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Special Section on Optical Diagnostic Imaging from Bench to Bedside Instrumentation

Second harmonic generation imaging microscopy studies of osteogenesis imperfecta

[+] Author Affiliations
Oleg Nadiarnykh

University of Connecticut Health Center, Department of Cell Biology, Center for Cellular Analysis and Modeling, Farmington, Connecticut 06030

Sergey Plotnikov

Laboratory of Cell and Tissue Morphodynamics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892

William A. Mohler

University of Connecticut Health Center, Department of Genetics and Developmental Biology, Center for Cellular Analysis and Modeling, Farmington, Connecticut 06030

Ivo Kalajzic

University of Connecticut Health Center, Department of Reconstructive Services Farmington, Connecticut 06030

Deborah Redford-Badwal

University of Connecticut Health Center, Department of Oral Rehabilitation, Department of Craniofacial Sciences, Farmington, Connecticut 06030

Paul J. Campagnola

University of Connecticut Health Center, Department of Cell Biology, Center for Cellular Analysis and Modeling, Farmington, Connecticut 06030

J. Biomed. Opt. 12(5), 051805 (October 29, 2007). doi:10.1117/1.2799538
History: Received February 15, 2007; Revised July 06, 2007; Accepted August 09, 2007; Published October 29, 2007
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We have used quantitative second harmonic generation (SHG) imaging microscopy to investigate the collagen matrix organization in the oim mouse model for human osteogenesis imperfecta (OI). OI is a heritable disease in which the type I collagen fibrils are either abnormally organized or small, resulting in a clinical presentation of recurrent bone fractures and other pathologies related to collagen-comprised tissues. Exploiting the exquisite sensitivity of SHG to supramolecular assembly, we investigated whether this approach can be utilized to differentiate normal and oim tissues. By comparing SHG intensity, fibrillar morphology, polarization anisotropy, and signal directionality, we show that statistically different results are obtained for the wild type (WT) and disease states in bone, tendon, and skin. All these optical signatures are consistent with the collagen matrix in the oim tissues being more disordered, and these results are further consistent with the known weaker mechanical properties of the oim mouse. While the current work shows the ability of SHG to differentiate normal and diseased states in a mouse model, we suggest that our results provide a framework for using SHG as a clinical diagnostic tool for human OI. We further suggest that the SHG metrics described could be applied to other connective tissue disorders that are characterized by abnormal collagen assembly.

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© 2007 Society of Photo-Optical Instrumentation Engineers

Citation

Oleg Nadiarnykh ; Sergey Plotnikov ; William A. Mohler ; Ivo Kalajzic ; Deborah Redford-Badwal, et al.
"Second harmonic generation imaging microscopy studies of osteogenesis imperfecta", J. Biomed. Opt. 12(5), 051805 (October 29, 2007). ; http://dx.doi.org/10.1117/1.2799538


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