The use of cerebral computed tomographic angiography as an ancillary investigation to support a clinical diagnosis of death using neurological criteria: a consensus guideline.

This multidisciplinary consensus statement was produced following a recommendation by the Faculty of Intensive Care Medicine to develop a UK guideline for ancillary investigation, when one is required, to support the diagnosis of death using neurological criteria. A multidisciplinary panel reviewed the literature and UK practice in the diagnosis of death using neurological criteria and recommended cerebral CT angiography as the ancillary investigation of choice when death cannot be confirmed by clinical criteria alone. Cerebral CT angiography has been shown to have 100% specificity in supporting a diagnosis of death using neurological criteria and is an investigation available in all acute hospitals in the UK. A standardised technique for performing the investigation is described alongside a reporting template. The panel were unable to make recommendations for ancillary testing in children or patients receiving extracorporeal membrane oxygenation.

Survey evaluating clinical equipoise around platelet transfusion after head injury and traumatic intracranial haemorrhage (ICH) in patients on antiplatelet medications.

INTRODUCTION: Patients aged 60 or over account for over half of the severely injured trauma patients and a traumatic brain injury is the most common injury sustained. Many of these patients are taking antiplatelet medications but there is clinical equipoise about the role of platelet transfusion in patients with traumatic intracranial haemorrhage (ICH) taking prior antiplatelet medications. METHOD: A prepiloted survey was designed to explore a range of clinical issues in managing patients taking antiplatelet medications admitted with a traumatic brain injury. This was sent via email to consultants and specialty registrar members of a variety of relevant UK societies and working groups in the fields of emergency medicine, critical care, neurosurgery and haematology. RESULTS: 193 responses were received, mostly from colleagues in emergency medicine, neurosurgery, anaesthesia and haematology. Respondents indicated that there is a lack of evidence to support the use of platelet transfusion in this patient population but also lack of evidence of harm. Results also demonstrate uncertainties as to whether platelets should be given to all or some patients and doubt regarding the value of viscoelastic testing. DISCUSSION: Our survey demonstrates equipoise in current practice with regards to platelet transfusion in patients with a traumatic ICH who are taking antiplatelet medication. There is support for additional trials to investigate the effect of platelet transfusion in this rising population of older, high-risk patients, in order to provide a better evidence-base for guideline development.

Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Systematic review of current randomised control trials in chronic subdural haematoma and proposal for an international collaborative approach.

BACKGROUND: Chronic subdural haematoma (CSDH) is a pathology that is frequently encountered by neurosurgeons. Nevertheless, there is a lack of guidelines based on solid evidence. There has been a recent and considerable increase in the interest on management and outcomes for CSDH. Therefore, we systematically reviewed all currently running randomised controlled trials (RCTs) in chronic subdural haematoma to understand the areas under investigation and plan future collaborative trials. METHODS: Clinical trials databases (Cochrane Controlled Register of Trials, WHO ICTRP and clinical trials.gov) were searched for trials relevant to chronic subdural haematoma. It was then established which trials were currently running and fulfilled robust research methodology for a RCT. RESULTS: There are 26 currently running RCTs in CSDH, with the most common topics covering application of steroids (7), surgical techniques (5) and tranexamic acid (5). Further to this, there are trials running on other pharmacological agents (4), middle meningeal artery (MMA) embolisation (2) and peri-operative management (3). CONCLUSIONS: Pharmacological agents are a particular focus of CSDH management currently, and a wealth of studies on steroids will hopefully lead to more harmonised, evidence-based practice regarding this in the near future. Surgical techniques and new procedures such as MMA embolisation are also important focuses for improving patient outcomes. There is an on-going need for future RCTs and evidence-based guidelines in CSDH, particularly including low- and middle-income countries, and it is hoped that the establishment of the iCORIC (International COllaborative Research Initiative on Chronic Subdural Haematoma) will help address this.

Social media for dissemination and public engagement in neurosurgery-the example of Brainbook.

