KINETIC MODELING OF TISSUE HETEROGENEITY IN METABOLISM AND BLOOD FLOW STUDIES

代谢和血流研究中组织异质性的动力学建模

• 批准号: 3759472
• 负责人: K SCHMIDT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3759472
• 关键词: analytical method; brain metabolism; chemical kinetics; clearance rate; contrast media; deoxyglucose; diethylenetriaminepentaacetate; fluorine; glucose metabolism; mathematical model; method development; model design /development; positron emission tomography

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.

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)，以及较小程度的磁力断层扫描 共振成像 (MRI)，使用这些成像研究大多数组织区域 模式在生理和/或方面是异质的 正在检查的生化过程以及关于浓度 组织中相关标记化合物的变化。 最定量 迄今为止的工作已经做出了简化的假设，即组织是 同质；这不仅导致量化不准确，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局部测定的影响 脑葡萄糖利用率和局部脑血流量。 数学 描述脱氧葡萄糖或氟脱氧葡萄糖动力学的模型 异质组织中的摄取和代谢得到开发并验证 最早出现在模拟、动物和人类研究中。 最合适的 用于测量的动力学模型和最佳实验方案 [18F]氟脱氧葡萄糖和 PET 检测人类脑葡萄糖利用率 被识别出来。 正在开发用于分析时间序列数据的其他工具 来自示踪剂研究。 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扩展 目前使用的示踪剂可用于额外的生理和病理生理学 状况。 我们优化并建立了新的属性 与传统分析不同的光谱分析技术 它不依赖于动力学模型的先验假设，也不依赖于 基于组织同质性的假设。我们目前正在应用 多指数模型的谱分析技术，例如那些为 从血浆中清除标记分子，以及解决 确定钆-二亚乙基三胺五-的动力学性质 乙酸 (Gd-DTPA)，一种用于 MRI 研究的顺磁性造影剂。