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

Abstract

Traumatic brain injury (TBI) triggers a series of complex pathophysiological processes. These include abnormalities in brain energy metabolism; consequent to reduced tissue pO2 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., 1H, 31P, and 13C, 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, 1H 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. 1H MRS acquired with shorter echo times produces a more complex spectrum, allowing detection of a wider range of metabolites.31 P 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.13 C MRS detects the 13C isotope of carbon in brain metabolites. As the natural abundance of 13C is low (1.1%), 13C MRS is typically performed following administration of 13C-enriched substrates, which permits tracking of the metabolic fate of the infused 13C 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 13C-enriched MRS in vivo studies shows promise in this field, and further developments are expected.

Lactate infusion increases brain energy content during euglycemia but not hypoglycemia in healthy men

“…In fact, our evaluations are based on PCr/inorganic phosphate (Pi) and ATP/Pi ratios, as these are indicators of the intracellular energy state. [25][26][27][28][29][30][31][32][33] Test-retest coefficients of variation were 5.3% for ATP, 4.8% for PCr, 13.6% for Pi, 12.3% for ATP/Pi and 11.4% for PCr/Pi. Cerebral intracellular pH was calculated from the chemical shift of Pi referenced to PCr.…”

Reproducibility of whole‐brain temperature mapping and metabolite quantification using proton magnetic resonance spectroscopy

“…Proton magnetic resonance spectroscopy ( 1 H‐MRS) has been widely applied to quantify brain metabolite changes in humans 1–6 . Another relatively new, but promising application of 1 H‐MRS is the noninvasive measurement of brain temperature 7–9 .…”

Alterations in Brain Metabolites in Patients with Epilepsy with Impaired Consciousness: A Case-Control Study of Interictal Multivoxel 1H-MRS Findings

“…These are found in high concentrations in metabolically active tissues such as the brain that produce energy by oxidative/aerobic metabolism. 28 Cr is a multifunctional molecule in the brain. It reflects energy metabolism and is particularly important for the maintenance of membrane potential.…”