BACKGROUND: Public engagement has become one of the most effective tools in gaining feedback and perspectives from members of the public, involving patients with decisions, and inspiring young people to carry the medical profession forwards. Brainbook is a multi-platform, social media-based resource that was created specifically to enhance public engagement in neurosurgery and results from one of its case discussions will be reported in this paper. METHODS: A Brainbook case was created in collaboration with the NIHR Global Health Research Group on Neurotrauma and presented over 3 days (23-25 February 2018). YouTube videos were created depicting the management of an acute subdural haematoma using patient interviews, medical illustration, consultant-led discussion and operative footage. Content was shared across all Brainbook social media platforms and analytics were gathered through social media applications. RESULTS: Over a 72-hour time period, and across multiple social media accounts, 101,418 impressions were achieved (defined as penetrance onto individual media feeds and total views of the content), with active discussion on social media. CONCLUSIONS: Neurosurgical content published across multiple social media outlets represents an encouraging and exciting potential for global engagement across multiple audiences. Social media can be an effective method of not only disseminating neurosurgical knowledge, but activating and engaging the public, allied healthcare professionals, medical students and neurosurgeons.

Pressure Reactivity-Based Optimal Cerebral Perfusion Pressure in a Traumatic Brain Injury Cohort.

OBJECTIVES: Retrospective data from patients with severe traumatic brain injury (TBI) indicate that deviation from the continuously calculated pressure reactivity-based "optimal" cerebral perfusion pressure (CPPopt) is associated with worse patient outcome. The objective of this study was to assess the relationship between prospectively collected CPPopt data and patient outcome after TBI. METHODS: We prospectively collected intracranial pressure (ICP) monitoring data from 231 patients with severe TBI at Addenbrooke's Hospital, UK. Uncleaned arterial blood pressure and ICP signals were recording using ICM+® software on dedicated bedside computers. CPPopt was determined using an automatic curve fitting procedure of the relationship between pressure reactivity index (PRx) and CPP using a 4-h window, as previously described. The difference between an instantaneous CPP value and its corresponding CPPopt value was denoted every minute as ΔCPPopt. A negative ΔCPPopt that was associated with impaired PRx (>+0.15) was denoted as being below the lower limit of reactivity (LLR). Glasgow Outcome Scale (GOS) score was assessed at 6 months post-ictus. RESULTS: When ΔCPPopt was plotted against PRx and stratified by GOS groupings, data belonging to patients with a more unfavourable outcome had a U-shaped curve that shifted upwards. More time spent with a ΔCPPopt value below the LLR was positively associated with mortality (area under the receiver operating characteristic curve = 0.76 [0.68-0.84]). CONCLUSIONS: In a recent cohort of patients with severe TBI, the time spent with a CPP below the CPPopt-derived LLR is related to mortality. Despite aggressive CPP- and ICP-oriented therapies, TBI patients with a fatal outcome spend a significant amount of time with a CPP below their individualised CPPopt, indicating a possible therapeutic target.

Comparison of ventricular drain location and infusion test in hydrocephalus.

OBJECTIVES: Suspected cerebrospinal fluid shunt (CSF) dysfunction in hydrocephalic patients poses a diagnostic uncertainty. The clinical picture can be non-specific and CT imaging alone is not always pathognomonic. Infusion tests are an increasingly used investigation for real-time hydrodynamic assessment of shunt patency. We report the correlation between infusion test results with the quality of ventricular drain placement on CT scans in a large retrospective group of hydrocephalic patients. MATERIALS & METHODS: Three hundred and six infusion test results performed in 200 patients were correlated with 306 corresponding CT head scans. Nominal logistic regression was used to correlate shunt catheter position on CT imaging to patency of ventricular drain as determined by infusion tests. RESULTS: Infusion test results of shunt patency are statistically congruent with the analysis of shunt catheter position on CT head scans. Catheter tips completely surrounded by either parenchyma or CSF on CT imaging are strongly associated with evidence of occlusion or patency from infusion tests, respectively (χ² = 51.68, P < 0.0001, n = 306 and χ² = 31.04, P < 0.0001, n = 306). CONCLUSIONS: The most important anatomical factor for shunt patency is the catheter tip being completely surrounded by CSF. Infusion tests provide functional and reliable assessment of shunt patency in vivo and are strongly correlated with the position of the ventricular catheter on CT imaging.

An evaluation of the clinical and cost-effectiveness of alternative care locations for critically ill adult patients with acute traumatic brain injury.

