OCT News 2013 Student Paper Awarded to Pei Ma from Case Western Reserve University
Pei Ma from Case Western Reserve University was a winner of the 2013 OCT News Student Paper Award for her submission “Developing Technologies for Electrophysiology Imaging in Embryonic Hearts.” Below is a summary of her work:
Abstract: Congenital heart defects (CHDs) are one of the most common and devastating birth defects. Abnormal electrical activity at early stage of heart development can lead to severe CHDs. However, most developmental cardiology studies have not addressed the influential role of electrical activity in CHD etiology due to difficulties in early stages such as the embryonic hearts being too fragile for electrode recording, signal being too weak, etc. All existing studies have been done in 2D. We, for the first time, built an optical mapping (OM) and optical coherence tomography (OCT) integrated system, acquired electrical-activation map on 3D heart surface, and achieved panoramic OM of embryonic hearts.
Significance: CHDs are frequently life-threatening and require surgical correction in the newborn. The mechanisms of CHDs have been the focus of much study but they remain largely unclear. Evidence has shown that many forms of CHDs initiate from the early looping stage by disturbing functions (conduction, contraction, biomechanical forces, etc). The regulatory feedback loop involving cardiac structure and cardiac function is poorly understood mainly because of the lack of proper imaging tools to assess forces on the early looping heart and their resultant effects on cardiogenesis. Cardiac conduction system (CCS) is crucial in heart development by generating coordinated beating. Defects in CCS can cause CHDs by altering patterns of contraction of the myocardium, in turn affecting blood flow and the hemodynamics of the heart. For example, a large percentage of CHDs involve valvular defects, which can result from abnormal conduction or flow patterns during early cardiogenesis. However, electrical activity in early stage heart development is very poorly studied because the small heart size causes difficulty for electrode recording and typical optical imaging methods suffer from low SNR. Among a few existing studies, all of them have been done in 2D, which limits the understanding of heterogeneity of conduction patterns.
Multi-modality imaging technology: Optical mapping (OM) uses potentiometric fluorescent dyes and fast cameras to image electrical activity of the heart over a large field of view. OM has made an enormous impact on the study of cardiac electrophysiology and has advanced our understanding of mechanisms of electrical propagation and metabolism. Optical coherence tomography (OCT) is a newly developed, powerful non-invasive imaging modality. Due to the high resolution (2-30μm), sufficient penetration into tissue (1-2mm), adequate field of view, and extremely high speed (500kHz line rate), OCT is the best suited imaging modality for imaging avian and mouse cardiac development in vivo. Being similar to ultrasound, Doppler OCT is the functional extension of OCT, which can acquire flow information and absolute velocity maps to determine shear rate on the endothelium and endocardium. These direct quantitative structural and biomechanical data provided by OCT will facilitate our understanding of how alterations in cardiac structure and function can affect each other to influence heart development. To gain more insight into the etiology of CHDs, it is crucial to understand the interplay between electrical activity and contraction at very early stages, when CHDs may be initiated. Thus, an OM and OCT integrated system was built to promote the study of conduction in 3D and the interplay between excitation and contraction mechanisms.
3D Activation Map and Panoramic OM: Conduction velocity is one of the most important parameters that OM brings. However, 2D conduction velocity calculations can be inaccurate and non-consistent because embryonic heart can be severely twisted and angled in many situations. Using the integrated system, OM activation information and OCT structural information can be acquired at the same time. Image registration technique has been used for matching multimodality images. Conduction velocity calculations by taking the structure and angle into consideration has the potential to be more accurate and consistent, thus bringing more reliable results. Heterogeneous property of conduction patterns ensures coordinated beating. Panoramic OM by imaging two sides of the heart tube using OM and OCT brought the possibility of studying the heterogeneity of conduction in early stage embryonic hearts. These new technologies will allow us to address numerous unanswered experimental questions.