Faculty Bibliography

Cardiac conduction abnormalities remain a major cause of death and disability worldwide. However, as of today, there is no standard clinical imaging modality that can noninvasively provide maps of the electrical activation. In this paper, electromechanical wave imaging (EWI), a novel ultrasound-based imaging method, is shown to be capable of mapping the electromechanics of all four cardiac chambers at high temporal and spatial resolutions and a precision previously unobtainable in a full cardiac view in both animals and humans. The transient deformations resulting from the electrical activation of the myocardium were mapped in 2D and combined in 3D biplane ventricular views. EWI maps were acquired during five distinct conduction configurations and were found to be closely correlated to the electrical activation sequences. EWI in humans was shown to be feasible and capable of depicting the normal electromechanical activation sequence of both atria and ventricles. This validation of EWI as a direct, noninvasive, and highly translational approach underlines its potential to serve as a unique imaging tool for the early detection, diagnosis, and treatment monitoring of arrhythmias through ultrasound-based mapping of the transmural electromechanical activation sequence reliably at the point of care, and in real time.

The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction. Good agreement (0.22% strain bias, 95% limits of agreement) using Bland-Altman analysis and good correlation (r = 0.84) were found between the ME and SM measurements. These findings demonstrate for the first time that ME could map angle-independent strains to non-invasively detect, localize and characterize the early onset of myocardial ischemia, i.e. at 40%, and possibly as low as 20%, LAD flow reduction, which could be further associated with the severity of coronary stenosis.

Electromechanical wave imaging (EWI) has recently been introduced as a noninvasive, ultrasound-based imaging modality, which could map the electrical activation of the heart in various echocardiographic planes in mice, dogs, and humans in vivo. By acquiring radio-frequency (RF) frames at very high frame rates (390-520 Hz), the onset of small, localized, transient deformations resulting from the electrical activation of the heart, i.e., generating the electromechanical wave (EMW), can be mapped. The correlation between the EMW and the electrical activation speed and pacing scheme has previously been reported. In this study, we pursue the development of EWI using both displacements and strains and analysis of the EMW properties in dogs in vivo for early detection of ischemia. EWI was performed in normal and ischemic open-chest dogs during sinus rhythm. Ischemia of increasing severity was obtained by gradually obstructing the left-anterior descending (LAD) coronary artery flow. We also introduce the novel method of motion-matching that achieves the reconstruction of the full EWI ciné-loop at very high frame rates even when the ECG may be irregular or unavailable. Incremental displacements were previously used by our group to map the EMW. This paper focuses on the associated incremental strains, which facilitate the interpretation of the EMW by relating it directly to contraction. Moreover, we define the onset of the EMW as the time, at which the incremental strains change sign after the onset of the QRS complex of the ECG. Based on this definition, isochronal representations of the EMW were generated using a semi-automated method. The isochronal representation of the EMW during sinus rhythm was reproducible and shown similar to electrical activation maps previously reported in the literature. After segmentation using a contour-tracking method, the two- and four-chamber views were imaged and displayed in bi-plane views, allowing a 3-D interpretation of the EMW. EWI was shown to be sensitive to the presence of intermediate ischemia. EWI localized the ischemic region when the LAD flow was obstructed at 60% and beyond and was capable of mapping the increase of the ischemic region size as the LAD occlusion level increased. In conclusion, the activation maps and wave patterns obtained with EWI were similar to the electrical equivalents previously reported in the literature. Moreover, EWI was found to be sensitive enough to detect and map intermediate ischemia. Those results indicate that EWI could be used to assess the conduction properties of the myocardium, and detect its ischemic onset and disease progression entirely noninvasively.

