Elsevier

NeuroImage

Volume 40, Issue 1, 1 March 2008, Pages 11-18
NeuroImage

Investigations on the effect of caffeine on cerebral venous vessel contrast by using susceptibility-weighted imaging (SWI) at 1.5, 3 and 7 T

https://doi.org/10.1016/j.neuroimage.2007.11.046Get rights and content

Abstract

Caffeine lowers the blood oxygenation level-dependent (BOLD) signal by acting as an adenosine antagonist, thus decreasing the cerebral blood flow (CBF). The aims of this study were to demonstrate the sensitivity of susceptibility-weighted imaging (SWI) to caffeine-induced changes in CBF and to investigate the time course and magnitude of signal change in caffeine-habituated and -abstinent volunteers. High-resolution susceptibility-weighted images were acquired with both groups at 1.5 T using a fully velocity compensated 3D gradient echo sequence. Following a native scan, subjects were given a tablet containing 200 mg of caffeine. Scans were repeated for about 1 h and the acquired 3D data sets were coregistered to each other. BOLD signal changes of several venous vessels were analyzed in dedicated ROIs. Maps of relative signal change clearly visualized the caffeine-induced signal response of veins. Only very weak signal changes of about − 2 ± 1% were found in both, grey and white matter and − 1 ± 2% in the ventricles. Maximum signal decrease of veins occurred 40–50 min after caffeine ingestion. The signal decrease was − 16.5 ± 6.5% and − 22.7 ± 8.3% for the caffeine users group and abstainers, respectively. The signal difference of both groups was statistically significant (Student's t-test, t = 2.16, p = 0.021). Data acquired at 1.5, 3 and 7 T with echo times scaled to the respective field strength display very similar temporal signal behavior.

Introduction

Susceptibility-weighted imaging (SWI) is a blood oxygenation level-dependent (BOLD) technique with high spatial resolution. This method is able to visualize veins with diameters in the submillimeter range even with conventional 1.5 T whole body MRI systems (Reichenbach et al., 1997). To detect the venous vessels, the deoxygenation state of hemoglobin is utilized as an intrinsic contrast mechanism (Reichenbach and Haacke, 2001). SWI has been successfully applied in imaging arteriovenous malformations (Essig et al., 1999), multiple sclerosis (Tan et al., 2000), trauma (Sehgal et al., 2005), stroke and hemorrhagic lesions (Hermier and Nighoghossian, 2004). The sensitivity of the SWI contrast mechanism has been further demonstrated by breathing carbogen, which is a gas mixture of 95% O2 and 5% CO2 that causes vasodilation and hence an increase in cerebral blood flow (CBF). The increased CBF causes an increasing venous blood oxygenation level which results in higher SWI signal (Rauscher et al., 2005). Recent work by Ge et al. (2007) also demonstrated venous signal changes during voluntary hyperventilation and apnea in SWI.

Caffeine is a widely used neuronal stimulant which is naturally available and mainly consumed in the form of coffee and tea. Caffeine absorption from the gastrointestinal tract is rapid and reaches nearly 100% in humans in about 45 min after ingestion (Fredholm et al., 1999). Peak blood plasma caffeine concentration is reached between 15 and 120 min after ingestion, with the plasma half-life time ranging from 2.5 to 4.5 h in humans (Fredholm et al., 1999).

Caffeine acts as an adenosine antagonist and inhibits A2A receptors (Ongini and Fredholm, 1996). The consequence of this inhibition is vasoconstriction of cerebral vessels (Meno et al., 2005, Nehlig et al., 1992) and thus a decrease in CBF (Cameron et al., 1990, Field et al., 2003, Lunt et al., 2004). In a recent study by Blaha et al. (2007), the vasoconstrictive effect of caffeine was demonstrated even in a dilated cerebral circulation induced by hypercapnia. While there is sufficient cerebral perfusion reserve in healthy subjects, the reduction in CBF of up to 30% (Cameron et al., 1990) may become a problem in, e.g., stroke patients (Kaufmann et al., 1999).

The effect of caffeine on the BOLD signal response was also demonstrated in fMRI experiments. Caffeine caused a faster and higher signal increase (Liu et al., 2004), as well as a disappearing of the initial dip (Behzadi and Liu, 2006). Liu et al. (2004) further demonstrated by using block-design paradigms that the quickly raised BOLD signal decreased shortly after the beginning of the stimulus. The quick and higher signal increase was used by Mulderink et al. (2002) to boost the BOLD contrast with event-related stimulation paradigms. However, due to the signal decrease shortly after the rise Laurienti et al. (2003) concluded that caffeine does not improve the BOLD response in block-design fMRI paradigms. In a recent SWI study, it was also shown that the use of caffeine enhanced the resting state BOLD effect and the ability of SWI to image small vessels in the brain (Haacke et al., 2003).

The aim of this study was to quantify and to monitor caffeine-induced signal changes in venous vessels using SWI during the first 60 min after intake. Signal changes were evaluated in caffeine habituated and abstained volunteers for a dose of 200 and 100 mg. Initial measurements at high and ultra high field strengths (3 and 7 T) were acquired to check the consistency of the observed effect and the potential of SWI at higher field strengths to detect small changes in venous blood oxygenation.

Section snippets

Subjects

Two groups of healthy subjects were investigated. The first group (6 females, 6 males, mean age = 25.0 ± 2.9 years, mean body mass = 69 ± 15 kg) consisted of coffee drinkers with a consumption of more than 200 mg of caffeine per day; the second group (7 females, 8 males, mean age = 24.1 ± 3.3 years, mean body mass = 72 ± 9 kg) consisted of abstinent volunteers.

The classification of subjects into the groups was based on a questionnaire about their eating and drinking habits. All measurements were carried out in

Abstainers and caffeine users

Fig. 2 shows the results of the quantitative analysis for all subjects of each group averaged over all venous ROIs. The signal, ΔS, decreases within the first 30 min after application of caffeine and reaches a minimum plateau between 40 and 50 min that lasts for the whole remaining measured time course. On the contrary, the signal of the ventricles, drawn for control, shows no apparent change.

Averaging the signal changes ΔS in the time interval from 40 to 50 min yields a mean value ± standard

Discussion

BOLD signal changes in small venous vessels induced by a common dose of orally applied caffeine (200 mg) were detected with SWI. In our study groups, the effect was found to be stronger in caffeine abstinent subjects compared to a group of coffee drinkers. This finding seems in disagreement with an earlier study by Field et al. (2003) who investigated caffeine-induced CBF changes by using an arterial spin labeling (ASL) technique. Field et al. (2003) reported a higher caffeine-induced response,

Conclusion

Visualization of the venous vascular system with exquisite detail and monitoring the response to changing blood oxygenation at the same time is possible by using high-resolution susceptibility-weighted imaging (SWI). Differences in induced signal change could be resolved between the two groups of caffeine users and abstainers after ingestion, underlining the sensitivity of the susceptibility-weighted method. Caffeine consumption influences the BOLD contrast of venous vessels which should be

Acknowledgments

We thank Johannes Bernarding and Claus Tempelmann (both Otto-von-Guericke University, Magdeburg, Germany) for their helpful discussions and remarks as well as their support to acquire 7 T data. Our team also gratefully acknowledges support from Siemens Medical Solutions.

This study was partly funded by the Deutsche Forschungsgemeinschaft (DFG) (grant no. RE 1123/7-1&2) and the Interdisciplinary Center for Clinical Research (IZKF) Jena (01ZZ0405). Katharina Helm was supported by a young

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