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Biomedical subjects

J D Pickard

Publications and source records attributed to J D Pickard.

At least 73 records · Page 4Linked to original sources
PubMed2003

Pressure-autoregulation, CO2 reactivity and asymmetry of haemodynamic parameters in patients with carotid artery stenotic disease. A clinical appraisal.

OBJECTIVES: Patients with carotid artery stenotic disease and poor cerebral haemodynamic reserve are in increased risk of stroke. Haemodynamic reserve can be estimated by measuring cerebrovascular reactivity induced by breathing CO2 and pressure-autoregulation by analyzing spontaneous slow fluctuation in arterial pressure and MCA blood flow velocity. We evaluated the relationship between clinical status, CO2 reactivity, pressure-autoregulation and other haemodynamic variables derived from Transcranial Doppler ultrasonography in patients with carotid artery disease. METHODS: 38 patients were investigated. Arterial pressure and blood flow velocity were monitored during CO2 reactivity tests. Arterial pressure-corrected and non-corrected indices of CO2 reactivity were calculated to compare an influence of rise in arterial pressure during the test. The pressure-autoregulation index was calculated as correlation coefficient between slow waves in blood flow velocity and arterial pressure. RESULTS: The increase in CO2 produced a consistent rise in arterial pressure and blood flow velocity and weakened the pressure autoregulation. The value of pressure-corrected CO2 reactivity was lower (p<0.0001) than the non-corrected one, indicating that the rise in arterial pressure during the test tends to over-estimate CO2 reactivity. The pressure-corrected reactivity was correlated with pressure autoregulation (r=-0.46; p<0.005). Both CO2 reactivity and pressure-autoregulation index correlated with a degree of carotid artery stenosis. Side-to-side difference of TCD pulsatility index demonstrated a close relationship with the asymmetry of stenosis (r=-0.61; p<0.0002) and symptoms (r=-0.49; p<0.003). CONCLUSIONS: When calculating CO2 reactivity in patients with carotid artery disease, changes in arterial pressure should be considered. Both CO2 reactivity and pressure-autoregulation describe the magnitude of haemodynamic deficit caused by stenosis, pulsatility index expresses the asymmetry of stenosis.

Aged↗
PubMed2003

Diffusion tensor imaging of brain tumours at 3T: a potential tool for assessing white matter tract invasion?

AIM: To determine whether diffusion tensor imaging (DTI) of brain tumours can demonstrate abnormalities distal to hyperintensities on T2-weighted images, and possibly relate these to tumour grade. MATERIALS AND METHODS: Twenty patients with histologically confirmed supratentorial tumours, both gliomas (high and low grade) and metastases, were imaged at 3T using T2-weighted and DTI sequences. Regions of interest (ROI) were drawn within the tumour, in white matter at various distances from the tumour and in areas of abnormality on DTI that appeared normal on T2-weighted images. The relative anisotropy index (RAI)-a measure of white matter organization, was calculated for these ROI. RESULTS: The abnormality on DTI was larger than that seen on T2-weighted images in 10/13 patients (77%) with high-grade gliomas. New abnormalities were seen in the contralateral white matter in 4/13 (30%) of these cases. In these high-grade tumours the RAI in areas of white matter disruption with normal appearance on T2-weighted images was reduced (0.19+/-0.04). Even excluding patients with previous radiotherapy this difference remains significant. In all non high-grade tumours (WHO grade II gliomas and metastases) the tumour extent on DTI was identical to the abnormalities shown on T2-weighted imaging and RAI measurements were not reduced (0.3+/-0.04). CONCLUSIONS: Subtle white matter disruption can be identified using DTI in patients with high-grade gliomas. Such disruption is not identified in association with metastases or low-grade gliomas despite these tumours producing significant mass effect and oedema. We suggest the changes in DTI may be due to tumour infiltration and that the DTI may provide a useful method of detecting occult white matter invasion by gliomas.

Adult↗
PubMed2003

Time course of cellular pathology after controlled cortical impact injury.

