André Döring1, Derek K Jones1, and Roland Kreis2,3
1Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, United Kingdom, 2Magnetic Resonance Methodology, Institute of Diagnostic and Interventional Neuroradiology, University Bern, Bern, Switzerland, 3Translational Imaging Center, sitem-insel, Bern, Switzerland
Synopsis
We demonstrate that, even without having water as an internal reference,
a combination of spectral registration and fitting can restore artificial
signal loss promoted by incoherent averaging due to frequency/phase drifts and
motion-induced dephasing for the cardinal brain metabolites (tCr, tCho, tNAA,
Glx and Ins) by using a set of synthetically distorted diffusion MR
spectra (including realistic phase, frequency and amplitude fluctuations).
Introduction
For non-water-suppressed diffusion MR spectroscopy (dMRS), the water
signal had been suggested as a high signal-to-noise-ratio (SNR) internal
reference to judge and compensate for motion-related signal distortions and
amplitude loss1. However, a strong water signal is not always
available, e.g., if conventional water-suppression is used or at high b-values
where water has largely decayed, but the need for correction of motion-related
amplitude fluctuation is biggest.
The aim of this work is to demonstrate, on a set of synthetic diffusion
MR spectra with realistic frequency, phase and motion distortions (but known
ground truth (GT) values) that a combination of spectral registration, advanced
fitting and motion compensation can restore artificial signal loss related to incoherent
averaging and motional dephasing even without using a water reference.Methods
Preparation of Synthetic Data (Fig. 1) uses GT diffusion decays provided during the
dMRS fitting challenge of the “Best practices and tools for Diffusion MR
Spectroscopy” workshop
2. The data-set is composed of 18 metabolites
and a macromolecular background at 9 different b-values (0…50k s/mm²) simulated
for a STEAM sequence (TE/TM: 45/60ms) at B0 of 7T. Realistic
spectral distortions were added to the GT in 4-steps:
- Amplitude Loss mimicking effects of
non-linear motion realized by rescaling individual acquisitions according to a Weibull distribution keeping 5/32 shots
(≈15%) above
a signal-level of 98% (portion of unaffected acquisitions). Signal decay
gradually amplified with b-value (at highest b-value maximum decay to below 20%).
- Phase
Distortions with a constant but
randomly-selected phase offset between ±30° for each b-value and modulated with a uniformly distributed random variation of
phases for single acquisitions (SD increases from 15° at bmin to
400° at bmax).
- Frequency
Shifts modeled by a gradually
increasing constant offset (0Hz at bmin to 30Hz at bmax)
plus random normally distributed
offsets for single acquisitions (SD 10Hz).
- White
Gaussian Noise random at each acquisition
and increased in amplitude to create a set of 6 noise realizations with
gradually worsening SNR.
Analysis of
Synthetic Data (Fig. 2) used
2 alternative preprocessing routines:
FID-A3 (2-steps) and
FID-A+FiTAID4 (3-steps), followed by diffusion modeling in
FiTAID imposing a bi-exponential prior
5:
- Pre-Frequency
alignment realized by identifying
and aligning NAA peak in the modulus spectrum of each acquisition, broadened by
10Hz Gauss.
- Spectral
registration (FID-A) done in
time-domain with FID-A6. For b=0s/mm² single scans aligned to the best
shot with the lowest unlikeness metric; for b>0s/mm² alignment referenced to
the average b=0s/mm² spectrum.
- Amplitude
compensation (FID-A+FiTAID) in
two sub-steps: (i) Single shots fitted to the initial averaged spectrum from
step 2 to estimate remaining frequency and phase offsets, but also amplitude
fluctuations. (ii) These offset data were imported into MatLab for
fine-tuned frequency/phase alignments and to apply signal rescaling to the 15%
quantile of shots with the highest amplitude to compensate for motion1. Estimated areas used as weights for weighted averaging
(square of the noise)1.
Results and Discussion
Root-Mean-Square-Errors (RMSEs) of frequency and phase drifts
(Fig. 3) with respect to GT show that fine-adjustment in the FID-A+FiTAID
pipeline only yields marginal improvements (at low b-value and noise-level). At
a specific noise threshold, depending on b-value and noise-level, it becomes
evident that spectral misalignment kicks in, which increases the RMSEs. Further,
we found that the pre-frequency alignment step was quite beneficial for
spectral registration, which particularly improved the frequency offset
correction, while phase alignment remained robust (not shown).
Comparing spectra corrected with FID-A and FID-A+FiTAID (Fig. 4)
reveals significant differences in peak amplitudes, where uncorrected motion
attenuation yields elevated residues for FID-A.
However, correction of signal loss is also limited for high noise levels and
b-values, where worsening SNR prevents a reliable quantification of signal
amplitudes in single shots.
If motion remains uncorrected, as in the standard dMRS FID-A processing
scheme (left in Fig. 5A) the resulting diffusivities are overestimated (spurious
signal decay). In contrast, motion compensation applied in FID-A+FiTAID (right
in Fig. 5A) widely mitigates this effect. However, aside from motion-induced
signal loss it is apparent that SNR deterioration at higher noise levels also
contributes to determination of an artificially faster diffusion (except for
tCho).
Fig. 5B juxtaposes both correction approaches where the
Root-Mean-Square-Relative-Errors7 (RMSREs) improve for all metabolites and
almost all noise levels after motion compensation. Indeed, the reliable
improvement of RMSREs for NAA at all noise levels indicates that motion
detection works accurately even at low SNR. The fluctuations in efficiency of
FID-A+FiTAID, as visible for Glx and Ins, thus can be expected to be rather
related to generally worse fitting efficiency at such high noise levels.
A limitation of this study should be noted: synthetically generated distortions do not include stronger
eddy-currents and line broadening at higher b-values.Conclusion
Using the novel motion-compensation scheme allows for more accurate
estimation of diffusion at high b-values where the water reference signal may
have substantially decayed and also macromolecular signals may often not be
available for amplitude rescaling. It may thus promote a more accurate
quantification of cellular parameters.Acknowledgements
Supported by the Swiss National Science Foundation (SNSF #188142 and #202962).References
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