PET scan in clinically suspected paraneoplastic neurological syndromes: a 6-year prospective study in a regional neuroscience unit.

BACKGROUND: The role of PET in the diagnosis of paraneoplastic neurological syndromes (PNS) has previously been reported in retrospective studies, from specialized neuro-oncology units, often selecting patients with positive paraneoplastic antibodies. OBJECTIVES: To prospectively assess the usefulness of PET in detecting malignancy in patients clinically suspected of having PNS. METHODS: PET was performed in patients suspected of PNS within 4 weeks of the normal CT body scan. All patients were followed up. RESULTS: Eighty patients suspected of having PNS underwent PET. 18/80 (23%) were abnormal and suspicious of malignancy. The total number of definite and probable PNS with abnormal PET was 11/18 (61%). The total number of definite and probable PNS with a normal PET was 3/62 (5%). Only 50% of patients with biopsy-proven malignancy were positive for paraneoplastic antibodies. The prevalence of abnormal PET in patients presenting with classical PNS was 41% as opposed to 21% in patients with non-classical PNS. The sensitivity and specificity of PET in diagnosing PNS was 75% and 87% respectively. CONCLUSIONS: PET is a valuable tool in clinically suspected PNS. Its use should not be restricted to specialized neuro-oncology units or in patients with positive paraneoplastic antibodies. Positive yield is the highest amongst patients with classical PNS.

The relationship between administered radiopharmaceutical activity in myocardial perfusion scintigraphy and imaging outcome.

INTRODUCTION: Lower radiopharmaceutical activities are used for myocardial perfusion scintigraphy (MPS) in the UK than in other countries. There is no evidence to suggest that higher activities improve imaging or clinical outcome. MATERIALS AND METHODS: We undertook a multicentre study of the relationship between radiopharmaceutical activity and imaging outcome. Fifty-one patients with clinical referrals for MPS followed a 2-day protocol with an injection of 1,000 MBq (99m)Tc-tetrofosmin for each of the stress and rest images. ECG-gated acquisition was performed in three rotations occupying 25, 35 and 40% of a standard acquisition, and rotations were summed to simulate administered activities of 250, 400, 750 and 1,000 MBq. Each set of images was reported by an experienced physician who was blinded to all clinical information and to the simulated activity. Scores were assigned for image quality, low count, attenuation and reconstruction artefact, segmental tracer uptake, segmental and global defect classification, and confidence in the global classification. The images were reported twice to assess intra-observer variability. RESULTS: Positive relationships were found between administered activity and overall image quality, observer confidence and intra-observer agreement of uptake score, and a negative relationship was found with low-count artefact. For the majority of comparisons, there was no additional improvement with increasing activity from 750 to 1,000 MBq. Intra-observer agreement was found to be better in female patients and in those below average body mass index. DISCUSSION: We conclude that higher administered radiopharmaceutical activities lead to better quality images and improved surrogate parameters for clinical outcome, but that activities above 750 MBq may be unnecessary in average patients.

The radioactive autopsy: safe working practices.

Autopsy cases involving individuals retaining radioactive substances are fortunately rare, but when they occur they can impose significant radiation safety and legal requirements. This review aims to improve the understanding of these issues so that appropriate precautions are implemented when necessary. This review describes the properties of ionizing radiations, natural and man-made sources of ionizing radiation and its use in healthcare. It identifies the most likely circumstances leading to radioactive substances being present during autopsy and sources of information, including radiation protection advice. It discusses precautions that may need to be implemented prior to, during and following autopsy. Despite the issue of appropriate information to patients and next of kin, it is inevitable that some cases will be identified only at autopsy and it is important that robust local procedures are maintained. Information must be communicated to assist safe management of the body and liaison between relevant professional groups may be needed to standardize methods of communication. Provided that appropriate precautions are implemented, determined through consultation with a qualified expert in radiation protection and by completion of risk assessment, the radioactive autopsy can be undertaken safely and in compliance with relevant legislative requirements.

Training of staff for the delivery of PET/CT services in the UK.

Evidence for the cost effectiveness of PET/CT imaging is now driving the widespread introduction of PET/CT services throughout the UK. The provision of PET/CT facilities will require a workforce of medical, scientific, technical and engineering staff who are adequately trained and fit for purpose. Suitably trained staff in this speciality are scarce. The development and accreditation of training courses and other educational resources for training programmes in all disciplines will therefore be required at a national and regional level. The implementation of PET/CT training can be achieved more cost-effectively by developing multi-professional learning resources whenever possible. It is intended that the recommendations would be implemented by close co-operation of both public and private healthcare providers together with educational establishments.

