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多种互补方法的结合能否提高基于光谱的胃肠道疾病诊断效果?以乳糜泻为模型疾病的原理研究

Can Coupling Multiple Complementary Methods Improve the Spectroscopic Based Diagnosis of Gastrointestinal Illnesses? A Proof of Principle Study Using Celiac Disease as the Model Illness.

机构信息

Dodd-Walls Centre for Photonic and Quantum Technologies, Department of Chemistry, University of Otago, Dunedin 9054, New Zealand.

Southern Community Laboratories, Dunedin 9016, New Zealand.

出版信息

Anal Chem. 2021 Apr 27;93(16):6363-6374. doi: 10.1021/acs.analchem.0c04963. Epub 2021 Apr 12.

DOI:10.1021/acs.analchem.0c04963
PMID:33844904
Abstract

Spectroscopic methods are a promising approach for providing a point-of-care diagnostic method for gastrointestinal mucosa associated illnesses. Such a tool is desired to aid immediate decision making and to provide a faster pathway to appropriate treatment. In this pilot study, Raman, near-infrared, low frequency Raman, and autofluoresence spectroscopic methods were explored alone and in combination for the diagnosis of celiac disease. Duodenal biopsies ( = 72) from 24 participants were measured using the full suite of studied spectroscopic methods. Exploratory principal component analysis (PCA) highlighted the origin of spectral differences between celiac and normal tissue with celiac biopsies tending to have higher protein relative to lipid signals and lower carotenoid spectral signals than the samples with normal histology. Classification of the samples based on the histology and overall diagnosis was carried out for all combinations of spectroscopic methods. Diagnosis based classification (majority rule of class per participant) yielded sensitivities of 0.31 to 0.77 for individual techniques, which was increased up to 0.85 when coupling multiple techniques together. Likewise, specificities of 0.50 to 0.67 were obtained for individual techniques, which was increased up to 0.78 when coupling multiple techniques together. It was noted that the use of antidepressants contributed to false positives, which is believed to be associated with increased serotonin levels observed in the gut mucosa in both celiac disease and the use of selective serotonin reuptake inhibitors (SSRIs); however, future work with greater numbers is required to confirm this observation. Inclusion of two additional spectroscopic methods could improve the accuracy of diagnosis (0.78) by 7% over Raman alone (0.73). This demonstrates the potential for further exploration and development of a multispectroscopic system for disease diagnosis.

摘要

光谱方法是提供胃肠道黏膜相关疾病即时诊断方法的一种很有前途的方法。这种工具旨在辅助即时决策,并提供更快的途径以获得适当的治疗。在这项初步研究中,单独和组合使用拉曼、近红外、低频拉曼和自发荧光光谱方法来诊断乳糜泻。对 24 名参与者的 72 份十二指肠活检样本使用全套研究光谱方法进行了测量。探索性主成分分析(PCA)突出了乳糜泻和正常组织之间光谱差异的起源,与具有正常组织学的样本相比,乳糜泻活检组织的蛋白质相对脂质信号更高,类胡萝卜素光谱信号更低。基于组织学和整体诊断对所有光谱方法组合的样本进行分类。基于分类的诊断(每个参与者的多数规则)为个别技术获得了 0.31 到 0.77 的灵敏度,当将多种技术结合在一起时,灵敏度提高到 0.85。同样,个别技术获得了 0.50 到 0.67 的特异性,当将多种技术结合在一起时,特异性提高到 0.78。值得注意的是,使用抗抑郁药会导致假阳性,这被认为与乳糜泻和使用选择性 5-羟色胺再摄取抑制剂(SSRIs)时观察到的肠道黏膜中 5-羟色胺水平升高有关;然而,需要进行更多的研究以确认这一观察结果。增加两种额外的光谱方法可以将诊断的准确性提高 7%(0.78),而仅使用拉曼则为 0.73。这表明进一步探索和开发用于疾病诊断的多光谱系统具有潜力。

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