High Spatial and Temporal Resolution MRI Mapping of Oxygen Consumption in Humans

人类耗氧量的高时空分辨率 MRI 绘图

• 批准号: 10490825
• 负责人: Felix W Wehrli
• 金额: $ 16.79万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490825
• 关键词: 3-Dimensional; Address; Affect; Blood; Blood Vessels; Blood flow; Brain; Breathing; Calibration; Carrying Capacities; Categories; Cells; Cerebrum; Clinic; Clinical; Clinical Medicine; Consumption; Coupling; Data; Degenerative Disorder; Development; Disease; Doctor of Philosophy; Equation; Erythrocytes; Evaluation; Fetus; Functional Magnetic Resonance Imaging; Gases; Heme Iron; Hemoglobin; Human; Hypercapnia; Hyperoxia; Imaging technology; Information Dissemination; Institution; Intervention; Knowledge; Laboratories; Life Style; Magnetic Resonance Imaging; Magnetism; Maps; Measurement; Measures; Mediating; Metabolic; Metabolic Diseases; Metabolism; Methods; Modeling; Mole the mammal; Optics; Organ; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Patients; Performance; Physiological; Placenta; Predisposition; Preparation; Protocols documentation; Publishing; Quantitative Evaluations; Relaxation; Reproducibility; Research Personnel; Response to stimulus physiology; Signal Transduction; Standardization; Techniques; Technology; Testing; Time; Tissues; Translating; Translations; Validation; Water; Work; base; blood oxygen level dependent; body system; diagnosis evaluation; extracellular; falls; imaging modality; in utero; in vivo; interest; magnetic field; metabolic imaging; metabolic rate; milliliter; neural stimulation; new technology; precision medicine; response; signal processing; technology development; temporal measurement; treatment response; water diffusion

TR&D2: High Spatial and Temporal Resolution MRI Mapping of Oxygen Consumption in Humans Project PI: Felix Wehrli, Ph.D. Abstract Disturbance of oxygen metabolism is at the core of many degenerative and acquired disorders. Therefore, knowledge of the metabolic rate of oxygen (MRO2), i.e. the rate of an organ’s O2 consumption, expressed in moles or milliliter of O2 metabolized per minute and unit mass of tissue, is fundamental to understanding tissue metabolism and one of the key physiologic parameters of interest to clinical medicine. Substrate and oxygen delivery to the cells are both mediated by blood flow. Thus, quantification of MRO2 demands knowledge of both, the change in fractional blood oxygen content following substrate metabolization - - usually expressed in terms of oxygen extraction fraction (OEF) -- and blood flow rate. MRI is the only imaging modality permitting truly noninvasive evaluation of MRO2. While blood flow can be measured accurately and reproducibly to render it clinically practical, the measurement of OEF proves to be a far more intricate problem. Two dominant approaches exploiting heme iron magnetism in hemoglobin’s deoxy state have emerged; direct measurement of blood magnetic susceptibility via some form of quantitative susceptibility mapping, or indirectly via measurement of blood water transverse relaxation resulting from rapid exchange between intra- and extracellular erythrocyte compartments as well as water diffusion in the locally induced magnetic fields. A number of embodiments of susceptometry-based oximetry, as well as T2-based whole-organ and regional BOLD-based oximetry, conceived by the investigators in preliminary work, or published by others, have shown promise. However, precision medicine demands robustness, accuracy and reproducibility of the derived quantitative measures in order to be applicable to diagnosis and evaluation of treatment response. None of these requirements are currently meet the necessary standard of rigor. Further, since the effects measured with any of the above methods scale with field strength, a rigorous quantitative evaluation will be needed. To attain these objectives, the present TR&D proposes to develop and validate; MRI-based imaging technologies for whole- organ MRO2 measurement at high temporal resolution applicable to multiple organ systems (Aim 1), spatially resolved MRO2 based on the principles of both calibrated and quantitative BOLD focusing on the human brain (Aim 2); and full cross-validation and expansion to 7T field strength (Aim 3). The results of the proposed technology developments and dissemination of the ensuing methods within the applicants’ institution and beyond, should provide effective means for the study of tissue energetics in vascular-metabolic disorders in response to treatment and lifestyle changes. Implementation, testing and validation of the new technologies, and their eventual translation to the clinic, will open new avenues for evaluating oxygen metabolism in multiple organs, thereby providing robust quantitative metrics for evaluation of patients with metabolic and degenerative disorders.

TR&D2：人类耗氧量的高时空分辨率 MRI 绘图 项目负责人：Felix Wehrli 博士 抽象的 氧代谢紊乱是许多退行性和获得性疾病的核心。 因此，了解氧代谢率 (MRO2)，即器官消耗 O2 的速率， 以每分钟和单位质量组织代谢的 O2 摩尔数或毫升数表示，是 了解组织代谢和临床医学感兴趣的关键生理参数之一。 基质和氧气向细胞的输送都是由血流介导的，因此，MRO2 的定量。 需要了解两者的知识，底物代谢后血氧含量分数的变化 - - 通常以氧提取分数 (OEF) 和血流量表示。 MRI 是唯一能够真正无创评估 MRO2 的成像方式，而血流可以。 准确且可重复地测量以使其在临床上实用，OEF 的测量被证明是 这是一个更为复杂的问题，有两种利用血红蛋白脱氧中血红素铁磁性的主要方法。 已经出现了通过某种形式的定量直接测量血液磁化率的方法 磁化率绘图，或间接通过测量快速产生的血水横向弛豫 细胞内和细胞外红细胞区室之间的交换以及局部的水扩散 磁感应场。 基于电纳测定法的血氧测定法以及基于 T2 的全器官和血氧测定法的许多实施例 由研究人员在前期工作中构思或由其他人发表的基于 BOLD 的区域血氧测定法 然而，精准医学要求衍生的稳健性、准确性和可重复性。 定量测量以适用于诊断和治疗反应评估这些都不是。 此外，由于用任何方法测量的效果，目前的要求都满足必要的严格标准。 上述方法与场强的关系，需要进行严格的定量评估才能实现这些。 目前的 TR&D 提议开发和验证基于 MRI 的整体成像技术； 高时间分辨率的器官 MRO2 测量适用于多器官系统（目标 1），空间 基于针对人脑的校准和定量 BOLD 原理解决了 MRO2 （目标 2）；以及完全交叉验证和扩展到 7T 场强（目标 3）。 拟议技术开发的结果以及后续方法的传播 申请人的机构及其他机构应为组织能量学的研究提供有效的手段 治疗和生活方式改变引起的血管代谢紊乱。 新技术的验证及其最终转化为临床将为治疗开辟新途径 评估多个器官的氧代谢，从而为评估提供可靠的定量指标 患有代谢性疾病和退行性疾病的患者。