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The European Risk Management Plan (EU-RMP) is a proactive planning tool for identification, characterisation and management of important risks and missing information throughout the lifecycle of a medicinal product. Over the past 15 years the EU-RMP has been a part of the pharmacovigilance practice in Europe, but there are no published studies assessing impact of the growing experience and evolving regulatory framework on the content and focus of the EU-RMP.The objectives were to study the real-world impact of evolving pharmacovigilance guidelines on the proactive lifecycle management of important risks and missing information through EU-RMPs, and to further explore the impact of different resources on the management of the benefit-risk profile.A retrospective study based on the review of 64 EU-RMPs dated between 01 January 2006 and 01 October 2020 for seven human medicinal products for which Boehringer Ingelheim holds the Marketing Authorisation in the European Union. Data on the timing and rational behind changes (i.e., inclusion, reclassification, removal) to the safety concerns (Important Identified Risks, Important Potential Risks, Missing Information) and associated additional Pharmacovigilance activities and/or Risk Minimisation measures were collected and assessed.The analysed EU-RMPs included a total of 197 safety concerns, 129 of which were removed and 19 were reclassified during the observation period. The implementation of the Guidelines on Good Pharmacovigilance Practices Module V in 2012 and Revision 2 in 2017 resulted in a noticeable decrease in the number of safety concerns. Clinical trial, non-clinical and routine post-marketing data were common sources that influenced the safety concern dynamics, and results from dedicated post-authorisation studies lead to the removal of 21 important risks and missing information. Many safety concerns were related to pharmacological class effect (n = 55) and target population characteristics (n = 37).This study demonstrated that the growing knowledge regarding benefit-risk of approved products and the introduction of new or revised regulatory guidelines influenced the EU-RMP lifecycle of safety concerns, and moreover, the results emphasise that exchange of knowledge about the pharmacological class and target population between stakeholders are important for keeping an up-to-date understanding of a medicinal product's safety profile. The aim of improving the efficiency of risk management has leveraged the accumulation of knowledge leading to revision of regulatory guidelines and increasingly, proactive Risk Management Plans focused on safety concerns that are important for patients and public health.

The climate fluctuations of the Quaternary shaped the movement of species in and out of glacial refugia. In Europe, the majority of species followed one of the described traditional postglacial recolonization routes from the southern peninsulas towards the north. Like most organisms, barn owls are assumed to have colonized the British Isles by crossing over Doggerland, a land bridge that connected Britain to northern Europe. However, while they are dark rufous in northern Europe, barn owls in the British Isles are conspicuously white, a contrast that could suggest selective forces are at play on the islands. However, analysis of known candidate genes involved in colouration found no signature of selection. Instead, using whole genome sequences and species distribution modelling, we found that owls colonised the British Isles soon after the last glaciation, directly from a white coloured refugium in the Iberian Peninsula, before colonising northern Europe. They would have followed a yet unknown post-glacial colonization route to the Isles over a westwards path of suitable habitat in now submerged land in the Bay of Biscay, thus not crossing Doggerland. As such, they inherited the white colour of their Iberian founders and maintained it through low gene flow with the mainland that prevents the import of rufous alleles. Thus, we contend that neutral processes likely explain this contrasting white colour compared to continental owls. With the barn owl being a top predator, we expect future research will show this unanticipated route was used by other species from its paleo community.

A large-area hybrid photodiode interfaced to scintillating crystals is being evaluated to determine its application as part of a positron camera dedicated to imaging the breast, positron emission mammography (PEM). The sensitive photocathode area of the HPD is 72 mm in diameter and the diode is divided into 61 separate pixels. The principal of the detector for PEM will be the use of analogue information from the individual diodes to provide 2D positional information. Simulations of the device attached to a low noise amplifier system show that a spatial resolution of a few mm should be possible. Estimates of the spatial resolution, sensitivity and energy resolution from different scintillating crystals detecting annihilation photons will be presented.

High-resolution scintillation spectrometers based on the use of large-volume spherical CsI(Tl) spectrometers viewed by conventional 1 cm/sup 2/ PIN diode have been shown to have excellent performance characteristics. In particular, their unique geometry, the small area of contact between the diode and the crystal's surface, and the high reflectivity of the packing material combine to provide a detector in which there is a very small variance in the signal generated by energy deposits in different regions of the crystal. In view of the unique spectral-resolution achieved using the first prototype Scintispheres (S100-PIN and S300-PIN) to be manufactured, it was natural to explore the boundaries within which this technology might be useful. This paper presents the results of a series of modeling exercises and experimental investigations aimed at finding the range of detector volumes that can usefully be constructed based on the use of PIN photodiodes. For a given amplifier performance, the predicted spectra-resolution of a range of Scintisphere volumes has been estimated as a function of energy. This study was made both for the CsI(Tl) material used in the original devices and for other materials which may be important when the speed of operation and stopping power are important design parameters. These studies also considered the performance limits that might be achievable in small volume Scintispheres. This paper also presents the results obtained when our deconvolution algorithm is applied to a wide range of standard scintillation spectrometers. These demonstrate the high spectra-resolution and sensitivity that can be achieved using this technique.