Several different models of brain trauma are currently used and each simulates different aspects of the clinical condition and to varying degrees of accuracy. While numerous studies have characterized the cellular pathology after weight-drop or fluid percussion injury, detailed information on the histopathology that evolves after the controlled cortical impact model is incomplete. We have determined the spatiotemporal pathologies of neuronal, axonal, vascular, and macro- and microglial elements at 1, 4, 7, and 28 days after moderate controlled cortical impact injury. Neuronal injury identified by pyknotic perikarya and disrupted neurofilament-stained axonal profiles were evident by 1 day in ipsilateral cortex and hippocampus and at later times in the thalamus. glial fibrillary acidic protein-reactive astrocytes were more widespread, reaching a maximum immunointensity at 4 days across the ipsilateral hemisphere but declining to control levels thereafter. Microglia/macrophage-OX42 staining was initially restricted to the contusion site and then later to the thalamus, consistent with the pattern of neuronal injury. Increases in nestin immunoreactivity-a postulated marker of neural progenitor cells, and in NG2 proteoglycan-a marker of oligodendrocyte precursor cells, were detected by 1 day, reaching maximal immunointensity at 4-7 days after injury. Mean density and diameter of cortical microvessels was significantly reduced and increased respectively but only at the initial time points, suggesting that some degree of vascular remodeling takes place after injury. We discuss these results in light of recent evidence that suggests there may be some degree of endogenous repair after central nervous system injury.

Animals↗
PubMed2003

Influence of baseline hematocrit on between-subject BOLD signal change using gradient echo and asymmetric spin echo EPI.

The dependence of BOLD signal change (BSC) on baseline hematocrit is in the process of being characterized, primarily using conventional Gradient Echo (GE) echo planar imaging (EPI). We describe the first empiric exploration of this relationship using, in addition to GE, Spin Echo (SE) and two Asymmetric Spin Echo EPI sequences (ASE10 and ASE20), which are less susceptible to large vessel noise. Motor cortex BSC was measured (N = 17) and regressed against hematocrit and hemoglobin concentration using linear and non-linear functions. GE measurements of BSC yielded a positive linear relationship (r(2) = 0.240, p = 0.0459) whereas a positive non-linear relationship was observed using ASE10 (r(2) = 0.571, p = 0.0146). Results suggest that between-subjects BSC is significantly dependent on baseline hematocrit. The nature of dependence, and implications for quantitative studies vary with the vessel size selectivity of the imaging sequence, and with the effect of hematocrit on blood viscosity in the imaged vessels.

Brain Mapping↗
PubMed2003

GABAergic inhibitory mechanisms for repetition-adaptivity in large-scale brain systems.

Molecular mechanisms for systems level adaptivity of brain activation are largely unknown but a key role for active inhibition by gamma-aminobutyric acid (GABA) is plausible. We used functional magnetic resonance imaging to contrast the modulatory effects on brain adaptivity to task repetition and task difficulty of two GABAergic drugs, lorazepam and flumazenil. In a working memory paradigm, occipitotemporal regions clearly demonstrated attenuation of activation as a function of within-session task repetition or practice in data acquired following placebo, but this spatiotemporal pattern of repetition adaptivity was abolished by both lorazepam and flumazenil. However, in other brain systems flumazenil enhanced repetition adaptivity compared to placebo: in frontal cortex, flumzenil induced attenuation of signal related to task repetition and in hippocampus it exaggerated normal enhancement of signal with repetition. In contrast, there were no significant effects of either flumazenil or lorazepam on areas of frontal cortex which normally demonstrated significant neurocognitive load response or adaptivity to task difficulty. We argue that repetition adaptivity of large-scale brain systems is regulated by GABAergic inhibitory mechanisms and that expression of repetition adaptivity in a given brain system may show an "inverted-U" form of relationship with pharmacologically manipulable levels of GABAergic inhibitory tone.

Adult↗
PubMed2003

Stereotactic MR imaging for planning neural transplantation: a reliable technique at 3 Tesla?

