New detection configuration for low activity levels of PET tracers during the analysis of plasma samples.

A new radio-HPLC detection system for measuring radioactivity in plasma samples during Positron Emission Tomography [PET] studies was developed. It is based on detecting both the positron and one of the annihilation photons. The system focused on improving the measurement of radioactivity concentrations on an unmetabolized positron emitting a radiopharmaceutical [PER] in the presence of its radioactive metabolites, all containing the same positron emitter. This paper presents a new detection configuration that improves the minimal detectible activity (MDA), simplify the measuring systems and reduces the error caused by the metabolites. The detector is based on a plastic scintillator and a BGO scintillation crystal, that produces different light output spectra for signal and noise events. By summing the positron and the annihilated photon light outputs, different spectra are obtained for the metabolite and for the parent compound tracer and for tracer marked by different positron emitting isotopes. This new detection system can improve quantitative analysis of plasma samples. The spectrum change provides up to a three-fold improvement in sensitivity compared to the currently used detection systems that measure only the annihilation coincidence events. Results showed that for 11C the MDA was improved by approximately 520%. Furthermore, it provides the additional advantage of reliability by providing a method for separating the signal and noise readings from the gross detector readout. Accurate reconstruction algorithm of the signal was achieved over a wide measuring range even when the signal was only 5% of the gross measurement.

Current controversy: Triage of acute onset chest pain: now a biochemical rule-out test?

The management of coronary disease has moved forward with the application of more sensitive blood biomarkers for early detection alongside more structured symptom assessment, examination and serial ECG measures. However every episode of exertional chest pain isn't symptomatic coronary disease and given massive public awareness campaigns we now face a different management issue with undiagnosed chest pain sent as a 'rule-out' activity. These urgent referrals are often justified based on the management of the minority with unstable coronary disease without preliminary medical review or examination. Avoiding delay which is valuable in coronary patients may be irrelevant to the majority. The overall effectiveness of this pathway is unclear where the patient does not have coronary disease but also where superficial interpretation can be misleading through non-specificity. Do biomarker assays become the answer to every chest pain patient and has the basic assessment of the individual patient and a prior probability of disease no role to play? Does this activity represent a burden or an irrelevant dead end for non-coronary patients? We have asked for comment from two leading authorities on the evolving role and application of cardiac biomarker technologies in managing this considerable and common clinical dilemma.

Wave envelopes method for description of nonlinear acoustic wave propagation.

A novel, free from paraxial approximation and computationally efficient numerical algorithm capable of predicting 4D acoustic fields in lossy and nonlinear media from arbitrary shaped sources (relevant to probes used in medical ultrasonic imaging and therapeutic systems) is described. The new WE (wave envelopes) approach to nonlinear propagation modeling is based on the solution of the second order nonlinear differential wave equation reported in [J. Wójcik, J. Acoust. Soc. Am. 104 (1998) 2654-2663; V.P. Kuznetsov, Akust. Zh. 16 (1970) 548-553]. An incremental stepping scheme allows for forward wave propagation. The operator-splitting method accounts independently for the effects of full diffraction, absorption and nonlinear interactions of harmonics. The WE method represents the propagating pulsed acoustic wave as a superposition of wavelet-like sinusoidal pulses with carrier frequencies being the harmonics of the boundary tone burst disturbance. The model is valid for lossy media, arbitrarily shaped plane and focused sources, accounts for the effects of diffraction and can be applied to continuous as well as to pulsed waves. Depending on the source geometry, level of nonlinearity and frequency bandwidth, in comparison with the conventional approach the Time-Averaged Wave Envelopes (TAWE) method shortens computational time of the full 4D nonlinear field calculation by at least an order of magnitude; thus, predictions of nonlinear beam propagation from complex sources (such as phased arrays) can be available within 30-60 min using only a standard PC. The approximate ratio between the computational time costs obtained by using the TAWE method and the conventional approach in calculations of the nonlinear interactions is proportional to 1/N2, and in memory consumption to 1/N where N is the average bandwidth of the individual wavelets. Numerical computations comparing the spatial field distributions obtained by using both the TAWE method and the conventional approach (based on a Fourier series representation of the propagating wave) are given for circular source geometry, which represents the most challenging case from the computational time point of view. For two cases, short (2 cycle) and long (8 cycle) 2 MHz bursts, the computational times were 10 min and 15 min versus 2 h and 8 h for the TAWE method versus the conventional method, respectively.

