Theoretical investigation of the signal performance of HgI2x-ray converters incorporating a Frisch grid structure at mammographic energies.

Active matrix, flat-panel imagers (AMFPIs) suffer from decreased detective quantum efficiency under conditions of low dose per image frame (such as for digital breast tomosynthesis, fluoroscopy and cone-beam CT) due to low signal compared to the additive electronic noise. One way to address this challenge is to introduce a high-gain x-ray converter called particle-in-binder mercuric iodide (PIB HgI2) which exhibits 3-10 times higher x-ray sensitivity compared to that of a-Se and CsI:Tl converters employed in commercial AMFPI systems. However, a remaining challenge for practical implementation of PIB HgI2is the high level of image lag, which is believed to largely originate from the trapping of holes. Towards addressing this challenge, this paper reports a theoretical investigation of the use of a Frisch grid structure embedded in the converter to suppress hole signal-which would be expected to reduce image lag. The grid acts as a third electrode sandwiched between a continuous top electrode and pixelated bottom electrodes having a 100µm pitch. Signal properties of such a detector are investigated as a function of VDR (the ratio of the voltage difference between the electrodes in the region below the grid to that above the grid), grid pitch (the center-to-center distance between two neighboring grid wires) andRGRID(the ratio of grid wire width to grid pitch) for mammographic x-ray energies. The results show that smaller grid pitch suppresses hole signal to a higher degree (up to ∼96%) while a larger gap between grid wires and higher VDR provide minimally impeded electron transport. Examination of the tradeoff between maximizing electron signal and minimizing hole signal indicates that a grid design having a grid pitch of 20µm withRGRIDof 50% and 65% provides hole signal suppression of ∼93% and ∼95% for VDR of 1 and 3, respectively.

Empirical noise performance of prototype active pixel arrays employing polycrystalline silicon thin-film transistors.

PURPOSE: In the spirit of overcoming the signal-to-noise limitations of active matrix, flat-panel imagers (AMFPIs) which employ array circuits based on a-Si:H thin-film transistors (TFTs), an empirical investigation of the noise properties of prototype active pixel arrays based on polycrystalline silicon (poly-Si) TFTs is reported. Like a-Si:H, poly-Si supports fabrication of large area, monolithic x-ray imaging arrays and offers good radiation damage resistance, while providing electron and hole mobility orders of magnitude higher. Compared to pixel circuits typically consisting of a single addressing switch in an AMFPI array, the pixel circuit of an active pixel array includes an amplifier that magnifies the imaging signal prior to readout by external acquisition electronics. Also, while readout erases signal stored in the pixels for AMFPI arrays, active pixel arrays allow multiple nondestructive readout, which can be used to reduce noise. The prototype arrays investigated in this paper were developed to explore the effect of variation in amplifier design on noise. METHODS: A pair of prototype arrays incorporating single-stage and two-stage poly-Si pixel amplifiers were examined. The arrays incorporate various amplifier designs in which dimensions of some of the three (or four) poly-Si TFTs per pixel circuit for the single-stage array, and some of the five poly-Si TFTs for the two-stage array, were varied. The arrays were operated using a recently developed electronic data acquisition system that allows variation of operational conditions such as voltages and timing of control signals. The arrays were operated in the absence of radiation in various correlated multiple sampling modes, with and without the injection of charge directly into the pixel circuits for measurements of in-pixel gain and pixel noise. Pixel noise, referred back to the input of the pixel amplifier, was compared to predictions generated by a sophisticated circuit simulation model. RESULTS: Across the various pixel circuit designs, the median in-pixel gain for the single-stage and two-stage arrays was measured to be ×9.3 and ×25, respectively. These gain levels were sufficient to reduce the contribution of external noise, defined as the electronic additive noise in the absence of noise contributions from circuitry in the pixel and referred back to the input of the pixel amplifier, to less than 340 e. As a result, median pixel noise results as low as ~695 e and 866 e, acquired using eight samples, were observed from the best-performing single-stage and two-stage designs, respectively. While the magnitude of pixel noise predicted by simulation was lower than the measured results, there was generally good agreement between simulation and measurement for the functional dependence of noise on operating voltages, timing, and sampling mode. CONCLUSIONS: The single-stage and two-stage arrays examined in this study demonstrated pixel noise well below that typically demonstrated by AMFPIs. Through proper design, it should be possible to maintain the noise levels observed in this study irrespective of the size and pitch of an active pixel array. Further reduction in pixel noise may be possible through more optimized pixel circuit design, faster readout, or improvements in fabrication.

