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Reliability of radionuclide gastroesophageal reflux studies using visual and time-activity curve analysis: inter-observer and intra-observer variation and description of minimum detectable reflux.

Radionuclide studies have gained wide acceptance in the evaluation of infants and children with gastroesophageal reflux (GER). For correct interpretation of scan results, knowledge of inter-observer and intra-observer variability and minimum detectable reflux volume is essential. In this study, we evaluated the methodological issues underlying the visual assessment of GER and time activity curve analysis. An in vitro model of stomach and oesophagus was established to determine the minimum detectable reflux by placing various volumes and concentrations representing the diluted activity in the stomach. In the clinical part 99 patients were imaged for 1 h after oral administration of 99mTc sulfur colloid. Eleven patients were excluded from the study either due to incomplete clinical data or suboptimal image quality. Frames of 16 s each, and time-activity curves which were generated after drawing regions of interest from the oesophagus, were read three times by an experienced nuclear medicine physician and a resident in training. On the phantom study, the concentration, volume and duration were the determining factor for the visualization of reflux. In the clinical part, the overall incidence of GER in 88 patients was 69%. The mean intra- and inter-observer reproducibility (kappa values) was 0.76 and 0.7065, respectively. Agreement was slightly higher in the analysis of time-activity curves (0.767 and 0.731). Our results indicate that GER may be reproducibly analysed on scintigraphy by the same and different observers with varying levels of training. Its visualization is associated with reflux duration, volume and dilution factor of radioactivity.

Child↗

Quantitative analysis in single photon emission tomography (SPET).

Quantitative analysis can improve the sensitivity and specificity of single photon emission tomography (SPET) procedures, as well as reduce inter- and intraobserver variabilities. Quantification of the radioactivity distribution is the ultimate goal of SPET. In this review we consider the basic requirements for an optimum three-dimensional reconstruction of the radionuclide distribution to enable quantification. Attenuation and scatter correction as well as varying resolution are the major problems. In the older SPET systems quantification was hampered by the lack of system sensitivity and sufficient computer power. Therefore, the imaging system was often assumed to be shift invariant and linear and the attenuation throughout the object uniform. More sophisticated solutions have been proposed and with more or less success implemented, but not for application in daily practice. Knowledge (measurement) of the attenuation is often required. New generation SPET systems employing multi-detectors and super minicomputers will ease the implementation of these solutions.

Humans↗

Site-specific cancer incidence and mortality after cerebral angiography with radioactive thorotrast.

Few opportunities exist to evaluate the carcinogenic effects of long-term internal exposure to alpha-particle-emitting radionuclides. Patients injected with Thorotrast (thorium-232) during radiographic procedures, beginning in the 1930s, provide one such valuable opportunity. We evaluated site-specific cancer incidence and mortality among an international cohort of 3,042 patients injected during cerebral angiography with either Thorotrast (n = 1,650) or a nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and Sweden) were estimated and relative risks (RR), adjusted for population, age and sex, were generated with multivariate statistical modeling. For U.S. patients, comparable procedures were used to estimate standardized mortality ratios (SMR) and RR, representing the first evaluation of long-term, site-specific cancer mortality in this group. Compared with nonexposed patients, significantly increased risks in Thorotrast patients were observed for all incident cancers combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident cancers were above expectation, with large excesses seen for cancers of the liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with time since angiography (P < 0.001) and was threefold at 40 or more years; significant excesses (SIR = 4.0) persisted for 50 years. Increasing cumulative dose of radiation was associated with an increasing risk of all incident cancers taken together and with cancers of the liver, gallbladder, and peritoneum and other digestive sites; similar findings were observed for U.S. cancer mortality. A marginally significant dose response was observed for the incidence of pancreas cancer (P = 0.05) but not for lung cancer. Our study confirms the relationship between Thorotrast and increased cancer incidence at sites of Thorotrast deposition and suggests a possible association with pancreas cancer. After injection with >20 ml Thorotrast, the cumulative excess risk of cancer incidence remained elevated for up to 50 years and approached 97%. Caution is needed in interpreting the excess risks observed for site-specific cancers, however, because of the potential bias associated with the selection of cohort participants, noncomparability with respect to the internal or external comparison groups, and confounding by indication. Nonetheless, the substantial risks associated with liver cancer and leukemia indicate that unique and prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic risks.

Adult↗

The role of cardiac imaging and biochemical markers in patients with acute chest pain.

