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Next generation MRI technologies for measuring brain oxygen metabolism

用于测量脑氧代谢的下一代 MRI 技术

基本信息

批准号：
EP/K025716/1
负责人：
Nicholas Blockley
金额：
$ 124.57万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FK025716%2F1
关键词：
Next generation MRI technologies measuring

项目摘要

The revolution of imaging the function of the brain using MRI, rather than just its structure, was kick started by the discovery of the blood oxygenation level dependent (BOLD) effect more than twenty years ago. As its name suggests this effect is dependent on blood oxygenation and is therefore sensitive to the rate at which the brain is consuming energy by burning glucose and oxygen (oxygen metabolism). Whilst BOLD functional MRI (fMRI) has enabled great improvements in our knowledge about the localisation of function it remains a qualitative measure of brain activity. By measuring oxygen metabolism we can take a direct look at the metabolic workload required to sustain this brain activity. Quantitative measurements of oxygen metabolism are possible using two techniques: calibrated BOLD and quantitative BOLD. Unfortunately neither method has reached its full potential. This is due in part to the complexity of these methods and requirements to perform complicated breathing challenges involving carbon dioxide. In both cases specialist knowledge is required, limiting the application of these methods to a small number of methodological research centres. The aim of this proposal is to remove these barriers enabling a broad spectrum of users to take advantage of these methods. Calibrated BOLD enables changes in oxygen metabolism, which are caused by performing a task or experiencing a stimulus, to be measured. However, in the current implementation of this method the participant must breathe air with added carbon dioxide. As well as the discomfort this causes, such experiments are difficult and time consuming to set up. In this proposal this so-called 'calibration' will be replaced by a simple measurement of the intrinsic relaxation properties of tissue. At a stroke, the set up of complicated equipment is removed and gas breathing is no longer required. This technique has the potential to be a required part of every fMRI experiment as it enables changes in baseline physiology to be obtained in a simple and quick manner. Such changes in baseline physiology between subjects and sessions can confound the interpretation of fMRI experiments leading to incorrect inferences.Quantitative BOLD enables resting baseline oxygen metabolism to be estimated by measuring the amount of oxygen extracted to serve metabolism (oxygen extraction fraction). The method relies on the theoretical understanding that the intrinsic relaxation properties of tissue are dependent on the total amount of deoxygenated haemoglobin that is present in the pixel being imaged. This is effectively dependent on the product of the blood volume and the oxygen extraction fraction. Therefore an accurate measurement of blood volume is critical for disentangling these effects. Currently this is achieved using a subtle signal variation predicted by theory. In this proposal blood volume will be measured using oxygen as a tracer. This new technique has the potential to realise much higher accuracy and reproducibility than the current method. It also fulfils an unmet need of the healthcare community: a measurement of resting oxygen metabolism. The only other established method to achieve this uses Positron Emission Tomography (PET). However, this method requires the use of three radioactive tracers and the associated dose of ionising radiation. The expense and complexity of this method means that there are very few sites within the UK that are able to perform such experiments. In contrast, MRI is widely available and most clinical sites have direct access to 100% oxygen within the imaging suite. Hence this method has the potential to vastly improve the diagnostic capability of the UK healthcare system at minimal expense.

使用MRI成像大脑功能而不仅仅是其结构的革命是由二十多年前发现的血氧水平依赖（BOLD）效应开始的。顾名思义，这种效应依赖于血液氧合，因此对大脑通过燃烧葡萄糖和氧气（氧代谢）消耗能量的速率敏感。虽然BOLD功能性磁共振成像（fMRI）使我们对功能定位的知识有了很大的提高，但它仍然是大脑活动的定性测量。通过测量氧代谢，我们可以直接观察维持这种大脑活动所需的代谢工作量。氧代谢的定量测量可以使用两种技术：校准BOLD和定量BOLD。不幸的是，这两种方法都没有充分发挥其潜力。这部分是由于这些方法的复杂性和执行涉及二氧化碳的复杂呼吸挑战的要求。在这两种情况下都需要专门知识，因此这些方法的应用仅限于少数方法研究中心。本提案的目的是消除这些障碍，使广大用户能够利用这些方法。校准BOLD可以测量由执行任务或经历刺激引起的氧代谢变化。然而，在该方法的当前实施方式中，参与者必须呼吸具有添加的二氧化碳的空气。除了这引起的不适之外，这样的实验设置起来也很困难和耗时。在这个提议中，这种所谓的“校准”将被组织的固有弛豫特性的简单测量所取代。在一个中风，设置复杂的设备被删除，不再需要气体呼吸。这项技术有可能成为每一个功能磁共振成像实验所需的一部分，因为它使基线生理学的变化能够以简单快速的方式获得。受试者和疗程之间的基线生理学的这种变化可能混淆fMRI实验的解释，导致不正确的推论。定量BOLD使静息基线氧代谢能够通过测量用于代谢的氧提取量（氧提取分数）来估计。该方法依赖于理论上的理解，即组织的固有弛豫特性取决于被成像的像素中存在的脱氧血红蛋白的总量。这实际上取决于血容量和氧提取分数的乘积。因此，准确测量血容量对于解开这些影响至关重要。目前，这是通过理论预测的微妙信号变化来实现的。在本提案中，将使用氧气作为示踪剂来测量血容量。这种新技术有可能实现比当前方法更高的准确性和再现性。它还满足了医疗保健界尚未满足的需求：静息氧代谢的测量。实现这一点的唯一其他已建立的方法是使用正电子发射断层扫描（PET）。然而，这种方法需要使用三种放射性示踪剂和相关的电离辐射剂量。这种方法的费用和复杂性意味着在英国很少有地点能够进行这样的实验。相比之下，MRI是广泛可用的，并且大多数临床站点在成像套件内可以直接获得100%的氧气。因此，这种方法有可能以最小的费用大大提高英国医疗保健系统的诊断能力。