Coregistration imaging of the foot. A new localisation technique.

We describe a new technique, known as coregistration imaging, which superimposes 99mTc isotope bone scans on to plain radiographs. We used the technique selectively in cases in which the nuclear medicine physician, who reported the isotope scan, had difficulty in localising the anatomical site of the abnormality. In the forefoot, coregistration of isotope scans did not help to localise pathology; the scan alone gave sufficient detail. In 17 patients with pain in the hind- and midfoot, isotope scanning identified eight sites of abnormality in those with normal radiographs. In those with more than one abnormality on plain radiographs the isotope scan eliminated 12 sites of suspicion. Coregistration of the images significantly increased the certainty of localisation of disease (p < 0.001). We recommend the selective use of coregistration scanning as a useful technique for investigating patients with pain in the foot and ankle.

Seven-hour stabilization of 99Tcm-exametazime (HMPAO) for cerebral perfusion.

The objective of this study was to increase the stability of 99Tcm-exametazime and to investigate the effects of relaxing the eluate restrictions imposed by the manufacturer. We added 1800 MBq freshly eluted pertechnetate to 0.5 ml aliquots of stannous-enhanced exametazime followed by the addition of 0.7 mg gentisic acid and 0.5 ml sterile absolute alcohol BP. The radiochemical purity as measured by thin-layer chromatography was maintained at over 80% (range 88-99%, n = 40) for up to 7 h after preparation. High-performance liquid chromatography confirmed that the primary complex was maintained at over 80% (ranges 89-92%) for up to 7 h. In a second series of studies using the first eluate from a newly delivered generator to prepare 99Tcm-exametazime, a radiochemical purity of more than 80% was achieved for up to 7 h (range 88-95%, n = 24). In a third series using a 3-hour-old generator eluate, a radiochemical purity of more than 80% (range 88-93%, n = 18) was achieved for up to 5 h (for logistic reasons, we were unable to continue readings beyond 5 h). These results suggest that the manufacturer's restrictions on the eluate may be relaxed. Clinical validation was performed in a blinded study of 21 patients using single photon emission tomography. Image quality was assessed on the basis of salivary activity, nasal activity and the overall (global) image quality. There was no significant difference between the images obtained using the stabilized exametazime and exametazime prepared without gentisic acid and ethanol (chi 2 = 2.85, P = 0.05). We conclude that stabilization of 99Tcm-exametazime can be achieved for up to 7 h by using gentisic acid and alcohol and that the eluate restrictions may be disregarded.

Skeletal muscle weakness and dysphagia caused by acid maltase deficiency: nutritional consequences of coincident celiac sprue.

BACKGROUND: A 30-year-old woman with celiac sprue had progressive weight loss, myalgia, limb-girdle weakness, and dysphagia. METHODS AND RESULTS: Barium swallow showed an atonic esophagus, and scintigraphic study confirmed esophageal dysmotility. Skeletal muscle biopsy showed characteristic appearances of acid maltase deficiency, which was confirmed by a reduction of leukocyte acid alpha-glucosidase activity. CONCLUSIONS: Nutritional factors may have accelerated the presentation of the lysosomal storage disorder. This is the first reported case of dysphagia caused by esophageal motor weakness in acid maltase deficiency.

Cerebral vasculitis--recognition, diagnosis and management.

Cerebral vasculitis is a serious but uncommon condition which presents considerable difficulties in recognition, diagnosis and treatment. We studied eight consecutive patients in whom this diagnosis was made. Despite the great diversity of symptoms and signs, we noted three clinical patterns: (i) acute or sub-acute encephalopathy, (ii) a picture with some similarities to multiple sclerosis ('MS-plus'), and (iii) features of a rapidly progressive space-occupying lesion. The identification of these patterns may help recognition of cerebral vasculitis. The diagnostic value of four investigative procedures not previously studied in cerebral vasculitis was assessed: ophthalmological examination using low-dose fluorescein angiography with slit-lamp video microscopy of the anterior segment (abnormal in 4/5 patients); spinal fluid oligoclonal band analysis (abnormal in 3/6 patients); anti-neutrophil cytoplasmic antibody assay (abnormal in 3/8 patients); and indium-labelled white-cell cerebral imaging (positive in only one patient). Treatment was with steroid alone (n = 2) or steroid with cyclophosphamide (n = 6). Seven patients responded clinically.