Acute chest pain syndromes are common, with over 6 million patients in the United States presenting to emergency departments with suggestive symptoms. This review concentrates on the previous models and new diagnostic testing procedures. The different modalities emphasized are computer-generated models, serum markers, echocardiography, and nuclear imaging in the emergency department. The use of new markers and imaging may help to risk-stratify patients earlier for potential treatment and triage decisions.

Biomarkers↗

Postoperative infection with the automatic implantable cardioverter defibrillator: clinical presentation and use of the gallium scan in diagnosis.

This report describes three patients with infection involving an automatic implantable cardioverter defibrillator. All three patients presented with fever, fluid in the pulse generator pocket, leukocytosis and an elevated erythrocyte sedimentation rate. A gallium scan, together with aspiration and culture of the fluid from the pocket, confirmed the diagnosis in each case.

Candidiasis↗

Simplified method for determining the modulation transfer function for the scintillation camera.

The modulation transfer function (MTF) has long been accepted as an index of scintillation camera system resolution, but the technique necessary for the derivation of the MTF has discouraged its widespread acceptance because of its tedious and time-consuming nature. We have shown that the generation of LSFs for input into computer programs for MTF generation can be accomplished very easily and in short periods of time by using a simplified method. Establishment of the validity of this simplified procedure should contribute to more widespread utilization of the MTF in routine quality control programs as a check for crystal deterioration, electronic circuitry degradation, and/or collimator damage.

Radionuclide Imaging↗

[Bone densitometry by monochromatic photon absorption. Study of a normal population and values obtained in various pathological conditions].

Monophotonic absorption densitometry of the forearm is an exact method for the evaluation of the bone mineralisation, provided the positioning of the forearm is strictly controlled. It is also able to demonstrate progressive enlargement of the bones with age, up until the ages of about 60 to 70 years. The measurements should be performed in two sites: diaphyseal (cortical bone) and epiphyseal (cortical and trabecular bone). The curves obtained from 1,011 controls are in agreement with the current state of knowledge concerning the variations in bone mass during life in both sexes. In women, the number of pregnancies has no influence on the mineralisation index (MI). The values obtained in 156 osteoporotic patients and in 53 subjects with idiopathic hypercalciuria were appreciably lower than those obtained in age-matched controls. In individual subjects, this method appears to be much more discrimination than the measurement of the trabecular bone volume (TBV) for the diagnosis of osteoporosis and no statistically significant correlation was observed between the MI and the TBV. In male controls, there was a depression of the mean curves around the age of 45 years in all four sites of measurement. This depression was also observed in male subjects with hypercalciuria. They correspond to the generations born between 1930 and 1940. The responsibility of a relative nutritional deficiency affecting growing boys during the 1939-45 war is proposed.

Adolescent↗

Comparative study of Dutch and German emergency-management models for near border nuclear accidents.

Four institutes, all of which are involved in nuclear-emergency management in the Dutch-German border region, have compared their short-range dispersion and radiological dose models using scenarios consisting of single-station meteorology and two dispersed radionuclides. After adjustment of some of the parameters, the consequence of the differences in parameters on the effective dose was quantified at several stages from source to exposure. Results for the neutral stability class agreed within a factor of four. Variations in wet deposition of radioactive material, giving rise to external radiation from the ground, can cause significant variations to the effective dose. Furthermore, the way the different emergency-management tools model the atmospheric dispersion for a stable stability class in the horizontal plane can generate large differences. Finally, the methodology of calculating cloudshine is not comparable among the models, which causes the effective dose near the source to show large deviations for high emission sources.

Accidents↗

Noninvasive diagnosis of renovascular disease.