This paper presents details of the design and performance of three prototype Scintisphere detectors for use in gamma-ray spectroscopy. In these detectors, spherical CsI(Tl) scintillation crystals, having diameters ranging from 3.4 cm (20 cm/sup 3/) to 8.3 cm (300 cm/sup 3'/), were polished and packed in dry MgO powder. The scintillation light from the crystal was viewed using a single 1 /spl times/ 1 cm/sup 2/ silicon PIN diode. A low-noise preamplifier was also integrated within the detector housing. The measured noise level was equivalent to /spl sim/800 electrons (FWHM). Such a configuration results in a relatively high light-collection efficiency. For example, in the 300 cm/sup 3/ (8.3 cm diameter) detector, an average of /spl sim/10 electron/hole pairs were generated for each keV deposited in the crystal. One of the key features of this detector design is that it minimizes the spatial variations in the light-collection efficiency throughout the detector. Compared with a standard 3-in NaI(Tl) scintillation counter, this leads to a much-improved energy resolution, particularly for photon energies above 1 MeV The results presented in this paper clearly demonstrate that these spherical CsI-photodiode detectors could be used as an ideal replacement for the standard 3-in NaI(Tl) detectors in many applications.

This paper presents details of the design and performance of a prototype large-volume scintillation detector used for gamma-ray spectroscopy. In this detector, a spherical CsI(Tl) scintillation crystal having a diameter of 5.7 cm was polished and packed in dry MgO powder. The scintillation light from the crystal was viewed using a single 1 � 1c m 2 silicon PIN diode. A low-noise preamplifier was also integrated within the detector housing. The measured noise level was equivalent to B800 electrons (FWHM). Such a configuration provided a very good light collection efficiency, which resulted in an average of 20 electrons being generated per keV of energy deposited in the crystal. One of the key features of the detector design is that it minimises spatial variations in the light collection efficiency throughout the detector. Compared with a standard 3 in. NaI scintillation counter, this feature leads to a much-improved energy resolution, particularly for photon energies above 1 MeV. The results presented in this paper clearly demonstrate that a spherical CsI-photodiode detector could be used as an ideal replacement for the standard 3 in. NaI detectors in many applications, but especially when the incident gamma-ray spectra extend up to B10 MeV as in neutron-activated gamma-ray analysis. r 2001 Elsevier Science B.V. All rights reserved.

An inspection technique based on angular dispersive X-ray diffraction (ADXRD) has been developed to chemically specific detection of explosives for screening applications. The technique identifies explosives from benign materials using the characteristic Bragg features seen in coherently scattered X-rays. To implement this technique in a prototype screening system, a detector has been designed which, when coupled with the appropriate analysis algorithm, provides chemically specific material identification. Profile analysis has been performed using the Singular Value Decomposition (SVD) maximum likelihood technique. The detector system combines a custom designed collimator with an X-ray image intensifier tube and is capable of acquiring diffraction profiles from several independent volume elements (voxels) within the region of interest. The acquisition of spatially and energy resolved diffraction profiles for both benign and explosive materials using a separate cooled germanium detector, has allowed the data analysis algorithm to be optimised. Results from the prototype detector system show that explosives such as Semtex, RDX, and PETN have sufficient order to produce unique diffraction profiles, which may then be differentiated from benign materials.

This paper presents a comparison of three deconvolution techniques, Maximum Likelihood, Maximum Entropy and Linear Regularisation for the unconstrained deconvolution of gamma-ray spectra. These convert the raw energy-loss spectra obtained using a standard scintillation counter, into a good representation of the incident gamma-ray spectrum. This work is based on the use of an industry-standard 3/spl times/3 inch NaI detector. Both simulated and measured data have been deconvolved using the three algorithms to provide a direct comparison between the qualities of the deconvolved spectra. For applications in which it is important to derive an accurate estimate of the number of counts in a particular full-energy peak, the Maximum Likelihood Method has been shown to be superior.

The results of a feasibility study for a high-resolution PET detector system are presented. The detector is based on the use of etched LSO scintillation crystals viewed from just one end. The authors have demonstrated that this configuration yields Depth-of-Interaction (DOI) information whilst also preserving good energy and coincidence-time resolution. A prototype detector was built using a 4/spl times/4 crystal array coupled to 61-pixel hybrid photodiodes. The measurements demonstrate a DOI resolution of 5/spl sim/7 mm FWHM in a 30 mm deep detector. The signal level was measured to be in the range 250 to 600 photoelectrons depending on the location of the 511 keV energy deposit in the crystal. A resolving-time of less than 5 ns FWHM was estimated based on indirect measurements. The technique depends on the assumption that all of the events detected above a selected threshold value are, in fact, full-energy deposits. The validity of this assumption and the impact of the photons scattered in the object have been studied using a Monte Carlo simulation of the proposed small animal PET imager.

