Brain Temperature Control During Functional Activation

现代人脑正电子发射断层扫描(PET)成像的一项基本发现，即流向正常人脑激活区域的血流量大大超过了氧气消耗，这一发现在文献中引发了关于导致这种现象的可能机制的广泛讨论。众所周知，氧气输送并不是体循环的唯一功能。其他作用包括向组织输送营养物质和其他必需物质，清除废物，调节温度。在这些功能中，局部脑血流量在局部脑温调节中的作用几乎没有受到关注。大脑中的热量主要是由于氧化代谢产生的。它主要是通过血液流动来清除的。在休息状态下，热量的产生和排出之间的平衡使大脑温度保持在恒定的水平。然而，在大脑功能活动期间，局部血流和新陈代谢的增加可能会局部破坏这种平衡，并改变功能活动区和周围组织的大脑温度。这是一个重要的问题，因为温度极大地改变了代谢反应的速度(每摄氏度约8%)，即血红蛋白对氧气的亲和力，因此可能会影响大脑的表现--无论是健康的还是患病的。这一建议旨在提供数据，扩展我们对神经系统生理和代谢控制之间的关系的理解。这项拨款申请的主要目标是：开发能够同时监测大脑温度和氧化代谢变化的磁共振技术。拟议的工作包括磁共振技术的实现，脑温度调节的生物物理模型的开发，以及基于贝叶斯概率理论的数据处理的数学算法。通过磁共振测量一系列健康受试者在功能激活过程中人脑温度变化的空间分布和相应的氧代谢变化，确定这些变化的范围及其对刺激强度和持续时间的依赖关系。以确定在功能激活过程中，与氧气消耗相比，血流量不成比例增加对大脑温度调节的影响。这些结果的潜在影响是重大的。这是一种强有力的工具，可用于分析代谢和生理控制的耦合，以及阐明MR的基础血氧水平依赖对比的细节。

A fundamental discovery of modern human brain imaging with positron emission tomography (PET) that blood flow to activated regions of the normal human brain increases substantially more than oxygen consumption has lead to a broad discussion in the literature concerning possible mechanisms responsible for this phenomenon. It is well known that oxygen delivery is not the only function of systemic circulation. Additional roles include delivery of nutrients and other required substances to the tissue, waste removal, and temperature regulation. Among these other functions, the role of regional cerebral blood flow in local brain temperature regulation has received scant attention. Heat in the brain is produced mostly due to oxidative metabolism. It is removed chiefly by blood flow. The balance between heat production and removal in resting state maintains brain temperature at a constant level. However, a local increase in the blood flow and metabolism during brain functional activity can locally destroy this balance and alter brain temperature in the region of functional activity and surrounding tissue. This is an important issue since temperature substantially changes (by about 8 percent per each degree of centigrade) rates of metabolic reactions, the affinity of hemoglobin for oxygen, and, consequently, may affect brain performance - both healthy and diseased. This proposal seeks to provide data extending our understanding of the relationship between physiologic and metabolic control in nervous system. The major goals of this grant application are: To develop MR techniques that allow simultaneous monitoring of changes in brain temperature and oxidative metabolism. The proposed work includes implementations of MR techniques, development of biophysical models of brain temperature regulation and mathematical algorithms based on Bayesian probability theory for data processing. To measure by means of MR the spatial distribution in the changes of human brain temperature and the corresponding changes in oxygen metabolism during functional activation in a series of healthy subjects; to determine the range of these changes and their dependence on stimulus strength and duration. To determine the consequences of the disproportionate increase in blood flow compared to oxygen consumption, which occurs during functional activation, on brain temperature regulation. The potential implications of these results are significant. A powerful tool presents itself for analysis of the coupling of metabolic and physiologic control and for elucidation of details of the fundamental Blood Oxygenation Level Dependent contrast in MR.