Department of Physics, University of Texas at El Paso, El Paso, TX 79968, USA.
Department of Biomedical Engineering, University of Texas at El Paso, El Paso, TX 79968, USA.
Biosensors (Basel). 2018 Apr 8;8(2):38. doi: 10.3390/bios8020038.
Defining the pathogenesis of renal osteodystrophy (ROD) and its treatment efficacy are difficult, since many factors potentially affect bone quality. In this study, confocal Raman microscopy and parallel statistical analysis were used to identify differences in bone composition between healthy and ROD bone tissues through direct visualization of three main compositional parametric ratios, namely, calcium content, mineral-to-matrix, and carbonate-to-matrix. Besides the substantially lower values found in ROD specimens for these representative ratios, an obvious accumulation of phenylalanine is Raman spectroscopically observed for the first time in ROD samples and reported here. Thus, elevated phenylalanine could also be considered as an indicator of the disease. Since the image results are based on tens of thousands of spectra per sample, not only are the average ratios statistically significantly different for normal and ROD bone, but the method is clearly powerful in distinguishing between the two types of samples. Furthermore, the statistical outcomes demonstrate that only a relatively small number of spectra need to be recorded in order to classify the samples. This work thus opens the possibility of future development of in vivo Raman sensors for assessment of bone structure, remodeling, and mineralization, where different biomarkers are simultaneously detected with unprecedented accuracy.
定义肾性骨营养不良(ROD)的发病机制及其治疗效果具有一定难度,因为许多因素可能会影响骨质量。在本研究中,通过直接观察钙含量、矿物质/基质和碳酸盐/基质这三个主要成分参数比值,利用共聚焦拉曼显微镜和并行统计分析,确定了健康和 ROD 骨组织之间的骨成分差异。除了在 ROD 标本中发现这些代表性比值明显降低外,本研究首次在 ROD 样本中拉曼光谱观察到苯丙氨酸的明显积累,并在此进行了报道。因此,升高的苯丙氨酸也可以被认为是该疾病的一个指标。由于图像结果基于每个样本数万次光谱的测量,因此正常和 ROD 骨之间的平均比值在统计学上具有显著差异,并且该方法在区分两种类型的样本方面显然非常有效。此外,统计结果表明,为了对样本进行分类,只需记录相对较少数量的光谱。因此,这项工作为未来开发用于评估骨结构、重塑和矿化的体内拉曼传感器开辟了可能性,在此过程中可以以前所未有的准确性同时检测到不同的生物标志物。