Therapeutic delivery of proteins to macrophages: implications for treatment of Gaucher's disease.

BACKGROUND: The primary defect in Gaucher's disease, a lysosomal disorder affecting macrophages, is in the activity of glucocerebrosidase. Treatment with exogenous enzyme (modified to increase its affinity for macrophage glycoprotein receptors) aims to restore this activity. However, the fate of the exogenous enzyme in vivo is unknown. We used radiolabelled enzyme to assess macrophage receptor activity for mannosylated ligands in vivo. METHODS: We examined the uptake and tissue distribution of radiolabelled enzyme molecules by gamma scintigraphy after bolus injection of iodine-123-labelled recombinant or placental enzyme (imiglucerase and alglucerase, respectively) in eight patients with type 1 Gaucher's disease, and in one healthy individual. The metabolism of the tracer enzyme was followed by scintigraphy and by analysis of blood, urine, and faeces. RESULTS: The tracer enzyme was rapidly cleared from blood (half-life 4.7 min [SD 1.0]). Concomitantly, there was avid uptake by the liver (about 30% of the injected dose), the spleen (about 15%), and the bone marrow. 40-55% of the tracer was cleared rapidly from the viscera (half-life 1-2 h) and 45-60% was cleared slowly (half-life 34-42 h). The half-life in the bone marrow was 14.1 h. Infusion of alglucerase at dose of 5 U/kg bodyweight normalised acid beta-glucosidase activity of splenic Gaucher's cells in vivo. When the enzyme was administered at a seven-fold higher dose (35 U/kg over 1 h), the receptor-mediated uptake in vivo was saturated, as shown by the increase in blood-clearance half-life of tracer enzyme from 4.5 min to 12 min. INTERPRETATION: Avid and saturable uptake of modified glucocerebrosidase was found, which indicates high-affinity targeting to the macrophage system in vivo. The rate of enzyme turnover suggests a rational basis for use of this therapy in treatment of Gaucher's disease.

The significance of low grade right iliac fossa uptake on 99Tcm-HMPAO labelled white cell scans.

Technetium-99m HMPAO labelled white cell scanning is now an accepted method for assessing the activity of inflammatory bowel disease. However, false positive results have been demonstrated. This study was conducted to assess the significance of low grade uptake on 99Tcm-HMPAO labelled white cell scans in the right iliac fossa (RIF) in the context of possible inflammatory bowel disease (IBD). 32 patients over a period of 1 year had low grade RIF uptake as the predominant abnormality. 20 of these had no prior diagnosis of inflammatory bowel disease. Only one case in this group was subsequently diagnosed as having Crohn's disease. Nodular lymphoid hyperplasia (NLHP) and non-steroidal anti-inflammatory drugs (NSAIDs) were also associated with low grade RIF uptake. Possible explanations for these findings are discussed.

Accuracy of serology for the diagnosis of Helicobacter pylori infection--a comparison of eight kits.

