99mTc-HMPAO labelled white blood cell scintigraphy in patients with osteoarticular infection: the value of late images for diagnostic accuracy and interobserver reproducibility.

The objectives of this study were to evaluate the diagnostic value of 99mTc-HMPAO labelled white blood cell scintigraphy (WBCS) in patients with suspected osteomyelitis using late images and to study interobserver reproducibility. This study prospectively included 120 patients, and after a follow-up of one year, only 70 patients (n = 49 with implants, n = 21 without implants) were selected. The final diagnosis of infection was based either on microbiological data (n = 54) or follow-up (n = 16). We performed WBCS with 4 h and 24 h scans. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 77%, 72%, 83%, 64%, and 75% at 4 h, and 74%, 87%, 91%, 59%, and 79% at 24 h, respectively. The interobserver reproducibility shows a 63% prevalence of agreement between results (kappa = 0.5) at 4 h and 80% (kappa = 0.74) at 24 h, respectively. WBCS with 24-h images improves specificity and interobserver reproducibility in patients with suspected osteoarticular sepsis.

[I131 in blood samples: management in the laboratory]. / Gestion au laboratoire d'échantillons de sang de patients traités par iode radioactif.

OBJECTIVES: Patients treated by (131)I may require blood sampling in the days following its administration. We investigated the safety of such samples in terms of radioactivity and the possible disturbance of the analyses by these "131I-spiked" samples. METHOD: 1) The radioactivity of blood samples from 131I-treated patients was measured (dose rate, surface activity, total activity) ; 2) The risk for the personnel was subsequently evaluated and ; 3) The interference of this 131I-generated radioactivity on the results of routine automated and IRMA assays was investigated. RESULTS: 1) All RA measures but two were found below the European limits ; 2) Irradiation of personnel was negligible ; 3) The faint radioactivity did not disturb any analyses. CONCLUSION: These data demonstrate the safety that results from the negligible radioactivity in these blood samples.

Characterisation, cloning and sequencing of a conformation-dependent monoclonal antibody to the alphaIIbbeta3 integrin: interest for use in thrombus detection.

The detection of newly formed thrombi is of primary importance in clinical medicine. The activated platelet is a potential target for the localization of thrombotic lesions in arteries. The integrin alpha(IIb)beta(3) membrane changes conformation upon activation. A novel anti-alpha(IIb)beta(3) monoclonal antibody (MAb), XIIF9, is described which recognizes an epitope whose expression was enhanced by activation. Radioiodinated XIIF9 bound to a single class of sites on the beta(3) subunit, with 13600 +/- 2000 molecules bound per unstimulated platelet and a K(d) of 34.5 nM. Platelets stimulated with 0.5 U/ml of thrombin bound 66000 +/- 4000 molecules/cell (K(d) = 51.6 nM). Moreover, XIIF9 binding to unstimulated platelets could be increased 4-fold by treatment of the alpha(IIb)beta(3) complex with 5 mM EDTA. Thus, XIIF9 recognized an epitope on the beta(3) subunit whose accessibility was increased upon thrombin activation or EDTA treatment. Sequence analysis of the gene segment encoding the XIIF9 heavy chain revealed interesting motifs shared with cyclic CX6-7C anti-alpha(IIb)beta(3) peptides or with AC7, a published MAb specific for activated alpha(IIb)beta(3). In vivo experiments in atherosclerotic rabbits followed by immunohistological analysis, revealed a specific binding of XIIF9 on platelets engaged in thrombus formation, demonstrating real clinical potential for such MAbs in imaging.

Lessons from an unpleasant surprise: a biochemical strategy for the diagnosis of pheochromocytoma.

