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PubMed1996

Automatic preparation of radiopharmacokinetic data for in vivo estimation of receptor biochemistry.

UNLABELLED: We present a fully automated region of interest (ROI) and motion correction program for the generation of heart and liver time-activity data resulting from a hepatic functional imaging study using [99mTc-]galactosyl-neoglycoalbumin (99mTc-NGA). METHODS: The program automatically draws heart and liver ROI and corrects for lateral movement of the subject. Eighty-four 99mTc-NGA studies, consisting of 32 healthy subjects and 52 patients with liver disease, were processed and submitted to an automated kinetic analysis that estimates the subject's asialoglycoprotein receptor concentration [R]o. RESULTS: When compared to time-activity data generated by operator-drawn ROIs without motion correction, the average reduced Chi-square of the kinetic analysis decreased significantly (p < 0.001) from 2.20 to 1.37 and the number of studies that satisfied quality control increased from 74 to 81 studies. Receiver operating characteristic of [R]o resulted in greater detectability (0.984 +/- 0.012 compared with 0.965 +/- 0.020) when automatic ROI generation was employed. Using the test criteria of 0.65 microM, the sensitivity of [R]o increased from 0.88 to 0.92 and the specificity increased from 0.96 to 0.97. CONCLUSION: Automated definition of liver and heart ROIs with motion correction, that reduces observational noise, increased the success rate of the radiopharmacokinetic analysis from 88% to 96%.

Albumins↗
PubMed1994

Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction.

BACKGROUND: Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction. METHODS AND RESULTS: One hundred twenty patients were randomized to receive placebo (n = 59) or h-SOD (n = 61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg.kg-1.min-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD. CONCLUSIONS: The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction.

Angioplasty, Balloon, Coronary↗
PubMed1988

Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody.

Current nuclear medicine techniques for the localization of inflammatory processes are based on injection of 111In labelled autologous granulocytes which need to be isolated and radiolabelled in vitro before reinjection. A new technique is presented here that obviates the need for cell isolation by the direct intravenous injection of a granulocyte specific 123I labelled monoclonal antibody. In this publication the basic parameters of the antibody granulocyte interaction are described. Antibody binding does not inhibit vital functions of the granulocytes, such as chemotaxis and superoxide generation. Scatchard analysis of binding data reveals an apparent affinity of the antibody for granulocytes of 6.8 X 10(9) l/mol and approximately 7.1 X 10(4) binding sites per cell. Due to the high specificity of the antibody, the only expected interference is from CEA producing tumors.

Animals↗
PubMed1989

A brief overview of nuclear medicine in China.

The year 1956 witnessed the birth of Nuclear Medicine in China, when the first course, Biomedical Applications of Isotopes, was offered in our country by the Peking Union Medical College (PUMC). This course was preceded by a training course in nuclear instruments in which students learned to construct the radiation detection devices required for performing experiments using radioisotopes. In 1958, several courses in clinical nuclear medicine brought up the first generation of nuclear medicine physicians in China. Historically, some of the chief events include: (1) operation of the first reactor, producing 33 radioactive isotopes in 1958; (2) first linear scanner built in 1960; (3) setting up an organization for the control of radiopharmaceuticals in 1961; (4) distribution of the first batch of cyclotron-produced isotopes in 1963; (5) development and use of the first radioimmunoassay (RIA) procedure in 1963; (6) production of tritium in 1964; (7) production of 99.8% enriched heavy water in 1965; (8) supply of 99mTc and 113mIn generators in 1972; (9) first gamma camera imported in 1972 and first homemade gamma camera installed in 1977; (10) founding of Chinese Society of Nuclear Medicine (CSNM) in 1980; (11) publication of the Chinese Journal of Nuclear Medicine beginning in 1981; (12) first single photon emission computed tomography (SPECT) imported in 1983. At present, there are 556 nuclear medicine departments in China with 4,000 staff.(ABSTRACT TRUNCATED AT 250 WORDS)

China↗
PubMed2001

Generative models, brain function and neuroimaging.

