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Biomedical subjects

John D Pickard

Publications and source records attributed to John D Pickard.

At least 19 recordsLinked to original sources
PubMed2007

Predicting patterns of glioma recurrence using diffusion tensor imaging.

Although multimodality therapy for high-grade gliomas is making some improvement in outcome, most patients will still die from their disease within a short time. We need tools that allow treatments to be tailored to an individual. In this study we used diffusion tensor imaging (DTI), a technique sensitive to subtle disruption of white-matter tracts due to tumour infiltration, to see if it can be used to predict patterns of glioma recurrence. In this study we imaged 26 patients with gliomas using DTI. Patients were imaged after 2 years or on symptomatic tumour recurrence. The diffusion tensor was split into its isotropic (p) and anisotropic (q) components, and these were plotted on T(2)-weighted images to show the pattern of DTI abnormality. This was compared to the pattern of recurrence. Three DTI patterns could be identified: (a) a diffuse pattern of abnormality where p exceeded q in all directions and was associated with diffuse increase in tumour size; (b) a localised pattern of abnormality where the tumour recurred in one particular direction; and (c) a pattern of minimal abnormality seen in some patients with or without evidence of recurrence. Diffusion tensor imaging is able to predict patterns of tumour recurrence and may allow better individualisation of tumour management and stratification for randomised controlled trials.

Adult↗
PubMed2007

Noninvasive evaluation of dynamic cerebrovascular autoregulation using Finapres plethysmograph and transcranial Doppler.

BACKGROUND AND PURPOSE: Mx is an index of cerebrovascular autoregulation. It is calculated as the correlation coefficient between slow spontaneous fluctuations of cerebral perfusion pressure (cerebral perfusion pressure=arterial blood pressure-intracranial pressure) and cerebral blood flow velocity. Mx can be estimated noninvasively (nMxa) with the use of a finger plethysmograph arterial blood pressure measurement instead of an invasive cerebral perfusion pressure measurement. We investigated the agreement between nMxa and the previously validated index Mx. METHODS: The study included 10 head-injured adults. Intracranial pressure was monitored with a parenchymal probe. Arterial blood pressure was monitored simultaneously with an arterial catheter and with the Finapres plethysmograph. Flow velocity in the middle cerebral artery was measured bilaterally with transcranial Doppler. Mx and nMxa were computed in both hemispheres, and asymmetry of autoregulation was calculated. RESULTS: Ninety-six measures of Mx and nMxa were obtained (48 for each side) in 10 patients. Mx correlated with nMxa (R=0.755, P<0.001; 95% agreement=+/-0.36; bias=0.01). Asymmetry in autoregulation assessed with Mx correlated significantly with asymmetry estimated with nMxa (R=0.857, P<0.0001; 95% agreement=+/-0.26; bias=-0.03). CONCLUSIONS: The noninvasive index of autoregulation nMxa correlates with Mx and is sensitive enough to detect autoregulation asymmetry. nMxa is proposed as a practical tool to assess cerebral autoregulation in patients who do not require invasive monitoring.

Adult↗
PubMed2007

Hyperventilation following head injury: effect on ischemic burden and cerebral oxidative metabolism.

