Basic Principles & Sequences for 2D MRS
M. Albert Thomas1, Zohaib Iqbal1, Manoj Kumar Sarma1, and Rajakumar Nagarajan1

1Radiology, UCLA Geffen School of Medicine, Los Angeles, CA, United States

Synopsis

In one-dimensional (1D) MR Spectroscopy (MRS), it is difficult to resolve the multitude of metabolite peaks that exist over a small spectral range. Spectral-editing techniques target a particular J-coupled metabolite selectively, such as lactate, GABA, glutamate, etc. with a drawback that only one metabolite is selected for each recording. Due to the added 2nd dimension, two-dimensional (2D) MRS can unambiguously resolve many overlapping peaks non-selectively. Instead of a standard 1D spectrum plotting intensity versus a single-axis (i.e., chemical shift + J-coupling), 2D MRS techniques produce a 2D spectrum plotting intensity versus two frequency axes, the dimensions of which depend on the specific 2D MRS technique. A major goal of this presentation is to give an overview of the basics of 2D MRS and describe several localized 2D MRS sequences which have been implemented on the whole body 1.5T, 3T, and 7T MRI scanners.

Target Audience

Basic Scientists and Medical Researchers interested in the basics of localized 2D MR Spectroscopy

Outcome/Objectives

To record localized 2D MR spectra with improved resolution that will facilitate better peak assignments and metabolite quantitation

Purpose

1) To discuss problems due to overlap and metabolite quantitation in water suppressed proton (1H) MR Spectroscopy;

2) To describe the basic theory of 2D MRS including localized correlated spectroscopy (L-COSY) and PRESS localized J-resolved Spectroscopy (JPRESS);

3) To discuss the necessary pulse sequences for 2D MRS: L-COSY, JPRESS, localized exchange spectroscopy (L-EXSY), constant time COSY (CT-COSY) and constant time PRESS (CT-PRESS)

Methods

Shown in Fig.1 and Fig.2 are 2D MRS sequences: L-COSY (Fig.1A), JPRESS (Fig.1B), L-EXSY (Fig.1C), CT-COSY (Fig.2A) and CT-PRESS (Fig.2B). As presented In Fig.1A, the 2D L-COSY sequence uses a combination of three slice-selective RF pulses (900-1800-900) to localize a volume of interest (VOI) or region of interest (ROI) in a single shot (1,2). An incremental period for the second spectral dimension (t1) was inserted immediately after the Hahn spin-echo using the first 900 and 1800 RF pulse pair. The last slice-selective 900 RF pulse acted also as the coherence transfer pulse, critical for recording the 2D spectrum (1-4). Refocusing B0 gradient crusher pulses around the slice-selective 1800 RF pulse and also, before and after the last 900 RF pulse enabled minimizing unwanted coherences. The coherence transfer between J-coupled protons of different metabolites crucial for the L-COSY sequence is presented in Fig.3. Fig. 4A shows a simulated 3T L-COSY of more than 16 metabolites using the GAMMA library (5). 2D cross peaks due to NAA, lactate (Lac). Glutamate (Glu) and myo-inositol (mI) are highlighted. Shown in Fig.4B and 4C are the same 3T 2D L-COSY spectrum recorded in a brain phantom containing all metabolites shown in Fig.4A showing the J-connectivity of NAA and glutathione (GSH) protons. The basic pulse sequence for JPRESS is shown in Fig.1B where the VOI is localized using the conventional PRESS sequence (6) containing three slice-selective RF pulses (900-1800-1800). The incremental duration (t1) was inserted immediately after the first Hahn echo and the signal was read-out along the t2 dimension (2, 7-8). The 2nd spectral bandwidth of JPRESS will be smaller than that of L-COSY due to the refocusing of chemical shifts between different protons of metabolites. The L-EXSY sequence is shown in Fig.1C, where the VOI is localized using the conventional STEAM sequence (9) including three slice-selective 900 RF pulses. The 2nd spectral dimension encoding variable t1 was inserted before the 2nd 900 RF pulse (10). Multiple averages could be used in combination with or without a multi-step RF phase-cycling to improve the SNR from the localized volume and also, to minimize any artifacts stemming from RF pulses with inaccurate flip-angles (900 and 1800). Two more variants of the localized 2D MRS, namely CT-COSY and CT-PRESS are shown in Fig.2A and 2B, respectively (11-13). Compared to the basic localized COSY spectrum, the CT-COSY spectrum can be easier to interpret with the reduced number of cross peaks for each metabolite due to decoupling along F1. CT-COSY spectra have more T2-weighting due to longer constant time (Tc) values. In contrast to the basic L-COSY and CT-COSY spectra, a further increase in SNR is possible by CT-PRESS for coupled resonances since there is no coherence transfer of magnetization between the J-coupled protons leading to the disappearance of cross-peaks. A second rf channel is not required to achieve broadband decoupling. However, two major drawbacks of the 2D CT-PRESS are: 1) The signal amplitude in CT-PRESS depends on Tc. 2) The spectrum has to be acquired in the 2D mode, which requires long acquisition time. Since the raw data acquired using 2D MRS has two dimensions (t1 and t2), a double Fourier transformation will be necessary to obtain the final 2D MR spectrum. Hence, shown in Fig.5 are the raw 2D data, data after the 1st FFT along the t2 dimension, data after the 2nd FFT along the t1 dimension and 2D stack/contour plots after the double FFT.