AIMS: To determine the accuracy of eight commercially available kits for the serological diagnosis of Helicobacter pylori infection, and hence whether a serology service could be introduced to reduce endoscopy workload. METHODS: Eighty four patients newly presenting to their general practitioners with dyspepsia were recruited. Gold standard diagnosis of H pylori infection was obtained both by a histological examination of gastroduodenal biopsy specimens and by the 14C-urea breath test (UBT). The performance of six quantitative and two qualitative enzyme linked immunosorbent assays for H pylori IgG, used according to the manufacturers' instructions, with serum samples obtained during the endoscopy visit, were compared. RESULTS: The study population had a median age of 45 years, and the prevalence of H pylori infection was 35%. With one exception, where the patient had received a course of anti-H pylori treatment between endoscopy and UBT, there was 100% concordance in the results of the two gold standard techniques. Discordant serology results were more common in patients aged > 50 years (42% of the total) than in younger patients (21%), and this was most noticeable in uninfected patients. The sensitivity of the kits was good (90-100%), but specificity was more variable (76-96%), and the rate of equivocal results was unacceptably high in some cases (0-12%). The overall accuracy of the kits ranged from 83 to 98%. Two kits in particular performed well (Pylori-Elisa II, Bio-Whitaker and Premier, Launch; qualitative) with 98% and 100% accuracy, respectively. CONCLUSIONS: In a symptomatic population with a prevalence of H pylori infection of 35%, particularly in patients aged < 50 years, some but not all serology kits may be used as a highly accurate and inexpensive alternative to the gold standard techniques.

Radionuclide studies in intestinal transplantation. Diagnosis of rejection and assessment of permeability.

Three patients who received intestinal allografts were studied using two distinct radionuclide investigations. In the first, 111In or 99mTc-labeled leukocyte scanning was performed to assist in the diagnosis of rejection. It was able to demonstrate the occurrence of rejection in the transplanted intestine, and the response to antirejection therapy. In 1 case, the abnormality on the scan preceded the histological confirmation of rejection. The second technique studied mucosal integrity by serial 51Cr-EDTA/14C-mannitol permeability tests. These studies demonstrated the initial marked impairment and the slow return to normal function of the intestinal mucosal barrier. In 1 patient, this occurred by 91 days; in another, it took 232 days. A single assay performed in the third patient at the time of allograft rejection was also abnormal. Both radionuclide tests were helpful in the care of these complicated cases.

Validation of 99Tcm-HMPAO leucocyte scintigraphy in ulcerative colitis by comparison with histology.

Leucocyte scintigraphy offers an alternative to more invasive techniques in the investigation of inflammatory bowel disease. The accuracy of 99Tcm-HMPAO leucocyte scintigraphy has not been assessed by comparison with colonic histology, which was the aim of this study. 15 patients with ulcerative colitis underwent 99Tcm-HMPAO leucocyte scintigraphy (TLS) less than 5 days before colonoscopy. Histological features of mucosal biopsies were compared with total and segmental colonic TLS scores. Segmental and total scintigraphy scores correlated most strongly with histological grades for acute inflammation (r = 0.75, p < 0.001 and r = 0.9, p < 0.001, respectively) and chronic inflammatory cell infiltration in the lamina propria (r = 0.76, p < 0.001 and r = 0.86, p < 0.001, respectively). 99Tcm-HMPAO leucocyte scintigraphy detected acute inflammation in the colon of patients with ulcerative colitis with a sensitivity of 91% and negative predictive value of 80% and localized acute inflammation to a particular colonic segment with a sensitivity of 82%, specificity of 94%, accuracy of 88%, positive predictive value of 94% and negative predictive value of 91%. 99Tcm-HMPAO leucocyte scintigraphy positivity predicts and localizes colonic acute inflammation with a high degree of confidence, but negative scintigraphy does not exclude acute inflammation.

Management of systemic vasculitis: contribution of scintigraphic imaging to evaluation of disease activity and classification.

The use of radio-isotope-labelled leucocyte scans has become established as a non-invasive and accurate means of diagnosing a variety of inflammatory conditions. We report a retrospective study on leucocyte imaging in the management of 50 patients with systemic vasculitis. Leucocyte imaging was useful for detecting unsuspected sites of disease and monitoring disease activity. Scintigraphy was superior to conventional radiography or CT scanning for detecting and monitoring vasculitic involvement of the respiratory tract. The scans were useful for differentiating between Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). There was a close and statistically significant relationship between the clinical diagnosis of WG and nasal uptake on leucocyte scans (p < 0.01), whereas in patients with MPA it was rare. Anti-proteinase 3 autoantibody specificity correlated significantly with nasal uptake of labelled leucocytes (p < 0.03). Leucocyte imaging is a useful non-invasive investigation in patients with systemic vasculitis.

