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。 正在开发和优化新的工具，用于分析 来自示踪剂研究的时间序列数据。这些工具有助于 新型示踪剂动力学模型的建立及扩展 目前使用的附加生理示踪剂的数学模型 以及病理生理条件。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。我们目前正在应用光谱分析技术 多指数模型，例如用于清除放射性示踪剂的模型 电浆。未来的计划包括研究 磁共振成像测量脑血流率的不均一性 动脉水的自旋反转和MRI血流的验证 动物放射自显影技术的比较 [C-14]本实验室先前发展的碘安替比林法。

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 are being 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 are currently applying the spectral analysis technique to multiexponential models, e.g. those for clearance of radiotracers from the plasma. Future plans include the study of the effects of heterogeneity on rates of cerebral blood flow measured with MRI using spin inversion of arterial water, and validation of the MRI blood flow technique in animals by comparison with the autoradiographic [C-14]iodoantipryine method previously developed in this laboratory.