Conclusion

Our preliminary results clearly indicate that 2D L-COSY and JPRESS have better resolution than 1D MRS. Several metabolite multiplets have been unambiguously resolved in contrast to 1D MRS. The 2D MRS sequences have been implemented in both single and multi-voxel modes and feasibility of recording 2D MR spectra in a clinical environment is established.

Acknowledgements

Grants support from 1) National Institute of Health (5R21NS080649-02,5R21NS090956-02, 5R21NS086449-02, P50CA092131) and Department of Defense CDMRP prostate cancer research program (PCRP #W81XWH-11-1-0248).

References

1) Thomas MA, Yue K, Binesh N et al. Localized Two-dimensional Shift Correlated MR Spectroscopy of Human Brain. Magn Reson in Med 2001; 46: 58-67

2) Thomas MA, Hattori N, Umeda M, Sawada T and Naruse S. Adding a new spectral dimension to localized 3T 1H MR Spectroscopy- From Phantoms to Human Brain in vivo. NMR Biomed 2003; 16:245-251.

3) Ernst RR, Bodenhausen G and Wokaun A. Principles of NMR Spectroscopy in one and two dimensions. Oxford Publications, Oxford, 1987.

4) Aue WP, Bartholdi E, and Ernst RR. Two-dimensional spectroscopy - application to nuclear magnetic resonance. J Chem Phys. 1976; 64(5):2229-2246.

5) Smith S, Levante T, Meier BH, Ernst RR. Computer simulations in magnetic resonance. An object-oriented programming approach. J. Magn. Reson., Ser. A 1994; 106(1): 75–105.

6) Bottomley PA. Spatial localization in NMR spectroscopy in vivo. Annals of the New York Academy of Sciences 1987;508:333-348.

7) Ryner LN, Sorenson JA and Thomas MA. 3-D Localized 2D-NMR Spectroscopy on an MRI Scanner. J Magn Reson B 1995; 107: 126-137.

8) Ryner LN, Sorenson JA and Thomas MA. Localized 2D J-Resolved H-1 MR Spectroscopy: Strong Coupling Effects in vitro and in vivo. Magn Reson in Imag 1995; 13: 853-869.

9) Bruhn H, Frahm J, Gyngell ML et al. Cerebral metabolism in man after acute stroke: New observations using localized proton NMR spectroscopy. Mag Reson Med 1989; 9: 126.

10) Thomas MA, Chung HK, Middlekauff H. Localized two-dimensional 1H magnetic resonance exchange spectroscopy: a preliminary evaluation in human muscle. Magn Reson Med. 2005 Mar;53(3):495-502.

11) Chung HK, Banakar S, Thomas MA.1143. Localized Constant-Time Correlated Spectroscopy (CT-COSY) of Human Brain In Vivo. Proc ISMRM. 2003, 1143.

12) Watanabe H, Takaya N, Mitsumori E. Absolute quantitation of glutamate, GABA and glutamine using localized 2D constant-time COSY spectroscopy in vivo. Magn Reson Med Sci 2014;13:25-32

13) Chung HK, Banakar S, Thomas MA. Broadband Decoupled and Single Voxel Localized 2D MR Spectroscopy. Proc ISMRM. 2004, 687.


Figures

Figure 1. 2D MRS sequences I: A) Localized correlated spectroscopy (L-COSY), B) Localized J-resolved Spectroscopy (JPRESS); C) Localized Exchange spectroscopy (L-EXSY).

Figure 2. 2D MRS sequences II: A) Constant Time correlated spectroscopy (CT-COSY), B) Constant Time PRESS (CT-PRESS).

Figure 3. The vector diagram to show the coherence transfer process in the L-COSY sequence.

Figure 4. A) A GAMMA-simulated 3T L-COSY spectrum; Also shown are J-coupling connectivities through 2D cross peaks of NAA (B) and GSH (C) of a brain phantom containing more than 16 metabolites at physiological concentrations and pH of 7.2.

Figure 5. The 2D MRS raw data [s(t1,t2)]; processed data after the first FT along the t2 dimension; data after the 2nd FT along the t1 dimension; 2D stack and contour plots.



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