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John D Pickard

Publications and source records attributed to John D Pickard.

At least 37 records · Page 2Linked to original sources

Using a hierarchical approach to investigate residual auditory cognition in persistent vegetative state.

Persistent vegetative state is arguably one of the least understood and most ethically troublesome neurological conditions in modern medicine. The term describes a rare disorder in which patients who emerge from coma appear to be awake, but show no signs of awareness. In recent years, a number of studies have demonstrated an important role for functional neuroimaging in the identification of residual cognitive function in patients meeting the clinical criteria for persistent vegetative state. Such studies, when successful, may be particularly useful where there is a concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected. Unfortunately, functional neuroimaging in persistent vegetative state is extremely complex and subject to numerous methodological, clinical and theoretical difficulties. In this chapter, we argue that in order to most effectively define the degree and extent of preserved cognitive function in persistent vegetative state, a hierarchical approach to cognition is required. To illustrate this point, a series of functional neuroimaging paradigms in the auditory domain are described, which systematically increase in complexity in terms of the auditory and/or linguistic processes required and, therefore, the degree of preserved cognition that can be inferred from "normal" patterns of activation in persistent vegetative patients. Preliminary results in a small series of patients provide a strong basis for the systematic study of possible residual cognitive function in persistent vegetative state.

Auditory Perception↗

Positron emission tomography using 18F-labelled endothelin-1 reveals prevention of binding to cardiac receptors owing to tissue-specific clearance by ET B receptors in vivo.

Our aim was to synthesise an (18)F analogue of endothelin-1 (ET-1), to dynamically image ET receptors in vivo by positron emission tomography (PET) and to elucidate the function of the ET(B) subtype as a clearing receptor in organs expressing high densities including kidney and lung.[(18)F]-ET-1 was characterised in vitro and bound with a single subnanomolar affinity (K(D)=0.43+/-0.05 nM, B(max)=27.8+/-2.1 fmol mg(-1) protein) to human left ventricle (n=4). The in vivo distribution of [(18)F]-ET-1 in anaesthetised rats was measured using a dedicated small animal PET scanner (microPET) and ex vivo analysis. Dynamic PET data demonstrated that high levels of radioligand accumulated rapidly in the lung, kidney and liver, consistent with receptor binding. The in vivo distribution correlated with the anatomical localisation of receptors detected in vitro using [(125)I]-ET-1. However, the receptor density visualised in the heart was unexpectedly low compared with that predicted from the in vitro measurements.[(18)F]-ET-1 binding in lungs could not be displaced by the ET(B) selective antagonist BQ788, in agreement with the proposed internalisation of ET-1 by ET(B) receptors. In contrast, infusion of BQ788 prior to injecting [(18)F]-ET-1 significantly reduce the amount of radioligand visualised in the ET(B) rich lung and kidney by 85% (P< 0.05, n=3) and 55% (P<0.05, n=3), respectively. Under conditions of ET(B) receptor blockade, the heart could be visualised by microPET imaging.These results suggest that clearance by ET(B) receptors in the lung and kidney prevents binding of ET-1 to receptors in the heart.

Animals↗

Effect of cerebral perfusion pressure augmentation on regional oxygenation and metabolism after head injury.

