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Subclinical and clinical thrombosis of bioprosthetic cardiac valves is more common than has been previously recognized. We present a unique case of acute thrombosis of a bioprosthetic mitral valve in a 40-year-old female patient undergoing hormonal stimulation as part of in vitro fertilization therapy, who also had concomitant protein C deficiency that was undiagnosed at the time. To the best of our knowledge, this is the first reported case of acute bioprosthetic valve thrombosis in this complex thrombophilic milieu, and suggests the need for increased screening for prothrombotic risk factors in female patients with bioprosthetic valves before they commence gonadotropin stimulation therapy.

This study evaluated the impact of influenza and vaccination coverage in Apulia, Italy, during the 2004–2005 and 2005–2006 seasons, using epidemiological and virological surveillance data collected through the Italian Net of Surveillance of Influenza (InfluNet) organized by the Superior Institute of Health (ISS) and the Inter-University Centre of Research on Influenza (CIRI). Vaccination coverage was calculated from the number of doses administered to individuals aged ≤ 65 years. Sentinel physicians reported weekly influenza-like illness (ILI) and acute respiratory illness (ARI) occurrences among patients. Influenza viruses were isolated and identified by cell culture on Madin-Darby Canine Kidney cells and polymerase chain reaction techniques. Vaccination coverage reached 72.7% and 77.0% during the 2004–2005 and 2005–2006 seasons, respectively. Incidence of ILI was higher during the 2004–2005 season compared with the 2005–2006 season, whereas the incidence ARI appeared to show a more constant trend. Incidence rates for ILI and ARI were higher in the 0 − 14-year age group. The increase in vaccination coverage and implementation of a network of epidemiological and virological surveillance are fundamental for the control and prevention of influenza.

We present some results obtained with silicon and gallium arsenide pixel detectors to be applied in the field of digital mammography. Even though GaAs is suitable for medical imaging applications thanks to its atomic number, which allows a very good detection efficiency, it often contains an high concentrations of traps which decrease the charge collection efficiency (CCE). So we have analysed both electrical and spectroscopic performance of different SI GaAs diodes as a function of concentrations of dopants in the substrate, in order to find a material by which we can obtain a CCE allowing the detection of all the photons that interact in the detector. Nevertheless to be able to detect low contrast details, efficiency and CCE are not the only parameters to be optimized; also the stability of the detection system is fundamental. In the past we have worked with Si pixel detectors; even if its atomic number does not allow a good detection efficiency at standard thickness, it has a very high stability. So keeping in mind the need to increase the Silicon detection efficiency we performed simulations to study the behaviour of the electrical potential in order to find a geometry to avoid the risk of electrical breakdown.

It is well known that a monochromatic X-ray source with an energy optimized for the organ thickness to be imaged could result in a better image quality in transmission radiology. In this paper we present the preliminary investigation for the implementation of this technique in computer tomography (CT) imaging. The detection system is based on a 1 mm thick silicon pixel detector bump bonded to a VLSI read-out, Medipix2. This detector ensures a good detection efficiency (46%) in the used energy range (60 kVp) with a good spatial resolution that arises from a 55 μm square pixel. The Medipix2 read-out electronics is not only a single photon counting system, but has also the capability of dual-energy threshold, that allows us to detect only photons that are in a chosen energy window. In this paper we present the results obtained in CT imaging of small samples, by selecting various energy windows within a standard X-ray tube spectrum so as to maximize the differentiation between significant attenuation coefficients. This study is preliminary for a future development of a dual-energy CT that could add functional information to the morphological information that is obtained in a CT examination.

Current pulses produced by absorption of picosecond near-infrared light pulses have been used in order to analyze the shape of the electric field and charge transport properties in semi-insulating (SI) GaAs Schottky barrier X- and gamma-ray detectors. Diodes with square pads of side 0.2–1 mm on 200, 600 and 1000-μm-thick SI GaAs substrates have been illuminated from the front (Schottky) contact, from the back (ohmic) side and laterally between the contacts. Current pulses have been recorded with a fast digital sampling oscilloscope, at room temperature, without using any signal amplification. Current and charge pulse shapes have been analyzed as a function of reverse bias voltage, positioned on the detector surface and optical wavelength around the near-infrared absorption edge of GaAs. The wavelength tuning allows for increasing light penetration lengths. Signal analysis gives the peak current, total collected charge and the charge collection time, which are related to the average strength of the electric field and the drift velocity field, while pulse shape depends on the local value of these fields. The experimental results show that a complete detector characterization is feasible with this optical technique, in a manner analogous to that commonly done with gamma- or X- or alpha-ray sources, with the advantage of analyzing the charge collection time. An additional advantage is represented by focusing the light beam on the detector surface, for 1D or 2D scan.