OBJECTIVE: To audit the performances of the analytes used in the diagnosis of pheochromocytoma and to present a graphical guideline to help the diagnosis. DESIGN: A 5 year retrospective study. SETTINGS: Laboratory and departments of a university hospital. PARTICIPANTS: In-patients, suspected of bearing a pheochromocytoma, were investigated for urinary metanephrines and catecholamines (photometric method) and vanillylmandelic acid, fractionated catecholamines and metanephrines [high pressure liquid chromatography (HPLC) coupled to electrochemical detection (ED)] urinary excretion. MAIN OUTCOME: Patients with a pheochromocytoma (24 out of 2003 patients) were diagnosed by the combination of normetanephrine and metanephrine determination. RESULTS: All analytes but dopamine were significantly elevated in patients with a pheochromocytoma. The area under the receiver operating characteristics (ROC) curves were the highest for total metanephrines, normetanephrine and metanephrine determinations. Because of analytical interferences in the metanephrines determination, the normetanephrine and metanephrine performed better. It is noteworthy that all pheochromocytomas had either normetanephrine or metanephrine levels above their respective optimal threshold (sensitivity 100%). The best optimal threshold performance was reached by the mean of three daily samples. Total or fractionated catecholamines or vanillylmandelic acid were less accurate tools. CONCLUSION: Amongst urinary tests, the combined use of HPLC/ED determination of normetanephrine and metanephrine seems the most effective screening strategy for the diagnosis of pheochromocytoma. The older total metanephrine photometric assay is grieved by analytical interferences.

Noninvasive assessment of pulmonary arterial hypertension by MR phase-mapping method.

We describe a magnetic resonance (MR) imaging method that emphasizes pressure wave velocity to noninvasively assess pulmonary arterial hypertension. Both the blood flow and the corresponding vessel cross-sectional area (CSA) were measured by MR phase mapping in the main pulmonary artery (MPA) in 15 patients. MPA pressures were also measured, in the same patients, by right-side heart catheterization. Two significant relationships were established: 1) between the pressure wave velocity in the MPA and the mean pressure in the MPA (Ppa) writing pressure wave velocity = 9.25 Ppa - 202.51 (r = 0.82) and 2) between the ratio of pressure wave velocity to the systolic blood velocity peak in the MPA (R) and the mean pressure in the MPA writing R = 0.68 Ppa - 4.33 (r = 0.89). Using these relationships, we estimated two pressure values to frame the actual Ppa value in each patient from the present series with a reasonable reliability percentage (87%).

Feasibility of endocardial edge detection by using an inversion recovery artifact.

An inversion recovery (IR) artifact was used to delineate the blood/wall boundary in left ventricles. The artifact consisted of a hypointensity signal in pixels located at the boundary of two contiguous tissues with different T(1) relaxation times. The feasibility of measuring the ejection fraction using the artifact was tested in ten healthy volunteers, with two IR snapshot-FLASH sequences possessing different times of repetition (TR = 11msec and TR = 3.5msec) and appropriate times of inversion. The comparison with a cine-MRI sequence showed that ejection fraction measurements are feasible when performed with a snapshot-FLASH sequence that has a sufficiently short TR (3.5msec).

Evaluation of indium-111 pentetreotide somatostatin receptor scintigraphy to detect recurrent thyroid carcinoma in patients with negative radioiodine scintigraphy.

