Dual-calibrated fMRI measurement of absolute cerebral metabolic rate of oxygen consumption and effective oxygen diffusivity

M Germuska,H.L Chandler,R.C Stickland,C Foster,F Fasano,T.W Okell,J Steventon,V Tomassini,K Murphy,R.G Wise

doi:10.1016/j.neuroimage.2018.09.035

Abstract

Dual-calibrated fMRI is a multi-parametric technique that allows for the quantification of the resting oxygen extraction fraction (OEF), the absolute rate of cerebral metabolic oxygen consumption (CMRO2), cerebral vascular reactivity (CVR) and baseline perfusion (CBF). It combines measurements of arterial spin labelling (ASL) and blood oxygenation level dependent (BOLD) signal changes during hypercapnic and hyperoxic gas challenges. Here we propose an extension to this methodology that permits the simultaneous quantification of the effective oxygen diffusivity of the capillary network (DC). The effective oxygen diffusivity has the scope to be an informative biomarker and useful adjunct to CMRO2, potentially providing a non-invasive metric of microvascular health, which is known to be disturbed in a range of neurological diseases. We demonstrate the new method in a cohort of healthy volunteers (n = 19) both at rest and during visual stimulation. The effective oxygen diffusivity was found to be highly correlated with CMRO2 during rest and activation, consistent with previous PET observations of a strong correlation between metabolic oxygen demand and effective diffusivity. The increase in effective diffusivity during functional activation was found to be consistent with previously reported increases in capillary blood volume, supporting the notion that measured oxygen diffusivity is sensitive to microvascular physiology.

Highlights

Calibrated fMRI measurement of absolute cerebral rate of oxygen metabolism (CMRO2) offers a non-invasive method of mapping oxygen consumption in the brain (Bulte et al, 2012; Gauthier et al, 2012; Wise et al, 2013), providing quantitative estimates of a critical physiological function
In this manuscript we have presented a novel framework for the analysis of dual-calibrated data to produce simultaneous estimates of CMRO2 and effective oxygen diffusivity
The effective diffusivity was found to increase during functional activation, with a 12.5% increase in diffusivity being associated with a 15.1% increase in CMRO2 and 21.4% increase in cerebral blood flow (CBF)

Summary

Introduction

Calibrated fMRI measurement of absolute cerebral rate of oxygen metabolism (CMRO2) offers a non-invasive method of mapping oxygen consumption in the brain (Bulte et al, 2012; Gauthier et al, 2012; Wise et al, 2013), providing quantitative estimates of a critical physiological function. The method does not directly consider the transport of oxygen into the tissue, which is principally constrained by cerebral blood flow (CBF) and the effective oxygen diffusivity of the capillaries (Buxton and Frank, 1997; Gjedde et al, 1999; Hayashi et al, 2003; Hyder et al, 1998; Mintun et al, 2001; Vafaee and Gjedde, 2000; Valabregue et al, 2003; Zheng et al, 2002). The effective diffusivity does not appear to be a fixed property of the tissue and may play a crucial role in neurovascular coupling, with oxygen diffusivity being observed to parallel increases in demand and compensate for reductions in oxygen delivery (Hayashi et al, 2003, 2004; Hyder et al, 1998; Vafaee and Gjedde, 2000)

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