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Mapping oxidative metabolism in the human brain with calibrated fMRI in health and disease

Conventional functional MRI (fMRI) with blood-oxygenation level dependent (BOLD) contrast is an important tool for mapping human brain activity non-invasively. Recent interest in quantitative fMRI has renewed the importance of oxidative neuroenergetics as reflected by cerebral metabolic rate of oxygen consumption (CMRO2) to support brain function. Dynamic CMRO2 mapping by calibrated fMRI require multi-modal measurements of BOLD signal along with cerebral blood flow (CBF) and/or volume (CBV). In human subjects this “calibration” is typically performed using a gas mixture containing small amounts of carbon dioxide and/or oxygen-enriched medical air, which are thought to produce changes in CBF (and CBV) and BOLD signal with minimal or no CMRO2 changes. However non-human studies have demonstrated that the “calibration” can also be achieved without gases, revealing good agreement between CMRO2 changes and underlying neuronal activity (e.g., multi-unit activity and local field potential). Given the simpler set-up of gas-free calibrated fMRI, there is evidence of recent clinical applications for this less intrusive direction. This up-to-date review emphasizes technological advances for such translational gas-free calibrated fMRI experiments, also covering historical progression of the calibrated fMRI field that is impacting neurological and neurodegenerative investigations of the human brain.