Imaging after brain injury
University Department of Anaesthesia, Addenbrooke's Hospital, Box 93, Hills Road, Cambridge CB2 2QQ, UK
* E-mail: jpc44{at}wbic.cam.ac.uk
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Abstract |
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Head injury remains an important cause of death and disability in young adults. This review will discuss the role of structural imaging using computed tomography (CT) and magnetic resonance imaging (MRI) and physiological imaging using CT perfusion, 131Xe CT, MRI and spectroscopy (MRS), single photon emission computed tomography, and positron emission tomography (PET) in the assessment, management, and prediction of outcome after head injury. CT allows rapid assessment of brain pathology which ensures patients who require urgent surgical intervention receive appropriate care. Although MRI provides greater spatial resolution, particularly within the posterior fossa and deep white matter, a complete assessment of the burden of injury requires imaging of cerebral physiology. Physiological imaging techniques can only provide ‘snap shots’ of physiology within the injured brain, but they can be repeated, and such data can be used to assess the impact of therapeutic interventions. Perfusion imaging based on CT techniques (xenon CT and CT perfusion) can be implemented easily in most hospital centres, and provide quantitative perfusion data in addition to structural images. PET imaging provides unparalleled insights into cerebral physiology and pathophysiology, but is not widely available and is primarily a research tool. MR technology continues to develop and is becoming generally available. Using a complex variety of sequences, MR can provide data concerning both structural and physiological derangements. Future developments with such imaging techniques should improve understanding of the pathophysiology of brain injury and provide data that should improve management and prediction of functional outcome.
Keywords: brain, blood flow; brain, ischaemia; brain, magnetic resonance imaging; brain, metabolism; brain, oxygen metabolism; head, injury
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Introduction |
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TopAbstractIntroductionImaging modalitiesConclusionsAcknowledgementsReferences |
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Head injury remains an important cause of death and disability in young adults, with over 50% of patients experiencing unfavourable outcomes.13 23 Although neuroimaging is central to how we define the extent of injury and manage patients with acute injury, we must improve our understanding of the critical pathophysiological derangements that remain and are responsible for such poor outcome. Advances in neuroimaging techniques may allow the development of new treatments and refinement of existing therapies aimed at preventing neuronal injury and ultimately improving functional outcome for patients.
This review will discuss the role of structural imaging using computed tomography (CT) and magnetic resonance imaging (MRI), and physiological imaging using CT perfusion, 131Xe, CT, MRI and spectroscopy (MRS), single photon emission computed tomography (SPECT), and positron emission tomography (PET) in the assessment, management, and prediction of outcome after head injury.
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Structural imaging
CT is routinely used to assess all patients with acute head injury who require admission and observation within hospital.57 Such imaging provides early assessment of the extent of the injury46 50 74 75 and can be obtained quickly using modern multi-detector high resolution scanners which are widely available. Patients admitted via emergency departments within neurosurgical centres and general hospitals can be transferred to the radiology suite and images reviewed on-line or transferred electronically for specialist review. The short imaging time and ease of acquisition is of considerable benefit in agitated patients and those who are ventilated but unstable due to severe trauma. Image slices that are degraded by motion artifact can easily be repeated. Imaging data can be visualized using brain or bone contrast windows and reconstructed into three-dimensional (3D) CT data sets in order to demonstrate bony injury58 (Fig. 1) and intracranial pathology.
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Imaging data sets demonstrate the differences between normal and abnormal brain in terms of the degree of X-ray attenuation. Blood clot, which has a high degree of X-ray attenuation, appears as a hyperdense or white area, whereas oedematous or ischaemic regions with increased water content and lower electron density appear dark due to reduced attenuation. Acute CT is useful in identifying those individuals in whom deterioration is a result of a mass lesion and demonstrate extradural, subdural or intracranial haemorrhage, and midline shift (Fig. 2), or traumatic subarachnoid haemorrhage and ventricular abnormality (Fig. 3). The ease of access and speed of data acquisition ensures that, where appropriate, patients benefit from early surgical management which has been shown to improve outcome.68
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Despite its usefulness, CT imaging is limited by beam hardening effects, which can partially obscure the posterior fossa, temporal and frontal regions, and partial volume errors. The latter occur when a region of injured tissue has one or more dimensions that are smaller than the resolution of the acquired data.46 This can mean that haemorrhage or other evidence of intracranial pathology may remain undetected. Such issues are of particular concern within the brain stem and spinal cord, where a small area of pathology can result in devastating injury, and in many patients who exhibit evidence of diffuse axonal injury (DAI) after trauma. DAI is a frequent finding after TBI, accounting for up to 50% of trauma patients.29 The regions of the brain that are commonly injured include the grey–white matter interface, corpus callosum and deep white matter, periventricular and hippocampal areas, and brainstem.29 Such regions are best visualized using MRI,63 and increasingly patients undergo acute MRI after TBI. Access to the MR suite has been improved through the provision of integrated monitoring and anaesthetic equipment suitable for critically ill patients. Patients, staff, and equipment must be verified to be safe before transfer, and contraindications prevent imaging in some cases.14 73 Despite the obvious advantages of MRI in terms of delineating the extent and severity of brain injury, the MRI suite is not immediately accessible, and CT remains the modality of choice in the acute phase.