OBJECTIVE: To determine whether hyperventilation exacerbates cerebral ischemia and compromises oxygen metabolism (CMRO2) following closed head injury. DESIGN: A prospective interventional study. SETTING: A specialist neurocritical care unit. PATIENTS: Ten healthy volunteers and 30 patients within 10 days of closed head injury. INTERVENTIONS: Subjects underwent oxygen-15 positron emission tomography imaging of cerebral blood flow, cerebral blood volume, CMRO2, and oxygen extraction fraction. In patients, positron emission tomography studies, somatosensory evoked potentials, and jugular venous saturation (SjO2) measurements were obtained at Paco2 levels of 36+/-3 and 29+/-2 torr. MEASUREMENTS AND MAIN RESULTS: We estimated the volume of ischemic brain and examined the efficiency of coupling between oxygen delivery and utilization using the sd of the oxygen extraction fraction distribution. We correlated CMRO2 to cerebral electrophysiology and examined the effects of hyperventilation on the amplitude of the cortical somatosensory evoked potential response. Patients showed higher ischemic brain volume than controls (17+/-22 vs. 2+/-3 mL; p<or=.05), with worse matching of oxygen delivery to demand (p<.001). Hyperventilation consistently reduced cerebral blood flow (p<.001) and resulted in increases in oxygen extraction fraction and ischemic brain volume (17+/-22 vs. 88+/-66 mL; p<.0001), which were undetected by SjO2 monitoring. Mean CMRO2 was slightly increased following hyperventilation, but responses were extremely variable, with 28% of patients demonstrating a decrease in CMRO2 that exceeded 95% prediction intervals for zero change in one or more regions. CMRO2 correlated with cerebral electrophysiology, and cortical somatosensory evoked potential amplitudes were significantly increased by hyperventilation. CONCLUSIONS: The acute cerebral blood flow reduction and increase in CMRO2 secondary to hyperventilation represent physiologic challenges to the traumatized brain. These challenges exhaust physiologic reserves in a proportion of brain regions in many subjects and compromise oxidative metabolism. Such ischemia is underestimated by common bedside monitoring tools and may represent a significant mechanism of avoidable neuronal injury following head trauma.

Adolescent↗
PubMed2006

Effects of acute treatment with statins on cerebral autoregulation in patients after aneurysmal subarachnoid hemorrhage.

OBJECT: The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs). In the current study, they test the hypothesis that these effects are associated with improvement in indices describing autoregulation of cerebral blood flow. METHODS: In this double-blind study, 80 patients between the ages of 18 and 84 years who had aneurysmal SAH were randomized equally to receive either 40 mg of oral pravastatin or placebo once daily for up to 14 days (medication was started 1.8 x 1.3 days after ictus). Autoregulation was measured using a daily transient hyperemic response test (THRT) on transcranial Doppler ultrasonography (800 measurements in 80 patients), and data were compared between the pravastatin and placebo groups and between patients with or without vasospasm, DINDs, or unfavorable outcome. Measurement of autoregulation also was performed using the pressure-reactivity index, a moving correlation coefficient between mean arterial and intracranial pressures (Days 0-5, 132 measurements in 32 patients). There was no difference in baseline autoregulation indices between the trial groups. The members of the pravastatin group not only had a shorter duration of impaired autoregulation but also had stronger transient hyperemic response ratios (THRRs) bilaterally. A negative correlation existed between the mean flow velocity in the middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index correlated significantly with ipsilateral impaired autoregulation. CONCLUSIONS: The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation. A routine and daily assessment of cerebral autoregulation by using the THRT may help identify patients at high risk of DINDs.

Adolescent↗
PubMed2006

Detecting awareness in the vegetative state.

We used functional magnetic resonance imaging to demonstrate preserved conscious awareness in a patient fulfilling the criteria for a diagnosis of vegetative state. When asked to imagine playing tennis or moving around her home, the patient activated predicted cortical areas in a manner indistinguishable from that of healthy volunteers.

Adult↗
PubMed2006

In vitro hydrodynamic properties of the Miethke ProGAV hydrocephalus shunt.

