Parameterization of measured macromolecular background in ultra-short acquisition delay 1H MRSI in the brain at 7T
Michal Považan1,2, Gilbert Hangel1, Bernhard Strasser1, Eva Heckova1, Lukas Hingerl1, Stephan Gruber1, Siegfried Trattnig1,2, and Wolfgang Bogner1

1High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Austria, 2Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

Synopsis

Ultra-short echo/acquisition delay MRS spectra have a strong characteristic background consisting of macromolecule (MM) resonances superimposed on the signal of metabolites. Typically a single metabolite-nulled MM spectrum is included into quantification routine to account for this. To detect more prominent regional and pathologic changes, we replaced this single MM spectrum by individual MM peaks. We found that the MM peaks in a 2.3-0.5 ppm region are higher in gray matter compared to white matter, whereas the MM peaks from 2.9 to 3.2 ppm were significantly higher in white matter of healthy volunteers and one MS patient.

Introduction

Ultra-short echo/acquisition delay MRS spectra have a strong characteristic background consisting of macromolecule (MM) resonances superimposed on the signal of metabolites. Omission of MM contribution in the quantification of such spectra may yield substantial errors in the quantified metabolite levels1. As shown previously, the simulation of MM background is insufficient at ultra-high fields and a separate acquisition of MM was found to be more accurate2. Since regional differences of MM exist even in the healthy brain and a further change of distinct MM resonances3,4 was observed in various diseases, this single MM background should be replaced by individual MM peaks to account for more prominent regional and pathologic changes.

Methods

An average MM spectrum of the full spectral range was acquired using double inversion MRSI as described previously5 from 6 healthy volunteers (28±2 years). Metabolite residuals were removed from the averaged spectrum and parameterized by fitting using HLSVD implemented in jMRUI 5.2. Individual components (altogether nine separate peaks - 0.91 ppm (MM1), 1.21 ppm (MM2), 1.43 ppm (MM3), 1.67 ppm (MM4), 2.04 ppm (MM5), 2.26 ppm (MM6), 2.99 ppm (MM7), 3.21 ppm (MM8), and 3.77 ppm(MM9)) were saved separately and included into the basis set. Additionally, to assess the risk of over-parameterization several peaks were combined into altogether 5 groups (MM1 (0.9ppm); MM2-MM4 (1.2-1.6ppm); MM5-MM6 (2.04-2.26ppm); MM7-MM8 (2.99-3.21ppm) and MM9 (3.77ppm)) and included in the basis set. Data from 3 volunteers (32±3 years) were measured with a Magnetom 7T (Siemens Healthcare, Erlangen, Germany) scanner and 32 channel head coil (Nova Medical, Wilmington, USA) with the following parameters: TR, 600 ms; TE*, 1.3 ms; flip angle, 45°; FoV, 220 × 220 mm2; matrix size, 64 × 64; nominal voxel size, 3.4 × 3.4 × 12mm3; scan time ~30 min; one average with an elliptically sampled k-space acquired in a pseudo-spiral pattern; Data from one Multiple Sclerosis patient were acquired using the same protocol and acceleration using 2D Caipirinha6 with acceleration factor R=6 and scan time of ~5 min. These data were quantified in LCModel 6.3 using three different basis sets: a) a full measured MM spectrum, b) parameterized MM peaks and c) MM groups (Fig.1) and compared between white matter (WM) and gray matter (GM). A small region of GM and WM (min. 80% of the tissue) was defined in every volunteer.

Results

The data from three volunteers are displayed in form of boxplots (Fig.4). The paired t-test showed a significant difference between GM and WM levels for MM1, MM2, MM3, MM4, MM6, MM7 and MM8. The MM1 through MM6 peaks ranging from approximately 2.3 ppm to 0.5ppm were found to be higher in GM compared to WM. On the contrary, the region from 3.2 ppm to 2.8 ppm showed to be significantly higher in WM than in GM.

Discussion

We have quantified MM levels of individual MM peaks, MM groups and the full MM spectrum as well as created maps of their spatial distribution (Fig.2). Although the overall MM background in healthy volunteers was found to be higher in GM than in WM5,7, according to our findings this applies only to MM resonances from 2.26 ppm to 0.9 ppm (MM1-MM6), whereas the peaks at 2.9 ppm and 3.2 ppm (MM7-MM8) were higher in WM (Fig.2 and Fig.4). These MM resonances play an important role in GABA quantification (the so called GABA+ signal). A possible over-parameterization was excluded based on the comparison of metabolite levels for all quantification methods (Fig.3). Results obtained from a patient (Fig. 5) show that the basis set with parameterized MM can be used also for MM mapping in diseases which was not possible with unparameterized MM spectra due to a wild baseline. These results are however preliminary and need further investigation.

Conclusion

Parameterization of an averaged MM spectrum allowed us to detect subtle changes of individual MM peaks and provided additional information on MM spatial distribution in brain without biasing the metabolite quantification by over-parameterization.

Acknowledgements

No acknowledgement found.

References

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5. Považan, M., Hangel, G., Strasser, B., Gruber, S., Chmelik, M., Trattnig, S., Bogner, W., 2015. Mapping of brain macromolecules and their use for spectral processing of 1H-MRSI data with an ultra-short acquisition delay at 7T. Neuroimage 121, 126–135. doi:10.1016/j.neuroimage.2015.07.042

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Figures

A standard basis set of metabolites was extended by inclusion of parameterized MMs derived from the measured MM spectrum. The measured MM spectrum (down), the parameterized MM combined into 5 groups (middle) and individual MM peaks (up) were included in basis set separately and the fitting results were compared.

T1-weighted MRI and maps of MM distribution for three different basis sets. GM/WM differences are apparent. Most of the MM resonances are higher in GM compared to WM (applies to MM1-MM6), whereas the MM7 and MM8 peak tend to be higher in WM, which we cannot see without parameterization.

An over-parameterization of MMs may lead to erroneous levels of underlying metabolites. Metabolic maps of three major metabolites showed no significant difference between various basis sets even when individual peaks were used for quantification.

Boxplots showing the WM/GM differences of various MM peaks or MM groups. The values represent the ratio of MM peak to NAA signal. * - statistical significance, p<0.001, paired t-test

Metabolic maps, MM maps and spectra from a lesion and contra-lateral voxel of a Multiple Sclerosis patient. We observe decreased signals of NAA, tCr as well as MM7-MM8 signal. Data were fitted on 4.2 to 0.5 ppm range. Reliable quantification was not achieved with basis set with full MM spectrum.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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