The representational capacity and inherent function of any neuron, neuronal population or cortical area in the brain is dynamic and context-sensitive. Functional integration, or interactions among brain systems, that employ driving (bottom up) and backward (top-down) connections, mediate this adaptive and contextual specialisation. A critical consequence is that neuronal responses, in any given cortical area, can represent different things at different times. This can have fundamental implications for the design of brain imaging experiments and the interpretation of their results. Our arguments are developed under generative models of brain function, where higher-level systems provide a prediction of the inputs to lower-level regions. Conflict between the two is resolved by changes in the higher-level representations, which are driven by the ensuing error in lower regions, until the mismatch is "cancelled". From this perspective the specialisation of any region is determined both by bottom-up driving inputs and by top-down predictions. Specialisation is therefore not an intrinsic property of any region but depends on both forward and backward connections with other areas. Because the latter have access to the context in which the inputs are generated they are in a position to modulate the selectivity or specialisation of lower areas. The implications for classical models (e.g., classical receptive fields in electrophysiology, classical specialisation in neuroimaging and connectionism in cognitive models) are severe and suggest these models may provide incomplete accounts of real brain architectures. Here we focus on the implications for cognitive neuroscience in the context of neuroimaging.

Brain↗
PubMed2002

Reversal of multidrug resistance: lessons from clinical oncology.

Modulation of P glycoprotein (Pgp) in clinical oncology has had limited success. Contributing factors have included the limitation in our understanding of the tumours in which Pgp overexpression is mechanistically important in clinical drug resistance; the failure to prove that concentrations of modulators achieved in patients were sufficient to inhibit Pgp; and the inability to conclusively prove that Pgp modulation was occurring in tumours in patients. New approaches are needed to determine the clinical settings in which Pgp overexpression plays a major role in resistance. (Clinical trials with third generation modulators are ongoing, including trials with the compounds LY335979, R101933 and XR9576. Using the Pgp substrate Tc-99m Sestamibi as an imaging agent, increased uptake has been seen in normal liver and kidney after administration of PSC 833, VX710 and XR9576. These studies confirm that the concentrations of modulator achieved in patients are able to increase uptake of a Pgp substrate. Furthermore, CD56+ cells obtained from patients treated with PSC 833 demonstrate enhanced rhodamine retention in an ex vivo assay after administration of the antagonist. Finally, a subset of patients treated with Pgp antagonists show enhanced Sestamibi retention in imaged tumours. These results suggest that Pgp modulators can increase drug accumulation in Pgp-expressing tumours and normal tissues in patients. Using third generation Pgp antagonists and properly designed clinical trials, it should be possible to determine the contribution of modulators to the reversal of clinical drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

A Monte Carlo and physical phantom evaluation of quantitative In-111 SPECT.

Accurate estimation of the 3D in vivo activity distribution is important for dose estimation in targeted radionuclide therapy (TRT). Although SPECT can potentially provide such estimates, SPECT without compensation for image degrading factors is not quantitatively accurate. In this work, we evaluated quantitative SPECT (QSPECT) reconstruction methods that include compensation for various physical effects. Experimental projection data were obtained using a GE VH/Hawkeye system and an RSD torso phantom. Known activities of In-111 chloride were placed in the lungs, liver, heart, background and two spherical compartments with inner diameters of 22 mm and 34 mm. The 3D NCAT phantom with organ activities based on clinically derived In-111 ibritumomab tiuxetan data was used for the Monte Carlo (MC) simulation studies. Low-noise projection data were simulated using previously validated MC simulation methods. Fifty sets of noisy projections with realistic count levels were generated. Reconstructions were performed using the OS-EM algorithm with various combinations of attenuation (A), scatter (S), geometric response (G), collimator-detector response (D) and partial volume compensation (PVC). The QSPECT images from the various combinations of compensations were evaluated in terms of the accuracy and precision of the estimates of the total activity in each organ. For experimental data, the errors in organ activities for ADS and PVC compensation were less than 6.5% except the smaller sphere (-11.9%). For the noisy simulated data, the errors in organ activity for ADS compensation were less than 5.5% except the lungs (20.9%) and blood vessels (15.2%). Errors for other combinations of compensations were significantly (A, AS) or somewhat (AGS) larger. With added PVC, the error in the organ activities improved slightly except for the lungs (11.5%) and blood vessels (3.6%) where the improvement was more substantial. The standard deviation/mean ratios were all less than 1.5%. We conclude that QSPECT methods with appropriate compensations provided accurate In-111 organ activity estimates. For the collimator used, AGS was almost as good as ADS and may be preferable due to the reduced reconstruction time. PVC was important for small structures such as tumours or for organs in close proximity to regions with high activity. The improved quantitative accuracy from QSPECT methods has the potential for improving organ dose estimations in TRT.

