Assessing Metabolism and injury in Acute Human Traumatic Brain injury with Magnetic Resonance Spectroscopy: Current and Future Applications

Traumatic brain injury (TBI) triggers a series of complex pathophysiological processes. These include abnormalities in brain energy metabolism; consequent to reduced tissue pO(2) arising from ischemia or abnormal tissue oxygen diffusion, or due to a failure of mitochondrial function. In vivo magnetic resonance spectroscopy (MRS) allows non-invasive interrogation of brain tissue metabolism in patients with acute brain injury. Nuclei with spin, e.g., H-1, P-31, and C-13, are detectable using MRS and are found in metabolites at various stages of energy metabolism, possessing unique signatures due to their chemical shift or spin-spin interactions (J-coupling). The most commonly used clinical MRS technique, H-1 MRS, uses the great abundance of hydrogen atoms within molecules in brain tissue. Spectra acquired with longer echo-times include N-acetylaspartate (NAA), creatine, and choline. NAA, a marker of neuronal mitochondrial activity related to adenosine triphosphate (ATP), is reported to be lower in patients with TBI than healthy controls, and the ratio of NAA/creatine at early time points may correlate with clinical outcome. H-1 MRS acquired with shorter echo times produces a more complex spectrum, allowing detection of a wider range of metabolites. P-31 MRS detects high-energy phosphate species, which are the end products of cellular respiration: ATP and phosphocreatine (PCr). ATP is the principal form of chemical energy in living organisms, and PCr is regarded as a readily mobilized reserve for its replenishment during periods of high utilization. The ratios of high-energy phosphates are thought to represent a balance between energy generation, reserve and use in the brain. In addition, the chemical shift difference between inorganic phosphate and PCr enables calculation of intracellular pH. C-13 MRS detects the C-13 isotope of carbon in brain metabolites. As the natural abundance of C-13 is low (1.1%), C-13 MRS is typically performed following administration of C-13-enriched substrates, which permits tracking of the metabolic fate of the infused C-13 in the brain over time, and calculation of metabolic rates in a range of biochemical pathways, including glycolysis, the tricarboxylic acid cycle, and glutamate-glutamine cycling. The advent of new hyperpolarization techniques to transiently boost signal in C-13-enriched MRS in vivo studies shows promise in this field, and further developments are expected.