OBJECTIVE: In this study we have used O positron emission tomography, brain tissue oxygen monitoring, and cerebral microdialysis to assess the effects of cerebral perfusion pressure augmentation on regional physiology and metabolism in the setting of traumatic brain injury. DESIGN: Prospective interventional study. SETTING: Neurosciences critical care unit of a university hospital. PATIENTS: Eleven acutely head-injured patients requiring norepinephrine to maintain cerebral perfusion pressure. INTERVENTIONS: Using positron emission tomography, we have quantified the response to an increase in cerebral perfusion pressure in a region of interest around a brain tissue oxygen sensor (Neurotrend) and microdialysis catheter. Oxygen extraction fraction and cerebral blood flow were measured with positron emission tomography at a cerebral perfusion pressure of approximately 70 mm Hg and approximately 90 mm Hg using norepinephrine to control cerebral perfusion pressure. All other aspects of physiology were kept stable. MEASUREMENTS AND MAIN RESULTS: Cerebral perfusion pressure augmentation resulted in a significant increase in brain tissue oxygen (17 +/- 8 vs. 22 +/- 8 mm Hg; 2.2 +/- 1.0 vs. 2.9 +/- 1.0 kPa, p < .001) and cerebral blood flow (27.5 +/- 5.1 vs. 29.7 +/- 6.0 mL/100 mL/min, p < .05) and a significant decrease in oxygen extraction fraction (33.4 +/- 5.9 vs. 30.3 +/- 4.6 %, p < .05). There were no significant changes in any of the microdialysis variables (glucose, lactate, pyruvate, lactate/pyruvate ratio, glycerol). There was a significant linear relationship between brain tissue oxygen and oxygen extraction fraction (r = .21, p < .05); the brain tissue oxygen value associated with an oxygen extraction fraction of 40% (the mean value for oxygen extraction fraction in normal controls) was 14 mm Hg (1.8 kPa). The cerebral perfusion pressure intervention resulted in a greater percentage increase in brain tissue oxygen than the percentage decrease in oxygen extraction fraction; this suggests that the oxygen gradients between the vascular and tissue compartments were reduced by the cerebral perfusion pressure intervention. CONCLUSIONS: Cerebral perfusion pressure augmentation significantly increased levels of brain tissue oxygen and significantly reduced regional oxygen extraction fraction. However, these changes did not translate into predictable changes in regional chemistry. Our results suggest that the ischemic level of brain tissue oxygen may lie at a level below 14 mm Hg (1.8 kPa); however, the data do not allow us to be more specific.

Adolescent↗

Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial.

BACKGROUND AND PURPOSE: Statins may improve cerebral vasomotor reactivity through cholesterol-dependent and -independent mechanisms. A phase II randomized controlled trial was conducted to examine the hypothesis that acute pravastatin treatment could improve cerebrovascular autoregulation and reduce vasospasm-related complications after aneurysmal subarachnoid hemorrhage (SAH). METHODS: A total of 80 aneurysmal SAH (aSAH) patients (18 to 84 years of age) within 72 hours from the ictus were randomized equally to receive either oral pravastatin (40 mg) or placebo daily for up to 14 days. Primary end points were the incidence, duration, and severity of cerebral vasospasm, and duration of impaired autoregulation estimated from transcranial Doppler ultrasonography. Secondary end points were the incidence of vasospasm-related delayed ischemic deficits (DIDs) and disability at discharge. RESULTS: Prerandomization characteristics were balanced between the 2 groups. No treatment-related complication was observed. The incidences of vasospasm and severe vasospasm were reduced by 32% (P=0.006) and 42% (P=0.044), respectively, and the duration of severe vasospasm was shortened by 0.8 days (P=0.068) in the pravastatin group. These measurements were maximal on the ipsilateral side of ruptured aneurysms. The duration of impaired autoregulation was shortened bilaterally (P< or =0.01), and the incidence of vasospasm-related DIDs and mortality were decreased by 83% (P<0.001) and 75% (P=0.037), respectively, in the pravastatin group. CONCLUSIONS: Acute treatment with pravastatin after aSAH is safe and ameliorates cerebral vasospasm, improves cerebral autoregulation, and reduces vasospasm-related DID. Unfavorable outcome at discharge was reduced primarily because of a reduction in overall mortality. This is the first demonstration of clinical benefits with immediate statin therapy for an acute cerebrovascular disorder.

Adolescent↗

Age, intracranial pressure, autoregulation, and outcome after brain trauma.

OBJECT: The object of this study was to investigate whether a failure of cerebrovascular autoregulation contributes to the relationship between age and outcome in patients following head injury. METHODS: Data obtained from continuous bedside monitoring of intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP = ABP - ICP) in 358 patients with head injuries and intermittent monitoring of transcranial Doppler blood flow velocity (FV) in the middle cerebral artery in 237 patients were analyzed retrospectively. Indices used to describe cerebral autoregulation and pressure reactivity were calculated as correlation coefficients between slow waves of systolic FV and CPP (autoregulation index [ARI]) and between ABP and ICP (pressure reactivity index [PRI]). Older patients had worse outcomes after brain trauma than younger patients (p = 0.00001), despite the fact that the older patients had higher initial Glasgow Coma Scale scores (p = 0.006). When age was considered as an independent variable, it appeared that ICP decreased with age (p = 0.005), resulting in an increasing mean CPP (p = 0.0005). Blood FV was not dependent on age (p = 0.58). Indices of autoregulation and pressure reactivity demonstrated a deterioration in cerebrovascular control with advancing age (PRI: p = 0.003; ARI: p = 0.007). CONCLUSIONS: An age-related decline in cerebrovascular autoregulation was associated with a relative deterioration in outcome in elderly patients following head trauma.