Count rate capabilities of polycrystalline silicon photon counting detectors for CBCT applications-a theoretical study.

The signal-to-noise properties of active matrix, flat-panel imagers (AMFPIs) limit the imaging performance of this x-ray imaging technology under conditions of low dose per image frame. This limitation can affect cone-beam computed tomography (CBCT) procedures where an AMFPI is used to acquire hundreds of image frames to form a single volumetric data set. An approach for overcoming this limitation is to replace the energy-integrating pixel circuits of AMFPI arrays with photon counting pixel circuits which examine the energy of each x-ray interaction and count those events whose signals exceed user-defined energy thresholds. A promising material for fabricating the circuits of such photon-counting detectors (PCDs) is polycrystalline silicon (poly-Si)-a semiconductor that facilitates economic manufacture of large area, monolithic arrays of the size presently provided by AMFPIs as well as provides good radiation damage resistance. In this paper, results are reported from a theoretical investigation of the potential for poly-Si PCDs to satisfy the count rate needs, while maintaining good energy resolution, of two CBCT applications-CBCT used for breast imaging and kilo-voltage CBCT used for providing localization information in image guided radiotherapy (referred to as BCT and kV-CBCT, respectively). The study focused on the performance of the critical first component of a PCD pixel circuit, the amplifier, under conditions relevant to the two applications. The study determined that, compared to the average input fluxes associated with BCT and kV-CBCT, a promising amplifier design employing poly-Si thin-film transistors can provide count rates two and four times in excess of those levels, respectively, assuming a dead time loss of 10%. In addition, calculational estimates based on foreseeable poly-Si circuit densities suggest that it should be possible to include sufficient circuitry to support 2 and 3 energy thresholds per pixel, respectively. Finally, prospects for further improvements are discussed.

Theoretical investigation of the count rate capabilities of in-pixel amplifiers for photon counting arrays based on polycrystalline silicon TFTs.

PURPOSE: Photon counting arrays (PCAs), capable of measuring the spectral information of individual x-ray photons and recording that information digitally, provide a number of advantages compared to conventional, energy-integrating active matrix flat-panel imagers - such as reducing the undesirable effects of electronic readout noise and Swank noise. While contemporary PCAs are based on crystalline silicon, our group has been examining the use of polycrystalline silicon (poly-Si, a semiconductor material better-suited for the manufacture of large-area devices) for such arrays. In this study, a theoretical investigation of the front-end amplifiers of array pixels incorporating photon counting circuits is described - building upon circuit simulation techniques developed in a previous study. Results for amplifier circuit designs corresponding to prototype PCAs currently under development, as well as for hypothetical circuit designs identified in the study, are reported. In the simulations, performance metrics (such as signal gain, linearity of signal response, and energy resolution) as well as various measures of count rate are determined. METHODS: The simulations employed various input energy distributions (i.e., a 72 kVp spectrum as well as monoenergetic x rays) in order to determine circuit performance. To make the results representative of the properties of poly-Si, the simulations incorporated transistor characteristics that were empirically obtained from test devices. Optimal operating conditions for the circuits were determined by applying criteria to the performance metrics and identifying which conditions minimized settling time. Once the optimal operating conditions were identified, trains of input pulses simulating x-ray flux were used to determine two measures of count rate corresponding to dead time losses of 10% and 30% (referred to as CR10 and CR30 , respectively). RESULTS: The best-performing prototype amplifier design (implemented at a pixel pitch of 1 mm) exhibited CR10 and CR30 values (expressed in counts per second per pixel) of 8.4 and 21.6 kcps/pixel, respectively. A hypothetical amplifier design was derived by modifying transistor, resistor, and capacitor elements of the prototype amplifier designs. This hypothetical design (implemented at a pitch of 1 mm) exhibited CR10 and CR30 values of 154 and 381 kcps/pixel, respectively. When implemented at a pitch of 0.25 mm, the performance of that design increased to 210 and 491 kcps/pixel, respectively (corresponding to counts per second per unit area of 3.4 and 7.9 Mcps/mm2 ). CONCLUSIONS: The simulation methodology described in this paper represents a useful tool for identifying promising designs for the amplifier component of photon counting arrays, as well as evaluating the analog signal and noise performance of those designs. The results obtained from the current study support the hypothesis that large-area, photon counting arrays based on poly-Si transistors can provide clinically useful count rates. Encouraged by these early results, further development of the methodology to assist in the identification and evaluation of even more promising designs, along with development and empirical characterization of prototype designs, is planned.

