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To assess the diagnostic value of indices measured on a first-pass curve, we performed 72 radionuclide renal first-pass studies (RFP) in 21 patients during the early weeks following renal allograft transplantation. The diagnosis was based on standard clinical and biochemical data and on fine needle aspiration biopsy (FNAB) of the transplant. Aortic and renal first-pass curves were filtered using a true low-pass filter and five different indices of renal perfusion were computed, using formulae from the literature. Statistical analysis performed on the aortic and renal indices indicated excellent reproducibility of the isotopic study. Although renal indices presented a rather large scatter, they all discriminated well between normal and rejection. Three indices have a particularly good diagnostic value. In the discrimination between rejection and Acute Tubular Necrosis (ATN), only one index gave satisfying results. The indices, however, indicate that there are probably ATN with an alternation of renal perfusion and rejection episodes where perfusion is almost intact. We conclude that radionuclide first-pass study allows accurate and reproducible quantitation of renal allograft perfusion. The measured parameters are helpful to followup the course of a post-transplantation renal failure episode and to gain more insight into renal ischemia following transplantation.

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Absorption 57Fe Mössbauer spectra have been carried out directly on fresh or lyophylized tissues of liver with either normal iron depot or iron overload. Two types of overloading have been studied: primary iron overload due to an excessive intestinal iron absorption and secondary iron overload (hemosiderosis) produced in beta-thalassemia patients by hypertransfusional therapeutics. The Mössbauer spectra, at room temperature, 77 and 4.2 K, on normal liver samples, are typical for the ferritin-hemosiderin compounds. In the spectra, performed on hemosiderosis liver samples, there appears, in addition to ferritin and hemosiderin, a new iron molecular environment, typical of high spin ferric iron and characterized by a superparamagnetic behaviour which begins at high temperature (above 77 K). This new component does not show up in the primary iron overload cases and seems characteristic of the physiological process which induces the iron overload.

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Positron emission tomography (PET) and 11C-labeled pimozide were used to study the dopaminergic (DA) receptor sites in the human striatum by comparing the latter with the cerebellum, which lacks DA receptors. Although 11C-pimozide concentration was not different in these two brain structures up to 53 minutes after IV injection (thus implying large nonspecific binding), a significant retention of radioactivity in striatum relative to cerebellum was found in controls but not in subjects pretreated with the unlabeled competitor haloperidol. This suggests that the striatal retention seen in controls was due to specific binding of 11C-pimozide to DA receptor sites, whereas prior occupation of the receptor sites by the unlabeled competitor was achieved in pretreated subjects.

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This work is a study of the radioinduced transformations undergone by intraglobular hemoglobin. Mössbauer spectrometry allows us to study in a wide range of doses the effect of X rays on deoxyhemoglobin as well as on oxyhemoglobin. Using this technique we have shown large differences between these two derivatives of hemoglobin. Deoxyhemoglobin leads to the formation of only one ferric nonheme compound while oxyhemoglobin produces this same compound as a last step after intermediary production of deoxyhemoglobin, methemoglobin, hemichromes, and hemochromes. We have also found that heat incubation and X rays have a similar effect on HbO2 except for the dissociation, which is absent in heat incubation. We have found a value for the energy needed for such a radiodissociation of HbO2 similar to that given by other authors utilizing other methods. Finally, we propose some explanations for the formation of the different compounds involved based on structural considerations.

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Algorithms for the estimation of organ volumes have been developed which may provide whole organ volumes and which may or may not, at the operator's choice, take into account any voids which may be contained within the organ. These algorithms have been applied to the estimation of the volume of the kidneys, in normal subjects and in patients with renal disease. The dimensions of the kidneys were similar to those derived from ultrasound study measurements which were performed independently. Kidney volume should prove especially useful in the diagnosis of early graft rejection and in the diagnosis of glomerulonephritis.

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Measurement of local Cerebral Blood Flow (CBF) using the C15O2 continuous inhalation technique coupled with Position Emission Tomography (PET) rests on the assumption that the in vivo labelled water (H215O) of blood diffuses freely within the brain water pool. This requirement however, may be disputed: in the rhesus monkey, Eichling et al (1974) showed a linear relationship between the single-pass extraction of water (E) and CBF after intra-carotid H215O injection, such that E decreases as CBF increases. Such a limitation in water transport across the blood brain barrier has also been suggested to exist in man (Paulson, 1977). In order to verify its possible effects on measured CBF in baboons, simple computer analysis was performed comparing the data obtained with CBF values reported in similar experiments, but using a freely diffusible inert gas (133Xe). This allowed calculation of a water extraction index (IE), which was shown to decline as CBF increased. This result may be considered as a presumption of the part played by the limited water diffusibility on the final CBF values, but other factors must also be considered, such as the inescapable admixture of grey and white matter (partial volume effect), a limitation of present day PET technology.