Adolescent↗

Sustained moderate reductions in arterial CO2 after brain trauma time-course of cerebral blood flow velocity and intracranial pressure.

OBJECTIVE: In healthy volunteers cerebral blood flow starts to recover towards baseline within a few minutes of continued hyperventilation due to normalisation of perivascular pH. We investigated the time-course of changes in middle cerebral artery mean flow velocity (FVm) and intracranial pressure (ICP) in head-injured patients during sustained moderate reductions in arterial partial pressure of CO(2) (PaCO(2)). DESIGN: Observational study. PATIENTS: Twenty-seven sedated, mechanically ventilated patients with severe head injury. INTERVENTIONS: Measurements were made during and after routine determination of CO(2)-reactivity: an acute 20% increase in respiratory minute volume was followed by a 10-min stabilisation period and 50 min of continued moderate hyperventilation at a constant PaCO(2) (>3.5 kPa). MEASUREMENTS AND RESULTS: FVm was monitored with transcranial Doppler, ICP was monitored with intraparenchymal probes. During the 50-min period with stable PaCO(2) FVm increased in 36% of patients. All other patients showed a decline in FVm over the same time period. Overall FVm recovery was -0.03+/-0.14%.min(-1). The time-course of ICP changes was significantly different from that of FVm, with ICP reaching its lowest value earlier than FVm (23+/-12 vs 37+/-20 min; P = 0.001) and returning more rapidly towards baseline than FVm (0.23+/-0.23 vs -0.03+/-0.14%.min(-1); P< 0.0001). CONCLUSIONS: Head-injured patients may adapt differently to hyperventilation than healthy volunteers. Potentially harmful reductions in cerebral blood flow may persist beyond the duration of useful ICP reduction.

Adolescent↗

Does induced hypertension reduce cerebral ischaemia within the traumatized human brain?

Recent changes in published guidelines for the management of patients with severe head injury are based on data showing that aggressive maintenance of cerebral perfusion pressure (CPP) can worsen outcome due to extracranial complications of therapy. However, it remains unclear whether CPP augmentation could reduce cerebral ischaemia, a finding which might prompt the search for CPP augmentation protocols that avoid these extracranial complications. We studied 10 healthy volunteers and 20 patients within 6 days of closed head injury. All subjects underwent imaging of cerebral blood flow (CBF), blood volume (CBV), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) using 15O PET. In addition, for patients, the EEG power ratio index (PRI), burst suppression ratio and somatosensory evoked potentials (SEP) were obtained and CPP was increased from 68 +/- 4 to 90 +/- 4 mmHg using an infusion of norepinephrine and measurements were repeated. Following elevation of CPP, CBF and CBV were increased and CMRO2 and OEF were reduced (P < 0.001 for all comparisons). Regions with a reduction in CMRO2 were associated with the greatest reduction in OEF (r2 = 0.3; P < 0.0001). Although CPP elevation produced a significant fall in the ischaemic brain volume (IBV) (from 15 +/- 16 to 5 +/- 4 ml; P < 0.01) and improved flow metabolism coupling, the IBV was small and clinically insignificant in the majority of these patients. However, the reduction in IBV was directly related to the baseline IBV (r2 = 0.97; P < 0.001) and patients with large baseline IBV showed substantial and clinically significant reductions. CPP augmentation increased the EEG PRI (5.0 +/- 1.5 versus 4.3 +/- 1.4, P < 0.01), implying an overall decrease in neural activity, but these changes did not correlate with the reduction in CMRO2 and there was no change in SEP cortical amplitude (N20-P27). These data provide support for recent changes in recommended CPP levels for head injury management across populations of patients with significant head injury. However, they do not provide guidance on whether the intervention may be more appropriate at earlier stages after injury, or in patients selected because of high baseline IBV. It also remains unclear whether CPP values below 65 mmHg can be safely used in this population. Clarification of the significance of a reduction in CMRO2 and neuronal electrical function will require further study.

