Optical Imaging to Help Eradicate Damage to the Cardiac Conduction System

by Micaela Harris
October 10, 2022

Currently, there are only rough anatomical landmarks to help cardiac surgeons prevent accidental damage to the cardiac conduction system (CCS) – a network of cells that send signals to the heart to contract, producing heartbeats. Because the CCS is not visible anatomically, inadvertent injury to the CCS remains a potential complication in heart surgery. It would be very valuable to have an optical imaging method to detect the CCS. Most previous research on optical imaging has focused on tumor detection, specifically labeling the tumor tissue that is to be surgically removed. A potential new method to help combat accidental damage to the CCS is to use antibodies coated with fluorescent dyes to label the CCS so it is visible during surgery. Therefore, optical imaging presents an opportunity to enable detection of tissue regions that normally are not seen by the naked eye, such as the CCS region in the heart.

3D volumetric analyses of a mouse heart, following anti-contactin 2 antibody-IR800 dye injection, illustrating the high-resolution labeling of the CCS. Please refer to the full article for real-time imaging in vivo and full details.

To enable direct visualization of the CCS and help prevent injuries during heart surgery, a team of researchers at Stanford University, led by William R. Goodyer, MD, PhD and Sean M. Wu, MD, PhD, focused on contactin 2, a cell surface marker specifically expressed within the CCS. By injecting anti-contactin 2 antibodies linked to a near infrared dye into mice, the investigators were able to illuminate and map out the entire conduction system. After successfully demonstrating CCS detection using anti-mouse contactin 2 antibodies, the investigators turned to human contactin 2 and screened and isolated a monoclonal Fab fragment to human contactin 2 by phage display and showed that the Fab can also bind human contactin 2 with high affinity. In addition to contactin 2, the investigators validated other candidate surface markers that exhibit specific expression in subcomponents (e.g. sinoatrial node, atrioventricular node, etc.) of the CCS and demonstrated the CCS-specific binding of an anti-neuroplastin antibody by imaging. These results confirm the broad utility of antibody-dye conjugates to visualize the entire CCS as well as its subcomponents within the heart.

This study, recently published in The Journal of Clinical Investigation, lays the groundwork for creating specific antibodies that can potentially be used in precision therapy and enable clinical imaging of heart structures that have been impossible to observe before. The investigators developed a human specific antibody that targets cells in the CCS, which can ultimately make the conduction system visible to heart surgeons during operations. To our knowledge, this is the first study to provide possible solutions for the in vivo molecular targeting of cardiac structures. In the future, this method has the potential to be translated to other structures of the heart, and perhaps even other organs. The methodologies detailed in this study provide the opportunity to improve treatments of life-threatening cardiac diseases and promote healthy cardiac function in patients who have undergone heart surgery.

Additional Stanford Cardiovascular Institute-affiliated investigators who contributed to this study include Benjamin M Beyersdorf, MD; Lauren Duan; Nynke S van den Berg, MD; Sruthi Mantri; Francisco X Galdos; Nazan Puluca, MD; Elise R Robinson, PhD; Dillan P. Cogan, PhD; Darren Salmi, MD; Stephan Rogalla, MD, PhD; and Chaitan Khosla, PhD.

William Goodyer, MD, PhD 

Sean M. Wu, MD, PhD