MRI-Based Regional Assessment of Cerebral Metabolism Via 3D Quantitative BOLD

项目总结 脑氧代谢的定量评估，通常用大脑代谢率来表示 氧气(CMRO2)，可以提供许多神经疾病以及正常大脑的重要信息 生理学。磁共振成像可以无创、无辐射地测量两个关键参数-脑血流量 以及氧提取分数(OEF)--这决定了氧气消耗的速率，从而决定了CMRO2。目前， 大脑中CMRO2的强健区域量化是不可能的，主要是因为OEF映射技术 仍处于发展的早期阶段。 基于磁共振成像的OEF映射方法通常是基于由参数调制引起的信号调制的。 血脱氧血红蛋白阴性(DHb)。目前的技术要么校准dHb的磁化率的影响- 或者通过估计RF可逆的横向弛豫率来获得参数 常量R2Ⅱ(称为定量粗体(QBOLD)的方法类别)。或者，一个模型可以解释几个 体素磁化率的来源已经基于定量磁化率图(QSM)被调用。其中包括 与其他方法相比，qBOLD是独一无二的，因为它不需要干预，因此基本上无需校准。 QBOLD中的一个主要挑战是将dHb对R2Ⅱ的贡献与其他来源分开，通常是非 例如，血红素铁以铁蛋白的形式储存在基底节中。虽然最近一种结合了qBOLD的方法 而QSM(称为qBOLD QSM)缓解了这一问题，但由于采集到的信号，该方法仍然容易出错 被RF不可逆的横向弛豫速率常数R2的影响以及宏观的纠缠 磁场变化，以及由R2Ⅱ引起的磁场变化。此外，目前用于直接定位R2？的技术 对于3D编码来说是非常慢的。此外，从血红素起源的R2的估计值中提取OEF是 具有挑战性，因为qBOLD模型的灵敏度有限。支持者最近的工作解决了 通过获取未知qBOLD参数的先验信息来解决此问题。 该项目的目标1旨在开发一种对R2？敏感的快速3D脉冲序列，并实现数据 通过先验信息引导的qBOLD解决上述混杂因素的处理流水线。这个 新开发的3D MRI血氧仪将在3T场强下在一组健康受试者身上进行验证 在不同的生理状态下，与qBOLD QSM进行比较，并在再现性方面(目标2)。最后， 我们将考察协议在临床翻译中的可行性。为此，Aim 3评估了单侧 颈动脉狭窄闭塞疾病，以解决假设，即实质性低氧表现为同侧 较大的OEF和较低的CMRO2，以及这些参数与脑血管反应性的关系。 拟议项目的成功完成将产生一种健壮、可靠和临床实用的三维核磁共振成像 血氧测定方案作为研究健康和疾病中的大脑生理学的一种手段，其长期目标是 该方法翻译到临床上，有助于指导神经代谢紊乱患者的治疗。

PROJECT SUMMARY Quantitative assessment of brain oxygen metabolism, usually expressed in terms of cerebral metabolic rate of oxygen (CMRO2), can provide important information on many neurological disorders as well as normal cerebral physiology. MRI permits noninvasive, nonradiative measurement of the two key parameters – cerebral blood flow and oxygen extraction fraction (OEF) – that determine the rate of oxygen consumption, thus CMRO2. Currently, robust regional quantification of CMRO2 in the brain is not possible, primarily as techniques for OEF mapping are still at an early stage of development. MRI-based OEF mapping methods are commonly based on signal modulations resulting from the paramag- netism of blood deoxyhemoglobin (dHb). Current techniques either calibrate the effect of dHb’s magnetic suscepti- bility in a separate procedure, or derive the parameter by estimating the RF-reversible transverse relaxation rate constant R2¢ (class of methods termed ‘quantitative BOLD (qBOLD)’). Alternatively, a model accounting for several sources in voxel susceptibility has been invoked based on quantitative susceptibility mapping (QSM). Among these approaches, qBOLD is unique in that it requires no intervention, and thus is essentially calibration-free. One major challenge in qBOLD is to separate dHb’s contribution to R2¢ from other sources, typically non- heme iron stored, for instance, in the form of ferritin in the basal ganglia. While a recent approach combining qBOLD and QSM (termed ‘qBOLD+QSM’) mitigates the issue, the method is still prone to errors because acquired signals are entangled by the effects from the RF-irreversible transverse relaxation rate constant R2, as well as macroscopic magnetic field variations, in addition to those arising from R2¢. In addition, current techniques for direct R2¢ mapping are impractically slow for 3D encoding. Furthermore, extracting OEF from the estimate of heme-originated R2¢ is challenging because of limited sensitivity in the qBOLD model. The proponents’ recent work has addressed the issue by deriving prior information for the unknown qBOLD parameters. Aim 1 of this project seeks to develop a rapid R2¢-sensitive 3D pulse sequence, and implement a data processing pipeline that addresses the above-mentioned confounders via prior information guided qBOLD. The newly developed 3D MRI oximetry protocol will be validated at 3T field strength in a group of healthy test subjects at various physiologic states in comparison to qBOLD+QSM and in terms of reproducibility (Aim 2). Finally, the protocol’s feasibility towards clinical translation will be examined. To this end, Aim 3 evaluates patients with unilateral carotid steno-occlusive disease to address the hypothesis that parenchymal hypoxia is manifested ipsilaterally by greater OEF and lower CMRO2, and these parameters’ association with cerebrovascular reactivity. Successful completion of the proposed project will yield a robust, reliable, and clinically practical 3D MRI oximetry protocol as a means to study brain physiology in health and disease, with the long-term goal of the method’s translation to the clinic to help guide treatment of patients with neurometabolic disorders.