NONINVASIVE MEASUREMENT OF DRUG CONCENTRATIONS

这项工作的目标是开发一种光学仪器和 实时测量的方法，并具有站点特异性， 组织中药物或其他化合物的绝对浓度。新的 将Mie理论融入蒙特卡罗的计算方法 用于模拟组织中的光子传输的传输代码将用于 首次允许确定有效路径历史 组织中不同距离的光子。关于光学特性的分析 光谱将使光学散射和 组织的吸收系数，并允许测定 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。 人体特定组织部位的药物浓度和动力学 身体通常很难确定，因为只有 给药剂量或血清测量。对于化疗来说，它是 正常组织和正常组织剂量-反应曲线的差异 在治疗过程中必须利用的肿瘤组织。有能力 快速、定量、非侵入性地测量空气中的 特定药物和其他化合物，特别是化疗药物，请参阅 具体的器官部位，将为研究提供简洁的好处 药代动力学和一般临床药理学。没有 目前存在一种非侵入性的药物浓度测量方法 在靶组织中，甚至是侵入性方法，如微透析， 应用有限。 我们将演示一个工具和一种诊断方法，它调用 光纤测量中的弹性散射光谱学 探测器，波长范围从近紫外光到 近红外线。改进后的光谱仪将被组装，并 计算代码将用于对光子传输进行建模，从而实现 改进了光纤探头的设计。分析这些数据的算法 光谱和推断药物浓度将得到精炼。这个 仪器将用于所选药物的药代动力学研究 实验动物的化学疗法和光动力疗法药物。 光学测量将与标准的侵入性检测进行比较 结果，通常是高效液相色谱法，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.