NONINVASIVE MEASUREMENT OF DRUG CONCENTRATIONS

这项工作的目标是开发一种光学仪器， 一种真实的时间测量方法， 组织中药物或其他化合物的绝对浓度。新 计算方法，将Mie理论纳入Monte Carlo 传输代码，用于组织中光子传输的建模，将用于 第一时间允许确定的有效路径历史， 光子在组织中的不同距离。光学分析 光谱将能够分离光散射， 吸收系数的组织，并允许确定 药物浓度。光纤探头将允许这样的测量， 直接或通过内窥镜进行。 药物在特定组织位置的浓度和动力学 身体通常很难确定，只有考虑到 给药剂量或血清测量。对于化疗， 正常组织的剂量反应曲线与 在治疗过程中必须利用的肿瘤组织。的能力 快速、定量和非侵入性地测量 特定的药物和其他化合物，特别是化疗剂， 具体的器官部位，将提供简洁的好处，研究 药代动力学和一般临床药理学。并没有 目前存在一种测量药物浓度的非侵入性方法 在靶组织中，甚至是侵入性方法，如微透析， 应用有限。 我们将展示一种仪器和诊断方法， 通过光纤测量的弹性散射光谱学 探测器，在广泛的波长范围内，从近紫外到 近红外线将组装改进的光谱仪，并且 计算代码将用于模拟光子传输， 光纤探头的改进设计。用于分析 光谱和推断药物浓度将被改进。的 仪器将应用于选定的药物的药代动力学研究 化学疗法和光动力治疗剂在实验室动物。 光学测量将与标准侵入性测定进行比较 结果，通常为HPLC，用于校准目的。

The goal of this work is the development of an optical instrument and method for measuring in real time, and with site-specificity, the absolute concentrations of drugs or other compounds in tissue. New computational methods, incorporating Mie theory into a Monte Carlo transport code, for modeling of photon transport in tissue, will for the first time allow determination of the effective path histories of photons over varying distances in tissue. Analysis of the optical spectra will enable the separation of the optical scattering and absorption co-efficients of the tissue, and permit determination of the drug concentrations. Fiber-optic probes will permit such measurements to be conducted directly or through endoscopes. The concentrations and kinetics of drugs at specific tissue locations in the body are generally difficult to determine, given only the administered dosage or blood serum measurements. For chemotherapy, it is the difference between the dose-response curves of normal tissue and tumor tissue that must be exploited during treatment. The ability to rapidly, quantitatively and non-invasively measure the concentration of specific drugs and other compounds, especially chemotherapy agents, at specific organ sites, would provide succinct benefits to the study of pharmacokinetics and to clinical pharmacology in general. There does not currently exits a non-invasive method of measuring drug concentrations in the target tissue, and even invasive methods, such as microdialysis, have limited application. We will demonstrate an instrument and a diagnostic method which invokes elastic scattering spectroscopy for measurements through fiber-optic probes, over a broad range of wavelengths from the near-ultraviolet to the near-infrared. Improved spectrometers will be assembled, and the computational codes will be used to model the photon transport, enabling improved designs of fiber-optic probes. The algorithms to analyze the spectra and deduce drug concentrations will be refined. The instrumentation will be applied to pharmacokinetic studies of selected chemotherapy and photodynamic-therapy agents in laboratory animals. Optical measurements will be compared with standard invasive assay results, generally HPLC, for purposes of calibration.