ClearPEM is a high resolution PET scanner dedicated to breast imaging that offers good lesion detectability and localization. To obtain quantitative images, corrections need to be applied to the ...acquired data, but since there are no transmission sources available, only emission data can be used. In this paper we present the application of a method for scatter correction - Estimation of Trues Method (ETM) - to data acquired with the ClearPEM scanner. This approach is based on the energy of the detected photons and can be implemented in the image domain. Also, it is applicable in cases where a large amount of activity exists outside the field of view and does not require transmission information. ETM is being validated with real data from acquisitions with gelatin phantoms, showing improvements in image contrast and thus potentially increasing the detectability of lesions.
Among 34 children with AIDS enrolled in a trial with 2'-3' dideoxyinosine (ddI), six (aged 1-6 years) developed liver abnormalities within 2-18 months after institution of ddI. Two children died of ...fulminant hepatic failure (one had also an adenovirus infection), and four had a striking elevation of alkaline phosphatases (AP: 1120-7000 IU/L). All of them received sulfa drugs and antifungic treatment with ketoconazole or fluconazole. Three had a serology positive for hepatitis C virus. The evolution of liver enzymes following withdrawal and rechallenge with ddI in the children with elevated AP was an indication of drug-induced toxicity in two patients. In both of the others, readministration of ddI did not cause any subsequent problems. Liver histology in the patients with fulminant hepatitis showed an extensive hepatic necrosis. Liver biopsy done in two other patients revealed a mild granulomatous hepatitis in one and nonspecific changes (i.e., steatosis and a mild inflammation) in the other. Hepatic toxicity has been described with ddI and other nucleoside analogs in adult patients. These six children had many potential causes of liver disease. It may be that ddI is not hepatotoxic per se but that it precipitates liver disease in predisposed patients. We recommend that liver functions be carefully monitored when using this drug.
We have developed a genetic barcode module, based on a parallel sorting facility of single nucleotide polymorphism for secure individual identification of cattle. Biotinylated allelespecific ...oligonucleotides were immobilized onto the predefined spots of streptavidin tethered self-assembled monolayers with long chain alkanethiols on biochips. The target DNAs for hybridization and subsequent on-chip minisequencing were produced by multiplex PCR method. After enzymatic extension, only the moiety-modified dideoxynucleotide triphosphate, when coupled to its complementary target sequence, could be detected by the corresponding antibody to the moiety in a specific and sensitive manner. The database SNPZoo was developed for storage of the sequence information consisting of cytosine/thymidine patterns. This SNP chip system can further be used in the detection of any replaceable point mutations occurring in the human and animal genes.
There are great hopes that the most common form of human genetic variation, single nucleotide polymorphisms (SNPs), can be used to improve radically biological understanding and to advance medicine. ...However, considerable controversy exists over just how SNPs can be applied to gain these insights. The second international SNP meeting, held at Schloss Hohenkammer, Munich, Germany, brought together leading international scientists from academia and industry to look at these issues from a multidisciplinary perspective. Topics that were covered spanned SNP discovery, scoring technologies, population genetics, disease studies, commercial dimensions, pharmacogenomics, bioinformatics, and legal considerations. SNP discovery is picking up speed; The SNP Consortium (TSC) is set to produce 300,000 publicly available SNPs within 2 years. Improved technologies for scoring SNPs are reducing hands-on time and cost, although truly high-throughput methods are still lacking for genome-wide population-based studies. Large numbers of SNPs have already been analysed in diverse populations. The results emphasise the importance of considering population history when using SNPs to search for genetic risk factors. Opinions on the feasibility of extensive SNP-based analysis of complex disease vary. However, combining expertise from several fields will be key to achieving optimal utilization of SNPs.
Oligonucleotide conjugated with water-soluble meso-tetra(4-carboxyphenyl) porphine (TPPC4) has been prepared by a supporting synthesis and novel solid-phase conjugation strategy. The conjugates could ...be used in dual fashion: i) on formation of iron complex, target DNA could be site-specifically cleaved on incubation with dithiothreitol; ii) on incubation of RR 1022 rat epithelial cell culture with non-metalized oligonucleotide TPPC4 conjugate, cytotoxic effect was detected after irradiation with laser light at 635 nm.