MRI is more sensitive at detecting white matter abnormalities than CT.27 In addition, Gradient echo 47 and fluid attenuation inversion recovery (FLAIR) MR sequences 1 demonstrate high sensitivity for DAI, and may help predict outcome.39 40 Differences in imaging contrast within both normal and injured brain are dependent on the particular MRI sequence employed. FLAIR sequences generate images in which areas of tissue T2 prolongation are bright whereas normal CSF signal is nulled and appears dark. This allows the detection of periventricular and superficial cortical lesions. Gradient echo MRI is sensitive to changes in magnetic susceptibility which results in lesions of low intensity after haemorrhage within the brain due to local magnetic field inhomogeneities caused by the paramagnetic properties of haemosiderin. By employing a variety of different MR sequences, the extent of brain injury can be demonstrated with high resolution across the brain (Figs 
4 and 5).
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Head injury can also lead to damage to the cerebral vasculature and result in cerebral ischaemia and infarction. Traumatic vascular injury is commonly associated with basal skull fracture, neck trauma, or penetrating head injury. Such injuries can result in cerebral ischaemia within the affected vascular territory and early assessment using cerebral angiography, CT or MR angiography is essential since prompt repair of treatable causes will prevent infarction and poor outcome. It would clearly be beneficial if imaging data could be used to predict patient outcome. Although imaging findings, based on CT and MR data,50 51 63 72 80 can predict survival, they do not provide sufficient information to allow accurate prediction of functional recovery. Indeed, although patients with lesions within the deep white matter and brain stem are more likely to suffer poor outcome, a consistent relationship based on the assessment of CT and MRI data remains elusive.46
Functional imaging
Although structural imaging enables early diagnosis, directs initial management, and helps to predict eventual outcome, imaging of cerebral function is desirable. It can define the early pathophysiological processes responsible for neuronal injury, assess the efficacy of therapeutic interventions, and potentially direct the design and implementation of future therapeutic interventions aimed at reversing or preventing neuronal injury. Several imaging techniques are available which can measure aspects of brain physiology, including cerebral blood flow (CBF) and metabolism. Xenon-enhanced computerized tomography (xenon CT), CT perfusion, and SPECT provide measurements of cerebral perfusion, whereas PET, MRI, and MRS are able to assess both perfusion and cerebral metabolism. These imaging modalities are helpful in defining the extent of injury, evidence of cerebral ischaemia, and predicting outcome.14 18 44
Xenon-enhanced CT
This technique uses stable non-radioactive 131Xe, which is a radio opaque, highly lipid soluble, diffusible indicator capable of crossing the blood brain barrier.14 44 It provides a measure of tissue perfusion with quantification based on a modification of the Fick principle.41 Data are acquired during inhalation of a gas mixture containing 28% 131Xe and oxygen.44 Acquisition of a baseline structural scan without xenon inhalation is followed by serial scans at regular intervals after beginning xenon inhalation. Typically, up to six slices of data are acquired over 4.5 min, with a further 10 min for data processing. Alveolar xenon concentration is measured by end-tidal sampling and assumed to be equal to arterial concentration. The degree of tissue enhancement of CT images [Hounsfield units (HU)] is calculated, and relates to an increase in the tissue 131Xe concentration which is proportional to the blood flow.22 44 Movement artifacts can be troublesome in patients due to the known sedative effects of xenon. However, such problems have been lessened by the gradual reduction in the concentration of xenon required, and are irrelevant in patients who are already sedated and ventilated. Although xenon can induce CBF increases of up to 30% and increase ICP, the available data suggest that both CBF and ICP data are not affected adversely during the short-term inhalation of xenon required for CBF imaging using this technique.44 48 Xenon CT provides rapid access to both structural and quantitative CBF data using equipment that is readily available. Studies can be repeated within a short period of time allowing assessment of clinical therapy, such as hyperventilation, CPP augmentation, or hypertonic saline.12 71 76 Such data have been used to demonstrate early hypoperfusion consistent with ischaemia after head injury, predict cerebral infarction, raised ICP secondary to hyperperfusion and abnormal CO2 reactivity and autoregulation.18 37 52 64 Despite these advantages, quantitative CBF studies can be difficult to perform in patients with associated pulmonary pathology since the technique is based on the assumption that the end-tidal xenon concentration is identical to the arterial concentration.14 60 83
CT perfusion
The development of high-speed helical CT scanners and the availability of image reconstruction software have allowed this technique to become clinically available. CT perfusion involves sequential acquisition of axial data during the i.v. administration of iodinated contrast material. Since the change in CT enhancement (HU) is proportional to the concentration of contrast, perfusion is calculated from the time course of contrast enhancement profiles for each pixel in relation to the profile of arterial contrast enhancement (the arterial input function).44 54 On the basis of the central volume theorem, CT perfusion is able to provide parametric images of cerebral blood volume (CBV), mean transit time (MTT), CBF, and CT angiography alongside structural data.14 44 67 It is a widely accessible, rapid, and accurate technique which can provide a means for directing therapy and predicting outcome after head injury,32 54 and assessing cerebral vasospasm after subarachnoid haemorrhage.30 82 A typical protocol allows acquisition of two 10 mm slices of data covering a region of interest within the brain.56
However, the number and location of selected brain slices is limited due to radiation exposure,28 44 83 and repeat imaging after a therapeutic intervention is limited by the volume of contrast agent that can be safely administered.
