This work focused on strategies to optimize lactate image quality and SNR while retaining those of pyruvate for multishot acquisitions. First, the strategy was based on an imaging acquisition window delayed to coincide with the lactate signal plateau. Second, sampling of the lactate signal was optimized by applying VFA. The VFA was designed based on the observed constant level of lactate over the imaging window. Therefore, no assumptions were required with respect to the balance of T1
and metabolic activity that created the lactate plateau. Under these conditions, the choice of phase encoding order should not affect the lactate SNR, as demonstrated by the simulation. For pyruvate, the dynamic signal decreases during the typical imaging window and, hence, the cPE strategy yielded better pyruvate SNR than sPE. With a very slight compromise in image quality but an overall good SNR, VFA/cPE was chosen to be the best strategy for multishot acquisitions based on the simulation and in vivo rat data of this work. This strategy has also been applied on dog prostate 13
C imaging using clinical coils and the 3D flyback EPSI sequence presented here, yielding good image quality and SNR of dog prostate (8
). Although this work focused on lactate, the same strategy can be applied to alanine, which may be of interest for liver disease applications.
The appropriate time delay depends on the period of bolus injection and blood circulation time to the organ of interest. In addition, the metabolic exchange rate is higher at lower dose concentration (23
) and, therefore, the lactate signal tends to reach a plateau earlier, at lower doses. Our experience with repeated dynamic scans is that the timing of lactate signal is fairly reproducible, as long as the injection method, dose concentration, the imaging organ, and the animal species are the same. Therefore, it is reasonable to use a priori timing information from a separate experiment to determine the appropriate time delay. However, when imaging organs in disease conditions, one should acquire dynamic information on the diseased organ and should not assume the uptake kinetics are the same as the normal organ.
Since the 3DEPSI protocol was not randomized, alternation of pyruvate metabolism over several hours of isoflurane anesthesia may be a concern for systematic errors. In a different study (not shown) where repeated measurements were performed three times in each of two rats with identical acquisition parameters, no systematic trend was found in lactate/pyruvate or alanine/pyruvate ratios during 6-h anesthesia sessions, and the intrasubject variability was 15% to 20%. In a recent dog study (8
) with multiple large-dose 13
C-pyruvate injections, blood samples drawn shortly before and after each pyruvate injection were analyzed for the amount of pyruvate and lactate in blood. The results (not shown here) indicated that pyruvate metabolism is rapid and no cumulative effect is expected at intervals of 1.5 h. The dose per kg of body weight used in the dog study is comparable to the 3-ml doses used in the rats in this study.
The SNR enhancement using VFA/cPE was found to be consistently low compared to the theoretical predictions. This discrepancy is likely due to in-flow effect. The simulation did not take into account the signal change due to in-flow for different flip angles used for imaging.The VFA for a 12 × 12 matrix in 3DEPSI started at 4.8° and then increased very slowly, with at least three-quarters of the excitations less than 10°. Therefore, compared to the constant 10° acquisition, the additional signal contribution from in-flow would be less in the VFA acquisition. This may explain the decrease of the advantage of VFA/cPE as compared to 10°/sPE. For the fast CSI acquisition, 204 excitations were performed, and one may expect an even larger discrepancy compared to the theoretical prediction. The trend in our data indicated the same: the SNR enhancement measured in fast CSI was only about 76% (=1.3/1.7 for lactate) of the enhancement predicted by simulation, whereas in 3DEPSI, it was 84% (=0.74/0.88). Another factor is the accuracy of the flip angle calibration. However, this would affect both the VFA and constant flip angle measurements and the effect is expected to be smaller than the in-flow effect.
Symmetric EPSI improved the lactate SNR by 35% compared to the flyback EPSI. There is no problem combining the odd- and even-echo data when the data are properly gridded on the kx vs. time domain. The effect of eddy currents is expected to be insignificant in this work because for 5-mm resolution, the waveform amplitude was 2.2 mT/m, much less than the maximum 40 mT/m. The close agreement between the theoretical and measured SNR enhancement factors further demonstrates this. For future imaging studies utilizing full gradient strength and slew-rate, it is advisable to use the measured trajectories in data gridding to eliminate potential image artifacts. The symmetric EPSI has other advantages. Bicarbonate, a metabolic byproduct, as pyruvate, enters the tricarboxylic acid cycle, has a chemical shift of about 700 Hz from lactate at 3T. With a spatial resolution of 5.6 mm and 720-Hz spectral BW, it is possible to capture the bicarbonate peak by using symmetric EPSI. It is also possible to use odd and even echoes separately in order to gain spectral BW. However, N/2 aliasing peaks may appear due to uncertainties of waveform timing, eddy current effects and T2*. The potential of symmetric EPSI for 13C imaging is worth exploring further.