Adolescent↗

Tissue signature characterisation of diffusion tensor abnormalities in cerebral gliomas.

The inherent invasiveness of malignant cells is a major determinant of the poor prognosis of cerebral gliomas. Diffusion tensor MRI (DTI) can identify white matter abnormalities in gliomas that are not seen on conventional imaging. By breaking down DTI into its isotropic (p) and anisotropic (q) components, we can determine tissue diffusion "signatures". In this study we have characterised these abnormalities in peritumoural white matter tracts. Thirty-five patients with cerebral gliomas and seven normal volunteers were imaged with DTI and T2-weighted sequences at 3 T. Displaced, infiltrated and disrupted white matter tracts were identified using fractional anisotropy (FA) maps and directionally encoded colour maps and characterised using tissue signatures. The diffusion tissue signatures were normal in ROIs where the white matter was displaced. Infiltrated white matter was characterised by an increase in the isotropic component of the tensor (p) and a less marked reduction of the anisotropic component (q). In disrupted white matter tracts, there was a marked reduction in q and increase in p. The direction of water diffusion was grossly abnormal in these cases. Diffusion tissue signatures may be a useful method of assessing occult white matter infiltration.

Adult↗

Critical closing pressure in subarachnoid hemorrhage: effect of cerebral vasospasm and limitations of a transcranial Doppler-derived estimation.

BACKGROUND AND PURPOSE: Critical closing pressure (CCP) is thought to be jointly influenced by intracranial pressure and cerebrovascular tone. We examined how CCP is affected by cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: In 15 patients with vasospasm of the middle cerebral artery, CCP was calculated using 2 methods previously reported (ad modem Aaslid and Michel, indexed CCP(Aaslid) and CCP(Michel), respectively) based on data of arterial blood pressure and flow velocity (FV) as assessed by transcranial Doppler. RESULTS: CCP decreased significantly (P<0.05) during vasospasm (CCP(Aaslid)=6.3+/-22.9 mm Hg, CCP(Michel)=14.9+/-16.5 mm Hg, mean+/-SD) as compared with baseline (CCP(Aaslid)=24.4+/-20.3 mm Hg, CCP(Michel)=27.8+/-19.4 mm Hg). This was not attributable to ICP, which remained unaffected by vasospasm. In addition, CCP was significantly lower on the side of vasospasm (CCP(Aaslid)=11.9+/-24.2 mm Hg, CCP(Michel)=18.4+/-19.6 mm Hg) as compared with the contralateral nonvasospastic side (CCP(Aaslid)=24.7+/-22.3 mm Hg, CCP(Michel)=28.2+/-18.0 mm Hg). CONCLUSIONS: Assuming that autoregulation-related distal vasodilatation outweighs proximal vasospasm, CCP should decrease. Alternatively, CCP might have increased during vasospasm as the tension of big vessels increase, but the turbulence occurring during vasospasm may have impaired the linear relationship between pressure and FV, thus leading to a marked underestimation of CCP. In conclusion, interpretation of CCP in vasospasm is difficult and may be overshadowed by nonlinear hemodynamic effects.

Adult↗

Pattern of white matter regional cerebral blood flow and autoregulation in normal pressure hydrocephalus.