Single photon emission computed tomography and positron emission tomography
SPECT uses conventional 
-emitting nuclear medicine isotopes with multiple detectors to generate tomographic images. 133Xe and technetium-99 m-hexamethyl-propylamine-oxime (99Tc-HMPAO) have been commonly employed to investigate blood flow within the brain.44 77 SPECT is a relatively simple and inexpensive technique which can be used to assess cerebral perfusion,55 but the images produced are of relatively low resolution and generally non-quantitative.44 77
PET measures the accumulation of positron-emitting radioisotopes within the brain.5 14 These positron-emitting isotopes can be administered via the i.v. or inhalation route, and for imaging of the brain, 15-oxygen (15O) is employed to measure CBF, CBV, oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF), whereas 18-fluorodeoxyglucose (18FDG) is used to measure cerebral glucose metabolism. The emitted positrons are annihilated in a collision with an electron resulting in the release of energy in the form of two photons (gamma rays) released at an angle of 180° to each other. This annihilation energy can be detected externally using coincidence detectors, and the region of each reaction localized within the object by computer algorithms. Although PET is clearly capable of defining many complex aspects of cerebral physiology and pathophysiology, it is a research tool which is relatively expensive and not universally available.14 Despite this, PET has been successfully used to investigate changes in physiology after head injury.15–18 53 59 62 78 These demonstrate that early reductions in cerebral perfusion can result in cerebral ischaemia that is associated with poor outcome, despite optimal management of ICP and cerebral perfusion pressure (CPP) (Fig. 6). However, other PET studies have failed to find conclusive evidence of cerebral ischaemia.20 21 Indeed, brain-injured patients commonly demonstrate evidence of global hypometabolism and metabolic stress which fails to recover in patients who have a poor outcome.7 78 84 PET studies can be repeated and used to assess changes in physiology with commonly applied therapeutic manoeuvres, such as hyperventilation and CPP augmentation. Such studies have helped to demonstrate that the efficacy of such therapies should be determined by measurement of cerebral perfusion and metabolism within individual patients and across the injured brain (Fig. 7).16 17 Blood flow and metabolism varies dramatically across the traumatized brain and different regions may require different therapeutic approaches. Although this is obviously not possible using global therapeutic manoeuvres, it is clear that the effect of common therapeutic interventions should be measured and only continued where benefit is demonstrated.16 17
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Although several PET studies have sought to define thresholds for tissue viability and ischaemia after ischaemic stroke4 and head injury,18 a recent review highlights the difficulties with such published thresholds.2 Although brain regions with dramatic reductions in CBF are clearly incapable of surviving, patients also demonstrate functional cognitive deficits in regions without clear evidence of structural injury. One possible cause for such findings is that a region which appears structurally intact may have suffered patchy neuronal injury which results in selective neuronal loss and functional deficit. Early PET studies of CBF and metabolism clearly help to predict outcome, but further studies using markers of such selective neuronal injury, such as MRS31 and Flumazenil PET,31 may improve the predictive power of such thresholds after head injury.
