Sebastian Thomas1, Simon Hubertus1, Alycia Lee2, Sabine Vollstädt-Klein*2, and Lothar R. Schad*1
1Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, 2Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Synopsis
The
effects of smoking on human brain hemodynamics have been investigated in PET
studies, but no real consensus has been found. In this study, an MRI-based
approach using arterial spin labelling and multi-parametric quantitative BOLD
is implemented to measure the chronic effects of cigarette smoking on the
cerebral blood flow, oxygen extraction fraction and cerebral metabolic rate of
oxygen. Chronic effects between smokers and never-smokers were detected in
three regions for CBF, three regions for OEF, and one region for CMRO2.
Introduction
Despite the fact that cigarette smoking
is one of the most common addictions worldwide, there is still no consensus
about the effects of smoking-induced nicotine administration on brain
metabolism.1-3 Hemodynamic parameters, such
as cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral
metabolic rate of oxygen (CMRO2) have been examined in positron emission
tomography (PET) studies with 15O tracer. In a previous work, we implemented an
MRI based approach to measure the acute effects of smoking on the brain
oxygenation and perfusion.4 Here, the chronic effects of
smoking are investigated with an arterial spin labelling (ASL) and multi-parametric
quantitative BOLD (qBOLD) approach.Methods
20
chronic smokers (29±9 (s.d.) years, 7 women) were recruited for this study,
which was approved by the local ethics committee. All participants were asked
to refrain from smoking at least 8 hours prior to the measurement and their abstinence was confirmed with a breath CO
monitor. The measurements consisted of two sessions, each lasting approximately
30 minutes, and an intermediate break of 30 minutes during which the
participants smoked one cigarette. Ten healthy never-smokers (21±4 (s.d.) years,
4 women) were also recruited for the study. They underwent the same procedure
except for the smoking break and second session of MRI measurements.
2D multi-gradient echo (mGRE), 2D multi-spin
echo (mSE), 2D-EPI pseudo-continuous arterial spin labelling (pCASL) and
T1-weighted MPRAGE data was acquired on a clinical 3T Magnetom TRIO scanner using
a 32-channel head-coil (Siemens Healthineers, Erlangen, Germany). The
parameters for mGRE were: TR/TE1/ΔTE = 2650/4.5/5.5 ms, 12 echoes, resolution =
1.7x1.7 mm² with 20% slice gap, slice thickness 1.5 mm, 66 slices, matrix size = 128x96,
acquisition time = 5:18 min. The mSE parameters were: TR/TE1/ΔTE =
2650/13.1/13.1 ms, 12 echoes, resolution = 2x2 mm² with 20% slice gap, slice thickness 2 mm, 45
slices, matrix size = 128x96, acquisition time = 7:19 min. The pCASL parameters
were: TR/TE = 5000/16 ms, resolution = 3x3 mm² with 20% slice gap, slice thickness 3 mm, 28 slices,
matrix size = 80x80, 48 averages, acquisition time = 8:05 min, post-label delay
(PLD) = 1500 ms, label duration (LD) = 1500 ms and the labelling plane was
placed perpendicular to the internal carotid artery roughly 80 mm below the
anterior-posterior-commissure line.
R2* and R2 values including a noise
offset were fitted to the mGRE and mSE magnitude data respectively. CBF in ml/100g/min
was estimated from the pCASL data according to the white paper5 with the deoxygenated blood
volume DBV in ml/100g given by6,7
DBV=0.77*2.1*CBF0.32. The MPRAGE data sets were registered to the
MNI305 standard
brain8 and segmented into cortical and subcortical regions of interest (ROIs)
using Freesurfer.9 OEF in % and CMRO2 in
µmol/100g/min were calculated as
$$\mathrm{OEF}=\frac{3}{4 \pi \gamma \mathrm{B}_{0}} \cdot \frac{R_{2}^{*}-R_{2}}{\mathrm{DBV}} \cdot \frac{1}{\Delta x_{\mathrm{do}} \cdot \mathrm{Hct}}$$
$$\mathrm{CMRO}_{2}=\mathrm{OEF} \cdot \mathrm{CBF} \cdot[\mathrm{H}]_{\mathrm{a}}$$
with the
haematocrit Hct = 0.357, susceptibility difference between fully oxy- and
deoxygenated blood10
Δχdo = 0.27 ppm and the heme molar concentration
[H]a = 7.377 μmol/ml for an arterial oxygen saturation11 of Ya = 0.98. Inter-subject
means of OEF, CBF and CMRO2 were calculated in all segmented brain regions
shown in Figure 2. Smokers in the pre- and post-smoking state were compared
with never-smokers for all parameters in all ROIs. In order to account for the significant
age difference between smokers and never-smokers, age was included in the tests
as covariate. For the statistical analysis, IBM SPSS Statistics version 24 (IBM
Corp., Armonk, NY, USA) was used. Four smokers were excluded from the
statistical analysis due to apparent artifacts in the R2* maps. Statistical
significance was assumed for p < 0.05.
Results
Figure 1 depicts a representative
slice of the R2*, R2, R2’ = R2*- R2, CBF, DBV, OEF and CMRO2 maps
of a single subject (pre-smoking) as well as the corresponding T2 weighted
image as reference. Contrast between gray and white matter can be observed in
CBF, OEF and CMRO2.
The ROIs defined by the cortical and
subcortical segmentation are depicted in Figure 2.
Boxplots comparing CBF, OEF and CMRO2
in the pre- and post-smoking state with the never-smoking state are illustrated
in Figure 3. Significant differences were found in CBF in the full brain,
parietal lobe and white matter, OEF in the full brain, cortical gray matter and
temporal lobe, CMRO2 in the putamen. ROIs not showing any significance were
omitted in the figure.Discussion
In
this study, we applied an ASL and multi-parametric qBOLD method in never-smokers
and smokers. Significant chronic effects were detected in three regions for
CBF, three regions for OEF, and one region for CMRO2. A difference in CBF
between post-smoking and never-smoking state was detected. In contrast, Vafaee et al.2 found a difference in the pre-smoking state
that normalized after smoking. This study may form the basis for further
MRI-based investigations that will hopefully contribute to a consensus on the chronic
implications of cigarette smoking on the brain metabolism.Conclusion
The
combination of qBOLD and ASL allows for the measurement of significant chronic
effects of cigarette smoking on the brain oxygenation and perfusion.Acknowledgements
No acknowledgement found.References
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