The purpose of this study was to assess the accuracy of high field (3 Tesla) MR in target localization for stem cell transplantation. Three patients with Huntington's disease were imaged with a stereotactic frame in place for both MRI and CT. Quality assurance procedures and manual shimming were performed before each MRI study to minimize image distortion. The images were fused using multi-modality rigid body image registration software. Image fusion demonstrated the MR images to be in agreement with CT to within 1.5 mm, as assessed by measuring the coordinates of markers on the frame and on the shape and size of the lateral ventricles. Target coordinates for transplantation were selected from the MR images. Postoperative imaging confirmed accurate graft placement.

Brain Tissue Transplantation↗
PubMed2003

Idiopathic intracranial hypertension: 12 cases treated by venous sinus stenting.

BACKGROUND: The high pressures documented in the intracranial venous sinuses in idiopathic intracranial hypertension (IIH) could be the result of focal stenotic lesions in the lateral sinuses obstructing cranial venous outflow. OBJECTIVE: To explore the relation between venous sinus disease and IIH. METHODS: 12 patients with refractory IIH had dilatation and stenting of the venous sinuses after venography and manometry had shown intracranial venous hypertension proximal to stenoses in the lateral sinuses. Intrasinus pressures were recorded before and after the procedure and correlated with clinical outcome. RESULTS: Intrasinus pressures were variably reduced by stenting. Five patients were rendered asymptomatic, two were improved, and five were unchanged. CONCLUSIONS: The importance of venous sinus disease in the aetiology of IIH is probably underestimated. Lateral sinus stenting shows promise as an alternative treatment to neurosurgical intervention in intractable cases.

Adult↗
PubMed2003

Cerebrovascular pressure reactivity is related to global cerebral oxygen metabolism after head injury.

BACKGROUND: After head injury, impaired cerebrovascular autoregulation has been associated with abnormally high or low cerebral blood flow. The physiological relevance of cerebral blood flow levels is difficult to assess in these patients, whose cerebral metabolic rate for oxygen (CMRO(2)) is known to be abnormal. Investigation of these relations requires quantitative measures of cerebral blood flow and CMRO(2), to allow assessment of oxygen supply and demand relations. OBJECTIVES: To investigate the relation between dysautoregulation and global cerebral oxygen metabolism following head injury. METHODS: Using positron emission tomography, global cerebral blood flow, CMRO(2), and oxygen extraction fraction were determined in 22 patients who were investigated in 26 examinations on days 1 to 11 (mean (SD), 3.5 (2.3)) after head injury. Cerebrovascular pressure reactivity was assessed using a pressure reactivity index, calculated as the moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure. Outcome was assessed six months after injury using the Glasgow outcome scale. RESULTS: Low CMRO(2) was associated with disturbed pressure reactivity (inverse function, R(2) = 0.21, p = 0.018) and there was a correlation between disturbed pressure reactivity and oxygen extraction fraction (quadratic function, R(2) = 0.55, p = 0.0001). There was no significant relation between pressure reactivity and cerebral blood flow. An unfavourable outcome was associated with disturbed pressure reactivity. There was no significant relation between outcome and CMRO(2) or oxygen extraction fraction. CONCLUSIONS: There is a close relation between dysautoregulation and abnormal cerebral metabolism but not blood flow. Further studies are needed to determine whether metabolic dysfunction is a result of or a cause of disturbed pressure reactivity, and to establish if there is a relation between cerebral oxygen metabolism and outcome.

Adolescent↗
PubMed2003

Evaluation of an MRI-based protocol for cell implantation in four patients with Huntington's disease.

The purpose of this study was to evaluate our surgical protocol for the preparation and delivery of suspensions of fetal tissue into the diseased human brain. We implanted suspensions of human fetal striatal anlage into the right caudate and putamen of four patients with Huntington's disease. Postoperative 3 tesla MR imaging confirmed accurate graft placement. Variability in graft survival was noted and the MR signal changes over 6 months revealed persistent hyperintense signal on T2-weighted images. Our results are consistent with those described by other groups and indicate that our surgical protocol is safe, accurate, and reproducible.