MRI techniques
Blood flow can be measured using two different measurement techniques. Perfusion MRI uses rapid sequential susceptibility-weighted imaging after injection of a bolus of MRI contrast medium [typically Gadopentate dimeglumine (Gd-DTPA, Magnevist®)] that induces a change in intravascular magnetic susceptibility44 to produce images of MTT, and relative CBF and CBV. Another MR technique uses an endogenous diffusible tracer to measure CBF by applying magnetic resonance pulses to tag in-flowing water protons.10 In this ‘arterial spin labelling’ approach, the changes in the amplitude of the MRI signal are used to construct quantitative images of cerebral perfusion. Although such techniques are now being successfully applied to clinical settings,33 42 there are outstanding issues regarding absolute quantification.10 24
Diffusion-weighted MRI (DWI) images the microscopic movement of water using powerful gradient coils that undergo rapid switching in polarity on either side of a 180° excitation pulse. The random motion of diffusion leads to phase shifts and signal loss, whereas regions with decreased motion show little or no signal loss and appear relatively bright on DWI images. Early hypointensity on apparent diffusion coefficient (ADC) DWI occurs after acute ischaemia and is associated with the movement of water into the intracellular compartment where it is relatively restricted (cytotoxic oedema).14 44 A region demonstrating an acute decrease on ADC maps is assumed to have suffered irreversible injury (core), whereas the presence of reduced perfusion but normal diffusion is representative of tissue at risk of ischaemic injury (ischaemic penumbra). For these reasons, a so-called perfusion/diffusion mismatch has been used to diagnose early cerebral ischaemia and direct therapy.19 44 DWI data can also be reconstructed to provide imaging of white matter tracts using diffusion tensor imaging (DTI) since the direction and magnitude of water diffusion is highly constrained within such regions (Fig. 8). Such data are useful in delineating the extent of brain injury, and evidence suggests that disruption of white matter tracts has important implications for cognitive recovery.65 81
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Magnetic resonance spectroscopy is a non-invasive imaging technique that allows the investigation of biochemical pathology within the brain.71 Although both proton (1H-MRS) and phosphorus (31P-MRS) spectroscopy are frequently used to study cerebral metabolism and ischaemia, 1H-MRS is the prominent technique in humans. 1H-MRS provides data on several biologically relevant molecules, including lactate, N-acetyl aspartate (NAA), total creatine [creatine and phosphocreatine (Cr+PCr)], glutamate/glutamine (Glx) and choline (Cho).14 Increased lactate suggests deranged energy metabolism and is consistent with cerebral ischaemia.3 70 NAA is located primarily within neurones, and a reduction in NAA can be indicative of neuronal death or dysfunction.3 A decrease in NAA has been found after head injury,11 25 26 69 and although this may represent neuronal loss, it may also be the consequence of mitochondrial dysfunction and metabolic depression.6 49 Although it is clear that MRS can provide important information regarding the metabolic state and potential viability of ischaemic brain tissue, at present, there are limitations to the technique. MRS imaging is hampered by limited coverage of the brain, poor spatial resolution, and the necessity for long imaging times. Despite this, MRS has been shown to be clinically useful in head injury.9 11 27 34 35 69 and promises to become widely available since it can be readily implemented on existing MRI machines.
MR has become an extremely useful clinical tool after head injury,14 36 43 65 66 since it combines the ability to image perfusion, the status of tissue (DWI and MRS), vascular patency (MR angiography), and white matter tracts (DTI) across the whole brain with high-resolution structural imaging. This thorough assessment of the derangements induced by brain injury can be used to predict the mechanism of injury, the likely response to therapeutic intervention and the degree of eventual functional recovery (Fig. 9).
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Functional MRI
Functional MRI (fMRI) can be used to measure neural activation by measurement of changes in blood oxygenation using the blood oxygen level dependent technique which is sensitive to local changes in the magnetic field induced by the presence of deoxygenated haemoglobin.79 This technique uses a rapid MRI sequence capable of demonstrating change after performance of a particular cognitive task aimed at inducing activation within a region of the brain. Neural activation results in an increase in regional blood flow and influx of oxygenated blood which causes a decrease in the level of deoxygenated haemoglobin. Such techniques have been used in the assessment of patients who appear to be in a vegetative state after brain injury and can demonstrate that some patients may remain cognitively aware and capable of some degree of recovery.45 61 62 Although such positive findings have clear implications for predicting outcome after brain injury, a negative response in a particular cognitive task does not confirm that a patient is, or will remain, in a persistent vegetative state. Despite this, the technique has significant implications for the assessment of patients recovering from various forms of brain injury that appear to be in a vegetative, minimally conscious or locked in state.
