2I-6 Imaging the Electromechanical Wave Activation of …orion.bme.columbia.edu/ueil/documents/inproceedings/2006-konofagou... · Imaging the electromechanical wave activation of

Imaging the electromechanical wave activation of the left ventricle in vivo

Elisa Konofagou1,2, Jianwen Luo1, Kana Fujikura1, Daniel Cervantes3 and James Coromilas3

1Department of Biomedical Engineering, 2Department of Radiology and 3Department of Medicine, Columbia University, New York, NY, USA

E-mail: [email protected]

Abstract— The heart is a mechanical pump that is electrically driven. We have previously shown that the contractility of the cardiac muscle can reliably be used in order to assess the extent of ischemia. In this paper, in vivo imaging (35 MHz) was performed on anesthetized mice before and after left anterior descending (LAD) coronary artery ligation at high frame rates (Vevo 770, Visualsonics, Inc.) in order to better explore the electromechanical coupling within the heart muscle. The acquisition was triggered on the mouse electrocardiogram (ECG) and yielded a high frame rate of 8 kHz. RF signals from long-axis views were digitized and stored in real-time at a similar sampling rate for off-line processing. Axial displacements were estimated using 1D cross-correlation (window size of 60 microns, overlapping at 90%) and displayed at 8 kHz. The mice were initially imaged during sinus rhythm (i.e., at the natural pacing of the heart (100 ms period)), right-atrial pacing (at 100 ms) and right-ventricular pacing (at 100 ms). Pacing was achieved using catheterization through the right side of the heart, where the catheter carried nine electrodes that could be separately activated for varying the pacing location. In some of the scans, the catheter was within the imaging field-of-view and allowed for imaging of the pacing wave during ventricular pacing. The most pronounced wave propagating during sinus rhythm and atrial pacing was the contraction wave, or wave originating at the isovolumic contraction phase, that propagated along the longitudinal direction of the myocardium initiating radial thickening in its path. The contraction wave started at the apex, right at the QRS peak, and then propagated along the septum first and then the posterior wall. So, the direction of propagation was counter-clockwise in a long-axis view. A relaxation wave was also detected propagating across the septum, i.e., from the endo- to the epicardial level. Right-atrial pacing, i.e., similar to sinus rhythm, induced the same counter-clockwise pattern as in the sinus rhythm during contraction. Right-ventricular pacing induced a reverse direction on the contraction wave that started from the tip of the catheter (close to the base) with two waves propagating from base to apex, one along the septum and one along the posterior wall. In summary, strong contraction waves were imaged at 8 kHz frame rate in the septum (from base to apex) and the posterior wall (from apex to base) that changed direction or speed according to the pacing scheme induced. These preliminary results indicate that through electromechanical coupling, motion estimation at high frame rates may yield a novel non-invasive method for conduction mapping of the live myocardium and diagnosis of related diseases.

Keywords- Contraction;Displacement; electromechanical; motion; myocardium; wave.

I. INTRODUCTION Cardiovascular diseases rank as America’s No. 1 killer, claiming the lives of over 41.4% of more than 2.4 million Americans who die each year. Cancer follows, killing 23%. All other causes of death account for about 35.3%. In addition, 61.8 million Americans have some form of cardiovascular disease. This includes diseases of the heart, stroke, high blood pressure, congestive heart failure, congenital heart defects, hardening of the arteries and other diseases of the circulatory system. Early detection of abnormality is thus the key in treating cardiovascular disease early and reducing the enormous death toll. The diagnosis of myocardial ischemia is often difficult to establish in its early stages when treatment is most effective. Patients suffering from myocardial ischemia may present to an emergency room or acute care facility with typical cardiac symptoms such as chest pain, described as tightness, pressure, or squeezing, but some patients may have other symptoms such as arm or chin pain, nausea, sweating, or abdominal pain. Standard techniques such as the electrocardiogram (ECG) often provide inconclusive findings regarding ischemia, and sometimes may even be unable to identify situations, in which ischemia has progressed to cell damage and myocardial infarction (MI).

