Daniel Alamidi1, Jan Weis2, Christine Nabuurs3, Mats Fredrikson4,5, Andreas Frick4,6, Fredrik Ahs4,5, Jakub Kraus5,7, Jonas Persson8, and Maarten Versluis3
1Philips, Stockholm, Sweden, 2Department of Medical Physics, Uppsala University Hospital, Uppsala, Sweden, 3Philips, Best, Netherlands, 4Department of Psychology, Uppsala University, Uppsala, Sweden, 5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, 6Department of Psychology, Stockholm University, Stockholm, Sweden, 7Centre for Neuroscience, Central European Institute of Technology, Masaryk University, Brno, Czech Republic, 8Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
Synopsis
Proton MRS of the anterior cingulate cortex (ACC) is an attractive biomarker as it provides non-invasive methods
to quantify GABA levels that are linked with several psychiatric disorders. This study validates a MEGA-PRESS sequence
that combines phase cycling with real time frequency drift correction to
measure GABA spectra in phantom and human brain. The GABA levels of the ACC
were repeatable and reproducible at two different scanning sites. Consequently,
the technique is appropriate
for future longitudinal psychiatric studies.
Purpose
The anterior cingulate cortex (ACC) acts as a central
node in the brain and is important for regulation of advanced brain functions
1. Lowered γ-aminobutyric
acid (GABA) levels in the ACC region have been associated with psychiatric disorders such as depression
2.
1H MRS at 3T is able to quantify GABA, which is the most important inhibitory
neurotransmitter in the brain, with MEGA-PRESS. From an MRS perspective the dorsal ACC is a
suitable region to focus on, as it is located far away from bone and air
inhomogeneities with high SNR potential. To make
MEGA-PRESS more robust to subtraction artefacts, the ON-OFF acquisitions were acquired
pair-wise while keeping phase cycling schemes for PRESS localization. Before
investigating longitudinal changes or response to therapy the accuracy of GABA
detection in the ACC needs to be assessed. The aim of this study was to
validate a modification of the MEGA-PRESS sequence for GABA detection with repeatability
and reproducibility measurements in phantom and in the ACC on two different 3T
MRI scanners.
Materials and methods
Three consecutive 1H-MRS
MEGA-PRESS acquisitions were acquired in a GABA phantom (200 mM) and in six
healthy male volunteers at two 3T (Philips, Best, the Netherlands) MRI scanners
with different receiver coils (site A: Ingenia CX; 16 channel head coil, site
B: Achieva dStream; 32 channel head coil). The voxel (3.2 cm3) was
placed in the center of the phantom and in the ACC (Fig.1A) using the following
parameters: TR/TE = 2000/68 ms, 320 alternating ON-OFF spectra, 14 ms editing
pulses at 1.9 (ON) and 7.5 (OFF) ppm, 1024 points with a total scan time ~12
min. Acquisition was divided into 40 dynamic scans; each dynamic started with
one water reference, used for prospective frequency correction3, and
four pairs of water suppressed ON-OFF spectra (phase cycling 4) (Fig.2). GABA phantom
concentration [mM] was estimated according to the equation: C = RGABAx(2/NGABA)x(WH2O/eff),
where RGABA is relaxation times corrected GABA/H2O
spectral intensity ratio, NGABA = 2 is number of protons
contributing to the spectral intensity at 3 ppm, WH2O = 55 550
mM is water concentration, eff = 0.5 is editing efficiency4,5, T1GABA=2770
ms6, T2GABA=260 ms7 and T1H2O (2850 ms); T2H2O
(200 ms) were measured with IR-mixed-TSE8.
Phantom spectra were processed using jMRUI9 and in vivo data
using Gannet 2.110, applying 3 Hz line-broadening. GABA in vivo
levels were estimated relative to Cr. The repeatability and
reproducibility of GABA were evaluated with repeated measures ANOVA, paired
t-test and coefficient of variation (CV). Results
A typical spectrum of the phantom is shown
in Fig.3. The GABA concentration measurements in the phantom were 206 ± 2 mM
(mean ± SD) at site A and 189 ± 4 mM at site B and the CVs were 1.0% and 2.3%,
respectively. A representative spectrum of one volunteer is provided in Fig.1B.
Mean GABA+/Cr levels of the volunteers were 0.09 ± 0.01 at both sites and the
CV was 19% at site A and 9% at site B (Fig.4). Repeatability of the three
measurements showed no significant GABA+/Cr changes within each volunteer at either
site (p>0.05). The measurements were reproducible as no significant GABA+/Cr
differences were found between the scanning sites (p>0.05) (Fig.4). Discussion and conclusion
The present study demonstrates good
repeatability and reproducibility of GABA quantification in phantoms and in the
ACC brain region at two scanning sites. The ability of the technique to assess GABA
levels was confirmed in phantoms, indicating stable, accurate and reproducible
results. The mean GABA+/Cr levels were the same on both sites and correspond to
recently reported values in the medial parietal lobe11. Site A had
an increased GABA+/Cr CV that might be explained by the lower RF coil
homogeneity and sensitivity due to fewer coil elements. The phase
cycling scheme improves robustness of the MEGA-PRESS technique to motion
artefacts and to certain hardware imperfections such as imperfect RF pulse flip
angles and unwanted FIDs from non-ideal slice profiles. Acquisition of
unsuppressed water spectra at the start of each dynamic and its real time processing
enables updating of the offset frequency and thereby an efficient real time
frequency drift correction. Also, the subsequent ON/OFF acquisition and
pair-wise rejection in the data processing increases the accuracy of the GABA
ratios. Only a small, if any, frequency and phase correction is needed before
ON-OFF spectra subtraction. In conclusion, GABA quantification of the ACC with
MEGA-PRESS is suited for future longitudinal studies and is an attractive MRS
biomarker of psychiatric diseases.Acknowledgements
No acknowledgement found.References
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