The follow-up of patients who underwent thyroidectomy for differentiated thyroid carcinoma is based on the combination of serum thyroglobulin (Tg) measurement and radioiodine total-body scan (ITBS). The diagnostic strategy to be used in patients with elevated serum Tg level but negative ITBS remains debatable. Somatostatin receptor scintigraphy (SRS) has been proposed. Our objective was to compare the results of SRS and conventional radiological imaging (CRI) for the diagnosis of recurrent disease and/or metastases in 15 patients who had had thyroidectomy for differentiated carcinoma (14 papillary, 1 Hurthle cell carcinoma) and who displayed elevated Tg levels (10 to 65000 ng/mL) together with negative ITBS performed after 100 mCi. All patients underwent SRS and CRI within 3 months, allowing comparison of the 2 approaches for the identification of thyroid carcinoma metastases. CRI first included a chest x-ray and ultrasonography of the neck. It was followed by computed tomography (CT) scanning and/or magnetic resonance imaging (MRI) of the neck, chest and occasionally abdomen, and 99mTc bone scintigraphy in case of negative results. In 6 patients with Tg levels ranging from 65 to 65000 ng/mL, CRI detected 12 histologically proven metastases among 9 organs. Among these patients, SRS identified only 6 metastases. SRS identified 1 case of mediastinal recurrence that was not detected by CRI. In another patient with a Tg level of 51 ng/mL, a cervical node was identified using both SRS and CRI but proved to be a false-positive (inflammatory cervical node). In the other 8 patients with Tg levels ranging from 10 to 580 ng/mL, SRS and CRI were negative, and the source of Tg secretion remains unknown. The results of SRS did not correlate with serum Tg level. In conclusion, the diagnostic accuracy of SRS in this study was disappointing and clearly lower than that of CRI. Our results do not support the use of SRS as a guide conventional imaging modalities in patients operated on for differentiated thyroid carcinoma who display elevated Tg levels together with negative ITBS.

Optimized radioiodine therapy of Graves' disease: analysis of the delivered dose and of other possible factors affecting outcome.

The best approach to radioiodine dose selection in the treatment of Graves' hyperthyroidism remains highly controversial. The formula to calculate the individual dose of (131)I to be delivered has been used for half a century and takes into account the thyroid mass, the effective half-life and the maximum uptake of (131)I. The objective of the present study was to evaluate the accuracy of this formula by determining the relationship between the administered dose of (131)I calculated to deliver a target dose of 50Gy to the thyroid and the actual exact organ dose. We further analyzed if therapeutic success, defined by euthyroidism following the individually calculated dose, can be predicted by different pretreatment parameters and particularly by organ dose. One hundred patients with a first episode of Graves' disease and who had received optimal thyroid irradiation after precise dosimetry were retrospectively reviewed. The patients were categorized according to their thyroid function (plasma free thyroxine (T(4)) serum concentration) as eu-, hyper- or hypothyroid during and 1 year after treatment. The relationship between the administered dose and organ dose was assessed by simple regression. We compared free T(4), free tri-iodothyronine, thyroid weight, the number of patients with antithyroperoxidase antibodies and TSH receptor autoantibodies, 24h urinary iodine excretion, (131)I uptake, and the exact dose of (131)I delivered to the thyroid as pretreatment variables. Although we found a correlation between administered dose (mCi) and organ dose (Gy) (r=0.3, P=0.003), the mean coefficient of variation for organ dose was 45%. Individualized radioiodine therapy enabled euthyroidism in 26% of patients and failed in 74% of patients (33% had persistent or recurrent hyperthyroidism and 41% permanent hypothyroidism). (131)I uptake was significantly higher in the hyperthyroidism group in comparison with the euthyroid group. However, organ dose and other pretreatment variables did not differ among the three groups. In conclusion, these results confirm the low performance of individual dosimetry using what are established ratios, since the delivered dose to the gland, although correlated to the intended dose, is highly variable. The finding that other usual pretreatment variables are not different between groups, gives little hope for improving the way of calculating the ideal dose of radioiodine. We suggest to those not yet ready to give a standard or an ablative dose for Graves' hyperthyroidism that they abandon this way to calculate the (131)I dose.

Optimization of a new scintillation gas detector used to localize electrons emitted by 99mTc.

