Doctor of Philosophy

dissertationAtrial fibrillation (AF) is the leading cause of ischemic stroke and is the most commonly observed arrhythmia in clinical cardiology. Catheter ablation of AF, in which specific regions of cardiac anatomy associated with AF are intenionally injured to create scar tissue, has been honed over the last 15 years to become a relatively common and safe treatment option. However, the success of these anatomically driven ablation strategies, particularly in hearts that have been exposed to AF for extended periods, remains poor. AF induces changes in the electrical and structural properties of the cardiac tissue that further promotes the permanence of AF. In a process known as electroanatomical (EAM) mapping, clinicians record time signals known as electrograms (EGMs) from the heart and the locations of the recording sites to create geometric representations, or maps, of the electrophysiological properties of the heart. Analysis of the maps and the individual EGM morphologies can indicate regions of abnormal tissue, or substrates that facilitate arrhythmogenesis and AF perpetuation. Despite this progress, limitations in the control of devices currently used for EAM acquisition and reliance on suboptimal metrics of tissue viability appear to be hindering the potential of treatment guided by substrate mapping. In this research, we used computational models of cardiac excitation to evaluate param- eters of EAM that affect the performance of substrate mapping. These models, which have been validated with experimental and clinical studies, have yielded new insights into the limitations of current mapping systems, but more importantly, they guided us to develop new systems and metrics for robust substrate mapping. We report here on the progress in these simulation studies and on novel measurement approaches that have the potential to improve the robustness and precision of EAM in patients with arrhythmias. Appropriate detection of proarrhythmic substrates promises to improve ablation of AF beyond rudimentary destruction of anatomical targets to directed targeting of complicit tissues. Targeted treatment of AF sustaining tissues, based on the substrate mapping approaches described in this dissertation, has the potential to improve upon the efficacy of current AF treatment options

An Ultrasound Matrix Transducer for High-Frame-Rate 3-D Intra-cardiac Echocardiography

Objective: Described here is the development of an ultrasound matrix transducer prototype for high-frame-rate 3-D intra-cardiac echocardiography. Methods: The matrix array consists of 16 × 18 lead zirconate titanate elements with a pitch of 160 µm × 160 µm built on top of an application-specific integrated circuit that generates transmission signals and digitizes the received signals. To reduce the number of cables in the catheter to a feasible number, we implement subarray beamforming and digitization in receive and use a combination of time-division multiplexing and pulse amplitude modulation data transmission, achieving an 18-fold reduction. The proposed imaging scheme employs seven fan-shaped diverging transmit beams operating at a pulse repetition frequency of 7.7 kHz to obtain a high frame rate. The performance of the prototype is characterized, and its functionality is fully verified. Results: The transducer exhibits a transmit efficiency of 28 Pa/V at 5 cm per element and a bandwidth of 60% in transmission. In receive, a dynamic range of 80 dB is measured with a minimum detectable pressure of 10 Pa per element. The element yield of the prototype is 98%, indicating the efficacy of the manufacturing process. The transducer is capable of imaging at a frame rate of up to 1000 volumes/s and is intended to cover a volume of 70° × 70° × 10 cm. Conclusion: These advanced imaging capabilities have the potential to support complex interventional procedures and enable full-volumetric flow, tissue, and electromechanical wave tracking in the heart.</p

Electrophysiology

The outstanding evolution of recording techniques paved the way for better understanding of electrophysiological phenomena within the human organs, including the cardiovascular, ophthalmologic and neural systems. In the field of cardiac electrophysiology, the development of more and more sophisticated recording and mapping techniques made it possible to elucidate the mechanism of various cardiac arrhythmias. This has even led to the evolution of techniques to ablate and cure most complex cardiac arrhythmias. Nevertheless, there is still a long way ahead and this book can be considered a valuable addition to the current knowledge in subjects related to bioelectricity from plants to the human heart

