Fluorescence optical imaging techniques have revolutionized the field of cardiac electrophysiology and advanced our understanding of complex electrical activities such as arrhythmias. However, traditional monocular optical mapping systems, despite having high spatial resolution, are restricted to a two-dimensional (2D) field of view. Consequently, tracking complex three-dimensional (3D) electrical waves such as during ventricular fibrillation is challenging as the waves rapidly move in and out of the field of view. This problem has been solved by panoramic imaging which uses multiple cameras to measure the electrical activity from the entire epicardial surface. However, the diverse engineering skill set and substantial resource cost required to design and implement this solution have made it largely inaccessible to the biomedical research community at large. To address this barrier to entry, we present an open source toolkit for building panoramic optical mapping systems which includes the 3D printing of perfusion and imaging hardware, as well as software for data processing and analysis. In this paper, we describe the toolkit and demonstrate it on different mammalian hearts: mouse, rat, and rabbit.
Heart rhythm disorders, known as arrhythmias, cause signi cant morbidity and are one of the leading causes of mortality. Cardiac arrhythmias are primarily treated by implantable devices, such as pacemakers and de brillators, or by ablation therapy guided by electroanatomical mapping.Pharmacological treatments are mostly ineffective. Both implantable and ablation therapies require sophisticated biointerfaces for electrophysiological measurements of electrograms and delivery of therapeutic stimulation or ablation energy. In this work, we report for the rst time on graphene biointerface for in vivo cardiac electrophysiology. Leveraging sub-micrometer thick tissue-conformable graphene arrays, we demonstrate sensing and stimulation of the open mammalian heart both in vitro and in vivo. Furthermore, we demonstrate graphene pacemaker treatment of a pharmacologically-induced arrhythmia, AV block. The arrays show effective electrochemical properties, namely interface impedance down to 40 Ohm×cm 2 , charge storage capacity up to 63.7 mC/cm 2 , and charge injection capacity up to 704 µC/cm 2 . Transparency of the graphene structures allows for simultaneous optical mapping of cardiac action potentials and calcium transients while performing electrical measurements and stimulation. Our report presents evidence of the signi cant potential of graphene biointerfaces for the future clinical device-and catheter-based cardiac arrhythmias therapies.
The human heart is an efficient electromechanical pump which provides oxygen and nutrients to all human organs. Each heartbeat is ignited and synchronized by an electrical action potential initiating and rapidly propagating through the heart's electrical system. Cardiovascular diseases, a leading cause of death in humans, disrupt this synchronous excitation. Heart rhythm disorders, known as arrhythmias, are particularly deadly. Cardiac arrhythmias are primarily treated by implantable pacemakers and defibrillators because pharmacological treatments are mostly ineffective. In this work, we report on graphene-only cardiac pacemakers as advanced cardiac biointerfaces. Leveraging sub-micrometer thick tissue-conformable graphene arrays, we are able to sense from and stimulate the heart, altering its functions, suggesting that the devices can be used for high-density functional interfacing with the heart. The arrays show effective electrochemical properties, namely interface impedance down to 40 Ohm x cm2, charge storage capacity up to 63.7 mC/cm2, and charge injection capacity up to 704 uC/cm2. Transparency of the structures allows for simultaneous optical mapping of cardiac action potentials and calcium transients while performing electrical measurements. Upon validating the graphene-based cardiac pacing in ex vivo mouse hearts, we performed in vivo cardiac pacing in a rat model with clinically induced arrhythmia. The condition was successfully diagnosed and treated using graphene biointerfaces.
Heart rhythm disorders, known as arrhythmias, cause significant morbidity and are one of the leading causes of mortality. Cardiac arrhythmias are primarily treated by implantable devices, such as pacemakers and defibrillators, or by ablation therapy guided by electroanatomical mapping. Pharmacological treatments are mostly ineffective. Both implantable and ablation therapies require sophisticated biointerfaces for electrophysiological measurements of electrograms and delivery of therapeutic stimulation or ablation energy. In this work, we report for the first time on graphene biointerface for in vivo cardiac electrophysiology. Leveraging sub-micrometer thick tissue-conformable graphene arrays, we demonstrate sensing and stimulation of the open mammalian heart both in vitro and in vivo. Furthermore, we demonstrate graphene pacemaker treatment of a pharmacologically-induced arrhythmia, AV block. The arrays show effective electrochemical properties, namely interface impedance down to 40 Ohm×cm2, charge storage capacity up to 63.7 mC/cm2, and charge injection capacity up to 704 µC/cm2. Transparency of the graphene structures allows for simultaneous optical mapping of cardiac action potentials and calcium transients while performing electrical measurements and stimulation. Our report presents evidence of the significant potential of graphene biointerfaces for the future clinical device- and catheter-based cardiac arrhythmias therapies.
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