J D Pickard

University of Cambridge, Cambridge, England, United Kingdom

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Publications (575)2219.75 Total impact

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    ABSTRACT: Plateau waves in intracranial pressure (ICP) are frequently recorded in neuro intensive care and are not yet fully understood. To further investigate this phenomenon, we analyzed partial pressure of cerebral oxygen (pbtO2) and a moving correlation coefficient between ICP and mean arterial blood pressure (ABP), called PRx, along with the cerebral oxygen reactivity index (ORx), which is a moving correlation coefficient between cerebral perfusion pressure (CPP) and pbtO2 in an observational study. We analyzed 55 plateau waves in 20 patients after severe traumatic brain injury. We calculated ABP, ABP pulse amplitude (ampABP), ICP, CPP, pbtO2, heart rate (HR), ICP pulse amplitude (ampICP), PRx, and ORx, before, during, and after each plateau wave. The analysis of variance with Bonferroni post hoc test was used to compare the differences in the variables before, during, and after the plateau wave. We considered all plateau waves, even in the same patient, independent because they are separated by long intervals. We found increases for ICP and ampICP according to our operational definitions for plateau waves. PRx increased significantly (p = 0.00026), CPP (p < 0.00001) and pbtO2 (p = 0.00007) decreased significantly during the plateau waves. ABP, ampABP, and HR remained unchanged. PRx during the plateau was higher than before the onset of wave in 40 cases (73 %) with no differences in baseline parameters for those with negative and positive ΔPRx (difference during and after). ORx showed an increase during and a decrease after the plateau waves, however, not statistically significant. PbtO2 overshoot after the wave occurred in 35 times (64 %), the mean difference was 4.9 ± 4.6 Hg (mean ± SD), and we found no difference in baseline parameters between those who overshoot and those who did not overshoot. Arterial blood pressure remains stable in ICP plateau waves, while cerebral autoregulatory indices show distinct changes, which indicate cerebrovascular reactivity impairment at the top of the wave. PbtO2 decreases during the waves and may show a slight overshoot after normalization. We assume that this might be due to different latencies of the cerebral blood flow and oxygen level control mechanisms. Other factors may include baseline conditions, such as pre-plateau wave cerebrovascular reactivity or pbtO2 levels, which differ between studies.
    Neurocritical Care 12/2014; · 3.04 Impact Factor
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    ABSTRACT: We employed functional MRI (fMRI) to assess whether (1) patients with disorders of consciousness (DOC) retain the ability to willfully engage in top-down processing and (2) what neurophysiologic factors distinguish patients who can demonstrate this ability from patients who cannot. Sixteen volunteers, 8 patients in vegetative state (VS), 16 minimally conscious patients (MCS), and 4 exit from MCS (eMCS) patients were enrolled in a prospective cross-sectional fMRI study. Participants performed a target detection task in which they counted the number of times a (changing) target word was presented amidst a set of distractors. Three of 8 patients diagnosed as being in a VS exhibited significant activations in response to the task, thereby demonstrating a state of consciousness. Differential activations across tasks were also observed in 6 MCS patients and 1 eMCS patient. A psycho-physiologic interaction analysis revealed that the main factor distinguishing patients who responded to the task from those who did not was a greater connectivity between the anterior section of thalamus and prefrontal cortex. In our sample of patients, the dissociation between overt behavior observable in clinical assessments and residual cognitive faculties is prevalent among DOC patients (37%). A substantial number of patients, including some diagnosed with VS, can demonstrate willful engagement in top-down cognition. While neuroimaging data are not the same as observable behavior, this suggests that the mental status of some VS patients exceeds what can be appreciated clinically. Furthermore, thalamo-frontal circuits might be crucial to sustaining top-down functions. © 2014 American Academy of Neurology.