Theoretical investigation of the noise performance of active pixel imaging arrays based on polycrystalline silicon thin film transistors.

PURPOSE: Active matrix flat-panel imagers, which typically incorporate a pixelated array with one a-Si:H thin-film transistor (TFT) per pixel, have become ubiquitous by virtue of many advantages, including large monolithic construction, radiation tolerance, and high DQE. However, at low exposures such as those encountered in fluoroscopy, digital breast tomosynthesis and breast computed tomography, DQE is degraded due to the modest average signal generated per interacting x-ray relative to electronic additive noise levels of ~1000 e, or greater. A promising strategy for overcoming this limitation is to introduce an amplifier into each pixel, referred to as the active pixel (AP) concept. Such circuits provide in-pixel amplification prior to readout as well as facilitate correlated multiple sampling, enhancing signal-to-noise and restoring DQE at low exposures. In this study, a methodology for theoretically investigating the signal and noise performance of imaging array designs is introduced and applied to the case of AP circuits based on low-temperature polycrystalline silicon (poly-Si), a semiconductor suited to manufacture of large area, radiation tolerant arrays. METHODS: Computer simulations employing an analog circuit simulator and performed in the temporal domain were used to investigate signal characteristics and major sources of electronic additive noise for various pixel amplifier designs. The noise sources include photodiode shot noise and resistor thermal noise, as well as TFT thermal and flicker noise. TFT signal behavior and flicker noise were parameterized from fits to measurements performed on individual poly-Si test TFTs. The performance of three single-stage and three two-stage pixel amplifier designs were investigated under conditions relevant to fluoroscopy. The study assumes a 20 × 20 cm2 , 150 µm pitch array operated at 30 fps and coupled to a CsI:Tl x-ray converter. Noise simulations were performed as a function of operating conditions, including sampling mode, of the designs. The total electronic additive noise included noise contributions from each circuit component. RESULTS: The total noise results were found to exhibit a strong dependence on circuit design and operating conditions, with TFT flicker noise generally found to be the dominant noise contributor. For the single-stage designs, significantly increasing the size of the source-follower TFT substantially reduced flicker noise - with the lowest total noise found to be ~574 e [rms]. For the two-stage designs, in addition to tuning TFT sizes and introducing a low-pass filter, replacing a p-type TFT with a resistor (under the assumption in the study that resistors make no flicker noise contribution) resulted in significant noise reduction - with the lowest total noise found to be ~336 e [rms]. CONCLUSIONS: A methodology based on circuit simulations which facilitates comprehensive explorations of signal and noise characteristics has been developed and applied to the case of poly-Si AP arrays. The encouraging results suggest that the electronic additive noise of such devices can be substantially reduced through judicious circuit design, signal amplification, and multiple sampling. This methodology could be extended to explore the noise performance of arrays employing other pixel circuitry such as that for photon counting as well as other semiconductor materials such as a-Si:H and a-IGZO.