OBJECTIVE: To present the epidemiologic and clinical features of renovascular disease and discuss various diagnostic approaches. DESIGN: We describe the findings in patients with fibromuscular dysplasia or atherosclerotic disease of the renal arteries and review pertinent studies from the literature. RESULTS: Renovascular disease is an important cause of resistant hypertension and progressive renal insufficiency, particularly in the elderly population. Improved blood pressure control and renal function after revascularization have generated intense interest in identifying those patients likely to benefit from this intervention. Fibromuscular dysplasia and atherosclerotic renal artery stenosis account for most cases of renovascular disease. Both entities produce resistant hypertension; the latter is the more common cause of progressive renal insufficiency--occasionally leading to end-stage renal disease. Angiotensin-converting enzyme inhibitor-related renal dysfunction, otherwise unexplained renal insufficiency, and recurrent pulmonary edema are increasingly recognized clinical manifestations of renovascular disease. Traditional screening tests such as intravenous pyelography, intravenous digital subtraction angiography, radionuclide scintirenography, and measurement of the peripheral venous plasma renin activity have limited accuracy for diagnosing renal artery stenosis and do not accurately predict the blood pressure response to revascularization. In comparison, recently developed noninvasive tests such as captopril renography, renal artery duplex sonography, and magnetic resonance angiography seem to be more accurate and, in the case of captopril renography, may be more predictive of the blood pressure response to revascularization. CONCLUSION: Future directions in the area of renovascular disease should include a direct comparison among these new noninvasive diagnostic techniques, with a particular focus on the identification of those patients most likely to benefit from revascularization in terms of both blood pressure control and improved renal function.

Humans↗

A kit formulation for the preparation of 188Re-lipiodol: preclinical studies and preliminary therapeutic evaluation in patients with unresectable hepatocellular carcinoma.

A lyophilized kit formulation for the efficient labelling of lipiodol with generator-produced rhenium-188 is described. The preliminary preparation of the lipophilic complex bis-(diethyldithiocarbamato)nitrido rhenium-188 (188ReN-DEDC) was carried out using a two-vial kit containing S-methyl-N-methyl-dithiocarbazate, SnCl2 and sodium oxalate in the first vial, and diethyldithiocarbamate and a carbonate buffer in the second vial. After mixing of the reaction solution with lipiodol, the complex 188ReN-DEDC was quantitatively extracted and retained by this hydrophobic substance, thus allowing the stable incorporation of the beta-emitting radionuclide. The radiochemical purity of the complex 188ReN-DEDC was 97+/-2%. The activity extracted into the lipiodol phase was 96+/-3% of the initial activity, indicating that the complex 188ReN-DEDC was almost quantitatively removed from the aqueous reaction solution. In vitro stability studies in human plasma, at 37 degrees C, demonstrated the release of less than 15% of the activity within three half-lives. The biodistribution of Re-lipiodol in non-tumour-bearing Wistar rats at 6, 24, 48 and 72 h after intraportal venous injection showed one-third of total activity in the liver at 6 h, declining to 2% retention at 72 h. Bowel uptake at 6 and 24 h declined to low levels at 48 and 72 h. Renal activity peaked at 1.7%, diminishing to 0.6% over 48 h. Rat whole body gamma imaging showed gut activity in addition to hepatic uptake at 6 and 24 h, but only liver was evident from 48 to 72 h. Kidneys were not demonstrable at any imaging time point. In nine patients, activity was localized in the tumours immediately following intrahepatic arterial injection. Computed tomography/single-photon emission computed tomography (CT/SPECT) imaging at 1 and 24 h confirmed the retention of 188Re-lipiodol in the hepatoma, with minimal gut uptake and no lung activity over 24 h. These patients were subsequently treated with activities of 2.5-5 GBq of 188Re-lipiodol fractions without adverse effects. Six patients followed for up to 2 years in the pilot study achieved stable disease and there was objective partial response in one patient. Repeated treatments were performed on two to three occasions in three patients without evident toxicity. An additional patient given 6 GBq of 188Re-lipiodol demonstrated myelosuppression, which recovered with granulocyte colony-stimulating factor (GCSF) and platelet support. It is concluded that 188Re-lipiodol, prepared using our novel kit formulation, is stable in vivo and provides safe and effective therapy of unresectable hepatocellular carcinoma when given via the hepatic artery, either alone or in combination with transarterial chemoembolization.

Animals↗

Prostate brachytherapy: comparison of dose distribution with different 125I source designs.

