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PubMed1989

Comparison of three Bayesian methods to estimate posttest probability in patients undergoing exercise stress testing.

To determine whether recent refinements in Bayesian methods have led to improved diagnostic ability, 3 methods using Bayes' theorem and the independence assumption for estimating posttest probability after exercise stress testing were compared. Each method differed in the number of variables considered in the posttest probability estimate (method A = 5, method B = 6 and method C = 15). Method C is better known as CADENZA. There were 436 patients (250 men and 186 women) who underwent stress testing (135 had concurrent thallium scintigraphy) followed within 2 months by coronary arteriography. Coronary artery disease ([CAD], at least 1 vessel with greater than or equal to 50% diameter narrowing) was seen in 169 (38%). Mean pretest probabilities using each method were not different. However, the mean posttest probabilities for CADENZA were significantly greater than those for method A or B (p less than 0.0001). Each decile of posttest probability was compared to the actual prevalence of CAD in that decile. At posttest probabilities less than or equal to 20%, there was underestimation of CAD. However, at posttest probabilities greater than or equal to 60%, there was overestimation of CAD by all methods, especially CADENZA. Comparison of sensitivity and specificity at every fifth percentile of posttest probability revealed that CADENZA was significantly more sensitive and less specific than methods A and B. Therefore, at lower probability thresholds, CADENZA was a better screening method. However, methods A or B still had merit as a means to confirm higher probabilities generated by CADENZA (especially greater than or equal to 60%).(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed2003

Somatostatin analogue scintigraphy in Merkel cell tumours.

BACKGROUND: Merkel cell tumours are rare neoplasms of the skin with frequent regional and distant metastases. Scintigraphy with the radiolabelled somatostatin analogue octreotide is a possible method for in vivo localization of the primary tumour and its metastases. OBJECTIVES: To estimate the diagnostic value of indium (111) -octreotide scintigraphy (Octreoscan in detecting metastases. METHODS: Scans of 11 patients with Merkel cell carcinoma were evaluated, in whom scintigraphy was performed in addition to the conventional investigations, chest X-ray, ultrasonography and computed tomography (CT). RESULTS: In four cases metastases were found both by scintigraphy and by conventional methods; two investigations showed a suspicious accumulation of radioactivity on scintigraphy that could not be confirmed by CT and clinical progression. In three cases CT-verified metastases were not found by scintigraphy. Two patients were found to be tumour free, i.e. free of metastases by scintigraphy and conventional methods, indicating true-negative results. CONCLUSION: These data confirm that scintigraphy with the radiolabelled somatostatin analogue octreotide is not clinically helpful in detecting metastases from Merkel cell carcinoma. In this relatively small sample the method generated false-positive or false-negative results in five of 11 cases.

Aged↗
PubMed1993

The correlation of indium-111 joint scans with clinical synovitis in rheumatoid arthritis.

OBJECTIVE: An inflammatory compartment radionuclide such as Indium-111 chloride (111InCl3) may offer advantages over bone seeking radionuclides in the assessment of active rheumatoid synovitis. As an iron analog, 111InCl3 binds iron complexing proteins including transferrin. Active rheumatoid synovitis is a transferrin receptor rich compartment, reflecting profound cellular activation and proliferation. We investigated 111InCl3 scanning for the detection of active rheumatoid arthritis (RA). METHODS: Nine patients satisfying ACR criteria for definite or probable RA were scanned twice at a 28-day interval. Patients were undergoing multiple medication changes with resultant fluctuating disease activity. Blinded readings were performed by an experienced nuclear medicine physician and correlated with simultaneous clinical examinations by a single rheumatologist. Sixteen assessed joint areas/patient and a total of 144 joint areas were available for analysis. RESULTS: Scintigraphy correlated with swollen and tender joint scores at both timepoints. Specificity was highest with stringent scoring. Sensitivity was lowest for small joints with lower 111InCl3 uptake relative to background. A receiver operator curve (ROC), generated to analyze the diagnostic value of varying 111InCl3 scan stringency, demonstrated utilization of the most accurate portion of the ROC curve by the reader. CONCLUSION: 111InCl3 joint scintigraphy correlates with clinically detectable rheumatoid synovitis, supporting the hypothesis that transferrin receptor levels reflect rheumatoid disease activity.