Brain↗
PubMed2002

Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography.

BACKGROUND: Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication of plaque inflammation. The glucose analogue [18F]-fluorodeoxyglucose (18FDG) can be used to image inflammatory cell activity non-invasively by PET. In this study we tested whether 18FDG-PET imaging can identify inflammation within carotid artery atherosclerotic plaques. METHODS AND RESULTS: Eight patients with symptomatic carotid atherosclerosis were imaged using 18FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in 18FDG-PET images acquired 3 hours post-18FDG injection. The estimated net 18FDG accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher than in contralateral asymptomatic lesions. There was no measurable 18FDG uptake into normal carotid arteries. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas of the plaque. CONCLUSIONS: This study demonstrates that atherosclerotic plaque inflammation can be imaged with 18FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions.

Aged↗
PubMed2002

Multi-modal monitoring of acute brain injury.

OBJECTIVE: To review the scientific basis for and utility of the traditional cerebral monitors used currently in neurointensive care, together with research techniques that are soon likely to become used in managing severe head injury and subarachnoid haemorrhage. DESIGN AND CONTENT: Firstly, the pathophysiology of acute brain injury including cerebral haemodynamics, oxygen and metabolism and the role of secondary insults are discussed. Secondly, the importance of assessment of cerebrovascular autoregulation and reactivity is reviewed together with methods for its continuous non-invasive measurement using transcranial Doppler and intracranial pressure/arterial pressure recordings. Thirdly, the respective roles of jugular venous oxygen and brain tissue oxygen monitoring are analysed. Fourthly, the use of cerebral microdialysis is described, together with an overview of its utility. CONCLUSION: Cerebral multimodal monitoring can be helpful for the optimal management of acute brain injury and essential for future exploratory trials of neuroprotective drugs.

Acute Disease↗
PubMed2002

Communicating hydrocephalus: the biomechanics of progressive ventricular enlargement revisited.

BACKGROUND: This article investigates the physical mechanisms involved in the chronic ventricular enlargement that accompanies communicating hydrocephalus (CH)--including its normal and low-pressure forms. In particular, it proposes that this phenomenon can be explained by the combined effect of: (a) a reversal of interstitial fluid flow in the parenchyma, and (b) a reduction in the elastic modulus of the cerebral mantle. METHOD: To investigate this hypothesis, these changes have been incorporated into a finite element computer simulation of CH, in which brain tissue is idealized as a sponge-like material. The fluid pressure in the lateral ventricles and the subarachnoid space has been set to 10 mmHg, while the fluid pressure inside the parenchyma has been set to 7.5 mmHg. The elastic moduli of white and gray matter have been set to the reduced values of 1 and 5 kPa, respectively. FINDINGS: The simulation revealed a substantial ventricular distension (6.5 mm mean outward displacement), which was accompanied by the appearance of stress concentrations in the cerebral mantle. INTERPRETATION: These results support the notion that a relative reduction in intraparenchymal fluid pressure coupled with low tissue elasticity can produce both a significant ventricular enlargement and periventricular solid stress concentrations.

Biomechanical Phenomena↗
PubMed2002

Clinical significance of cerebral autoregulation.

