Hyperpolarised 129Xe Nuclear Magnetic Resonance (NMR) Spectroscopic Brain Oximetry (360G-Wellcome-306193_Z_23_Z)

Reductions in brain blood flow are the earliest biomarker of cognitive decline and neurodegeneration. Brain perfusion declines during ageing (Christie 2022) yet the relationship between brain blood flow and hypoxia is not well understood. The aim of this fellowship is to perform a detailed investigation of a brain imaging method, to determine whether this method is sensitive to brain oxygen and useful as a midlife biomarker for poor brain health. I propose to reverse translate a non-invasive quantitative, magnetic resonance imaging (MRI) method which follows the uptake of 129Xe gas into the brain. First, in laboratory animals, I will simulate acute and chronic hypoxia while collecting 129Xe MRI data from the brain, simultaneously making invasive oxygen measurements from the brain and manipulating cerebral perfusion with pharmacology. 129Xe brain imaging was pioneered by physicists in Sheffield and is safe for humans (Rao 2019). However, the physiological sensitivity of the method is unclear; this proposal addresses this knowledge gap. After the key goal is addressed, pre-clinical and human scans will be performed on second MRI scanners to validate the reproducibility of the method. The ultimate goal is to validate a new biomarker of brain health and metabolic deficit in the human brain.