Adult↗
PubMed1999

Formation and processing of organics in the early solar system.

Until pristine samples can be returned from cometary nuclei, primitive meteorites represent our best source of information about organic chemistry in the early solar system. However, this material has been affected by secondary processing on asteroidal parent bodies which probably did not affect the material now present in cometary nuclei. Production of meteoritic organic matter apparently involved the following sequence of events: Molecule formation by a variety of reaction pathways in dense interstellar clouds; Condensation of those molecules onto refractory interstellar grains; Irradiation of organic-rich interstellar-grain mantles producing a range of molecular fragments and free radicals; Inclusion of those interstellar grains into the protosolar nebula with probable heating of at least some grain mantles during passage through the shock wave bounding the solar accretion disc; Agglomeration of residual interstellar grains and locally produced nebular condensates into asteroid-sized planetesimals; Heating of planetesimals by decay of extinct radionuclides; Melting of ice to produce liquid water within asteroidal bodies; Reaction of interstellar molecules, fragments and radicals with each other and with the aqueous environment, possibly catalysed by mineral grains; Loss of water and other volatiles to space yielding a partially hydrated lithology containing a complex suite of organic molecules; Heating of some of this organic matter to generate a kerogen-like complex; Mixing of heated and unheated material to yield the meteoritic material now observed. Properties of meteoritic organic matter believed to be consistent with this scenario include: Systematic decrease of abundance with increasing C number in homologous series of characterisable molecules; Complete structural diversity within homologous series; Predominance of branched-chain isomers; Considerable isotopic variability among characterisable molecules and within kerogen-like material; Substantial deuterium enrichment in all organic fractions; Some fractions significantly enriched in nitrogen-15; Modest excesses of L-enantiomers in some racemisation-resistant molecules but no general enantiomeric preference. Despite much speculation about the possible role of Fischer-Tropsch catalytic hydrogenation of CO in production of organic molecules in the solar nebula, no convincing evidence for such material has been found in meteorites. A similarity between some meteoritic organics and those produced by Miller-Urey discharge synthesis may reflect involvement of common intermediates rather than the operation of electric discharges in the early solar system. Meteoritic organic matter constitutes a useful, but not exact, guide to what we shall find with in situ analytical and sample-return missions to cometary nuclei.

Amino Acids↗
PubMed1991

Progress in research on ligands, nuclides and techniques for labeling monoclonal antibodies.

This paper reviews the current methods for radiolabelling monoclonal antibodies with particular emphasis on radiometals useful for radioimmunoscintigraphy. The discussion, however, is equally applicable to therapeutic radionuclides. The advantages and the pitfalls of the various techniques are critically evaluated. Both direct labeling methods, as well as indirect methods using the bifunctional chelating agent approach, are covered. Recent work on the development and synthesis of new and more specific chelating agents, including the approach of utilizing rigid polyaminocarboxylates, is described. Preliminary promising results with these newer generation chelating agents are presented.

Aged↗
PubMed1999

A novel biochemical approach to congestive heart failure: cardiac troponin T.

BACKGROUND: The major structural characteristic of congestive heart failure is myocardial cell death. The aim of our study was to determine whether the level of cardiac troponin T, a protein specific for cardiac necrosis, was increased in patients with congestive heart failure. METHODS AND RESULTS: Plasma samples were obtained from 33 patients and 47 healthy control subjects. Quantitative determination of cardiac troponin T was achieved with a second-generation enzyme immunoassay without cross-reactivity with the skeletal muscle troponin T. The mean circulating level of cardiac troponin T was 0.140 +/- 0.439 ng/mL in patients with heart failure and 0.0002 +/- 0.001 ng/mL in the healthy controls (P =. 0001). To evaluate the relation between structural degradation and functional impairment, patients in heart failure were categorized according to their radionuclide left ventricular ejection fraction (LVEF). In the 23 patients with LVEF </=45%, cardiac troponin T was 0.163 +/- 0.50 ng/mL, a level significantly higher than that in patients with LVEF >45% (P =.04). There was also a negative correlation between cardiac troponin T and LVEF (R = -0.41, P =.01). CONCLUSIONS: These data show that cardiac troponin T is increased in patients with congestive heart failure and that the level parallels the severity of the disease. We conclude that cardiac troponin T is a suitable candidate-marker molecule to monitor congestive heart failure from a structural perspective.

