Current epidemiology of cerebrospinal fluid shunt surgery in the UK and Ireland (2004-2013).

OBJECTIVES: To determine current epidemiology and clinical characteristics of cerebrospinal fluid (CSF) shunt surgery, including revisions. METHODS: A retrospective, multicentre, registry-based study was conducted based on 10 years' data from the UK Shunt Registry, including primary and revision shunting procedures reported between 2004 and 2013. Incidence rates of primary shunts, descriptive statistics and shunt revision rates were calculated stratified by age group, geographical region and year of operation. RESULTS: 41 036 procedures in 26 545 patients were submitted during the study period, including 3002 infants, 4389 children and 18 668 adults. Procedures included 20 947 (51.0%) primary shunt insertions in 20 947 patients, and 20 089 (49.0%) revision procedures. Incidence rates of primary shunt insertions for infants, children and adults were 39.5, 2.4 and 3.5 shunts per 100 000 person-years, respectively. These varied by geographical subregion and year of operation. The most common underlying diagnoses were perinatal intraventricular haemorrhage (35.3%) and malformations (33.9%) in infants, tumours (40.5%) and malformations (16.3%) in children, and tumours (24.6%), post-haemorrhagic hydrocephalus (16.2%) and idiopathic normal pressure hydrocephalus (14.2%) in adults. Ninety-day revision rates were 21.9%, 18.6% and 12.8% among infants, children and adults, respectively, while first-year revision rates were 31.0%, 25.2% and 17.4%. The main reasons for revision were underdrainage and infection, but overdrainage and mechanical failure continue to pose problems. CONCLUSIONS: Our report informs patients, carers, clinicians, providers and commissioners of healthcare, researchers and industry of the current epidemiology of shunting for CSF disorders, including the potential risks of complications and frequency of revision.

Hydrocephalus shunt technology: 20 years of experience from the Cambridge Shunt Evaluation Laboratory.

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.

Cessation of diastolic cerebral blood flow velocity: the role of critical closing pressure.

BACKGROUND: Reducing cerebral perfusion pressure (CPP) below the lower limit of autoregulation (LLA) causes cerebral blood flow (CBF) to become pressure passive. Further reductions in CPP can cause cessation of CBF during diastole. We hypothesized that zero diastolic flow velocity (FV) occurs when diastolic blood pressure becomes less than the critical closing pressure (CrCP). METHODS: We retrospectively analyzed studies of 34 rabbits with CPP below the LLA, induced with pharmacologic sympathectomy (N = 23) or cerebrospinal fluid infusion (N = 11). Basilar artery blood FV and cortical Laser Doppler Flow (LDF) were monitored. CrCP was trended using a model of cerebrovascular impedance. The diastolic closing margin (DCM) was monitored as the difference between diastolic blood pressure and CrCP. LDF was recorded for DCM values greater than and less than zero. RESULTS: Arterial hypotension caused a reduction of CrCP (p < 0.001), consistent with decreased wall tension (p < 0.001) and a drop in intracranial pressure (ICP; p = 0.004). Cerebrospinal infusion caused an increase of CrCP (p = 0.002) accounted for by increasing ICP (p < 0.001). The DCM was compromised by either arterial hypotension or intracranial hypertension (p < 0.001 for both). When the DCM reached zero, diastolic FV ceased for a short period during each heart cycle (R = 0.426, p < 0.001). CBF pressure passivity accelerated when DCM decreased below zero (from 1.51 ± 0.51 to 2.17 ± 1.17 % ΔLDF/ΔmmHg; mean ± SD; p = 0.010). CONCLUSIONS: The disappearance of diastolic CBF below LLA can be explained by DCM reaching zero or negative values. Below this point the decrease in CBF accelerates with further decrements of CPP.

The SILVER (Silver Impregnated Line Versus EVD Randomized trial): a double-blind, prospective, randomized, controlled trial of an intervention to reduce the rate of external ventricular drain infection.

