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© 2017 IEEE. Interest in using commercial electronic portal imaging devices (EPIDs) as dosimeters in radiotherapy has grown in recent years. However, their widespread clinical implementation for dosimetry has been limited due to their non water-equivalent dose response. We have developed a novel solution to this problem using an array of water-equivalent plastic scintillating fibers with the photodetector of a commercial EPID, and have previously demonstrated its suitability for dosimetry. The aim of this work was to quantify our prototype's imaging performance in terms of its modulation transfer function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE) relative to a standard EPID. Based on results from a previous Monte Carlo (MC) modelling study, we hypothesized that the prototype's DQE would exceed that of a standard EPID. The prototype array detector comprised 300×300 plastic scintillating fibers, each measuring 30\times0.5 \times0.5 mm 3 and composed of a polystyrene core, polymethyl methacrylate cladding and extramural absorber (EMA) to prevent optical cross-talk. A standard EPID was modified into a water-equivalent configuration by removing components above the photodetector and placing the prototype array directly on the imaging panel. The MTF and NPS were measured in both standard and water-equivalent configurations and the DQE was then calculated from these metrics. Measurements were also used to empirically validate optical transport parameters in our MC model. Results demonstrated that the water-equivalent EPID exhibited lower spatial resolution, but also less noise relative to the standard EPID, resulting in an overall D QE(0) of 3%, approximately double that of the standard EPID. Comparison against MC-calculated results suggests that the EMA is an imperfect absorber and core/cladding boundaries are not perfectly smooth. Simulations also demonstrated that significant gains in performance may be realized by further optimizing the p

Purpose A GEANT4 model of a novel, water-equivalent electronic portal imaging device (EPID) prototype for radiotherapy imaging and dosimetry utilising an array of plastic scintillating fibres (PSFs) has been developed. Monte Carlo (MC) simulations were performed to quantify the PSF-EPID imaging performance and to investigate design aspects affecting performance for optimisation. Methods Using the GEANT4 model, the PSF-EPID's imaging performance for 6 MV photon beams was quantified in terms of its modulation transfer function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE). Model parameters, including fibre dimensions, optical cladding reflectivity and scintillation yield, were varied to investigate impact on imaging performance. Results The MC-calculated DQE(0) for the reference PSF-EPID geometry employing 30 mm fibres was approximately nine times greater than values reported for commercial EPIDs. When using 10 mm long fibres, the PSF-EPID DQE(0) was still approximately three times greater than that of a commercial EPID. Increased fibre length, cladding reflectivity and scintillation yield produced the greatest decreases in NPS and increases in DQE. Conclusions The potential to develop an optimised next-generation water-equivalent EPID with MV imaging performance at least comparable to commercial EPIDs has been demonstrated. Factors most important for optimising prototype design include fibre length, cladding reflectivity and scintillation yield.

The aim of this study was to analyse the osseointegrative potential of phosphoserine-tethered dendrons when applied as surface functionalisation molecules on titanium implants in a sheep model after 2 and 8 weeks of implantation. Uncoated and dendron-coated implants were implanted in six sheep. Sandblasted and etched (SE) or porous additive manufactured (AM) implants with and without additional dendron functionalisation (SE-PSD; AM-PSD) were placed in the pelvic bone. Three implants per group were examined histologically and six implants were tested biomechanically. After 2 and 8 weeks the bone-to-implant contact (BIC) total values of SE implants (43.7±12.2; 53.3±9.0%) and SE-PSD (46.7±4.5; 61.7±4.9%) as well as AM implants (20.49±5.1; 43.9±9.7%) and AM-PSD implants (19.7±3.5; 48.3±15.6%) showed no statistically significant differences. For SE-PSD and AM-PSD a separate analysis of only the cancellous BIC demonstrated a statistically significant difference after 2 and 8 weeks. Biomechanical findings proved the overall increased stability of the porous implants after 8 weeks. Overall, the great effect of implant macro design on osseointegration was further supported by additional phosphoserine-tethered dendrons for SE and AM implants.

