Understanding brain energy metabolism and cerebral blood flow using advanced MRI approaches

脑氧代谢率(CMRO2)是大脑耗氧率，是反映大脑活力和功能的最重要的生理指标之一。区域CMRO2的量化为了解大脑能量需求和神经信号的代谢成分提供了关键工具。我们的主要假设是，脑代谢的区域性测量，加上脑血流量(CBF)的同步区域性测量，将为更好地定量理解大脑生理学和功能神经成像研究提供基础。 目前用于量化区域性CMRO2的金标准是正电子发射断层扫描。然而，这种方式使受试者暴露在高剂量的辐射下，因此不适合重复研究。目前MRI对CMRO2无创定量的研究主要集中在质子(1H)成像上，使其成为迄今为止最有前途的技术。然而，存在许多技术挑战，如采集时间长、空间分辨率差、非特异性信号定位等，这些问题必须得到解决，然后才能使用区域CMRO2来了解基本的人脑生理。这项提议将解决这些技术挑战，并使用1H MRI实现快速和强大的区域新陈代谢全脑地图。一种有前景的替代方法是超极化129Xe(HP 129Xe)MRI，它可以快速测量血流量和动、静脉氧合，血池特定信号，并且没有背景干扰，但尚未用于CMRO2标测。尽管HP 129Xe MRI带来了更多的技术挑战，但它可能使我们能够放松对1H MRI所做的一些生理假设。 该项目的长期目标是利用MRI增强我们对局部脑生理和新陈代谢的了解。短期目标是开发一种新的可靠的1H MRI方法，用于基于CBF和静脉血氧饱和度的测量来对啮齿动物的CMRO2进行高分辨率区域定量。我们还将利用我们令人鼓舞的飞行员数据，使用HP 129Xe MRI开发第一个在体内测量啮齿动物大脑中局部CMRO2的方法，并将其与我们的1H MRI测量进行比较。 总而言之，我的计划将利用先进的MRI方法开发新的、非侵入性的、活体的、局部的CMRO2测量方法，这将为研究大脑能量代谢和血流提供一个框架。这将使广泛的应用成为可能，例如研究发育中的大脑以及在运动和睡眠期间的局部氧合。此外，CMRO2的绝对区域性测量将促进对由多个相互竞争的生理过程组成的功能神经成像信号的解释。在更好地理解单个信号成分之前，无法对神经活动的MRI测量进行唯一解释。

The cerebral metabolic rate of oxygen (CMRO2) is the rate of oxygen consumption by the brain and is one of the most important physiological indicators of brain vitality and function. The quantification of regional CMRO2 provides a critical tool for understanding cerebral energy demands and the metabolic components of neural signalling. Our overarching hypothesis is that regional measures of cerebral metabolism, coupled with simultaneous regional measures of cerebral blood flow (CBF) will provide the basis for a better quantitative understanding of cerebral physiology and functional neuroimaging studies. The current gold standard for quantification of regional CMRO2 is positron emission tomography. However, this modality exposes subjects to high doses of radiation and thus is not suitable for repeated studies. Recent MRI research on non-invasive CMRO2 quantification has mostly focused on proton (1H) imaging, making it the most promising technique to date. However, there are many technical challenges, such as long acquisition time, poor spatial resolution and non-specific signal localization, which must be addressed before regional CMRO2 can be used to gain an understanding of basic human cerebral physiology. This proposal will address these technical challenges and enable rapid and robust whole-brain maps of regional metabolism using 1H MRI. A promising alternative approach is hyperpolarized 129xenon (HP 129Xe) MRI, which offers rapid measurement of blood flow and arterial and venous oxygenation, blood pool specific signal, and no background interference, but has not yet been utilized for CMRO2 mapping. Although HP 129Xe MRI presents more technical challenges, it may enable us to relax some of the physiological assumptions made with 1H MRI. The long-term goal of this program is to enhance our understanding of regional brain physiology and metabolism using MRI. The short term objectives are to develop a novel robust 1H MRI protocol for high resolution regional quantification of CMRO2 in rodents based on measures of CBF and venous oxygen saturation. We will also develop the first in vivo measurement of regional CMRO2 in the rodent brain by exploiting our encouraging pilot data using HP 129Xe MRI and compare it against our 1H MRI measurements. In summary, my program will develop novel, non-invasive, in vivo, regional CMRO2 measures using advanced MRI methods which will provide a framework for investigating brain energy metabolism and blood flow. This will enable a wide range of applications such as investigating regional oxygenation in the developing brain, and during exercise and sleep. Moreover, absolute regional measures of CMRO2 will advance the interpretation of functional neuroimaging signals, which are comprised of multiple competing physiological processes. MRI measures of neural activity cannot be uniquely interpreted until individual signal components are better understood.