Imaging the Cardiac Extracellular Matrix

Abstract

Cardiovascular disease is the global leading cause of death. One route to address this problem is using biomedical imaging to measure the molecules and structures that surround cardiac cells. This cellular microenvironment, known as the cardiac extracellular matrix, changes in composition and organization during most cardiac diseases and in response to many cardiac treatments. Measuring these changes with biomedical imaging can aid in understanding, diagnosing, and treating heart disease. This chapter supports those efforts by reviewing representative methods for imaging the cardiac extracellular matrix. It first describes the major biological targets of ECM imaging, including the primary imaging target of fibrillar collagen. Then it discusses the imaging methods, describing their current capabilities and limitations. It categorizes the imaging methods into two main categories: organ-scale noninvasive methods and cellular-scale invasive methods. Noninvasive methods can be used on patients, but only a few are clinically available, and others require further development to be used in the clinic. Invasive methods are the most established and can measure a variety of properties, but they cannot be used on live patients. Finally, the chapter concludes with a perspective on future directions and applications of biomedical imaging technologies.

Extracellular Matrix in Cardiac Tissue Mechanics and Physiology: Role of Collagen Accumulation

“…Medical imaging techniques are generally noninvasive because they can be performed on a live subject with negligible risks; they are sometimes referred to as organ-scale imaging [25]. Primary medical imaging techniques include Magnetic Resonance Imaging (MRI), ultrasound and nuclear imaging.…”

“…Using the known mechanical properties of elastin and collagen (i.e., Young's Modulus), one can distinguish the relative contributions of ECM proteins to the tissue. Finally, cardiac nuclear imaging, including single-photon emission computed tomography (SPECT) and positron-emission tomography (PET), has been used to quantify the ECM content [25]. Radioactive molecular probes are used in these techniques.…”

Extracellular Matrix in Regulation of Contractile System in Cardiomyocytes

“…Cardiac ECM has been investigated with different methods. Pinkert et al overviewed the imaging technics for cardiac ECM [35], and Hacker [36] summarized different animal models with altered expression of genes related to cardiac ECM that reveal the role of individual matrix components. There are some excellent reviews that describe the composition and distribution of ECM in heart tissue [37] and characterize its alterations during heart development [13,38] and aging [39].…”

Collagen fiber regulation in human pediatric aortic valve development and disease

“…Pediatric CAVS produces excessive collagen deposition that mixes with other ECM proteins, creating a disorganized ECM structure, altering valvular function and leading to cardiac failure 5 , 15 , 16 . Although collagen deregulation is a hallmark of adult and pediatric valvular stenosis 5 , 17 , 18 and a potential prognostic and therapeutic target 19 , 20 , very little is known about the complexities of collagen fiber regulation in the human valve.…”