Multimodal imaging of harmonophores and application of high content imaging for early cancer detection

Abstract

Multimodal imaging techniques aim to improve the efficiency of current cancer diagnostic methods and provide greater insight into the tumor microenvironment. Second harmonic generation microscopy (SHG) is a non-destructive imaging technique available to researchers for detecting the changes in the morphology of collagen. Researchers aim to understand the role played by changes in collagen morphology in tumor development. Hybrid imaging methods are able to combine the specificity of collagen detection by SHG with other narrow ranged fluorescent or biochemical markers, leading to higher efficiency of cancer diagnosis and grading. Different cancer diagnoses have been detected efficiently by these methods, with higher clarity than standard protocols. Higher contrast between malignant and normal tissue, achieved using high content imaging using SHG, have also allowed for development of non-invasive follow-up of cancer treatment methods. The aim of this review is to provide an overview of the analysis techniques currently used to further improve the efficiency of cancer detection.

Poly-l-arginine modifications alter the organization and secretion of collagen in SKH1-E mice

“…26 SHG microscopy is a high information, dyeless, non-linear optical technique that can visualize collagen organization and type in diverse tissues. 6,16,27 By examining how chemical modifications alter collagen organization, rational design of biomaterials can be improved.…”

“…14,15 SHG microscopy of triple helical collagen fibers can provide more information about the collagen response through susceptibility tensor analysis. 12,16 These parameters are linked to the materials properties, based on the molecular origins of the collagen signal arising from the ratio of their methylene to peptide bonds. 17 Polarization resolved SHG microscopy is capable of differentiating between diverse types of collagen in dermal samples by generating a map of the susceptibility tensor components.…”

Second Harmonic Generation Imaging Reveals Entanglement of Collagen Fibers in the Elephant Trunk Skin Dermis

“…Collagen I (COL1) is the primary collagen found within the skin; it has a fibrillar structure and can therefore be detected with second harmonic generation (SHG) imaging. SHG is a nonlinear optical imaging technique that selectively detects noncentrosymmetric molecules, including type I and II collagen with no labelling (Boddupalli and Bratlie, 2015;Chen, Nadiarynkh, Plotnikov, and Campagnola, 2012). SHG microscopy works by viewing the skin sample at a specific frequency that excites the fibrillar structure of COL1; the resulting image exhibits half the wavelength of the original wavelength used, hence the term "second harmonic."…”

Second harmonic generation microscopy of collagen organization in tunable, environmentally responsive alginate hydrogels

“…41,42 Second harmonic generation (SHG) microscopy allows for sensitive, high-content-imaging of not just secreted collagen, but also collagen organization. 43,44 In this study, we use SHG microscopy and subsequent data analysis to examine how hydrogel stiffness can tune collagen organization from aligned to stochastic when encapsulating NIH/3T3 fibroblasts. The ability to influence collagen organization is a relatively unexplored area with previous research focused on visualizing the collagen alignment in neocartilage secreted by primary mesenchymal stem cells showing no direct cause-effect relationships.…”