Rigid-body transformation of list-mode projection data for respiratory motion correction in cardiac PET.

High-resolution cardiac PET imaging with emphasis on quantification would benefit from eliminating the problem of respiratory movement during data acquisition. Respiratory gating on the basis of list-mode data has been employed previously as one approach to reduce motion effects. However, it results in poor count statistics with degradation of image quality. This work reports on the implementation of a technique to correct for respiratory motion in the area of the heart at no extra cost for count statistics and with the potential to maintain ECG gating, based on rigid-body transformations on list-mode data event-by-event. A motion-corrected data set is obtained by assigning, after pre-correction for detector efficiency and photon attenuation, individual lines-of-response to new detector pairs with consideration of respiratory motion. Parameters of respiratory motion are obtained from a series of gated image sets by means of image registration. Respiration is recorded simultaneously with the list-mode data using an inductive respiration monitor with an elasticized belt at chest level. The accuracy of the technique was assessed with point-source data showing a good correlation between measured and true transformations. The technique was applied on phantom data with simulated respiratory motion, showing successful recovery of tracer distribution and contrast on the motion-corrected images, and on patient data with C15O and 18FDG. Quantitative assessment of preliminary C15O patient data showed improvement in the recovery coefficient at the centre of the left ventricle.

Improving secondary prevention in coronary bypass patients: closing the audit loop.

OBJECTIVES: To complete the audit loop assessing secondary preventative care of patients who had had coronary artery bypass graft (CABG) surgery. DESIGN: Two separate surveys of 1000 patients who had had CABG at the regional centre between 1988 and 1997, selected in 1998 and 2001. A single page questionnaire was sent to the patient's general practitioner. INTERVENTIONS: A list was sent to each general practice in Lothian, Scotland, of their patients on the CABG database and the results of the original survey. Lothian Health organised a project to contact and recall patients with cardiac disease in each practice. Sixty five (of 128) practices participated. MAIN OUTCOME MEASURES: Blood pressure, smoking status, serum cholesterol concentrations, and prescription of lipid lowering drugs and aspirin. RESULTS: 918 questionnaires (92%) in the second survey were returned describing 875 patients: 151 (17%) patients smoked and 752 patients (86%) took aspirin. Mean (SD) systolic blood pressure was lower in the second survey (142.5 (19.2) mm Hg in the first survey v 139.4 (19.1) mm Hg, p < 0.005). In our first survey 34% of patients had cholesterol concentrations less than target (5.2 mmol/l). This increased from 12% of patients operated on in 1988 to 50% of patients operated on in 1997 (Spearman rank correlation 0.77, p < 0.01). In the second survey this proportion had risen to 65% and the correlation with year of operation was abolished. CONCLUSIONS: By closing the audit loop, substantial improvements were shown in the management of risk factors in patients who have had coronary artery surgery in Lothian.

Antibiotics for acute pyelonephritis in children.

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infection in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent renal damage. Published guidelines recommend treatment of acute pyelonephritis initially with intravenous (IV) therapy followed by oral therapy for seven to 14 days though there is no consensus on the duration of either IV or oral therapy. OBJECTIVES: To determine the benefits and harms of different antibiotic regimens for the treatment of acute pyelonephritis in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings without language restriction. Date of most recent search: June 2004. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0 to 18 years with proven UTI and acute pyelonephritis were selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weight mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Eighteen trials (2612 children) were eligible for inclusion. No significant differences were found in persistent renal damage at six months (one trial, 306 infants: RR 1.45, 95% CI 0.69 to 3.03) or in duration of fever (WMD 0.80, 95% CI -4.41 to - 6.01) between oral cefixime therapy (14 days) and IV therapy (three days) followed by oral therapy (10 days). Similarly no significant differences in persistent renal damage (three trials, 315 children: RR 0.99, 95% CI 0.72 to 1.37) were found between IV therapy (3-4 days) followed by oral therapy and IV therapy for 7-14 days. In addition no significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (one trial, 179 children, persistent symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53). AUTHORS' CONCLUSIONS: These results suggest that children with acute pyelonephritis can be treated effectively with oral cefixime or with short courses (2-4 days) of IV therapy followed by oral therapy. If IV therapy is chosen, single daily dosing with aminoglycosides is safe and effective. Trials are required to determine the optimal total duration of therapy and if other oral antibiotics can be used in the initial treatment of acute pyelonephritis.