The mean cerebral blood flow (CBF) has generally been demonstrated to be lower in normal pressure hydrocephalus (NPH) than in normal controls. We investigated the distribution of the regional peri- and paraventricular white matter CBF (WM CBF) in NPH at baseline and during a controlled rise in intracranial pressure (ICP). Twelve patients with idiopathic NPH (mean age 69 years) underwent a CSF infusion study. CBF was measured by H2(15)O PET at baseline and then during the steady-state plateau of raised ICP. The PET images were co-registered and resliced to 3D structural T1-weighted MRIs. Ten healthy normal volunteers served as control subjects for baseline CBF determination only. Profiles of the regional distribution of the baseline WM CBF and of the percentage change in WM CBF as a function of distance from the ventricles were plotted. The global mean baseline CBF in patients (28.4 +/- 5.2 ml/100 ml/min) was lower than in the control subjects (33 +/- 5.4 ml/100 ml/min) (P < 0.005). In patients, the profile of the regional WM CBF at baseline showed an increase with distance from the ventricles (P < 0.0001), with a maximal reduction adjacent to the ventricles and progressive normalization with distance, whereas in controls no relationship was apparent (P = 0.0748). In 10 patients, the rise in ICP during the infusion produced a fall in cerebral perfusion pressure (CPP) and a significant decrease of the global mean CBF from 27.6 +/- 3.1 to 24.5 +/- 2.9 ml/100 ml/min (P < 0.0001). The profile of the percentage changes in regional WM CBF in patients showed a U-shaped relationship with distance from the ventricles (P = 0.0007), with a maximal decrease skewed on the side of the lateral ventricles at around a mean distance of 9 mm. The WM CBF is reduced in NPH, with an abnormal gradient from the lateral ventricles towards the subcortical WM. An excessive decrease in CBF is brought about by reductions in CPP and appears to be maximal in the paraventricular watershed region. These results are discussed in the light of previous hypotheses concerning the aetiology of periventricular CBF reduction in NPH.

Aged↗

Cerebrospinal fluid dynamics.

Hydrocephalus is far more complicated than a simple disorder of CSF circulation. Historically, it has been diagnosed using clinical and psychomotor assessment plus brain imaging. The role of physiological measurement to aid diagnosis becomes more appreciated in current clinical practice. This has been reflected by recently formulated guidelines for the management of normal pressure hydrocephalus. Clinical measurement in hydrocephalus is mainly related to intracranial pressure (ICP) and cerebral blood flow. This review lists and discusses most common forms of the methods: CSF infusion study, overnight ICP monitoring, assessment of slow ICP waves, testing pressure reactivity, cerebral autoregulation, CO2 reactivity and PET-CBF studies combined with MRI co-registration. The basics of CSF dynamics modelling are presented and the principles of the assessment of functioning of the implanted hydrocephalus shunts are also discussed. The descriptions of multiple forms of measurement along with clinical illustrations are mainly based on in-house experience of a multidisciplinary group of scientists and clinicians from Cambridge, UK.

Brain↗

Changes in cerebral blood flow during cerebrospinal fluid pressure manipulation in patients with normal pressure hydrocephalus: a methodological study.

The combination of cerebral blood flow measurement using (15)O-water positron emission tomography with magnetic resonance coregistration and CSF infusion studies was used to study the global and regional changes in CBF with changes in CSF pressure in 15 patients with normal pressure hydrocephalus. With increases in CSF pressure, there was a variable increase in arterial blood pressure between individuals and global CBF was reduced, including in the cerebellum. Regionally, mean CBF decreased in the thalamus and basal ganglia, as well as in white matter regions. These reductions in CBF were significantly correlated with changes in the CSF pressure and with proximity to the ventricles. A three-dimensional finite-element analysis was used to analyze the effects on ventricular size and the distribution of stress during infusion. To study regional cerebral autoregulation in patients with possible normal pressure hydrocephalus, a sensitive CBF technique is required that provides absolute, not relative normalized, values for regional CBF and an adequate change in cerebral perfusion pressure must be provoked.

Aged↗

Direct comparison of cerebrovascular effects of norepinephrine and dopamine in head-injured patients.

OBJECTIVE: To directly compare the cerebrovascular effects of norepinephrine and dopamine in patients with acute traumatic brain injury. DESIGN: Prospective randomized crossover trial. SETTING: Neurosciences critical care unit of a university hospital. PATIENTS: Ten acutely head-injured patients requiring vasoactive drugs to maintain a cerebral perfusion pressure of 65 mm Hg. INTERVENTIONS: Patients were randomized to start the protocol with either norepinephrine or dopamine. Using an infusion of the allocated drug, cerebral perfusion pressure was adjusted to 65 mm Hg. After 20 mins of data collection, cerebral perfusion pressure was increased to 75 mm Hg by increasing the infusion rate of the vasoactive agent. After 20 mins of data collection, cerebral perfusion pressure was increased to 85 mm Hg and again data were collected for 20 mins. Subsequently, the infusion rate of the vasoactive drug was reduced until a cerebral perfusion pressure of 65 mm Hg was reached and the drug was exchanged against the other agent. The protocol was then repeated. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure were monitored and cerebral blood flow was estimated with transcranial Doppler. Norepinephrine led to predictable and significant increases in flow velocity for each step increase in cerebral perfusion pressure (57.5+/-19.9 cm x sec, 61.3+/-22.3 cm x sec, and 68.4+/-24.8 cm x sec at 65, 75, and 85 mm Hg, respectively; p <.05 for all three comparisons), but changes with dopamine were variable and inconsistent. There were no differences between absolute values of flow velocity or intracranial pressure between the two drugs at any cerebral perfusion pressure level. CONCLUSIONS: Norepinephrine may be more predictable and efficient to augment cerebral perfusion in patients with traumatic brain injury.

