The Effects of Capillary Transit Time Heterogeneity (CTH) on the Cerebral Uptake of Glucose and Glucose Analogs: Application to FDG and Comparison to Oxygen Uptake
The Effects of Capillary Transit Time Heterogeneity (CTH) on the Cerebral Uptake of Glucose and Glucose Analogs: Application to FDG and Comparison to Oxygen Uptake
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DOI：
10.3389/fncom.2016.00103
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发表时间：
2016-10-13
影响因子：
3.2
通讯作者：
Ostergaard, Leif
中科院分区：
文献类型：
--
作者：
Angleys, Hugo;Jespersen, Sune N.;Ostergaard, Leif
葡萄糖是大脑 ATP 的主要来源，但脑葡萄糖消耗 (CMRglc) 与其耗氧量 (CMRO2) 的关联程度仍不清楚。大脑氧葡萄糖指数 OGI = CMRO2/CMRglc 的测量表明，其摄氧量很大程度上足以满足氧化磷酸化。然而，在功能激活期间和某些疾病状态下，尽管脑血流（CBF）提供了足够的氧气，即所谓的有氧糖酵解，但脑组织似乎会产生乳酸。反过来，OGI 测量又依赖于方法，因为基于葡萄糖类似物摄取的估计取决于所谓的集总常数 (LC) 来得出 CMRglc。毛细血管通过时间异质性（CTH）被认为在功能激活期间和某些疾病状态下会发生变化，影响从血液中提取氧气的效率。我们开发了葡萄糖提取的三室模型来检查 CTH 是否也影响葡萄糖提取到脑组织中。然后，我们将该模型与之前的氧提取模型结合起来，以检查差异葡萄糖和氧提取是否可能有利于某些条件下的非氧化葡萄糖代谢。我们的模型预测葡萄糖摄取很大程度上不受血浆浓度变化的影响，而CBF和CTH的变化会不同程度地影响葡萄糖和氧的摄取。因此，功能性充血比氧摄取更促进葡萄糖摄取，在能量需求增加期间有利于有氧糖酵解。将我们的模型应用于葡萄糖类似物，我们观察到 LC 取决于生理状态，存在高估功能激活期间 CMRglc 相对增加高达 50% 的风险。
Glucose is the brain's principal source of ATP, but the extent to which cerebral glucose consumption (CMRglc) is coupled with its oxygen consumption (CMRO2) remains unclear. Measurements of the brain's oxygen-glucose index OGI = CMRO2/CMRglc suggest that its oxygen uptake largely suffices for oxidative phosphorylation. Nevertheless, during functional activation and in some disease states, brain tissue seemingly produces lactate although cerebral blood flow (CBF) delivers sufficient oxygen, so-called aerobic glycolysis. OGI measurements, in turn, are method-dependent in that estimates based on glucose analog uptake depend on the so-called lumped constant (LC) to arrive at CMRglc. Capillary transit time heterogeneity (CTH), which is believed to change during functional activation and in some disease states, affects the extraction efficacy of oxygen from blood. We developed a three-compartment model of glucose extraction to examine whether CTH also affects glucose extraction into brain tissue. We then combined this model with our previous model of oxygen extraction to examine whether differential glucose and oxygen extraction might favor non-oxidative glucose metabolism under certain conditions. Our model predicts that glucose uptake is largely unaffected by changes in its plasma concentration, while changes in CBF and CTH affect glucose and oxygen uptake to different extents. Accordingly, functional hyperemia facilitates glucose uptake more than oxygen uptake, favoring aerobic glycolysis during enhanced energy demands. Applying our model to glucose analogs, we observe that LC depends on physiological state, with a risk of overestimating relative increases in CMRglc during functional activation by as much as 50%.