    Neurology 12/2014; · 8.30 Impact Factor
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    ABSTRACT: OBJECT The pressure reactivity index (PRx) correlates with outcome after traumatic brain injury (TBI) and is used to calculate optimal cerebral perfusion pressure (CPPopt). The PRx is a correlation coefficient between slow, spontaneous changes (0.003-0.05 Hz) in intracranial pressure (ICP) and arterial blood pressure (ABP). A novel index-the so-called long PRx (L-PRx)-that considers ABP and ICP changes (0.0008-0.008 Hz) was proposed. METHODS The authors compared PRx and L-PRx for 6-month outcome prediction and CPPopt calculation in 307 patients with TBI. The PRx- and L-PRx-based CPPopt were determined and the predictive power and discriminant abilities were compared. RESULTS The PRx and L-PRx correlation was good (R = 0.7, p < 0.00001; Spearman test). The PRx, age, CPP, and Glasgow Coma Scale score but not L-PRx were significant fatal outcome predictors (death and persistent vegetative state). There was a significant difference between the areas under the receiver operating characteristic curves calculated for PRx and L-PRx (0.61 ± 0.04 vs 0.51 ± 0.04; z-statistic = -3.26, p = 0.011), which indicates a better ability by PRx than L-PRx to predict fatal outcome. The CPPopt was higher for L-PRx than for PRx, without a statistical difference (median CPPopt for L-PRx: 76.9 mm Hg, interquartile range [IQR] ± 10.1 mm Hg; median CPPopt for PRx: 74.7 mm Hg, IQR ± 8.2 mm Hg). Death was associated with CPP below CPPopt for PRx (χ(2) = 30.6, p < 0.00001), and severe disability was associated with CPP above CPPopt for PRx (χ(2) = 7.8, p = 0.005). These relationships were not statistically significant for CPPopt for L-PRx. CONCLUSIONS The PRx is superior to the L-PRx for TBI outcome prediction. Individual CPPopt for L-PRx and PRx are not statistically different. Deviations between CPP and CPPopt for PRx are relevant for outcome prediction; those between CPP and CPPopt for L-PRx are not. The PRx uses the entire B-wave spectrum for index calculation, whereas the L-PRX covers only one-third of it. This may explain the performance discrepancy.
    Journal of neurosurgery. 11/2014;
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    ABSTRACT: Increased 'anaerobic' glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route is the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis to perfuse 1,2-(13)C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in six patients undergoing surgery for benign tumors, and to simultaneously collect products for nuclear magnetic resonance (NMR) analysis. (13)C enrichment for glycolytic 2,3-(13)C2 lactate was the median 5.4% (interquartile range (IQR) 4.6-7.5%) in TBI brain and 4.2% (2.4-4.4%) in 'normal' brain (P<0.01). The ratio of PPP-derived 3-(13)C lactate to glycolytic 2,3-(13)C2 lactate was median 4.9% (3.6-8.2%) in TBI brain and 6.7% (6.3-8.9%) in 'normal' brain. An inverse relationship was seen for PPP-glycolytic lactate ratio versus PbtO2 (r=-0.5, P=0.04) in TBI brain. Thus, glycolytic lactate production was significantly greater in TBI than 'normal' brain. Several TBI patients exhibited PPP-lactate elevation above the 'normal' range. There was proportionally greater PPP-derived lactate production with decreasing PbtO2. The study raises questions about the roles of the PPP and glycolysis after TBI, and whether they can be manipulated to achieve a better outcome. This study is the first direct comparison of glycolysis and PPP in human brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 22 October 2014; doi:10.1038/jcbfm.2014.177.
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    ABSTRACT: Theoretical advances in the science of consciousness have proposed that it is concomitant with balanced cortical integration and differentiation, enabled by efficient networks of information transfer across multiple scales. Here, we apply graph theory to compare key signatures of such networks in high-density electroencephalographic data from 32 patients with chronic disorders of consciousness, against normative data from healthy controls. Based on connectivity within canonical frequency bands, we found that patient networks had reduced local and global efficiency, and fewer hubs in the alpha band. We devised a novel topographical metric, termed modular span, which showed that the alpha network modules in patients were also spatially circumscribed, lacking the structured long-distance interactions commonly observed in the healthy controls. Importantly however, these differences between graph-theoretic metrics were partially reversed in delta and theta band networks, which were also significantly more similar to each other in patients than controls. Going further, we found that metrics of alpha network efficiency also correlated with the degree of behavioural awareness. Intriguingly, some patients in behaviourally unresponsive vegetative states who demonstrated evidence of covert awareness with functional neuroimaging stood out from this trend: they had alpha networks that were remarkably well preserved and similar to those observed in the controls. Taken together, our findings inform current understanding of disorders of consciousness by highlighting the distinctive brain networks that characterise them. In the significant minority of vegetative patients who follow commands in neuroimaging tests, they point to putative network mechanisms that could support cognitive function and consciousness despite profound behavioural impairment.