UNLABELLED: We have developed a scintillation gas detector to localize electrons emitted by 99mTc. This type of detector allows direct quantification of images and so provides a clear advantage over autoradiographic film. We have optimized the device to give an image spatial resolution that closely approximates that of typical autoradiographic film. To improve this resolution, it was necessary to select only low-energy electrons (2 and 15 keV) and to devise novel detection and localization techniques for the ionizing particles. METHODS: A parallel-plate proportional avalanche chamber is subject to a uniform electrical field and amplifies the number of released electrons through collisions of ionizing particles in the gas mixture. Light emitted by the gas scintillator during the avalanche process is collected by a highly intensified charge coupled device camera. The centroid of each resulting light distribution is calculated, resulting in a quantitative mapping of the sample's activity. Insertion of the sample within the gas volume improves the efficiency and so provides a method that is both very sensitive and linear. RESULTS: We have shown that in a parallel-plate structure, the application of a high electrical field to the surface of the sample and the selection of appropriate light spots, according to their morphology, can overcome localization errors due to the particles' trajectories. We have obtained a resolution of the order of 30 microm, using electrons from 99mTc. CONCLUSION: This detection technique allows considerable improvement in image resolution. This "electron camera" is a serious rival to existing autoradiographic techniques, because it provides certain other advantages, including direct quantification, linearity, high dynamic range and low noise levels. Thus, new perspectives are made available in quantitative double tracer autoradiography, because electrons can be selected for imaging as a function of their energy.

Segmented 5 versus nonsegmented flow quantitation: comparison of portal vein flow measurements.

RATIONALE AND OBJECTIVES: Times of acquisition, mean velocities, mean flows, and their respective standard deviations provided by segmented and nonsegmented flow quantifications (FQ) were compared in the main portal veins of ten healthy adults. METHODS: The segmented FQ performed five phase-encoding lines per segment. The authors successively applied the two electrocardiogram-triggered techniques in the same slice perpendicular to the portal flow direction. Their measurements were compared in particular by means of the statistical analysis proposed by Bland and Altman. RESULTS: The segmented 5 FQ reduced the acquisition time by two compared with the nonsegmented FQ. The mean velocity and mean flow values of the two techniques were not significantly different. The standard deviations were similar. CONCLUSIONS: The segmented 5 FQ showed its major advantage in the portal vein: the acquisition time was reduced without any loss of accuracy or any uncertainty enhancement.

Value of captopril renal scintigraphy in hypertensive patients with renal failure.

UNLABELLED: The aims of this study were to show the value of captopril renal scintigraphy for detecting a renovascular cause in hypertensive patients with renal failure and to assess the ability to predict the beneficial effect of revascularization on renal function. METHODS: Thirty-eight patients with renal failure (mean glomerular filtration rate = 35 mL/min) underwent renal scintigraphy after injection of 99mTc-mercaptoacetyltriglycine. Baseline scintigraphy was performed, and the test was repeated 24 h later after oral administration of 50 mg captopril given 60 min before the test. RESULTS: In 5 of 6 patients with a renovascular cause for renal failure, and 2 of 3 patients with a probable arterial pathology, scintigraphy had a high probability. The result was indeterminate in the other 2 patients. In 5 of 11 patients with negative arteriography and 14 of 18 patients with probable absence of renovascular pathology, we found a low probability of functional renal artery stenosis. Six revascularization procedures were performed and were predictive of a beneficial effect in 5 patients. Time of peak activity was an effective predictor in each case. CONCLUSION: In hypertensive patients with renal failure, captopril renal scintigraphy can detect hemodynamic dysfunction downstream from a renal artery stenosis and can predict the beneficial effect of revascularization in some cases.

Homocysteine, hypothyroidism, and effect of thyroid hormone replacement.

Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethylation pathway of homocysteine, we prospectively evaluated fasting and postload t-Hcy in patients before and after recovery of euthyroidism. Fasting and postload t-Hcy levels were higher in 40 patients with peripheral hypothyroidism (14 with autoimmune thyroiditis and 26 treated for thyroid cancer) in comparison with those of 26 controls (13.0 +/- 7.5 vs. 8.5 +/- 2.6 micromol/L, p < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 micromol/L p < .001, respectively). On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate.

Overnight urinary free cortisol determination: a screening test for the diagnosis of Cushing's syndrome.