OBJECTIVES: Disturbed cerebral autoregulation is believed to be associated with an unfavourable outcome following head injury. Previously, using ICP monitoring and transcranial Doppler ultrasonography, we investigated whether cerebral response to spontaneous variations in arterial pressure (ABP) or cerebral perfusion pressure (CPP) provide reliable information on cerebral autoregulatory reserve. In the present study we have correlated these methods with clinical findings. METHODS: 188 head injured sedated and ventilated patients were studied daily. Waveforms of intracranial pressure (ICP), arterial pressure and transcranial Doppler flow velocity (FV) were captured over a half to two hour periods. Time averaged mean flow velocity (FV) and CPP were resolved. The correlation coefficient indices between FV and CPP (Mx) and between ICP and ABP (PRx) were calculated over 3 minutes epochs, and averaged for each investigation. RESULTS: The relationship between indices of autoregulation and outcome (favourable-unfavourable) was significant and stronger than the association between admission GCS and outcome. With rigorously maintained CPP-oriented therapy relationship between CPP and outcome became non-significant. Mortality in patients with consistently disturbed autoregulation ranged 47%, while in patients with good autoregulation mortality was 11% (difference: p < 0.0001). CONCLUSIONS: Positive values of indices of autoregulation, expressing positive association between slow waves of CPP and blood flow velocity or ABP and ICP, indicate disturbed autoregulation. These indices correlate with unfavourable outcome following head injury and should be used to guide intensive therapy.

Blood Flow Velocity↗
PubMed2002

Asymmetry of cerebral autoregulation following head injury.

OBJECTIVES: To investigate asymmetry of cerebra autoregulation in head-injured patients with lateral brain contusions. METHODS: Sixty five patients were admitted to Addenbrooke's Hospital suffering from head injuries with mean Glasgow Coma Score 6 (range 3 to 10). The patients were paralyzed, sedated and ventilated to achieve mild hypocapnia. Intracranial pressure (ICP), arterial pressure (ABP) were monitored directly. The left and right Middle Cerebral Arteries were insonated daily and flow velocity (FV) was recorded. Correlation coefficients between slow waves in cerebral perfusion pressure (CPP) and FV were calculated for every 3 minute period. Positive value of Mx denotes a positive association between waves in FV and CPP, therefore deranged autoregulation. Zero or slightly negative value of Mx denotes a good autoregulatory capacity. In each patient all CT scans were reviewed to assess a dominant side of brain contusion and a level of brain compression. RESULTS: The side-to-side difference in FV, pulsatility indices or critical closing pressures, did not correlate with the side of contusion or midline shift. In contrary, the side-to-side difference in Mx indices were significantly (p < 0.05) worse at a side of contusion and at the side of brain expansion in patients presenting with a midline shift (p < 0.05). Of those patients who died in hospital, significantly more presented within meaningful (ABS(Mx) > 0.2) asymmetry in cerebral autoregulation (40% versus 12%; p < 0.05). CONCLUSIONS: Side-to-side difference in cerebral hemodynamic reserve of injured brain is a predictor of fatal outcome following head injury and correlates with the side of contusion or brain expansion.

Blood Flow Velocity↗
PubMed2002

Factors determining mean ICP in hydrocephalic patients with Hakim-programmable valve: implications of the parallel arrangement of the CSF outflow resistance and shunt.

OBJECTIVE: Measurement of CSF pressure is used clinically to test shunt function in vivo in hydrocephalic patients. Criteria for appropriate shunt function have never been validated. METHOD: Hakim-Programmable valve was tested in a model of CSF circulation with variable resistance to CSF outflow (from 12 to 50 mm Hg/ml/min), increased hydrodynamic compliance (> 1.5 ml/mm Hg), and constant perfusion of a rate of 0.4 ml/min, i.e. conditions typical for hydrocephalus. The main question was how the simulated CSF pressure was influenced by the shunt setting and the residual resistance to CSF outflow. RESULTS: Measured baseline CSF pressure correlated well with shunt operating pressure only when high resistance to CSF outflow (50 mm Hg/(ml/min)) was used. For the medium resistance (20 mm Hg/(ml/min)) operating pressure was strongly affected by system's absorption capacity. For low resistance (12 mm Hg/(ml/min)) operating pressure through the valve was independent on valve's settings and no fluid drainage through the valve was recorded. CONCLUSION: Patients with moderately elevated resistance to CSF outflow (12-18 mm Hg/(ml/min)) cannot possibly react to changes of the valve's settings above 100 mm H2O. Mean CSF pressure results both from shunt setting and patient's own re-absorption capacity.