A design for a large area, position-sensitive gamma-ray spectrometer for use in imaging explosive materials is described. The design has been optimised for use in the energy range from 2 to 12 MeV. At 5 MeV, the spectral resolution of each CsI(Tl)-photodiode pixel is better than 3% FWHM. The multi-element detector system, when used in conjunction with a coded-aperture mask, is able to provide a “multi-colour” image of the scene when illuminated by a neutron source. The feasibility of using such a system to identify the unique elemental composition and location of the explosive materials is discussed.

In this paper, the performance characteristics of a small prototype gamma-camera system based on the use of the recently developed Multi-pixel Hybrid Photodiode (M-HPD) are described. A compact read-out system has been developed to record the signals from all 61 pixels in the device. Single photo-electrons can be detected in each pixel. This provides an excellent means for calibrating the signal detected in each pixel in terms of the number of photo-electrons. The position-resolution of the detector has been measured as a function of the number of photo-electrons by using a finely collimated beam of light. The spatial resolution (FWHM) was measured to be 0.5 mm for a signal level of 100 photo-electrons. The M-HPD has also been used in a miniature Anger-camera system to locate the position of interaction of gamma-ray photons in a scintillator. The light-pool generated by each event in a continuous scintillation crystal is spread in the 2mm thick entrance window of the M-HPD so that the photo-electron cloud is detected by a small cluster of anode pixels. The light-spread information has been measured and is compared with optical Monte Carlo simulations.

A gamma-ray imaging system optimised for use in the nuclear environment has been developed. The system allows the simple selection of either pinhole or coded aperture image formation techniques depending on the nature of the scene. The detector portion of the instrument is the same for both options and comprises a 3′′ diameter PSPMT coupled to an array of CsI(Tl) crystals each with dimensions 3.5×3.5×25 mm on a 3.8 mm pitch. The detector is mounted within a tungsten shell, which provides at least 35 mm of shielding to sources outside of the FOV. The field of view for both imaging techniques is 12.8°. The pinhole diameter of 6 mm provides an angular resolution of ∼2° at 662 keV. The coded aperture comprises a 127 hexagonal-URA produced by machining 3 mm holes on a 3.5 mm pitch in a 3 mm deep tungsten sheet and provides an angular resolution of ∼1° at 662 keV. Both imaging techniques have been used to view a range of radiation scenes to determine their relative performance. As expected the coded aperture showed better sensitivity in high background environments however for scenes with low and moderate background rates with several sources in the FOV the pinhole system performed better. The results suggest that a lightweight system, which allows both coded aperture and pinhole imaging, can provide excellent sensitivity and dynamic range coverage for a wide range of radiation scenes.

This paper describes the results obtained from various scintillators when viewed by a Hybrid PhotoDiode (HPD) with several different scintillation crystals. The energy loss spectra produced by gamma-ray photons having energies in the range of 20 to 662 keV were measured using a commercially available HPD. An excellent single photo-electron response was measured using a low-noise preamplifier. Measurements of the number of photo-electrons produced and the energy resolution of the full-energy peak as a function of the gamma-ray energy and the acceleration voltage were made. Finally, optical Monte Carlo simulations were used to estimate the light loss in the entrance window and to optimise its geometry. The potential advantage of incorporating a BGO entrance window for some applications was also explored.

Open-water leads in sea ice dominate the exchange of heat between the ocean and atmosphere in ice-covered regions, and so must be included in climate models. A parameterization of leads used in one such model is compared to observations and the results of a detailed Arctic sea-ice model. Such comparisons, however, are hampered by the errors in observed lead fraction, but the parameterization appears to compare better in winter than in summer. Simulations with an atmospheric general circulation model (AGCM), using prescribed sea-surface temperatures and ice extent, are used to illustrate the effect of parameterized lead fraction on atmospheric climate, and so provide some insight into the importance of improved lead-fraction parameterizations and observations. The effect of leads in the AGCM is largest in Northern Hemisphere winter, with zonal mean surface-air temperatures over ice increasing by up to 5 K when lead fraction is increased from 1% to near 5%. The effect of leads on sensible heat loss in winter is more important than the effect on radiative heat gain in summer. No significant effect on sea-level pressure, and hence on atmospheric circulation, is found, however. Indirect effects, due to feedbacks between the atmosphere and ice thickness and extent, were not included in these simulations, but could amplify the response.

