Nadiarnykh Oleg, Plotnikov Sergey, Mohler William A, Kalajzic Ivo, Redford-Badwal Deborah, Campagnola Paul J
University of Connecticut Health Center, Department of Cell Biology, Center for Cellular Analysis and Modeling, Farmington, Connecticut 06030, USA.
J Biomed Opt. 2007 Sep-Oct;12(5):051805. doi: 10.1117/1.2799538.
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.
我们使用定量二次谐波产生（SHG）成像显微镜来研究人成骨不全症（OI）的oim小鼠模型中的胶原基质组织。OI是一种遗传性疾病，其中I型胶原纤维要么组织异常，要么细小，导致临床表现为反复骨折以及与胶原组成组织相关的其他病症。利用SHG对超分子组装的极高敏感性，我们研究了这种方法是否可用于区分正常组织和oim组织。通过比较SHG强度、纤维形态、偏振各向异性和信号方向性，我们表明在骨、肌腱和皮肤的野生型（WT）和疾病状态下获得了统计学上不同的结果。所有这些光学特征都与oim组织中更无序的胶原基质一致，并且这些结果进一步与oim小鼠已知的较弱力学性能一致。虽然目前的工作显示了SHG在小鼠模型中区分正常和疾病状态的能力，但我们认为我们的结果为将SHG用作人类OI的临床诊断工具提供了一个框架。我们进一步认为，所描述的SHG指标可应用于其他以胶原组装异常为特征的结缔组织疾病。
