rats and 120 healthy alert humans. Strain parameters were calculated from the scans using a layer-specific speckle tracking echocardiography program. The results showed that layer longitudinal strain is equal in rats and humans, whereas segmental strain is heterogeneous (P < 0.05) in a different way in rats and humans (P < 0.05). Furthermore, layer circumferential strain is larger in humans (P < 0.001), and the segmental results showed different segmental heterogeneity in rats and humans (P < 0.05). Radial strain was found to be homogeneous at the apex and papillary muscle levels in humans and heterogeneous in rats (P < 0.001). Additionally, whereas LV twist was equal in rats and humans, in rats the rotation was larger at the apex (P < 0.01) and smaller at the base (P < 0.001). The torsion-to-shortening ratio parameter, which indicates the transmural distribution of contractile myofibers, was found to be equal in rats and humans. Thus, when evaluating LV function of sedated rats under ketamine-xylazine, it is recommended to measure the global longitudinal strain, LV twist, and torsion-to-shortening ratio, since no scaling is required when converting these parameters and inferring them to humans.