BACKGROUND: Cerebrospinal fluid (CSF) infections associated with external ventricular drain (EVD) placement attract major consequences. Silver impregnation of catheters attempts to reduce infection. OBJECTIVE: To assess the efficacy of silver catheters against CSF infection. METHODS: We performed a randomized, controlled trial involving 2 neurosurgical centers (June 2005 to September 2009). A total of 356 patients requiring an EVD were assessed for eligibility; 325 patients were enrolled and randomized (167 plain, 158 silver); 278 patients were analyzed (140 plain, 138 silver). The primary outcome measure was CSF infection as defined by organisms seen on Gram stain or isolated by culture. Secondary outcome measures included ventriculoperitoneal (VP) shunting. RESULTS: There was a significant difference in infection risk between the 2 study arms: 21.4% (30/140) for plain catheters vs 12.3% (17/138) for silver catheters (P = .0427; 95% confidence interval [CI]: 1.015-3.713). Patients who had an EVD infection had more than double the risk of requiring a VP shunt compared with patients without an EVD infection (45.7% [21/46] vs 19.7% [45/229], respectively, P = .0002; 95% CI: 1.766-6.682). There was also a significant difference in VP shunt risk with infection: plain (55.2%; 16/29) vs the silver arm (29.4%; 5/17); P = .0244 (95% CI: 1.144-11.695). A multivariate analysis demonstrated that infection risk was increased by duration of EVD placement (odds ratio: 1.160), spontaneous intracranial hemorrhage (odds ratio 4.958) and decreased by silver catheters (odds ratio: 0.423). CONCLUSION: The study provides Class I evidence that silver-impregnated catheters reduce CSF infection.

Dynamic in vivo imaging of receptors in small animals using positron emission tomography.

Positron emission tomography (PET) is a functional imaging technique with the potential to image and quantify receptors in vivo with high sensitivity. PET has been used extensively to study major neurotransmitters such as dopamine, serotonin, and benzodiazepine in humans as well as proving to be a very powerful tool to accelerate development and assessment of existing and novel drugs. With the recent development of dedicated PET scanners for small animals, such as the microPET, it is now possible to perform functional imaging in small animals such as rodents at high resolution. This will allow the study of animal models of disease and longitudinal studies in these models to monitor disease progression or effect of treatment in the same animal. Furthermore, the complete pharmacokinetics of a drug as well as pharmacodynamic information can be obtained in a single animal. Thus, small animal imaging will significantly reduce the number of animals needed for this type of experiment as well as reducing the effect of inter-animal variation. Experimental protocols in small animal imaging potentially can be very labor intensive. In this chapter, we discuss methods and practical aspects related to this type of experiment using the microPET system.

Preventing flow-metabolism uncoupling acutely reduces axonal injury after traumatic brain injury.

We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. Local cerebral metabolic rate for glucose (LCMRglc) and LCBF measurements were obtained 3 h post-trauma in the same rat via ¹8F-fluorodeoxyglucose and ¹4C-iodoantipyrine co-registered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections, and in additional groups at 24 h used to assess different populations of injured axons stereologically. ACZ treatment significantly and globally elevated LCBF twofold above untreated-injured rats at 3 h (p<0.05), but did not significantly affect LCMRglc. As a result, ipsilateral LCMRglc:LCBF ratios were reduced by twofold to sham-control levels, and the density of ß-APP-stained axons at 24 h was significantly reduced in most brain regions compared to the untreated-injured group (p<0.01). Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3-24 h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of ß-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons.

Cerebrovascular time constant: dependence on cerebral perfusion pressure and end-tidal carbon dioxide concentration.