Cerebrospinal Fluid Shunts↗
PubMed2002

Shunt testing in-vivo: a method based on the data from the UK shunt evaluation laboratory.

OBJECTIVES: The objective of the UK Shunt Evaluation Laboratory was to perform an independent testing of hydrodynamic performance of hydrocephalus shunts and provide systematic reviewing for neurosurgeons and patients. METHODS: Valves were tested long-term in a computer-controlled rig to evaluate their pressure-flow performance both at baseline and under conditions mimicking phenomena, which may alter CSF drainage in vivo. The operating pressures (Poperating) and hydrodynamic resistances (R) of all types of valves, currently in use in the UK, have been evaluated (Codman: Hakim-Precision, Hakim-Programmable, Uni-Shunt, Accu-flo, Holter. Medtronic PS Medical: Delta, Flow Control, Lumbo-peritoneal. NMT: Orbis-Sigma, Omni-shunt, Hakim Valve. Heyer-Schulte: In-line, Pudenz-Flushing, LowProfile. Radionics ContourFlex. Sophy Programmable). 67 patients, who had improved in the past following shunting but had recent recurrence of their clinical symptoms, were admitted to undergo a computerized infusion test through the shunt pre-chamber or Ommaya reservoir implanted prior to shunting. The criterion used to detect shunt underdrainage was an increase in ICP during constant infusion above (Poperating) + R * Infusion rate + 5 mm Hg. The validity of this formula has been confirmed in a laboratory study. RESULTS: 35 patients met the criteria for shunt underdrainage while in 24 normal drainage was demonstrated. Mean ICP achieved during the test was 24 mm Hg in patients with underdrainage versus 14 mm Hg with normally functioning shunts (p < 0.01). Out of 35 patients 25 improved and 10 were seen again to have the test repeated. In 7 patients shunt was blocked again. Only 3 patients with primarily confirmed shunt underdrainage did not improve following revisions. In 8 patients overdrainage related to body posture was confirmed using tilt-test. CONCLUSIONS: Shunt testing in-vivo is easy, clinically useful and has good prediction power (90%).

Cerebrospinal Fluid↗
PubMed2002

Effects of variation in cerebral haemodynamics during aneurysm surgery on brain tissue oxygen and metabolism.

OBJECTIVES: This study explores the sensitivities of multiparameter tissue gas sensors and microdialysis to variations in blood pressure, CSF drainage and to well-defined periods of ischaemia accompanying aneurysm surgery, and their predictive value for infarction. METHODS: A Neurotrend sensor [brain tissue partial pressure of oxygen (PBO2), carbon dioxide (PBCO2), brain pH (pHB) and temperature] and microdialysis catheter were inserted into the appropriate vascular territory prior to craniotomy. RESULTS: Baseline data showed a clear correlation between PBO2 and mean arterial pressure (MAP) below a threshold of 80 mmHg. PBO2 improved with CSF drainage in 20 out of 28 (Wilcoxon: P < 0.05) cases where data was available. In 26 patients the effects of temporary vascular clipping (TC) (mean duration 16 minutes) were assessed. 2 patients subsequently declared infarction in the region of the probes. PBO2 fell from a mean 3.2 (95% CI 2.4-4.1) kPa to a minimum of 1.5 (95% CI 1.0-2.0) kPa in the non-infarct group. There was a lower baseline PBO2 (mean 0.8 kPa) in the patients who infarcted. PBCO2 mirrored PBO2 changes, whereas pHB did not change significantly in either group. Microdialysis changes associated with decreased PBO2 included a delayed increase in lactate, a raised lactate/pyruvate ratio and more rarely an increased glutamate. These changes were seen in 11 patients but were not predictive of infarction. CONCLUSION: Hypotension during aneurysm surgery is associated with a low PBO2. Multiparameter sensors can be sensitive to acute ischaemia. Microdialysis shows potential in the detection of metabolic changes during tissue hypoxia.

Adult↗