Reduced Brain Oxygen Metabolism in Patients with Multiple Sclerosis: Evidence from Dual-Calibrated Functional MRI.

Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBV dHb ), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO 2 ) in patients with MS (PwMS) and age/sex matched controls. By integrating a flow-diffusion model of oxygen transport, we evaluated the effective oxygen diffusivity of the capillary network (D C ) and the partial pressure of oxygen at the mitochondria (PmO 2 ). Significant between-group differences were observed as decreased CBF ( p = 0.010), CMRO 2 ( p < 0.001) and D C ( p = 0.002), and increased PmO 2 ( p = 0.043) in patients compared to controls. No significant differences were observed for CBV dHb ( p = 0.389), OEF ( p = 0.358), or GM volume ( p = 0.302). Regional analysis showed widespread reductions in CMRO 2 and D C for PwMS. Our findings may be indicative of reduced oxygen demand or utilisation in the MS brain and mitochondrial dysfunction. Our results suggest changes in brain physiology may precede MRI-detectable GM loss and may contribute to disease progression and neurodegeneration.