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

通过 3D 定量 BOLD 进行基于 MRI 的脑代谢区域评估

• 批准号: 10578782
• 负责人: Felix W Wehrli
• 金额: $ 20.31万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10578782
• 关键词: 3-Dimensional; Accounting; Address; Affect; Basal Ganglia; Blood; Brain; Brain Hypoxia; Breathing; Calibration; Cells; Cerebrovascular Circulation; Cerebrovascular system; Cerebrum; Characteristics; Circulation; Clinic; Clinical; Clinical Management; Complex; Contralateral; Coupling; Data; Deoxygenated Sickle Hemoglobin; Derivation procedure; Development; Disease; Disorder of neurometabolic regulation; Effectiveness; Erythrocytes; Exhibits; Ferritin; Functional Magnetic Resonance Imaging; Gases; Goals; Health; Heme; Hemoglobin; Hypercapnia; Hyperoxia; Hypoxia; Immunity; Impairment; Intervention; Ipsilateral; Iron; Ischemic Stroke; Knowledge; Magnetic Resonance Imaging; Magnetism; Maps; Measurement; Measures; Metabolism; Methods; Microscopic; Modeling; Neurons; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Parameter Estimation; Parents; Participant; Patients; Performance; Phase; Physiologic pulse; Physiological; Physiology; Predisposition; Procedures; Protocols documentation; Relaxation; Reproducibility; Signal Transduction; Source; Stenosis; Stimulus; Techniques; Testing; Translating; Translations; Validation; Variant; Venous; Work; blood flow measurement; blood oxygen level dependent; brain magnetic resonance imaging; cerebral blood volume; cerebral hemodynamics; cerebrovascular; clinical translation; data analysis pipeline; deoxyhemoglobin; insight; magnetic field; metabolic rate; nervous system disorder; neurovascular coupling; response; 3-Dimensional; Accounting; Address; Affect; Basal Ganglia; Blood; Brain; Brain Hypoxia; Breathing; Calibration; Cells; Cerebrovascular Circulation; Cerebrovascular system; Cerebrum; Characteristics; Circulation; Clinic; Clinical; Clinical Management; Complex; Contralateral; Coupling; Data; Deoxygenated Sickle Hemoglobin; Derivation procedure; Development; Disease; Disorder of neurometabolic regulation; Effectiveness; Erythrocytes; Exhibits; Ferritin; Functional Magnetic Resonance Imaging; Gases; Goals; Health; Heme; Hemoglobin; Hypercapnia; Hyperoxia; Hypoxia; Immunity; Impairment; Intervention; Ipsilateral; Iron; Ischemic Stroke; Knowledge; Magnetic Resonance Imaging; Magnetism; Maps; Measurement; Measures; Metabolism; Methods; Microscopic; Modeling; Neurons; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Parameter Estimation; Parents; Participant; Patients; Performance; Phase; Physiologic pulse; Physiological; Physiology; Predisposition; Procedures; Protocols documentation; Relaxation; Reproducibility; Signal Transduction; Source; Stenosis; Stimulus; Techniques; Testing; Translating; Translations; Validation; Variant; Venous; Work; blood flow measurement; blood oxygen level dependent; brain magnetic resonance imaging; cerebral blood volume; cerebral hemodynamics; cerebrovascular; clinical translation; data analysis pipeline; deoxyhemoglobin; insight; magnetic field; metabolic rate; nervous system disorder; neurovascular coupling; response

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.

项目摘要 对脑氧代谢的定量评估，通常以脑代谢率表示 氧（CMRO2）可以提供有关许多神经系统疾病以及正常脑的重要信息 生理。 MRI允许对两个关键参数的无创，非辐射测量 - 脑血流 和氧提取部分（OEF） - 确定氧气消耗的速率，从而确定CMRO2。现在， 不可能对CMRO2进行强大的区域定量，主要是OEF映射技术 仍处于发展的早期阶段。 基于MRI的OEF映射方法通常是基于paramag-产生的信号调制。 血液脱氧血红蛋白（DHB）的网络主义。当前的技术要么校准DHB的磁性敏感的影响 在单独的过程中自由，或通过估计RF可逆横向松弛率来得出参数 常数r2¢（称为“定量粗体（qbold）”的方法类）。或者，一个模型占多个 基于定量敏感性映射（QSM），已经调用了体素敏感性的来源。其中 方法是，Qbold的独特之处在于它不需要干预，因此基本上是无校准的。 Qbold中的一个主要挑战是将DHB对R2¢的贡献与其他来源分开，通常是非 - 血红素铁在基底神经节中以铁蛋白的形式储存。虽然最近结合了Qbold的方法 和QSM（称为“ Qbold+QSM”）缓解了该问题，该方法仍然容易出错，因为获得了信号 RF - 横向松弛速率常数R2和宏观纠缠在一起 除了由R2¢产生的磁场变化。此外，直接R2¢映射的当前技术 对于3D编码而言，不切实际。此外，从血红素原始R2¢的估计中提取OEF为 由于Qbold模型的灵敏度有限，具有挑战性。支持者最近的工作解决了 通过得出未知Qbold参数的先验信息来发出问题。 该项目的目标1旨在开发快速的R2敏感3D脉冲序列，并实施数据 处理管道通过先前的信息指导Qbold来解决上述混杂因素。 新开发的3D MRI血氧仪方案将在一组健康的测试受试者中以3T场强度进行验证 与Qbold+QSM相比，在各种生理状态下，就可重复性而言（AIM 2）。最后， 方案将检查临床翻译的可行性。为此，AIM 3评估单侧患者 颈动脉steno-钙化疾病解决了以下假设，即实质性缺氧是由同侧表现出来的 更大的OEF和较低的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强大，可靠和临床实用的3D MRI 血氧仪方案是研究健康和疾病中脑生理的一种手段，其长期目标是 方法转化为诊所，以帮助指导神经代谢疾病患者的治疗。