Adult↗

Diffusion limited oxygen delivery following head injury.

OBJECTIVE: To use a range of techniques to explore diffusion limitation as a mechanism of cellular hypoxia in the setting of head injury. DESIGN: A prospective interventional study. SETTING: A specialist neurocritical care unit. PATIENTS: Thirteen patients within 7 days of closed head injury underwent imaging studies. Tissue for ultrastructural studies was obtained from a cohort of seven patients who required surgery. INTERVENTIONS: Cerebral tissue PO2 (PtO2) was obtained using a multiple-variable sensor, and images of oxygen extraction fraction (OEF), derived from positron emission tomography, were used to calculate cerebral venous PO2 (PvO2). These data were used to derive the PvO2-PtO2 gradient in a region of interest around the sensor, which provided a measure of the efficiency of microvascular oxygen delivery. Measurements were repeated after PaCO2 was reduced from 37 +/- 3 to 29 +/- 3 torr (4.9 +/- 0.4 to 3.9 +/- 0.4 kPa) to assess the ability of the microvasculature to increase oxygen unloading during hypocapnia-induced hypoperfusion. Pericontusional tissue was submitted to electron microscopy to illustrate the structural correlates of physiologic findings. MEASUREMENTS AND MAIN RESULTS: Tissue regions with hypoxic levels of PtO2 (<10 torr) had similar levels of PvO2 compared with nonhypoxic areas and hence displayed larger PvO2-PtO2 gradients (27 +/- 2 vs. 9 +/- 8 torr, p <.001). Despite similar cerebral blood flow reductions with hyperventilation, hypoxic regions achieved significantly smaller OEF increases compared with normoxic regions (7 +/- 5 vs. 16 +/- 6 %, p <.05). Pericontusional tissue showed varying degrees of endothelial swelling, microvascular collapse, and perivascular edema. CONCLUSIONS: Increased diffusion barriers may reduce cellular oxygen delivery following head injury and attenuate the ability of the brain to increase oxygen extraction in response to hypoperfusion. Global or regional OEF underestimates tissue hypoxia due to such mechanisms.

Adolescent↗

In vivo imaging of cardiovascular endothelin receptors using the novel radiolabelled antagonist [18F]-SB209670 and positron emission tomography (microPET).

The aim of this study was to develop an F-labelled analogue of SB209670 with subnanomolar affinity for the endothelin receptor and to test whether it would have the required pharmacokinetic properties to permit binding and imaging of endothelin receptors in rat heart in vivo using small animal positron emission tomography (PET) imaging. [18F]-SB209670 could be produced in a total radiochemical yield of 14.9 +/- 3.8% in 162 +/- 7 minutes (n = 6). The radiochemical purity of the isolated radioligand was 99% and the specific activity was 100-150 GBq/micromol. In vitro characterization using ligand-binding assays demonstrated that [18F]-SB209670 bound with a single subnanomolar affinity to human heart tissue (n = 3) with a KD = 0.67 +/- 0.14 nM and a Bmax = 168.3 +/- 29.3 fmol/mg protein. The binding was time-dependent with a half-time (t(1/2)) for association of 3.8 minutes and an association rate constant (kobs) of 0.182 +/- 0.032/min. In vivo distribution in the rat was studied using microPET. Dynamic imaging revealed a fast clearance of [F]-SB209670 from the circulation by the liver, indicative of a high degree of metabolism. However, visualization of uptake in the rat heart was achievable and dynamic PET data together with the in vitro results suggest that [F]-SB209670 binds rapidly and primarily to endothelin-A receptors in the heart.

Animals↗

Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values.

Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.

Aged↗