We are implementing an X-ray breast Computed Tomography (CT) system on the gantry of a dedicated single photon emission tomography system for breast Tc-99 imaging. For the breast CT system we investigated the relevance of the beam hardening artifact. We studied the use of a single photon counting silicon pixel detector (0.3 mm thick, 256 � 256 pixel, 55mm pitch, bump-bonded to the Medipix2 photon counting readout chip) as detector unit in our X-ray CT system. We evaluated the beam hardening ‘‘cupping’’ artifact using homogeneous PMMA slabs and phantoms up to 14 cm in diameter, used as uncompressed breast tissue phantoms, imaged with a tungsten anode tube at 80 kVp with 4.2 mm Al filtration. For beam hardening evaluation we used a bimodal energy model. The CT data show a ‘‘cupping’’ artifact going from 4% (4-cm thick material) to 18% (14-cm thick material). This huge artifacts is influenced by the low detection efficiency and the charge sharing effect of the silicon pixel detector. r 2007 Published by Elsevier B.V. PACS: 85.57.cp; 87.57.Q

The aim of this work is to evaluate the capability of a single photon counting acquisition system based on the Medipix2 read-out chip for Computed Tomography (CT) applications in Small Animal Imaging. We used a micro-focus X-ray source with a W anode. The detection system is based on the Medipix2 read-out chip, bump-bonded to a 1 mm thick silicon pixel detector. The read-out chip geometry is a matrix of 256×256 cells, 55 μm×55 μm each. This system in planar radiography shows a good detection efficiency (about 70%) at the anode voltage of 30 kV and a good spatial resolution (MTF=10% @ 16.8 lp/mm). Starting from these planar performances we have characterized the system for the tomography applications with phantoms. We will present the results obtained as a function of magnification with two different background medium compositions. The effect of the reconstruction algorithm on image quality will be also discussed.

In digital imaging the ability to detect low contrast details is an aim that must be pursued. In order to achieve this result we have developed an acquisition system based on silicon pixel detector. The detector is a matrix of 256×256 square pixels of 55 μm size. It is bump-bonded to a readout chip developed by the Medipix2 Collaboration [X. Llopart, et al., IEEE Trans. Nucl. Sci, NS-49 (5) (2002) 2279]. To see the low contrast details with this system, it is necessary to reduce inside the image the fluctuations of pixel-to-pixel counts, [1] down to statistical fluctuations. This has been achieved equalizing the phantom image with a high statistics flat field acquired in the same irradiation condition. We have studied the dependence of the image uniformity for different flat field and we have investigated the dependence of the image quality on the thickness of the phantom and on the energy window selected inside the incident spectrum.

Digital mammography is entering routine clinical use and many commercial systems are now in use in the radiological units for screening and diagnostic mammography. At the same time, the research in the digital mammography field is very active in the development of more and more performing devices. In this paper we present the performance of single photon counting pixel detectors (MedipixI) tailored for digital mammographic applications. These devices are based on semiconductor (Si and GaAs) pixel detectors of different thickness, read-out by custom designed integrated circuits. To assess the imaging capability of such systems, the images of a mammographic phantom have been acquired in standard conditions for a clinical examination. The signal-to-noise ratio (SNR) of details simulating tumor masses has been evaluated. The same phantom has been also radiographed by three different commercial digital mammographic systems in the same reference conditions and a comparison in terms of SNR has been carried out. The spatial resolution of the single photon counting systems has also been evaluated by measuring the line spread function with the edge technique and then calculating the Modulation Transfer Function (MTF). The MTFs of the single photon counting systems have been compared with the MTFs of the commercial systems.

