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: 3845352
• 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/3845352
• 关键词: brain metabolism; computer simulation; deoxyglucose; fluorine; glucose metabolism; mathematical model; model design /development; positron emission tomography; radionuclides; radiotracer

Due to the limited spatial resolution and partial volume effects of positron emission tomography (PET), most tissue regions studied with PET 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. All quantitative work up to now has made the simplifying assumption that the tissues are homogeneous, and serious misinterpretations of results obtained by use of these methods have occurred. We have studied the effects of tissue heterogeneity on determination of local cerebral glucose utilization. Mathematical models to describe the kinetics of deoxyglucose or flurordeoxyglucose 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 [18F]fluorodeoxyglucose and PET were identified. We are currently developing new techniques for analysis of time-series data from tracer studies in which the underlying kinetic models have not yet been established. These techniques will enable us to build appropriate kinetic models of new tracers and to extend mathematical models of currently used tracers to additional physiological and pathophysiological conditions.

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)，大多数组织区域均采用 PET 研究 在生理和/或生化方面是异质的 正在检查的过程以及有关浓度 组织中相关的标记化合物。到目前为止所有的定量工作 做出了简化的假设，即组织是均匀的，并且 对使用这些方法获得的结果的严重误解 已经发生。 我们研究了组织异质性对 局部脑葡萄糖利用率的测定。 数学模型 描述脱氧葡萄糖或氟脱氧葡萄糖摄取的动力学 在异质组织中的代谢得到开发和验证 模拟、动物和人类研究。 最合适的动力 脑测量模型和最佳实验方案 [18F]氟脱氧葡萄糖和 PET 的人类葡萄糖利用率 确定。 我们目前正在开发用于时间序列分析的新技术 来自示踪剂研究的数据，其中基础动力学模型尚未 尚未成立。 这些技术将使我们能够构建 新示踪剂的适当动力学模型并扩展数学 目前使用的示踪剂模型以附加生理和 病理生理条件。