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

TR&D2：人类耗氧量的高时空分辨率MRI映射 项目PI：Felix Wehrli，Ph.D. 摘要 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（MRO 2），即器官的O2消耗率， 以每分钟代谢的O2的摩尔或毫升和组织的单位质量表示， 了解组织代谢和临床医学感兴趣的关键生理参数之一。 基质和氧气输送到细胞都是由血流介导的。因此，MRO 2的定量 需要了解这两方面的知识，即底物代谢后血氧含量的变化- - 通常用氧摄取分数（OEF）和血液流速来表示。 MRI是唯一允许真正无创评估MRO 2的成像方式。虽然血流可以 准确和可重复地测量，使其临床实用，OEF的测量被证明是 一个更复杂的问题利用血红素铁磁性的两种主要途径 通过某种形式的定量测量直接测量血液磁化率 敏感性映射，或间接通过测量血液水横向弛豫造成的快速 红细胞内和细胞外室之间的交换以及局部 感应磁场 基于血氧饱和度测定法的血氧测定法以及基于T2的全器官和 由研究者在前期工作中设想或由其他人发表的基于BOLD的区域血氧测定法， 显示承诺。然而，精准医学要求衍生产品的鲁棒性，准确性和重现性 定量测量，以便适用于治疗反应的诊断和评价。没有这些 目前的要求符合必要的严格标准。此外，由于任何测量的效果 上述方法与场强的比例，将需要严格的定量评估。实现这些 目标，目前的TR&D建议开发和验证;基于MRI的成像技术， 适用于多器官系统的高时间分辨率器官MRO 2测量（目标1），空间 基于校准和定量BOLD聚焦于人脑的原理， (Aim 2）;和全面的交叉验证和扩展到7 T场强（目标3）。 拟议技术开发的结果和随后方法的传播， 申请人的机构和其他机构应提供有效的组织能量学研究手段， 血管代谢紊乱对治疗和生活方式改变的反应。实施、测试和 新技术的验证，以及它们最终转化为临床，将为以下方面开辟新的途径： 评估多个器官的氧代谢，从而为评估提供可靠的定量指标 代谢和退行性疾病患者。

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.