Performance of in-pixel circuits for photon counting arrays (PCAs) based on polycrystalline silicon TFTs.

Photon counting arrays (PCAs), defined as pixelated imagers which measure the absorbed energy of x-ray photons individually and record this information digitally, are of increasing clinical interest. A number of PCA prototypes with a 1 mm pixel-to-pixel pitch have recently been fabricated with polycrystalline silicon (poly-Si)-a thin-film technology capable of creating monolithic imagers of a size commensurate with human anatomy. In this study, analog and digital simulation frameworks were developed to provide insight into the influence of individual poly-Si transistors on pixel circuit performance-information that is not readily available through empirical means. The simulation frameworks were used to characterize the circuit designs employed in the prototypes. The analog framework, which determines the noise produced by individual transistors, was used to estimate energy resolution, as well as to identify which transistors contribute the most noise. The digital framework, which analyzes how well circuits function in the presence of significant variations in transistor properties, was used to estimate how fast a circuit can produce an output (referred to as output count rate). In addition, an algorithm was developed and used to estimate the minimum pixel pitch that could be achieved for the pixel circuits of the current prototypes. The simulation frameworks predict that the analog component of the PCA prototypes could have energy resolution as low as 8.9% full width at half maximum (FWHM) at 70 keV; and the digital components should work well even in the presence of significant thin-film transistor (TFT) variations, with the fastest component having output count rates as high as 3 MHz. Finally, based on conceivable improvements in the underlying fabrication process, the algorithm predicts that the 1 mm pitch of the current PCA prototypes could be reduced significantly, potentially to between ~240 and 290 µm.

Expression of recombinant MDA-BF-1 with a kinase recognition site and a 7-histidine tag for receptor binding and purification.

Prostate cancer metastasizes predominantly to bone, where it induces osteoblastic lesions. Paracrine factors secreted by the metastatic cancer cells are thought to mediate these events. We previously isolated a novel bone metastasis-related factor (MDA-BF-1) from bone marrow aspirate samples from patients with prostate cancer and bone metastasis, and found that this factor stimulated osteoblast differentiation, possibly by interacting with a receptor on the osteoblasts. Identifying this putative MDA-BF-1 receptor biochemically requires the expression of MDA-BF-1 for receptor binding assays and for the preparation of a ligand-affinity column. We tagged MDA-BF-1 with a peptide containing a protein kinase A phosphorylation site plus a 7-histidine sequence to facilitate the labeling of MDA-BF-1 for receptor binding assay and the binding of MDA-BF-1 to an immobilized metal affinity column. The recombinant MDA-BF-1 protein (MDA-BF1-kinase-his) was expressed in Sf9 cells using a baculovirus expression system. About 0.8 mg of purified MDA-BF1-kinase-his protein was obtained from 4 x 10(8) Sf9 cells. MDA-BF1-kinase-his can be phosphorylated by PKA with a specific activity around 10(5)cpm/mug protein. Receptor binding assays using this (32)P-labeled MDA-BF-1 showed that MDA-BF-1 bound to membranes prepared from Saos-2, an osteosarcoma cell line, and C2C12, a mouse pluripotent mesenchymal precursor cell line that can be induced to become osteoblast by BMP-2. In contrast, MDA-BF-1 did not bind to membranes from PC-3 human prostate cancer cells or HEK293 human embryonic kidney cells. These observations suggest that the MDA-BF-1 receptor is expressed in cells of osteoblastic lineage. In addition to its use as a ligand for receptor binding assays, a ligand affinity column can be prepared by binding MDA-BF1-kinase-his to an IMAC for the purification of MDA-BF-1 receptor.