OBJECTIVE: The cerebrovascular time constant (τ) describes the time to establish a change in cerebral blood volume after a step transient in arterial blood pressure (ABP). We studied the relationship between τ, ABP, intracranial pressure (ICP), and end-tidal carbon dioxide concentration (EtCO2). METHOD: Recordings from 46 anaesthetized, paralysed and ventilated New Zealand rabbits were analysed retrospectively. ABP was directly monitored in the femoral artery, transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) from the basilar artery, and ICP using an intraparenchymal sensor. In nine animals end-tidal CO2 (EtCO2) was monitored continuously. ABP was decreased with injection of trimetophan (n = 11) or haemorrhage (n = 6) and increased by boluses of dopamine (n = 11). ICP was increased by infusion of normal saline into the lumbar cerebrospinal fluid space (n = 9). Changes in cerebral compliance (C(a)) were estimated as a ratio of the pulse amplitude of the cerebral arterial blood volume (CBV) and the pulse amplitude of ABP. Changes in cerebrovascular resistance (CVR) were expressed as mean ABP or cerebral perfusion pressure (CPP) divided by mean CBFV. Time constant τ was calculated as the product of CVR and C(a). RESULTS: The time constant changed inversely to the direction of the change in ABP (during arterial hypo- and hypertension) and CPP (during intracranial hypertension). C(a) increased with decreasing CPP, while CVR decreased. During a decrease in CPP, changes in C(a) exceeded changes in CVR. In contrast, during hypercapnia, the decrease in CVR was more pronounced than the increase in C(a), resulting in a decrease in τ. CONCLUSION: Cerebrovascular time constant τ is modulated by ABP, ICP, and EtCO2.

Positron emission tomography of [18F]-big endothelin-1 reveals renal excretion but tissue-specific conversion to [18F]-endothelin-1 in lung and liver.

BACKGROUND AND PURPOSE: Big endothelin-1 (ET-1) circulates in plasma but does not bind to ET receptors until converted to ET-1 by smooth muscle converting enzymes. We hypothesized that tissue-specific conversion of [(18)F]-big ET-1 to [(18)F]-ET-1 could be imaged dynamically in vivo within target organs as binding to ET receptors. METHODS: [(18)F]-big ET-1 conversion imaged in vivo following infusion into rats using positron emission tomography (PET). KEY RESULTS: [(18)F]-big ET-1 was rapidly cleared from the circulation (t(1/2)= 2.9 +/- 0.1 min). Whole body microPET images showed highest uptake of radioactivity in three major organs. In lungs and liver, time activity curves peaked within 2.5 min, then plateaued reaching equilibrium after 10 min, with no further decrease after 120 min. Phosphoramidon did not alter half life of [(18)F]-big ET-1 but uptake was reduced in lung (42%) and liver (45%) after 120 min, consistent with inhibition of enzyme conversion and reduction of ET-1 receptor binding. The ET(A) antagonist, FR139317 did not alter half-life of [(18)F]-big ET-1 (t(1/2)= 2.5 min) but radioactivity was reduced in all tissues except for kidney consistent with reduction in binding to ET(A) receptors. In kidney, however, the peak in radioactivity was higher but time to maximum accumulation was slower ( approximately 30 min), which was increased by phosphoramidon, reflecting renal excretion with low conversion and binding to ET receptors. CONCLUSIONS AND IMPLICATIONS: A major site for conversion was within the vasculature of the lung and liver, whereas uptake in kidney was more complex, reflecting excretion of [(18)F]-big ET-1 without conversion to ET-1.