BACKGROUND: For critically ill adult patients with acute traumatic brain injury (TBI), we assessed the clinical and cost-effectiveness of: (a) Management in dedicated neurocritical care units versus combined neuro/general critical care units within neuroscience centres. (b) 'Early' transfer to a neuroscience centre versus 'no or late' transfer for those who present at a non-neuroscience centre. METHODS: The Risk Adjustment In Neurocritical care (RAIN) Study included prospective admissions following acute TBI to 67 UK adult critical care units during 2009-11. Data were collected on baseline case-mix, mortality, resource use, and at six months, Glasgow Outcome Scale Extended (GOSE), and quality of life (QOL) (EuroQol 5D-3L). We report incremental effectiveness, costs and cost per Quality-Adjusted Life Year (QALY) of the alternative care locations, adjusting for baseline differences with validated risk prediction models. We tested the robustness of results in sensitivity analyses. FINDINGS: Dedicated neurocritical care unit patients (N = 1324) had similar six-month mortality, higher QOL (mean gain 0.048, 95% CI -0.002 to 0.099) and increased average costs compared with those managed in combined neuro/general units (N = 1341), with a lifetime cost per QALY gained of £14,000. 'Early' transfer to a neuroscience centre (N = 584) was associated with lower mortality (odds ratio 0.52, 0.34-0.80), higher QOL for survivors (mean gain 0.13, 0.032-0.225), but positive incremental costs (£15,001, £11,123 to £18,880) compared with 'late or no transfer' (N = 263). The lifetime cost per QALY gained for 'early' transfer was £11,000. CONCLUSIONS: For critically ill adult patients with acute TBI, within neuroscience centres management in dedicated neurocritical care units versus combined neuro/general units led to improved QoL and higher costs, on average, but these differences were not statistically significant. This study finds that 'early' transfer to a neuroscience centre is associated with reduced mortality, improvement in QOL and is cost-effective.

Neurotrauma - a multidisciplinary disease.

Traumatic brain injury is one of the most important diseases of our time, both in terms of morbidity, mortality and economic loss. Public health policy is key to reducing its incidence. Integrated multidisciplinary clinical care is vital to minimise its morbidity and mortality.

Advanced neuromonitoring powered by ICM+ and its place in the Brand New AI World, reflections at the 20th anniversary boundary.

Introduction: Adoption of the ICM+® brain monitoring software by clinical research centres worldwide has been continuously growing over the past 20 years. This has necessitated ongoing updates to accommodate evolving neuromonitoring research needs, including recent explosion of artificial intelligence (AI). Research question: We sought to provide an update on the current features of the software. In particular, we aimed to highlight the new options of integrating AI models. Material and methods: We reviewed all currently available ICM+ analytical areas and discussed potential AI based extensions in each. We tested a proof-of-concept integration of an AI model and evaluated its performance for real-time data processing. Results: ICM+ current analytical tools serve both real-time (bed-side) and offline (file based) analysis, including the calculation engine, Signal Calculator, Custom Statistics, Batch tools, ScriptLab and charting. The ICM+ Python plugin engine allows to execute custom Python scripts and take advantage of complex AI frameworks. For the proof-of-concept, we used a neural network convolutional model with 207,000 trainable parameters that classifies morphology of intracranial pressure (ICP) pulse waveform into 5 pulse categories (normal to pathological plus artefactual). When evaluated within ICM+ plugin script on a Windows 10 laptop the classification of a 5 min ICP waveform segment took only 0.19s with a 2.3s of initial, one-off, model loading time required. Conclusions: Modernised ICM+ analytical tools, reviewed in this manuscript, include integration of custom AI models allowing them to be shared and run in real-time, facilitating rapid prototyping and validating of new AI ideas at the bed-side.

Community consultation in emergency neurotrauma research: results from a pre-protocol survey.

