Ultrafast Acoustoelectric Imaging of the Heart In Vivo – ULTRAFASTACOUSTOELEC

The heart is driven by an electrical activation that propagates in cells and triggers their concerted contraction, which results in efficient pumping of the blood. The electrical activation sequence can be disrupted by disease, a condition referred to as conduction disorder, or arrhythmia. For example, upper chamber, i.e., atrial, fibrillation (AF) is the most prevalent arrhythmia and is associated with a 5-fold increase in risk of stroke. Moreover, ventricular conduction disorders can lead to heart failure (HF), which is the leading cause of hospitalization in patients above 65 years old, and is associated with exceptionally high morbidity and mortality rates: 50% of patients die within five years of being diagnosed. However, there exists no clinical imaging modality that can noninvasively and directly map the electrical activation of tissues to improve our understanding of these complex diseases, perform better diagnoses, and contribute to the development of novel therapeutic approaches.
The acoustoelectric effect has recently been shown to provide contrast directly from current densities by detecting the signature of ultrasound-modulated electrical impedance using high frequency electrodes. A few studies have been conducted and demonstrated the potency of the approach by mapping the electrical currents in ex vivo tissues. Yet, to this day, the acoustoelectric effect associated with biological action potentials has never been observed in vivo, due to the challenges inherent in the detection of small electrical signals at high frequency and the limited imaging frame rate of conventional ultrasound emission techniques.
In this study, our objective is to demonstrate the feasibility of the real-time, noninvasive, and direct mapping of the electrical activation of heart tissues in vivo. Our method of Ultrafast Acoustoelectric Imaging (UAI) can image one hundred times faster than conventional methods and relies on the latest high-performance electronics for high signal-to-noise ratio measurements. Our specific aims are
A) Optimize UAI instrumentation and image formation algorithms using a Langendorf rat heart model
B) Validate UAI against electrical mapping in an open-chest sheep heart model
C) Demonstrate the feasibility of transthoracic Ultrafast Acoustoelectric Imaging in the normal human heart
These specific aims reflect the high risk associated with the development of an imaging modality for the electrical activation of tissue. Indeed, while most imaging modalities are typically developed and optimized using ‘phantoms’, i.e., tissue-mimicking objects with controlled physical properties, no existing phantom can reproduce, even approximately, the complex biochemistry leading to the generation of action potentials. Therefore, the optimization and validation of UAI for biological application must be performed in active tissue, in which the electrical activation can be artificially controlled, such as in the heart. Specific aim 1 will determine the imaging parameters required, i.e., emission frequency, frame rate, and pressure, to obtain the optimal UAI signals and images using isolated beating rat hearts in a Langendorf model in a controlled environment. Specific Aim 2 will validate, in a large animal heart model, the agreement between the UAI images and the true electrical activation sequence measured with implanted electrodes in the in vivo setting. Finally, Specific Aim 3 will demonstrate the clinical feasibility in normal human subjects.
The outcomes of this study are expected to yield the only imaging methodology for the organ-independent mapping of the electrical activation in vivo, at no or little additional cost to that of standard ultrasound imaging. No imaging modality can currently map the electrical activation of tissue directly. The high impact of this OH Risque application lies in the fact that UAI can easily be integrated into any commercial echographic system for immediate translation to the clinic.