Improved EMCCD gamma camera performance by SiPM pre-localization.

High spatial resolution γ-imaging can be achieved with scintillator readout by low-noise, fast, electron-multiplying charge-coupled devices (EMCCDs). Previously we have shown that false-positive events due to EMCCD noise can be rejected by using the sum signal from silicon photomultipliers (SiPMs) mounted on the sides of the scintillator. Here we launch a next generation hybrid CCD-SiPM camera that utilizes the individual SiPM signals and maximum likelihood estimation (MLE) pre-localization of events to discriminate between true and false events in CCD frames. In addition, SiPM signals are utilized for improved energy discrimination. The performance of this hybrid detector was tested for a continuous CsI:Tl crystal at 140 keV. With a pre-localization accuracy of 1.06 mm (full-width-at-half-maximum) attained with MLE the signal-to-background ratio (SBR) was improved by a factor of 5.9, 4.0 or 2.2 compared to the EMCCD-only readout, at the cost of rejecting, respectively, 47%, 9% or 4% of the events. Combining the pre-localization and SiPM energy estimation improved the energy resolution from 50% to (19 ± 3)% while maintaining the spatial resolution at 180 µm.

An efficient simulator for pinhole imaging of PET isotopes.

Today, small-animal multi-pinhole single photon emission computed tomography (SPECT) can reach sub-half-millimeter image resolution. Recently we have shown that dedicated multi-pinhole collimators can also image PET tracers at sub-mm level. Simulations play a vital role in the design and optimization of such collimators. Here we propose and validate an efficient simulator that models the whole imaging chain from emitted positron to detector signal. This analytical simulator for pinhole positron emission computed tomography (ASPECT) combines analytical models for pinhole and detector response with Monte Carlo (MC)-generated kernels for positron range. Accuracy of ASPECT was validated by means of a MC simulator (MCS) that uses a kernel-based step for detector response with an angle-dependent detector kernel based on experiments. Digital phantom simulations with ASPECT and MCS converge to almost identical images. However, ASPECT converges to an equal image noise level three to four orders of magnitude faster than MCS. We conclude that ASPECT could serve as a practical tool in collimator design and iterative image reconstruction for novel multi-pinhole PET.

An enhanced high-resolution EMCCD-based gamma camera using SiPM side detection.

Electron-multiplying charge-coupled devices (EMCCDs) coupled to scintillation crystals can be used for high-resolution imaging of gamma rays in scintillation counting mode. However, the detection of false events as a result of EMCCD noise deteriorates the spatial and energy resolution of these gamma cameras and creates a detrimental background in the reconstructed image. In order to improve the performance of an EMCCD-based gamma camera with a monolithic scintillation crystal, arrays of silicon photon-multipliers (SiPMs) can be mounted on the sides of the crystal to detect escaping scintillation photons, which are otherwise neglected. This will provide a priori knowledge about the correct number and energies of gamma interactions that are to be detected in each CCD frame. This information can be used as an additional detection criterion, e.g. for the rejection of otherwise falsely detected events. The method was tested using a gamma camera based on a back-illuminated EMCCD, coupled to a 3 mm thick continuous CsI:Tl crystal. Twelve SiPMs have been mounted on the sides of the CsI:Tl crystal. When the information of the SiPMs is used to select scintillation events in the EMCCD image, the background level for (99m)Tc is reduced by a factor of 2. Furthermore, the SiPMs enable detection of (125)I scintillations. A hybrid SiPM-/EMCCD-based gamma camera thus offers great potential for applications such as in vivo imaging of gamma emitters.

Tumour tracking with scanned proton beams: assessing the accuracy and practicalities.

The potential of tumour tracking for active spot-scanned proton therapy was assessed. Using a 4D-dose calculation and simulated target motion, a tumour tracking algorithm has been implemented and applied to a simple target volume in both homogenous and heterogeneous in silico phantoms. For tracking and retracking (a hybrid solution combining tumour tracking and rescanning), three tracking modes were analysed: 'no tracking' (uncorrected irradiation of a moving target), 'perfect tracking' (no time delays and exact knowledge of target position) and 'imperfect tracking' (simulated time delays or position prediction errors). For all plans, dose homogeneity in the target volume was assessed as the difference between D5 and D95 in the CTV. For the homogeneous phantom, perfect tracking could retrieve nominal dose homogeneity for all motion phases and amplitudes while severe deterioration of treatment outcomes was found for imperfect tracking. The use of retracking reduced the sensitivity to position errors significantly in the homogeneous phantom. In the heterogeneous phantoms (simulated rib proximal to target), the nominal dose homogeneity could not be obtained with perfect tracking. Adjustments in pencil beam positions could cause pencil beams to deform under the influence of the bone, resulting in loss of dose homogeneity. As retracking was not capable of reducing these effects, rescanning provided the best treatment outcomes for moving heterogeneous targets in this study.

2D dosimetry in a proton beam with a scintillating GEM detector.