BACKGROUND: Adjustable shunts are very popular in the management of hydrocephalus and are believed to help in minimizing the number of surgical revisions. The drawback with almost all constructions is that they may be accidentally readjusted in relatively weak magnetic fields (around 30-40 mTesla) MATERIALS AND METHODS: The ProGav Miethke shunt is composed of an adjustable balloon-spring valve unit and an integrated over-drainage compensating gravitational device (known as the shunt assistant). A mechanical 'brake' is intended to prevent changes to the valve's performance level in a strong magnetic field. We evaluated the performance and hydrodynamic properties of a sample of three valves in the UK Shunt Evaluation Laboratory. RESULTS: All the shunts showed good mechanical durability over the three-month period of testing, and good stability of hydrodynamic performance over a one-month period. The pressure-flow performance curves, operating, opening and closing pressures fell within the limits specified by the manufacturer, and changed according to the programmed performance levels. The operating pressure increased when the shunt assistant was in the vertical position, as specified. The valve has a low hydrodynamic resistance (0.53 mm mmHg ml(-1) min(-1)). External programming proved to be easy and reliable. Strong magnetic fields from a 3 Tesla MR scanner were not able to change the programming of the valve. CONCLUSION: The ProGAV shunt is an adjustable, low resistance valve that is able to limit posture-related over-drainage. Unlike other adjustable valves, the ProGAV cannot be accidentally re-adjusted by external magnetic field such as a 3T MR scanner.

Journal Article↗
PubMed2006

Impulsivity, reward sensitivity, and decision-making in subarachnoid hemorrhage survivors.

Subarachnoid hemorrhage (SAH) survivors often report psychosocial and emotional changes, including a diminished capacity for decision making. However, systematic investigations into the nature of the changes have been limited to those patients surviving SAH secondary to aneurysms of the anterior communicating artery. This study aimed to explore the nature of decision making in survivors of SAH secondary to aneurysms of the middle cerebral or posterior communicating artery using a series of computerized tasks. Twenty SAH survivors and 20 matched controls completed a battery of computerized decision-making tasks. These included tasks examining an individual's ability to make probabilistic choices and risk-taking behavior, as well as tasks examining aspects of impulsivity. The results revealed two key patterns of abnormal decision-making behavior in the SAH survivors: altered sensitivity to both reward and punishment, and impulsive responding. These complex deficits may contribute to difficulties in daily living resulting from apathy, poor judgment, or inhibition in SAH survivors.

Case-Control Studies↗
PubMed2006

Intersubject variability and reproducibility of 15O PET studies.

Oxygen-15 positron emission tomography (15O PET) can provide important data regarding patients with head injury. We provide reference data on intersubject variability and reproducibility of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolism (CMRO2) and oxygen extraction fraction (OEF) in patients and healthy controls, and explored alternative ways of assessing reproducibility within the context of a single PET study. In addition, we used independent measurements of CBF and CMRO2 to investigate the effect of mathematical correlation on the relationship between flow and metabolism. In patients, intersubject coefficients of variation (CoV) for CBF, CMRO2 and OEF were larger than in controls (32.9%+/-2.2%, 23.2%+/-2.0% and 22.5%+/-3.4% versus 13.5%+/-1.4%, 12.8%+/-1.1% and 7.3%+/-1.2%), while CoV for CBV were lower (15.2%+/-2.1% versus 22.5%+/-2.8%) (P<0.001). The CoV for the test-retest reproducibility of CBF, CBV, CMRO2 and OEF in patients were 2.1%+/-1.5%, 3.8%+/-3.0%, 3.7%+/-3.0% and 4.6%+/-3.5%, respectively. These were much lower than the intersubject CoV figures, and were similar to alternative measures of reproducibility obtained by fractionating data from a single study. The physiological relationship between flow and metabolism was preserved even when mathematically independent measures were used for analysis. These data provide a context for the design and interpretation of interventional PET studies. While ideally each centre should develop its own bank of such data, the figures provided will allow initial generic approximations of sample size for such studies.

Adolescent↗
PubMed2006

Cognitive reserve as a resilience factor against depression after moderate/severe head injury.

Depression is one of the most frequently reported and distressing residual complaints in survivors of head injury. Studies investigating the pattern of neuropathology associated with depression post head injury have found little consistency. One explanation for this is that cognitive reserve "protects" against depression either through more efficient processing or more effective compensation. An alternative explanation is that previous studies have used relatively gross measures of lesion location, and variable inclusion criteria and times between scan and injury. This study explored these possibilities in a cohort of survivors of moderate-severe head injury at least 6 months post-injury. Volunteers completed neuropsychological assessments and structural magnetic resonance imaging (MRI) scans. A significant difference between depressed and non-depressed survivors was found, with higher intelligence associated with lower rates of depression. No significant anatomical differences were found between depressed and non-depressed survivors. These results suggest that premorbid intelligence may provide a resilience factor against depression in head injury survivors.

