The consolidation of newly formed memories and their retrieval are energetically demanding processes. Aerobic glycolysis (AG), also known as the Warburg effect, consists of the production of lactate from glucose in the presence of oxygen. The astrocyte neuron lactate shuttle hypothesis posits that astrocytes process glucose by AG to generate lactate, which is used as a fuel source within neurons to maintain synaptic activity. Studies in mice have demonstrated that lactate transport between astrocytes and neurons is required for long-term memory formation, yet the role of lactate production in memory acquisition and retrieval has not previously been explored. Here, we examined the effect of dichloroacetate (DCA), a chemical inhibitor of lactate production, on spatial learning and memory in mice using the Morris water maze (MWM). In vivo hyperpolarized 13 C-pyruvate magnetic resonance spectroscopy revealed decreased conversion of pyruvate to lactate in the mouse brain following DCA administration, concomitant with a reduction in the phosphorylation of pyruvate dehydrogenase. DCA exposure before each training session in the MWM impaired learning, which subsequently resulted in impaired memory during the probe trial. In contrast, mice that underwent training without DCA exposure, but received a single DCA injection before the probe trial exhibited normal memory. Our findings indicate that AG plays a key role during memory acquisition but is less important for the retrieval of established memories. Thus, the activation of AG may be important for learning-dependent synaptic plasticity rather than the activation of signaling cascades required for memory retrieval.

Metabolic changes associated with RP may be mapped as early as five days post conformal radiotherapy. Over the small sample size in each cohort, elevated macrophage count, consistent with early phase of inflammation was highly correlated to increases in lac/pyr in both the irradiated and unirradiated lungs. Further experiments with larger sample size may improve the confidence of this finding.

This study presents the first longitudinal measurement of the intracellular/extracellular pH gradient in a rat glioma model using noninvasive magnetic resonance imaging. The acid–base balance in the brain is tightly controlled by endogenous buffers. Tumors often express a positive pH gradient (pHi – pHe) compared with normal tissue that expresses a negative gradient. Alkaline pHi in tumor cells increases activity of several enzymes that drive cellular proliferation. In contrast, acidic pHe is established because of increased lactic acid production and subsequent active transport of protons out of the cell. pHi was mapped using chemical exchange saturation transfer, whereas regional pHe was determined using hyperpolarized 13C bicarbonate magnetic resonance spectroscopic imaging. pHi and pHe were measured at days 8, 12, and 15 postimplantation of C6 glioma cells into rat brains. Measurements were made in tumors and compared to brain tissue without tumor. Overall, average pH gradient in the tumor changed from −0.02 ± 0.12 to 0.10 ± 0.21 and then 0.19 ± 0.16. Conversely, the pH gradient of contralateral brain tissue changed from −0.45 ± 0.16 to −0.25 ± 0.21 and then −0.34 ± 0.25 (average pH ± 1 SD) Spatial heterogeneity of tumor pH gradient was apparent at later time points and may be useful to predict local areas of treatment resistance. Overall, the intracellular/extracellular pH gradients in this rat glioma model were noninvasively measured to a precision of ∼0.1 pH units at 3 time points. Because most therapeutic agents are weak acids or bases, a priori knowledge of the pH gradient may help guide choice of therapeutic agent for precision medicine.

A surface coil can be integrated with a switch-tuned (13) C - (1) H coil for (13) C TORO operation producing improved SNR. In vivo metabolic imaging of [1-(13) C]pyruvate in a rat model of glioma is demonstrated using TORO operation, which is co-registered with (1) H-imaged anatomy.

MRI using the balanced steady-state free precession (bSSFP) sequence can be used to monitor tumor growth in orthotopic PC-3M tumors as early as 9 days post-injection. Hyperpolarized pyruvate MRI has potential to assess tumor metabolism and necrosis.