Interrogating changes in cerebral glucose availability, delivery, uptake and phosphorylation after traumatic brain injury; an (15)oxygen and F-18-fluorodeoxyglucose positron emission tomography study

Abstract

Objectives Metabolic derangements are common after traumatic brain injury (TBI), but few studies have used multi-tracer positron emission tomography (PET) to interrogate underlying pathophysiology (1,2). We examined relationships between oxygen and glucose metabolism using 15oxygen (15O) and 18F-fluorodeoxyglucose (FDG) PET. Methods Twenty-six TBI patients underwent combined 15O and FDG-PET on 34 occasions; 10 and 18 healthy volunteers (controls) underwent 15O and FDG-PET respectively. FDG rate constants were determined with an irreversible two-compartment model: transport across BBB (K1,k2), hexokinase activity (k3), and influx rate (Ki). Regions of interest were defined for haemorrhagic lesion (core), hypodense tissue (penumbra), 1 cm border zone of normal appearing tissue (peri-penumbra), and remote normal appearing tissue (normal). Plasma and microdialysis glucose were recorded. Results In patients, glucose delivery (K1) was dependent on supply with significantly lower values occurring below a threshold cerebral blood flow (CBF) of 25ml/100ml/min. K1 was particularly driven by CBF within lesion core (R=0.87,p<0.001) where CBF values were lower. Changes in hexokinase activity (k¬3) were variable across the injured brain and not driven by CBF. While k3 hot-spots were found close to lesions they were often found within non-lesion brain with normal K1, and in the absence of increases in OEF consistent with cerebral ischaemia. Increases in k3 were associated with low microdialysis glucose (R=-0.73,p=0.016). Conclusions: These findings demonstrate that while glucose utilisation is reduced within the vicinity of lesions due to low CBF and impaired glucose delivery (K1), regional increases in utilisation occur across the injured brain and result from increases in hexokinase activity (k3) associated with reduced glucose availability. Such evidence of non-ischaemic hyperglycolysis may relate to pathophysiological derangements such as inflammation, excitotoxicity or spreading depression. Future studies should address whether treatment based on microdialysis glucose can ameliorate such findings and improve outcome. References: 1.Hattori,et al.J Nucl Med.2004 2.Abate,et al.Neurocrit Care.200