In this study of influenza vaccination, 37 human immunodeficiency virus (HIV)-1-seropositive patients were randomized to receive either a vaccine with a conventional subunit or one adjuvanted with MF59. Blood samples were collected at the time of vaccination, and then 30 and 180 days later, to evaluate immunogenicity, CD4+ T-lymphocyte count and HIV-1 RNA levels. Seroconversion rates against the three viral strains included in the vaccine ranged between 44% and 72% and 53% and 68% for the adjuvanted vaccine and the subunit vaccine, respectively. Other criteria of the European Medicines Evaluation Agency were also met. Vaccination was not associated with serious adverse events. Local and systemic effects were mild and of short duration. CD4+ T-lymphocyte counts and viraemia levels were not negatively affected by vaccination. These results confirmed the safety and immunogenicity of these currently available vaccines in HIV-1-seropositive patients, thus supporting the recommendation for influenza immunization in this high-risk category.

The Integrated Mammographic Imaging (IMI) project aims to realize innovative instrumentations for morphological and functional mammography, in particular, one of the research topics is the design and development of a prototype of a mammographic head. Innovative industrial processes for the production of GaAs pixel detectors and for their bump-bonding to the read-out VLSI electronics have been developed by AMS. The data acquisition and processing have been developed by LABEN; the power supply and distribution system has been realized by CAEN; while the integration of the head in a standard mammograph has been carried on by the Laboratori di Ricerca Gilardoni.

Our group is working at the development of a prototype for digital mammography based on semiconductor detectors inside the “Integrated Imaging Mammographic” project, which is a collaboration between some industries and some research groups (I” and University Physics Departments of Pisa, Ferrara, Roma, Laben, AleniaMarconiSystems, CAEN, Pol.Hi.Tech., Gil ardoni). The detection unit has an active area of 1.2 cm2 and is composed by a semiconductor pixel detector and a single photon counting chip (PCC, developed within the framework of the MEDIPIX collaboration [I], [2]). The chip contains 64 x 64 square cells, 170 pm in side, connected to each pixel of the detector by bump bonding. Each cell is an asynchronous read-out channel, equipped with a low noise charge preamplifier, a latched comparator, a digital shaper and a 15 bits counter. In order to improve the detection efficiency in the energy range of mammography, we designed and simulated 300 pm and 525 pm thick Si detector, that have been produced by ITC-IRST (Trento, Italy). We have simulated the behaviour of the electric potential inside the detector in order to find a geometry to optimize the performances of our detector and to avoid the risk of breakdown that will be more likely as one will increase the thickness.

As the use of digital radiographic equipment in the morphological imaging field is becoming largely diffuse, the research of new and more performing devices from public institutions and industrial companies is in constant progress. Many of these devices are based on solid-state detectors as X-ray sensors. Semiconductor pixel detectors, originally developed in the high energy physics environment, have been then proposed as digital detector for medical imaging applications. In this paper a digital single photon counting device, based on silicon and GaAs pixel detectors, is presented. The detector is a thin slab of semiconductor crystal equipped with an array of 64 by 64 square contacts, 170-μm side. The data read-out is performed by a VLSI integrated circuit named Photon Counting Chip (PCC), developed within the MEDIPIX collaboration. Each chip cell geometrically matches the sensor pixel. It contains a charge preamplifier, a threshold comparator and a 15 bits pseudo-random counter and it is coupled to the detector by means of bump-bonding. Most important advantages of such a system, with respect to a traditional X-rays film/screen device, are the wider linear dynamic range (3x10 4 ) and the higher performance in terms of MTF and DQE. Electronics read-out performance as well as imaging capabilities of the digital device will be presented. Images of mammographic phantoms acquired with a standard mammographic tube will be compared with radiographs obtained with traditional film/screen systems.

In this work we exploit the advantages of using a bi-chromatic X-rays source coupled with a single photon counting pixel detector to perform a feasibility study for dual energy mammography. This technique allows enhancing the contrast between different breast tissues by composing two images acquired at two different energies. The high and low energy images have been acquired by a single X-ray shot. The bi-chromatic beam has been produced per diffraction of polychromatic photons by a monochromator crystal. The imaging system is based on a single photon counting silicon pixel detector. The data read-out is performed by a VLSI Integrated Circuit bump-bonded to the sensor. The energy threshold of each electronics channel can be individually trimmed. We set the threshold of one pixel below 16 keV while the threshold of the neighboring pixel between 16 and 32 keV. With a single exposure the information from both energies is recorded. After separation between low and high threshold pixels, we obtained two independent images. We acquired radiographs of phantoms made of three different materials. Appling a dual energy algorithm, we obtained synthesized images where any of the three materials is removed from the radiograph, enhancing the contrast between the two remaining.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

In mammography, the first cause of image contrast reduction arises from the photons scattered inside the examined organ. The amount of Compton scattering strongly depends on the irradiation area and on the distance between the organ and the X-ray detector. We have experimentally evaluated how these geometrical conditions affect the scattering fraction. Our experimental setup includes a single photon counting device based on a silicon pixel detector as X-ray sensor; a lucite cylinder to simulate the breast tissue, and a lead collimator to define the irradiation area. We have evaluated the contrast and the signal-to-noise ratio for images acquired in different conditions.

