Mapping the energetic pathways of the brain: Ultra-high-field MRI of cerebral oxygen and glucose utilisation

Aerobic glycolysis (AG) plays a vital role in brain disease, development, and ageing.

Elevated AG has been linked to axonal elongation and synaptogenesis in childhood, synaptic plasticity in adulthood, and is a hallmark of cancer. There is also evidence of a significant reduction in AG in older age and in neurodegeneration.

The development of a non-invasive method for imaging AG has the potential for significant impact in basic neuroscience and clinical practice.

For example, in cancer therapy, post-treatment mapping of AG is anticipated to be a sensitive measure for assessing recurrence and for the planning of salvage therapy.

I propose to develop ultra-high field (7T) MRI methods to safely and non-invasively map aerobic glycolysis and tissue oxygen availability in the human brain, providing a new window into brain metabolism and metabolic dysfunction.

The methods development involves two main paths. 1) Glucose labeled deuterium imaging to directly map cerebral AG. 2) Development of vascular imaging methods, including deuterium perfusion and blood volume imaging.

The combination of these two methods will enable calculation of cerebral glucose metabolism, oxygen metabolism, and tissue oxygen availability.

These methods will be validated experimentally using a controlled pharmacological modulation of aerobic glycolysis with sub-anaesthetic ketamine administration.