Lactate is a metabolic marker that is observed in many brain pathologies.8
Neoplastic processes that are present in tumors have low oxygen supply and depend on non-oxidative glycolysis for energy production.31
This means that lactate can be considered as an indicator of anaerobic glycolysis and reduced cellular oxygenation, which is of interest for evaluating response to radiation or other therapies. The potential for identifying regions of metabolic stress and ischemic area in brain means that in vivo
measurements of lactate are of interest in patients with a number of different brain pathologies. Previous studies performed at 1.5 Tesla (1.5 T) have shown that the presence of lactate and lipid peaks in 1
H magnetic resonance spectroscopic imaging (MRSI) data is associated with a diagnosis of high-grade tumor.15
Elevated signals from lactate and lipid were associated with short survival in patients with glioblastoma multiforme (GBM) who were evaluated either prior to surgery or radiation treatment at 1.5 T.2
In these cases, increased lactate was interpreted as an indication of increased tumor metabolism and growth.1
The detection of lactate is thus of interest for evaluating prognosis and response to therapy in brain tumor patients.
H magnetic resonance spectroscopy (MRS) of lactate demonstrates two resonances: a doublet at 1.3 ppm from methyl protons (CH3
) and a quartet at 4.1 ppm from methine protons (CH). The methyl protons and the methine protons are weakly coupled to each other with a J-coupling constant of 6.93 Hz. For proton in vivo
spectroscopy, the methyl doublet has been the target for lactate detection because the methine peaks are close to the water resonance and are not usually visible because of their relatively low signal intensity. Despite this advantage, the methyl doublet can be difficult to quantify because of lipid peaks, which overlap in the range of 0.9–1.3 ppm. In order to overcome this problem, a number of techniques have been developed to measure and separate the lactate doublet from lipid resonances.6
One such technique is based on spectral editing using dual band selective inversion with gradient dephasing (BASING) pulses.29
This technique allows for simultaneous detection of lactate at 1.3 ppm as well as uncoupled metabolites such as choline (Cho), creatine (Cr), N
-acetyl-aspartate (NAA), and lipid. Based on J-difference editing, this technique exploits the fact that the phase of the doublet depends on the carrier frequency of the BASING pulse acting on the quartet at 4.1 ppm, which is weakly coupled to the doublet. The BASING pulse, which is a frequency selective inversion pulse surrounded by bipolar crusher gradients on orthogonal axes, places the methine quartet within the BASING inversion band for the first cycle (edit-on), while the carrier frequency of the BASING pulse is shifted in the second cycle so that the quartet is removed from the inversion band (edit-off).29
As a result, the doublet becomes in-phase in the first cycle and 180° out-of-phase in the second cycle relative to uncoupled spins for echo time TE = 144 ms. Summing the two data sets provides only uncoupled spins including Cho, Cr, NAA, and lipid, whereas subtracting them renders only lactate (Fig. c).
Figure 1 The new BASING pulse waveform designed for 3 T (a) and its inversion profile (b). Carrier frequency of the second cycle was shifted 198 Hz from the first cycle so that the lactate methine quartet was placed in either the passband or the (more ...)
Lactate editing combined with point resolved spectroscopy (PRESS) localized 3D MRSI has been applied to glioma patients at 1.5 T for non-invasive detection of lactate and other brain metabolites.2
These studies demonstrated the detection of lactate as well as Cho, Cr, NAA and lipid, and suggested that in vivo
measurement of lactate as well as other MR-derived parameters may help in diagnosis and proper therapy selection for glioma patients. Although the increased signal strength at higher field is expected to enhance the sensitivity of brain metabolites including lactate, the detection of brain lactate using 1
H MRS based on J-difference editing at 3 Tesla (3 T) scanner has not been reported. Several studies have reported their unsuccessful attempts at measuring lactate in brain tumor patients using single voxel PRESS-localized MRS at 3 T.12
The poor lactate detection that was observed at 3 T in these studies was due to chemical shift mis-registration artifact caused by the limited bandwidth of refocusing pulses used for the localization of spectroscopic data.
Several studies have investigated the signal cancellation of J-coupled resonance due to the chemical shift difference between J-coupled spin partners in PRESS MRSI sequence in the context of lactate and GABA.9
This artifact is produced because spatially selective RF pulses cause a relative shift in the location of the selected volume for J-coupled resonances, thereby leading to net signal loss when the final signal is contributed from different regions. Kelley et al.10
demonstrated in phantoms that BASING pulses incorporated into non-editing PRESS sequence reduced the artifact for the detection of lactate methyl resonance in single voxel and MRSI data. For our editing scheme, this artifact may happen in the second cycle with BASING editing off, which is basically regular J-evolution. In the present study, we sought to eliminate this artifact by using higher-bandwidth RF pulses since the spatial offset due to chemical shift difference is inversely proportional to RF bandwidth. In addition, we over-prescribed PRESS-localized volume and applied high bandwidth saturation pulses in order to further minimize this artifact.
The clinical use of lactate-edited MRSI based on J-difference editing has been limited by the requirement of two successive acquisitions per phase encoding step and the acquisition time which has typically been 20 min.15
Flyback echo-planar spectroscopic imaging has been used to allow the acquisition of MRSI data in a shorter scan time. Cunningham et al.3
demonstrated the feasibility and potential of MRSI data acquisition at 3 T with high spatial resolution and large coverage in a short scan time with flyback echo-planar readout gradient waveforms.
The purpose of this study was to implement a lactate-edited 3D PRESS 1H MRSI sequence at 3 T with new high bandwidth 180° pulses, new BASING pulses and a flyback echo-planar readout gradient in order to allow a clinically suitable scan time of 10 min and demonstrate the feasibility of using this sequence for the detection of brain lactate as well as Cho, Cr, NAA, and lipid in patients. We addressed the effect of chemical shift artifact on lactate signal with different PRESS over-prescription (over-PRESS) factors and compared the metabolite SNR and its ratio of the lactate-edited MRSI data between a flyback echo-planar readout gradient method and conventional MRSI with elliptical k-space sampling. The method was then applied to patients with gliomas in order to determine whether it could detect lactate within lesions.