Technetium-99m-tetrofosmin: retention of nitrogen atmosphere in kit vial as a cause of poor quality material.

Technetium-99m (99Tc(m))-tetrofosmin was prepared using four different reconstitution methods. The radiochemical purity (RCP) of these products was assessed 8 h later using thin layer chromatography (TLC). Material produced using the original method supplied by the manufacturer and using an newer method, which involves the use of a vent needle and the addition of air, had acceptable RCP (mean +/- SD 94.2 +/- 1.1% and 94.7 +/- 1.7%, respectively) and similar chromatograms. In addition, both products showed good clinical efficacy and exhibited normal biodistribution behaviour. Preparing 99Tc(m)-tetrofosmin using the two other methods, one using a high radioactive concentration and the other maintaining the nitrogen content of the kit vial, gave rise to chromatograms with reduced RCP (63.5 +/- 10.9% and 61.9 +/- 7.6%, respectively) and greater levels of impurities. Although neither of these last two preparations was used clinically, we suggest that reports of poor quality images may be the result of administration of materials similar to these. Results for the high radioactive concentration method were as expected and are consistent with the restrictions imposed by the manufacturer. However, results using the last method are surprising and would suggest that the production of good quality 99Tc(m)-tetrofosmin is dependent on the quantity of nitrogen in the kit vial. We believe that the amount of nitrogen removed from the kit vial during the process of reconstitution is critical. If too much nitrogen is present this will result in poor quality material. In practice it is conceivable that there could be occasions when insufficient nitrogen is removed when following the manufacturer's original guidance, thereby leading to low RCP material. To ensure adequate nitrogen is removed during reconstitution, adoption of the manufacturer's revised method, involving the deliberate introduction of air, is therefore appropriate.

A study of doses to the hands during dispensing of radiopharmaceuticals.

Radiation doses to both the fingertip and finger base of staff preparing radiopharmaceuticals in a radionuclide dispensary have been monitored for more than 5 years. The records show a fall in dose thought to be due, largely, to the introduction of all-glass (lead) syringe shields. In 1998, the annual radiation dose (mean +/- standard deviation) to the fingertip had fallen to 83+/-11 mSv, which corresponded to 0.18 mSv per 10 GBq 99Tc(m) handled. There was less reduction in dose to the finger base, which, in 1998, was 70% of that to the fingertip. To study the effect of a syringe shield on the distribution of dose across the hands, model hands were constructed and a gamma extremity monitoring system (GEMS) was used to measure dose. When a radiopharmaceutical is dispensed, contributions to the dose from activity in the vial and syringe change during the procedure. As a result, relative doses to different fingers and the ratios of doses to the tip and base of each finger will fluctuate throughout dispensing. In the absence of a syringe shield, the front tip of the index finger received the greatest radiation dose. When a syringe shield was used, doses were lower and the dose distribution was completely different. These findings have important implications in terms of compliance with the new UK Ionizing Radiations Regulations, where the dose limit is applied to 'the dose averaged over any area of 1 cm2 regardless of the area exposed'.

99Tcm-MAG3: problems with radiochemical purity testing.

The radiochemical purity (RCP) of 99Tcm-MAG3 was determined using solid-phase extraction (SPE), high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). The difference between the HPLC and SPE methods was highly significant (P < 0.001), yielding values for RCP of 94.4 +/- 1.4% and 86.0 +/- 5.1% [corrected] respectively (mean +/- s). Further qualitative analysis of the SPE fractions obtained, was carried out using HPLC and TLC. The unexpected presence of 99Tcm-MAG3 in one of the fractions was observed together with the appearance of hydrophilic impurities in the hydrophobic extract. This lack of specificity may be the reason for the discrepancy between the SPE and HPLC methods. Use of the SPE method leads to an underestimation of the RCP of 99Tcm-MAG3 and, indeed, had we been relied solely on this method of analysis, we would have had to reject most kits we prepared. In a separate study, we compared a TLC method with HPLC. Differences were found to be highly significant (P < 0.001), yielding values of 98.3 +/- 0.6% and 95.8 +/- 0.9% respectively. Comparison of the data points showed that TLC gave consistently higher RCP yield than HPLC. This elevated value was found to be due to the inability of the TLC method to separate 99Tcm-lipophilic impurity, seen on HPLC, from the 99Tcm-MAG3. Therefore, use of this TLC method leads to an overestimation of the RCP of 99Tcm-MAG3.