OBJECTIVE: The collection of urine over 24 h to measure free cortisol (UFC) is used to diagnose Cushing's syndrome. However, a complete collection of urine is not easy to achieve and the sampling is frequently inaccurate, so a 24 h collection for the determination of UFC excretion is used as a confirmatory rather than a screening test for Cushing's syndrome. Our objective was to evaluate a more convenient urine collection for screening patients suspected of Cushing's syndrome. DESIGN: We have studied the possibility of using night-time (from 2000 h to 0800 h) UFC excretion as a screening test for Cushing's syndrome ('overnight UFC'). PATIENTS: Thirty patients with proven Cushing's syndrome were studied before treatment (21 cases of Cushing's disease, two cases of ectopic ACTH secretion, seven of adrenal adenoma). The results were compared to those from 150 control obese subjects. MEASUREMENTS: Overnight UFC, and creatininuria (UC), were evaluated at least once in the patients and in all subjects. The 24 h-UFC and UC were determined at least once in the patients and in 56 control subjects. RESULTS: The overnight UFC/UC ratio clearly separated all but one patient of the two groups: 194 +/- 386 vs 5.7 +/- 3.4 nmol/mumol (P < 0.0005) (ranges 16.2-2024 vs 0.6-17.4, Cushing's syndrome vs controls, respectively). The only patient with Cushing's syndrome who had an overnight UFC/UC ratio that overlapped with that of controls suffered from renal failure. The 24 h UFC/UC ratio of the patients differed from the ratio of controls: 184 +/- 365 vs 8.4 +/- 4.1 nmol/mumol (P < 0.0005) (ranges 14-1639 vs 1.5-21.2, respectively). Four patients with Cushing's syndrome had 24 h UFC/UC ratios lower than the upper control ratio. CONCLUSION: The overnight urinary sampling is a simple procedure compared to the 24 h urine collection performed in out-patients. For a sensitivity set at 100%, the specificities were 97% for the overnight UFC/UC ratio and 87% for the 24 h-UFC/UC ratio. This therefore appears to provide a good screening method for Cushing's syndrome.

Initial evaluation of CYFRA 21-1 diagnostic performances as a urinary marker in bladder transitional cell carcinoma.

PURPOSE: CYFRA 21-1, an immunoradiometric assay developed for the detection of a soluble cytokeratin 19 fragment, is evaluated for its diagnostic performance in urine of patients with transitional cell carcinoma. MATERIALS AND METHODS: CYFRA 21-1 was investigated in serum and urine of 128 patients, including 48 with bladder transitional cell carcinoma (group 1), 44 with other urological pathological conditions (group 2) and 36 free of urothelial disease (group 3). Urinary cytopathology was also performed. RESULTS: Mean urinary CYFRA was 123.5 +/- 53, 11.9 +/- 4.8 and 2.3 +/- 0.2 ng./ml. for groups 1 to 3, respectively, and was significantly different. From the receiver operating characteristics curve, the optimal combination of 96% sensitivity and 74% specificity was determined for a threshold value of 4 ng./ml. while overall cytopathology sensitivity was 43%. CONCLUSIONS: Urinary CYFRA 21-1 may be a useful marker for diagnosing transitional cell carcinoma.

Comparison of two Hologic DXA systems (QDR 1000 and QDR 4500/A).

Bone mineral content is reliably measured by dual energy X-ray absorptiometry (DXA), if manufacturers' recommendations and quality control (QC) procedures are followed. Several phantoms (Hologic anthropomorphic spine phantom, the Groupe de Recherche et d'Informations sur les Osteoporoses (GRIO) test objects and the European semi-anthropomorphic phantoms) were used to evaluate reproducibility, linearity, accuracy and spatial resolution of two DXA devices in vitro. These parameters were also evaluated in vivo from measurements performed on 120 volunteer patients. It was found that when one device (a single beam monodetector QDR 1000) is replaced by another (a fan beam multidetector QDR 4500/A), the novel combination of procedures described here, ensures that the accuracy of DXA study results is maintained when both devices are used in succession for the same patient. To study the possible responses in clinical situations, the influence of bone environment (soft and adipose tissues) was also evaluated. In both systems, similar performances (in vitro coefficients of variation of 0.5%) were established. At extreme bone density values, slight differences in linearity were found, as well as differences in accuracy and spatial resolution. Lumbar spine and femoral neck measurements were performed with both systems in 120 volunteers, both measurements being made on the same day. The corresponding bone mineral density (BMD) values were highly correlated (r2 = 0.985 for lumbar spine and 0.948 for the femoral neck), and the mean BMD differences were 0.68% and 0.37% for each anatomical site, respectively. Although small, these differences add to the precision error of the method, which is near 1%. A calibration curve has to be obtained in order that both devices can be equally used in regular clinical study. We concluded that when a DXA system is replaced by a new one, appropriate QC procedures must be strictly observed.