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Conclusions |
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TopAbstractIntroductionImaging modalitiesConclusionsAcknowledgementsReferences |
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Imaging is an important clinical tool used in the management of patients with brain injury. CT allows rapid assessment of the extent and type of brain pathology which ensures patients who require urgent surgical intervention receive such care at the earliest opportunity. Access to high field MRI is improving and patients benefit from its greater spatial resolution, particularly within the posterior fossa and deep white matter, and its ability to combine imaging of structure and function across the brain. Although the extent and distribution of structural lesions within the brain is associated with outcome, such data do not allow accurate prediction of functional outcome. A more complete assessment of the burden of injury within the brain requires imaging of cerebral physiology, both in the acute phase and into the recovery period. Several techniques are currently available which provide imaging of cerebral blood flow and metabolism. Although such imaging techniques can only provide ‘snap shots’ of physiology within the injured brain, they can be repeated and used to assess the impact of therapeutic interventions. Perfusion imaging based on CT techniques (xenon CT and CT perfusion) can be implemented easily in most hospital centres, and provide quantitative perfusion data in addition to structural images. PET imaging provides unparalleled insights into cerebral physiology and pathophysiology, but is not widely available and is primarily a research tool. MR technology continues to develop and is becoming generally available. Using a complex variety of sequences, MR can provide data concerning both structural and physiological derangements. Future developments with such imaging techniques should improve understanding of the pathophysiology of brain injury and provide data that might improve management and prediction of functional outcome.
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The research published by this author was supported by the Medical Research Council, a Technology Foresight Award from the UK Government and by a Royal College of Anaesthetists/British Journal of Anaesthesia project grant. Dr Coles has previously been funded by Research Training Fellowships from the Addenbrooke's Charities, the Wellcome Foundation and by a Beverley and Raymond Sackler studentship award. Currently, Dr Coles is supported through an Academy of Medical Sciences and Health Foundation Clinician Scientist Fellowship. www.acmedsci.ac.uk www.health.org.uk.
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1 Ashikaga R, Araki Y, Ishida O. MRI of head injury using FLAIR. Neuroradiology (1997) 39:239–42.[CrossRef][Web of Science][Medline]
2 Bandera E, Botteri M, Minelli C, Sutton A, Abrams KR, Latronico N. Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review. Stroke (2006) 37:1334–9.
3 Barker PB. Fundamentals of MR spectroscopy. In: Clinical MR Neuroimaging—Gillard JH, Waldman AD, Barker PB, eds. (2005) Cambridge: Cambridge University Press. 7–26.
4 Baron JC. Stroke research in the modern era: images versus dogmas. Cerebrovasc Dis (2005) 20:154–63.[CrossRef][Web of Science][Medline]
5 Baron JC, Frackowiak RS, Herholz K, et al. Use of PET methods for measurement of cerebral energy metabolism and hemodynamics in cerebrovascular disease. J Cereb Blood Flow Metab (1989) 9:723–42.[Web of Science][Medline]
6 Belli A, Sen J, Petzold A, et al. Extracellular N-acetylaspartate depletion in traumatic brain injury. J Neurochem (2006) 96:861–9.[CrossRef][Web of Science][Medline]
7 Bergsneider M, Hovda DA, Lee SM, et al. Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury. J Neurotrauma (2000) 17:389–401.[Web of Science][Medline]
8 Bouma GJ, Muizelaar JP, Stringer WA, Choi SC, Fatouros P, Young HF. Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg (1992) 77:360–8.[Web of Science][Medline]
9 Brooks WM, Friedman SD, Gasparovic C. Magnetic resonance spectroscopy in traumatic brain injury. J Head Trauma Rehabil (2001) 16:149–64.[Web of Science][Medline]
10 Calamante F, Thomas DL, Pell GS, Wiersma J, Turner R. Measuring cerebral blood flow using magnetic resonance imaging techniques. J Cereb Blood Flow Metab (1999) 19:701–35.[CrossRef][Web of Science][Medline]
11 Carpentier A, Galanaud D, Puybasset L, et al. Early morphologic and spectroscopic magnetic resonance in severe traumatic brain injuries can detect ‘invisible brain stem damage’ and predict ‘vegetative states. J Neurotrauma (2006) 23:674–85.[CrossRef][Web of Science][Medline]
12 Chieregato A, Fainardi E, Tanfani A, et al. Induced acute arterial hypertension and regional cerebral flow in intracontusional low density area. Acta Neurochir Suppl (2003) 86:361–5.[Medline]
13 Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med (2001) 344:556–63.
14 Coles JP. Imaging of cerebral blood flow and metabolism. Curr Opin Anaesthesiol (2006) 19:473–80.[Medline]
15 Coles JP, Fryer TD, Smielewski P, et al. Incidence and mechanisms of cerebral ischemia in early clinical head injury. J Cereb Blood Flow Metab (2004) 24:202–11.[CrossRef][Web of Science][Medline]
16 Coles JP, Minhas PS, Fryer TD, et al. Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical relevance and monitoring correlates. Crit Care Med (2002) 30:1950–9.[CrossRef][Web of Science][Medline]
17 Coles JP, Steiner LA, Johnston AJ, et al. Does induced hypertension reduce cerebral ischaemia within the traumatized human brain? Brain (2004) 127:2479–90.