In order to address the challenge of reliably differentiating between Naturally Occurring Radioactive Materials (NORM) and threat sources using low-cost detector materials, Symetrica has applied de-convolution based spectrum-processing techniques to data generated by enhanced PVT detectors. This paper presents data and performance analysis of a range of large-volume PVT detectors (6, 20 and 27 liters) acquired independently and by Symetrica at a range of test facilities. This data will include; results recorded on the Symetrica Radiation Portal Monitor (RPM) test track, at the JRC premises (Ispra) during the ITRAP+10 and the first benchmarking exercise of the SCINTILLA* program. These results demonstrate the power of this new technique. In particular: the ability of portal-scale detectors to resolve the doublet in an HEU source, identify many bare radio-isotopes, to reliably classify containerized NORM and to detect the presence of threat sources both in isolation and in the presence of a containerized NORM.

Using the Mellor-Yamada level II closure scheme, a numerical study is made of the bottom boundary layer on a uniform, stratified shelf with slope α. For constant interior along-slope currents ug and molecular background diffusion, a new timescale for shutdown of bottom stress is derived for the downwelled layer as well as a new estimate for the maximum height of the upwelled layer, hU = (CD/fN)1/2ug(1 + S1/2)−1 where CD = 2.5 × 10−3 is a drag coefficient, f and N are the Coriolis and buoyancy frequencies, and S = (Nα/f)2 is the Burger number. The Richardson number is also shown to fix the thermal-wind shear at the top of the upwelled layer to be approximately uz≃N(RiS)−1, while within the layer, a depth-averaged form of the geostrophic balance is shown to hold. In the case of large interior vertical diffusivities (10−4 m2s−1), the fluxes of momentum and buoyancy into the interior are quantified and shown to result in the arrest (enhancement) of shutdown in the upwelling (downwelling) boundary layers. Advective restratification of mixed water is not found to occur, and for an 8-day periodic interior current ug(t), the thermal-wind shear that remains during the downwelling and upwelling phases can result in a 1.2-day lag of interior current with bottom stress. Bottom stress and the cross-slope Ekman flux are found to be surprisingly symmetric during the upwelling and downwelling phases of the interior current. The lag with bottom stress and effects of shutdown are shown to persist in the presence of tidal currents and large background diffusion and may well be significant on the continental shelf.

A pinhole camera based on the use of a 3 in. square position-sensitive photomultiplier (PSPMT) to view a two-dimensional segmented CsI(Tl) scintillation crystal has been designed to operate in the range 2 to 200 keV. It has also been used to generate extended test images by rotating two radioactive sources of different energies in the the field of view. The optical characteristics of the system have been simulated using a Monte-Carlo package in order to optimise the detector crystal geometry. The detector performance has also been investigated experimentally as a function of crystal dimensions, and measurements made using different readout techniques are presented. Also outlined is a design for an auroral imager based on the use of an array detector modules which will form part of the Auroral Imaging Observatory (AURIO), selected for inclusion within the payload complement of ENVISAT II. This will be located on a polar orbiting platform at an altitude of 800 km.

Use of 1 cm 2 CsI(T1) scintillators with photodiode readout in the hard X-ray band is currently limited to above ∼ 40 keV by the lack of intrinsic gain in the photodiode and the electronic noise in the readout system. However, below this energy the photodiode itself becomes a practical X-ray detector. We report on the use of a pulse-shape analysis technique in an attempt to separate the signals from direct X-ray interactions in the photodiode and from scintillation events in the CsI(T1). We have demonstrated that separation of the two types of event is certainly possible, and the use of an appropriate spectral reconstruction algorithm enables us to normalise the signals from the two detectors. In this way we have constructed a hybrid detector capable of operating in the energy range 10 keV to 1 MeV. We discuss, using both simulations and laboratory measurements, the optimisation which can be carried out by changing the thickness of the silicon photodiode. We present details of the pulse-shape analysis system, demonstrate the identification and separation of the two types of signal, and present energy spectra for a range of energies.

The position and energy resolution characteristics of three scintillation detectors viewed by a 3 in. square position-sensitive photomultiplier tube have been measured as a function of photon energy. Pixellated detectors having a pitch that ranges between 1.5 mm and 3.5 mm have been studied. The FWHM of the distribution in measured positions was as little as 0.9 mm at 122 keV. In this case, the tube was read out using individual amplifiers to record the charge detected on each individual anode wire and the location found using a peak-fitting algorithm. Comparative measurements were also made using the conventional hardware-centroiding technique.

A detailed study of small, discrete, CsI(Tl)—PIN photodiode detectors has been carried out for the INTEGRAL project. Optical Monte Carlo simulations and noise calculations show that the maximum signal-to-noise ratio may be obtained by using photodiodes whose sensitive area covers approximately 50–60% of the scintillator output surface area. The measured performance for a range of photodiode sizes coupled to a 1 cm 2 scintillator has been compared with the results of the simulations.

