Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, with an estimated prevalence of 0.4% to 1% in the general population, increasing with age (8% for people over 80). In addition to drug treatments, electrophysiology-based treatment modalities such as ablation treatment are wide employed for arrhythmias. To treat the AF the most common anatomical target for ablation is the entrance of pulmonary veins and the surrounding tissue. Currently, radio-frequency (RF) energy is generally used to ablate the described sites in the heart. It is difficult to control the ablation pattern using RF ablation which also has limitations in creating deep lesions. If the total electrical isolation in cardiac tissue cannot be achieved, recurrence becomes highly likely. High-intensity focused ultrasound (HIFU) methods have been attempted lately for pulmonary vein isolation, mainly motivated by the promise of creating deep and controlled ablation patterns. However, these attempts suffered from a lack of direct imaging guidance and consequently collateral damage in surrounding tissues such as the phrenic nerve and the esophagus. The well-known shortcomings of RF ablation methods and the limitations presented by the early HIFU results clearly indicate the need for a system that integrates image guidance with effective and well-controlled ablation methods. We propose to develop devices and systems to address the summarized issues. In our proposed scheme, conventional ultrasound imaging is used for anatomical guidance and target identification, HIFU for tissue ablation, and photoacoustic imaging for monitoring lesion formation. The proposed device is based on the capacitive micromachined ultrasonic transducer (CMUT) technology. CMUTs are proven to have minimal self-heating in continuous wave operation, unlike their piezoelectric counterparts with high internal dielectric losses. This self-heating of piezoelectric transducers was partly responsible for the collateral damage experienced in early cardiac HIFU attempts. CMUTs can also be implemented in large arrays that are suitable for dual imag- ing/therapeutic operation.
The specific aims of the proposed work are as follows: 1) Develop a large-scale prototype (15-mm footprint) CMUT array for use in initial feasibility studies and a clinically suitable, small-scale (7-mm footprint) CMUT array integrated with supporting frontend circuits and backend systems, capable of HIFU delivery combined with ultrasound and photoacoustic imaging. 2) Conduct initial feasibility studies on ex-vivo tissue samples and in-vivo open-chest and open-thigh animal models using system subcomponents to determine optimal parameters for both HIFU ablation and photoacoustic imaging. 3) Conduct cardiac studies in the porcine model utilizing the miniaturized integrated probe (7-mm footprint) utilizing a closed chest, minimally invasive model for insertion of the probe through a small incision through the intercostal space.

Public Health Relevance

The successful development of a combined high-intensity focused ultrasound (HIFU) and photoacoustic/ultrasound imaging system will significantly improve the treatment of atrial fibrillation, which is a common form of arrhythmia that affects an estimated 2.7 million Americans. The successful completion of this project will also provide the necessary imaging and therapy technologies that will improve the effectiveness of interventions to the heart for treating other cardiac anomalies.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Lee, Albert
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Stanford University
Overall Medical
United States
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Zhang, Xiao; Wu, Xun; Adelegan, Oluwafemi Joel et al. (2018) Backward-Mode Photoacoustic Imaging Using Illumination Through a CMUT With Improved Transparency. IEEE Trans Ultrason Ferroelectr Freq Control 65:85-94
Yoon, Hyo-Seon; Chang, Chienliu; Jang, Ji Hoon et al. (2016) Ex Vivo HIFU Experiments Using a $32 times 32$ -Element CMUT Array. IEEE Trans Ultrason Ferroelectr Freq Control 63:2150-2158
Yamaner, F Yalç?n; Zhang, Xiao; Oralkan, Ömer (2015) A three-mask process for fabricating vacuum-sealed capacitive micromachined ultrasonic transducers using anodic bonding. IEEE Trans Ultrason Ferroelectr Freq Control 62:972-82
Rajendran, Pradeep S; Buch, Eric; Shivkumar, Kalyanam (2014) Marshaling the autonomic nervous system for treatment of atrial fibrillation. J Am Coll Cardiol 63:1902-3