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

Prevalence and development of additional cardiac abnormalities in 1448 patients with congenital ventricular septal defects.

OBJECTIVE: To determine by modern echocardiographic techniques the prevalence and development of cardiac abnormalities associated with ventricular septal defect (VSD). METHODS: Consecutive patients referred to a tertiary centre for paediatric cardiology and attenders at an adult congenital heart disease clinic had details of clinical outcome prospectively recorded. Patients with VSD in association with conotruncal abnormalities, atrioventricular septal defects, and univentricular heart were not included in the study. RESULTS: 1448 patients with VSD were assessed between 1991 and 1998. 1127 (78%) patients had isolated defects; of these 862 (76%) were perimembranous and 265 (24%) were muscular. Of the remainder, 284 (19.6% of the total population) patients had VSD associated with one other significant cardiac abnormality: 35 (2.4%) with two and two (0.1%) with three other abnormalities. The most common associated cardiac abnormalities were infundibular pulmonary stenosis (5.8%), aortic valve prolapse (3.6%), pulmonary valvar stenosis (2.7%), osteum secundum atrial septal defect (2.2%), persistent ductus arteriosus (1.9%), and coarctation of the aorta (1.5%). In the cohort of 743 patients followed up from birth, cumulative mortality was 4% by the age of 8 years and most deaths occurred within the first year of life in infants with associated genetic abnormalities such as trisomy 13 or 18. Of the 594 patients attending the adult congenital clinic with VSD, aortic regurgitation due to aortic root prolapse developed in 45 (7.6%) patients. Most of these cases were detected before the patient was 30 years old. CONCLUSIONS: In 22% of patients with congenital VSD there were significant associated cardiac abnormalities. Some of these abnormalities, such as aortic prolapse and regurgitation or infundibular pulmonary stenosis, may develop or progress subsequently and therefore should be sought during the initial assessment and monitored during follow up. Follow up to the age of 30 years allows the detection of most cases of aortic regurgitation. The prognosis from VSD is excellent and the risk of endocarditis in a population informed of the need for antibiotic prophylaxis is small.

Bacteraemia and antibiotic use in respiratory syncytial virus infections.

AIMS: To examine the frequency of and risk factors for bacteraemia in children hospitalised with respiratory syncytial virus (RSV) infection; and to determine current use of antibiotics in hospitalised children with RSV infection. METHODS: Retrospective study of all children, aged 0-14 years, admitted to a tertiary children's hospital with proven RSV infection over a four year period. Children with concurrent bacteraemia and RSV infection were identified, and risk factors examined for bacteraemia. The case notes of a randomly selected comparison sample of 100 of these RSV infected children were examined to assess antibiotic use and population incidence of risk factors for severe RSV infection. RESULTS: A total of 1795 children had proven RSV infection, and blood cultures were sent on 861 (48%). Eleven (0.6%) of the 1795 RSV positive children had bacteraemia. RSV positive children had a significantly higher incidence of bacteraemia if they had nosocomial RSV infection (6.5%), cyanotic congenital heart disease (6.6%), or were admitted to the paediatric intensive care unit (2.9%). Forty five (45%) of the random comparison sample of RSV infected children received antibiotics. CONCLUSIONS: Bacteraemia is rare in RSV infection. Children with RSV infection are more likely to be bacteraemic, however, if they have nosocomial RSV infection, cyanotic congenital heart disease, or require intensive care unit admission.

Antibiotics for acute pyelonephritis in children.

