Abstract

Physiological fluctuations are expected to be a dominant source of noise in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) experiments to assess tumour oxygenation and angiogenesis. This work investigates the impact of various physiological noise regressors: retrospective image correction (RETROICOR), heart rate (HR) and respiratory volume per unit time (RVT), on signal variance and the detection of BOLD contrast in the breast in response to a modulated respiratory stimulus. BOLD MRI was performed at 3 T in ten volunteers at rest and during cycles of oxygen and carbogen gas breathing. RETROICOR was optimized using F-tests to determine which cardiac and respiratory phase terms accounted for a significant amount of signal variance. A nested regression analysis was performed to assess the effect of RETROICOR, HR and RVT on the model fit residuals, temporal signal-to-noise ratio, and BOLD activation parameters. The optimized RETROICOR model accounted for the largest amount of signal variance ( = 3.3 ± 2.1%) and improved the detection of BOLD activation (P = 0.002). Inclusion of HR and RVT regressors explained additional signal variance, but had a negative impact on activation parameter estimation (P < 0.001). Fluctuations in HR and RVT appeared to be correlated with the stimulus and may contribute to apparent BOLD signal reactivity.

Highlights

  • Blood oxygenation level-dependent (BOLD) contrast exploits the differential magnetic properties of oxygenated and deoxygenated haemoglobin to enable detection of changes in blood oxygenation and flow

  • BOLD contrast is extensively used in functional magnetic resonance imaging experiments to map brain activation in response to a stimulus or to depict resting-state functional connectivity

  • Summary statistics for heart rate (HR) and respiratory volume per unit time (RVT), and the correlation between these two physiological time courses, are shown for each subject in table 1

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Summary

Introduction

Blood oxygenation level-dependent (BOLD) contrast exploits the differential magnetic properties of oxygenated and deoxygenated haemoglobin to enable detection of changes in blood oxygenation and flow. There is growing interest in applying BOLD contrast outside of the brain to assess tumour oxygenation and angiogenesis via vasomotor response to modulated hyperoxic and hypercapnic gas stimuli These experiments are analogous to fMRI of the brain, with the exception that a respiratory stimulus is needed to directly modulate blood oxygenation and flow. A pilot study in breast cancer patients undergoing neoadjuvant chemotherapy (n = 7 ) demonstrated that oxygen-induced BOLD contrast changes were significantly greater (P < 0.001) in patients exhibiting a complete pathological response versus those exhibiting partial response or stable disease (Jiang et al 2013). Background physiological variations and motion increase signal variance, and may even give rise to false-positive activation effects if they happen to be correlated with the stimulus

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