Single photon emission computed tomography (SPECT) is a tomographic imaging modality based on the radiotracer principle [1]. It is used to measure the 3D distribution of radiolabelled molecules in vivo using very sensitive radiation detectors and mathematical image reconstruction algorithms. Although SPECT has been used as a clinical tool for several decades, it is also well suited to imaging small animal models of human disease, such as laboratory mice and rats, for pre-clinical research. Because of the relatively long physical half-lives of single photon emitters (Table 4.1), SPECT is best suited to the study of macromolecules, such as antibodies and proteins, which have relatively slow rates of accrual at their target sites and slow plasma clearance. Additionally, proteins and antibodies are easily labelled with one of the radioisotopes of iodine (125I, 123I or 131I), or else by attaching a chelating agent incorporating one of the other common single photon emitters with suitable imaging properties, such as 99mTc or 111In. Conversely, the closely related radiotracer technique positron emission tomography (PET), which is discussed in the following chapter, is best suited to the study of small molecules such as synthetic drugs which have relatively fast kinetics in the body. Thus, the two techniques are highly complementary in the pre-clinical research environment.

Purpose: The conformity of the achieved dose distribution to the treatment plan strongly correlates with the accuracy of seed implantation in a prostate brachytherapy treatment procedure. Incorrect seed placement leads to both short and long term complications, including urethral and rectal toxicity. The authors present BrachyView, a novel concept of a fast intraoperative treatment planning system, to provide real-time seed placement information based on in-body gamma camera data. BrachyView combines the high spatial resolution of a pixellated silicon detector (Medipix2) with the volumetric information acquired by a transrectal ultrasound (TRUS). The two systems will be embedded in the same probe so as to provide anatomically correct seed positions for intraoperative planning and postimplant dosimetry. Dosimetric calculations are based on the TG-43 method using the real position of the seeds. The purpose of this paper is to demonstrate the feasibility of BrachyView using the Medipix2 pixel detector and a pinhole collimator to reconstruct the real-time 3D position of low dose-rate brachytherapy seeds in a phantom. Methods: BrachyView incorporates three Medipix2 detectors coupled to a multipinhole collimator. Three-dimensionally triangulated seed positions from multiple planar images are used to determine the seed placement in a PMMA prostate phantom in real time. MATLAB codes were used to test the reconstruction method and to optimize the device geometry. Results: The results presented in this paper show a 3D position reconstruction accuracy of the seed in the range of 0.5-3 mm for a 10-60 mm seed-to-detector distance interval (Z direction), respectively. The BrachyView system also demonstrates a spatial resolution of 0.25 mm in the XY plane for sources at 10 mm distance from Medipix2 detector plane, comparable to the theoretical value calculated for an equivalent gamma camera arrangement. The authors successfully demonstrated the capability of BrachyView for real-ti

Present Positron Emission Tomography (PET) detectors suffer from degradation of the spatial resolution due to the lack of depth-of-interaction (DOI) information leading to uncertainty in deducing the Lines of Response (LOR) between coincident events. The Centre for Medical Radiation Physics at the University of Wollongong has developed a novel detector module which will provide depth of interaction information while retaining the sensitivity of current scanners. This will result in superior imaging together with the ability to locate smaller lesions. This work focuses on preliminary investigations of the suitability of replacing the bulky scintillator crystals and photomultiplier tubes of traditional PET detector modules with compact 3 × 3 × 3 mm3 LYSO scintillator crystals individually coupled to Si photdetectors. The simulations were undertaken using GATE, a high level front end for GEANT4, specifically designed for use in the simulation of PET and SPECT. The simulation results quantify the level of improvement that can be potentially gained using a new detector module capable of providing a uniform spatial resolution across the entire field of view (FOV). Data is analysed using a newly developed sinogram binning technique. Simulation results show a resolution of 1.6 mm FWHM can be obtained for the entire FOV of this scanner (approximately 230 mm). This represents an improvement of approximately 75% in the resolution at the edges of field of view compared to traditional detector module design. Comparison of spatial resolution data for the novel detector module and phoswich detectors is also presented.

Attenuation Correction is important among other corrections for quantitative Positron Emission Tomography (PET). A common method is to acquire transmission data using an external source from which attenuation correction factors are derived. The aim of this work was to compare different transmission methodologies for the microPET Focus 220 animal scanner in terms of accuracy, signal-to-noise and scatter. This study included experiments in coincidence mode with and without rod windowing, singles mode with two different energy sources (68Ge and 57Co) and post-injection transmission scanning. In addition, the effectiveness of transmission segmentation was investigated. The propagation of transmission bias and noise into the emission images was also examined. Singles transmission scanning resulted in substantially improved signal-to-noise compared with coincidence measurements. The 57Co measurements provided attenuation coefficients close to the theoretical value for an energy window of 120-125 keV, while the 68Ge single measurements were degraded due to scattering from the object. Transmission scatter correction improved the accuracy for a 10 cm phantom but over-corrected for a mouse phantom. 57Co also resulted in low bias and noise in post-injection transmission scans for emission activities up to 20 MBq. Segmentation worked most reliably for transmission data acquired with 57Co but the minor improvement in accuracy of attenuation coefficients and signal-to-noise did not justify its use, particularly for small subjects. The accuracy and signal-to-noise of activity concentration measurements reflected the accuracy and signal-to-noise of transmission measurements. We conclude that 57Co singles transmission scanning is the most suitable method of attenuation correction on the microPET Focus 220 animal scanner.

