Diagnosis of Crystalopathies via Raman Spectroscopy

通过拉曼光谱诊断晶体病

• 批准号: 7276958
• 负责人: Ozan Akkus
• 金额: $ 6.93万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-25 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276958
• 关键词: Raman spectrometry; arthritis; bioimaging /biomedical imaging; calcium phosphate; cholesterol; clinical research; crystallization; cystine; diagnosis design /evaluation; gout; human subject; hydroxyapatites; joint disorder; molecular /cellular imaging; musculoskeletal disorder diagnosis; oxalates; patient oriented research; pseudogout; synovial fluid; urate; xanthines

DESCRIPTION (provided by applicant): Misdiagnosis of the presence and the identity of crystal species in joint space are often penalized with the incorrect treatment of the arthropathic condition. The existing diagnostic standard of polarized imaging lacks specificity and sensitivity and it is largely limited to microscopically visible birefringent crystals. In the current study we propose Raman spectroscopy as an alternative for diagnostic technology for improved identification of crystal species in joint spaces. In Raman spectroscopy molecular vibrations are triggered through laser excitation and the reflected light holds information on the identity as well as on the amount of species in the observed region. The technique is currently utilized for arthroscopic in vivo diagnosis of other diseases; thus, based on this clinical potential it would be worthwhile to explore its analytical and clinical feasibility towards the assessment of crystal species involved in arthropathic conditions. The first phase of the proposed exploratory study will reveal the identification thresholds of various crystals that can be detected by Raman spectroscopy. Synthetic analogs of monosodium urate, calcium pyrophosphate dihydrate, hydroxyapatite, octacalcium phosphate, tricalcium phosphate, calcium oxalate, cholesterol, cystine and xanthine will be mixed with healthy synovial fluid samples at various concentrations and these mixtures will be analyzed at the macro level to detect the cumulative signal emanating from crystals. We will attempt to lower the identification thresholds by employing surf ace-enhanced Raman spectroscopy and by principal component analysis of the spectral data. During the second phase synovial fluid samples will be taken from patients and the presence or absence of crystals will be confirmed via compensated polarized microscopy, X-ray diffraction and alizarin staining. Aliquots of these samples will be subjected to Raman analysis to determine whether Raman analysis can detect the presence and identity of crystals in clinical samples. If this exploratory study demonstrates that the analytical limits of Raman analysis suffice to cover clinical concentrations of crystal species than comprehensive clinical studies can be conducted to assess the specificity and the sensitivity of the technique finally leading to the development of an arthroscopic Raman device.

描述（由申请人提供）：关节空间中晶体物种的存在和身份的误诊通常会因关节疗法的不正确治疗而受到惩罚。偏光成像的现有诊断标准缺乏特异性和灵敏度，并且在很大程度上仅限于显微可见的双重晶体。在当前的研究中，我们建议拉曼光谱法作为改善关节空间中晶体鉴定的诊断技术的替代方法。在拉曼光谱中，通过激光激发触发分子振动，并且反射的光符合所观察到的区域中的物种量以及有关物种的量。该技术目前用于关节镜在其他疾病的体内诊断中；因此，基于这种临床潜力，值得探索其分析性和临床可行性，以评估涉及关节炎条件的晶体物种。拟议的探索性研究的第一阶段将揭示可以通过拉曼光谱检测到的各种晶体的识别阈值。单钠尿酸钙，焦磷酸二氢酸钙，羟基磷灰石，磷酸二钙，磷酸二钙，磷酸三酸三酸酯，草酸钙，胆固醇，胱氨酸，氰固醇和Xananthine的合成类似物将与各种浓度和这些混合物的健康混合物在Macro cromporative cromprowing contration contry croment contry crompros contry contry crompros中混合。我们将尝试通过采用冲浪王牌增强的拉曼光谱和光谱数据的主要成分分析来降低识别阈值。在第二阶段，滑液样品将取自患者，并通过补偿的极化显微镜，X射线衍射和艾丽莎白染色来确认晶体的存在或不存在。这些样品的等分试样将进行拉曼分析，以确定拉曼分析是否可以检测到临床样品中晶体的存在和身份。如果这项探索性研究表明，与全面的临床研究相比，拉曼分析的分析限制足以覆盖晶体物种的临床浓度，以评估该技术的特异性和敏感性最终导致关节镜拉曼装置的发展。