    PLoS Computational Biology 10/2014; · 4.87 Impact Factor
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    ABSTRACT: Objective: To examine the epidemiology of referrals to a specialist neurotrauma clinic and explore and highlight implications for clinical practice and service development for persons with head injury/traumatic brain injury (HI/TBI). Design and methods: A retrospective population-based cohort study of all referrals to a specialist neurotrauma clinic over a 9-year period. Data from a specialist head injury database (which included all persons presenting to hospital with traumatic brain injury) were analysed. Results: In total, 1235 new patients of all ages, severities of injury, both admitted and non-admitted were referred. Referrals have increased due to successful integration with new service developments and resulting optimization of resources. Conclusions: Data gathered from the cohort gives increased understanding of the characteristics and numbers of patients requiring rehabilitation and adds to the evidence-base. Integration with new and complementary service developments has optimized the function/aims of the clinic and enhanced its role in terms of patient service and outcome and as a research resource. The model provides principles which may be applied to planning, organizing and providing follow-up/rehabilitation services for HI/TBI.
    Brain Injury 08/2014; · 1.51 Impact Factor
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    ABSTRACT: The extent of hemodynamic disturbances following subarachnoid hemorrhage (SAH) varies. We aim to determine the prognostic implications of unilateral and bilateral autoregulatory failure on delayed cerebral ischemia (DCI) and outcome.
    Neurosurgery 08/2014; 61 Suppl 1:203. · 2.53 Impact Factor
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    ABSTRACT: In the healthy brain, small oscillations in intracranial pressure (ICP) occur synchronously with those in cerebral blood volume (CBV), cerebrovascular resistance, and consequently cerebral blood flow velocity (CBFV). Previous work has shown that the usual synchrony between ICP and CBFV is lost during intracranial hypertension. Moreover, a continuously computed measure of the ICP/CBFV association (Fix index) was a more sensitive predictor of outcome after traumatic brain injury (TBI) than a measure of autoregulation (Mx index). In the current study we computed Fix during ICP plateau waves, to observe its behavior during a defined period of cerebrovascular vasodilatation.
    Neurocritical Care 05/2014; · 3.04 Impact Factor
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    ABSTRACT: Cerebral vasospasm has traditionally been regarded as an important cause of delayed cerebral ischaemia (DCI) which occurs after aneurysmal subarachnoid haemorrhage, and often leads to cerebral infarction and poor neurological outcome. However, data from recent studies argue against a pure focus on vasospasm as the cause of delayed ischaemic complications. Findings that marked reduction in the incidence of vasospasm does not translate to a reduction in DCI, or better outcomes has intensified research into other possible mechanisms which may promote ischaemic complications. Early brain injury and cell death, blood-brain barrier disruption and initiation of an inflammatory cascade, microvascular spasm, microthrombosis, cortical spreading depolarisations and failure of cerebral autoregulation, have all been implicated in the pathophysiology of DCI. This review summarises the current knowledge about the mechanisms underlying the development of DCI. Furthermore, it aims to describe and categorise the known pharmacological treatment options with respect to the presumed mechanism of action and its role in DCI.