Elasticity imaging is a relatively new field that has dealt with the estimation and imaging of mechanically-related responses and properties for detection of pathological diseases, most notably cancer [1-3] and has thus emerged as an important field complementary to ultrasonic imaging. Only recently has the focus of the elasticity imaging field been steered towards cardiac applications [4-6]. This technique encompasses imaging of several kinds of mechanical functions, such as displacement, strain, strain rate, velocity, shear strain, rotation angle, etc. that can highlight the mechanical properties of the myocardium and their changes at the presence of disease.

However, the heart will not contract unless it is electrically activated. The path of activation originates at the sinoatrial node propagating to the atrioventricular node, along the Bundle of His until it activates both ventricles starting from the apex and along the Purkinje fibers (Fig. 1). The propagation of the

This work was supported in part by the American Heart Association and Wallace H. Coulter Foundation, and startup funds from Columbia University.

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conduction wave has been determined to have a speed of 0.5-5 m/s depending on the animal model and the presence of disease. Tissue Doppler has been proposed as a technique to successfully detect dyssyncrony in the heart through measurements of the time delays, at which contraction occurs at different regions of the heart [7]. However, 2D mapping of the wave has been restricted to invasive techniques that entail the use of epicardial electrode measurements. The main reason for the lack of noninvasive techniques for accurate electrical mapping is the fact that standard imaging modalities are either limited by the penetration depth (i.e., optical techniques) or by the frame rate required (ultrasound or MRI). Previously, we identified that ultrafast, retrospective acquisition so that elastographic techniques can be used off-line to take advantage of the electromechanical coupling and thus image the conduction wave propagating in the canine [8] and murine [9] as well as human [10] left ventricles in vivo. In this paper, we aim at more accurately identifying the nature and origin of the waves imaged by controlling the electrical activation of the mouse, both the pacing origin and wave direction using the same system as before that guaranteed both high temporal and spatial resolution [8].

Figure 1. The cardiac conduction system of the heart.

II. METHODS

A. Animal Preparation Wild-type mice were anesthetized with 125 mg/kg

intraperitoneal injection of tribromoethanol. The ultrasound probe was placed on the mouse chest using degassed ultrasound gel (Aquasonic 100, Parker Laboratories, Inc., Orange, Fairfield, NJ) as a coupling medium. The mouse was placed supine on an ECG platform and the ECG was acquired simultaneously while imaging.

B. Data Acquisition The high frame-rate data acquisition system developed

previously [8] was used in this study. A 30-MHz ultrasound probe (VisualSonics Inc., Toronto, ON, Canada) was placed on the mouse chest in the parasternal position to obtain a longitudinal (long-axis) view of the LV of the heart. The field of view is 12 mm ×12 mm, the axial resolution was equal to 50 µm, and the lateral resolution was equal to 115 µm.

In the EKVTM (ECG-based kilohertz visualization) mode provided by the imaging system, the transducer worked on a line-by-line basis. The ultrasound echo signals were recorded at a pulse-repetition frequency (PRF) of 8 kHz at each position of the transducer. A two-channel, 14-bit waveform digitizer (CompuScope 14200, Gage Applied Technologies, Inc., Lachine, QC, Canada) was used to simuntaneously acquire the RF signals of the ultrasound scanner and the associated ECG at 160 MS/s. After data acquisition, the acquired RF signals were gated between two consecutive R-waves in the ECG to reconstruct the RF image sequence for a complete heart cycle at the extremely high frame rate of 8 kHz [8]. This allowed for a maximum wave speed calculation of approximately 96 m/s, which was considered high enough for the contraction speeds measured in the mouse heart.

RF signals from long-axis views were digitized and stored in real-time at the same sampling rate for off-line processing. The mice were initially imaged during sinus rhythm (i.e., at the natural pacing of the heart (100 ms period)), right-atrial pacing (at 100 ms) and right-ventricular pacing (at 100 ms). Pacing was achieved using catheterization through the right side of the heart, where the catheter carried nine electrodes that could be separately activated for varying the pacing location. In some of the scans, the catheter was within the imaging field-of-view and allowed for imaging of the pacing wave during ventricular pacing.