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infection in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent renal damage. Published guidelines recommend treatment of acute pyelonephritis initially with intravenous (IV) therapy followed by oral therapy for 7-14 days though there is no consensus on the duration of either IV or oral therapy. OBJECTIVES: To determine the benefits and harms of different antibiotic regimens for the treatment of acute pyelonephritis in children. SEARCH STRATEGY: We searched the Cochrane Register of Controlled Trials (Cochrane Library Issue 3, 2002), MEDLINE (1966 - September 2002), EMBASE (1988 -September 2002), reference lists of articles and abstracts from conference proceedings without language restriction. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0-18 years with proven UTI and acute pyelonephritis were selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weight mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Sixteen trials involving 1872 children were eligible for inclusion. No significant differences were found in persistent renal damage at six months (one trial, 306 infants: RR 1.45, 95% CI 0.69 to 3.03) or in duration of fever (WMD 0.80, 95% CI -4.41 to - 6.01) between oral cefixime therapy (14 days) and IV therapy (three days) followed by oral therapy (10 days). Similarly no significant differences in persistent renal damage (three trials, 315 children: RR 0.99, 95% CI 0.72 to 1.37) were found between IV therapy (3-4 days) followed by oral therapy and IV therapy for 7-14 days. In addition no significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (one trial, 179 children, persistent symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53). REVIEWER'S CONCLUSIONS: These results suggest that children with acute pyelonephritis can be treated effectively with oral cefixime or with short courses (2-4 days) of IV therapy followed by oral therapy. If IV therapy is chosen, single daily dosing with aminoglycosides is safe and effective. Trials are required to determine the optimal total duration of therapy and if other oral antibiotics can be used in the initial treatment of acute pyelonephritis.

Twenty year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses.

OBJECTIVE: To compare survival and outcome in patients receiving a mechanical or bioprosthetic heart valve prosthesis. DESIGN: Randomised prospective trial. SETTING: Tertiary cardiac centre. PATIENTS: Between 1975 and 1979, patients were randomised to receive either a Bjork-Shiley or a porcine prostheses. The mitral valve was replaced in 261 patients, the aortic in 211, and both valves in 61 patients. Follow up now averages 20 years. MAIN OUTCOME MEASURES: Death, reoperation, bleeding, embolism, and endocarditis. RESULTS: After 20 years there was no difference in survival (Bjork-Shiley v porcine prosthesis (mean (SEM)): 25.0 (2.7)% v 22.6 (2.7)%, log rank test p = 0.39). Reoperation for valve failure was undertaken in 91 patients with porcine prostheses and in 22 with Bjork-Shiley prostheses. An analysis combining death and reoperation as end points confirmed that Bjork-Shiley patients had improved survival with the original prosthesis intact (23.5 (2.6)% v 6.7 (1.6)%, log rank test p < 0.0001); this difference became apparent after 8-10 years in patients undergoing mitral valve replacement, and after 12-14 years in those undergoing aortic valve replacement. Major bleeding was more common in Bjork-Shiley patients (40.7 (5.4)% v 27.9 (8.4)% after 20 years, p = 0.008), but there was no significant difference in major embolism or endocarditis. CONCLUSIONS: Survival with an intact valve is better among patients with the Bjork-Shiley spherical tilting disc prosthesis than with a porcine prosthesis but there is an attendant increased risk of bleeding.

Repeat chlamydia screening by mail, San Francisco.

OBJECTIVES: To assess the feasibility and acceptability of home screening for repeat chlamydial infection using urine test kits sent through the mail. METHODS: A letter offering home rescreening was mailed to 399 adults who previously tested positive for chlamydia. Kits were then mailed to anyone who did not actively decline. The home testing kits contained instructions on how to collect a urine specimen and return the specimen by mail. Specimens were tested with strand displacement amplification. A short survey asked individuals their level of concern about confidentiality, safety, and privacy of mail screening. RESULTS: Among the 313 potential test kit recipients, 22.4% responded. Response rates were highest among homosexual and bisexual men (38.6%), people 35 years or older (34.3%), and white people (34.6%). The overall positivity rate was 3.2% (2/63). In women 18-25 years old, the positivity was 13.3% (2/15). CONCLUSIONS: Home testing with mailed urine collection kits is feasible and an acceptable method to screen for recurrent chlamydial infection. Young women would probably benefit most because of their higher rates of reinfection and risk for sequelae.