Adult↗
PubMed2005

Characteristics of high-energy neutrons estimated using the radioactive spallation products of Au at the 500-MeV neutron irradiation facility of KENS.

We carried out a shielding experiment of high-energy neutrons, generated from a tungsten target bombarded with primary 500-MeV protons at KENS, which penetrated through a concrete shield in the zero-degree direction. We propose a new method to evaluate the spectra of high-energy neutrons ranging from 8 to 500 MeV. Au foils were set in a concrete shield, and the reaction rates for 13 radionuclides produced by the spallation reactions on the Au targets were measured by radiochemical techniques. The experimental results were compared with those obtained by the MARS14 Monte-Carlo code. A good agreement (between them) was found for energies beyond 100 MeV. The profile of the neutron spectrum, ranging from 8 to 500 MeV, does not depend on the thickness of the concrete shield.

Algorithms↗
PubMed1989

[Regional left ventricular diastolic function in hypertrophic cardiomyopathy: application of "sector analysis" to ECG forward and reverse gated radionuclide ventriculography].

To estimate regional left ventricular (LV) diastolic filling patterns in hypertrophic cardiomyopathy (HCM), a computer-assisted method by applying "sector analysis" to ECG forward and reverse gated radionuclide ventriculography was developed. Fourteen patients with HCM (four with localized septal hypertrophy, seven with apical hypertrophy and three with septal and apical hypertrophy according to echocardiography) were observed at rest. After establishing serial 20 msec imaged frames, the LV region of interest was subdivided into eight sectors radiating from the geometric center. A time-activity curve was generated for each sector and was fitted by third-order harmonics of the Fourier series. From each fitted curve, the regional peak filling rate (rPFR) and the time of rPFR (rTPFR) in the forward gating method and regional atrial contribution to filling (rAC/FV) in the reverse gating method were calculated. The coefficient of variance of rTPFR was used as an index of LV diastolic asynchrony. In HCM, a prominent delay of rTPFR was observed in the hypertrophied regions. The coefficient of variance of rTPFR correlated inversely with global LVPFR (r = -0.62, p less than 0.05), indicating that diastolic asynchrony is one of the determinants of the LV early filling rate. Regional AC/FV was augmented in the hypertrophied regions, indicating the important role of atrial systolic LV filling for slowed early filling. Thus, this new method provides valuable information concerning regional diastolic LV wall mechanics in HCM.

Adult↗
PubMed2004

A method for calculation of dose per unit concentration values for aquatic biota.

A dose per unit concentration database has been generated for application to ecosystem assessments within the FASSET framework. Organisms are represented by ellipsoids of appropriate dimensions, and the proportion of radiation absorbed within the organisms is calculated using a numerical method implemented in a series of spreadsheet-based programs. Energy-dependent absorbed fraction functions have been derived for calculating the total dose per unit concentration of radionuclides present in biota or in the media they inhabit. All radionuclides and reference organism dimensions defined within FASSET for marine and freshwater ecosystems are included. The methodology has been validated against more complex dosimetric models and compared with human dosimetry based on ICRP 72. Ecosystem assessments for aquatic biota within the FASSET framework can now be performed simply, once radionuclide concentrations in target organisms are known, either directly or indirectly by deduction from radionuclide concentrations in the surrounding medium.

Animals↗
PubMed2004

Single injection hepatic radionuclide angiography and hepatobiliary scintigraphy in the evaluation of liver transplant function.

