Optical Imaging of Dynamic Collagen Processes in Health and Disease

Abstract

Collagen is a major structural component of nearly every tissue in the human body, whose hierarchical organization imparts specific mechanical properties and defines overall tissue function. Collagenous soft tissues are dynamic structures that are in a constant state of remodeling but are also prone to damage and pathology. Optical techniques are uniquely suited for imaging collagen in these dynamic situations as they allow for non-invasive monitoring with relatively high spatiotemporal resolution. This review presents an overview of common collagen dynamic processes associated with human health and disease and optical imaging approaches that are uniquely suited for monitoring, sensing, and diagnosing these changes. This review aims to 1) provide researchers with an understanding of the underlying optical properties of collagen that can be leveraged for extracellular matrix visualization and 2) present emerging opportunities for machine learning approaches to drive multiscale and multimodality solutions.

Effect of matrix properties on transmission and reflectance mode division-of-focal-plane Stokes polarimetry

“…Imaging in this mode involves the collection of mostly forward-scattered photons that provide thickness-averaged information of light interactions within the tissue, thus leaving no room for extraction of depth-dependent signals 20 . Reflectance mode polarimetry is more suitable for non-contact, ex vivo and in vivo imaging of bulk tissues because photons collected in this mode are backscattered and have undergone substantially more scattering events compared with their transmission mode counterparts 21 …”

“…20 Reflectance mode polarimetry is more suitable for non-contact, ex vivo and in vivo imaging of bulk tissues because photons collected in this mode are backscattered and have undergone substantially more scattering events compared with their transmission mode counterparts. 21 Despite its widespread usage, the full interpretation of results obtained from polarimetrybased techniques remains poorly defined. Output polarimetry values have been interpreted as being due to several different ECM properties: structural anisotropy, collagen crosslinking, or even differences in the molecular structure of the collagen type (e.g., type I versus type III collagen).…”

Label-free optical imaging of cell function and collagen structure for cell-based therapies

“…Label-free optical imaging provides advantages over other optical imaging techniques for quality control of cytotherapies. Although collagen architecture can be detected by other imaging techniques, such as polarized light microscopy (PLM) [ 24 ], optical coherence tomography (OCT) [ 25 ], and Raman spectroscopy [ 26 - 28 ], SHG imaging provides high specificity for collagen detection and high spatial resolution at deeps up to ~ 1 mm in tissue [ 29 ]. Similarly, NADH, FAD, and collagen structures can also be imaged with single-photon excitation, but the red-shifted excitation light of nonlinear imaging techniques including SHG imaging and autofluorescence lifetime imaging enables increased light penetration in 3D samples and tissues.…”

Quantifyingin vivocollagen reorganization during immunotherapy in murine melanoma with second harmonic generation imaging

“…2,3 Within the context of cancer, homeostasis is dysfunctional and cancer cells secrete excess amounts of MMPs, degrading the basement membrane and promoting malignant cell invasion into the interstitial matrix. 1,3 As the tumor progresses, cancer associated fibroblasts (CAFs) secrete excess type I and type II fibrillar collagen, and remodel the collagen morphology within the ECM. 4 Often, ECM morphology reconstruction results in linearized collagen and increased stiffening within cancer tissue.…”