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

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.