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Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of 11C-L-methionine, 4-12 transverse sections 2 cm thick were obtained. In 85 patients with a definite diagnosis (45 normal, 9 acute pancreatitis, 18 chronic pancreatitis, and 13 cancer), PET showed a sensitivity of 85.0%, a specificity of 97.8%, and an accuracy of 91.8%, higher than with transmission computed tomography (CT) or ultrasonography, despite relatively low spatial resolution; this can be explained by the fact that exocrine pancreatic function was altered prior to morphological change. In 22 normal subjects, 0.011 +/- 0.003% (mean +/- S.D). of injected 11C was found in 1 ml of liver tissue and 0.015 +/- 0.005% in 1 ml of pancreatic tissue; the pancreas-to-liver concentration ratio was 1.3 +/- 0.4. Hepatic 11C concentration was identical in the four groups of patients. Pancreatic uptake of 11C-L-methionine was significantly lower in patients with chronic pancreatitis (n = 13) and pancreatic carcinoma (n = 10) (p less than 0.001); however, it was not possible to distinguish cancer from chronic pancreatitis because the same functional alteration occurred in both.

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The problem of transverse plane reconstruction from an ensemble of projections is considered in its general formulation and an analytically exact solution to the attenuated tomographic operator is proposed. Such a technique, called the regularizing iterative method (RIM), allows the introduction of a priori knowledge on the size and shape of the activity distribution and in principle on the exact attenuation distribution. The relaxation factor used is so named because it provides noise filtering for a small number of iterations. The effectiveness of RIM was studied in the single photon emission computed tomography (SPECT) problem with the aim of correcting for attenuation before quantitative study. Its application involves the use of a rotating scintillation camera connected to a mini-computer system. Various mathematical and physical phantoms were studied, and a satisfactory attenuation correction was always obtained in the final image with an improvement in the contrast and signal-to-noise ratio. Preliminary clinical studies on liver transverse sections seems to indicate an improvement in deep lesion detectability, compared with images obtained by the filtered (Ramp) back projection technique.

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Emission Mössbauer spectra and Perturbed Angular Correlation measurements have been performed on samples of mineral bone powder labelled with 161Tb3+ or 133Ba2+ ions after either in vitro absorption or uptake by metabolic pathway. The study of these hyperfine spectra, compared with those carried out when 161Tb or 133Ba are situated in either hydroxyde lattice or phosphate one, shows that the uptake modes of rare-and alkaline-earth ions on the bone matrix are different. The rare earth ion seems to be absorbed on the surface bone in an environment of hydroxyl groups similar to the structure of a rare earth hydroxyde. The alkaline earth ion bone uptake appears more complicated and would make according to the following process : at first, surface absorption on the hydroxylapatite in a hydroxyde environment and then cationic exchange with the calcium phosphate groups into bone crystals.

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A whole-body single-photon emission computed tomography system has been evaluated in terms of its physical performance. It consists of a standard GE 400 T maxi camera rotating on a ring stand, coupled to an Informatek Simis 3 computer system. In its standard mode of operation, 64 or 128 successive views of 64 X 64 or 128 X 64 matrices are collected at regular angular samples. The reconstruction of up to 64 possible adjacent transverse sections, sorted into coronal, sagittal, and oblique sections, is obtained by filtered backprojection. A conventional parallel-hole collimator is used. The uniformity of the camera field of view is corrected by the GE hardware module. The resolution in the transverse plane is typically of 15.5 mm in a 20 cm Lucite phantom, and independent of radial distance. The physical slice thickness is 19 mm (full width at half maximum of the longitudinal response using a point source) with only slight variations along the diameter of the image. The sensitivity is approximately 7,000 cps mCi-1 as measured using a 99m Tc thin source, enabling images of reasonable signal-to-noise ratio to be obtained in 10 min. The effect of the energy window, the number of angular samples, and the linear sampling modes on the transverse resolution and contrast is measured and discussed.

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TDPAC measurements of the 356-81 keV gamma-ray cascade resulting from electron capture decay of 133Ba have been performed at room temperature on BaCl2 (aqueous solution and polycrystalline powder), and on samples where the 133Ba nucleus is bound to bone powder, and also to synthesised hydroxylapatite, all after absorption in vitro. As expected, the angular correlation is not perturbed in the solution. However, in the polycrystalline chloride the time dependence of the anisotropy of the cascade of 133Cs nuclide indicates that the decaying nucleus undergoes electric interactions due to different electric field gradients acting at the site of the nucleus. In 133Ba-bone powder the results show a static quadrupolar interaction differing with the absorption contact time during sample preparation, indicating that depth of 133Ba ion fixation in the bone crystal is dependent on this contact time. These results seem to be confirmed by the TDPAC measurements performed on 133Ba-hydroxylapatite samples where the contact times for absorption of active-ion 133Ba and hydroxylapatite in suspension were very different.

