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

人体耗氧量的高时空分辨率 MRI 绘图

• 批准号: 10669230
• 负责人: Felix W Wehrli
• 金额: $ 16.69万
• 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/10669230
• 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; Diagnosis; Disease; Doctor of Philosophy; Equation; Erythrocytes; Evaluation; Fetus; 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; blood fractionation; blood oxygen level dependent; body system; 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：高空间和时间分辨率的MRI映射人类氧的消耗 PI pi：Felix Wehrli博士 抽象的 氧代谢的紊乱是许多退化性和获得性疾病的核心。 因此，了解氧的代谢率（MRO2），即器官的O2消耗率， 用摩尔或毫升的O2代谢每分钟和单位组织质量表示，至关重要 了解组织代谢和临床医学感兴趣的关键生理参数之一。 底物和向细胞的氧递送都由血流介导。那是MRO2的定量 要求对两者的了解，底物代谢后分数血氧含量的变化 - - 通常以氧气提取分数（OEF）和血流量表示。 MRI是唯一允许对MRO2进行真正无创评估的成像方式。而血流可以 准确且可重复地测量以使其在临床上实用，OEF的测量结果被证明为 一个更复杂的问题。在血红蛋白的脱氧中利用血红素铁磁性的两种主要方法 国家出现了；通过某种形式的定量直接测量血液磁敏感性 敏感性映射，或间接通过测量快速的血液横向松弛的测量 在细胞内和细胞外红细胞室之间的交换以及局部的水扩散 诱导的磁场。 许多基于苏联的血氧仪的实施方案，以及基于T2的全器官和 研究人员在初步工作中构思或其他人出版的基于区域大胆的血氧仪 显示的承诺。但是，精密药物需要衍生的鲁棒性，准确性和可重复性 定量措施，以适用于治疗反应的诊断和评估。这些都不是 当前要求符合严格的必要标准。此外，由于效果用任何 在上述方法尺度上，将需要进行严格的定量评估。获得这些 目的，目前的TR＆D提案要开发和验证；基于MRI的成像技术 在高临时分辨率下进行的器官MRO2测量适用于多个器官系统（AIM 1），空间上 基于校准和定量粗体的原理解决了MRO2，重点是人脑 （目标2）;以及完全交叉验证和扩展到7T场强（AIM 3）。 提议的技术发展的结果和随后的方法的传播 申请人的机构及其他地区应为研究组织能量提供有效的手段。 响应治疗和生活方式改变的血管代谢疾病。实施，测试和 验证新技术及其最终转换为诊所的验证将为 评估多个器官中的氧代谢，从而提供了可靠的定量指标来评估 具有代谢和退化性疾病的患者。