C. Data Processing The axial displacement was estimated off-line using the

normalized cross-correlation function [4]. The RF window size was equal to 480 µm, while the window overlap was equal to 95%, deemed high enough to retain the high axial resolution [11]. The aforementioned displacements were the instantaneous or incremental displacements occurring between two consecutive frames, i.e., 0.125 ms apart. Ciné-loops of the incremental displacements were generated to monitor the wave propagation.

III. RESULTS AND DISCUSSION The most pronounced wave propagating during sinus

rhythm (Fig. 2) and atrial pacing (Fig. 3) was the contraction wave, or wave originating at the isovolumic contraction phase, that propagated along the longitudinal direction of the myocardium initiating radial thickening in its path. The contraction wave started at the apex right at the QRS peak and then propagated along the septum first and then the posterior wall. Therefore, in a long-axis view, the wave propagation was shown to be counter-clockwise (Figs. 2 and 3). Right-ventricular pacing (Fig. 4) induced a reverse direction on the contraction wave that started from the tip of the catheter (close to the base) with two waves propagating from base to apex, one along the septum and one along the posterior wall. Therefore, the direction of the contraction wave when pacing is induced from the right ventricle is completely reversed in direction, indicating that the waves mapped through electromechanical coupling are electrically induced and conduction dependent unlike previous reports where heart waves were mechanically induced [12].

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a) b)

c) d)

Figure 2. Sinus rhythm (100 ms) in mouse 1at a) 8.75, b) 10.00 , c) 11.25 and d) 12.50 ms after the R-wave. Note that the contraction starts at the apex (left, center edge) in (a) and propagates along the posterior wall finally covering the entire wall in (d) so that contraction can start. Red denotes motion upwards while blue denotes motion downwards. The range of displacements is from -4 to 4 microns.

a) b)

c) d)

Figure 3. Right-atrial pacing at 100 ms in mouse 2 at a) 16.25, b) 18.75 , c) 21.25 and d) 23.75 ms after the R-wave. Note the slight difference in the propagation due to the change of origin (pacing now is from a region closer to the middle of the right atrium, i.e., below the sinoatrial node) and the field of view. A similar wave to that seen propagating along the posterior wall in Fig. 2 can also be seen from (a) to (d), indicating that the origin is similar.

a) b)

c) d)

Figure 3. Right-ventricular pacing at 100 ms in mouse 2 at a) 10.00 , b) 11.25 , c) 12.50 and d) 13.75 ms after the R-wave. Note the reversal in the direction of propagation in the posterior wall due to the change of origin (pacing now is performed from the right ventricle) and the field of view. The wave propagates from the base to the apex, i.e., clockwise.

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IV. CONCLUSION In summary, strong contraction waves were imaged at 8

kHz frame rate in the septum (from base to apex) and the posterior wall (from apex to base) that changed direction or speed according to the pacing scheme induced. These preliminary results indicate that based on the electromechanical coupling in the heart, motion estimation at high frame rates may yield a novel noninvasive method for conduction mapping of the live myocardium and diagnosis of related diseases. Ongoing investigations entail imaging to detect and characterize presence of dyssynchrony or arrhythmias, corroboration with electrical mapping, and applications of the proposed technique in a clinical setting.

V. ACKNOWLEDGMENTS We wish to express our sincere appreciation to Shunichi

Homma, M.D., Department of Medicine at Columbia University for kindly allowing us access to the Vevo 770 scanner.

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[8] M. Pernot and E. E. Konofagou, “Electromechanical imaging of the myocardium at normal and pathological states,” IEEE Ultrasonics Symp. Proc., 1091-1094, 2005.

[9] M. Pernot., K. Fujikura, S. Fung-Kee-Fung and E.E. Konofagou, ECG-synchronized, ultrafast ultrasound imaging of cardiovascular tissues in intact mice, Ultrasound in Med. Biol., 2006 (in press).

[10] E. E. Konofagou E., S. Fung-Kee-Fung, J. Luo and M. Pernot, Imaging the mechanics and electromechanics of the heart, IEEE EMBS Symposium in Biomedical Engineering, New York, NY, Aug 30-Sep 2, 2006.

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