This article focuses on the characterisation of three versions of a custom designed silicon photodetector using nuclear spectroscopy techniques. Room temperature gamma ray spectroscopy experiments have been performed using an LYSO excited by /sup 137/Cs and /sup 22/Na sources and read out by the new photodiodes. We have measured an energy resolution of 13.1% FWHM for the 511 keV gamma rays from a /sup 22/Na source and 11.2% FWHM for the 662 keV gamma rays from a /sup 137/Cs source. This is one of the best ever-reported energy resolutions for a lutetium based scintillator crystal read out by a silicon photodetector.

ABSTRACT It is widely thought that the biological outcomes of Raf-1 activation are solely attributable to the activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. However, an increasing number of reports suggest that some Raf-1 functions are independent of this pathway. In this report we show that mutation of the amino-terminal 14-3-3 binding site of Raf-1 uncouples its ability to activate the MEK/ERK pathway from the induction of cell transformation and differentiation. In NIH 3T3 fibroblasts and COS-1 cells, mutation of serine 259 resulted in Raf-1 proteins which activated the MEK/ERK pathway as efficiently as v-Raf. However, in contrast to v-Raf, RafS259 mutants failed to transform. They induced morphological alterations and slightly accelerated proliferation in NIH 3T3 fibroblasts but were not tumorigenic in mice and behaved like wild-type Raf-1 in transformation assays measuring loss of contact inhibition or anchorage-independent growth. Curiously, the RafS259 mutants inhibited focus induction by an activated MEK allele, suggesting that they can hyperactivate negative-feedback pathways. In primary cultures of postmitotic chicken neuroretina cells, RafS259A was able to sustain proliferation to a level comparable to that sustained by the membrane-targeted transforming Raf-1 protein, RafCAAX. In contrast, RafS259A was only a poor inducer of neurite formation in PC12 cells in comparison to RafCAAX. Thus, RafS259 mutants genetically separate MEK/ERK activation from the ability of Raf-1 to induce transformation and differentiation. The results further suggest that RafS259 mutants inhibit signaling pathways required to promote these biological processes.

We have designed and constructed a small animal SPECT system based on compact, high resolution detectors and multipinhole apertures. The scanner is currently configured with two detectors mounted on a rotating gantry. Each detector comprises a NaI(Tl) crystal array (1/spl times/1/spl times/5 mm elements), a 12 cm diameter position-sensitive photomultiplier tube (Hamamatsu R3292) and a tungsten aperture with 1 or more pinholes. In this study, we performed phantom experiments to characterise the planar and tomographic performance of the scanner. Intrinsic resolution measured with a highly collimated /sup 99m/Tc point source stepped across the detector face was 1.0 /spl plusmn/ 0;.1 FWHM and 2.9 /spl plusmn/ 0.1 mm FWTM. Energy resolution at 140 keV varied from 14% FWIIM for central crystals to 19% for edge crystals and was 20% FWHM for the whole detector normalised spectrum. Intrinsic uniformity for the central field of view was 2.4% differential and 3.8% integral. Reconstructed spatial resolution was 1.2 mm FWHM at the centre of the field of view and 1.2, 1.7 mm FWHM (radial, tangential) at 10 mm off-axis, using typical geometric parameters for mouse and rat brain imaging. Reconstructed images of a micro deluxe hot rod phantom demonstrate the high resolution of the system and indicate similar resolution and improved signal-to-noise is obtained with a 2 pinhole aperture compared with a single pinhole. We conclude that the performance characteristics of this system make it suitable for high resolution imaging of small laboratory animals.