BACKGROUND: Uncertainty remains as to the role of decompressive craniectomy (DC) for primary evacuation of an acute subdural haematoma (ASDH). In 2011, a collaborative group of neurosurgeons, neuro-intensive care physicians and trial methodologists was formed in the UK with the aim of answering the following question: "What is the clinical- and cost-effectiveness of DC, in comparison to simple craniotomy for adult patients undergoing primary evacuation of an ASDH?" The proposed RESCUE-ASDH trial (Randomised Evaluation of Surgery with Craniectomy for patients Undergoing Evacuation of Acute Subdural Haematoma) is a multi-centre, pragmatic, parallel group randomised trial of DC versus simple craniotomy for adult head-injured patients with an ASDH. Clinical trials in the emergency setting face the problem that potential participants may be incapacitated and their next of kin initially unavailable. As a result, consent and enrolment of participants can often be difficult. METHOD: In the current study, we aimed to assess public opinion regarding participation in the RESCUE-ASDH trial and acceptability of surrogate consent by conducting a pre-protocol community consultation survey. RESULTS: One hundred and seventy-one subjects completed the survey. Eighty-four percent of participants responded positively when asked if they would participate in the proposed trial. Ninety-six percent and 91 % answered positively when asked if they found surrogate consent by their next of kin and an independent doctor acceptable, respectively. None of the characteristics of the study population were found to affect the decision to participate or the acceptability of surrogate consent by the next of kin. Being religious showed a trend towards higher acceptability of surrogate consent by a doctor. Conversely, an education to degree level and above showed a trend towards reduced acceptability of surrogate consent by a doctor. CONCLUSIONS: Our community consultation survey shows that the proposed trial is acceptable to the public. In addition, the results suggest high levels of acceptability of surrogate consent by next of kin or independent doctor amongst our community.

Surgical management of acute subdural haematomas: current practice patterns in the United Kingdom and the Republic of Ireland.

INTRODUCTION: Uncertainty remains as to the role of decompressive craniectomy (DC) for primary evacuation of acute subdural haematomas (ASDH). In 2011, a collaborative group was formed in the UK with the aim of answering the following question: "What is the clinical- and cost-effectiveness of decompressive craniectomy, in comparison with craniotomy for adult patients undergoing primary evacuation of an ASDH?" The proposed RESCUE-ASDH trial (Randomised Evaluation of Surgery with Craniectomy for patients Undergoing Evacuation of Acute Subdural Haematoma) is a multicentre, pragmatic, parallel group randomised trial of DC versus craniotomy for adult head-injured patients with an ASDH. In this study, we used an online questionnaire to assess the current practice patterns in the management of ASDH in the UK and the Republic of Ireland, and to gauge neurosurgical opinion regarding the proposed RESCUE-ASDH trial. MATERIALS AND METHODS: A questionnaire survey of full members of the Society of British Neurological Surgeons and members of the British Neurosurgical Trainees Association was undertaken between the beginning of May and the end of July 2012. RESULTS: The online questionnaire was answered by 95 neurosurgeons representing 31 of the 32 neurosurgical units managing adult head-injured patients in the UK and the Republic of Ireland. Forty-five percent of the respondents use primary DC in at least 25% of patients with ASDH. In addition, of the 22 neurosurgical units with at least two Consultant respondents, only three units (14%) showed intradepartmental agreement regarding the proportion of their patients receiving a primary DC for ASDH. CONCLUSION: The survey results demonstrate that there is significant uncertainty as to the optimal surgical technique for primary evacuation of ASDH. The fact that the majority of the respondents are willing to become collaborators in the planned RESCUE-ASDH trial highlights the relevance of this important subject to the neurosurgical community in the UK and Ireland.

Decompressive craniectomy - operative technique and perioperative care.

With improvements in neurocritical care advanced measures of treating raised intracranial pressure (ICP) are more frequently utilised. Decompressive craniectomy is an effective ICP-lowering procedure; however its benefits are maximised with optimal surgical technique and perioperative care, as well as by paying attention to possible complications. This article focuses on the current indications and rationale for decompressive craniectomy, and the surgical technique of bifrontal and unilateral decompression. The key surgical points include a large craniectomy window and opening of the dura, leaving it unsutured or performing a wide non-constricting duroplasty. Perioperative care and possible complications are also discussed.

A perinuclear actin cap regulates nuclear shape.

