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

TR&D2：人体耗氧量的高时空分辨率磁共振成像 项目PI：Felix Wehrli博士。 摘要 氧代谢障碍是许多退行性和获得性疾病的核心。 因此，了解氧的代谢率(MRO2)，即器官的耗氧率， 以每分钟和单位组织质量新陈代谢的O2摩尔或毫升表示，是 了解组织代谢和临床医学感兴趣的关键生理参数之一。 底物和氧气向细胞的输送都是由血流调节的。因此，MRO2的量化 需要两方面的知识，底物代谢后部分血氧含量的变化- -通常用氧提取分数(OEF)和血流率表示。 MRI是唯一一种能够对MRO2进行真正无创评估的成像手段。而血液流动可以 测量准确和可重复性，使其在临床上可行，OEF的测量被证明是 一个复杂得多的问题。利用血红蛋白脱氧中的血红素铁磁性的两种主要途径 状态已经出现；通过某种形式的定量测量直接测量血液磁化率 磁化率图，或间接通过测量快速引起的血水横向松弛 红细胞室内外的交换和局部的水扩散 感应磁场。 基于敏感度的血氧测定法以及基于T2的整体器官和 由研究人员在前期工作中构思的基于区域BOLD的血氧测定仪，或由其他人发表的 展现出了希望。然而，精密医学要求派生的健壮性、准确性和重复性 量化措施，以适用于诊断和评价治疗反应。这些都不是 目前的要求符合必要的严格标准。此外，由于使用任何 在上述方法中，需要根据场强进行严格的定量评估。要达到这些目标 目标，本研发计划开发和验证基于磁共振成像的全脑成像技术。 适用于多个器官系统的高时间分辨率器官MRO2测量(目标1)，空间 基于校准和定量大胆聚焦于人脑的原理来解析MRO2 (目标2)；充分交叉验证并扩大到7T场强(目标3)。 拟议的技术开发和随后方法的传播的结果 申请人所在机构及其他机构应为组织能量学的研究提供有效的手段。 对治疗和生活方式改变作出反应的血管代谢紊乱。实施、测试和 对新技术的验证，并最终将其转化为临床，将开辟新的途径 评估多个器官的氧代谢，从而为评估 患有代谢和退行性疾病的患者。

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.