BACKGROUND: The aim of the study was the evaluation of the perfusion, morphology and biliary three patency of liver transplants employing two radionuclide methods. MATERIAL AND METHODS: The study was performed on 10 controls and 10 patients after an orthotopic transplantation (up to two years). "First pass" dynamic acquisition was performed with a scintillation camera, after a bolus injection of 360 MBq 99mTc-diethyl- IDA, (60 frames/60s), continued by a 59 minute (1 frame/min) slower dynamic study. From the liver and kidney activity during the "first pass" study, the hepatic perfusion index (HPI) was calculated using slope-analysis. Hepatobiliary scintigrams obtained during second phase of the study were analyzed for morphology, and parenchymal and hepatobiliary TA curves were generated and analyzed according to the time to maximal activity (Tmax) and the time to half of maximum activity (T/2). RESULTS: In comparison to the controls (HPI, X = 0.64.5 +/- 0.05%) portal perfusion had slightly (X = 0.68 +/- 0.04%), but not significantly (p > 0.05) increased. In 3 patients, the biliary phase of hepatobiliary scintigraphy showed an increased accumulation of the radiopharmaceutical in the left (n = 1) or right (n = 2) hepatic duct. The uptake of the radiopharmaceutical (Tmax, X = 18.5 +/- 2.9 min) was slightly, but not significantly (p > 0.05) delayed in comparison to the controls (X = 14.2 +/- 3.4 min), while excretion was significantly (p < 0.05) prolonged (X = 59.5 +/- 12.1 min) (X = 34.2 +/- 4.1 min). Intrahepatic bile flow was insignificantly (p > 0.05) prolonged (X = 31.3 +/- 3.7 min) in comparison to the controls (X = 25.7 +/- 3.5 min) while extrahepatic bile flow was high, significantly (p < 0.01) prolonged (X = 89.0 +/- 14.3 min) than physiological one (X = 45.0 +/- 7.2 min). CONCLUSIONS: Radionuclide methods are noninvasive, sensitive and valuable in monitoring liver transplants.

Biliary Tract↗
PubMed1991

Measurement of blood flow from first-pass radionuclide angiography: influence of bolus volume.

Fractionation of cardiac output on first-pass radionuclide angiography is a recently described technique for measuring blood flow. In order to determine the influence of bolus volume, splenic blood flow (SBF) and renal blood flow (RBF) were measured from widely differing bolus volumes given in sequence over a period of a few minutes in patients undergoing routine bone scintigraphy with technetium 99m methylene diphosphonate. A bolus volume of 0.5 ml, followed by 20 ml of rapidly delivered saline "chaser", was regarded as a "gold standard" bolus. A 50 ml bolus, but not a 20 ml bolus, resulted in a significant underestimation of both SBF and RBF. Thus, using a left ventricular region of interest to generate an arterial first-pass time-activity curve, RBF from a 50 ml bolus was 58% (SEM 4%) that given by a 0.5 ml bolus, while RBF for a 20 ml bolus was 98% (8%). Corresponding values for SBF were 52% (10%) and 102% (12%). A quality control adjustment did not correct the underestimation given by the 50 ml bolus. Bolus volumes greater than 20 ml give unreliable estimates of organ blood flow by this technique.

Bone and Bones↗
PubMed2001

[Study of blood flow in liver hemangiomas using radionuclide angiography].

Hepatic radionuclide angiography (HRA) is a recognised method of investigation of liver blood flow disorders caused by: diffuse and focal diseases of liver parenchyma or disorders of blood flow in extrahepatic liver vessels. Hepatic perfusion index (HPI) based on Sarper's slope method is significantly lower in patients with e.g. liver cirrhosis, malignant primary and metastatic liver diseases and portal vene thrombosis, but not in patients with benign focal liver leasions. Determined in liver as a whole, HPI is a sensitive indicator of the presence of malignant liver tumours, but is within normal range in patients with hepatic hemangioma. The aim of the study was to investigate characteristic of blood flow in hemangioma itself, separately from but in relation to the liver blood flow, using hepatic radionuclide angiography. We have examined 12 patients with liver hemangioma confirmed mainly by positive 99mTc-labeled red blood cell scintigraphy, which diagnostic specificity for liver hemangiomas is near 100%. 8/12 hemangiomas resulted in photopenic areas on angioscintigrams, indicating lower blood flow, and rest were isoactive to surrounding liver tissue. Regions of interest have been delineated around the photopenic areas (hemangiomas) and surrounding liver tissue. Time-activity curves have been generated and slope of the fitted hepatic artery and (portal) venous portions of the hemangioma and liver curves have been determined. Perfusion indexes of hemangioma (PIH) and liver (HPI) have been calculated from the slopes, expressing portal venous flow as a portion of entire blood flow to the region. In addition, times of arrival and transit of intravenous bolus of 99mTc-pertechnetate through the hemangioma and liver tissue have also been derived from time-activity curves. Slope of the venous portion of the hemangioma time-activity curve is significantly lower then that of the venous portion of the liver curve (p < 0.01). So that, perfusion index of hemangioma (PIH = 0.34 +/- 0.12 (mean +/- SD) is significantly lower then hepatic perfusion index (HPI = 0.57 +/- 0.08) (p < 0.05). Bearing in mind interference of superimposed liver activity with that of hemangioma, these results indicate that liver hemangiomas are dominantly if not exclusively irrigated by hepatic artery branches. There are no data regarding relation between arterial and venous blood flow in liver hemangiomas determined by HRA. Obtained results are in harmony with arteriography data which confirm slow arterial blood flow through hemangiomas. Portal venous inflow of some angiomatous liver lesions in infants and children, and arterio-portal shunting in hemangiomas have been rarely reported. Results of this study indicate that regional determination of perfusion index and other HRA parameters in patients with focal liver lesion enables differentiation between tissues with different intensity and pattern of blood flow. The method could be used in examination of vascularisation pattern of other focal liver lesions.