Hypertonic saline in patients with poor-grade subarachnoid hemorrhage improves cerebral blood flow, brain tissue oxygen, and pH.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia and infarction due to reduced CBF remains the leading cause of poor outcome after aneurysmal subarachnoid hemorrhage. Hypertonic saline (HS) is associated with an increase in CBF. This study explores whether CBF enhancement with HS in patients with poor-grade subarachnoid hemorrhage is associated with improved cerebral tissue oxygenation. METHODS: Continuous monitoring of arterial blood pressure, intracranial pressure, cerebral perfusion pressure, brain tissue oxygen, carbon dioxide, pH, and middle cerebral artery flow velocity was performed in 44 patients. Patients were given an infusion (2 mL/kg) of 23.5% HS. In 16 patients, xenon CT scanning was also performed. CBF in a region surrounding the tissue oxygen sensor was calculated. Data are mean+/-SD. RESULTS: Thirty minutes postinfusion, a significant increase in arterial blood pressure, cerebral perfusion pressure, flow velocity, brain tissue pH, and brain tissue oxygen was seen together with a decrease in intracranial pressure (P<0.05). Intracranial pressure remained reduced for >300 minutes and flow velocity elevated for >240 minutes. A significant increase in brain tissue oxygen persisted for 240 minutes. Average baseline regional CBF was 33.9+/-13.5 mL/100 g/min, rising by 20.3%+/-37.4% (P<0.05) after HS. Patients with favorable outcome responded better to HS in terms of increased CBF, brain tissue oxygen, and pH and reduced intracranial pressure compared with those with an unfavorable outcome. A sustained increase in brain tissue oxygen (beyond 210 minutes) was associated with favorable outcome (P<0.023). CONCLUSIONS: HS augments CBF in patients with poor-grade subarachnoid hemorrhage and significantly improves cerebral oxygenation for 4 hours postinfusion. Favorable outcome is associated with an improvement in brain tissue oxygen beyond 210 minutes.

FDG-PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis.

The presence of activated macrophages is an important predictor of atherosclerotic plaque rupture. In this study, our aim was to determine the accuracy of (18)F- fluorodeoxyglucose (FDG) microPET imaging for quantifying aortic wall macrophage content in a rabbit model of atherosclerosis. Rabbits were divided into a control group and two groups post aortic balloon injury: 6 months high-cholesterol diet (HC); and 3 months HC followed by 3 months low-cholesterol diet plus statin (LCS). In vivo and ex vivo microPET, ex vivo well counting and histological quantification of the atherosclerotic aortas were performed for all groups. Macrophage density was greater in the HC group than the LCS group (5.1 +/- 1.4% vs. 0.6 +/- 0.7%, P < 0.001) with a trend towards greater macrophage density in LCS compared to controls (P = 0.08). There was a strong correlation across all groups between macrophage density and standardized uptake value (SUV) derived from ex vivo microPET (r = 0.95, P < 0.001) and well counting (r = 0.96, P < 0.001). Ex vivo FDG SUV was significantly different between the three groups (P < 0.001). However, the correlation between in vivo microPET FDG SUV and macrophage density was insignificant (r = 0.16, P = 0.57) with no statistical differences in FDG SUV seen between the three groups. This study confirms that in an animal model of inflamed and non-inflamed atherosclerosis, significant differences in FDG SUV allow differentiation of highly inflamed atherosclerotic aortas from those stabilized by statin therapy and low cholesterol diet and controls.

Efficacy of antibiotic-impregnated shunt catheters in reducing shunt infection: data from the United Kingdom Shunt Registry.

OBJECT: In recent years CSF shunt catheters impregnated with rifampicin and clindamycin have been introduced to the United Kingdom (UK) market. These catheters have been shown to be effective in vitro against cultures of Staphylococcus epidermidis. The authors used data collected by the UK Shunt Registry to assess the efficacy of antibiotic-impregnated catheters (AICs) against shunt infection by using a matched-pair study design. METHODS: The UK Shunt Registry contains data on nearly 33,000 CSF shunt-related procedures. The authors identified 1139 procedures in which impregnated catheters had been used, and accurate information was known about diagnosis, number of revisions, sex, and age in these cases. The database was ordered chronologically and searched forward and backward for cases with these same characteristics but involving conventional catheters. Matches were found for 994 procedures. RESULTS: Among the 994 procedures in which AICs had been used, 30 shunts were subsequently revised because of shunt infection. Among the 994 controls, 47 were subsequently revised for infection (p = 0.048, chi-square test). CONCLUSIONS: The UK Shunt Registry does not collect data on causative organisms, and the surgeon is relied on entirely for the diagnosis of infection. However, with the large number of matched pairs evaluated, the authors attempted to reduce bias to a minimum. Their data suggest that AICs have the potential to significantly reduce shunt infections.

Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.

BACKGROUND: Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes. METHODS: We did a randomised controlled trial at one UK centre between November, 2004, and November, 2007. 269 patients aged 18 years and older with a chronic subdural haematoma for burr-hole drainage were assessed for eligibility. 108 were randomly assigned by block randomisation to receive a drain inserted into the subdural space and 107 to no drain after evacuation. The primary endpoint was recurrence needing redrainage. The trial was stopped early because of a significant benefit in reduction of recurrence. Analyses were done on an intention-to-treat basis. This study is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 97314294). FINDINGS: Recurrence occurred in ten of 108 (9.3%) people with a drain, and 26 of 107 (24%) without (p=0.003; 95% CI 0.14-0.70). At 6 months mortality was nine of 105 (8.6%) and 19 of 105 (18.1%), respectively (p=0.042; 95% CI 0.1-0.99). Medical and surgical complications were much the same between the study groups. INTERPRETATION: Use of a drain after burr-hole drainage of chronic subdural haematoma is safe and associated with reduced recurrence and mortality at 6 months. FUNDING: Academy of Medical Sciences, Health Foundation, and NIHR Biomedical Research Centre (Neurosciences Theme).

Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a Phase II randomized, double-blind, placebo-controlled trial. Clinical article.

OBJECT: Delayed ischemic deficits (DIDs), a major source of disability following aneurysmal subarachnoid hemorrhage (aSAH), are usually associated with severe cerebral vasospasm and impaired autoregulation. Systemic erythropoietin (EPO) therapy has been demonstrated to have neuroprotective properties acting via EPO receptors on cerebrovascular endothelia and ischemic neurons. In this trial, the authors explored the potential neuroprotective effects of acute EPO therapy following aSAH. METHODS: Within 72 hours of aSAH, 80 patients (age range 24-82 years) were randomized to receive intravenous EPO (30,000 U) or placebo every 48 hours for a total of 90,000 U. Primary end points were the incidence, duration, and severity of vasospasm and impaired autoregulation on transcranial Doppler ultrasonography. Secondary end points were incidence of DIDs and outcome at discharge and at 6 months. RESULTS: Randomization characteristics were balanced except for age, with the EPO group being older (mean age 59.6 vs 53.3 years, p=0.034). No differences were demonstrated in the incidence of vasospasm and adverse events; however, patients receiving EPO had a decreased incidence of severe vasospasm from 27.5 to 7.5% (p=0.037), reduced DIDs with new cerebral infarcts from 40.0 to 7.5% (p=0.001), a shortened duration of impaired autoregulation (ipsilateral side, p<0.001), and more favorable outcome at discharge (favorable Glasgow Outcome Scale score, p=0.039). Among the 71 survivors, the EPO group had fewer deficits measured with National Institutes of Health Stroke Scale (median Score 2 vs 6, p=0.008). CONCLUSIONS: This preliminary study showed that EPO seemed to reduce delayed cerebral ischemia following aSAH via decreasing severity of vasospasm and shortening impaired autoregulation.

Critical closing pressure: comparison of three methods.

Critical closing pressure (CCP) is an arterial pressure threshold below which small arterial vessels collapse. Our aim was to compare different methods to estimate CCP in the cerebrovascular circulation using the relationships between transcranial Doppler flow velocity (FV), laser-Doppler flux (LDF), and arterial blood pressure (ABP). A total of 116 experiments in rabbits were analyzed retrospectively. At the end of each recording, cardiac arrest (CA) was induced. Arterial blood pressure in femoral artery, basilar artery FV, cortical blood LDF, intracranial pressure (ICP) was recorded. Critical closing pressure was estimated using linear regression between decreasing mean ABP values, FV, and LDF during CA. In addition, CCP was calculated from FV waveform just before CA. The correlation between CCP evaluated using LDF and FV during CA was 0.98 (P<0.0001). The correlation between CCP measured during CA and CCP estimated from the transcranial Doppler ultrasonography (TCD) waveform was weaker (R=0.39; P<0.001), with CCP calculated from waveform being significantly greater than CCP from CA (median difference 9 mm Hg; P<0.003). Critical closing pressures obtained from FV waveform and CA correlated with mean ICP before CA (R=0.40; P=0.001). In conclusion strong correlation exists between CCP values obtained by means of FV and LDF during cardiac arrest. However, predictions of CCP using TCD waveform analysis show substantial differences from values of CCP recorded during cardiac arrest.