The clinical impact of a combined gamma camera/CT imaging system on somatostatin receptor imaging of neuroendocrine tumours.

AIM: With a combined gamma camera/CT imaging system, CT images are obtained which are inherently registered to the emission images and can be used for the attenuation correction of SPECT and for mapping the functional information from these nuclear medicine tomograms onto anatomy. The aim of this study was to evaluate the clinical impact of SPECT/CT using such a system for somatostatin receptor imaging (SRI) of neuroendocrine tumours. MATERIALS AND METHODS: SPECT/CT imaging with (111)In-Pentetreotide was performed on 29 consecutive patients, the majority of whom had carcinoid disease. All SPECT images were first reported in isolation and then re-reported with the addition of the CT images for functional anatomical mapping (FAM). RESULTS: Fifteen of the 29 SPECT images were reported as abnormal, and in 11 of these abnormal images (73%) FAM was found to either establish a previously unknown location (7/11) or change the location (4/11) of at least one lesion. The revised location could be independently confirmed in 64% of these cases. Confirmation of location was not possible in the other patients due to either a lack of other relevant investigations, or the fact that lesions seen in the SPECT images were not apparent in the other investigations. FAM affected patient management in 64% of the cases where the additional anatomical information caused a change in the reported location of lesions. CONCLUSION: These results imply that FAM can improve the reporting accuracy for SPECT SRI with significant impact on patient management.

Procedure guidelines for radionuclide myocardial perfusion imaging.

Radionuclide myocardial perfusion imaging (MPI) is an established and non-invasive imaging technique with diagnostic and prognostic efficacy in the investigation of coronary artery disease. It is the only widely available test for assessing myocardial perfusion directly but there are variations in the way it is performed in different centres. Harmonization of practice, at least at a national level, is therefore essential, and clinical governance now makes it mandatory for practice to be based upon evidence whenever possible [ 1]. This is best achieved by expert analysis of the evidence and to this end the British Nuclear Cardiology Society (BNCS) in association with the British Cardiac Society (BCS) and the British Nuclear Medicine Society (BNMS) have developed procedure guidelines for tomographic myocardial perfusion imaging. A systematic literature search was performed and every effort was made to conform with the AGREE recommendations [ 2]. All recommendations are therefore based on either evidence from clinical studies, previous published guidelines or expert consensus of the writing and advisory groups. The guidelines cover the clinical indications of MPI, the methods used for stress testing, the radiopharmaceuticals and the injected activities and also issues related to acquisition, processing and interpretation of images. They do not cover the benefits or drawbacks of the technique in specific circumstances; neither do they address its cost effectiveness in clinical diagnosis and management nor its potential impact on clinical outcomes. The guidelines aim to assist medical practitioners and other health care professionals in recommending, performing, interpreting and reporting single photon emission computed tomography (SPECT) of myocardial perfusion.

Introduction, audit and review of guidelines for delegated authorization of nuclear medicine investigations in compliance with the Ionising Radiation (Medical Exposure) Regulations 2000.

The introduction of the Ionising Radiation (Medical Exposure) Regulations 2000 in Great Britain required every nuclear medicine investigation to be justified by a practitioner holding an appropriate Administration of Radioactive Substances Committee (ARSAC) certificate. The task of authorizing the radiation exposure may be performed by the practitioner (direct authorization) or delegated to an appropriately trained operator working to written guidelines approved by the practitioner (delegated authorization). In this study, we look at the process of implementation, audit and review of a set of Delegated Authorization Guidelines (DAG). The process of drafting the DAG is outlined. Following the introduction of the DAG, an audit of nuclear medicine referrals was performed at two sites for a period of 3 months. Each referral was compared with the DAG to determine whether it matched the criteria set out. If it did not match, it was further categorized as being due to: (1) insufficient referral information; or (2) clinical indication not included in the DAG. All non-matching requests were reviewed by the practitioner. Four hundred and thirty-seven of 632 (69%) referrals fitted the DAG, 12% (n=75) required clarification from the referrer before fitting with the criteria and 19% (n=120) were directly authorized by the practitioner. From those referrals that were directly authorized, some additional indications were identified and the DAG were subsequently revised. In conclusion, a delegated authorization procedure for nuclear medicine investigations can be implemented successfully. Regular audit is essential. This study identified the need to improve the format of the request card and to obtain additional referral information from the referrer.