A two-dimensional position-sensitive dosimetry system based on a scintillating gas detector is being developed for pre-treatment verification of dose distributions in particle therapy. The dosimetry system consists of a chamber filled with an Ar/CF(4) scintillating gas mixture, inside which two gas electron multiplier (GEM) structures are mounted (Seravalli et al 2008b Med. Phys. Biol. 53 4651-65). Photons emitted by the excited Ar/CF(4) gas molecules during the gas multiplication in the GEM holes are detected by a mirror-lens-CCD camera system. The intensity distribution of the measured light spot is proportional to the 2D dose distribution. In this work, we report on the characterization of the scintillating GEM detector in terms of those properties that are of particular importance in relative dose measurements, e.g. response reproducibility, dose dependence, dose rate dependence, spatial and time response, field size dependence, response uniformity. The experiments were performed in a 150 MeV proton beam. We found that the detector response is very stable for measurements performed in succession (sigma = 0.6%) and its response reproducibility over 2 days is about 5%. The detector response was found to be linear with the dose in the range 0.05-19 Gy. No dose rate effects were observed between 1 and 16 Gy min(-1) at the shallow depth of a water phantom and 2 and 38 Gy min(-1) at the Bragg peak depth. No field size effects were observed in the range 120-3850 mm(2). A signal rise and fall time of 2 micros was recorded and a spatial response of

Characterization of a scintillating GEM detector with low energy x-rays.

A two-dimensional position-sensitive dosimetry system based on a scintillating gas detector is being developed with the aim of using it for pre-treatment verification of dose distributions in charged particle therapy. The dosimetry system consists of a chamber filled with an Ar/CF(4) scintillating gas mixture, inside which two cascaded gas electron multipliers (GEMs) are mounted. A GEM is a thin kapton foil with copper cladding structured with a regular pattern of sub-mm holes. In such a system, light quanta are emitted by the scintillating gas mixture during the electron avalanches in the GEM holes when radiation traverses the detector. The light intensity distribution is proportional to the energy deposited in the detector's sensitive volume by the beam. In the present work, we investigated the optimization of the scintillating GEM detector light yield. The light quanta are detected by means of a CCD camera or a photomultiplier tube coupled to a monochromator. The GEM charge signal is measured simultaneously. We have found that with 60 microm diameter double conical GEM holes, a brighter light signal and a higher electric signal are obtained than with 80 microm diameter holes. With an Ar + 8% CF(4) volume concentration, the highest voltage across the GEMs and the largest light and electric signals were reached. Moreover, we have found that the emission spectrum of Ar/CF(4) is independent of (1) the voltages applied across the GEMs, (2) the x-ray beam intensity and (3) the GEM hole diameter. On the other hand, the ratio of Ar to CF(4) peaks in the spectrum changes when the concentration of the latter gas is varied.

A scintillating gas detector for 2D dose measurements in clinical carbon beams.

A two-dimensional position sensitive dosimetry system based on a scintillating gas detector has been developed for pre-treatment verification of dose distributions in hadron therapy. The dosimetry system consists of a chamber filled with an Ar/CF4 scintillating gas mixture, inside which two cascaded gas electron multipliers (GEMs) are mounted. A GEM is a thin kapton foil with copper cladding structured with a regular pattern of sub-mm holes. The primary electrons, created in the detector's sensitive volume by the incoming beam, drift in an electric field towards the GEMs and undergo gas multiplication in the GEM holes. During this process, photons are emitted by the excited Ar/CF4 gas molecules and detected by a mirror-lens-CCD camera system. Since the amount of emitted light is proportional to the dose deposited in the sensitive volume of the detector by the incoming beam, the intensity distribution of the measured light spot is proportional to the 2D hadron dose distribution. For a measurement of a 3D dose distribution, the scintillating gas detector is mounted at the beam exit side of a water-bellows phantom, whose thickness can be varied in steps. In this work, the energy dependence of the output signal of the scintillating gas detector has been verified in a 250 MeV/u clinical 12C ion beam by means of a depth-dose curve measurement. The underestimation of the measured signal at the Bragg peak depth is only 9% with respect to an air-filled ionization chamber. This is much smaller than the underestimation found for a scintillating Gd2O2S:Tb ('Lanex') screen under the same measurement conditions (43%). Consequently, the scintillating gas detector is a promising device for verifying dose distributions in high LET beams, for example to check hadron therapy treatment plans which comprise beams with different energies.

Dissociated vertical nystagmus and internuclear ophthalmoplegia from a midbrain infarction.

We describe a patient with a dissociated vertical nystagmus and an internuclear ophthalmoplegia. The vertical nystagmus consisted of a left downward nystagmus with a synchronous right intorting nystagmus when the patient looked down and to the left. This rare type of nystagmus has been described both in isolation and in association with an internuclear ophthalmoplegia. Previous authors postulated a lesion in the midbrain in the region of the medial longitudinal fasciculus. In our patient, a discrete midbrain infarction was demonstrated on magnetic resonance imaging in the hypothesized location, thus providing supportive anatomical evidence for a vertical gaze coordination pathway in the region of the medial longitudinal fasciculus.

Kinetic studies of xenon trioxide as an oxidant-I Determination of alcohols.

A kinetic study of the oxidation of some alcohols by xenon trioxide has revealed the optimum conditions for analysis of these alcohols. The rate of reaction may be increased by adding a catalyst or by increasing the pH of the solution; it may be decreased by adding an inhibitor. The initiation time of the reaction is used to determine t-butanol in amounts as low as 22 mug or 880 parts per milliard (ppM). Primary and secondary alcohols which catalyse the reaction between t-butanol and xenon trioxide may be determined in amounts as low as 2.3 mug or 92 ppM. Tertiary butanol in amounts less than 40mug is determined with a coefficient of variation of 4% while methanol, ethanol and isopropanol are determined with a coefficient of variation of 10% at the level of 25mug or more. The precision in determination of t-butanol increases with increasing concentration, while for isopropanol, ethanol and methanol it decreases.