Modelling human drug abuse and addiction with dedicated small animal positron emission tomography.

Drug addiction is a chronically relapsing brain disorder, which causes substantial harm to the addicted individual and society as a whole. Despite considerable research we still do not understand why some people appear particularly disposed to drug abuse and addiction, nor do we understand how frequently co-morbid brain disorders such as depression and attention-deficit hyperactivity disorder (ADHD) contribute causally to the emergence of addiction-like behaviour. In recent years positron emission tomography (PET) has come of age as a translational neuroimaging technique in the study of drug addiction, ADHD and other psychopathological states in humans. PET provides unparalleled quantitative assessment of the spatial distribution of radiolabelled molecules in the brain and because it is non-invasive permits longitudinal assessment of physiological parameters such as binding potential in the same subject over extended periods of time. However, whilst there are a burgeoning number of human PET experiments in ADHD and drug addiction there is presently a paucity of PET imaging studies in animals despite enormous advances in our understanding of the neurobiology of these disorders based on sophisticated animal models. This article highlights recent examples of successful cross-species convergence of findings from PET studies in the context of drug addiction and ADHD and identifies how small animal PET can more effectively be used to model complex psychiatric disorders involving at their core impaired behavioural self-control.

Magnetic field interactions in adjustable hydrocephalus shunts.

OBJECT: Exposing patients with ventricular shunts to magnetic fields and MR imaging procedures poses a significant risk of unintentional changes in shunt settings. Shunt valves can also generate considerable imaging artifacts. The purpose of this study was to determine the magnetic field safety and MR imaging compatibility of 5 adjustable models of hydrocephalus shunts. METHODS: The Codman Hakim (regular and with SiphonGuard), Miethke ProGAV, Medtronic Strata, Sophysa Sophy and Polaris programmable valves were tested in a low-intensity magnetic field, and then translational attraction (TA), magnetic torque (MT), and volume of artifacts on T1-weighted spin echo (SE) and gradient echo (GE) pulse sequences in a 3-T MR imaging unit were measured. RESULTS: The ProGAV and Polaris valves were immune to unintentional reprogramming by magnetic fields up to 3 T. Other valves randomly changed settings, starting from the intensity of field: Sophy valve 24 mT, Strata valve 30 mT, and both Codman Hakim programmable valves from 42 mT. Shunt performances in the 3-T MR imaging unit are reported in the order of compatibility: 1) Codman Hakim regular, TA = 0.005 N, MT = 0.000 Nm, GE = 30 cm(3), SE = 2 cm(3); 2) Miethke ProGAV, TA = 0.001 N, MT = 1.4 x 10(3) Nm, GE = 231 cm(3), SE = 13 cm(3); 3) Codman Hakim with SiphonGuard, TA = 0.005 N, MT = 2.3 x 10(3) Nm, GE = 233 cm(3), SE = 19 cm(3); 4) Medtronic Strata, TA = 0.27 N, MT = 18.0 x 10(3) Nm, GE = 484 cm(3), SE = 86 cm(3); 5) Sophysa Sophy, TA = 0.82 N, MT = 38.9 x 10(3) Nm, GE = 758 cm(3), SE = 72 cm(3); and 6) Sophysa Polaris, TA = 0.80 N, MT = 39.6 x 10(3) Nm, GE = 954 cm(3), SE = 100 cm(3). CONCLUSIONS: All valves, with the exception of the Polaris and ProGAV models, are prone to unintentional reprogramming when exposed to heterogeneous magnetic fields stronger than 40 mT. All tested valves can be considered safe for 3-T MR imaging. All valves generated a distortion of the MR image, especially the GE sequences.

