Impact of collagen crosslinking on the second harmonic generation signal and the fluorescence lifetime of collagen autofluorescence

Lutz, Vivien; Sattler, Martin; Gallinat, Stefan; Wenck, Horst; Poertner, Ralf; Fischer, F.

doi:10.1111/j.1600-0846.2011.00549.x

Cited by 63 publications

(55 citation statements)

References 18 publications

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“…For significantly thicker whole tissue samples, the SHG signal detected in the backward direction (B-SHG) could be employed, though the use of B-SHG signal as a metric of collagen content requires more detailed studies focused on the dependence of the signal on fiber diameter and organization [40, 41], and warrants further investigation. For example, inhibition of LOX in dermal fibroblast culture increased B-SHG intensity by nearly twofold compared to control [42]. Additionally, more detailed analysis of the SHG signal, either in terms of its polarization dependence [28, 43] or through algorithms that assess organization at the fiber level [44] could improve understanding of the interdependence of collagen crosslinking, organization and local or bulk mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

Lysyl oxidase-mediated collagen crosslinks may be assessed as markers of functional properties of tendon tissue formation

et al. 2014

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Mechanical property elaboration of engineered tissues is often assumed on the basis of gene and protein characterizations, rather than mechanical testing. However, we recently demonstrated mechanical properties are not consistently correlated with matrix content and organization during embryonic tissue development. Based on this, mechanical properties should be assessed independently during natural or engineered tissue formation. Unfortunately, mechanical testing is destructive, and thus alternative means of assessing these properties are desirable. In this study, we examined lysyl oxidase (LOX)-mediated crosslinks as markers for mechanical properties during embryonic tendon formation and the potential to detect them non-destructively. We used tandem mass spectrometry (LC-MS/MS) to quantify changes in hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP) crosslink density in embryonic chick tendon as a function of developmental stage. In addition, we assessed a multiphoton imaging approach that exploits the natural fluorescence of HP and LP. With both techniques, we quantified crosslink density in normal and LOX-inhibited tendons, and correlated measurements with mechanical properties. HP and LP crosslink density varied as a function of developmental stage, with HP-to-dry mass ratio correlating highly to elastic modulus, even when enzymatic crosslink formation was inhibited. Multiphoton optical imaging corroborated LC-MS/MS data, identifying significant reductions in crosslink density from LOX inhibition. Taken together, crosslink density may be useful as a marker of tissue mechanical properties that could be assessed with imaging non-destructively and perhaps non-invasively. These outcomes could have significant scientific and clinical implications, enabling continuous and long-term monitoring of mechanical properties of collagen-crosslinked tissues or engineered constructs.

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Section: Discussionmentioning

confidence: 99%

Lysyl oxidase-mediated collagen crosslinks may be assessed as markers of functional properties of tendon tissue formation

et al. 2014

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“…Second harmonic generation (SHG) has a rich history in structural analysis of biological tissues (1)(2)(3)(4)(5), having been used to visualize structures including microtubule assemblies in brain tissue (6) and Caenorhabditis elegans embryos (7), collagen organization in tumors (8), pericardial tissue (9), human atrial myocardium (10), rat tails (11,12), corneas (13), and human skin (14), to cite just a select handful of representative studies. SHG has several properties that make it advantageous in biological imaging.…”

Section: Introductionmentioning

confidence: 99%

Imaging the Nonlinear Susceptibility Tensor of Collagen by Nonlinear Optical Stokes Ellipsometry

Dow

DeWalt

Sullivan

et al. 2016

Biophysical Journal

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Nonlinear optical Stokes ellipsometric (NOSE) microscopy was demonstrated for the analysis of collagen-rich biological tissues. NOSE is based on polarization-dependent second harmonic generation imaging. NOSE was used to access the molecular-level distribution of collagen fibril orientation relative to the local fiber axis at every position within the field of view. Fibril tilt-angle distribution was investigated by combining the NOSE measurements with ab initio calculations of the predicted molecular nonlinear optical response of a single collagen triple helix. The results were compared with results obtained previously by scanning electron microscopy, nuclear magnetic resonance imaging, and electron tomography. These results were enabled by first measuring the laboratory-frame Jones nonlinear susceptibility tensor, then extending to the local-frame tensor through pixel-by-pixel corrections based on local orientation.

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“…This increase in lifetime is in agreement with previous reports [40] that demonstrated collagen synthesis and cross-link formation in the tissue that is distantly or mildly affected by DMBA treatment used to induce breast tumors in rat. Increase in collagen cross-links has been associated with increase fluorescence lifetime [41]. Note that for the case shown in Fig.…”

Section: Flim Comparative Analysismentioning

confidence: 95%

Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques

Fatakdawala

Poti

Zhou

et al. 2013

Biomed. Opt. Express

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This work reports a multimodal system for label-free tissue diagnosis combining fluorescence lifetime imaging (FLIm), ultrasound backscatter microscopy (UBM), and photoacoustic imaging (PAI). This system provides complementary biochemical, structural and functional features allowing for enhanced in vivo detection of oral carcinoma. Results from a hamster oral carcinoma model (normal, precancer and carcinoma) are presented demonstrating the ability of FLIm to delineate biochemical composition at the tissue surface, UBM and related radiofrequency parameters to identify disruptions in the tissue microarchitecture and PAI to map optical absorption associated with specific tissue morphology and physiology. ©2013 Optical Society of America

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Impact of collagen crosslinking on the second harmonic generation signal and the fluorescence lifetime of collagen autofluorescence

Cited by 63 publications

References 18 publications

Lysyl oxidase-mediated collagen crosslinks may be assessed as markers of functional properties of tendon tissue formation

Lysyl oxidase-mediated collagen crosslinks may be assessed as markers of functional properties of tendon tissue formation

Imaging the Nonlinear Susceptibility Tensor of Collagen by Nonlinear Optical Stokes Ellipsometry

Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques

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