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.

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.

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.

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.

Value of technetium-99m HMPAO-labelled leucocyte scintigraphy as an initial screening test in patients suspected of having inflammatory bowel disease.

OBJECTIVE: This study was designed to evaluate the role of technetium-99m (99mTc) hexamethyl propylene amine oxime (HMPAO)-labelled leucocyte imaging as an initial screening test in patients suspected of having inflammatory bowel disease (IBD). PATIENTS AND METHODS: Thirty-one patients in whom a final diagnosis of irritable bowel syndrome (IBS) was made (group 1) and another 33 patients with established Crohn's disease (group 2) were studied. All patients had 99mTc HMPAO-labelled leucocyte scan with imaging at 40 and 120 min. Scans with abnormal bowel uptake were considered positive and this uptake was quantified by visual grading and computer-based methods (scan score). Group 1 patients with positive 99mTc HMPAO scan underwent an indium-111 (111In)-labelled leucocyte scan (imaging at 180 min) followed by endoscopy and barium radiology as deemed necessary in order to verify the 99m Tc HMPAO result. RESULTS: Three scan patterns were seen: well localized and unequivocally positive scans at both 40 min and 2 h were obtained from 28 patients. All but one had established Crohn's disease. Diffuse bowel uptake was seen in 14 scans. Ten of these (false positive) were obtained from symptomatic patients with IBS and four (false negative) from patients with asymptomatic Crohn's disease. No bowel uptake at 40 min and 2 h was seen in 22 scans. All but two of these (who had quiescent Crohn's disease) were obtained from patients with IBS. Active Crohn's disease is associated with significantly higher scan score (mean +/- SEM, 82.1 +/- 13.6) than the false positive scans (12.5 +/- 3.1, P > or = 0.001). Patients with false positive 99mTc HMPAO scans had negative 111In scans, endoscopy and barium radiology. CONCLUSION: Bowel scanning using either 111In or 99mTc HMPAO is useful in excluding active IBD. Because of radiation dose, image quality and availability 99mTc may be preferred to 111In.

A survey of close contact regimes between patients undergoing diagnostic radioisotope procedures and children.

When following diagnostic radioisotope procedures, UK legislation requires that we advise patients to avoid close contact with children [1, 2]. How does this advice affect the average nuclear medicine patient? Over a 4 month period, 90 patients in contact with children were asked about their home circumstances, how they coped with avoidance of close contact and the problems caused. On average, the patients were in contact with two children with a mean age of 7 years. Thirty-nine per cent of patients spent < 5 h per day and 30% between 5 and 10 h per day in close contact. However, 13% spent 20-24 h in close contact with children. For most patients (55%), it is easy to avoid close contact, but 25% found it difficult or very difficult. The average in-patient received one visit a day from children of 0.5-1 h duration and 65% of children sat on the patient's bed. Restriction of visits was a problem for 14% of patients. Initially, over one-third of the out-patients felt a medium level of anxiety or higher regarding close contact with children. Given more detailed written information and the opportunity to discuss any queries with a member of staff (70% wished to do so), the proportion fell to less than one-tenth. We found it important to question patients carefully, because home circumstances and levels of close contact cannot be deduced from the age of the child or the relationship between the child and the patient.

The virtual gamma camera room.

The installation of a gamma camera is time-consuming and costly and, once installed, the camera position is unlikely to be altered during its working life. Poor choice of camera position therefore has long-term consequences. Additional equipment such as collimators and carts, the operator's workstation and wall-mounted display monitors must also be situated to maximize access and ease of use. The layout of a gamma camera room can be optimized prior to installation by creating a virtual environment. Super-Scape VRT software running on an upgraded 486 PC microprocessor was used to create a 'virtual camera room'. The simulation included an operator's viewpoint and a controlled tour of the room. Equipment could be repositioned as required, allowing potential problems to be identified at the design stage. Access for bed-ridden patients, operator ergonomics, operator and patient visibility were addressed. The display can also be used for patient education. Creation of a virtual environment is a valuable tool which allows different camera systems to be compared interactively in terms of dimensions, extent of movement and use of a defined space. Such a system also has applications in radiopharmacy design and simulation.

Computer aided test selection (CATS) for nuclear medicine--a prototype system for renal investigations.

An expert system for renal test selection in nuclear medicine has been developed as the first stage of a collaborative project on test selection in nuclear medicine. The stages of knowledge elicitation and knowledge representation were addressed by means of a questionnaire which was completed by five experts in the field of renal nuclear medicine. A flow chart was developed from the responses and implemented using a commercially available expert system shell (Crystal 4.5). A menu specifying clinical problems, for which renal nuclear medicine is useful, is displayed to the user who is prompted for a choice. Specific aspects of the chosen problem are then shown and again a choice is requested. Selected tests, in order of expert preference, are displayed and further information on any of these is available, if required, on selection from a menu subdivided into categories such as patient preparation, preliminary investigations, etc. The system provides cross-referencing to other areas of investigation and is currently being evaluated using a structured approach commonly employed in the assessment of user interfaces.

Air contamination following aerosol ventilation in the gamma camera room.

Air contamination levels arising from lung aerosol ventilation studies have previously been monitored [1]. Residence time in the room used for ventilation was perceived to be an important factor in dose received. This study was designed to assess air contamination levels when ventilation and imaging are carried out in the same room. Air samples were taken before, during and after aerosol administration, over 24 studies where a mouthpiece was used. The mean airborne contamination during administration was 4.39 kBq m-3, implying an effective dose equivalent (EDE) to the operator from inhaled activity of 0.004 microSv. Measurements made during studies on three patients where a mask was used gave a mean EDE of 0.065 microSv (the highest EDE was 0.08 microSv). Ten minutes after nebulizing had stopped, the contamination had reduced to background levels in all but two cases; in these cases, the levels were less than 1.1 kBq m-3. Aerosol ventilation in the gamma camera room does not constitute a significant radiation hazard to staff. Patient compliance is an important factor in minimizing doses. Clear instructions and practice are a vital part of the procedure.

Quantitative assessment of overall inflammatory bowel disease activity using labelled leucocytes: a direct comparison between indium-111 and technetium-99m HMPAO methods.

The ideal imaging method in inflammatory bowel disease would reliably detect inflammation, identify the correct intestinal location, and assess the severity of the disease. The aim of this study was to compare scintigraphic methods of quantifying overall disease activity using both indium-111 (111In) and technetium-99M (99mTc) HMPAO labelled leucocyte scans. The four day faecal excretion of 111In was measured after 111In scintigraphy in 24 patients known to have inflammatory bowel disease. The same patients also underwent 99mTc HMPAO scanning. The scans were performed 10 days or less apart with no changes in treatment between scans. Bowel activity on the 99mTc HMPAO scans was assessed using a computer based method (scan score) and a visual grading method in a further 54 99mTc HMPAO. The results showed a close correlation between inflammatory activity defined by faecal 111In excretion and the scan score generated from the computer analysis of the 99mTc HMPAO image (Spearman rank correlation: rs = 0.78; p < 0.001). Accurate information to localise inflammatory activity could be obtained by simple visual assessment of both types of scan images, although image quality was superior with 99mTc HMPAO. Qualification of disease activity from 99mTc HMPAO images by visual grading was associated with a large variability, only 69% of scans had similar scores when graded by three observers. Computer generated image analysis was more reproducible. In conclusion, in inflammatory bowel disease 99mTc HMPAO scintigraphy and faecal 111In excretion correlated well. Either method can quantify and localise the inflammation. As 99mTc HMPAO scanning provides a quicker result, with a lower radiation dose, and avoids faecal collection, it may be the preferred method.