18 Cunningham AS, Salvador R, Coles JP, et al. Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury. Brain (2005) 128:1931–42.
19 Davis SM, Donnan GA, Butcher KS, Parsons M. Selection of thrombolytic therapy beyond 3 h using magnetic resonance imaging. Curr Opin Neurol (2005) 18:47–52.[Web of Science][Medline]
20 Diringer MN, Videen TO, Yundt K, et al. Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury. J Neurosurg (2002) 96:103–8.[Web of Science][Medline]
21 Diringer MN, Yundt K, Videen TO, et al. No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury. J Neurosurg (2000) 92:7–13.[Web of Science][Medline]
22 Drayer BP, Wolfson SK, Reinmuth OM, Dujovny M, Boehnke M, Cook EE. Xenon enhanced CT for analysis of cerebral integrity, perfusion, and blood flow. Stroke (1978) 9:123–30.
23 Edwards P, Arango M, Balica L, et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet (2005) 365:1957–9.[CrossRef][Web of Science][Medline]
24 Ewing JR, Cao Y, Knight RA, Fenstermacher JD. Arterial spin labeling: validity testing and comparison studies. J Magn Reson Imaging (2005) 22:737–40.[CrossRef][Web of Science][Medline]
25 Garnett MR, Blamire AM, Corkill RG, Cadoux-Hudson TA, Rajagopalan B, Styles P. Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury. Brain (2000) 123:2046–54.
26 Garnett MR, Blamire AM, Rajagopalan B, Styles P, Cadoux-Hudson TA. Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: a magnetic resonance spectroscopy study. Brain (2000) 123:1403–9.
27 Garnett MR, Cadoux-Hudson TA, Styles P. How useful is magnetic resonance imaging in predicting severity and outcome in traumatic brain injury? Curr Opin Neurol (2001) 14:753–7.[CrossRef][Web of Science][Medline]
28 Gillard JH, Minhas PS, Hayball MP, et al. Assessment of quantitative computed tomographic cerebral perfusion imaging with H2(15)O positron emission tomography. Neurol Res (2000) 22:457–64.[Web of Science][Medline]
29 Hammoud DA, Wasserman BA. Diffuse axonal injuries: pathophysiology and imaging. Neuroimaging Clin N Am (2002) 12:205–16.[CrossRef][Web of Science][Medline]
30 Harrigan MR, Leonardo J, Gibbons KJ, Guterman LR, Hopkins LN. CT perfusion cerebral blood flow imaging in neurological critical care. Neurocrit Care (2005) 2:352–66.[CrossRef][Web of Science][Medline]
31 Heiss WD, Kracht LW, Thiel A, Grond M, Pawlik G. Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia. Brain (2001) 124:20–9.
32 Hemphill JC 3rd, Smith WS, Sonne DC, Morabito D, Manley GT. Relationship between brain tissue oxygen tension and CT perfusion: feasibility and initial results. Am J Neuroradiol (2005) 26:1095–100.
33 Hendrikse J, van der Zwan A, Ramos LM, et al. Altered flow territories after extracranial-intracranial bypass surgery. Neurosurgery (2005) 57:486–94. discussion 494.[CrossRef][Web of Science][Medline]
34 Holshouser BA, Tong KA, Ashwal S. Proton MR spectroscopic imaging depicts diffuse axonal injury in children with traumatic brain injury. Am J Neuroradiol (2005) 26:1276–85.
35 Hunter JV, Thornton RJ, Wang ZJ, et al. Late proton MR spectroscopy in children after traumatic brain injury: correlation with cognitive outcomes. Am J Neuroradiol (2005) 26:482–8.
36 Inglese M, Makani S, Johnson G, et al. Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study. J Neurosurg (2005) 103:298–303.[Web of Science][Medline]
37 Inoue Y, Shiozaki T, Tasaki O, et al. Changes in cerebral blood flow from the acute to the chronic phase of severe head injury. J Neurotrauma (2005) 22:1411–8.[CrossRef][Web of Science][Medline]
38 Johnston AJ, Steiner LA, Coles JP, et al. Effect of cerebral perfusion pressure augmentation on regional oxygenation and metabolism after head injury. Crit Care Med (2005) 33:189–95. discussion 255–7.[CrossRef][Web of Science][Medline]
39 Kampfl A, Franz G, Aichner F, et al. The persistent vegetative state after closed head injury: clinical and magnetic resonance imaging findings in 42 patients. J Neurosurg (1998) 88:809–16.[CrossRef][Web of Science][Medline]
40 Kampfl A, Schmutzhard E, Franz G, et al. Prediction of recovery from post-traumatic vegetative state with cerebral magnetic-resonance imaging. Lancet (1998) 351:1763–7.[CrossRef][Web of Science][Medline]
