Imaging Collagen in Scar Tissue: Developments in Second Harmonic Generation Microscopy for Biomedical Applications

Abstract

The ability to respond to injury with tissue repair is a fundamental property of all multicellular organisms. The extracellular matrix (ECM), composed of fibrillar collagens as well as a number of other components is dis-regulated during repair in many organs. In many tissues, scaring results when the balance is lost between ECM synthesis and degradation. Investigating what disrupts this balance and what effect this can have on tissue function remains an active area of research. Recent advances in the imaging of fibrillar collagen using second harmonic generation (SHG) imaging have proven useful in enhancing our understanding of the supramolecular changes that occur during scar formation and disease progression. Here, we review the physical properties of SHG, and the current nonlinear optical microscopy imaging (NLOM) systems that are used for SHG imaging. We provide an extensive review of studies that have used SHG in skin, lung, cardiovascular, tendon and ligaments, and eye tissue to understand alterations in fibrillar collagens in scar tissue. Lastly, we review the current methods of image analysis that are used to extract important information about the role of fibrillar collagens in scar formation.

Autofluorescence imaging for recurrence detection in skin cancer postoperative scars

“…More sophisticated scar imaging techniques had been also proposed, but clinical application associated with detection of recurrence of cancer is still lacking. For example, nonlinear optical microscopy can be used to examine fibrilar collagen in scar tissue, delivering noninvasive and depth resolved diagnostic metrics for collagen structure alterations and collagen volume density . The differentiation between keloids and normal skin is possible, based on collagen bundles disorientation, thickness increase and swirling pattern specifically found in keloids .…”

Study on collagen parameters in vulvar cancer and preneoplastic lesions by Second Harmonic Generation microscopy

“…The use of SHG can be considered a drawback, because of the costs of the equipment and difficulty in managing it. However, it should be acknowledged that this cost has been decreasing over the last few years, what may allow SHG to become included in the diagnostic practice in the near future 11,12 .…”

“…The SHG has been increasingly being used to study COL, due to its high sensitivity and specificity. It is a quantitative nonlinear optical microscopy technique that captures images from biological tissues having polarized anisotropic structures, such as COL 11,12 .…”

Imaging the Cardiac Extracellular Matrix

“…Consequently, these methods are currently used to image patient tissue samples or for preclinical research. For example, they have been used to characterize how diseases alter collagen networks in the myocardium and vasculature [23, 28, 46, 71]. Each of these two categories contains several imaging methods, which range in sensitivity (signal strength), specificity (signal source), and cost.…”