A novel multichannel readout technique has been developed for a position-sensitive photomultiplier with a crossed-wire anode. A new charge-sensitive shift register has been used to record the charge collected by each of the anode wires. The performance of a position-sensitive scintillation counter as a function of photon energy and position has been studied using this new technique. A variety of algorithms for reconstructing the energy and position of each event using the individual anode signals are discussed and the potential benefits of this more complex readout system will be illustrated. Compared with the traditional centroiding technique, the individual anode readout method promises better spatial linearity over the entire photomultiplier sensitive area as well as a significant reduction in the low energy threshold.

A new digital 2-axis control system for pointing balloon-borne payloads has been developed. From the outset the system was designed to be both versatile and modular in order to meet requirements for pointing different payloads. Most other designs have been for a dedicated application. User selectable plug-in hardware and software modules reduce the development time needed to adapt the system for different applications. For example, tuning the servo loops is now only a software task. The system has been implemented on payloads of widely different inertias (200 kgm2 and 2500kgm2) without encountering problems.

A position-sensitive phoswich detector designed to cover a wide energy band from 15 keV to 1 MeV has been investigated. The detector concept is based on the use of an array of discrete 1 × 1 × 5 cm phoswich scintillation bars, the top 3 cm of which is CsI(Na) whilst the rear 2 cm is a GSO (Cerium-doped Gadolinium Orthosilicate Gd 2 SiO 5 (Ce), [1,2]) veto crystal. The array is viewed by a single position-sensitive photomultiplier tube (PSPMT). The test results show that energy resolution ranges from 31% FWHM at 60 keV to 13% FWHM at 511 keV. The FWHM of the point-spread function for the location of each event is smaller than the cross section of a single bar over the entire energy range. This guarantees good separation between energy deposits in adjacent bars. The outputs from the CsI(Na) main detectors and GSO veto crystals can be distinguished by a simple pulse-shape discriminator (PSD). Those multi-bar events which deposit energy only in the CsI(Na) array can be recognised using the position sensing capability of the tube. When used in conjunction with a coded-mask imaging system, an array of such detector modules could provide a competitive telescope for a future gamma-ray astronomy mission.

As part of the INTEGRAL (International Gamma-Ray Astrophysical Laboratory) project, CsI(Tl) scintillation elements with a cross-sectional area of 1 cm/sup 2/ and between 1 and 6 cm in length have been developed to form the basis of the imager detector plane. The crystal preparation and wrapping, crystal geometry, optical coupling, and matching to the photodiode have all been optimized in order to maximize the light output from the crystal, and hence produce the lowest energy threshold and best spectral resolution for any given readout electronics. Energy resolutions of 22% of 122 keV and 7% at 662 keV have been obtained using a 1 cm/sup 3/ crystal on a 10*10 mm crystal. With standard laboratory electronics, a low energy threshold of approximately 40 keV has been obtained. >

This paper describes the results of a feasibility study into a spectroscopic-imaging system having a ∼60° field of view, with the capability to locate and identify a 1mCi source of Cs137 at a range of 100m. At this range, the location accuracy will be ∼1m. Small and light enough for mounting on a variety of vehicles. The compact, stand-off imaging system is based on the use of a standard gamma-camera coupled to a coded-aperture mask. The predicted performance of this system will be presented when used to locate and identify radiological sources in both the marine and terrestrial environments. The paper will demonstrate the particular advantages that the use of Symetrica's proprietary spectrum-processing software offers to improve both the detection efficiency and the isotope identification capability at energies beyond the normal range of such a clinical camera.

The design requirements for a new generation hard X-ray imaging telescope are examined and various detector options are considered. A prototype array of 6×8 diodes (each 5 mm×5 mm) has been fabricated by Micron Semiconductors Limited on a 300 μm thick high resistivity silicon wafer to provide a basic module for a position sensitive detector for such an application. The design calls for the silicon to be totally depleted so that rear illumination by light from a scintillation crystal is possible. Tests have been carried out to determine the performance of the detector in comparison with commercially produced discrete diodes. These tests were carried out using a hybrid preamplifier but a design based on a new RAL multichannel amplifier is considered.

Imaging telescopes for hard X-ray astronomy require either the use of a spinning telescope to facilitate the use of a rotating modulation collimator or a good 2D position-sensitive scintillation counter. The background in such a space-borne detector can be significantly reduced if an anti-Compton veto crystal can be combined with the primary detector using a phoswich technique. The design and performance of a position-sensitive phoswich detector based on the use of a position-sensitive photomultiplier will be described.

This paper explores the performance characteristcs of a compact neutron detector based on the use of a silicon photo-multiplier (SiPM). These devices offer the first true solid-state alternative to traditional photomultiplier tubes in that they provide similar gain and photon-detection efficiency but with the small size and ruggedness of PIN diodes. The performance of a design based on the use of a 23mm diameter LiI crystal, viewed by a 14×14mm square SiPM, has been modeled and tested experimentally using Cf252 fission-neutrons. The design incorporates a 10mm thick HDPE moderator in front of the 3mm crystal and an acrylic light-guide behind it. This provides the ability to detect a 104 n/s source at 25cm in 12s with a confidence level of 93.5%. The gamma-ray rejection capability of the detector is excellent, allowing reliable detection of neutrons in a Co60 gamma-ray background equivalent to a count-rate equivalent to 100kcps in a 2×2” NaI crystal. The impact of temperature changes on the performance of the detector, have also been explored along with methods to compensate for these changes.