Erythrocytes↗
PubMed1983

Assessment of regional left ventricular function by sector analysis: a method for objective evaluation of radionuclide blood pool studies.

Regional wall motion abnormalities are most often detected visually, and hence subjectively, in gated blood pool studies of the heart. Therefore, an automated method was developed to objectively assess regional left ventricular (LV) function. The method was tested in 26 normal volunteers and 29 patients with angiographically proved coronary artery disease. Fifteen patients with coronary artery disease had a normal LV ejection fraction (EF) at rest, and all had an abnormal EF response with exercise; 23 had visual regional wall motion abnormalities with rest or exercise. The left ventricle was divided into 28 sectors that radiated from the LV center of gravity, with 1 region at the LV center. A time-activity curve was generated for each sector and the EF and Fourier phase were computed from each curve. Rest and exercise sector EF versus sector number plots were superimposed and the area difference between these 2 curves was taken as an index of regional contraction. Similarly, an estimator of sector phase differences, obtained from the plot of phase versus sector number, was taken as an index of wall motion asynchrony. Analysis of the reliability of these 2 indexes suggests that this automated technique has at least the same efficiency as subjective evaluation of gated blood pool studies, but possesses the advantage of objectivity. The technique may also be useful in localizing regional defects and, perhaps, in detecting mild abnormalities not readily perceived visually.

Coronary Disease↗
PubMed1981

Kit preparation of radioiodinated o-iodohippuran.

The purpose of this study ws to evaluate a kit preparation for radioiodinated o-iodohippuran (I). All ingredients, excluding the radionuclide, were packaged in a ready-to-use kit for easy, quick formulation. Electrophoresis was utilized to evaluate the radiochemical purity of the labeled product and indicated that the radiolabeling technique provided a product with greater than 95% radiochemical purity. Biodistribution studies in rats and rabbits provided an indication of the tissue distribution and localization of the radiopharmaceutical. Computer-generated renogram curves plotted from gamma-camera images of rabbits showed the equivalency of the 131I-labeled I and 123I-labeled I to the commercially available radiopharmaceutical.

Animals↗
PubMedDate not supplied

Development and validation of a novel technique for murine first-pass radionuclide angiography with a fast multiwire camera and tantalum 178.

