Caldwell J H, Kroll K, Li Z, Seymour K, Link J M, Krohn K A
Department of Bioengineering, Veterans Administration Medical Center, and the University of Washington, Seattle 98108, USA.
J Nucl Med. 1998 Aug;39(8):1327-34.
The purpose of this study was to validate an axially distributed blood-tissue exchange model for the quantitation of cardiac presynaptic sympathetic nervous system function that could be applied to PET images. The model accounts for heterogeneity in myocardial blood flow, differences in transport rates of 11C-meta-hydroxyephedrine (mHED) across the capillary endothelium and/or neuronal membranes, the virtual volumes of distribution in the interstitial space and neuron and retention of mHED in the neuronal vesicles.
Multiple indicator outflow dilution and residue detection methods were used to measure the kinetics of radiolabeled intravascular space and interstitial space markers and 11C-mHED in isolated perfused rat heart at baseline and during norepinephrine neuronal transporter blockade with desipramine (DMI). The outflow dilution and residue detection data were modeled with a multiple pathway, four-region, axially distributed model of blood-tissue exchange describing flow in the capillary and exchange between regions using permeability-surface area products with units of clearance of milliliters per minute per gram. Meta-hydroxyephedrine may enter the nerve terminal via membrane transport, where it may be sequestered by first-order unidirectional uptake within vesicles. Release of mHED from the vesicles is modeled via exchange with the interstitial space.
After intracoronary injection, mHED transport across the capillary endothelium and in the interstitial space closely followed that of sucrose. Subsequently, mHED was retained in the heart, whereas sucrose washed out rapidly. With DMI the outflow dilution curves more closely resembled those of sucrose. Model parameters reflecting capillary-interstitial kinetics and volumes of distribution were unchanged by DMI, whereas parameters reflecting the neuronal transporter process and volumes of distribution in the nerve terminal and vesicular sequestration were markedly decreased by DMI. Application of the model to a pilot set of canine PET images of mHED suggests the feasibility of this approach.
Meta-hydroxyephedrine kinetics in the heart can be quantitated using an axially distributed, blood-tissue exchange model that accounts for heterogeneity of flow, reflects changes in neuronal function and is applicable to PET images.
本研究的目的是验证一种轴向分布的血液-组织交换模型，用于定量心脏突触前交感神经系统功能，该模型可应用于正电子发射断层扫描（PET）图像。该模型考虑了心肌血流的异质性、11C-间羟基麻黄碱（mHED）跨毛细血管内皮和/或神经元膜的转运速率差异、间质空间和神经元中的虚拟分布容积以及mHED在神经元囊泡中的滞留情况。
采用多指示剂流出稀释和残留检测方法，在基线状态以及用去甲丙咪嗪（DMI）阻断去甲肾上腺素神经元转运体期间，测量离体灌注大鼠心脏中放射性标记的血管内空间和间质空间标志物以及11C-mHED的动力学。流出稀释和残留检测数据用一种多途径、四区、轴向分布的血液-组织交换模型进行建模，该模型描述了毛细血管中的血流以及各区域之间的交换，使用的通透表面积乘积单位为每分钟每克清除毫升数。间羟基麻黄碱可能通过膜转运进入神经末梢，在那里它可能被囊泡内的一级单向摄取所隔离。mHED从囊泡中的释放通过与间质空间的交换进行建模。
冠状动脉内注射后，mHED跨毛细血管内皮和在间质空间中的转运与蔗糖的转运密切相关。随后，mHED保留在心脏中，而蔗糖迅速被清除。使用DMI时，流出稀释曲线更类似于蔗糖的曲线。反映毛细血管-间质动力学和分布容积的模型参数不受DMI影响，而反映神经元转运过程以及神经末梢和囊泡隔离中的分布容积的参数则被DMI显著降低。将该模型应用于一组mHED犬PET图像的初步研究表明了这种方法的可行性。
心脏中的间羟基麻黄碱动力学可以使用一种轴向分布的血液-组织交换模型进行定量，该模型考虑了血流的异质性，反映了神经元功能的变化，并且适用于PET图像。