A multiple-exposure technique in digital mammography has been developed to suppress the physical background in the image due to Compton scattering in the body. A pair of X-ray masks, shaped in a projective geometry and positioned upstream and downstream the patient, are coupled mechanically and moved in four steps along a square pattern in order to irradiate the full area in four consecutive short exposures. A proof-of-principle apparatus is under test with a breast phantom and a standard mammographic X-ray unit. Results are reported.

In this work we present the results of a systematic study about SI GaAs detectors as a function of substrate and contact type, geometry and thickness. This study has been stimulated from the interest in using GaAs as a detector for medical imaging applications. GaAs detectors have been produced using crystals grown with different techniques and changing both the thickness (in the range 200 μm-1 mm) and the contacts type and geometry. We have measured the current-voltage characteristics and, using radioactive sources (109Cd, 20 keV photons, 241Am, 60 keV photons, 99mTc, 140 keV photons), we have studied the performance of our detectors in terms of charge collection efficiency and energy resolution as a function of the bias voltage. Besides we have also studied the electrical and spectroscopic properties of GaAs detectors with different types and concentrations of the dopants in the substrate. So we have found the optimal doping type and concentration to have the best spectroscopic performances and the higher breakdown voltage. Simulation programs made with Monte Carlo methods have been developed to describe the electric field distribution and the transport of charge carriers toward the electrodes in GaAs detectors. In these simulations we have considered the presence of deep energy levels in the bandgap, the thickness, the bias voltage and the charge deposition in the crystal after photon interaction.

Semi-insulating gallium arsenide (SI-GaAs) detectors, in the form of Schottky diodes, have been irradiated from the front or from the back contact or from the side, with light pulses from picosecond laser source, tunable in the range of 780–1020 nm and focused to a 50–100 μm spot on the surface of the detector. Energy per pulse was in the range of 4–25 pJ, with a 10 or 100 Hz repetition rate. Each pulse mimics the interaction of a single energetic particle with the substrate, but with a photon mean free path modulated in the range of 1 μm–1 cm, depending on the light wavelength. The SI-GaAs substrates have a thickness of 200 μm (VGF grown), or 600 μm (LEC) or 1000 μm (VGF). The time response of the detectors, analysed with the Transient Current Technique (using a fast digital sampling oscilloscope) in terms of peak signal amplitude and charge rise time, has been evaluated as a function of: reverse voltage bias (50–1200 V), light wavelength (780–1020 nm), side position between the electrodes, position on the front contact. The results are: (1) the shape of the transient current signal may show the presence of two peaks, about 1 ns apart; (2) the charge rise time, considered to be dominated by the charge collection time, is between 2 and 13 ns; (3) the charge rise time, as due to electron drift or hole drift in the region between the contacts, has been measured as 2–5 ns, also dependent on the applied bias; (4) the transient current (exponential) decay time, for front or back irradiation, increases with the bias voltage up to 2–20 ns and these data are considered to be consistent with the electron detrapping time; (5) under reverse bias, for 1 mm pad side and a large ohmic contact on the back, the electric field extends around the front contact up to about 200 μm.