Indium-111 labelled leucocyte uptake in aortitis.

Inflammatory conditions of the aorta may present with non-specific clinical features, including unexplained fever. Indium-111 labelled leucocyte imaging may be performed in such patients to look for the presence of occult sepsis or to assess the activity of a known vasculitis. Of approximately 1100 patients to undergo leucocyte scintigraphy for these indications over a 5 year period, three had focal leucocyte uptake in the aorta. The final diagnoses were: (1) periaortitis in Wegener's granulomatosis; (2) aortic dissection in giant cell arteritis; and (3) streptococcal aortitis with impending rupture. In all three cases the uptake was initially not thought to be in the aorta, but in bowel, a paravertebral abscess and in the lumbar spine respectively. Further imaging with CT and MRI led to the correct diagnoses. As the aorta is a rare site of focal leucocyte uptake, errors in image interpretation are likely. The rapid diagnosis of inflammatory conditions of the aorta is essential, however, as they may be life-threatening if unrecognized; therefore awareness of the aorta as a potential site of uptake is important. Urgent referral for further imaging is imperative in these cases as a false or delayed diagnosis may lead to avoidable morbidity and mortality.

Evaluation of the skull base by SPECT. A comparison with planar scintigraphy and computed tomography.

Computed tomography is currently the standard diagnostic tool for the evaluation of the skull base. The complex anatomy of this area is the primary reason why planar bone scintigraphy is often unsatisfactory; exact localization of abnormalities may be very difficult. These limitations may be overcome by SPECT. Seventeen patients with clinical features of basal skull involvement were assessed by CT, SPECT, and planar scintigraphy. Subsequent clinical diagnoses were malignancy in 15 patients, vasculitis in 1 patient, and osteomyelitis in 1 patient. Computed tomography with IV contrast was performed through the skull base at 5 mm intervals. Planar scintigraphy with Tc-99m MDP was followed by SPECT. Bony involvement compatible with the clinical findings was demonstrated by CT scans in 6 patients, by planar scintigraphy in 7 patients, and by SPECT in 9 patients. The abnormalities that were identified by CT were all identified by SPECT. This study suggests that, in imaging the skull base, SPECT is more sensitive and provides better anatomical localization than planar imaging and appears useful in patients with a negative CT study.

Scintigraphic appearances in patients with pulmonary infection and lung scintigrams of intermediate or low probability for pulmonary embolism.

Out of 294 patients with lung scintigrams of low or intermediate probability for pulmonary embolism, the appearances in 54 patients with a final diagnosis of pulmonary infection were reviewed. The most common finding was a matched defect in ventilation and perfusion occurring in 40 patients (76%). Regional reverse mismatch occurred in 13 patients (24%) and both appearances were found in one patient (2%). Reverse mismatch was also present in a further seven patients, four of whom had bronchial obstruction. Although occurring less frequently than matched defects, 81% of regional reverse mismatched defects were because of chest infection. The presence of regional reverse mismatch in patients investigated for pulmonary embolism suggests the alternative diagnosis of chest infection.

Stabilization and multidose use of exametazime for cerebral perfusion studies.

