MOTIVATION One of the central events in acute ischemic stroke is the decrease in delivery of oxygen to the brain, which leads to cell death and irreversible injury. To counteract this, the brain has mechanisms to increase its extraction of oxygen from the arterial blood, which can be imaged with oxygen-15 positron emission tomography (PET). Some evidence from PET exists that suggests that regions with increased oxygen extraction fraction (OEF) are particularly vulnerable in ischemic stroke. Given the sensitivity of MRI to paramagnetic deoxy- hemoglobin (the basis of the BOLD effect), it is possible to image tissue oxygen saturation (SO2). The motivation for the current study is to implement and validate two promising MR oxygenation methods, multiparametric quantitative BOLD and MR oxygenation fingerprinting for use in stroke patients. This latter technique builds on pioneering work extending the fingerprinting approach from anatomical to physiological imaging.
AIMS AND METHODS Over a two-year period, we aim to perform studies to validate the performance of both of these MR oxygenation imaging protocols in normal subjects exposed to inspired gas challenges that will alter the global brain oxygenation. We will then apply the best of these two techniques to a cohort of acute ischemic stroke patients to determine the performance of the oxygenation-diffusion (O2- DWI) mismatch as a potential improved substitute for the traditional DWI-PWI mismatch. SIGNIFICANCE We believe successful attainment of these aims will markedly improve acute stroke care by validating a non-invasive MRI-based method to assess tissue oxygenation. We believe that there will be wide-reaching benefits to the development of a robust MR oxygenation method in a wide range of other neurological diseases, including carotid steno-occlusive disease, brain tumors, multiple sclerosis, and neurodegenerative disease.
While we have learned a tremendous amount about ischemic stroke from the diffusion/perfusion mismatch paradigm, the failure of recent image-guided stroke trials has made it clear that additional information regarding tissue physiological is needed. However, tissue oxygenation is of central importance, and has traditionally only been imaged with invasive oxygen-15 positron emission tomography (PET). Over the last few years, much progress has been made using MRI to measure tissue oxygenation, given the sensitivity of the blood-oxygen level dependent (BOLD) effect to paramagnetic deoxyhemoglobin. In this submission, we propose to test two promising MR oxygenation methodologies that our group has developed, multiparametric quantitative BOLD (qBOLD) and MR fingerprinting. The best performing of these two methods will then be applied to a cohort of acute stroke patients. We believe that incorporation of MR oxygenation measurements into the acute stroke triage strategy will improve decision-making regarding the need for endovascular therapies and ultimately result in better outcomes in stroke patients. Additionally, we believe the development of a robust MR oxygenation method will have applications far beyond ischemic stroke, impacting our basic understanding of a wide range of neurological diseases, including carotid steno-occlusive disease, brain tumors, multiple sclerosis, and neurodegenerative disease.
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