Algorithms↗
PubMed1988

Improvement of parathyroid Tl-Tc scintigraphy by using a new image subtraction method.

Forty five thallium-technetium parathyroid scans were performed preoperatively in patients with a high suspicion of parathyroid adenoma or hyperplasia. The patients were imaged after sequential IV injection of 201Tl-thallous chloride (74 MBq) and 99mTc-pertechnetate (222 MBq) using a gamma camera with a pinhole collimator. According to surgical findings, the prevalence of parathyroid abnormalities was 42/45: single (34 patients) and double (1 patient) adenomas, hyperplasia (7 patients, 16 hyperplastic glands). Three methods of analysis of scintigraphic images were compared. Method one was the visual comparison of the thallium and the technetium images. Method two used the subtraction image obtained after normalisation. Method three used a new image comparison method which performs the geometric and gray level registrations of the two images and generates the image of the significant differences. Three observers were involved in the evaluation procedures. Surgery and histological examinations were taken as the gold standard. Results show that the sensitivity is increased by applying method three. The interobserver reproducibility of the results is also higher for method three. We conclude that an adequate image subtraction technique significantly increases the diagnostic value of parathyroid scintigraphy.

Adenoma↗
PubMed1982

Distribution, retention and dosimetry of plutonium and americium in the rat, dog and monkey after inhalation of an industrial-mixed uranium and plutonium oxide aerosol.

This study provides information on patterns of radiation dose in laboratory animals after inhalation exposure to an aerosol of one form of mixed uranium and plutonium oxide. The aerosol contained a mixture of UO2 and 750 degrees C heat-treated PuO2 obtained from the ball milling operation in a mixed-oxide fuel fabrication process. Americium-241 from the decay of 241Pu was also present in the PuO2 matrix. Fischer-344 rats, Beagle dogs, and Cynomolgus and Rhesus monkeys inhaled aerosols re-generated from dry mixed oxide powders with particle size distribution characteristics similar to those observed in samples collected at the industrial site. Clearance from the lung and distribution in other tissues of the plutonium from this UO2 + PuO2 admixture was similar to what has been observed for PuO2 from laboratory-produced aerosols. The UO2-PuO2 aerosol was relatively insoluble in the lungs of all species. Monkeys and rats cleared plutonium and americium from their lungs faster than dogs. Very little plutonium or americium translocated within the first 2 yr after exposure to tissues other than tracheobronchial lymph nodes. The greater accumulation of plutonium and americium in the tracheobronchial lymph nodes of dogs as compared to monkeys and rats combined with the more rapid initial clearance of these radionuclides from the lungs of rats and monkeys suggests that errors could result from using data from a single animal species to estimate risk to humans from inhalation of these industrial aerosols.

Aerosols↗
PubMed1979

Evaluation of nuclear imaging for detecting posttransplant fluid collection.

A series of 26 renal allograft recipients studied by both B-mode gray scale ultrasonography and 99mTc DTPA renal nuclear imaging was reviewed. All conclusions were based on written reports generated at the original examination, and B-mode gray scale ultrasonography was considered the definitive examination for fluid collection detection. Sensitivity of nuclear imaging for the detection of fluid was 73%; however, it becomes 85% when fluid collections in close proximity to the bladder are excluded. Renal allograft nuclear imaging is a useful examination for primary detection of lymphoceles and also for demonstrating abnormalities in renal dynamics and drainage.

Body Fluids↗
PubMed1983

Comparative pathogenesis of radium-induced intracortical bone lesions in humans and beagles.