In a previous simulation study, we demonstrated the feasibility of using coded apertures together with pixelated detectors tors for small animal SPECT. In this paper; we further explore the potential of this approach with a prototype detector and simulated multipinhole apertures. We also investigated the effect of multiplexing due to overlapped projections on convergence properties, image signal-to-noise ratio (SNR) and spatial resolution. The detector comprises a 48/spl times/44 array of NaI(Tl) crystals, each 1 mm/spl times/1 mm/spl times/5 mm on a 1.25-mm pitch. The crystal array is directly coupled to a Hamamatsu R3941 8 cm position sensitive photomultiplier tube. Multipinhole apertures were simulated by performing repeated SPECT acquisitions of the same object with a single tungsten pinhole translated to different positions in the aperture plane. Image reconstruction is based on a three-dimensional ray driven projector which is an extension of a method described for single pinhole SPECT with a displaced center of rotation. Image estimates are updated using the maximum likelihood expectation maximization (ML-EM) algorithm. The effect of multiplexing was to slow convergence and reduce the achievable SNR by approximately 15% compared with nonmultiplexed data (but the result may be achieved in a fraction of the time). The reconstructed resolution obtained with a resolution phantom was 1.5-mm full width at half maximum and there was no appreciable difference between the resolution of multiplexed and nonmultiplexed data. These results encourage us to develop a prototype coded aperture system for high sensitivity, high resolution small animal SPECT.

We have previously demonstrated the potential of multi-pinhole coded apertures when used in conjunction with compact pixelated detectors for high resolution, high sensitivity small animal SPECT. We are now constructing a prototype SPECT system with three such detectors mounted on a rotating gantry. Each detector comprises a 12 cm diameter circular array of NaI(Tl) crystals, each 1/spl times/1/spl times/5 mm/sup 3/ on a 1.25 mm pitch. Each crystal array is coupled to a Hamamatsu R3292 12.7 cm diameter PS-PMT. Signals from the three detectors are read out by a custom subtractive resistive circuit and multiplexed. Data are acquired by a National Instruments PCI-6110E board running on a Macintosh dual processor G4 computer under Kmax software control. Images are reconstructed using a 3D iterative MAP-EM algorithm based on a multi-pinhole forward and back projector. The trade-off between contrast and variance was studied by simulation for a number of multi-pinhole configurations. We also performed initial planar imaging studies on one of the detectors. Our results indicate that spatial resolution approaching 1 mm full width at half maximum (FWHM) can be achieved with a single pinhole aperture, while improved contrast and variance may result from using optimized multi-pinhole apertures.

In this paper, we report on spectral response data and gamma ray spectroscopy measurements using two newly developed silicon photodetectors that are designed to have enhanced sensitivity in the blue spectral region. The enhanced sensitivity is a result of our newly developed ion implantation profile used to create the active area of the photodetector. The quantum efficiency of the new photodetectors (without any optimized antireflective coating) has been measured to be ~40% at a wavelength of 420 nm. Gamma ray spectroscopy experiments have been performed using a thallium doped cesium iodide, [CsI(Tl)], and a cerium doped lutetium oxy-orthosilicate, (LSO) crystal excited by a 137 Cs or 22Na source and read out by the new photodetectors. We have measured an energy resolution of 7.7% and 22.7% full-width at half-maximum (FWHM) for the 662-keV gamma rays from a 137Cs for the CsI(Tl) and LSO scintillator crystal respectively. We intend to use the photodetectors, in the form of a detector array optically coupled to CsI(Tl) or LSO, in the development of a new scintillator detector module for use in positron emission tomography (PET).

Presents results of simulations performed as part of the development of a gamma-ray detector module comprising a non-pixellated scintillator and pixellated photodiode detector. The simulations have been carried out to determine the effect of surface treatment and dimensions of the scintillator on the ability to determine to 2-D position of interaction. A set of 32 different combinations of surface treatments have been considered for each crystal size. Scintillator dimensions considered have been 25 mm×25 mm×(3-6 mm). For scintillator thicknesses at the low end of this range, an average accuracy of 0.5 to 0.6 mm is achievable for many different surface treatments. At the higher end of the thickness range, 6 mm, the average accuracy reduces to around 0.8 mm, and is more dependent on the surface treatment.

In this work we report on spectral response data and gamma ray spectroscopy measurements using two newly developed silicon photodetectors that are designed to have enhanced sensitivity in the blue spectral region. The enhanced sensitivity is a result of our newly developed ion implantation profile used to create the active area of the photodetector. The quantum efficiency of the new photodetectors (without any optimised antireflective coating) has been measured to be ~40% at a wavelength of 420 nm. Gamma ray spectroscopy experiments have been performed using a CsI(Tl) and a LSO crystal excited by a 137Cs or 22Na source and read out by the new photodetectors. We have measured an energy resolution of 7.7% and 22.7% FWHM for the 662 keV gamma rays from a 137Cs for the CsI(Tl) and LSO scintillator crystal respectively. We intend to use the photodetectors, in the form of a detector array optically coupled to CsI(Tl) or LSO, in the development of a new scintillator detector module for use in positron emission tomography.