期刊
BRAIN
卷 144, 期 -, 页码 3492-3504出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awab255
关键词
traumatic brain injury; PET; cerebral blood flow; glucose metabolism; microdialysis
资金
- Horizon 2020
- Novonordisk Ltd
- European Society of Anaesthesiology
- Netherlands Organisation for Health Research and Development
- University of Amsterdam
- NIHR (Biomedical Research Centre Cambridge)
- NIHR (Invention for Innovation)
- UK Medical Research Council
- Royal College of Surgeons of England
- British Brain and Spine Foundation
- Academy of Medical Sciences/Health Foundation
- NIHR
- NIHR (Cambridge BRC)
- NIHR (Global Health Research Group on Neurotrauma)
- Academy of Medical Sciences/Health Foundation Clinician Scientist Fellowship
- Royal College of Anaesthetists/British Journal of Anaesthesia
- National Institute of Academic Anaesthesia
- Addenbrooke's Charities
- Wellcome Trust
- Beverley and Raymond Sackler
- UK Biotechnology and Biological Sciences Research Council [BB/H008217/1]
- University of Cambridge, UK
- University of Cambridge
- BBSRC [BB/H008217/1] Funding Source: UKRI
Metabolic derangements following traumatic brain injury were comprehensively characterized using a combination of PET techniques, revealing reduced glucose utilization in the brain of patients, with regional increases associated with reductions in glucose availability, blood flow, and oxygen metabolism in the absence of ischemia.
Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited. Eighteen volunteers were excluded for age over 60 years (n = 11), movement-related artefact (n = 3) or physiological instability during imaging (n = 4). We measured cerebral blood flow, blood volume, oxygen extraction fraction, and F-18-FDG transport into the brain (K-1) and its phosphorylation (k(3)). We calculated oxygen metabolism, F-18-FDG influx rate constant (K-i), glucose metabolism and the oxygen/glucose metabolic ratio. Lesion core, penumbra and peri-penumbra, and normal-appearing brain, ischaemic brain volume and k(3) hotspot regions were compared with plasma and microdialysis glucose in patients. Twenty-six head injury patients, median age 40 years (22 male, four female) underwent 34 combined F-18-FDG and oxygen-15 PET at early, intermediate, and late time points (within 24 h, Days 2-5, and Days 6-12 post-injury; n = 12, 8, and 14, respectively), and were compared with 20 volunteers, median age 43 years (15 male, five female) who underwent oxygen-15, and nine volunteers, median age 56 years (three male, six female) who underwent F-18-FDG PET. Higher plasma glucose was associated with higher microdialysate glucose. Blood flow and K-1 were decreased in the vicinity of lesions, and closely related when blood flow was 525 ml/100 ml/min. Within normal-appearing brain, K-1 was maintained despite lower blood flow than volunteers. Glucose utilization was globally reduced in comparison with volunteers (P<0.001). k(3) was variable; highest within lesions with some patients showing increases with blood flow <25 ml/100 ml/min, but falling steeply with blood flow lower than 12 ml/100 ml/min. k(3) hotspots were found distant from lesions, with k(3) increases associated with lower plasma glucose (Rho -0.33, P<0.001) and microdialysis glucose (Rho -0.73, P = 0.02). k(3) hotspots showed similar K-1 and glucose metabolism to volunteers despite lower blood flow and oxygen metabolism (P<0.001, both comparisons); oxygen extraction fraction increases consistent with ischaemia were uncommon. We show that glucose delivery was dependent on plasma glucose and cerebral blood flow. Overall glucose utilization was low, but regional increases were associated with reductions in glucose availability, blood flow and oxygen metabolism in the absence of ischaemia. Clinical management should optimize blood flow and glucose delivery and could explore the use of alternative energy substrates.
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