compares ideal and measured gradient waveform and the corresponding full k-space trajectories for the 3-shot spCSI case. The measured gradient waveform trailed by approximately one sample point and did not reach the full prescribed amplitude. The mean absolute difference for all three interleaves was 11.0 mT/m with a maximum of 23.5 mT/m. As a consequence, the distance between the spiral arms and the maximum value of the k-space trajectory were reduced. This corresponded to the FOV and the nominal voxel size being slightly larger than designed. In first approximation, the scaling factor was 1.036. Similar results were obtained for the single-shot spiral data but the deviations were less pronounced. The mean absolute difference for the gradient waveform was 9.8 mT/m with a maximum of 18.4 mT/m. FOV and voxel size were approximately 1.5% larger than designed.
Figure 1 (a) Ideal (dashed) and measured (solid) gradient waveform along the x-axis from one of three interleaves for the 3-shot spiral trajectory. The difference between measured and ideal waveform is plotted as a dotted line. (b) Same as (a), but zoomed in on (more ...)
Results from the time-resolved imaging experiments are shown in and . The series of metabolic maps () illustrate the temporal dynamics and spatial distributions of Pyr and its metabolic products. The maps from a single animal, superimposed onto a high-resolution 1H-FSE image, were averaged over data from three injections. Taking into account the spatial apodization and the measured k-space trajectory, the effective voxel size was 130.8 µL compared to the nominal voxel size of 72.9 µL. While Pyr was highest in the vasculature, it was also detected in the brain. Lac signal was detected in the brain already at the first time point and quickly increased over the next 12 s. Although Lac could have also been produced elsewhere in the body, e.g., in the heart, and then have crossed the blood-brain barrier (BBB), the different ratios of brain and vasculature signal, e.g. 0.6 for Pyr and 1.5 for Lac at 21 s, suggest that most Lac was produced in the brain. Ala was high in muscular tissue of the jaw and tongue. Bic was only detected in the brain, in particular in the cortex. The observed Bic was most likely formed through decarboxylation of pyruvate to acetyl coenzyme A. However, another pathway would comprise first the carboxylation of pyruvate to oxaloacetate with subsequent turnover in the tricarboxylic acid cycle. The bicarbonate would later be formed through decarboxylation of isocitrate to alpha-ketoglutarate. The time curves of all four metabolites from a region-of-interest (ROI) predominantly in the cortex are shown in . The curves were calculated from a single animal averaged over three injections and from three animals with three injections for each animal. The error bars given by the corresponding standard deviations demonstrate good reproducibility, both between multiple injections and between animals.
Figure 2 Time series of 16 metabolic maps acquired with single-shot spCSI (nominal FOV = 43×43 mm2) of (a) Pyr, (b) Lac, (c) Ala, and (d) Bic superimposed onto the corresponding 1H-FSE image. The threshold (relative to maximum signal) of the metabolic (more ...)
Figure 3 Time course of (a) Pyr, (b) Lac, (c) Ala, and (d) Bic from an ROI predominantly in the cortex. The position of the ROI is indicated in the FSE image in (a). Data in black (solid, ×) are from a single animal averaged over 3 injections. Data in (more ...)
Due to the low spatial resolution, the time course of Pyr was also affected by signal contributions from Pyr in the sagittal sinus. This may explain the relatively large variations of Pyr in the early time points as the vascular Pyr signal was the most sensitive to small variations during the course of the manual bolus injections. Lac and Bic exhibited similar time courses with the maximum for Bic approximately 10 s delayed compared to the Lac. Similar to Pyr, the time course of Ala in the ROI, which showed a steady increase, was dominated by signal contributions from the tissue surrounding the brain due to partial volume effects. The continuing rise of the alanine signal was mainly due to the relatively short observation window (until 52 s after start of injection). Although alanine could still be produced after that time frame, the loss of polarization due to T1 decay ultimately dominates. The intensity increase at the last two time points, particularly noticeable in the Lac dynamics, presumably was due to in-flow, i.e., from spins that have not experienced all excitation pulses. Although the inflow is a cumulative effect and can be present thought the whole acquisition window, its effect is most obvious during the last time points, because of the rapid increase in excitation flip angle at those time points due to the applied variable-flip-angle scheme.
High-resolution metabolic imaging was performed to reduce partial volume effects and to further investigate the spatial origin of the metabolite signals. To compensate for the smaller voxel size, a variable flip angle scheme was used for the three-shot acquisition that excites the full longitudinal magnetization in the imaging slice at a single time point. The nominal voxel size was 11.3 µL and the effective voxel size was 19.2 µL. The metabolic maps () acquired 27 s after start of injection show a similar metabolite distribution as the dynamic data, but with reduced contamination from signal outside the brain. Compared to the corresponding values for the low-resolution images at the same time point (cf. ), the average signal intensities in the cortex ROI were similar for Lac (1.2 i.u.) and even higher for Bic (0.3 i.u.), but they were considerably reduced for both Pyr (1.5 i.u.) and Ala (0.0 i.u.). The fact that no alanine was detected in the brain is consistent with measurements by Erakovic et al. (21
) who report activity levels for alanine aminotransferase in multiple regions of the rat brain approximately 50 times lower than for lactate dehydrogenase.The greater heterogeneity of the lactate distribution in the brain in the high-resolution image compared to singe-shot data at the same time point is most likely due to the lower SNR. However, it could also reflect a more accurate depiction of the true metabolite distribution.
Figure 4 High-resolution metabolic maps acquired with 3-shot spCSI (nominal FOV = 48×48 mm2) of (a) Pyr, (b) Lac, (c) Ala, and (d) Bic superimposed onto the corresponding 1H-FSE image. The images were acquired 27 s after the start of the injection. The (more ...)