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

项目摘要 脑氧代谢的定量评估，通常用脑代谢率表示， 氧（CMRO 2），可以提供重要的信息，许多神经系统疾病以及正常的大脑 physiology. MRI允许无创、无辐射测量两个关键参数-脑血流量 和氧提取分数（OEF）-决定氧消耗率，因此CMRO 2。目前， 脑中CMRO 2的可靠区域定量是不可能的，主要是因为OEF绘图技术 仍处于早期发展阶段。 基于MRI的OEF映射方法通常基于由参数产生的信号调制。 血液脱氧血红蛋白（dHb）的中性化。目前的技术要么校准dHb的磁共振效应， 在一个单独的程序，或通过估计RF可逆的横向弛豫速率推导参数 常数R2（称为“定量BOLD（qBOLD）”的方法类）。或者，一个模型占几个 体素磁化率中的源已经基于定量磁化率映射（QSM）被调用。其中 qBOLD的独特之处在于它不需要任何干预，因此基本上无需校准。 qBOLD的一个主要挑战是将dHb对R2的贡献与其他来源（通常为非血红蛋白来源）分开。 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”）缓解了该问题，但是该方法仍然容易出错，因为所采集的信号 被来自RF不可逆横向弛豫速率常数R2的影响纠缠，以及宏观的 磁场的变化，除了那些由R2引起的。此外，目前用于直接R2 TM映射的技术 对于3D编码来说是不切实际的慢。此外，从血红素来源的R2的估计值中提取OEF是可行的。 由于qBOLD模型的灵敏度有限，因此具有挑战性。支持者最近的工作已经解决了 通过推导未知qBOLD参数的先验信息来解决问题。 本项目的目标一是研制一种快速的R2敏感三维脉冲序列，并实现一种数据采集系统。 处理流水线，其通过先验信息引导的qBOLD来解决上述混杂因素。的 新开发的3D MRI血氧测定方案将在3 T场强下在一组健康受试者中进行确认 与qBOLD+QSM相比，在各种生理状态下的再现性（目标2）。最后 将检查方案向临床转化的可行性。为此，目标3评价了单侧 颈动脉狭窄闭塞性疾病，以解决实质缺氧表现为同侧的假设， OEF增大、CMRO 2降低，这些参数与脑血管反应性相关。 成功完成拟议的项目将产生一个强大的，可靠的，临床实用的3D MRI 血氧测定方案作为研究健康和疾病中大脑生理学的一种手段，其长期目标是 方法的翻译到临床，以帮助指导治疗患者的神经代谢紊乱。

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.