Task activation results in regional 13C-lactate signal increase in the human brain

Abstract

Hyperpolarized-¹³C magnetic resonance imaging (HP-¹³C MRI) was used to image changes in ¹³C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain ¹³C-pyruvate, ¹³C-lactate and ¹³C-bicarbonate production was imaged in healthy volunteers (N = 6, ages 24-33) for the two conditions using two separate hyperpolarized ¹³C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation. ¹³C-metabolite signal was normalized by ¹³C-metabolite signal from the brainstem and the percentage change in ¹³C-metabolite signal conditions was calculated. A one-way Wilcoxon signed-rank test showed a significant increase in ¹³C-lactate in regions of activation when compared to the remainder of the brain ($p=0.02$). No significant increase was observed in ¹³C-pyruvate signal ($p=0.11$) or ¹³C-bicarbonate signal ($p=0.95$). The results show an increase in ¹³C-lactate production in activated regions that is measurable with HP-¹³C MRI.

Keywords: Energy metabolism; MR metabolite; MRI; lactate; molecular imaging.

Figure 1.

Image acquisition workflow for the visual stimulus scans. Two sets of ¹³C-images were acquired with a thirty minute wait period between acquisitions to allow for washout of residual ¹³C-metabolites. During this wait period, anatomical images and BOLD-fMRI images were acquired.

Figure 2.

Example BOLD fMRI t-statistic map for the visual stimulus registered to the MNI152 atlas. The inset is an example time series curve from a voxel with significant activation (yellow) and the stimulus regressor used in the general linear model (red).

Figure 3.

Group average ¹³C-lactate images overlaid on the MNI152 atlas for the control (left) and task (right) conditions. Increased ¹³C-lactate signal can be observed in the occipital lobe, predominantly in the left hemisphere. A sagittal slice (top) and coronal slice (bottom) are shown with the same color scale used for ¹³C-lactate signal. The A, P, R and L markers denote anterior, posterior, right and left.

Figure 4.

(a) The percentage change between task and control ¹³C-scans for the non-activated volume (left) and activated volume (right). The lines connect the data points from the same individual, the box centre line indicates the mean and whiskers at the 25th and 75th percentile and (b) the percentage change between task and control ¹³C-scans for each BrainCOLOR region. The BOLD-fMRI t-statistic maps were used to designate ‘activation volume regions’ and ‘non-activation volume regions’. An elevated $\Delta \%$ in ${\hspace{0.17em}}^{13}$ C-lactate is visible in the activation volume regions.

Figure 5.

Correlation between the level of BOLD activation (t-statistic) within the activation volume and the percentage ¹³C-lactate signal change between the task and control conditions.