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

doi:10.1177/0271678X221121849

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

Department of Psychology

Research output: Contribution to journal › Article › peer-review

6 Citations (SciVal)

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 (CBV_dHb), 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 (D_C) 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 D_C (p = 0.002), and increased PmO₂ (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 CMRO₂ 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.

Original language	English
Pages (from-to)	115-128
Number of pages	14
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	43
Issue number	1
Early online date	7 Sept 2022
DOIs	https://doi.org/10.1177/0271678X221121849
Publication status	Published - 31 Jan 2023

Data Availability Statement

We do not have ethical consent to make the in-vivo participant datasets acquired for this study publicly available in an unrestricted manner. However, the authors may be contacted for collaborative research enquiries involving the data presented.

Acknowledgements

For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. We thank the patients with MS and their families, along with the healthy volunteers, for their time and support that made this research possible.

Keywords

cerebral blood flow
cerebral oxygen consumption
disability
Multiple sclerosis
neurodegeneration

ASJC Scopus subject areas

Neurology
Clinical Neurology
Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1177/0271678X221121849Licence: CC BY

Cite this

Chandler, H. L., Stickland, R. C., Patitucci, E., Germuska, M., Chiarelli, A. M., Foster, C., Bhome-Dhaliwal, S., Lancaster, T. M., Saxena, N., Khot, S., Tomassini, V., & Wise, R. G. (2023). Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI. Journal of Cerebral Blood Flow and Metabolism, 43(1), 115-128. https://doi.org/10.1177/0271678X221121849

Chandler, HL, Stickland, RC, Patitucci, E, Germuska, M, Chiarelli, AM, Foster, C, Bhome-Dhaliwal, S, Lancaster, TM, Saxena, N, Khot, S, Tomassini, V & Wise, RG 2023, 'Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI', Journal of Cerebral Blood Flow and Metabolism, vol. 43, no. 1, pp. 115-128. https://doi.org/10.1177/0271678X221121849

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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.",

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AU - Germuska, Michael

AU - Chiarelli, Antonio M.

AU - Foster, Catherine

AU - Bhome-Dhaliwal, Shona

AU - Lancaster, Thomas M.

AU - Saxena, Neeraj

AU - Khot, Sharmila

AU - Tomassini, Valentina

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

Abstract

Data Availability Statement

Acknowledgements

Keywords

ASJC Scopus subject areas

UN SDGs

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