A survey of the role of the UK physicist in nuclear medicine: a report of a joint working group of the British Institute of Radiology, British Nuclear Medicine Society, and the Institute of Physics and Engineering in Medicine.

Guidelines for the provision of physics support to nuclear medicine were published in 1999 by a joint working group of the British Institute of Radiology, the British Nuclear Medicine Society, and the Institute of Physics and Engineering in Medicine. Following publication of the guidelines, a survey was conducted by the working group to gather data on the actual level of physicist support in UK hospitals of different types and on the activities undertaken by physicists. The data were collected in the 12 months following the publication of guidelines and cover different hospital models and seven UK regions. The results provide evidence that many of the smaller units - small teaching hospitals and, particularly, small district general hospitals - have insufficient physics support. Although, on average, there is good agreement between the guidelines and the survey data for medium and large district general hospitals, there is wide variation in the level of physics provision between hospitals delivering apparently similar services. This emphasizes the need for national guidelines, against which institutions may be bench-marked and which may be used as a recommendation for the staffing levels necessary to ensure services are delivered safely and standards are not compromised. The complexity and variety of workload is an important factor in determining the level of physics support. As services develop, it is vital that this aspect is recognized to ensure that appropriate resources are available for the required physics input, even if any new service represents only a modest clinical throughput in terms of patient numbers.

Radioiodine therapy: care of the helpless patient and handling of the radioactive corpse.

Nurses caring for a helpless patient following a nominal 800 MBq administration of radioiodine were concerned about their radiation dose. Using published data, a nurse could receive an estimated 650 microSv per shift. A regime to restrict their dose was planned using a 500 microSv dose constraint. Thermoluminescent dosimeters indicated a maximum whole-body effective dose of 250 microSv. Three days post 131I administration the patient died (estimated activity in the body 400 MBq). A minimum delay of two weeks was advised prior to a post-mortem. Special precautions were issued to minimise contamination. Dose rates (microSv h(-1)), measured one day after the patient died, at the level of the thyroid, chest and bladder at 0.01 m from the corpse were 1800, 290 and 73 respectively. At 1.0 m the dose rate was 26 microSv h(-1) at all levels. The pathologist was estimated to have received a maximum whole-body dose of 400 microSv during the post-mortem. Contamination measurements (Bq cm(-2)) made following the post-mortem were as follows: pathologist's hands 5, clothes 0, towels 1.8, saw 5, instruments 0.5, plastic sheet 0.8, scales 0.4 and floors/walls 1.1. These data indicate that with appropriate radiation protection guidelines, staff can be reassured that their doses in these circumstances are very low.

Subcortical hypoperfusion following surgery for aneurysmal subarachnoid haemorrhage: implications for cognitive performance?

The incidence and severity of cognitive deficits after surgery for aneurysmal subarachnoid haemorrhage and their relationship to aneurysm site remains controversial. The aim of this study was to investigate the pattern of regional cerebral blood flow which exists in patients one year post-surgery and to identify whether different patterns exist which may be related to the type of cognitive deficit or the location of the aneurysm. 62 patients underwent cognitive assessment and HMPAO SPECT imaging at a mean time of 12 months following surgery. Results were compared to those from healthy control subjects (n = 55 for neuropsychological testing; n = 14 for SPECT imaging). In the patient group, significant stable cognitive deficits occurred in all cognitive domains but no cognitive measure differentiated aneurysm site. On SPECT images, statistical parametric mapping identified a large common area of subcortical hypoperfusion in the patient group as a whole. The findings of this study suggest a possible link between reduced subcortical function and the extent and severity of cognitive deficits.

Gastric emptying and intestinal transit of pancreatic enzyme supplements in cystic fibrosis.

OBJECTIVE: To investigate gastric emptying and intestinal transit of pelleted pancreatin in relation to food boluses. METHODS: Dual isotope scintigraphy combined with breath hydrogen sampling was used to track the concurrent gastric emptying and intestinal transit of 111indium labelled microspheres and a 99mtechnetium labelled tin colloid test meal. Twelve pancreatic insufficient cystic fibrosis patients aged 5 to 38 years performed the study. RESULTS: 50% gastric emptying times showed patient to patient variation. The mean discrepancy in 50% gastric emptying times between the two labels was > 67 minutes. Mean small bowel transit time for the food bolus was prolonged at 3.6 minutes. A significant correlation was seen between weight standard deviation score and 50% emptying time for pancreatin (r = +0.73). CONCLUSION: Gastric mixing of food and pancreatin may be limited by rapid emptying of microspheres. Patients with high dosage requirements could benefit from changing the pattern of their pancreatin supplementation.

