Hideto Kuribayashi1, Yuta Urushibata1, Thuy Ha Duy Dinh2, Hirohiko Imai3, Sinyeob Ahn4, Ravi Teja Seethamraju5, Tadashi Isa2, and Tomohisa Okada2
1Siemens Healthcare K.K., Tokyo, Japan, 2Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan, 3Kyoto University Graduate School of Informatics, Kyoto, Japan, 4Siemens Medical Solutions, Berkeley, CA, United States, 5Siemens Medical Solutions, Boston, MA, United States
Synopsis
Single voxel MRS
pulse sequences of semi-LASER and short-TE STEAM were compared for cerebral
glucose quantification via detecting H1-α-glucose peak at 5.23 ppm. Young healthy non-fasted subjects were
scanned on a whole-body 7T MRI. Spectra
were analyzed on LCModel and in-house MATLAB software. Semi-LASER (32-ms TE) detected the H1-α-glucose
peak at posterior cingulate cortex (27-mL volume) with higher SNR (9.1 vs 5.1)
than short-TE STEAM (5-ms TE) in shorter scan time (11 vs. 12.5 minutes), respectively,
and estimated glucose concentration to be 1.26 mM. More robust water suppression techniques are
required to stabilize baselines around the peak.
Introduction
Cerebral
neurochemicals are effectively detected using 1H MRS at ultra-high
field due to high sensitivity and peak separation. However, it has seldom been used to measure cerebral
glucose due to its low sensitivity in detecting glucose peaks, which are
separated by anomeric configurations, split further by J-coupling, and overlap
with peaks from other metabolites and macromolecules.1 H1-α-glucose peaks at 5.23 ppm are free of
spectral overlap and has been recorded in the human brain at 4 T.2-3 Recently, 1H downfield MRS has been
performed in the human brain at 7 T,4-5 which includes the H1-α-glucose
peaks. In the report5 using short-TE
STEAM pulse sequence, the spectra were severely contaminated by extracranial
lipid signals due to chemical shift displacement (CSD). Semi-localized by adiabatic selective refocusing
(semi-LASER) pulse sequence has been proposed for effective signal detection
and CSD reduction.6 The current study
compared those pulse sequences for cerebral glucose quantification.Methods
This study was
approved by an institutional review board, and written informed consent was
obtained from subjects. The 11 healthy non-fasted
subjects (aged 20-23 years) were scanned on a whole-body 7T scanner (MAGNETOM
7T-prototype, Siemens Healthcare, Erlangen, Germany). A single-channel transmit, and 32-channel
receive head coil (Nova Medical, MA, USA) was used. An MRS voxel was positioned at the posterior
cingulate cortex (27 mL) in the mid-sagittal plane on T1-weighted
images. B0 shimming was
achieved using FASTESTMAP (Siemens prototype sequence) (7). B1 amplitude was adjusted for the
MRS voxels.
MR spectra were acquired using Siemens prototype
sequences of semi-LASER (TR/TE = 6500/32 ms, signal average = 96, scan time =
11 min) and short-TE STEAM (TR/TE/TM = 5700/5/45 ms, signal average = 128, scan
time = 12.5 min) with VAPOR water suppression8 and outer volume
suppression. Identical
MRS parameters were RF transmitter offset = 4.2 ppm, spectral width = 6
kHz, data points = 2048. In pilot studies with volunteers, order and polarity of
slice gradients were chosen to reduce lipid contamination and the TRs
were determined as the shortest values under SAR limitation. Water
spectra in the MRS voxels were acquired too.
Spectra were analyzed using LCModel
(version 6.3-1L). A semi-LASER basis set
was developed in-house. Spectral phase
parameters were determined with automatic phase correction for a spectral range
of 0.2-4.0 ppm and were applied to that of 0.2-6.0 ppm for further analysis. Eddy current correction9 and water-scaling
for quantification10 were performed using the water spectra. Estimated concentrations were corrected with
water content in the MRS voxels11-12 and with institutional calibration
factors for the sequences tested using a 1 % agar gel phantom containing 5 mM
creatine monohydrate. A
sum of fitted spectra of creatine and phosphocreatine was served as a reference.
The H1-α-glucose peaks in the
baseline-corrected spectra were fitted to a Lorentzian peak with additional
linear baseline correction in 5.05-5.45 ppm using in-house software on MATLAB
(The MathWorks, Natick, MA, USA). The height,
linewidth, and integral of the peaks were measured. SNR was calculated with the noise level as the
SD of the signals in 0.2-0.6 ppm. The glucose
concentration was calculated using ratios of the peak integrals, of the number
of protons producing those peaks, of D-glucose isomers, and the concentration
of the reference. Metabolite
concentrations are expressed in mM without correction for relaxation times. Statistical analysis was conducted between
the sequences, and a P < 0.05 was considered significant.Results
Lipid contamination
was not observed in all the spectra except one short-TE STEAM spectrum. The spectra acquired from all the subjects are
shown in Figure 1. The H1-α-glucose peak
was detected in all the semi-LASER spectra but was not identified in two
short-TE STEAM spectra. In a subject, the
peak could not be fitted in both spectra due to strong nuisance signals between
the peaks of glucose and water. Results
from the spectral analysis are shown in Table 1. The linewidths and SNRs of the H1-α-glucose
peak were significantly broader and higher in the semi-LASER spectra than those
in the short-TE STEAM spectra, respectively.
The median glucose concentrations based on semi-LASER and short-TE STEAM
were 1.26 and 0.74 mM, respectively.
Line
shapes of the residual water peak resembled in each sequence. Water peaks were significantly better
suppressed in the short-TE STEAM spectra than those in the semi-LASER spectra. Baselines around the H1-α-glucose peak were
instable, especially in the semi-LASER spectra. Discussion
In this study,
semi-LASER demonstrated higher sensitivity to detect the H1-α-glucose peak than
short-TE STEAM. Even though the SNR of
the peak in the short-TE STEAM spectra was in a range of acceptable values (SNR
> 5) for estimating a detection limit in analytical chemistry guideline,13 the lower SNR inherent in STEAM sequence
might lead to the results of the narrow line width and underestimation of glucose
concentration. Another reason for the
concentration difference might be CSD. More
robust water suppression techniques are required to stabilize baseline around
the H1-α-glucose peak for fitting.Conclusion
Semi-LASER has an
advantage to detect the H1-α-glucose peak in the human brain over short-TE
STEAM, but water suppression technique should be improved for quantification. Acknowledgements
The authors thank
Mr. Koji Yasuda (LA Systems) to support LCModel, Dr. Lana G Kaiser (University
of California, Berkeley) to provide the semi-LASER basis set, Dr. Tobias Kober
(Siemens Healthcare GmbH) to provide the prototype MPRAGE sequence.References
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