Electromechanical wave imaging is a novel technique for the noninvasive mapping of conduction waves in the left ventricle through the combination of ECG gating, high frame rate ultrasound imaging and radio-frequency (RF)-based displacement estimation techniques. In this paper, we describe this new technique and characterize the origin and velocity of the wave under distinct pacing schemes. First, in vivo imaging (30 MHz) was performed on anesthetized, wild-type mice (n=12) at high frame rates in order to take advantage of the transient electromechanical coupling occurring in the myocardium. The RF signal acquisition in a long-axis echocardiographic view was gated between consecutive R-wave peaks of the mouse electrocardiogram (ECG) and yielded an ultra-high RF frame rate of 8000 frames/s (fps). The ultrasound RF signals in each frame were digitized at 160 MHz. Axial, frame-to-frame displacements were estimated using 1D cross-correlation (window size of 240 microm, overlap of 90%). Three pacing protocols were sequentially applied in each mouse: (1) sinus rhythm (SR), (2) right-atrial (RA) pacing and (3) right-ventricular (RV) pacing. Pacing was performed using an eight-electrode catheter placed into the right side of the heart with the capability of pacing from any adjacent bipole. During a cardiac cycle, several waves were depicted on the electromechanical wave images that propagated transmurally and/or from base to apex, or apex to base, depending on the type of pacing and the cardiac phase. Through comparison between the ciné-loops and their corresponding ECG obtained at different pacing protocols, we were able to identify and separate the electrically induced, or contraction, waves from the hemodynamic (or, blood-wall coupling) waves. In all cases, the contraction wave was best observed along the posterior wall starting at the S-wave of the ECG, which occurs after Purkinje fiber, and during myocardial, activation. The contraction wave was identified based on the fact that it changed direction only when the pacing origin changed, i.e., it propagated from the apex to the base at SR and RA pacing and from base to apex at RV pacing. This reversal in the wave propagation direction was found to be consistent in all mice scanned and the wave velocity values fell within the previously reported conduction wave range with statistically significant differences between SR/RA pacing (0.85+/-0.22 m/s and 0.84+/-0.20 m/s, respectively) and RV pacing (-0.52+/-0.31 m/s; p<0.0001). This study thus shows that imaging the electromechanical function of the heart noninvasively is feasible. It may therefore constitute a unique noninvasive method for conduction wave mapping of the entire left ventricle. Such a technology can be extended to 3D mapping and/or used for early detection of dyssynchrony, arrhythmias, left-bundle branch block, or other conduction abnormalities as well as diagnosis and treatment thereof.

The abdominal aortic aneurysm (AAA) is a common vascular disease. The current clinical criterion for treating AAAs is an increased diameter above a critical value. However, the maximum diameter does not correlate well with aortic rupture, the main cause of death from AAA disease. AAA disease leads to changes in the aortic wall mechanical properties. The pulse-wave velocity (PWV) may indicate such a change. Because of limitations in temporal and spatial resolution, the widely used foot-to-foot method measures the global, instead of regional, PWV between two points at a certain distance in the circulation. However, mechanical properties are nonuniform along the normal and pathological (e.g., the AAA and atherosclerosis) arteries; thus, such changes are typically regional. Pulse-wave imaging (PWI) has been developed by our group to map the pulse-wave propagation along the abdominal aorta in mice in vivo. By using a retrospective electrocardiogram (ECG) gating technique, the radio-frequency (RF) signals over one cardiac cycle were obtained in murine aortas at the extremely high frame rate of 8 kHz and with a field-of-view (FOV) of 12 x 12 mm(2). The velocities of the aortic wall were estimated using an RF-based speckle tracking method. An Angiotensin II (AngII) infusion-based AAA model was used to simulate the human AAA case. Sequences of wall velocity images can noninvasively and quantitatively map the propagation of the pulse wave along the aortic wall. In the normal and sham aortas, the propagation of the pulse wave was relatively uniform along the wall, while in the AngII-treated aortas, the propagation was shown to be nonuniform. There was no significant difference ( p > 0.05) in the PWV between sham (4.67 +/- 1.15 m/s, n=5) and AngII-treated (4.34 +/- 1.48 m/s, n=17) aortas. The correlation coefficient of the linear regression was significantly higher ( p < 0.005) in the sham aortas (0.89 +/- 0.03, n=5 ) than in the AngII-treated ones (0.61 +/- 0.15, n=17). The wall velocities induced by the pulse wave were lower and the pulse wave moved nonuniformly along the AngII-treated aorta ( p < 0.005), with the lowest velocities at the aneurysmal regions. The discrepancy in the regional wall velocity and the nonuniform pulse-wave propagation along the AngII-treated aorta indicated the inhomogeneities in the aortic wall properties, and the reduced wall velocities indicated stiffening of the aneurysmal wall. This novel technique may thus constitute an early detection tool of vascular degeneration as well as serve as a suitable predictor of AAA rupture, complementary to the current clinical screening practice.