41 Kety SS, Schmidt CF. The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am J Physiol (1945) 143:53–6.
42 Kimura H, Kado H, Koshimoto Y, Tsuchida T, Yonekura Y, Itoh H. Multislice continuous arterial spin-labeled perfusion MRI in patients with chronic occlusive cerebrovascular disease: a correlative study with CO2 PET validation. J Magn Reson Imaging (2005) 22:189–98.[CrossRef][Web of Science][Medline]
43 Kinoshita T, Moritani T, Hiwatashi A, et al. Conspicuity of diffuse axonal injury lesions on diffusion-weighted MR imaging. Eur J Radiol (2005) 56:5–11.[CrossRef][Web of Science][Medline]
44 Latchaw RE, Yonas H, Hunter GJ, et al. Guidelines and recommendations for perfusion imaging in cerebral ischemia: a scientific statement for healthcare professionals by the writing group on perfusion imaging, from the Council on Cardiovascular Radiology of the American Heart Association. Stroke (2003) 34:1084–104.
45 Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol (2004) 3:537–46.[CrossRef][Web of Science][Medline]
46 Lee B, Newberg A. Neuroimaging in traumatic brain imaging. NeuroRx (2005) 2:372–83.
47 Liu AY, Maldjian JA, Bagley LJ, Sinson GP, Grossman RI. Traumatic brain injury: diffusion-weighted MR imaging findings. Am J Neuroradiol (1999) 20:1636–41.
48 Marion DW, Crosby K. The effect of stable xenon on ICP. J Cereb Blood Flow Metab (1991) 11:347–50.[Web of Science][Medline]
49 Marmarou A, Signoretti S, Fatouros P, Aygok GA, Bullock R. Mitochondrial injury measured by proton magnetic resonance spectroscopy in severe head trauma patients. Acta Neurochir Suppl (2005) 95:149–51.[Medline]
50 Marshall LF, Marshall SB, Klauber MR, et al. A new classification of head injury based on computerized tomography. J Neurosurg (1991) 75:S14–27.[Web of Science]
51 Mannion RJ, Cross J, Bradley P, et al. Mechanism-based MRI classification of traumatic brainstem injury and its relationship to outcome. J Neurotrauma (2007) 24:128–35.[CrossRef][Web of Science][Medline]
52 McLaughlin MR, Marion DW. Cerebral blood flow and vasoresponsivity within and around cerebral contusions. J Neurosurg (1996) 85:871–6.[CrossRef][Web of Science][Medline]
53 Menon DK, Coles JP, Gupta AK, et al. Diffusion limited oxygen delivery following head injury. Crit Care Med (2004) 32:1384–90.[CrossRef][Web of Science][Medline]
54 Miles KA. Brain perfusion: computed tomography applications. Neuroradiology (2004) 46((Suppl 2)):s194–200.[CrossRef][Web of Science][Medline]
55 Munari M, Zucchetta P, Carollo C, et al. Confirmatory tests in the diagnosis of brain death: comparison between SPECT and contrast angiography. Crit Care Med (2005) 33:2068–73.[CrossRef][Web of Science][Medline]
56 Nabavi DG, Cenic A, Craen RA, et al. CT assessment of cerebral perfusion: experimental validation and initial clinical experience. Radiology (1999) 213:141–9.
57 National Institute for Clinical Excellence. Head injury: triage, assessment, investigation and early management of head injury in infants, children and adults. (2003).
58 Newberg AB, Alavi A. Neuroimaging in patients with head injury. Semin Nucl Med (2003) 33:136–47.[CrossRef][Web of Science][Medline]
59 O'Connell MT, Seal A, Nortje J, et al. Glucose metabolism in traumatic brain injury: a combined microdialysis and [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) study. Acta Neurochir Suppl (2005) 95:165–8.[Medline]
60 von Oettingen G, Bergholt B, Ostergaard L, Jensen LC, Gyldensted C, Astrup J. Xenon CT cerebral blood flow in patients with head injury: influence of pulmonary trauma on the input function. Neuroradiology (2000) 42:168–73.[CrossRef][Web of Science][Medline]
61 Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science (2006) 313:1402.