Defects in nuclear morphology often correlate with the onset of disease, including cancer, progeria, cardiomyopathy, and muscular dystrophy. However, the mechanism by which a cell controls its nuclear shape is unknown. Here, we use adhesive micropatterned surfaces to control the overall shape of fibroblasts and find that the shape of the nucleus is tightly regulated by the underlying cell adhesion geometry. We found that this regulation occurs through a dome-like actin cap that covers the top of the nucleus. This cap is composed of contractile actin filament bundles containing phosphorylated myosin, which form a highly organized, dynamic, and oriented structure in a wide variety of cells. The perinuclear actin cap is specifically disorganized or eliminated by inhibition of actomyosin contractility and rupture of the LINC complexes, which connect the nucleus to the actin cap. The organization of this actin cap and its nuclear shape-determining function are disrupted in cells from mouse models of accelerated aging (progeria) and muscular dystrophy with distorted nuclei caused by alterations of A-type lamins. These results highlight the interplay between cell shape, nuclear shape, and cell adhesion mediated by the perinuclear actin cap.

Critical thresholds for cerebrovascular reactivity after traumatic brain injury.

INTRODUCTION: Pressure-reactivity index (PRx) is a useful tool in brain monitoring of trauma patients, but the question remains about its critical values. Using our TBI database, we identified the thresholds for PRx and other monitored parameters that maximize the statistical difference between death/survival and favorable/unfavorable outcomes. We also investigated how these thresholds depend on clinical factors such as age, gender and initial GCS. METHODS: A total of 459 patients from our database were eligible. Tables of 2 × 2 format were created grouping patients according to survival/death or favorable/unfavorable outcomes and varying thresholds for PRx, ICP and CPP. Pearson's chi square was calculated, and the thresholds returning the highest score were assumed to have the best discriminative value. The same procedure was repeated after division according to clinical factors. RESULTS: In all patients, we found that PRx had different thresholds for survival (0.25) and for favorable outcome (0.05). Thresholds of 70 mmHg for CPP and 22 mmHg for ICP were identified for both survival and favorable outcomes. The ICP threshold for favorable outcome was lower (18 mmHg) in females and patients older than 55 years. In logistic regression models, independent variables associating with mortality and unfavorable outcome were age, GCS, ICP and PRx. CONCLUSION: The prognostic role of PRx is confirmed but with a lower threshold of 0.05 for favorable outcome than for survival (0.25). Results for ICP are in line with current guidelines. However, the lower value in elderly and in females suggests increased vulnerability to intracranial hypertension in these groups.

Sugar or salt ("SOS"): A protocol for a UK multicentre randomised trial of mannitol and hypertonic saline in severe traumatic brain injury and intracranial hypertension.

Hyperosmolar solutions are widely used to treat raised intracranial pressure following severe traumatic brain injury. Although mannitol has historically been the most frequently administered, hypertonic saline solutions are increasingly being used. However, definitive evidence regarding their comparative effectiveness is lacking. The Sugar or Salt Trial is a UK randomised, allocation concealed open label multicentre pragmatic trial designed to determine the clinical and cost-effectiveness of hypertonic saline compared with mannitol in the management of patients with severe traumatic brain injury. Patients requiring intensive care unit admission and intracranial pressure monitoring post-traumatic brain injury will be allocated at random to receive equi-osmolar boluses of either mannitol or hypertonic saline following failure of routine first-line measures to control intracranial pressure. The primary outcome for the study will be the Extended Glasgow Outcome Scale assessed at six months after randomisation. Results will inform current clinical practice in the routine use of hyperosmolar therapy as well as assess the impact of potential side effects. Pre-planned longer term clinical and cost effectiveness analyses will further inform the use of these treatments.

Temporal trends in head injury outcomes from 2003 to 2009 in England and Wales.