    Journal of neurology, neurosurgery, and psychiatry. 05/2014;
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    ABSTRACT: AimIdiopathic intracranial hypertension (IIH) is prone to misdiagnosis. Our aim was to identify the reasons for this in children in our region referred for suspected IIH.Method We reviewed the records of all children referred with symptoms and/or signs consistent with raised intracranial pressure (ICP) and normal magnetic resonance imaging of the brain to our tertiary neurology unit over 4 years. IIH was confirmed after expert ophthalmology including ultrasound/tomography and advanced cerebrospinal fluid (CSF) pressure studies.ResultsOf 15 children (six males, nine females; median age 12y, range 3–15y), six (five females, one male) were confirmed to have IIH. All weighed above the 91st centile and were over 10 years old. Four of the six had raised ICP secondary to other causes. Four had been misdiagnosed locally with papilloedema, three had drusen, and one had ‘crowded discs’. Two had raised CSF pressures on standard lumbar puncture, but 20-minute steady state and infusion studies were normal, with symptoms settling after therapy was withdrawn.InterpretationMisdiagnosis of IIH was frequent, but could be reduced by (1) expert ophthalmological fundoscopy, orbital ultrasound, and optical coherence tomography; (2) expert neuroradiology; and (3) assessment of steady state CSF pressure rather than standard opening pressure in centimetres of water.
    Developmental Medicine & Child Neurology 05/2014; · 2.68 Impact Factor
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    ABSTRACT: The vascular wall tension (WT) of small cerebral vessels can be quantitatively estimated through the concept of critical closing pressure (CrCP), which denotes the lower limit of arterial blood pressure (ABP), below which small cerebral arterial vessels collapse and blood flow ceases. WT can be expressed as the difference between CrCP and intracranial pressure (ICP) and represent active vasomotor tone. In this study, we investigated the association of WT and CrCP with autoregulation and outcome of a large group of patients after traumatic brain injury (TBI). We retrospectively analysed recordings of ABP, ICP and transcranial Doppler (TCD) blood flow velocity from 280 TBI patients (median age: 29 years; interquartile range: 20-43). CrCP and WT were calculated using the cerebrovascular impedance methodology. Autoregulation was assessed based on TCD-based indices, Mx and ARI. Low values of WT were found to be associated with an impaired autoregulatory capacity, signified by its correlation to FV-based indices Mx (R = -0.138; p = 0.021) and ARI (R = 0.118; p = 0.048). No relationship could be established between CrCP and any of the autoregulatory indices. Neither CrCP nor WT was found to correlate with outcome. Impaired autoregulation was found to be associated with a lower WT supporting the role of vasoparalysis in the loss of autoregulatory capacity. In contrast, no links between CrCP and autoregulation could be identified.
    Neurocritical Care 03/2014; · 3.04 Impact Factor
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    ABSTRACT: Infusion tests are important tools to assess cerebrospinal fluid (CSF)dynamics used in the preoperative selection of patients for shunt surgery, or to predict the scope of improvement from shunt revision. The aim of this study was to assess the repeatability of the key quantitative parameters describing CSF dynamics that are determined with infusion testing. Eighteen patients in whom a constant infusion test was repeated within 102 days, without any intermediate surgical intervention, were studied. From each test baseline ICP, baseline pulse amplitude, outflow resistance, elastance coefficient and slope of the amplitude-pressure line were calculated and investigated with a regression and Bland-Altman analysis. Significant correlations (P < 0.01) were found for the outflow resistance (R = 0.96), the elastance coefficient (R = 0.778) and the slope of the amplitude-pressure line (R = 0.876). The estimated 95% confidence level for outflow resistance was 3 mmHg/ml min. Likewise, the elastance coefficient lay within a range of 0.16/ml and the slope of the amplitude-pressure line within 0.25. The most inconsistent parameter found were baseline ICP (R = 0.272) and baseline pulse amplitude (R = 0.171). The results of this study imply that the parameters resulting from an infusion study have to be considered within a range rather than as an absolute value.
    Acta Neurologica Scandinavica 03/2014; · 2.47 Impact Factor
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    ABSTRACT: Objectives: We studied possible link between cerebrospinal fluid (CSF) compensation and indices describing pulsatile inflow of cerebral arterial blood. Methods: A total of 50 infusion tests performed in patients with symptoms of normal pressure hydrocephalus (NPH) were examined retrospectively. Waveforms of CSF pressure, noninvasive arterial blood pressure (ABP), and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) were used to estimate relative changes in cerebral arterial compliance (Ca) and cerebrovascular resistance (CVR). Product of Ca and CVR, called cerebral arterial time constant (τ, unit: seconds), was calculated at the baseline and plateau phase of the test and compared with CSF compensatory parameters such as resistance to CSF outflow, elasticity, slope of amplitude-pressure line, and pulse amplitude of CSF pressure. Results: Neither of CSF compensatory parameters correlated with hemodynamic indices. However, the change in cerebral perfusion pressure (CPP) provoked change in τ (R = 0·33; P = 0·017) secondary to a change in CVR (R = 0·81; P < 0·0001). Changes in CVR and Ca had a reciprocal character (R = -0·64; P < 0·0001) with magnitude of variation in CVR (68%) prevailing over magnitude of changes in Ca (49%). Discussion: Hemodynamics of pulsatile inflow of cerebral arterial blood assessed by cerebral arterial time constant is not directly linked to dynamics of CSF circulation and pressure-volume compensation but is sensitive to changes in CPP during infusion test.
