KINETIC MODELING OF TISSUE HETEROGENEITY IN METABOLISM AND BLOOD FLOW STUDIES

由于有限的空间分辨率和部分体积效应 正电子发射断层扫描(PET)，以及较小程度的磁学成像 磁共振成像(MRI)，大多数组织区域都使用这些成像进行研究 对于生理和/或 正在检查的生化过程和关于 相关标记化合物在组织中的浓度。多数 到目前为止的定量工作做出了一个简化的假设，即 组织是同质的；这不仅导致了不准确 量化，也给一些对结果的严重曲解 学习。我们研究了组织异质性对 局部脑葡萄糖利用率和局部脑组织葡萄糖利用率的测定 血液流动。描述脱氧葡萄糖动力学的数学模型 或异质组织中氟脱氧葡萄糖的摄取和代谢 在模拟、动物和人体研究中开发和验证。这个 最合适的动力学模型和最优实验方案 慢性阻塞性肺疾病患者脑葡萄糖利用的测定 [F-18]氟代脱氧葡萄糖和正电子发射计算机断层扫描。 开发和优化了用于时间序列分析的新工具 来自示踪剂研究的数据。这些工具有助于构建 新型示踪剂的动力学模型及数学模型的推广 目前使用的示踪剂的其他生理和 病理生理条件。我们已经优化并建立了 一种新的光谱分析技术的特性 常规分析，因为它不依赖先验 动力学模型的假设也不是基于组织的假设 同质性。我们还验证了光谱分析技术以 多指数模型，例如放射性示踪剂清除模型 电浆。我们发展了一种新的参数稳健方法 不依赖于统计量估计和假设检验 测量数据的分布。

Due to the limited spatial resolution and partial volume effects of positron emission tomography (PET), and, to a lesser extent, of Magnetic Resonance Imaging (MRI), most tissue regions studied with these imaging modalities are heterogeneous with respect to the physiological and/or biochemical processes being examined and with respect to the concentrations of the relevant labeled compounds in the tissue. Most quantitative work up to now has made the simplifying assumption that the tissues are homogeneous; this has led not only to inaccurate quantification, but also to serious misinterpretations of results in some studies. We have studied the effects of tissue heterogeneity on determination of local cerebral glucose utilization and local cerebral blood flow. Mathematical models to describe the kinetics of deoxyglucose or fluorodeoxyglucose uptake and metabolism in heterogeneous tissues were developed and validated in simulation, animal, and human studies. The most appropriate kinetic model and optimal experimental protocol for the measurement of cerebral glucose utilization in man with [F-18]fluorodeoxyglucose and PET were identified. New tools were developed and optimized for the analysis of time-series data from tracer studies. These tools facilitate the construction of kinetic models of new tracers and the extension of mathematical models of currently-used tracers to additional physiological and pathophysiological conditions. We have optimized and established the properties of a new spectral analysis technique that differs from conventional analyses in that it does not rely on the a priori postulation of a kinetic model nor on the assumption of tissue homogeneity. We have also validated the spectral analysis technique to multiexponential models, e.g. those for clearance of radiotracers from the plasma. We have developed a new robust method for parameter estimation and hypothesis testing that doe snot depend on the statistical distribution of the measured data.