The Clear-PEM scanner was developed by the Portuguese PET Consortium under the framework of the Crystal Clear Collaboration for detection of early stage breast cancer. The scanner relies on a modular ...design in which detection modules are readout by low-noise ASICs that extract the pulse shape information for energy and timing measurements. The developed module has a dual readout, in which avalanche photodiodes arrays are used to extract the light from 20 mm long 2×2 mm 2 cross section LYSO:Ce crystals, with a typical depth of interaction (DOI) resolution of 2.2 mm FWHM. The packing fraction of the module is 64%. In order to further improve the detection sensitivity of the scanner, by increasing the packing fraction while maintaining the already achieved DOI resolution, experimental work on the upgrade of the detector module was carried out. The work consisted on the exploration of arrays with 30 mm long crystals as well as the use of crystals with 2.2×2.2 mm 2 cross section wrapped in a specular reflector, yielding a larger packing fraction, of about 78%. Energy, DOI resolution and the relative light collection were measured for polished and unpolished crystal arrays. For the polished crystal array, the variation of the photopeak position within the same matrix, was 6% r.m.s. For the 30 mm unpolished crystal array the energy resolution was 14.7% with a DOI resolution of 2.7 mm FWHM. An approach to improve the light collection efficiency is reported in which individual crystals have a mixture of different number of polished and un-polished longitudinal faces. Using crystals with two longitudinal sides polished, leaving the remaining as-cut, allows extracting the DOI coordinate with a resolution of 2.8 mm FWHM, an energy resolution of 16% and the improvement in light collection of about 30%, in respect to the unpolished matrices. Based on these measurements a new set of detector modules were produced and characterized using the Clear-PEM frontend and data acquisition electronics. Preliminary results for the total light collection, light collection asymmetry and energy resolution are reported.
2'3'-Dideoxyinosine (didanosine) is a nucleoside analog active in vitro against human immunodeficiency virus. Few data are available regarding its use for the treatment of children. In a ...single-center, randomized, open-label trial, we compared two dosages of didanosine (120 vs 270 mg/m2 per day) for at least 6 months in 34 children infected with human immunodeficiency virus who had become resistant to or were intolerant of zidovudine. Serum levels of didanosine 1 hour after administration were significantly different in the two groups and remained stable with time. There was a significant reduction in human immunodeficiency virus-p24 antigenemia and quantitative cellular viremia with time but no difference between the two groups. The intensity of the biologic response, however, was significantly higher in the patients who had more than 50 CD4+ cells 10(6)/L at inclusion. No pancreatic or neurologic toxic effects were observed. In five children, liver function abnormalities developed that are unusual in this setting, and the death of one child from unexplained hepatocellular failure suggests that didanosine may be hepatotoxic. Three of these five children had preexisting liver disease. Although no definite conclusion can be made as to the optimal dose, there were no major differences between the two administration schedules in terms of biologic effects and tolerability.
Obtaining images with high resolution and contrast from short exams is crucial for the viability of Positron Emission Mammography as an early breast cancer detection technique. The Clear-PEM detector ...is a Positron Emission Mammography scanner, developed by the Portuguese Consortium in the framework of the Crystal Clear Collaboration at CERN, based on high-granularity avalanche photodiodes readout with 12288 channels, coupled to pixilated 2x2x20 mm 3 LYSO:Ce crystals in a double readout configuration. The scanner features a high bandwidth three-level acquisition system with negligible dead time in order to minimize exam time. The frontend is instrumented with low-noise amplifier/discriminator/multiplexer ASICs (L0 trigger) and free-running ADCs while the off-ddetector electronics, implemented in FPGAs, computes the trigger primitives from the pulse amplitude and timing. With this information the readout electronics selects interesting photoelectric events and groups multi-hit events due to in-Compton scatter into possible coincidences. After a first-level trigger (L1) is generated, filtered data is read out over a high speed data link into a second-level (L2) software trigger which reprocesses the selected events in temporal coincidence with more accurate energy and time extraction algorithms. The DOI coordinate and the re-validated energy and time allow to achieve an improved reconstruction of in-detector Compton scattering and rejection of random and scattered coincidences. On this paper, we report on the experimental validation, characterization and optimization of the L1 data acquisition electronics, readout link and L2 software trigger and present performance results. We discuss the validation of the associated operation software.
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