Morphologic changes resulting from the effects of chronic radionuclide toxicity (226Ra) in the skeletons of workers in the radioluminescent dial painting industry with preterminal body burdens ranging from about 1.5 to 0.042 muCi were compared with the pathologic alterations in the skeletons of a group of 38 beagle dogs injected with 1.12 muCi/kg. Similarities observed in the skeletal responses of the two species were the presence of (1) dead bone tissue with delayed resolution, (2) a chronic disturbance in the remodeling mechanism of bone tissue, and (3) radiation-induced bone sarcomas. A detailed analysis of sequential changes in radiographic lesions arising in the beagle skeletons, complemented by histopathologic evaluation at the time of limb amputation or at necropsy, has enabled us to examined the disturbance in the bone remodeling process. The perturbation of critical importance in the generation of primary bone tumors appears to lie in the bone tissue formation and deposition phase of the bone remodeling process and gives rise to a spectrum of histologic patterns which we have termed "radiation osteodystrophy." While some of the newly generated patterns demonstrate indolent behavior with fibrous tissue replacement and bone marrow refill, other sites of bone resorption are replaced by a unique fibro-osseous tissue response resembling fibrous dysplasia or osteoblastoma. Some of these proliferative lesions may undergo progressive malignant degeneration. While the more indolent part of the spectrum was also seen in human skeletal tissues, only premalignant and early sarcomatous stages were seen in canine tissues.

Animals↗
PubMed1993

The role of nuclear medicine in the evaluation of the male genital tract.

Scintigraphic techniques for evaluation of impotence are still evolving. Blood pool studies are most useful in assessing the integrity of arterial inflow, but may also be used to generate indices of venous leak. A non-imaging version of this test may represent a simple and cost-effective alternative. Washout of intracavernosal xenon during erection seems the most useful method of testing venous integrity. Washout using Tc-RBC may emerge as a convenient alternative to the more technically difficult xenon examinations. Development of more effective pharmacologic stimuli may further improve the utility of this quantitative and physiologic examination.

Erectile Dysfunction↗
PubMed2005

[Extrahepatic cholestasia during therapy with Zolmitriptan (AscoTop)].

Because of recurrent abdominal pain, jaundice and elevated liver function tests, a sixty-two-year old man had been referred to hospital several times within the preceding six months. By means of ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonant cholangiopancreatography, dilated extrahepatic bile ducts were diagnosed. Stones and a tumorous process were excluded. ERCP showed hypermotility of the upper gastrointestinal tract. Quantitative hepatobiliary scintigraphy demonstrated retention of activity in the intra- and extrahepatic bile ducts and delayed transit of activity to the duodenum as signs of papillary dysfunction. Drug anamnesis revealed that the patient had started migraine treatment with Zolmitiptan, a 5-HT (1B/1D)-receptor agonist of the second generation, six months before the beginning of the cholestasia syndrome. Because of the known increase in amplitudes of oesophageal motor waves and of lower oesophageal sphincter tone by Sumatriptan, a 5-HT (1B/1D)-receptor agonist of the first generation, Zolmitriptan treatment was stopped. Thereupon, laboratory findings normalised and the patient has been feeling well for more than one year. Serotonin is an important monamine neurotransmitter that acts both in the CNS and in the gastrointestinal tract on identical receptors and is transported by the same systems. Thus it is not surprising that therapeutic measures which influence the serotoninergic system in the CNS are also effective in the enteric nervous.

Bile Ducts, Extrahepatic↗
PubMed1987

An in vivo method for the evaluation of catheter thrombogenicity.

A new method has been developed to evaluate the relative thrombogenicity of vascular catheters. The technique provides a means to quantitatively differentiate between catheters made from different polymeric materials. Autologous In-111 labeled platelets were infused into a dog model and catheters were then inserted into the external jugular vein of the dog. The neck region was scanned using gamma camera imaging. Comparisons between catheter materials were made using computer generated uptake slopes during the first 40 min of the scan. In addition to scintigraphy, visual assessment of thrombus deposition, thrombus weight, platelet deposition, and scanning electron microscopy were used to validate the technique. Poly(vinyl chloride), polyurethane, heparinized polyurethane, and silicone catheter materials were tested. It was found that heparinized polyurethane was the least thrombogenic of all materials evaluated.

Animals↗
PubMed1986

Symbolic reasoning about myocardial scintigrams in PROLOG.

PROLOG (PROgramming in LOGic) is the declarative programming language at the heart of the Japanese fifth-generation computer project. It is proposed that PROLOG is a suitable tool for symbolic image processing, once standard preprocessing has been done. In the present application, the problem of prediction of coronary anatomy from myocardial scintigrams is addressed. Uncertainty is dealt with by a combination of fuzzy-set theoretic and probabilistic reasoning. Heuristic classification rules are based on clinical experience and on a set of 247 myocardial scintigrams with their corresponding coronary angiograms.