Hypercholesterolaemia and lipid lowering treatment do not affect the acute endogenous fibrinolytic capacity in vivo.

OBJECTIVE: To assess acute tissue plasminogen activator (t-PA) release in vivo in patients with hypercholesterolaemia in the presence and absence of lipid lowering treatment and in matched normocholesterolaemic controls. DESIGN: Parallel group comparison and double blind randomised crossover. SETTING: University hospital. PATIENTS: Eight patients with hypercholesterolaemia (> 7.8 mmol/l) and eight matched normocholesterolaemic controls (< 5.5 mmol/l). METHODS: Blood flow and plasma fibrinolytic factors were measured in both forearms during unilateral brachial artery infusions of the endothelium dependent vasodilator substance P (2-8 pmol/min) and the endothelium independent vasodilator sodium nitroprusside (1-4 microg/min). INTERVENTIONS: In patients, measurements were made on three occasions: at baseline and after six weeks of placebo or pravastatin 40 mg daily administered in a double blind randomised crossover design. MAIN OUTCOME MEASURES: Acute release of t-PA. RESULTS: Compared with patients, in normocholesterolaemic control subjects substance P caused greater dose dependent increases in forearm blood flow (p < 0.05) but similar increases in plasma t-PA antigen and activity concentrations. During pravastatin treatment in patients, total serum cholesterol fell by 22% from a mean (SEM) of 8.1 (0.3) to 6.4 (0.4) mmol/l (p = 0.002) and substance P induced vasodilatation was no longer significantly impaired in comparison with controls. However, despite reproducible responses, pravastatin treatment was not associated with significant changes in basal or substance P induced t-PA release. CONCLUSIONS: Hypercholesterolaemia and lipid lowering treatment cause no demonstrable effects on acute substance P induced t-PA release in vivo. This suggests that the preventative benefits of lipid lowering treatment are unlikely to be mediated by improvements in endogenous fibrinolysis.

Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy?

BACKGROUND: Calcific aortic stenosis may have common etiological factors with atherosclerosis. HYPOTHESIS: In this retrospective, case-control study, we aimed to determine whether there is an association between hypercholesterolemia and calcific aortic valve stenosis. METHODS: Consecutive patients undergoing single aortic or mitral valve replacement in a regional cardiothoracic surgical center were reviewed and preoperative patient characteristics were recorded: demographics, comorbidity (including coronary artery disease and associated risk factors), serum total cholesterol, lipid-lowering therapy, and serum creatinine. RESULTS: Serum total cholesterol concentrations were significantly higher in patients with calcific aortic stenosis than in controls (6.2+/-1.1 vs. 5.3+/-1.1 mmol/l; p < 0.001). The significant difference in serum cholesterol concentrations remained following correction for gender and body mass index (p = 0.02) and when patients with coronary artery disease were excluded (6.3+/-1.1 vs. 5.3+/-1.4 mmol/l; p<0.001). Subgroup analysis demonstrated that the association between elevated serum cholesterol concentrations and calcific aortic stenosis was particularly strong in patients with tricuspid aortic valves (6.4+/-1.2 vs. 5.3+/-1.1 mmol/l; p < 0.001) compared with those with bicuspid valves (5.9+/-1.1 vs. 5.3+/-1.1 mmol/l; p = 0.06). CONCLUSIONS: We conclude that hypercholesterolemia is associated with calcific aortic stenosis and may be implicated in its pathogenesis and progression. We believe that there is now a need for a randomized, controlled trial of cholesterol-lowering therapy in patients with calcific aortic stenosis.

Histochemical correlates of (15)O-water-perfusable tissue fraction in experimental canine studies of old myocardial infarction.