BACKGROUND: The use of genetically altered mice as a model system to study cardiovascular disease has created a need for accurate and quantitative assessment of murine ventricular function. To address this very challenging problem, we have developed a technique of murine first-pass radionuclide angiography using pinhole imaging and the short-lived isotope tantalum 178 (Ta-178) with a high-speed multiwire proportional camera (MPC). METHODS AND RESULTS. An MPC was fitted with a pinhole lens of 2-mm-diameter aperture positioned 15 cm from the camera face. The short-lived isotope Ta-178 (half-life 9.3 minutes) was generated from the tungsten 178 (W-178) (half-life 21.7 days)/Ta-178 generator and concentrated on site to an injection volume of 15 to 20 microL. Mice were imaged in the supine position with the chest wall 3 mm from the camera pinhole aperture, and images were acquired at 160 frames per second after a rapid bolus injection of Ta-178. In the absence of a true gold standard, the technology was validated with measurements in control mice and mice with surgically ligated left anterior descending arteries (LADs). In addition, the effects of pharmacologic intervention with verapamil and with dobutamine were observed. Finally, peak aortic velocity measurements obtained with this technology were compared with those obtained with echocardiographic Doppler ultrasonography, the only available quantitative comparator. There was a significant decrease in the mean left ventricular ejection fraction (LVEF) between normal mice (62% +/- 4.6% [mean +/- SEM], n = 12) and mice with experimentally induced myocardial infarction produced by surgical LAD ligation (22% +/- 2.0%, n = 41; P <.01). The LVEF decreased from 51% +/- 5.8% to 37% +/- 3.5% in a group of normal mice receiving verapamil (P <.05, n = 8) and increased from 34% +/- 2.2% to 43% +/- 2.3% in a group of LAD-ligated mice receiving dobutamine (P <.01, n = 48). Peak camera sensitivity during first pass was 25,000 cps/mCi injected. Intraobserver and interobserver variability of LVEF was studied, yielding r = 0.9639 and 0.9529 and SE of the estimate 2.6% and 3.1%, respectively. Reproducibility in serial studies was excellent (r = 0.92, SE of the estimate 5.18). CONCLUSIONS: This study demonstrates the development and use of a promising new method that uses the short-lived radioisotope Ta-178 and MPC for noninvasive quantification of murine ventricular function, that produces accurate and highly reproducible results, and that can be applied in multiple serial studies.

Animals↗
PubMed1999

A comparison of ventricular function during high right ventricular septal and apical pacing after his-bundle ablation for refractory atrial fibrillation.

This study compares LV performance during high right ventricular septal (RVS) and apical (RVA) pacing in patients with LV dysfunction who underwent His-bundle ablation for chronic AF. We inserted a passive fixation pacing electrode into the RVA and an active fixation electrode in the RVS. A dual chamber, rate responsive pulse generator stimulated the RVA through the ventricular port and the RVS via the atrial port. Patients were randomized to initial RVA (VVIR) or RVS (AAIR) pacing for 2 months. The pacing site was reversed during the next 2 months. At the 2 and 4 month follow-up visit, each patient underwent a transthoracic echocardiographical study and a rest/exercise first pass radionuclide ventriculogram. We studied nine men and three women (mean age of 68 +/- 7 years) with congestive heart failure functional Class (NYHA Classification): I (3 patients), II (7 patients), and III (2 patients). The QRS duration was shorter during RVS stimulation (158 +/- 10 vs 170 +/- 11 ms, P < 0.001). Chronic capture threshold and lead impedance did not significantly differ. LV fractional shortening improved during RVS pacing (0.31 +/- 0.05 vs 0.26 +/- 0.07, P < 0.01). RVS activation increased the resting first pass LV ejection fraction (0.51 +/- 0.14 vs 0.43 +/- 0.10, P < 0.01). No significant difference was observed during RVS and RVA pacing in the exercise time (5.6 +/- 3.2 vs 5.4 +/- 3.1, P = 0.6) or the exercise first pass LV ejection fraction (0.58 +/- 0.15 vs 0.55 +/- 0.16, P = 0.2). The relative changes in QRS duration and LV ejection fraction at both pacing sites showed a significant correlation (P < 0.01). We conclude that RVS pacing produces shorter QRS duration and better chronic LV function than RVA pacing in patients with mild to moderate LV dysfunction and chronic AF after His-bundle ablation.

Aged↗
PubMed2003

Radiolabelled lymphokines and growth factors for in vivo imaging of inflammation, infection and cancer.

Radiolabelled cytokines and chemokines are a new group of radiopharmaceuticals. These, by binding to specific receptors expressed on selected cell populations, enable the histological and functional characterization of immune-mediated processes, in vivo. Clinical studies have demonstrated the efficacy of using this type of scintigraphy in detecting sites of acute inflammation (infection) and chronic (T-cell-mediated) inflammation. Recent studies are focusing on the possible use of radiolabelled cytokines and chemokines for the biological characterization of cancer cells in vivo. In particular, the homing of metastases into specific tissues could depend on the chemoattraction of these tissues, mediated by soluble chemokines that bind to specific receptors expressed on cancer cells. These studies will generate a deeper knowledge of the molecular mechanism of tumor metastasis and lead to new therapies in nuclear medicine.

Breast Neoplasms↗