Simultaneous MEGA-PRESS editing of valine and lactate
Thomas Lange1, Cheng-Wen Ko2, Shang-Yueh Tsai3, Martin Buechert4, and Ping-Hong Lai5

1Medical Physics, Department of Radiology, University Medical Center Freiburg, Freiburg, Germany, 2Dept. of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan, 3Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan, 4Magnetic Resonance Development and Application Center, University Medical Center Freiburg, Freiburg, Germany, 5Dept. of Radiology, Veterans General Hospital Kaohsiung, Kaohsiung, Taiwan


The MEGA-PRESS sequence allows difference editing of J-coupled metabolites on the basis of their specific coupling behavior. In this work, we demonstrate MEGA-PRESS editing of valine and lactate from a large background of lipid signal. Exploiting the very similar J-coupling constants of valine and lactate, it is demonstrated that both metabolites can be edited simultaneously with an echo time of 142 ms, allowing an editing efficiency of 100% with negligible lipid co-editing. Simultaneous valine/lactate editing is validated in vitro and successfully demonstrated in one brain abscess patient. The method may prove clinically useful for distinguishing brain abscesses from brain tumors.


Valine and lactate have been recognized as key metabolic markers to distinguish brain abscess from tumor 1. However, macromolecular contamination constitutes a major impediment for signal quantification of brain metabolites resonating in the spectral region between 1 and 2 ppm when conventional PRESS or STEAM protocols are used. MEGA-PRESS difference editing has recently been proposed for filtering out the resonances of J-coupled metabolites such as GABA 2, glutathione 3, ascorbate 4, N-acetylaspartateglutamate 5 and lactate 6 from a background of other metabolite signals. Furthermore, simultaneous MEGA-PRESS editing of two metabolites (glutathione and ascorbate) has been proposed 7. In this work, simultaneous MEGA-PRESS editing of valine and lactate from a large background of lipid signal is validated in vitro and demonstrated in a patient with a brain abscess.


All experiments were performed on 3T MR systems (Trio for phantom studies and Skyra for brain abscess case, Siemens Healthcare, Germany). The original MEGA-PRESS sequence used for GABA editing was modified to enable complete refocusing of weak J-coupling evolution over variable echo time (TE) intervals by using two frequency-selective refocusing pulses (bandwidth = 30 Hz) with an inter-pulse delay of TE/2. For editing of both valine and lactate with J ≈ 7 Hz, an echo time of TE = 142 ms was used for complete inversion of the target resonances at 1.0 ppm and 1.33 ppm, respectively, in the unedited spectra. The spectrally selective editing pulses were irradiated at ν = 2.25 ppm for valine editing and at ν = 4.11 ppm for lactate editing (shot 1). For the acquisition of the unedited spectra (shot 2), the frequency-selective refocusing pulses were irradiated in the down-field region at 7.15 ppm and 5.29 ppm for valine and lactate editing, respectively, to ensure optimal water suppression in the difference editing spectrum. For combined valine and lactate editing the frequency-selective pulses were irradiated at 2.25 ppm (shot 1) and 4.11 ppm (shot 2) in the two interleaved acquisitions. In vitro experiments were performed in a phantom solution containing valine, lactate and a mixture of soja and olive oil. In vivo data were acquired from a patient with brain abscess.


Figure 1 shows the spectra acquired for valine editing, lactate editing and combined valine/lactate editing. All shots contain contamination of lipid resonances in the region of interest. The lactate and valine resonances at 1.33 and 1.0 ppm are contaminated by lipid signal arising from methylene protons (1.3 ppm) and methyl protons (0.9 ppm) respectively. However, the difference spectra exhibit uncontaminated valine triplets and lactate doublets. Combined valine and lactate editing yields a positive valine triplet and a negative lactate doublet in the difference spectrum. PRESS and MEGA-PRESS editing spectra acquired from the brain abscess patient are presented in Fig. 2. Combined valine/lactate editing successfully filters lactate and valine resonances from a strong lipid background. While large lipid peaks (at 1.3 ppm) are visible in the PRESS spectrum as well as in the valine- and lactate-edited MEGA-PRESS shots, the difference spectrum shows only minor lipid signal at 1.3, suggesting some lipid co-editing. However, compaired to the lipid signal in the unedited PRESS spectrum, contamination is negligible in the dual-edited MEGA-PRESS spectrum.


MEGA-PRESS was optimized for valine and lactate editing and successfully applied in vivo. Both metabolites can be detected with an editing efficiency of 100% since their most prominent resonances exhibit full inversion at TE = 142 ms. This is in contrast to GABA detection where only the two outer lines of the triplet resonances are inverted, resulting in an editing efficieny of only 50%. The almost identical J-coupling constants of valine and lactate benefit simultaneous MEGA-PRESS editing of these two metabolites. The long echo time required for valine and lactate inversion enables the utilisation of frequency-selective editing pulses with a very small bandwidth (16 Hz). However, it has to be noted that such small-bandwidth pulses make the sequences susceptible to frequency drifts during the scan, e.g. through temperature changes or subject motion, and can strongly decrease the editing efficiency. On the other hand, editing pulses with larger bandwidths may increase co-editing of other resonances, e.g. arising from lipids. An editing pulse bandwidth of 30 Hz empirically turned out to be a good compromise. The proposed method may prove beneficial for the distinction of brain abscesses and tumors where lactate (in tumors and abscesses) and valine (in abscesses only) have been recognized as key metabolic markers.


The authors thank Siemens Healthcare for providing MEGA-PRESS sequence source code for GABA spectral editing. This work was funded in part by the Ministry of Science and Technology Taiwan (MOST, 101-2221-E-110-001-MY3), German Research Foundation (DFG, grant number LA 3353/2-1) and Helmholtz Alliance ICEMED - Imaging and Curing Environmental Metabolic Diseases.


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Figure 1. Phantom spectra acquired from a solution of valine, lactate and oil with MEGA-PRESS for valine editing, lactate editing and combined valine and lactate editing.

Figure 2. Spectra acquired from a patient with a brain abscess. Combined valine/lactate MEGA-PRESS editing successfully filtered lactate and valine resonances from a strong lipid background. The residual lipid signal at 1.3 ppm becomes negligible compared to the edited valine and lactate peaks.

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