Adult↗
PubMed2006

Impact of intracranial pressure and cerebral perfusion pressure on severe disability and mortality after head injury.

OBJECTIVE: To investigate the relationships between intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome after traumatic brain injury. MATERIAL AND METHODS: A retrospective analysis of prospectively recorded data from 429 patients after head injury requiring intensive treatment on the Neuroscience Intensive Annex and the Neuro Critical Care Unit, Cambridge, UK. ICP, CPP, and arterial blood pressure (ABP) were continuously recorded. Mean values of pressures were compared to outcome assessed at 6 months after injury (using the Glasgow Outcome Scale). RESULTS: The mortality rate was greater in those having mean ICP greater than 20 mmHg (17% below versus 47% above; p < 0.0001). The mortality rate was dramatically increased for CPP below 55 mmHg (81% below versus 23% above; p < 0.0001). For values of CPP greater than 95 mmHg, favorable outcome was less frequent (50% below versus 28% above; p < 0.033). The rate of severe disability showed the tendency to increase with CPP ( r = 0.87; p = 0.02), suggesting that a higher CPP does not help in achieving favorable outcomes. ICP was greater in those who died in comparison to those who survived (27 +/- 19 mmHg versus 16 +/- 6 mmHg; p < 0.10 - 7), and CPP was lower (68 +/- 21 versus 76 +/- 10 mmHg; p < 0.0002). There was no difference between mean ICP and CPP in good/moderate and severe disability outcome groups. CONCLUSION: High ICP is strongly associated with fatal outcome. Excessive CPP seems to reduce the probability of achieving a favorable outcome following head trauma.

Adolescent↗
PubMed2006

Predictive value of initial computerized tomography scan, intracranial pressure, and state of autoregulation in patients with traumatic brain injury.

OBJECT: The authors explored the relationship between computerized tomography (CT) scan findings and intracranial pressure (ICP) measurements obtained in the first 24 hours of monitoring to identify parameters predicting outcome in patients with severe traumatic brain injury (TBI). METHODS: Intracranial pressure, mean arterial blood pressure, cerebral perfusion pressure (CPP), and pressure reactivity index were measured continuously in 126 patients with severe TBI who were admitted to a neuroscience critical care unit. Mean values in the initial 24 hours of monitoring and in the total period of monitoring were compared with types of injury categorized on the basis of the initial CT scan according to the classification of Marshall, et al., and with Glasgow Outcome Scale scores. The initial CT scan classification correlated significantly but weakly with ICP measured during the first 24 hours of monitoring (p = 0.036) but not with mean ICP over the total time of intensive care. Both midline shift and the ratio of frontal horn diameter to internal diameter correlated with ICP in the first 24 hours (p < 0.007) and with ICP over the total monitoring period (p < 0.03). Outcome score correlated with initial CT scan findings (p = 0.018), ICP over the total monitoring period (p < 0.0023), pressure reactivity over the total monitoring period (p < 0.0002), and pressure reactivity in the first 24 hours (p < 0.0001) but not with ICP in the first 24 hours. Patients with disturbed pressure reactivity in the first 24 hours after injury had a significantly higher mortality rate than patients with intact pressure reactivity (28.6% compared with 9.5%; p < 0.001). CONCLUSIONS: Patients with severe TBI who have early loss of autoregulation have a worse prognosis. Mean ICP values in patients with diffuse TBI cannot be predicted by using the Marshall CT scan classification.

Adolescent↗
PubMed2006

Imaging endothelin ET(B) receptors using [18F]-BQ3020: in vitro characterization and positron emission tomography (microPET).