UNLABELLED: A method has been proposed to quantitate the myocardial water-perfusable tissue fraction (PTF) in the area of hypoperfused asynergic segments using (15)O-water (H2(15)O) and PET. This study investigated the histochemical correlates of PTF (and perfusable tissue index, PTI) in a canine model of old myocardial infarction. METHODS: Myocardial infarction was produced in 12 mongrel dogs, and PET was performed 1 mo later, providing quantitative parametric images of PTF, regional myocardial blood flow (MBF), and extravascular density from H2(15)O, (15)O-carbon monoxide, and transmission datasets. At the end of scanning, the myocardium was sectioned, and the PET images were compared directly with the corresponding myocardial sections. RESULTS: The distribution of tissue necrosis identified by histochemical staining corresponded well with the defect in PTF but not in MBF. PTF agreed with the equilibrium images of myocardial H2(15)O distribution, obtained after injection of a large bolus of H2(15)O. The defect surface area identified on PTF agreed well quantitatively with the morphometric estimates of the surface area of myocardial infarction. PTI agreed with the absolute proportion of histochemically defined normal myocardium (0.87 +/- 0.09 and 0.83 +/- 0.08, respectively; P < 0.01). Both PTF and PTI decreased significantly in segments of myocardial infarction and showed a significant difference between the transmural and nontransmural myocardial infarction. CONCLUSION: The absolute mass and proportion of histochemically defined noninfarcted tissue may be quantitated with PTF and PTI in the area of myocardial infarction segments.

The effect of the nitric oxide donor glyceryl trinitrate on global and regional cerebral blood flow in man.

Despite their potential use as cerebral vasodilatory agents there are few studies of the effect of nitric oxide (NO) donors on the cerebral circulation in non-anaesthetised man. We determined the effect of the NO donor glyceryl trinitrate (GTN) at clinically relevant doses on global and regional cerebral blood flow (CBF) in healthy non-anaesthetised volunteers, using H(2)(15)O PET, ultrasonic colour velocity flow imaging of carotid artery flow, and transcranial Doppler (TCD) of middle cerebral artery velocities (MCAv). Three rates of GTN infusion (0.1, 0.4, 1.0 microg/kg/min) were used. There was no significant change in common or internal carotid artery flow following GTN administration although a dose dependent fall in MCAv post GTN was observed. There was no significant change in either global or regional CBF following GTN. Thus intravenous GTN at therapeutic doses in awake humans does not alter global or regional CBF. However it does produce basal cerebral artery vasodilatation as evidenced by a fall in MCAv in the absence of a change in internal carotid artery flow.

Physical characteristics of the ECAT EXACT3D positron tomograph.

The 'EXACT3D' positron tomograph, which is now in routine clinical research use, was developed with the aim of achieving unprecedented sensitivity, high spatial and temporal resolution and simplicity of design using proven detector technology. It consists of six rings of standard detector blocks (CTI/Siemens EXACT HR+) with 4.39 mm x 4.05 mm x 30 mm elements, giving an axial field of view (FOV) of 23.4 cm. This extended FOV and the absence of interplane septa and retractable transmission rod sources has allowed greatly simplified gantry and detector cassette design. Operation in exclusive 3D mode requires an alternative to the conventional coincidence method for transmission scanning, and a single photon approach using a hydraulically driven 137Cs point source has been implemented. The tomograph has no other moving parts. A single time frame of data without any compression is very large (> 300 Mbyte) and two approaches are employed to overcome this difficulty: (a) adjacent sinograms can be summed automatically into different combinations and (b) listmode (event-by-event) acquisition has been instituted, which is both storage efficient (particularly for acquisition of sparse data sets) and maximizes temporal resolution. The high-speed I/O and computing hardware can maintain a sustained acquisition rate of about 4 million coincidence events per second. A disadvantage of the large axial FOV in 3D is the increased sensitivity to activity outside the coincidence FOV. However, this can be minimized by additional side shielding. The mean spatial resolution is 4.8 +/- 0.2 mm FWHM (transaxial, 1 cm off-axis) and 5.6 +/- 0.5 mm (axial, on-axis). Its absolute efficiency is 5.8% for a line source in air (just spanning the axial FOV) and 10% for a central point source (with thresholds of 350-650 keV). For a uniform 20 cm diameter cylinder, the efficiency is 69 kcps kBq(-1) ml(-1) (after subtraction of a scatter fraction of 42%). Sensitivity relative to the EXACT HR+ (with four rings of blocks) is 2.5 (3D) and 12 (2D) times respectively. The rate of random events in blood flow studies in the brain and body, using 15O-labelled water, can be controlled by limiting the administered dose and inserting additional side shielding.