基于可调谐低相干激光光谱的新生儿经皮胆红素浓度的测定

Due to the fast and noninvasive detection way, transcutaneous bilirubin (TCB) measurement is widely applied in the clinical aided diagnosis of jaundice and bilirubin encephalopathy of the newborn. However at present TCB is still confined to the screening for hyperbilirubinemia as a result of the relatively poor accuracy of TCB, rather than a replacement technique for the total serum bilirubin (TSB) determination from an invasive blood sample. Reasons for this limited clinical application are that absorption and scattering of optical signal with broad spectrum will lead to the large error of bilirubin chromophore concentration, and measurement inaccuracy of TCB in the process of detecting local positioning signals will also give rise to the measurement error. For the above reasons, this project is planned to establish the experimental test system of neonatal transcutaneous bilirubin concentration based on low-coherencespectroscopy (LCS) of the wide-band tunable semiconductor laser which will be used to overcome defects resulted from a wide range measurement by a traditional TCB way. Meanwhile dispersion compensation feedback loop or parallel coupling loop will be constructed by the use of adjustable delay fiber to build low coherence spectrum.with high resolution. We will exploit more accurate spectroscopic technique to improve the accuracy and clinical applicability of noninvasive neonatal bilirubin measurement. By carrying on this project, we hope to achieve some breakthroughs in the basic application research on the measurement of bilirubin concentration, which will provide some key technical supports for constructing the new detection system of neonatal bilirubin measurement.

经皮胆红素浓度测定(TCB)因其快捷无创的检测方式在临床新生儿的黄疸及胆红素脑病辅助诊断方面有着广泛的应用，但TCB较差的测量准确性使其在临床上仍然局限于对高胆红素病症的甄别方面，而不是作为侵入式血液采样胆红素测量(TSB)的替代技术。其原因是宽光谱光信号的吸收和散射会导致胆红素色团的浓度出现较大误差，且TCB在测量过程中探测信号局部定位的不准确性也会导致测量误差的出现。本项目基于以上原因拟构建基于可调谐低相干激光光谱的新生儿经皮胆红素浓度实验测试系统，采用宽带可调谐半导体激光克服传统TCB大范围测定所造成的缺陷；同时利用可调延时光纤构成的色散补偿反馈回路或并行耦合回路来构建高分辨率的低相干光谱，探究通过更为准确的光谱学手段来提高新生儿无创式胆红素浓度测量的准确性和临床适用性。该项目的实施，有望在胆红素浓度检测的基础应用研究方面获得突破，为构建新型经皮新生儿胆红素测量提供若干关键技术支持。

项目基于可调谐半导体激光器传输理论，构建光注入可调谐激光经皮胆红素浓度测量系统，探究通过低相干激光光谱测量手段来实现对新生儿无创式经皮胆红素浓度测量(TCB)。项目首先建立单光注入可调谐激光器传输模型，对不同注入条件和测量条件下获取低相干、高复杂度测量光信号的系统参数范围进行标定研究。以此为基础，构建单光注入可调谐激光TCB系统，完成对新生儿皮肤及其下毛细血管中胆红素色团和血红蛋白色团光谱散射系数的测定，发现对于相干程度低、复杂度大的光波信号，胆红素色团光谱散射系数覆盖的光谱范围更广，更有利于胆红素浓度的测量。研究还发现，TCB与侵入式血液采样胆红素测量(TSB)存在正相关性，对于复杂度较高的测量光信号，TCB表现出与TSB之间更强的关联性，表明低相干、高复杂度光信号更有利于TCB准确测定。项目还构建了双光注入可调谐激光器传输系统，利用有效带宽和自相关函数对偏振分辨可调谐激光信号的带宽、复杂度及相干特征进行了定量评价，获取了高质量探测光信号的参数调控区域。并基于此架构建立双光注入光反馈可调谐激光TCB系统，发现双光注入可调谐系统相较于单光注入系统，有着相对更好的测量敏感度，同时双光注入可调谐系统可提供更为丰富的参数调节，更有利于获取复杂度更高的光信号，从而能准确的反映出胆红素浓度随光谱散射强度变化的关系。此外，我们初步研究了可变偏振光注入可调谐激光器传输模型，分析可变偏振光注入可调谐半导体激光器系统中的传输光信号的强度特性，以及此系统注入光偏振角变化输出低相干高复杂度光信号的参数范围，这为后续采用此架构开展的TCB测量提供了有力的参数依据。通过该项目的实施，使我们对可调谐激光光谱信号在胆红素浓度测量方面开展一些有意义的科学研究，探索并掌握基于可调谐低相干激光调控的科学方法，希望该研究内容能为构建临床新生儿血液胆红素测量提供相关技术支持。