The endothelin (ET) receptor system has been shown to play a role in a number of vascular diseases. We have synthesized 18F-and 11C-labeled radioligands to enable in vivo imaging of the fundamental processes involved in ET receptor pharmacology in normal and diseased tissue using positron emission tomography (PET). One aim is to elucidate the proposed role of the ET(B) subtype as clearing receptor, removing ET-1 from the circulation, and whether this is an important mechanism to limit the detrimental effects caused by upregulated ET-1 in disease. To image ET(B) receptors we have labeled the selective agonist BQ3020 with 18F. In vitro characterization verified that [18F]-BQ3020 bound with a single subnanomolar affinity (K(D) = 0.34 +/- 0.10 nM, B(max) = 9.23 +/- 3.70 fmol/mg protein) to human left ventricle. Binding of [18F]-BQ3020 to human kidney was inhibited by ET-1 and unlabeled BQ3020 but not by the ET(A) selective antagonist FR139317, confirming that selectivity for the ET(B) receptor was retained. In vitro autoradiography revealed, as expected, high levels of ET(B) receptor densities in lung and kidney medulla, whereas kidney cortex and heart showed lower levels of ET(B) receptor densities. Furthermore, a high level of [18F]-BQ3020 binding was found to colocalize to macrophages in atherosclerotic coronary arteries. MicroPET studies demonstrated high uptake of [18F]-BQ3020 in ET(B) receptor-rich tissue, including lung, liver and kidney. The in vivo biodistribution of [18F]-BQ3020 was comparable to that previously obtained for [18F]-ET-1, supporting our hypothesis that the ET(B) receptor plays a significant role in the uptake of ET-1. In conclusion, [18F]-BQ3020 has retained high affinity and selectivity, allowing imaging of ET(B) receptor distributions in vitro and in vivo in human and animal tissue. Furthermore, in vitro data suggest that [18F]-BQ3020 potentially can be used to image atherosclerotic lesions in vivo using PET.

Animals↗
PubMed2005

Analysis of intracranial pressure during and after the infusion test in patients with communicating hydrocephalus.

The cerebrospinal fluid (CSF) infusion test is used to evaluate the dynamics of CSF circulation in patients with communicating hydrocephalus and is based on constant-rate infusion of the normal saline into cerebrospinal fluid space. The aim of the study was to refine methods of the analysis of intracranial pressure (ICP) recorded during and after the infusion test. The mathematical model of cerebrospinal fluid circulation was extended by the equation describing ICP decrease after the infusion. The nonlinear least-squares method of Levenberg-Marquardt was used to estimate the parameters describing the CSF compensatory mechanisms. Twenty-seven infusion tests were studied. Both phases of the test-the increase and the decrease of ICP-were recorded and the compensatory parameters were calculated for each of them. ICP often does not return to the resting level after the infusion test within the period equivalent to the time of infusion in all cases. In 20 tests the differences between post- and pre-infusion resting ICP (DeltaICP) was higher than 1 mmHg, which was considered as significant. The mean value of DeltaICP for 20 infusion tests was 3.0 +/- 0.7 mmHg. The cerebral elasticity evaluated during the infusion was greater than the elasticity estimated from the decreasing phase after the infusion (0.24 +/- 0.07 ml(-1) versus 0.14 +/- 0.03 ml(-1); p < 0.01).

Adult↗
PubMed2005

Head circumference and brain and hippocampal volume after severe traumatic brain injury in childhood.

