Elucidation of the downfield spectrum of human brain at 7T using multiple inversion recovery delays and echo times
Nicole D Fichtner1,2, Anke Henning2,3, Niklaus Zoelch2, Chris Boesch1, and Roland Kreis1

1Depts. Radiology and Clinical Research, University of Bern, Bern, Switzerland, 2Institute for Biomedical Engineering, UZH and ETH Zurich, Zurich, Switzerland, 3Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

Synopsis

Characterization of the full 1H spectrum may allow for better monitoring of pathologies and metabolism in humans. The downfield part (5-10ppm) is currently less well characterized than upfield; this work aims to benefit from higher field strength in order to quantify T1 and T2 in the downfield spectrum in human grey matter at 7T. We fitted downfield spectra to a heuristic model and obtained relaxation times for twelve peaks of interest. The T1’s are higher than those at 3T downfield; peaks with lower T1’s may include macromolecules. The T2’s are mostly shorter than those reported for upfield peaks at 7T.

Introduction and Purpose

Characterization of the full 1H spectrum may allow for better monitoring of pathologies and metabolism in humans than is currently possible using upfield spectra only. The focus is usually on characterization of the upfield part of the spectrum, even at very high fields[1]. The downfield part at 5-10ppm is less well characterized, and a confirmation of peak or metabolite identification as well as determination of relaxation and exchange parameters may substantially aid in clinical and basic research. Some data is available on downfield peaks for animal brain at high fields[2], as well as human brain at 3T[3]. The current work aims to elucidate the downfield spectrum in human brain and to quantify T1 and T2 in grey matter at 7T using series of spectra with variable TE and inversion recovery (IR) delays.

Materials and Methods

Acquisition methods were similar to those used in Ref.[4]; i.e. a Philips 7T scanner; quadrature transmit/receive surface coil (Rapid Biomedical); STEAM localization with VAPOR water presaturation; ROI size of 16 cm3; second-order B0 shimming; TM=26.0ms, TR=4000/7000ms for the TE/IR series, respectively. A series of TEs at 13, 23, 35, 47, and 60ms was acquired in 12 healthy volunteers (two data sets discarded due to excessive line broadening). For the IR series, an adiabatic inversion pulse was interleaved with the VAPOR sequence, and a series of IR times was acquired for 10 healthy volunteers at: 45, 150, 290, 580, 800, 1200, 2500, 4000, and 6000ms IR delay time.

The overall averaged data sets from both series were combined to develop a spectral model of partially overlapping signals in FiTAID[5]; prior knowledge was defined with twelve peaks in the 5 to 9ppm region. The N-acetylaspartate (NAA) and α-glucose (Glc) peaks were defined as binary patterns, as modeled in VESPA[6]. Homo­carnosine (hCs) was modeled as 2 peaks at well-defined chemical shifts[7]. The TE and IR data sets were then fitted simultaneously for each case with T2 and T1 as fitting variables, and water T1 and T2 values were also calculated. Errors were estimated as Cramer-Rao lower bounds (CRB). Results from very poor fits were removed such that the data for the 5.8 and 6.1 ppm peaks are not well defined.

Results

Individual and average TE and IR spectra are shown in Fig. 1. The average short-TE spectrum overlaid with the derived heuristic model and the individual peaks is presented in Fig. 2. The relaxation parameter estimates are listed in Table 1, including the average CRB.

Discussion

The heuristic model describes the experimental data well and the results for many of the peaks are very consistent across subjects (e.g. NAA and peaks around 6.8-7.3ppm, as seen from the SD and mean CRB in the table). Other peaks were more difficult to fit; although clearly visible in the averaged spectrum used to create the model, SNR is limited in the individual spectra, or they are partially affected by water suppression (Glc).

