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 生物化学过程被检查，并相对于浓度， 组织中相关标记化合物的含量。 最定量 到目前为止的工作已经做出了简化的假设，即组织是 均匀;这不仅导致不准确的量化，而且 对某些研究结果的严重误解。 我们有 研究了组织异质性对测定局部 脑葡萄糖利用和局部脑血流量。 数学 描述脱氧葡萄糖或氟脱氧葡萄糖的动力学的模型 在异质组织中的摄取和代谢得到了发展， 在模拟、动物和人体研究中的日期。 最合适的 动力学模型和最佳实验方案的测量 用[18F]氟脱氧葡萄糖和PET研究人脑葡萄糖利用 被确认了身份 正在开发其他工具，用于分析时间序列数据 从示踪剂研究。 这些工具将有助于构建 新示踪剂的动力学模型和数学模型的推广 目前使用的示踪剂，以其他生理和病理生理 条件 我们优化并建立了一个新的 光谱分析技术不同于传统的分析， 它不依赖于动力学模型的先验假设， 假设组织均匀。我们目前正在应用 多指数模型的谱分析技术，例如 从血浆中清除标记的分子，以及 确定钆-二亚乙基三胺五， 乙酸（Gd-DTPA），一种用于MRI研究的顺磁性造影剂。

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 concentra- tions 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 vali- dated 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 [18F]fluorodeoxyglucose and PET were identified. Additional tools are being developed for the analysis of time-series data from tracer studies. These tools will 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 are currently applying the spectral analysis technique to multiexponential models, e.g. those for clearance of labeled molecules from the plasma, and to the problem of identifying the kinetic properties of gadolinium-diethylenetriaminepenta- acetic acid (Gd-DTPA), a paramagnetic contrast agent used in MRI studies.