Electromechanical Wave Imaging

Cardiac conduction abnormalities and arrhythmias are associated with stroke, heart failure, and sudden cardiac death, and remain a major cause of death and disability. However, the imaging tools currently available to the physician to guide these treatments by mapping the activation sequence of the heart are invasive, ionizing, time-consuming, and costly. In this dissertation, Electromechanical Wave Imaging (EWI) is described with an aim to characterize normal and abnormal rhythms noninvasively, transmurally, at the point of care, and in real time. More specifically, the methods to map the electromechanical wave (EW), i.e., the transient deformations occurring in response to the electrical activation of the heart, are developed and optimized. The correlation between EW and the electrical activation sequence during both normal and abnormal rhythms is demonstrated in canines in vivo and in silico. Finally, EWI is shown to noninvasively detect and characterize arrhythmias and conduction disorders in humans. Novel ultrasound imaging methodologies were developed to track the EW. Radio-frequency (RF) frames acquired at high frame rates were used in conjunction with cross-correlation algorithms to map the onset of the small, localized, transient deformations resulting from the electrical activation and forming the EW. To validate the capability of the EW to characterize cardiac rhythm, it was compared against the electrical activation in vivo and in silico. A high correlation between the electrical and electromechanical activations was obtained in normal canines in vivo during various pacing schemes and sinus rhythm. An in vivo-in silico framework was also developed to demonstrate that this correlation is maintained transmurally and independently of the imaging angle. EWI was also validated in abnormal canine hearts in vivo during ischemia, left bundle branch block, or atrio-ventricular dissociation. In a clinical feasibility study, we demonstrated that EWI was capable of noninvasively mapping normal and abnormal activation patterns in all four cardiac chambers of human subjects using a readily available clinical ultrasound scanner. Specifically, EWI maps were generated for three heart failure patients with cardiac resynchronization therapy (CRT) devices and for three patients with atrial flutter who subsequently underwent catheter mapping and radiofrequency ablation. Preliminary validation of EWI maps against invasive transcutaneous electroanatomical cardiac mapping was also demonstrated. EWI has the potential of becoming a noninvasive and highly translational technology that can serve as a unique imaging tool for the early detection, diagnosis and treatment monitoring and follow-up of arrhythmias and conduction disorders through ultrasound-based mapping of the transmural electromechanical activation sequence reliably, at the point of care, and in real time

On the efficiency and accuracy of the single equivalent moving dipole method to identify sites of cardiac electrical activation

We have proposed an algorithm to guide radiofrequency catheter ablation procedures. This algorithm employs the single equivalent moving dipole (SEMD) to model cardiac electrical activity. The aim of this study is to investigate the optimal time instant during the cardiac cycle as well as the number of beats needed to accurately estimate the location of a pacing site. We have evaluated this algorithm by pacing the ventricular epicardial surface and inversely estimating the locations of pacing electrodes from the recorded body surface potentials. Two pacing electrode arrays were sutured on the right and left ventricular epicardial surfaces in swine. The hearts were paced by the electrodes sequentially at multiple rates (120–220 bpm), and body surface ECG signals from 64 leads were recorded for the SEMD estimation. We evaluated the combined error of the estimated interelectrode distance and SEMD direction at each time instant during the cardiac cycle, and found the error was minimum when the normalized root mean square (RMS[subscript n]) value of body surface ECG signals reached 15 % of its maximum value. The beat-to-beat variation of the SEMD locations was significantly reduced (p < 0.001) when estimated at 15 % RMS[subscript n] compared to the earliest activation time (EAT). In addition, the 5–95 % interval of the estimated interelectrode distance error decreased exponentially as the number of beats used to estimate a median beat increased. When the number of beats was 4 or larger, the 5–95 % interval was smaller than 3.5 mm (the diameter of a commonly used catheter). In conclusion, the optimal time for the SEMD estimation is at 15 % of RMS[subscript n], and at that time instant a median beat estimated from 4 beats is associated with a beat-to-beat variability of the SEMD location that is appropriate for catheter ablation procedures.National Institutes of Health (U.S.) (grant 1RO1HL103961

Cardiac Activation Mapping using Ultrasound Current Source Density Imaging.

Intracardiac ablation procedures to correct drug-resistant arrhythmias require accurate maps of cardiac activation. Conventional methods are time-consuming and have poor spatial resolution (5- 10 mm). The goal of this dissertation was to develop a new method, Ultrasound Current Source Density Imaging (UCSDI), to map biological currents. UCSDI is based on the acousto-electric (AE) effect, a modulation of the electric resistivity by acoustic pressure. If a current passes through the focal region of an ultrasound transducer, a voltage modulated at the ultrasonic frequency can be measured with a pair of electrodes located distal to the focal zone. By sweeping the focal zone, UCSDI can map a distributed current field. UCSDI has several potential advantages as a technique for mapping cardiac activation currents: high spatial resolution determined by the typically sub-mm focal characteristics of the ultrasound beam, short mapping time using electronically steered ultrasonic beams, and automatic registration with B-mode ultrasound images without sophisticated mathematical algorithms. UCSDI was first validated by mapping an artificially generated 2D current distribution. It was compared to sequential electrode mapping, computer simulation as well as to an inverse algorithm. In this study it was possible to use UCSDI to locate monopolar current sources to within 1-mm of their true locations without making any prior assumptions about the source geometry. UCSDI was then used to detect and map biological currents in an isolated rabbit heart. Both UCSDI and normal low frequency electrocardiograms (ECG) were measured simultaneously by tungsten electrodes embedded in the left ventricle. The motion of the heart was significantly reduced by perfusing it with an excitation contraction de-coupler. Measured UCSDI maps showed temporal and spatial patterns consistent with a spreading activation wave and timing consistent with normal ECG signals. UCSDI was then combined with ultrasonic strain imaging in a new method for electromechanical imaging. This combined method was used to make localized measurements of electromechanical delay. This method could be useful in cardiac resynchronization therapy for placing pacemaker leads.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60687/1/rolafsso_1.pd