Friedrich-Alexander-Universität Erlangen-Nürnberg

Quantitative Morphometry of cells and tissues in chronic diseases and tissue engineering using Second Harmonic Generation Microscopy

Quantitative Morphometry of Cells and Tissues in Chronic Diseases and Tissue Engineering Using Second Harmonic Generation Microscopy

Chronic inflammatory diseases are associated with vast tissue remodeling that can lead to scarring and functional impairment especially in organs that are highly organized in their 3D structure. This is the case in inflammatory muscle disorders or heart diseases where contractile proteins become disorganized and out of regular lattice. Some biomolecules serve as intrinsic scatter’s for pulsed-laser excitation to produce second harmonic generation signals. Amongst medically relevant biomolecules, collagen and myosin are the most prominent. Multiphoton microscopy is suitable to perform a quantitative optical metrology approach to tissue remodeling already at the cellular level. This can be impressively demonstrated in muscle samples from disease models (muscular dystrophy) where chronic inflammation results in degeneration with imperfect cell repair (Fig.1) where diseased cells show twisted and distorted contractile myosin streaks within cells. This can be best appreciated in 3D reconstructions of cells. The technique is also suitable to monitor matrix architecture in natural cartilage or tissue engineered scaffolds that are being used for cell seeding. Many more medical and life science applications are to be established through the MBT group within SAOT.

Fig.1: A, Principle of optical tissue and cell slicing with two-photon excitation of biomolecules that produce second harmonic generation signals. B, example images from a healthy and a diseased (dystrophic) muscle including the 3D reconstruction of a whole XYZ volume. Natural cartilage also produces strong SHG signals through collagen.

References:

Wegner F, Schürmann S, Fink RHA, Vogel M & O FRIEDRICH (2009). Motor protein function in skeletal muscle: a multiple scale approach to contractility. IEEE Trans Med Imaging 28(10): 1632-1642.

Friedrich O, Both M, Weber C, Schürmann S, Teichmann MDH, v Wegner F, Fink RHA, Vogel M, Chamberlain JS & C Garbe (2009). Microarchitecture is severely compromised but motor protein function is preserved in dystrophic mdx skeletal muscle. Biophys J 98(4): 606-616.

Schürmann S, von Wegner F, Fink RH, FRIEDRICH O & M Vogel (2010). Second harmonic generation microscopy probes different states of motor protein interaction in myofibrils. Biophys J 99(6): 1842-1851.

Garbe C, Buttgereit A, Schürmann S & O FRIEDRICH (2011). Automated multi-scale morphometry of muscle disease from second-harmonic generation microscopy using tensor based image processing. IEEE Trans Biomed Eng, in press.

 

Mission

SAOT provides an interdisciplinary research and education program of excellence within a broad international network of distinguished experts to promote innovation and leadership in the areas

Optical Metrology
Optical Material Processing
Optics in Medicine
Optics in Communication and Information Technology
Optical Materials and Systems
and Computational Optics.