[Alteration of myocardial viability and systemic ventricular dysfunction after Senning procedure]. / Altération de la viabilité myocardique et dysfonction ventriculaire systémique après intervention de Senning.

After a Senning procedure for transposition of the great arteries (TGA), systolic dysfunction of the right ventricle (RV) is common. Pre and peroperative chronicale hypoxia may be the cause of this ventricular myocardial alteration. In order to detect abnormalities of myocardial viability and to study their relationship to RV function, the authors studied 41 patients (pts), 11.3 +/- 3 years after a Senning procedure. All patients underwent myocardial scintigraphy of the RV under basal conditions. 1 hour after injection of 1.5 mCi of Thallium 201. The RV ejection fraction (n = 41) and at peak effort (n = 25). Exercise ability and aerobic capacity were assessed by exercise testing (Bruce) with gas exchange measurement and compared with 41 normal matched subjects. The cardiorespiratory response to exercise was altered in the Senning group : duration of effort (10.5 +/- 2 vs 13.2 +/- 2 min; p < 0.0001), peak VO2 (33 +/- 5 vs 44.4 +/- 6 ml/min/kg; p < 0.0001), anaerobic threshold (6 +/- 1 vs 8.4 +/- 1.9 min; p < 0.05) were lower compared to controls. Abnormalities of RV viability were observed in 18/41 pts (44%), moderate in 12 cases and severe in 6 cases. Resting and exercise RVEF were significantly lower in patients with myocardial defects (45 +/- 5 vs 51 +/- 7%; p < 0.0005, and 49 +/- 9 vs 58 +/- 9%; p < 0.05 respectively). In conclusion, after the Senning procedure for TGA, scintigraphic abnormalities of the systemic ventricule are common and associated with an alteration of systolic function at rest and on exercise.

Functional upregulation of granulocytes labeled with technetium-99m-HMPAO and indium-111-oxinate.

UNLABELLED: Indium-111-oxinate-labeled granulocytes have been used in vivo for several years for the detection of abscesses. Technetium-99-m-hexamethylpropyleneamine oxime (99mTc-HMPAO) labeling has more recently been described. METHODS: The influence of radiolabeling by both radiotracers on adhesion glycoprotein CD11b quantification was studied in quiescent and formyl-methionylleucylphenylalanine (fMLP)-activated neutrophils (PMN). Adhesion was assessed on human umbilical endothelial cells (HUVEC) as well as the repercussion of the granulocyte labeling on HUVEC viability (neutral red) and metabolic activity (MTT). Chemotaxis of PMN was evaluated by measuring migration under agarose with fMLP as chemoattractant. We also measured phagocytosis and the production of hydrogen peroxide induced by staphylococcus aureus. RESULTS: Whereas whole functional integrity is maintained after labeling, most of the functions (CD11b expression, adhesion, HUVEC metabolic activity) are up-regulated while chemotaxis is decreased in the presence of both radiotracers. Indium-111-oxinate induces larger alterations than 99mTc-HMPAO. CONCLUSION: These data were obtained in normal volunteers. In patients, alterations due to the in vitro labeling procedure, in addition to potential functional alterations caused by the underlying pathology, should be taken into account during image interpretation.