    Neurological Research 03/2014; 36(3):255-61. · 1.18 Impact Factor
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    ABSTRACT: Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day for 5 days in 20 patients randomized 1:1. We provide safety data (primary outcome) in this pathology, utilize cerebral microdialysis to directly determine brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and use principal component analysis (PCA) to explore the resultant cerebral cytokine profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and the brain extracellular fluid. The PCA showed a separation in cytokine profiles after IL1ra administration. A candidate cytokine from this analysis, macrophage-derived chemoattractant, was significantly lower in the rhIL1ra-treated group. Our results provide promising data for rhIL1ra as a therapeutic candidate by showing safety, brain penetration and a modification of the neuroinflammatory response to TBI by a putative neuroprotective agent in humans for the first time.Journal of Cerebral Blood Flow & Metabolism advance online publication, 26 February 2014; doi:10.1038/jcbfm.2014.23.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 02/2014; · 5.46 Impact Factor
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    ABSTRACT: Object Based on continuous monitoring of the pressure reactivity index (PRx), the authors defined individualized intracranial pressure (ICP) thresholds by graphing the relationship between ICP and PRx. These investigators hypothesized that an "ICP dose" based on individually assessed ICP thresholds would correlate more closely with the 6-month outcome when compared with ICP doses derived by the recommended universal thresholds of 20 and 25 mm Hg. Methods This study was a retrospective analysis of prospectively collected data from 327 patients with severe traumatic brain injury. Results Individualized thresholds were visually identified from graphs of PRx versus ICP; PRx > 0.2 was the cutoff. Intracranial pressure doses were then computed as the cumulative area under the curve above the defined thresholds in graphing ICP versus time. The term "Dose 20" (D20) was used to refer to an ICP threshold of 20 mm Hg; the markers D25 and DPRx were calculated similarly. Separate logistic regression models were fit with death as the outcome and each dose as the predictor, both alone and adjusted for covariates. The discriminative ability of each dose for mortality was assessed by receiver operating characteristic AUC analysis in which 5-fold cross-validation was used. A clearly identifiable PRx-based threshold was possible in 224 patients (68%). The DPRx (AUC 0.81, 95% CI 0.74-0.87) was found to have the highest area under the curve (AUC) over both D20 (0.75, 95% CI 0.68-0.81) and D25 (0.77, 95% CI 0.70-0.83); in the cross-validation model, DPRx remained the best discriminator of mortality (DPRx: AUC 0.77 [95% CI 0.68-0.89]; D20: 0.72 [95% CI 0.66-0.81]; and D25: 0.65 [95% CI 0.56-0.73]). Conclusions The authors explored the importance of different ICP thresholds for outcome by calculating patient-specific ICP doses based on the continuous monitoring of cerebrovascular pressure reactivity. They found that these individualized doses of intracranial hypertension were stronger predictors of death than doses derived from the universal thresholds of 20 and 25 mm Hg. The PRx could offer a method that can be directed toward individualizing the ICP threshold.
