Brain Advance Access originally published online on May 11, 2005
Brain 2005 128(8):1931-1942; doi:10.1093/brain/awh536
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Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury
1 Division of Anaesthesia, Department of Medicine, 2 Wolfson Brain Imaging Centre and 3 Academic Neurosurgery Unit, Department of Clinical Neurosciences and 4 Department of Radiology, University of Cambridge, Cambridge, UK
Correspondence to: Professor D. K. Menon, Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Cambridge CB2 2QQ. E-mail: dkm13{at}wbic.cam.ac.uk
Cerebral ischaemia appears to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI) and is an important predictor of outcome. To date, the thresholds of cerebral blood flow (CBF) and cerebral oxygen utilization (CMRO2) for irreversible tissue damage used in TBI studies have been adopted from experimental and clinical ischaemic stroke studies. Identification of irreversibly damaged tissue in the acute phase following TBI could have considerable therapeutic and prognostic implications. However, it is questionable whether stroke thresholds are applicable to TBI. Therefore, the aim of this study was to determine physiological thresholds for the development of irreversible tissue damage in contusional and pericontusional regions in TBI, and to determine the ability of such thresholds to accurately differentiate irreversibly damaged tissue. This study involved 14 patients with structural abnormalities on late-stage MRI, all of whom had been studied with 15O PET within 72 h of TBI. Lesion regions of interest (ROI) and non-lesion ROIs were constructed on late-stage MRIs and applied to co-registered PET maps of CBF, CMRO2 and oxygen extraction fraction (OEF). From the entire population of voxels in non-lesion ROIs, we determined thresholds for the development of irreversible tissue damage as the lower limit of the 95% confidence interval for CBF, CMRO2 and OEF. To test the ability of a physiological variable to differentiate lesion and non-lesion tissue, we constructed probability curves, demonstrating the ability of a physiological variable to predict lesion and non-lesion outcomes. The lower limits of the 95% confidence interval for CBF, CMRO2 and OEF in non-lesion tissue were 15.0 ml/100 ml/min, 36.7 µmol/100 ml/min and 25.9% respectively. Voxels below these values were significantly more frequent in lesion tissue (all P < 0.005, MannWhitney U-test). However, a significant proportion of lesion voxels had values above these thresholds, so that definition of the full extent of irreversible tissue damage would not be possible based upon single physiological thresholds. We conclude that, in TBI, the threshold of CBF below which irreversible tissue damage consistently occurs differs from the classical CBF threshold for stroke (where similar methodology is used to define such thresholds). The CMRO2 threshold is comparable to that reported in the stroke literature. At a voxel-based level, however (and in common with ischaemic stroke), the extent of irreversible tissue damage cannot be accurately predicted by early abnormalities of any single physiological variable.
Key Words: traumatic brain injury; CBF; cerebral metabolism; physiological thresholds; prediction
Abbreviations: CBF = cerebral blood flow; CMRO2 = cerebral metabolic rate of oxygen utilization; FLAIR = fluid-attenuated inversion recovery; NPV = negative predictive value; OEF = oxygen extraction fraction; PPV = positive predictive value; ROI = region of interest; TBI = traumatic brain injury
Received November 21, 2004. Revised April 6, 2005. Accepted April 10, 2005.
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