The characteristics of a new type of radiation imaging system based on the use of a cylindrical, rotating, coded-aperture mask will be described. The system makes use of a number of combined mask-detection elements that are arranged in such a way as to provide a 360 degree field of view. The angular resolution and sensitivity of the system can be selected to suit the particular application. The sensitivity of the imager depends on the total volume of the detector used whilst the angular resolution is related to the diameter of the cylindrical mask.

Although large-volume plastic scintillation detectors have been widely used in Homeland Security applications for the detection of potential radiological and nuclear threats using cargo portals, they generally provide little or no spectroscopic information. Such information is key to the achievement of reduced nuisance-alarm rates. This paper outlines the improvements that have been achieved in the design and performance capability of large-volume PVT scintillation counters. In particular, they have an improved light-collection efficiency and uniformity of response. This improvement has been important in making it feasible to use Symetrica’s spectrum-processing algorithms in order to provide an accurate estimate of the gamma-ray spectrum that is incident on the detectors. Such spectra have then been used as the input to an isotope-identification algorithm. This paper provides an indication of how the certainty of the isotope identification depends both on the number of lines in the spectrum and the total number of counts recorded. In view of this progress, we believe that large PVT detectors will soon be able to provide a very useful degree of isotope specificity in addition to their high detection-sensitivity.

A design for a compact gamma camera based on the use of a position-sensitive photomultiplier is presented. Tests have been carried out on a prototype detector system, having a sensitive area of 25 cm 2 , using both a simple pinhole aperture and a parallel collimator. Images of a thyroid phantom are presented, and after processing to reduce the artefacts introduced by the use of a pinhole aperture, the quality is compared with that obtained using a standard Anger camera.

In this paper, we present the design and the results of a feasibility study of a novel, ultra-fast and high-resolution PET detector. It is based on the use of an LSO crystal array read-out by a Multi pixel Hybrid PhotoDiode (M-HPD) using an encoded fiber light-guide. The fiber encoding method enables one to readout more than 400 discrete crystal elements using a single M-HPD tube having 61 pixels. One of the key features of the detector is that the encoded fiber light-guide, used in conjunction with a digital readout system, eliminates the need for the use of ADCs in finding the address of the crystal in which interaction occurred. The readout time of a detector comprising around four hundred 2/spl times/2/spl times/10 mm discrete crystals, defined as the time between identifying a coincidence and providing the address of the crystal hit, can be reduced to less than 0.1 /spl mu/s. As a consequence, one could significantly improve the noise-effective-count-rate (NECR) performance of a PET system based on this detector design. Another advantage of this detector design is that the parallel readout scheme used, greatly simplifies the readout electronics by eliminating the use of ADC in the readout system. The feasibility of this detector design has been confirmed by measurements using a prototype detector module based on a 5/spl times/5 array of 2/spl times/2/spl times/10 mm LSO crystals. A signal level of around 200 photoelectrons has been measured for 511 keV energy deposited in the detector. An energy-resolution of /spl sim/30% and a timing resolution of less than 4 ns were achieved in this study.

Arrays of small scintillation crystals are being used increasingly for high-resolution imaging applications in nuclear medicine. Although the degree of pixellation now available is high for some scintillation materials, this spatial resolution is often achieved at the expense of degraded energy resolution due to the lower, and more variable, light-collection efficiency. The energy resolution of a detector is, however, especially important in nuclear medicine, where events that have been scattered in the body need to be rejected efficiently. The light output from a range of CsI(Tl) arrays was measured in terms of the number of photoelectrons; detected, using a hybrid photodiode (HPD). This data, used in conjunction with the measured energy resolution and an estimate of the intrinsic energy resolution of CsI(Tl), were used to assess the magnitudes of the various contributions to the overall energy resolution of these detectors. This information suggested that there is an opportunity to improve their energy resolution by carefully choosing the geometry and reflector material to minimize the variance in the light collection. If the nature of this variance is understood sufficiently well, there may be an opportunity to apply a postprocessing technique similar to that that has dramatically improved the performance of other standard scintillation detectors. This possibility depends on the use of either the uniform quantum efficiency of the multipixel HPD photocathodes or a monolithic array of PIN diodes. This would ensure that no additional or indeterminate variance in the light collection is introduced. Measurements made using fine BGO arrays for higher energy applications and columnar grown CsI(Tl) for X-ray imaging will also be presented.