Investigation of the hydrodynamic properties of a new MRI-resistant programmable hydrocephalus shunt.

BACKGROUND: The Polaris valve is a newly released hydrocephalus shunt that is designed to drain cerebrospinal fluid (CSF) from the brain ventricles or lumbar CSF space. The aim of this study was to bench test the properties of the Polaris shunt, independently of the manufacturer. METHODS: The Polaris Valve is a ball-on-spring valve, which can be adjusted magnetically in vivo. A special mechanism is incorporated to prevent accidental re-adjustment by an external magnetic field. The performance and hydrodynamic properties of the valve were evaluated in the UK Shunt Evaluation Laboratory, Cambridge, UK. RESULTS: The three shunts tested showed good mechanical durability over the 3-month period of testing, and a stable hydrodynamic performance over 45 days. The pressure-flow performance curves, operating, opening and closing pressures were stable. The drainage rate of the shunt increased when a negative outlet pressure (siphoning) was applied. The hydrodynamic parameters fell within the limits specified by the manufacturer and changed according to the five programmed performance levels. Hydrodynamic resistance was dependant on operating pressure, changing from low values of 1.6 mmHg/ml/min at the lowest level to 11.2 mmHg/ml/min at the highest performance level. External programming proved to be easy and reliable. Even very strong magnetic fields (3 Tesla) were not able to change the programming of the valve. However, distortion of magnetic resonance images was present. CONCLUSION: The Polaris Valve is a reliable, adjustable valve. Unlike other adjustable valves (except the Miethke ProGAV valve), the Polaris cannot be accidentally re-adjusted by an external magnetic field.

Strategy for improved [(11)C]DAA1106 radiosynthesis and in vivo peripheral benzodiazepine receptor imaging using microPET, evaluation of [(11)C]DAA1106.

INTRODUCTION: The peripheral benzodiazepine receptor (PBR) has shown considerable potential as a clinical marker of neuroinflammation and tumour progression. [(11)C]DAA1106 ([(11)C]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)-acetamide) is a promising positron emission tomography (PET) radioligand for imaging PBRs. METHODS: A four-step synthetic route was devised to prepare DAA1123, the precursor for [(11)C]DAA1106. Two robust, high yielding methods for radiosynthesis based on [(11)C]-O-methylation of DAA1123 were developed and implemented on a nuclear interface methylation module, producing [(11)C]DAA1106 with up to 25% radiochemical yields at end-of-synthesis based on [(11)C]CH(3)I trapped. Evaluation of [(11)C]DAA1106 for in vivo imaging was performed in a rabbit model with microPET, and the presence of PBR receptor in the target organ was further corroborated by immunohistochemistry. RESULTS: The standard solution method produced 2.6-5.2 GBq (n=19) of [(11)C]DAA1106, whilst the captive solvent method produced 1.6-6.3 GBq (n=10) of [(11)C]DAA1106. Radiochemical purities obtained were 99% and specific radioactivity at end-of-synthesis was up to 200 GBq/micromol for both methods. Based on radiochemical product, shorter preparation times and simplicity of synthesis, the captive solvent method was chosen for routine productions of [(11)C]DAA1106. In vivo microPET [(11)C]DAA1106 scans of rabbit kidney demonstrated high levels of binding in the cortex. The subsequent introduction of nonradioactive DAA1106 (0.2 micromol) produced considerable displacement of the radioactive signal in this region. The presence of PBR in kidney cortex was further corroborated by immunohistochemistry. CONCLUSIONS: A robust, high yielding captive solvent method of [(11)C]DAA1106 production was developed which enabled efficacious in vivo imaging of PBR expressing tissues in an animal model.

Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement.

Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.