Mapping the pharmacological modulation of brain oxygen metabolism: The effects of caffeine on absolute CMRO2 measured using dual calibrated fMRI

Abstract

This study aims to map the acute effects of caffeine ingestion on grey matter oxygen metabolism and haemodynamics with a novel MRI method. Sixteen healthy caffeine consumers (8 males, age=24.7±5.1) were recruited to this randomised, double-blind, placebo-controlled study. Each participant was scanned on two days before and after the delivery of an oral caffeine (250mg) or placebo capsule. Our measurements were obtained with a newly proposed estimation approach applied to data from a dual calibration fMRI experiment that uses hypercapnia and hyperoxia to modulate brain blood flow and oxygenation. Estimates were based on a forward model that describes analytically the contributions of cerebral blood flow (CBF) and of the measured end-tidal partial pressures of CO and O to the acquired dual-echo GRE signal. The method allows the estimation of grey matter maps of: oxygen extraction fraction (OEF), CBF, CBF-related cerebrovascular reactivity (CVR) and cerebral metabolic rate of oxygen consumption (CMRO). Other estimates from a multi inversion time ASL acquisition (mTI-ASL), salivary samples of the caffeine concentration and behavioural measurements are also reported. We observed significant differences between caffeine and placebo on average across grey matter, with OEF showing an increase of 15.6% (SEM±4.9%, p<0.05) with caffeine, while CBF and CMRO showed differences of -30.4% (SEM±1.6%, p<0.01) and -18.6% (SEM±2.9%, p<0.01) respectively with caffeine administration. The reduction in oxygen metabolism found is somehow unexpected, but consistent with a hypothesis of decreased energetic demand, supported by previous electrophysiological studies reporting reductions in spectral power with EEG. Moreover the maps of the physiological parameters estimated illustrate the spatial distribution of changes across grey matter enabling us to localise the effects of caffeine with voxel-wise resolution. CBF changes were widespread as reported by previous findings, while changes in OEF were found to be more restricted, leading to unprecedented mapping of significant CMRO reductions mainly in frontal gyrus, parietal and occipital lobes. In conclusion, we propose the estimation framework based on our novel forward model with a dual calibrated fMRI experiment as a viable MRI method to map the effects of drugs on brain oxygen metabolism and haemodynamics with voxel-wise resolution.

Caffeine-induced Plasticity of Grey Matter Volume in Healthy Brains: A placebo-controlled multimodal within-subject study

“…These apparent total GM changes emphasize the importance of controlling for caffeine consumption in repeated fMRI measures, especially with a region of interests in the most impacted regions (cuneus, precuneus, cerebellum, and subcortices). The observation of the typical caffeine-induced reductions in CBF 42,57,58 in our study, moreover add to the current knowledge that the history of caffeine intake at least within 4.5 hours strongly impacts on both CBF and apparent tissue change.…”

Vascular effects of caffeine found in BOLD fMRI

“…gray matter), while the opposite was found in the white matter and lower part of the brain. Our results are consistent with previous ASL findings, which reported that decreasing CBF were widespread in the grey matter after caffeine intake (Buch et al 2017; Merola et al 2017). Compared to the delay map difference shown in Figure 5.a, we found that the regions of vessel constriction after caffeine intake overlap largely with the regions where the blood flow speed increases.…”

Three‐Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple Sclerosis

“…The CSF regions of interest (ROI) was obtained in native space based on a surface‐based atlas using FreeSurfer following cortical reconstruction . Estimated values of CBF were masked within range (0‐200) mL/100 g/minute to exclude implausible physiologic values . Baseline CBF and BOLD values were then averaged across time to reduce variability and maximize statistical power.…”

“…29 Estimated values of CBF were masked within range (0-200) mL/100 g/minute to exclude implausible physiologic values. 30 Baseline CBF and BOLD values were then averaged across time to reduce variability and maximize statistical power. Lesion and perimeter 1-4 masks were applied to average baseline CBF and BOLD maps to obtain average BOLD and CBF in and around MS lesions.…”