BACKGROUND: Case fatality rates after blunt head injury (HI) did not improve in England and Wales between 1994 and 2003. The United Kingdom National Institute of Clinical Excellence subsequently published HI management guidelines, including the recommendation that patients with severe head injuries (SHIs) should be treated in specialist neuroscience units (NSU). The aim of this study was to investigate trends in case fatality and location of care since the introduction of national HI clinical guidelines. METHODS: We conducted a retrospective cohort study using prospectively recorded data from the Trauma and Audit Research Network (TARN) database for patients presenting with blunt trauma between 2003 and 2009. Temporal trends in log odds of death adjusted for case mix were examined for patients with and without HI. Location of care for patients with SHI was also studied by examining trends in the proportion of patients treated in non-NSUs. RESULTS: Since 2003, there was an average 12% reduction in adjusted log odds of death per annum in patients with HI (n=15,173), with a similar but smaller trend in non-HI trauma mortality (n=48,681). During the study period, the proportion of patients with HI treated entirely in non-NSUs decreased from 31% to 19%, (p <0.01). INTERPRETATION: The reduction in odds of death following HI since 2003 is consistent with improved management following the introduction of national HI guidelines and increased treatment of SHI in NSUs.

Implementation of duty of candour within neurosurgery: a national survey and framework for improved application in clinical practice.

INTRODUCTION: Statutory duty of candour was introduced in November 2014 for NHS bodies in England. Contained within the regulation were definitions regarding the threshold for what constitutes a notifiable patient safety incident. However, it can be difficult to determine when the process should be implemented. The aim of this survey was to evaluate the interpretation of these definitions by British neurosurgeons. MATERIALS AND METHODS: All full (consultant) members of the Society of British Neurological Surgeons were electronically invited to participate in an online survey. Surgeons were presented with 15 cases and asked to decide in the case of each one whether they would trigger the process of duty of candour. Cases were stratified according to their likelihood and severity. RESULTS: In all, 106/357 (29.7%) members participated in the survey. Responses varied widely, with almost no members triggering the process of duty of candour in cases where adverse events were common (greater than 10% likelihood) and required only outpatient follow-up (7/106; 6.6%), and almost all members doing so in cases where adverse events were rare (less than 0.1% likelihood) and resulted in death (102/106; 96.2%). However, there was clear equipoise in triggering the process of duty of candour in cases where adverse events were uncommon (0.1-10% likelihood) and resulted in moderate harm (38/106; 35.8%), severe harm (57/106; 53.8%) or death (49/106; 46.2%). CONCLUSION: There is considerable nationwide variation in the interpretation of definitions regarding the threshold for duty of candour. To this end, we propose a framework for the improved application of duty of candour in clinical practice.

Imaging regional variation of cellular proliferation in gliomas using 3'-deoxy-3'-[18F]fluorothymidine positron-emission tomography: an image-guided biopsy study.

AIM: To compare regional variations in uptake of 3'-deoxy-3'- [(18)F]-fluorothymidine (FLT) images using positron-emission tomography (PET) with measures of cellular proliferation from biopsy specimens obtained by image-guided brain biopsies. MATERIALS AND METHODS: Fourteen patients with a supratentorial glioma that required an image-guided brain biopsy were imaged preoperatively with dynamic PET after the administration of FLT. Maps of FLT irreversible uptake rate (K(i)) and standardized uptake value (SUV) were calculated. These maps were co-registered to a gadolinium-enhanced T1-weighted spoiled gradient echo (SPGR) sequence that was used for biopsy guidance, and the mean and maximum K(i) and SUV determined for each biopsy site. These values were correlated with the MIB-1 labelling index (a tissue marker of proliferation) from these biopsy sites. RESULTS: A total of 57 biopsy sites were studied. Although all measures correlated with MIB-1 labelling index, K(i)(max) provided the best correlation (Pearson coefficient, r=0.68; p<0.001). In low-grade gliomas the K(i)(mean) (+/-SD) was significantly higher than in normal tissue (3.3+/-1.7x10(-3)ml(plasma)/min/ml(tissue) versus 1.2+/-0.7x10(-3)ml(plasma)/min/ml(tissue); p=0.001). High-grade gliomas showed heterogeneous uptake with a mean K(i) of 7.7+/-4x10(-3)ml(plasma)/min/ml(tissue). A threshold K(i)(mean) of 1.8x10(-3) differentiates between normal tissue and tumour (sensitivity 84%, specificity 88%); however, the latter threshold underestimated the extent of tumour in half the cases. SUV closely agreed with K(i) measurements. CONCLUSION: FLT PET is a useful marker of cellular proliferation that correlates with regional variation in cellular proliferation; however, it is unable to identify the margin of gliomas.