Maike Hoefemann1, André Döring1, and Roland Kreis1
1Departments of Radiology and Biomedical Research, University of Bern, Bern, Switzerland
Synopsis
A new sequence design was used to combine the
CEST saturation method with traditional MRS. Using non-water suppressed metabolite-cycled
spectroscopy offers the time-saving simultaneous recording of the traditional
CEST z-spectrum and the metabolite spectrum under frequency selective
saturation and allows the detection of exchange and magnetization transfer effects on metabolites
and macromolecules. This technique might offer additional possibilities for quantifying the
metabolite and macromolecular content or give further insight into the composition of the
traditional CEST z-spectrum and is also relevant for judging the influence of
water-suppression on absolute metabolite signals.
Introduction
CEST MRI is by now an established method to investigate
metabolites that show magnetization exchange with water, thus complementing
traditional spectroscopy for a specific range of metabolites with the benefit
of drastically improved sensitivity, but also with the challenge of limited
specificity (spectral overlap, other effects on exchange rates) and
applicability. Aspects of sequence design and quantification of the components
of the z-spectrum have recently been reviewed in detail1–4. Spectroscopy has been combined
with CEST previously to correct the z-spectrum for fat signals in extracranial human
applications5 and in rat brain6. Specific magnetization transfer
(MT) effects from water to metabolites have also been studied in human and
animal brain and muscle7–10. However, the acquisition of the
complete metabolite spectrum in combination with CEST saturation over the whole
spectral range has not been reported for human studies previously, and furthermore
the currently proposed method allows for acquisition of MRS and CEST water data
in simultaneous fashion. Methods
Sequence Design:
The basic design of
the sequence is shown in Figure 1. A CEST saturation block consisting of a
train of Gaussian RF pulses and spoiler gradients is placed before a metabolite-cycled
semiLASER spectroscopy localization sequence. The saturation parameters (number
of pulses, duty cycle, flip angle, saturation duration) are adjustable to allow
optimization of the saturation for a specific target.
Data acquisition:
Data was acquired on 10
healthy volunteers (aged 37±16 years) with the following
conditions: 3T MR scanner (Prisma, Siemens, Germany), 64-channel headcoil; supraventricular
voxel (45x70x20 mm3); second-order shim (option “brain”); TR 3300
ms; TE 45 ms; 41 measurements with saturation from -6 to 6 ppm (0.3 ppm spacing;
one scan at -100 ppm), 24 averages each (60 min acquisition); 2000 ms
saturation, duty cycle 80% (see Figure 1), 50 pulses (32 ms each), flip angle
180° (B1 =0.36 µT); additional reference scan
without CEST train with 64 averages.
Data evaluation:
Metabolite-cycled
data was aligned and eddy-current-corrected in MATLAB and residual water
removed using HLSVD. Z-spectra were calculated from the water intensity of each
measurement (second point in time domain) and fitted using a 8-pool Lorentzian
model, including direct saturation, MT effect, exchange effects from amines,
amides, guanidines, hydroxyls, plus two NOE pools (at -1.6 and -3.5 ppm). MT
effect was approximated as Lorentzian given the small ppm range investigated.
Metabolite spectra
fitted in FitAID11 using a model consisting of 18
metabolites and a macromolecular background (MMBG) represented by 64 equally
spaced Voigt lines (∆=0.05 ppm, 0.7-4.1 ppm, 5 Hz Gaussian, 9 Hz Lorentzian
broadening). Offset, phase, Lorentzian/Gaussian broadening fitted
simultaneously for the whole dataset, areas of metabolites and macromolecules (MM)
allowed to adapt for each measurement independently in a subsequent step.
Results and Discussion
The effect of the saturation on
water and metabolite signals is illustrated in Figure 2. Figure 3 illustrates the
water signal intensity used to evaluate the traditional CEST z-spectrum for a
representative subject. Fitting of the z-spectrum showed the expected exchange
and NOE effects. The MT effect is small‑as expected for a low B1
value. The standard deviations of the fitting results for the cohort reflect good
agreement between subjects. No NOE effect at -1.6 ppm (reported for rat brain12) was found in this study.
The magnetization transfer effect from water to
metabolites is visualized in Figure 4 for a single subject and the cohort average.
The average spectrum also reflects effects on certain parts of the MMBG, especially
between 2.0 - 2.8 ppm and 3.4 - 4.1 ppm. Parts of the signal drop might be caused
by interfering influence of direct saturation effects close to the water
resonance. Furthermore, irradiation at -100 ppm did not have any effect on main
metabolites compared to the non-saturated reference scan.
Figure 5 shows the fitted signal intensity of
selected metabolites and selected MM regions vs. saturation frequency. Besides
the signal drop due to direct saturation, an additional effect is apparent for some
metabolites and the MMBG around the water frequency, visualizing the MT effect
for single metabolites. For the cholines and largely also for N-acetylaspartate
(NAA) this effect is strikingly missing.
The simultaneous
recording of the water signal and the metabolite spectrum under frequency-selective
saturation provides the results from two time-consuming methods at the same time.
Using an optimized voxel size13 yields high quality spectra
regarding signal-to-noise-ratio even for a few acquisitions only. Recording of spectra
under saturation promises further information on exchange factors and MT
effects for metabolites and also MM.
Conclusions
Using non-water suppressed spectroscopy offers the
time-saving simultaneous recording of the traditional CEST z-spectrum and the
metabolite spectrum under frequency-selective saturation. In addition, exchange
and MT effects on metabolites and MM can be detected, which might offer
additional possibilities for quantifying the metabolite and MM content or give
further insight into the composition of the traditional CEST z-spectrum. Effects
on MMBG have been found which have previously not been reported. Future research
will be directed at investigation of the effect of varying the B1 saturation
amplitude. Detailed knowledge of MT effects is also relevant to judge the
influence of water-suppression sequences on absolute metabolite signals. Acknowledgements
This work is supported by the Swiss
National Science Foundation (SNSF #320030‐175984).References
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