Vulnerability of the hippocampus to traumatic brain injury (TBI) in adults is related to severity of injury and white matter atrophy. The objectives of this study were to determine features of anthropometry and cerebral morphometry late after TBI in childhood and to assess whether hippocampal volume is related to severity of initial ictus and changes in white matter at follow-up. Thirty-three patients underwent magnetic resonance imaging 4.9 y after severe TBI that necessitated intensive care; 23 had mechanical ventilation and intracranial pressure monitoring longer than 3 d. Magnetic resonance imaging analyses included volume of brain, hemisphere, ventricles, and hippocampal and perihippocampal regions; spatial distribution of voxel-based morphometry differences in white matter; and eigenvalues of diffusion tensor imaging diffusivity. Patients with longer intensive care ictus had smaller-than-expected occipitofrontal head circumference. Eight of these, identified by voxel-based morphometry, had periventricular white matter loss and smaller-than-expected brain volume for OFC, suggesting "atrophy"; the remainder had expected volume for a smaller OFC, suggesting "growth disturbance." Ninety-three percent of the variation in right hippocampal volume was accounted for by factors related to severity of injury and white matter atrophy. It is concluded that anthropometry and cerebral morphometric measurements late after severe TBI in childhood provides useful outcome data and indicate that, despite adequate growth in stature, effects of TBI on brain growth and hippocampal volume may extend into adulthood.

Adolescent↗
PubMed2005

Neurophysiological architecture of functional magnetic resonance images of human brain.

We investigated large-scale systems organization of the whole human brain using functional magnetic resonance imaging (fMRI) data acquired from healthy volunteers in a no-task or 'resting' state. Images were parcellated using a prior anatomical template, yielding regional mean time series for each of 90 regions (major cortical gyri and subcortical nuclei) in each subject. Significant pairwise functional connections, defined by the group mean inter-regional partial correlation matrix, were mostly either local and intrahemispheric or symmetrically interhemispheric. Low-frequency components in the time series subtended stronger inter-regional correlations than high-frequency components. Intrahemispheric connectivity was generally related to anatomical distance by an inverse square law; many symmetrical interhemispheric connections were stronger than predicted by the anatomical distance between bilaterally homologous regions. Strong interhemispheric connectivity was notably absent in data acquired from a single patient, minimally conscious following a brainstem lesion. Multivariate analysis by hierarchical clustering and multidimensional scaling consistently defined six major systems in healthy volunteers-- corresponding approximately to four neocortical lobes, medial temporal lobe and subcortical nuclei- - that could be further decomposed into anatomically and functionally plausible subsystems, e.g. dorsal and ventral divisions of occipital cortex. An undirected graph derived by thresholding the healthy group mean partial correlation matrix demonstrated local clustering or cliquishness of connectivity and short mean path length compatible with prior data on small world characteristics of non-human cortical anatomy. Functional MRI demonstrates a neurophysiological architecture of the normal human brain that is anatomically sensible, strongly symmetrical, disrupted by acute brain injury, subtended predominantly by low frequencies and consistent with a small world network topology.

Adult↗
PubMed2005

Formal characterization and extension of the linearized diffusion tensor model.

We analyzed the properties of the logarithm of the Rician distribution leading to a full characterization of the probability law of the errors in the linearized diffusion tensor model. An almost complete lack of bias, a simple relation between the variance and the signal-to-noise ratio in the original complex data, and a close approximation to normality facilitated estimation of the tensor components by an iterative weighted least squares algorithm. The theory of the linear model has also been used to derive the distribution of mean diffusivity, to develop an informative statistical test for relative lack of fit of the ellipsoidal (or spherical) model compared to an unrestricted linear model in which no specific shape is assumed for the diffusion process, and to estimate the signal-to-noise ratios in the original data. The false discovery rate (FDR) has been used to control thresholds for statistical significance in the context of multiple comparisons at voxel level. The methods are illustrated by application to three diffusion tensor imaging (DTI) datasets of clinical interest: a healthy volunteer, a patient with acute brain injury, and a patient with hydrocephalus. Interestingly, some salient features, such as a region normally comprising the basal ganglia and internal capsule, and areas of edema in patients with brain injury and hydrocephalus, had patterns of error largely independent from their mean diffusivities. These observations were made in brain regions with sufficiently large signal-to-noise ratios (>2) to justify the assumptions of the log Rician probability model. The combination of diffusivity and its error may provide added value in diagnostic DTI of acute pathologic expansion of the extracellular fluid compartment in brain parenchymal tissue.

Adult↗