Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI

Hannah L. Chandler, Rachael C. Stickland, Eleonora Patitucci, Michael Germuska, Antonio M. Chiarelli, Catherine Foster, Shona Bhome-Dhaliwal, Thomas M. Lancaster, Neeraj Saxena, Sharmila Khot, Valentina Tomassini, Richard G. Wise

Research output: Contribution to journalArticlepeer-review

Abstract

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 (CBVdHb), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO2) 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 (DC) and the partial pressure of oxygen at the mitochondria (PmO2). Significant between-group differences were observed as decreased CBF (p = 0.010), CMRO2 (p < 0.001) and DC (p = 0.002), and increased PmO2 (p = 0.043) in patients compared to controls. No significant differences were observed for CBVdHb (p = 0.389), OEF (p = 0.358), or GM volume (p = 0.302). Regional analysis showed widespread reductions in CMRO2 and DC 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.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Early online date7 Sep 2022
DOIs
Publication statusE-pub ahead of print - 7 Sep 2022

Keywords

  • cerebral blood flow
  • cerebral oxygen consumption
  • disability
  • Multiple sclerosis
  • neurodegeneration

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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