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

项目概要 脑氧代谢的定量评估，通常用脑代谢率来表示 氧（CMRO2），可以提供许多神经系统疾病以及正常大脑的重要信息 生理学。 MRI 允许对两个关键参数——脑血流量进行无创、非辐射测量 和氧提取分数 (OEF) – 决定氧气消耗率，即 CMRO2。目前， 对大脑中 CMRO2 进行稳健的区域定量是不可能的，主要是因为 OEF 绘图技术还不够成熟。 仍处于发展的早期阶段。 基于 MRI 的 OEF 映射方法通常基于顺磁产生的信号调制。 血液脱氧血红蛋白（dHb）的净重。当前的技术要么校准 dHb 磁化率的影响 能力在一个单独的过程中，或通过估计射频可逆横向弛豫率来导出参数 常数 R2¢（称为“定量 BOLD (qBOLD)”的方法类）。或者，一个模型考虑了几个 体素磁化率来源已根据定量磁化率绘图 (QSM) 调用。其中 qBOLD 的独特之处在于它不需要干预，因此本质上是免校准的。 qBOLD 的一个主要挑战是将 dHb 对 R2¢ 的贡献与其他来源（通常是非来源）区分开来。 例如，血红素铁以铁蛋白的形式储存在基底神经节中。虽然最近的方法结合了 qBOLD QSM（称为“qBOLD QSM”）缓解了这个问题，但该方法仍然容易出错，因为获取的信号 受到 RF 不可逆横向弛豫速率常数 R2 以及宏观 磁场变化，除了由 R2 产生的变化之外。此外，当前的直接 R2¢ 映射技术 对于 3D 编码来说速度慢得不切实际。此外，从血红素来源的 R2 的估计中提取 OEF 是 由于 qBOLD 模型的灵敏度有限，因此具有挑战性。支持者最近的工作解决了 通过导出未知 qBOLD 参数的先验信息来解决问题。 该项目的目标 1 旨在开发一种快速 R2∷ 敏感的 3D 脉冲序列，并实现数据 通过先验信息引导 qBOLD 解决上述混杂因素的处理管道。的 新开发的 3D MRI 血氧测定协议将在一组健康测试对象中在 3T 场强下进行验证 与 qBOLD QSM 相比以及在再现性方面（目标 2），在各种生理状态下的结果。最后， 将检查协议临床转化的可行性。为此，目标 3 评估单侧 颈动脉狭窄闭塞性疾病解决了实质缺氧在同侧表现的假设 更大的 OEF 和更低的 CMRO2，以及这些参数与脑血管反应性的关联。 拟议项目的成功完成将产生稳健、可靠且临床实用的 3D MRI 血氧测定协议作为研究健康和疾病中脑生理学的一种手段，其长期目标是 将方法转化为临床，以帮助指导神经代谢疾病患者的治疗。

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.