PURPOSE: To evaluate the interchangeability of various commercially available iodine 125 ((125)I) sources and to assess the dosimetric effect of a change in source. MATERIALS AND METHODS: A modified peripherally loading prostate brachytherapy plan to deliver 145 Gy was devised by using a model (125)I source, which until recently was the only available (125)I source. A dose-volume histogram was generated. By using the available radial dose functions and anisotropy distributions for eight other currently commercially available sources, the same implant placement was planned and dose-volume histogram distributions tabulated. This exercise was performed for 15-, 45-, and 60-cm(3) glands. No implants were placed, and no physical radiation measurements were made. Dose calculations were theoretic: They were generated by using a widely available treatment planning system. RESULTS: There was little difference in dose distribution to the volume receiving 100% of the prescribed dose (<6%); only one source showed a difference greater than 2%. Large differences, up to -40% to +60%, were seen in the volume of tissue encompassed within internal high-dose regions receiving 150% or 200% of the prescribed dose. These findings held true, irrespective of gland size, within a clinically relevant range (15-60 cm(3)) and for a uniformly loaded radionuclide distribution. CONCLUSION: Reviewing only peripheral dose at or near the prescription dose of 145 Gy revealed little difference in doses for various source designs. Marked differences in high-dose regions were seen and may affect the dose received by internal sites. Effects of these changes on cure and/or complications remain speculative.

Brachytherapy↗

[Radionuclide cisternography: SPECT- and 3D-technique].

Radionuclide cisternography is indicated in the clinical work-up for hydrocephalus, when searching for CSF leaks, and when testing whether or not intracranial cystic lesions are communicating with the adjacent subarachnoid space. This paper demonstrates the feasibility and diagnostic value of SPECT and subsequent 3D surface rendering in addition to conventional rectilinear CSF imaging in eight patients. Planar images allowed the evaluation of CSF circulation and the detection of CSF fistula. They were advantageous in examinations 48 h after application of 111In-DTPA. SPECT scans, generated 4-24 h after tracer application, were superior in the delineation of basal cisterns, especially in early scans; this was helpful in patients with pooling due to CSF fistula and in cystic lesions near the skull base. A major drawback was the limited image quality of delayed scans, when the SPECT data were degraded by a low count rate. 3D surface rendering was easily feasible from SPECT data and yielded high quality images. The presentation of the spatial distribution of nuclide-contaminated CSF proved especially helpful in the area of the basal cisterns.

Adult↗

Computer-assisted static/dynamic renal imaging: a screening test for renovascular hypertension?

Computer-assisted static/dynamic renal imaging with [197Hg] chlormerodrin and [99mTc]pertechnetate was evaluated prospectively as a screening test for renovascular hypertension. Results are reported for 51 patients: 33 with benign essential hypertension and 18 with renovascular hypertension, and for 21 normal controls. All patients underwent renal arteriography. Patients with significant obesity, renal insufficiency, or renoparenchymal disease were excluded from this study. Independent visual analyses of renal gamma images and time-activity transit curves identified 17 of the 18 patients with renovascular hypertension; one study was equivocal. There were five equivocal and three false-positive results in the essential hypertension and normal controls groups. The sensitivity of the method was 94% and the specificity 85%. Since the prevalence of the renovascular subset of hypertension is approximately 5%, the predictive value is only 25%. Inclusion of computer-generated data did not improve this result. Accordingly, this method is not recommended as a primary screening test for renovascular hypertension.

Adult↗

Implementation and evaluation of patient-specific three-dimensional internal dosimetry.

UNLABELLED: Current methods for calculating the absorbed dose in a target region from a source region rely on a standard "reference man" geometry and assume an uniform distribution of radiolabel. While this approach is acceptable at the low levels of radioisotope administered for most diagnostic purposes, the generality of the calculations is not adequate for doses at the higher levels required for therapy and is not easily extendible to tumor dosimetry. METHODS: We have developed an integrated system which utilizes patient anatomy and radionuclide distribution in the calculation of absorbed dose rate or total dose to any user-defined target region. Images of radionuclide distribution (PET/SPECT) are registered to anatomic images (CT/ MRI) and then entered into a three-dimensional internal dosimetry software system (3D-ID) where regions of interest are defined. Dose calculations are performed by the mathematical convolution between a user-specified, dose-point kernel with the activity in the source volume over the target volume. The resulting dose rate distribution may be scaled by cumulated activity to yield absorbed dose. In addition to calculating the mean dose, dose-volume histograms may be generated which plot absorbed dose with respect to percent of volume. The method was evaluated using selected standard man phantom organs. RESULTS: Dose estimates for two patient studies are included to illustrate differences between patient-specific and MIRD-based calculations. The package provides an alternative approach to image display and three-dimensional internal dose calculations. CONCLUSION: The dose-volume histogram representation of absorbed dose to a target volume provides valuable information in assessing tumor control probability and normal tissue toxicity.

Dose-Response Relationship, Radiation↗

Alterations in left ventricular diastolic function in chronic ischemic heart failure. Assessment by radionuclide angiography.