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Uptake of C-11 chlorpromazine (CPZ) was measured to evaluate the nonrespiratory function of lung in patients. A multiple-indicator dilution technique was used with external detection. Following intravenous bolus injection of C-11 CPZ, with In-113m transferrin as an intravascular reference molecule, counts were recorded with a scintillation camera using two energy windows. The residue functions, R(t), for C-11 CPZ and In-113m transferrin were plotted against time for selected areas of interest, and the CPZ area-weighted extraction, E(t), was computed for the same areas every 250 msec using the formula: E(t) = [RT(t) - RR(t)]/[1 - RR(t)], where RT and RR are the normalized residue functions for CPZ and transferrin, respectively. The initial extraction was 90 +/- 5% in four normal subjects and 64 +/- 7% in six patients with chronic obstructive lung disease (C.O.L.D.), these values being significantly different (p less than 0.001). The large initial extraction of CPZ in a single passage through the pulmonary vasculature resulted from a fixation to membranes, due to its high liposolubility. The lower extraction seen in patients with C.O.L.D. was explained by weaker fixation to lung tissue.

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Metabolic phenomena can be studied and measured non-invasively using positron emitting radionuclides and a suitably adapted tomographic system. The choice of a single slice ring camera is justified by its physical performance, which is presented here and discussed. A series of measurements with geometrical phantoms and analytical simulations have been performed to determine the critical characteristics of the system. This has permitted optimization of certain parameters enabling very interesting clinical results to be obtained at SHFJ, particularly in the area of cerebral physiopathology. In addition, the potential of obtaining absolute quantitative values of regional activity is presented. The calibration of the regional activity is presented. The calibration of the system, spatial non-stationarities, and attenuation correction, which represent the main sources of error, are considered in detail. A precision of the order of 10% should be obtainable. Such a quantitation method has been successfully applied to the in vivo study of the regional extraction of cerebral oxygen.

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By the use of [11C]methionine and positron computed tomography (PCT), images of the pancreas were obtained in 32 patients. The injection of between 10 and 20 mCi of this product enables four to six transverse sections to be obtained. Seventeen of the patients studied had no exocrine pancreatic disease, and in all these cases the pancreas was clearly visible. In four cases of pancreatic carcinoma and one of retroperitoneal tumor, there were abnormalities visible. In five cases of chronic pancreatitis, no pancreatic uptake was observed. In a sixth case, concentration was visible, but only in the head of the pancreas. One case of acute pancreatitis, which showed no concentration during the acute phase, returned to normal after recovery. When visible, the pancreas was easily located and distinguishable from the intestinal image, except in two cases that were uninterpretable for technical reasons. No false positive or negative was observed, but a differential diagnosis between cancer and pancreatitis was impossible.

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The positron emitter 11C (20 minutes half-life) permits the labeling of chlorpromazine (CPZ) and the study of its distribution in humans by external counting. Trace amounts of 11C-CPZ were injected intravenously into 22 schizophrenic patients all untreated for several months with neuroleptics. The brain uptake was 6.04 +/- 1.6% of the injected dose 15 minutes after the injection, and it remained constant for 45 minutes. By positron emission tomography, the drug distribution was shown to be in the gray matter, and such structures as the cortex, caudate nucleus, thalamus and putamen could be identified. This new methodology will be helpful in studying specific receptors in humans in a noninvasive way.

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Transverse axial tomographic imaging of regional cerebral blood flow (rCBF) and regional oxygen extraction fraction (rOEF) were obtained in 13 patients hospitalizedfor ischemic strokes (eleven middle cerebral artery territory infarcts, one capsular or pontine lacune, one transient hemispheric attack) by continuous inhalation of 15O2 and C15O2 to equilibrium and exclusive detection of the gamma rays emitted in coincidence by means of a tomograph for positron emitting agents. In the transient ischemic attack and in the case of lacune the rCBF and the rOEF images were found to be normal, and they were abnormal in all cases of middle cerebral artery territory infarcts. In recent infarcts, rOEF was always strikingly decreased in the clinically suspected area, whilst the rCBF was either decreased, normal or increased. In infarcts older than 30 days rCBF was always clearly decreased over the clinically suspected area whilst rOEF was in most cases normal or only slightly decreased. These results are briefly discussed. Some practical and theoretical limitations of this method are mentioned. The potential of the present technique appears great however, since it is possible to simultaneously visualize in tomographic fashion the blood flow and the oxygen metabolism in areas of the brain that are of small volume, and however deep they are. A quantification of these parameters is presently under investigation, as well as the verification of the theoretical model on which such method is based. The non-invasiveness of the present method, the feasibility of repeating it at regular intervals of time, and the possibility of measuring the immediate effects of a given therapeutic mode on the regional metabolism of brain all constitute further advantages whose action apply preeminently in the field of the cerebral ischemic diseases.

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