Applications of Intravital Nonlinear Microscopy in Cardiovascular Research

Abstract

Coordinated contraction of the heart allows for efficient pumping of blood to the body, supplying organs with oxygen necessary for metabolism. In heart disease, reduction of blood flow to heart muscle tissue can result in damage to the tissue over time. The adult heart, unlike other organs, has a limited capacity to recover from this damage causing the mechanical work the heart can perform to decline over time. While our ability to restore flow to the heart and mitigate abnormal electrically conducting tissue has improved over the last few decades, therapies which restore mechanical function improving cardiac output, through repair and healing of the cardiac muscle have not been realized in the clinic. Historic models used to study heart disease lack the ability to quantitative study the progression of individual cells within the living heart following an injury. Here I have taken some first steps in providing imaging methods and tools to allow the study of a more complete picture of heart disease in the context of the whole animal using multiphoton microscopy. I present methods for quantification of cellular resolved excitation and contraction, demonstrate the potential of THG as a label free signal to study the atherosclerotic plaque environment, and characterize some of the optical properties of the heart necessary to push the imaging depth accessible with current multiphoton technology.