Dose rate measurements from radiopharmaceuticals: implications for nuclear medicine staff and for children with radioactive parents.

Following the introduction of a number of radiopharmaceuticals, we assessed the dose received by staff working in the nuclear medicine department and also by children who may be in close contact with a radioactive parent. We measured departure dose rates (microSv.h-1) at distances of 0.1, 0.5 and 1.0 m from the skin surface at the level of the thyroid, chest and bladder of patients undergoing the following nuclear medicine procedures: MUGA scans using 99Tcm-labelled red blood cells, myocardial perfusion scans using 99Tcm-labelled radiopharmaceuticals, lymphoscintigraphy using colloidal 99Tcm (Re) sulphide, bone scans using 99Tcm-labelled oxidronate, 111In-octreotide scans, 111In-labelled leukocyte studies and cardiac reinjection studies using 201Tl. The maximum dose rates at 0.1 m were those from MUGA studies (167.3 microSv.h-1) and myocardial perfusion studies (one-day protocol = 391.7 microSv.h-1, two-day protocol = 121.8 microSv.h-1). The implications of these dose rates on both technical and nursing staff are assessed. Also, the dose received by an infant in close contact with a parent following a nuclear medicine investigation was estimated.

The use of image registration in the analysis of bone scans for the assessment of temporomandibular joint uptake.

Bone scanning is a commonly used technique in the assessment of patients with facial asymmetry. Uptake in the temporomandibular joints can be assessed quantitatively, either as a right-to-left ratio or as the uptake in the joint relative to some other bony structure. We used image registration techniques in the development of an automatic method of quantitative analysis and compared this with a manual region of interest method. Both image warping and region warping were studied. Normal ranges were established in a series of 25 subjects with no evidence of temporomandibular disorder. The results of this study indicate that, by using image registration and standard regions of interest, the results from normal subjects show a smaller standard deviation and improved correlation between observers when compared with manual analysis.

The use of dual-isotope imaging to compare the gastrointestinal transit of food and pancreatic enzyme pellets in cystic fibrosis patients.

Cystic fibrosis patients require pancreatic enzyme supplements to aid food digestion. It is suspected that incorrect delivery of this enzyme may result in both significant malabsorption and the development of strictures in the proximal colon caused by the high-dose supplement reaching this region before the food. Investigations into the drug's delivery were performed using dual-isotope imaging; a method was developed to directly label the enteric-coated enzyme pellets with 111In, re-applying the enteric coating afterwards, and this was then ingested with a pancake meal labelled with 99Tcm-tin colloid. Consecutive image data, acquired over a period of > or = 4 h using a dual-headed gamma camera, were analysed to assess intestinal transit. In-vitro stability checks on these labelling techniques were encouraging, showing < 2% 99Tcm and < 7% 111In elution over 90 min in hydrochloric acid. In 5 of the 12 patients studied to date, the pellets were seen to pass through significantly faster than the food, with a mean difference in 50% gastric emptying time of greater than 93 min. The mean absolute difference in emptying time for all 12 patients was > 67 min. Thus, a technique has been developed to effectively radiolabel pancreatic enzyme pellets, and analysis of dual-isotope images using this preparation, together with radiolabelled solid food, has demonstrated significant differences in the transit of these two substances through the gastrointestinal tract of some cystic fibrosis patients.

Modelling dual isotope parathyroid scans: objective decision making for tumour detection.

Parathyroid subtraction imaging using the radioisotopes thallium-201 and technetium-99m was first described in 1983. Since then it has become a routine method for the pre-operative localization of parathyroid tumours. Despite its widespread use, the interpretation of the subtraction images remains very subjective. This paper describes and evaluates an automatic objective method for the analysis of parathyroid scans. The method is based on the calculation of a likelihood ratio (the probability of obtaining a count in a given pixel if a tumour is present divided by the probability of obtaining that same count if a tumour is not present). The likelihood ratio is calculated for each pixel in a subtraction image. The calculated value is compared with a threshold. Pixels with likelihood ratios greater than the threshold are classified as belonging to tumour sites. Pixels with likelihood ratios less than, or equal to, the threshold are classified as belonging to 'no tumour' sites. The probability density functions required were obtained from computer simulated images. The likelihood ratio technique has a similar sensitivity and specificity to that of experienced human observers analysing computer simulated images. Furthermore, it is a completely automatic method which can provide the basis of a decision support system.