High-resolution scintillation spectrometers based on the use of large-volume spherical CsI(Tl) spectrometers viewed by conventional 1 cm/sup 2/ PIN diodes, have been shown to have excellent performance characteristics. In particular, their unique geometry, the small area of contact between the diode and the crystal's surface and the high reflectivity of the packing material, combine to provide a detector in which there is a very small variance in the signal generated by energy deposits in different regions of the crystal. In view of the unique spectral-resolution achieved using the first prototype Scintispheres (S100-PIN and S300-PIN) to be manufactured, it was natural to explore the boundaries within which this technology might be useful. This paper presents the results of a series of modelling exercises and experimental investigations aimed at finding the range of detector volumes that can usefully be constructed based on the use of PIN photodiodes. For a given amplifier performance, the predicted spectral-resolution of a range of Scintisphere/sup /spl reg// volumes have been estimated as a function of energy. This study was made both for the CsI(Tl) material used in the original devices and for other materials which may be important when the speed of operation and stopping power are important design parameters. These studies also considered the performance limits that might be achievable in small volume Scintispheres. This paper also presents the results obtained when our deconvolution algorithm is applied to a wide range of standard scintillation spectrometers. These demonstrate the high spectral-resolution and sensitivity that can be achieved using this technique.

The basis for a design of a high-resolution PET imaging system, utilising a wavelength-shifting (WLS) fibre readout technique is presented here. Scintillation light is transported from the individual LSO pixels in the detector array through the WLS fibres to a multi-pixel hybrid photodiode (M-HPD). Each detector array consists of a number of 2/spl times/2/spl times/10 mm LSO crystals viewed by two orthogonal ribbons of WLS fibres. An array of as many as 30/spl times/31 crystals can thus be read-out by a single, small 61-pixel M-HPD tube. The design is both compact, inexpensive and suitable for application not only in the field of small-animal PET or in a dedicated PEM system, but could also operate in a combined PET/MRI system. Initial tests have shown that the signal level generated at the detector by a single 511 keV energy-deposit, is 20-25 photoelectrons. Separate tests have indicated that, at this signal-level, a resolving time of /spl sim/25 ns could be achievable.

Describes the design of a fast imaging system aimed at providing the accurate location of the centroid of a sentinel lymph node. Through the proposed use of a new 80 mm diameter multi-pixel hybrid photo-diode, equipped with a fibre-optic window, a CsI(Tl) scintillation crystal and a specially optimised collimator, the authors expect to achieve a precision of /spl plusmn/3 mm within 20 s for the location of a lymph node. It has been assumed that the affected gland has a 10 mm diameter and had accumulated 3 /spl mu/Ci of /sup 99/Tc through drainage of the region of the breast. The paper discusses the likely imaging quality of the larger tube based on measurements made with a smaller prototype detector. The design of two collimators is presented; one to provide a rapid location of the centroid of the SLN and the other to provide the surgeon with a measure of the depth of the potentially infected organ. A method for relating the image information to the patient's anatomy to guide the surgeon is also presented.

Recent developments in photomultiplier technology have enabled the construction of 5-in-diameter position-sensitive scintillation counters. A 5-in-diameter hard X-ray imager has been built and a position resolution of 4.0 mm full width half maximum (FWHM) has been obtained at 122 keV using a standard 3-mm-thick, 125-mm-diameter NaI(Tl) crystal with a 100-mm-diameter exit window. The spatial resolution can be improved by making some simple changes in the crystal design. The results show that the light output and spatial resolution vary considerably over the surface of such a detector. In order to make the best use of the imaging capability of these tubes, individual photon events must be corrected both in energy and position. The results of a 300-point detailed survey of the characteristics of the position-sensitive detector demonstrate its overall performance. A thyroid phantom image was obtained using this imager. >

A pinhole camera based on the use of a 3 inch square position-sensitive photomultiplier (PSPMT) to view a two-dimensional pixellated CsI(Tl) scintillation crystal has been designed to operate in the range 2 keV to 200 keV. It has also been used to generate extended test images by rotating two radioactive sources of different energies in the the field of view. The optical characteristics of the system have been simulated using a Monte-Carlo package in order to optimise the detector crystal geometry. The detector performance has also between investigated experimentally as a function of crystal dimensions, and measurements made using different readout techniques are presented. Also outlined is a design for an auroral imager based on the use of an array of such detector modules, for inclusion as part of the Auroral Imaging Observatory (AURIO), selected for inclusion within the payload complement for ENVISAT II. This will be located on a polar orbiting platform at an altitude of 800 km. >

Recent measurements of the performance of the newly available multi-pixel hybrid photo-detector (M-HPD) have demonstrated their particular value in the detection of very low light-level signals. The single and multiple photo-electron response characteristics of these devices is unmatched by any other room-temperature device. This characteristic, coupled with their speed of response and the availability of an internally-generated trigger signal when any one of the pixels detects an event, makes them well suited for the detection of minimum ionizing particles (MIPs). These detectors may therefore be expected to find application in particle-tracking applications both in High-Energy Physics and Gamma-ray Astronomy. The result of tests made using single and double-clad plastic fibres have confirmed the usefulness of these devices. The technique used to read-out 61 channels of data is described along with a way of viewing as many as 2000 fibres with just two 61-pixel M-HPDs.