    Journal of Neurosurgery 02/2014; · 3.15 Impact Factor
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    ABSTRACT: Object The Cambridge Shunt Evaluation Laboratory was established 20 years ago. This paper summarizes the findings of that laboratory for the clinician. Methods Twenty-six models of valves have been tested long-term in the shunt laboratory according to the expanded International Organization for Standardization 7197 standard protocol. Results The majority of the valves had a nonphysiologically low hydrodynamic resistance (from 1.5 to 3 mm Hg/[ml/min]), which may result in overdrainage related to posture and during nocturnal cerebral vasogenic waves. A long distal catheter increases the resistance of these valves by 100%-200%. Drainage through valves without a siphon-preventing mechanism is very sensitive to body posture, which may result in grossly negative intracranial pressure. Siphon-preventing accessories offer a reasonable resistance to negative outlet pressure; however, accessories with membrane devices may be blocked by raised subcutaneous pressure. In adjustable valves, the settings may be changed by external magnetic fields of intensity above 40 mT (exceptions: ProGAV, Polaris, and Certas). Most of the magnetically adjustable valves produce large distortions on MRI studies. Conclusions The behavior of a valve revealed during testing is of relevance to the surgeon and may not be adequately described in the manufacturer's product information. The results of shunt testing are helpful in many circumstances, such as the initial choice of shunt and the evaluation of the shunt when its dysfunction is suspected.
    Journal of Neurosurgery 01/2014; · 3.15 Impact Factor
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    ABSTRACT: Cerebrovascular autoregulation and reactivity are two important processes which maintain CBF at metabolically appropriate levels in response to fluctuations in cerebral perfusion pressure. Additionally, intact vascular reactivity protects the cerebral capillary bed against excessive hydrostatic pressures that may precipitate vasogenic oedema. The importance of vascular reactivity is amplified in the acute phase of injury by disruption to the integrity of the blood–brain barrier (BBB), known to occur even in mild cases of TBI. Monitoring of pressure reactivity in combination with measures of cerebrospinal compensatory reserve may assist in identifying those patients at risk for the development of vasodilatory, short-term increases in ICP. The state of pressure reactivity is also a robust, independent predictor of outcome after TBI. This chapter discusses CBF autoregulation, the careful regulation of vascular resistance, and the measurement of pressure reactivity in the cerebral vasculature.
    Vascular Mechanisms in CNS Trauma, Edited by Eng H. Lo, Josephine Lok, MingMing Ning, Michael J. Whalen, 01/2014: chapter 23: pages 401-420; Springer New York., ISBN: 9781461486893
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    ABSTRACT: The study of structural and functional magnetic resonance imaging data has greatly benefitted from the development of sophisticated and efficient algorithms aimed at automating and optimizing the analysis of brain data. We address, in the context of the segmentation of brain from non-brain tissue (i.e., brain extraction, also known as skull-stripping), the tension between the increased theoretical and clinical interest in patient data, and the difficulty of conventional algorithms to function optimally in the presence of gross brain pathology. Indeed, because of the reliance of many algorithms on priors derived from healthy volunteers, images with gross pathology can severely affect their ability to correctly trace the boundaries between brain and non-brain tissue, potentially biasing subsequent analysis. We describe and make available an optimized brain extraction script for the pathological brain (optiBET) robust to the presence of pathology. Rather than attempting to trace the boundary between tissues, optiBET performs brain extraction by (i) calculating an initial approximate brain extraction; (ii) employing linear and non-linear registration to project the approximate extraction into the MNI template space; (iii) back-projecting a standard brain-only mask from template space to the subject's original space; and (iv) employing the back-projected brain-only mask to mask-out non-brain tissue. The script results in up to 94% improvement of the quality of extractions over those obtained with conventional software across a large set of severely pathological brains. Since optiBET makes use of freely available algorithms included in FSL, it should be readily employable by anyone having access to such tools.
