Table 1.
Examples of biomarker methodology in human brain.
| Biomarkers in human brain | Technique | Extent of measurement | Timeframe (and frequency) | Invasive? |
|---|---|---|---|---|
| Intracranial dynamics: ICP, CPP, ABP, PRx, PbtO2 (8–10) | Sensors for pressure and O2 concentration | ICP–global PbtO2–regional/focal | 100–0.1 Hz. Multi-day. Often expressed averaged over time (e.g., hourly) | Yes (insertion of probes into brain) |
| Net changes (import or export) by brain for glucose and lactate (11) | Arteriovenous difference | Global | Multi-day (sampling twice daily) | Yes (insertion of arterial line and jugular venous catheter) |
| Brain extra-cellular concentrations of small molecules (e.g., glucose, lactate, pyruvate, glutamate, and glycerol) (8) | Microdialysis | Focal | Multi-day (hourly vial changes) | Yes (insertion of catheter into brain) |
| Regional cerebral metabolic rate of glucose (CMRglc) or oxygen (CMRO2) (12, 13) | PET | Global and regional | Usually single scan session (<1 h), sometimes repeated after a few days | Yes (i.v. injection of radioactivity with short half-life) |
| Cerebral inflammation: presence of activated microglia (ligand PK11195) (14, 15) | PET | Global and regional | Usually single scan session (<1 h), sometimes repeated after a few days | Yes (i.v. injection of radioactivity with short half-life) |
| Brain extra-cellular proteins < 100 kDa (e.g., cytokines and chemokines) (16) | Microdialysis | Focal | Multi-day (hourly vial changes)–usually several hours pooled (e.g., 4–8 × 1 h vials) for analysis | Yes (insertion of catheter into brain) |
| Small molecules in brain tissue (e.g., NAA, creatine, choline, myo-inositol, glutamate and glutamine, GABA, lactate) (17) | 1H-MRS | Regional and voxel | Usually single scan session (<1 h), sometimes repeated after a few days | No |
| Phosphorus-containing small molecules in brain tissue (e.g., ATP, phosphocreatine, inorganic phosphate) and brain intracellular pH (18) | 31P MRS | Regional and voxel | Usually single scan session (<1 h), sometimes repeated after a few days | No |
| 13C-labeling in metabolites in brain tissue (e.g., glutamate and glutamine) for calculating TCA cycle rate, other 13C-labeled species also detectable (e.g., GABA, aspartate, NAA) (19) | 13C MRS | Regional and voxel | Usually single scan session (ca. 2 h) | Moderately (i.v. bolus and infusion of stable-isotope 13C-labeled substrate, e.g., glucose) |
| 13C-labeling patterns in metabolites detected extracellularly (e.g., glutamine or lactate) diagnostic for biochemical pathways such as TCA cycle, glycolysis, PPP (20, 21) | 13C-labeled microdialysis | Focal | Typically 24 h (24 × 1 h vials pooled) | Yes (insertion of catheter into brain, perfused with solution of stable-isotope 13C-labeled substrate, e.g., glucose, lactate, or acetate) |
Table adapted from Jalloh et al. (22).
ABP, arterial blood pressure; ATP, adenosine triphosphate; CMRglc, cerebral metabolic rate of glucose; CMRO2, cerebral metabolic rate of oxygen; CPP, cerebral perfusion pressure; GABA, gamma-aminobutyric acid; ICP, intracranial pressure; i.v., intravenous; MRS, magnetic resonance spectroscopy; NAA, N-acetylaspartate; PbtO2, brain tissue oxygen concentration; PET, positron emission tomography; PPP, pentose phosphate pathway; PRx, pressure reactivity index.