Artificial Intelligence↗
PubMed1995

Impact of the high tyrosine fraction in complementarity determining regions: measured and predicted effects of radioiodination on IgG immunoreactivity.

Although iodine-131 is the most widely used radionuclide for radioimmunotherapy, direct radiolabeling methods yield decreased immunoreactivity of the antibody as a function of increased iodine incorporation. We have studied the amino acid sequences of a therapeutic IgG (HuM195), and in particular its complementarity determining regions (CDR), in order to correlate the iodination of tyrosine residues in the antigen binding site with changes in immunoreactivity. The CDR contained an overabundance of tyrosines relative to an expected random distribution of amino acids. In contrast, lysine residues that can be used for ligand attachment were evenly distributed throughout the IgG. HuM195 was first trace labeled with 111In and then labeled with stable 127I at various specific activities. The immunoreactivity of each product was determined using the 111In tracer. The immunoreactivity measured after varying levels of iodination fit a theoretical curve that was generated based on the assumption that a single iodine incorporation anywhere on a tyrosine residue in a CDR destroys the immunoreactivity of the antibody. Similar theoretical curves for antibody fragments (Fab, Fv) suggest an even faster decrease in immunoreactivity with increasing iodination. A review of the sequences of other therapeutic IgG shows that a similar overabundance of tyrosine residues is found in the CDRs. Using enzyme digestion, the distribution of iodine on different parts of the antibody was also studied. The iodinated residues were distributed non uniformly throughout the IgG, with the heavy chain variable region tyrosines having a higher propensity for iodine incorporation than tyrosines in the other regions of the IgG. The common abundance of tyrosine in the CDR of IgG and its correlation with loss of function have important implications for therapeutic use of high specific activity radioiodinated monoclonal antibodies or fragments.

Amino Acid Sequence↗
PubMedDate not supplied

Computed tomographic cholangiography in a canine model of biliary obstruction.

The CT scanner was used to generate the time-density relationship for hepatic parenchyma following Iodipamide (Cholografin, E.R. Squibb Co., New York, N.Y.) infusion. The curves which resulted from the normal, acutely obstructed, and chronically obstructed biliary system are shown. The peak enhancement of parenchyma is seen to be blunted in acute obstruction prior to anatomic evidence of dilated ducts. This finding may be of value in the early diagnosis of obstructive jaundice.

Absorptiometry, Photon↗
PubMed2006

Decomposition analysis of differential dose volume histograms.

Dose volume histograms are a common tool to assess the value of a treatment plan for various forms of radiation therapy treatment. The purpose of this work is to introduce, validate, and apply a set of tools to analyze differential dose volume histograms by decomposing them into physically and clinically meaningful normal distributions. A weighted sum of the decomposed normal distributions (e.g., weighted dose) is proposed as a new measure of target dose, rather than the more unstable point dose. The method and its theory are presented and validated using simulated distributions. Additional validation is performed by analyzing simple four field box techniques encompassing a predefined target, using different treatment energies inside a water phantom. Furthermore, two clinical situations are analyzed using this methodology to illustrate practical usefulness. A comparison of a treatment plan for a breast patient using a tangential field setup with wedges is compared to a comparable geometry using dose compensators. Finally, a normal tissue complication probability (NTCP) calculation is refined using this decomposition. The NTCP calculation is performed on a liver as organ at risk in a treatment of a mesothelioma patient with involvement of the right lung. The comparison of the wedged breast treatment versus the compensator technique yields comparable classical dose parameters (e.g., conformity index approximately = 1 and equal dose at the ICRU dose point). The methodology proposed here shows a 4% difference in weighted dose outlining the difference in treatment using a single parameter instead of at least two in a classical analysis (e.g., mean dose, and maximal dose, or total dose variance). NTCP-calculations for the mesothelioma case are generated automatically and show a 3% decrease with respect to the classical calculation. The decrease is slightly dependant on the fractionation and on the alpha/beta-value utilized. In conclusion, this method is able to distinguish clinically important differences between treatment plans using a single parameter. This methodology shows promise as an objective tool for analyzing NTCP and doses in larger studies, as the only information needed is the dose volume histogram.

Algorithms↗