Using radionuclide angiography at rest, we studied several parameters of left ventricular systolic and diastolic function in 60 patients divided into three groups, a control group (G1) of 15 patients and two groups of patients with chronic ischemic heart disease and previous anterior wall myocardial infarction but without aneurysm or dyskinetic wall motion, a second group (G2) of 23 patients with no history of heart failure, and a third group (G3) of 22 patients in New York Heart Association (NYHA) class II or III of heart failure. Ejection fraction, peak emptying, and peak filling rates, in addition to times to reach peak rates, were evaluated after constructing a global time-activity curve and its first time derivative. In addition, we computed the first time-derivative curves for each image pixel and obtained functional images (MIN/MAX images) representing the distribution of times to peak emptying or filling rates Using a left ventricular region of interest, time histograms were generated, and indexes of dispersion of times to peak rates, defined as the full width at half maximum of the histograms, were obtained. Significant (p less than or equal to 0.01) differences were observed among all groups for ejection fraction, peak emptying rate, and peak filling rate. The decrease of the peak filling rate still remained significant from group G1 to group G3 even after adjustment for differences in ejection fraction and heart rate. Peak filling rate was linearly correlated with ejection fraction in the population with ischemic heart disease (G2 + G3) (r = 0.68, p less than or equal to 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Characterization of Fe(III)-reducing enrichment cultures and isolation of Fe(III)-reducing bacteria from the Savannah River site, South Carolina.

The Savannah River site, South Carolina (SRS), has been subjected to heavy metal and radionuclide contamination. Dissimilatory Fe(III)-reducing bacteria, by reducing insoluble Fe(III) to soluble Fe(II), may enhance contaminant mobility through subsurface environments. In order to investigate populations of the indigenous iron-reducing microbes from the SRS, duplicate enrichment cultures were initiated using a 10% inoculum of 7 sediment/soil samples, and serial dilutions were made into Wolfe's minimal salts media amended with 50 mM Fe(III) floc, 10 mM acetate and 0.01% yeast extract. Terminal restriction fragment length polymorphism (T-RFLP) analysis was used to generate fingerprints of the cultures and track changes in the microbial communities through the dilutions. Cluster analysis determined the relatedness of individual fingerprints. Initial enrichment cultures exhibited complex fingerprints consisting of many individual T-RF peaks, and demonstrated low similarity between sites. After four serial dilutions the fingerprints were less complex and clustered at higher similarities. Several individual T-RF peaks became dominant in a majority of the fingerprints. Cloning and sequence analysis revealed the presence of microbes closely related to Clostridium and Bacillus species and to known iron reducers such as Geobacter species and Pantoea agglomerans. Several Fe(III)-reducing isolates related to Aeromonas, Bacillus and Clostridium species were obtained.

Aeromonas↗

Cytogenetic study on children living in Southern Urals contaminated areas (nuclear incidents 1948-1967).

As a result of the activities of the first Soviet plutonium production reactor, large territories of the Southern Urals were exposed to radioactive contamination. Three different incidents occurring between 1948 and 1967 lead to major exposure. A total of 280,000 people residing on the contaminated territories were exposed both to external and internal contamination particularly due to the long-lived radionuclides 137Cs and 90Sr. The highest doses were received by 28,000 people living on the Techa riverside villages. In the present paper 15 presumably exposed children coming from the Muslyumovo village on the Techa river have been analyzed using conventional cytogenetic procedure in order to assess a radiation-induced damage. The data obtained have been compared to a group of matched unexposed controls. The results show a statistical difference between the two cohorts which suggests a possible residual contamination representing a continuous hazard for the new generations.

Blood Cells↗

[123-I-labeled fatty acids for myocardial functional diagnosis].

For 17-123I-heptadecanoic acid (IHA) and 15-(para-123I-phenyl)-pentadecanoic acid (IPPA) the biochemical and pharmacokinetic results show a physiological behaviour similar to the normally occurring fatty acids. For the nuclear medical application both 123I-fatty acids are very well suited; they are fast and efficiently accumulated in the myocardium and, keeping the patient at rest, they allow to record scintigrams of the myocardium with a quality which is obtained with thallium 201 only under stress conditions of the patient. By sequential registration of the scintigrams time activity curves can be generated reflecting the regional in-vivo turnover of fatty acids in the myocardium. Thus in a non-invasive way it is possible to obtain differential informations of the myocardial function in-vivo.

Animals↗