First SPET images of glutamate (NMDA) receptor activation in vivo in cerebral ischaemia.

This report describes the initial clinical assessment of (+)-3-[123I]Iodo-MK-801 and its potential to provide single photon emission tomographic (SPET) images in vivo of NMDA receptor activation during cerebral ischaemia. Multiple SPET images were obtained in the 120 min after the administration of 150 MBq of (+)-3-[123I]Iodo-MK-801 to five patients with cerebral ischaemia (due to cerebral haemorrhages) and to five normal volunteers. In normal subjects, (+)-3-[123I]Iodo-MK-801 has a rapid uptake into the brain. The tracer has a high non-specific retention in the central nervous system due to its lipophilicity, which was made evident by the retention of tracer in the cerebellum and white matter (brain areas with few NMDA receptors). In all patients with cerebral haemorrhages, the initial uptake of (+)-3-[123I]Iodo-MK-801 into the ipsilateral hemisphere was markedly reduced, consistent with a reduced level of cerebral blood flow. In two of five patients, relatively increased tracer retention at later time points (60-120 min after tracer administration) could be seen in cortical areas adjacent to the site of the haemorrhage, consistent with activated NMDA receptors. In three of the patients, no relatively enhanced tracer retention could be identified. Using (+)-3-[123I]Iodo-MK-801, it may be possible to image excessive glutamate (NMDA) receptor activation during an ischaemic episode in living human patients. The utility of (+)-3-[123I]Iodo-MK-801 as a SPET ligand for assessing modest alterations in NMDA receptor activity may ultimately be limited by its lipophilicity and consequent high non-specific binding.

Automatic detection of diabetic retinopathy using an artificial neural network: a screening tool.

AIMS: To determine if neural networks can detect diabetic features in fundus images and compare the network against an ophthalmologist screening a set of fundus images. METHODS: 147 diabetic and 32 normal images were captured from a fundus camera, stored on computer, and analysed using a back propagation neural network. The network was trained to recognise features in the retinal image. The effects of digital filtering techniques and different network variables were assessed. 200 diabetic and 101 normal images were then randomised and used to evaluate the network's performance for the detection of diabetic retinopathy against an ophthalmologist. RESULTS: Detection rates for the recognition of vessels, exudates, and haemorrhages were 91.7%, 93.1%, and 73.8% respectively. When compared with the results of the ophthalmologist, the network achieved a sensitivity of 88.4% and a specificity of 83.5% for the detection of diabetic retinopathy. CONCLUSIONS: Detection of vessels, exudates, and haemorrhages was possible, with success rates dependent upon preprocessing and the number of images used in training. When compared with the ophthalmologist, the network achieved good accuracy for the detection of diabetic retinopathy. The system could be used as an aid to the screening of diabetic patients for retinopathy.

Functional imaging of the retina using the multifocal electroretinograph: a control study.

BACKGROUND: A new technique exists that enables functional mapping of the retina. A control population was examined to obtain normative values and to assess the reproducibility of this new test. METHODS: Twenty healthy volunteers were tested using a 61 hexagonal array stimulus with a 14 minute recording period. Median 5th and 95th percentiles were determined for implicit times and amplitude measures for the 61 test areas. Repeat measurements were performed on 10 individuals. Wilcoxon and Bland and Altman techniques were used to quantify reproducibility of the test. RESULTS: The implicit time of the wave-form components was not found to vary over the retina (peak or b-wave component, 35.52 (1.4) ms; trough or a-wave component, 17.76 (0.8) ms). Reproducibility was found to decrease with eccentricity (coefficient of repeatability 17.4% for the central area increasing to 30.3% for the peripheral ring). CONCLUSIONS: The findings suggest that reproducibility, although variable with eccentricity, is comparable with conventional electrophysiology. These limits of variation were used to assign confidence intervals to individual retinal areas and will be used (future work) in the examination of diseased states.

The effect of filter bandwidth on the multifocal electroretinogram.