The efficient use of exametazime for cerebral blood flow imaging is restricted by the short useful life of the reconstituted kit due to the instability of the primary complex. It is therefore recommended that 99Tcm-exametazime be used within half an hour after preparation allowing only a single patient dose to be prepared from one vial of exametazime. The shelf-life of 'cold' reconstituted exametazime has been extended by means of stannous enhancement. Freshly prepared stannous fluoride solution, 0.8 ml (5.4 micrograms SnF2), was mixed with 0.5 ml (42 micrograms) exametazime solution followed by the addition of up to 1500 MBq pertechnetate. The radiochemical purity of the chelate was 91% (S.D. 3.6%, n = 3). The rate of conversion of the primary complex (kc = 0.012 +/- 0.011 h-1) was considerably slower than the rate of degradation obtained using the recommended method of preparation (kc = 0.17 +/- 0.02 h-1). Radiochemical purity levels greater than 80% were maintained for up to 2.5 h after preparation and the level of free pertechnetate did not exceed 7%. There was only a slight deterioration of the cold reconstituted exametazime on storage of 0.3 +/- 0.1% per day. However, exametazime reconstituted up to 3 weeks previously produced more than 80% purity. The mean radiochemical purity obtained in 22 studies was 90% with a range of 81-98%. Clinical validation was performed in a blinded study of 38 patients using single photon emission computed tomography (SPECT). There was no significant difference between the images obtained using the tin enhancement method of preparation and the manufacturer's method (chi 2 = 3.62, P = 0.16).(ABSTRACT TRUNCATED AT 250 WORDS)

Short communication: venous uptake of 99Tcm-MIBI during resting cardiac imaging: incidence and the effect of using a flush.

99Tcm-methoxy-isobutyl-isonitrile (99Tcm-MIBI) is taken up by the vein through which it is injected in some individuals. We prospectively analysed technical and clinical factors that may be associated with this uptake. Imaging was performed over 1 h after injection so excluding a blood pool effect. The frequency of uptake could be reduced from 25.9% to 4.2% by using a 20 ml saline flush (p < 0.05). Other factors appeared irrelevant. The presence of venous uptake did not affect myocardial counting statistics but, if unrecognized, it could cause confusion in studies of the neck or chest that use 99Tcm-MIBI.

Technetium (99mTc)-labelled white cell scanning, 51Cr-EDTA and 14C-mannitol-labelled intestinal permeability studies: non-invasive methods of diagnosing acute intestinal graft-versus-host disease.

We describe a case of a 38-year-old female who presented with diarrhoea and abdominal pain 27 days after a second 'top-up' allogeneic marrow infusion for acute myeloid leukaemia (AML) in first remission. A clinical diagnosis of gut graft-versus-host disease (GVHD) was made. Technetium (99mTc)-labelled white cell scanning and intestinal permeability studies using 51Cr-EDTA and 14C-mannitol were undertaken to confirm the diagnosis. The 99mTc white cell scan showed extensive uptake in the small bowel and the urinary excretion of 51Cr-EDTA was increased, the results being consistent with intestinal inflammation and gut GVHD. 99mTc white cell scanning and intestinal permeability studies may assist in the diagnosis of gut GVHD and in assessing its extent and response to treatment.

Can 99Tcm HMPAO leucocyte scintigraphy distinguish between Crohn's disease and ulcerative colitis?

This paper has retrospectively analysed the ability of 99Tcm HMPAO leucocyte scintigraphy to distinguish Crohn's disease from ulcerative colitis. The diagnostic criteria were established by reviewing 99Tcm HMPAO leucocyte scintigrams in 123 patients with histologically proven Crohn's disease (83) or ulcerative colitis (40). Uptake in the right iliac fossa with or without other segments of colon, irregular bowel uptake, small bowel uptake or colonic activity with rectal sparing were all strongly suggestive of Crohn's disease. Left sided colitis was found to indicate ulcerative colitis. Total colitis occurred in both ulcerative colitis and Crohn's disease. The criteria were later tested in an additional 62 patients with excellent results (accuracy 98%). In 63 patients in whom the results of barium radiology were also available, the accuracy of scintigraphy was higher (93% and 83%, respectively). We conclude that 99Tcm HMPAO leucocyte scintigraphy can accurately distinguish between Crohn's disease and ulcerative colitis in a large proportion of cases and appears to be more reliable than conventional radiology.