Sources of systematic error in calibrated BOLD based mapping of baseline oxygen extraction fraction

Nicholas P Blockley,Valerie E.M Griffeth,Alan J Stone,Hannah V Hare,Daniel P Bulte

doi:10.1016/j.neuroimage.2015.07.059

Nicholas P Blockley, Valerie E.M Griffeth + Show 3 more

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https://doi.org/10.1016/j.neuroimage.2015.07.059

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Abstract

Recently a new class of calibrated blood oxygen level dependent (BOLD) functional magnetic resonance imaging (MRI) methods were introduced to quantitatively measure the baseline oxygen extraction fraction (OEF). These methods rely on two respiratory challenges and a mathematical model of the resultant changes in the BOLD functional MRI signal to estimate the OEF. However, this mathematical model does not include all of the effects that contribute to the BOLD signal, it relies on several physiological assumptions and it may be affected by intersubject physiological variability. The aim of this study was to investigate these sources of systematic error and their effect on estimating the OEF. This was achieved through simulation using a detailed model of the BOLD signal. Large ranges for intersubject variability in baseline physiological parameters such as haematocrit and cerebral blood volume were considered. Despite this the uncertainty in the relationship between the measured BOLD signals and the OEF was relatively low. Investigations of the physiological assumptions that underlie the mathematical model revealed that OEF measurements are likely to be overestimated if oxygen metabolism changes during hypercapnia or cerebral blood flow changes under hyperoxia. Hypoxic hypoxia was predicted to result in an underestimation of the OEF, whilst anaemic hypoxia was found to have only a minimal effect.

Highlights

A new class of calibrated blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (MRI) methods were introduced to quantitatively measure the baseline oxygen extraction fraction (OEF) (Bulte et al, 2012; Gauthier et al, 2012; Wise et al, 2013)
In addition a discontinuity is observed at low E0 values, consistent with the scatter observed in the hyperoxia BOLD response
Investigation of the assumptions that underlie the Davis model revealed that OEF measurements are likely to be overestimated if CMRO2 is reduced during hypercapnia but constant CMRO2 is assumed by the model

Summary

Introduction

A new class of calibrated blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (MRI) methods were introduced to quantitatively measure the baseline oxygen extraction fraction (OEF) (Bulte et al, 2012; Gauthier et al, 2012; Wise et al, 2013) These methods rely on two respiratory challenges to induce hypercapnia and hyperoxia resulting in changes in the BOLD signal. The change in the end-tidal partial pressure of oxygen (PETO2) during hyperoxia is measured using a gas analyser These data are combined with a mathematical model of the BOLD response (Davis et al, 1998; Hoge et al, 1999) to estimate the baseline OEF. These errors are difficult to investigate experimentally as the ground

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