T1 values found at 7T are mostly substantially higher than those found at 3T[3], in particular for the NAA peak. Several peaks show a particularly short T1 in comparison to the others, indicating that they predominantly originate from macromolecules, which is confirmed visually in Fig. 1d, where traces with IR delays of 0.29-0.80s correspond to metabolite nulling (in particular the 6.8 ppm peak (blue arrow), which features short T1 and T2). The T2 values are in general much shorter than those found for upfield peaks[2]. For NAA, it is interesting to note that both the T1 and T2 experiments show that it is composed of more than one peak with different resonance frequency and linewidth (Fig. 1b,d red arrows, comparing the spectra at 1.20s recovery time, the one at TE=60ms, and those at shorter TE and other inversion times); strong inhomogeneous broadening likely contributed to the broad peak. Exchange might account for some of the shorter T2’s, but it is unlikely to affect the NAA value, as the exchange rate of NAA is quite low[3].

For the peaks with confirmed assignment, i.e. NAA, homocarnosine, and α-glucose, the concentrations were found to match those of the literature very well (data not shown)[7,8].

Assignments for the other peaks are still unconfirmed; however, some suggestions have been made based on literature in previous work[8,9]. Peaks with moderate to fast exchange are not expected to be visible in these spectra due to the use of VAPOR water suppression. In particular, this includes those from amides at 8.2-8.5ppm and even more so for amine protons which are a basis for CEST contrast[10].

Acknowledgements

This research was supported by the Swiss National Science Foundation (#320030_156952).

References

1. Tkac I, Andersen P, Adriany G, Merkle H, Ugurbil K, Gruetter R. In vivo 1H NMR spectroscopy of the human brain at 7 T. Magn Reson Med 2001;46:451-456.

2. De Graaf RA, Brown PB, McIntyre S, Nixon TW, Behar KL, Rothman DL. High magnetic field water and metabolite proton T1 and T2 relaxation in rat brain in vivo. Magn Reson Med 2006;56:386-394.

3. MacMillan EL, Chong DGQ, Dreher W, Henning A, Boesch C, Kreis R. Magnetization exchange with water and T1 relaxation of the downfield resonances in human brain spectra at 3.0 T. Magn Reson Med 2011;65:1239-1246.

4. Fichtner, N. D., Henning, Anke, Zoelch, Niklaus, Boesch, Chris, and Kreis, Roland. T2 estimation of downfield metabolites in human brain at 7T [abstract]. Proc Intl Soc Mag Reson Med 2015: 745.

5. Chong DGQ, Kreis R, Bolliger C, Boesch C, Slotboom J. Two-dimensional linear-combination model fitting of magnetic resonance spectra to define the macromolecule baseline using FiTAID, a Fitting Tool for Arrays of Interrelated Datasets. Magn Reson Mater Phy 2011;24:147-164.

6. Soher, B. J., Semanchuk, P., Todd, D., Steinberg, J., and Young, K. VeSPA: Integrated applications for RF pulse design, spectral simulation and MRS data analysis [abstract]. Proc Intl Soc Mag Reson Med 2011: 1410.

7. Rothman DL, Behar KL, Prichard JW, Petroff OA. Homocarnosine and the measurement of neuronal pH in patients with epilepsy. Magn Reson Med 1997;38:924-929.

8. Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 2000;13:129-153.

9. Henning, A., Fuchs, A., Boesch, C., Boesiger, P., and Kreis, R. Downfield spectra at ultrahigh field [abstract]. Proc Intl Soc Mag Reson Med 2008: 777.

10. van Zijl PC, Zhou J, Mori N, Payen JF, Wilson D, Mori S. Mechanism of magnetization transfer during on-resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids. Magn Reson Med 2003;49:440-449.

Figures

Fig. 1: a)Individual TE spectra from one volunteer, b)All volunteers’ TE spectra, averaged. c)Individual IR spectra from one volunteer, d)All volunteers’ IR spectra, averaged. Red arrows indicate inhomogeneously broadened component underlying NAA amide signal, with longer T2 than the narrower NAA peaks. Blue arrow indicates faster relaxation of 6.8ppm peak.

Fig. 2: Averaged spectrum overlaid with the fit and the individual basis peaks. Below the spectrum are the residuals for the fit. Unknown peaks are labelled with letters; j* corresponds to an artifact present in three subjects’ data.

Table 1: T2 and T1 values for the twelve peaks and unsuppressed water for all the labeled peaks in Fig. 2. Shown are the mean values, the standard deviations over the individual volunteers, and the mean CRB over the individual volunteers.



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