62 Owen AM, Coleman MR, Menon DK, et al. Residual auditory function in persistent vegetative state: a combined PET and fMRI study. Neuropsychol Rehabil (2005) 15:290–306.[CrossRef][Web of Science][Medline]
63 Pierallini A, Pantano P, Fantozzi LM, et al. Correlation between MRI findings and long-term outcome in patients with severe brain trauma. Neuroradiology (2000) 42:860–7.[CrossRef][Web of Science][Medline]
64 Poon WS, Ng SC, Chan MT, Lam JM, Lam WW. Cerebral blood flow (CBF)-directed management of ventilated head-injured patients. Acta Neurochir Suppl (2005) 95:9–11.[Medline]
65 Salmond CH, Menon DK, Chatfield DA, et al. Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices. Neuroimage (2006) 29:117–24.[Web of Science][Medline]
66 Schaefer PW, Huisman TA, Sorensen AG, Gonzalez RG, Schwamm LH. Diffusion-weighted MR imaging in closed head injury: high correlation with initial glasgow coma scale score and score on modified Rankin scale at discharge. Radiology (2004) 233:58–66.
67 Scharf J, Brockmann MA, Daffertshofer M, et al. Improvement of sensitivity and interrater reliability to detect acute stroke by dynamic perfusion computed tomography and computed tomography angiography. J Comput Assist Tomogr (2006) 30:105–10.[CrossRef][Web of Science][Medline]
68 Seelig JM, Becker DP, Miller JD, Greenberg RP, Ward JD, Choi SC. Traumatic acute subdural hematoma: major mortality reduction in comatose patients treated within four hours. N Engl J Med (1981) 304:1511–8.[Abstract]
69 Shutter L, Tong KA, Lee A, Holshouser BA. Prognostic role of proton magnetic resonance spectroscopy in acute traumatic brain injury. J Head Trauma Rehabil (2006) 21:334–49.[Web of Science][Medline]
70 Stengel A, Neumann-Haefelin T, Singer OC, et al. Multiple spin-echo spectroscopic imaging for rapid quantitative assessment of N-acetylaspartate and lactate in acute stroke. Magn Reson Med (2004) 52:228–38.[CrossRef][Web of Science][Medline]
71 Stringer WA, Hasso AN, Thompson JR, Hinshaw DB, Jordan KG. Hyperventilation-induced cerebral ischemia in patients with acute brain lesions: demonstration by xenon-enhanced CT. Am J Neuroradiol (1993) 14:475–84.[Abstract]
72 Takaoka M, Tabuse H, Kumura E, et al. Semiquantitative analysis of corpus callosum injury using magnetic resonance imaging indicates clinical severity in patients with diffuse axonal injury. J Neurol Neurosurg Psychiatry (2002) 73:289–93.
73 The Association of Anaesthetists of Great Britain and Ireland. Provision of anaesthetic services in magnetic resonance units. (2002).
74 The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Computed tomography scan features. J Neurotrauma (2000) 17:597–627.[Medline]
75 Toyama Y, Kobayashi T, Nishiyama Y, Satoh K, Ohkawa M, Seki K. CT for acute stage of closed head injury. Radiat Med (2005) 23:309–16.[Medline]
76 Tseng MY, Al-Rawi PG, Pickard JD, Rasulo FA, Kirkpatrick PJ. Effect of hypertonic saline on cerebral blood flow in poor-grade patients with subarachnoid hemorrhage. Stroke (2003) 34:1389–96.
77 Ueda T, Yuh WT. Single-photon emission CT imaging in acute stroke. Neuroimaging Clin N Am (2005) 15:543–51.[CrossRef][Web of Science][Medline]
78 Vespa P, Bergsneider M, Hattori N, et al. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab (2005) 25:763–4.[CrossRef][Web of Science][Medline]
79 Ward NS, Frackowiak RS. The functional anatomy of cerebral reorganisation after focal brain injury. J Physiol Paris (2006) 99:425–36.[CrossRef][Web of Science][Medline]
80 Wardlaw JM, Easton VJ, Statham P. Which CT features help predict outcome after head injury? J Neurol Neurosurg Psychiatry (2002) 72:188–92. discussion 51.
81 Wilde EA, Chu Z, Bigler ED, et al. Diffusion tensor imaging in the corpus callosum in children after moderate to severe traumatic brain injury. J Neurotrauma (2006) 23:1412–26.[CrossRef][Web of Science][Medline]
82 Wintermark M, Ko NU, Smith WS, Liu S, Higashida RT, Dillon WP. Vasospasm after subarachnoid hemorrhage: utility of perfusion CT and CT angiography on diagnosis and management. Am J Neuroradiol (2006) 27:26–34.
83 Wintermark M, Thiran JP, Maeder P, Schnyder P, Meuli R. Simultaneous measurement of regional cerebral blood flow by perfusion CT and stable xenon CT: a validation study. Am J Neuroradiol (2001) 22:905–14.
84 Wu HM, Huang SC, Hattori N, et al. Selective metabolic reduction in gray matter acutely following human traumatic brain injury. J Neurotrauma (2004) 21:149–61.[CrossRef][Web of Science][Medline]
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