The effect of filter bandwith on the multifocal electroretinogram was assessed by means of theoretical calculation, electronic simulation and real multifocal electroretinogram recordings. Waveform distortion by high-pass filtering on simulated square waves, normal electroretinogram waveforms and negative electroretinogram waveforms was demonstrated. The theory of the effect of differentiation on electroretinogram waveform shape by electronic filtering indicates that little effect would be observed by changing the input filter cut-off for normal electroretinographic waveform shapes. However, negative electroretinogram waveforms are differentiated when the high-pass filter setting is increased. The differentiation effect artificially recreates a positive component that could be mistaken as a b-wave component. To eliminate this effect when recording multifocal electroretinograms, a high-pass filter setting of less than 1 Hz should be used to preserve the true electroretinographic waveform shape.

Comparison of repeatability of the multifocal electroretinogram and Humphrey perimeter.

Functional mapping of the retina by multifocal electroretinographic recordings is now possible. We compared the normal range, repeatability and response topography of this new technique with conventional static Humphrey perimetry to assess its suitability in clinical practice. The multifocal technique was performed on 60 age-matched controls. Measures of repeatability and reproducibility were obtained. Results were then compared with those obtained from a customized perimetry test. In both tests the coefficients of repeatability were found to decrease with eccentricity. The inherent measurement variation between techniques was comparable. Overall system variation indicates that the technique could be a useful tool at the clinical level.

UK nuclear medicine survey, 1992-93.

A postal survey of UK nuclear medicine departments was undertaken to collate information on equipment, numbers of procedures and staffing levels for the years 1992 and 1993. It was estimated that there are 235 sites undertaking nuclear medicine, the total number of procedures performed being some 490,000 in 1993 compared with 430,000 in 1989. Informal investigation suggests that the increase is due to greater usage of myocardial perfusion and lung ventilation/perfusion studies. Wide variations were noted in staffing levels, with only 22% of departments having medical cover of half-time equivalent or better: over 30% of departments have less than one consultant session per week. Approximately 20% of departments claimed to have no physics input, with a further 20% having less than one session per week.

A reappraisal of current methods for the assessment of planar gamma camera performance.

This study reappraises the acquisition parameters defined by three current protocols for the specification of planar gamma camera performance. These are the manufacturer Standards of the National Electrical Manufacturers' Association [1] and the International Electrotechnical Commission [2], and the user-orientated protocol of the UK Department of Health (DoH, formerly DHSS) Gamma Camera Performance Assessment Group [3]. The study looks specifically at three major planar performance characteristics: intrinsic non-uniformity, intrinsic spatial resolution and intrinsic non-linearity (spatial distortion). Acquisition parameters specified for these characteristics are investigated by testing a range of values for each parameter around those figures currently advocated by the three protocols. Those acquisition parameters which may be relaxed without loss of data integrity are identified and the adoption of revised parameters for some measurements within the DoH assessment protocol is suggested. Reviewing the data obtained, observations are made regarding the accuracy of some tests performed regularly for quality control purposes. The feasibility and advantages of incorporating some suitably modified DoH performance assessment tests within a routine quality assurance protocol for the gamma camera are also discussed.

UK nuclear medicine survey, 1989/90.

A postal survey of UK nuclear medicine departments was carried out to obtain information on activity during the year 1989/90. A rise of 14% in the number of administrations of radiopharmaceuticals was found compared to 1982: a rise of 22% in imaging studies was offset by a 30% decrease in the number of nonimaging investigations. The estimated total number of administrations in the UK was 430,000.

The design and construction of a central radiopharmacy.

Following an inspection by the Medicines Control Agency (MCA) of the existing radiopharmacy, it was necessary to design and build a new facility at the Western Infirmary to supply radiopharmaceuticals for patient use throughout the West of Scotland. This is one of the largest radiopharmacies in Europe, supplying some 40,000 patient doses per year prepared using both closed and open procedures. The design parameters and construction details of the new facility are presented.

An investigation of the magnitude and causes of count loss artifacts in SPECT imaging.

A quantitative evaluation and an investigation of the mechanism of the count losses that can occur in SPECT imaging is described. The most common clinical example of the artifacts which result from this is encountered when sections are taken through the femoral heads in skeletal studies of the pelvis. From some simple phantom studies, it was identified that the count losses were associated with the presence of a high dynamic range in the projection data. Further information was obtained from simulation studies. It was found that the count loss phenomenon is caused by the combined effects of the presence of a high count density area and a structure with a relatively high attenuation level. An appreciation of the presence, magnitude, and mechanism of this effect is important if erroneous clinical findings are to be avoided. This is particularly relevant because of the existence of a variety of techniques that can be used to remove the resulting artifacts.