Imaging capabilities, spatial resolution and spectroscopic analysis have been performed to compare the characteristics of imaging systems based on pixel detectors of different thickness. Each system consists of a single photon counting chip (PCC), developed in the framework of the Medipix Collaboration, bump bonded to a silicon detector. The detector is a matrix of 64times64 square pixels, with 170 mum pitch and thickness ranging from 300 to 800 mum. As expected, the intrinsic detection efficiency increases with detector thickness (for 22 keV photons the detection efficiency doubles in the examined thickness range), nevertheless the spatial resolution can be affected by a charge sharing mechanism between adjacent pixels due to charge diffusion. We have studied this effect and its dependence on the detector bias voltage and the threshold value of PCC with the aim of optimizing both the detection efficiency and the spatial resolution

To compare the characteristics of imaging systems based on pixel detectors of different thickness, we have measured the respective imaging capabilities, spatial resolution and spectroscopic characteristics. Each system consists of a single photon counting chip, developed in the framework of the Medipix Collaboration, bump bonded to a silicon detector. The detector is a matrix of 64 /spl times/ 64 square pixels, with 170 /spl mu/m pitch and thickness ranging from 300 to 800 /spl mu/m. As expected, the intrinsic detection efficiency increases with the detector thickness; nevertheless the spatial resolution can be affected by a charge sharing mechanism between adjacent pixels due to charge diffusion. The aim of the work reported in this paper is to demonstrate that, optimizing the settings of the image systems, we can increase the detection efficiency without losing in spatial resolution.

Tests on silicon pixel detector in the mammographic energy range have shown good imaging performances so, in order to improve the efficiency in this energy range, we have designed thicker detectors of the p+/n type. The detectors have been fabricated by ITC-IRST (Trento, Italy) in high resistivity silicon substrates (300 and 525 μm thick). A TCAD simulation work has been carried out to optimize the electric field distribution and to enhance the breakdown voltage. Very low leakage current and high breakdown voltage characteristics have been measured on detectors in preliminary on-wafer tests. After that, detectors have been bump-bonded to a dedicated VLSI electronic chips, realizing an assembly. Choosing the best set-up condition and using a standard mammographic tube, we have acquired a large area image (8×8 cm2) of the RMI 156 phantom, recommended for mammographic quality checks. In order to cover the whole surface, we have acquired different images translating the phantom over the assembly. We present some selected results for these assemblies both for the electrical characteristics and for the imaging performances.

To realize innovative instrumentation for mammography, a digital mammographic head based on several gallium arsenide detectors and on the Medipix chip (developed by the Medipix collaboration at CERN) has been designed. This device is able to perform single photon counting readout and allows a full detection efficiency at the mammographic energies. To make such detection units, industrial processes for the production of GaAs pixel detectors and for their bump-bonding to the read-out VLSI electronics have been developed by Alenia Marconi Systems (AMS S.p.A.). The detection unit is a 200 /spl mu/m thick GaAs matrix of 64/spl times/64 square pixels (170 /spl mu/m pitch), previously optimized and fully characterized, connected via bump bonding to the electronic chip. Specific studies were performed to develop a process that meets the requirements of low cost, high yield and high reliability for the bump bonding process of the GaAs detector to the silicon electronics. To ensure a high-quality electrical contact between the matrix detector and the silicon read out electronics a bump-bonding process has been set-up. It is based on a In evaporation process. In this work we present the technical characteristics of the bump bonding process and the results obtained in terms of bump-bonding yield and detection performance of the GaAs based detection units which have been realized and fully tested and are now ready to be implemented in the mammographic head.

We present the imaging capabilities of a system based on a single photon counting chip, bump-bounded to a Si pixel detector. The detector is 300 µm thick a matrix of 64 x 64 square pixels with a dimension side of 170 µm. The active area is about 1.2 cm2. The photon counting chip matches the geometry of the detector so it has 4096 asynchronous read-out cells, each containing a charge preamplifier, a leading edge comparator and a pseudorandom counter. We have tested the image quality and the stability of our acquisition system imaging some phantoms used for mammografic quality checks. Our system allows to see low contrast details with a patient dose comparable with that given in mammographic examinations.

Pixel detectors for mammographic applications have been fabricated at ITC-irst on 800 μm thick silicon wafers adopting a double side n + -on-n fabrication technology. The activity aims at increasing the X-ray detection efficiency in the energy range of interest minimizing the risk of electrical discharges in hybrid systems operating at high voltages. The detectors, having a layout compatible with the Medipix2 photon counting chip, feature two different design solutions for the p-isolation between neighboring n + -pixels. We report on the characterization of the fabrication process and on preliminary results of electrical measurements on full detectors and pixel test structures. In particular, we found that the detectors can be reliably operated above the full depletion voltage regardless of the isolation design, that however, impacts the performances in terms of current–voltage characteristics, single pixel currents, inter-pixel resistances and inter-pixel capacitances.