Many different gamma-ray imaging systems have been proposed for, or used in the nuclear radiation environment for the localization of radioisotopes. Examples include the simple scanning collimator, pinhole cameras, radon transform imagers and coded aperture imagers. In this paper we present the results of a series of Monte Carlo simulations aimed at quantifying the relative merits of these quite different imaging techniques. In particular the paper compares image quality with respect to angular resolution and sensitivity for a range of test scenes which includes both point-like and extended/structured sources. Whilst one technique may be preferred for technical reasons such as size or mass constraints, the comparison presented here provides a valuable insight into which imaging system is optimum for certain observation scenarios.

A description of a prototype X-ray imaging system based upon a rotating one dimensional silicon microstrip detector is provided along with simulations of the detector's performance. Two-dimensional images have been reconstructed from a series of one-dimensional projections using a fast version of the Maximum Entropy algorithm. A one-dimensional silicon detector, having 256 strips with a pitch of 0.3 mm, is rotated in steps through 180 degrees in the image plane. The charge deposited in each strip for each angular position provides the series of projections from which the image may be reconstructed. Simulated images of a range of test scenes have been obtained at 256 by 256 resolution. The prototype detector described has an intended operating energy range of 5-30 keV.

Recent developments in the application of maximum likelihood expectation maximisation (MLEM) techniques to the deconvolution of low-resolution gamma-ray spectra have demonstrated a substantial improvement in both the energy-resolution and sensitivity achievable with the industry-standard 3" NaI scintillation counter. This technique can be used to determine the specific activities of the radioisotopes present in low-activity materials. In this paper, a practical application of this method for measuring the cement content of concrete in real-time is presented. However, the technique can be applied in many other fields.

This work presents preliminary measurements taken with the first prototype Hamamatsu (R6970) 8-inch Position Sensitive Photomultiplier Tube (PSPMT). These measurements are compared with similar ones obtained using a 5 inch PSPMT (Hamamatsu R3292). The new 8 inch PSPMT has 12 dynode stages, 11 with a proximity mesh structure whilst the last one is a back reflector. The entrance window is 7.5 mm thick and has an active area of 180 mm diameter. The crossed-wire anode of the 8 inch tube consists of 36/spl times/36 wires on a 4 mm pitch. These are paired together to give an 18/spl times/18 wire outputs. Both PSPMTs were coupled to a 110 mm diameter, 3 mm thick CsI(Tl) scintillating array in which each pixel has dimensions of 2/spl times/2 mm/sup 2/. Two read-out methods are compared in this paper. The first being the conventional resistive-divider technique. The second method uses a new multi-wire readout technique in which, the charge on each anode wire is individually read out and digitized. Measurements of the spatial resolution, position linearity, energy resolution and intrinsic charge distribution were carried out for both tubes using both read-out systems. Spatial resolution values of approximately 2 mm FWHM were obtained using the 8-inch PSPMT and the multiwire read-out technique. The other measured characteristics were similar to those obtained using the 5-inch PSPMT. These results obtained using the prototype 8-inch PSPMT underline the potential of this detector in the field of imaging in Nuclear Medicine.

A long standing problem in the identification of GRBs is the inability of current instruments to provide rapidly an accurate source location. An accuracy of a few arcminutes is required to allow follow-up observations at other wavelengths to be meaningful. An imaging system which employs one-dimensional coded masks in conjunction with silicon strip detectors can be used to locate bursts with an accuracy within a few arcminutes. The field of view of such an instrument could be more than 2 sr. This paper addresses the imaging principles and the design of a γ-ray burst telescope which uses this technology.

A new position-sensitive gamma-ray detector to cover the energy band from 15 keY to 1 MeV has been investigated. The detector concept is based on the use of an array of discrete 1 x 1 x 5 cm phoswich scintillation bars viewed by position-sensitive photomultiplier tube(PSPMT). The test results show that the energy resolution, about 40%FWHM at 60 keY and 12% FWHM at 511 keY, can be easily obtained when using CsI(Na) crystals. The point-spread function for the location of each event is smaller than the cross section of a single bar over the entire energy range. This means that there is virtually no ambiguity in locating signals from different bars. The outputs from the CsI(Na) and GSO veto crystals can be distinguished by a pulse-shape discriminator designed especially for thissystem. Those multi-site events which deposit energy only in the CsI(Na) array can be recognised using the positionsensing capability of the tube. 1. INTRODUCTION In order to image hard X-rays, some telescopes have incorporated multi-wire proportional counters as the position-sensitive detector1 . Whilst their energy and position-resolutions are superior to that of scintillation detectors, their