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），并在较小程度上，磁 共振成像（MRI），使用这些成像研究的大多数组织区域 模态相对于生理和/或 生物化学过程正在审查，并就 组织中相关标记化合物的浓度。 最 到目前为止，定量研究已经做出了简化的假设， 组织是同质的;这不仅导致了不准确的 量化，但也严重误解的结果，在一些 问题研究我们研究了组织异质性对 局部脑葡萄糖利用和局部脑 血流 脱氧葡萄糖动力学的数学模型 或氟脱氧葡萄糖摄取和代谢的异质组织， 在模拟、动物和人体研究中开发和验证。 的 最合适的动力学模型和最佳的实验方案， 脑葡萄糖利用率的测定 鉴定了[F-18]氟脱氧葡萄糖和PET。 为分析时间序列开发和优化了新的工具 示踪剂研究的数据。 这些工具有助于构建 新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，以额外的生理和 病理生理条件。 我们优化并建立了 一种新的光谱分析技术，不同于 传统的分析，因为它不依赖于先验 动力学模型的假设，也不基于组织的假设 同质性我们还验证了频谱分析技术， 多指数模型，例如，用于清除放射性示踪剂的模型 血浆 我们开发了一种新的鲁棒方法， 估计和假设检验不依赖于统计 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.