Rapid, robust and non-invasive cerebral oxygenation measurements using MRI

描述(申请人提供)：氧提取分数(OEF)是一项重要的脑氧代谢参数，它为了解脑血管疾病的病理生理学、预测组织梗塞和患者预后提供关键信息，并可能确定将从治疗干预中受益的患者。已有研究表明，在慢性动脉粥样硬化性颈动脉闭塞患者中，脑组织氧摄取分数(OEF)的升高预示着随后发生中风的风险增加6-7倍。此外，在急性缺血性中风期间，以OEF升高和血流量减少为标志的“痛苦血流”已被用作“危险”组织的指示器，而该组织是治疗的目标。另一方面，在不筛查高危组织的情况下不加区别地进行治疗，可能会导致与治疗相关的严重并发症。因此，一种可靠的、非侵入性的OEF测量方法可以在常规的临床设置下获得，这将对适当的患者诊断和治疗有很大的影响。尽管它很重要，但大脑的氧合作用只能用15O正电子发射断层扫描(PET)来量化。然而，对现场回旋加速器的要求仅限于世界上少数几个医疗中心进行150度PET测量。在过去的十年中，在使用磁共振成像(MRI)的非侵入性定量OEF测量方面取得了重大的技术进步。虽然在健康人身上已经成功地获得了绝对的OEF测量，但由于许多未解决的问题在患者研究中特别具有挑战性，这些方法的临床实用性仍然很小。此外，全球或地区性OEF验证尚未在患者身上进行。在这项研究中，一个集成的PET/MR系统，允许真正同时采集PET和MR图像，将用于MR和PET OEF之间的直接比较，而不会出现与顺序成像相关的潜在混杂因素。该项目的总体目标是(1)开发一种新的MR OEF测量方法，该方法快速且可靠，以满足临床研究的需要；以及(2)在局灶性病理患者中使用同步的O15 PET测量来验证MR OEF测量方法。由于MR广泛可用，该项目的成功将允许在许多患者中获得PET可比OEF测量，并为未来将该方法整合到对时间敏感的患者管理决策中铺平道路。此外，这项建议的技术发展--减少磁共振成像伪影，提高测量效率，以及PET和MR扫描的协同作用--可以推广到许多其他神经成像研究。

DESCRIPTION (provided by applicant): Oxygen extraction fraction (OEF) is an important cerebral oxygen metabolic parameter that provides critical information for understanding the pathophysiology of cerebrovascular disease, predicting tissue infarction and patient outcome, and may identify patients who will benefit from therapeutic intervention. It has been demonstrated that elevation of oxygen extraction fraction (OEF) in brain tissue portends a 6-7 fold increased risk of subsequent stroke in patients with chronic atherosclerotic carotid artery occlusion. Moreover, during acute ischemic stroke, "misery perfusion", marked by an elevation of OEF and decreased blood flow, has been used as an indicator of "at-risk" tissue that is a target of therapeutic treatments. On the other hand, indiscriminate treatment without screening for "at-risk" tissue may lead to serious treatment- related complications. Therefore, a reliable and non-invasive measure of OEF that can be obtained with a routine clinical setup will have a great impact on appropriate patient diagnosis and treatment. Despite its importance, cerebral oxygenation can only be quantified using 15O positron emission tomography (PET). However, the requirement of an onsite cyclotron has limited 15O PET measurements to only a few medical centers around the world. In the past decade, significant technical progress has been made towards non-invasive quantitative OEF measurements using magnetic resonance imaging (MRI). Though absolute OEF measurements have been successfully obtained in healthy human subjects, the clinical utility of these methods remains minor due to a host of unaddressed issues that are particularly challenging in patient studies. Moreover, neither global nor regional OEF validation has yet been performed in patients. In this study, an integrated PET/MR system which allows truly simultaneous PET and MR image acquisition will be utilized for a direct comparison between MR and PET OEF without potential confounding factors associated with sequential imaging. The overall objectives of this project are (1) to develop a novel MR OEF measurement that is rapid and robust to meet the need of clinical studies; and (2) to validate the MR OEF measurements using simultaneous O15 PET measurements in patients with focal pathology. Since MR is widely available, the success of this project will permit the acquisition of PET comparable OEF measurements in many patients, and pave the way for future integration of this method into time-sensitive patient management decisions. Furthermore, the technical developments from this proposal-- minimizing MR imaging artifacts, improving measurement efficiency, and synergizing PET and MR scans--can be generalized to many other neuroimaging studies.