Metabolic imaging of energy metabolism in traumatic brain injury using hyperpolarized [1-13C]pyruvate

Abstract

Traumatic brain injury (TBI) is known to cause perturbations in the energy metabolism of the brain, but current tests of metabolic activity are only indirect markers of energy use or are highly invasive. Here we show that hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) can be used as a direct, non-invasive method for studying the effects of TBI on energy metabolism. Measurements were performed on rats with moderate TBI induced by controlled cortical impact on one cerebral hemisphere. Following injection of hyperpolarized [1-13C]pyruvate, the resulting 13C-bicarbonate signal was found to be 24 ± 6% lower in the injured hemisphere compared with the non-injured hemisphere, while the hyperpolarized bicarbonate-to-lactate ratio was 33 ± 8% lower in the injured hemisphere. In a control group, no significant difference in signal was found between sides of the brain. The results suggest an impairment in mitochondrial pyruvate metabolism, resulting in a decrease in aerobic respiration at the location of injury following TBI.

Hypoxia preconditioning protects neuronal cells against traumatic brain injury through stimulation of glucose transport mediated by HIF-1α/GLUTs signaling pathway in rat

“…The bar graphs show that the mRNA expressions of GLUT1, GLUT3, and HIF-1α were significantly increased in the HPCT group. Data are expressed as means ± SD (n = 6 animals per group); *p < 0.05 vs. Sham group, #p < 0.05 vs. TBI group sequelae after TBI [29]. In this study, we provide significant evidence that HPC increases the glucose transport activity of brain tissues after TBI.…”

Development of methods and feasibility of using hyperpolarized carbon‐13 imaging data for evaluating brain metabolism in patient studies

“…This is particularly relevant for monitoring tumor growth and assessing response to therapy because malignant cells frequently have upregulated lactate dehydrogenase A, which is the enzyme that regulates this pathway (3,4). Preclinical studies that have shown promising results include the assessment of a wide range of different cancers, as well as cardiac disease, traumatic brain injury, and multiple sclerosis (5)(6)(7)(8)(9)(10)(11)(12)(13).…”

Dynamic metabolic imaging of copolarized [2‐13C]pyruvate and [1,4‐13C2]fumarate using 3D‐spiral CSI with alternate spectral band excitation

“…Additionally, conversion of hyperpolarized 13 C-labeled fumarate (Fum) to malate (Mal) has been proposed as a biomarker for cell necrosis. 3 Metabolic imaging of hyperpolarized 13 Clabeled Pyr [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and Fum 3,19-21 has shown great potential in characterizing multiple diseases and assessing response to treatment with Pyr already translated into the clinic. [8][9][10][11] Thus, performing their measurements with a single injection of copolarized substrates would be advantageous particularly for the clinical translation of this technology.…”