    PLoS ONE 01/2014; 9(12):e115551. · 3.53 Impact Factor
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    ABSTRACT: Backround The extent of hemodynamic disturbances following subarachnoid hemorrhage (SAH) varies. We aim to determine the prognostic implications of unilateral and bilateral autoregulatory failure on delayed cerebral ische-mia (DCI) and outcome. Methods Ninety-eight patients with aneurysmal SAH were recruited. Autoregulation was assessed using systolic flow index—Sxa. Interhemispheric difference in autoreg-ulation was calculated to assess the spatial distribution and symmetry of autoregulatory changes. Assessment of interhemispheric difference in autoregulation in combina-tion with overall autoregulation was used to measure the extent of autoregulatory impairment. Patients were dichotomized by the presence of DCI and 3-month mRS. Results Higher flow velocity and worse autoregulation (p < 0.0000001, 95 % CI 10.7–21.3 and p = 0.00001, 95 % CI 0.03–0.07 for difference in FV and Sxa, respec-tively) were found ipsilateral to the ischemic hemisphere or location of aneurysm (if no ischemia detected). DCI group had a higher interhemispheric difference of autoregulation than non-DCI group (p = 0.035, 95 % CI 0.003–0.08). 16/18 patients with unfavorable outcome vs. 17/72 with favorable outcome had overall poor autoregulation with low interhemispheric differences (p = 0.0013, v 2). Uni-lateral autoregulatory failure was seen on a median day 3, bilateral on day 4, and vasospasm was detected on day 6. Conclusions Unilateral autoregulation failure was seen in patients who developed DCI (worse ipsilateral to the ischemic hemisphere). Bilateral autoregulation failure was seen more frequently in patients with unfavorable outcome. Analysis of the temporal profile showed unilateral dysau-toregulation as the primary event predisposing to DCI, which in selected cases led to bilateral failure and unfa-vorable outcomes.
    Neurocritical Care 01/2014; · 3.04 Impact Factor
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    Adult Hydrocephalus, Edited by D. Rigamonti, 01/2014: chapter 17: pages 186-202; Cambridge University Press.

Publication Stats

13k Citations
2,219.75 Total Impact Points


  • 1994–2014
    • University of Cambridge
      • • Department of Clinical Neurosciences
      • • Neurosurgery Unit
      • • Department of Engineering
      • • Brain Repair Centre
      • • Division of Clinical Pharmacology
      Cambridge, England, United Kingdom
  • 2012–2013
    • University Hospital RWTH Aachen
      Aachen, North Rhine-Westphalia, Germany
    • University of California, Los Angeles
      • Department of Neurosurgery
      Los Angeles, California, United States
    • Cambridge University Hospitals NHS Foundation Trust
      Cambridge, England, United Kingdom
  • 2007–2012
    • Alfred Hospital
      • Department of Neurosurgery
      Melbourne, Victoria, Australia
    • East Coast Community Healthcare CIC
      Beccles, England, United Kingdom
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2005–2012
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
    • University of Saskatchewan
      • Department of Psychology
      Saskatoon, Saskatchewan, Canada
    • Royal Prince Alfred Hospital
      Camperdown, New South Wales, Australia
    • Centre Hospitalier Universitaire de Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2003–2012
    • Wroclaw University of Technology
      • • Institute of Biomedical Engineering and Instrumentation
      • • Faculty of Electronics
      Vrotslav, Lower Silesian Voivodeship, Poland
  • 1999–2012
    • MRC Cognition and Brain Sciences Unit
      Cambridge, England, United Kingdom
    • McGill University
      Montréal, Quebec, Canada
  • 1993–2012
    • King's College London
      • • Department of Palliative Care, Policy and Rehabilitation
      • • School of Biomedical Sciences
      London, ENG, United Kingdom
  • 2011
    • University of Barcelona
      • Departament de Psiquiatria i Psicobiologia Clínica
      Barcelona, Catalonia, Spain
    • The University of Western Ontario
      • The Brain and Mind Institute
      London, Ontario, Canada
  • 2007–2009
    • The University of Calgary
      • Department of Clinical Neurosciences
      Calgary, Alberta, Canada
  • 2006
    • University of Sydney
      Sydney, New South Wales, Australia
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom
  • 2005–2006
    • The University of Memphis
      • Department of Electrical and Computer Engineering
      Memphis, TN, United States
  • 2004–2005
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
    • Karolinska Institutet
      • Institutionen för klinisk neurovetenskap
      Solna, Stockholm, Sweden
    • Anglia Ruskin University
      Cambridge, England, United Kingdom
    • University of Bonn
      Bonn, North Rhine-Westphalia, Germany
  • 1990–2000
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
  • 1998
    • The University of Sheffield
      • Academic Urology Unit
      Sheffield, ENG, United Kingdom
  • 1991–1994
    • University of Southampton
      • Division of Clinical Neuroscience
      Southampton, ENG, United Kingdom