C. D. Arvanitis

Empirical electro-optical and x-ray performance evaluation of CMOS active pixels sensor for low dose, high resolution x-ray medical imaging

Monolithic complementary metal oxide semiconductor (CMOS) active pixel sensors with high performance have gained attention in the last few years in many scientific and space applications. In order to evaluate the increasing capabilities of this technology, in particular where low dose high resolution x-ray medical imaging is required, critical electro-optical and physical x-ray performance evaluation was determined. The electro-optical performance includes read noise, full well capacity, interacting quantum efficiency, and pixels cross talk. The x-ray performance, including x-ray sensitivity, modulation transfer function, noise power spectrum, and detection quantum efficiency, has been evaluated in the mammographic energy range. The sensor is a 525 x 525 standard three transistor CMOS active pixel sensor array with more than 75% fill factor and 25 x 25 microm pixel pitch. Reading at 10 f/s, it is found that the sensor has 114 electrons total additive noise, 10(5) electrons full well capacity with shot noise limited operation, and 34% interacting quantum efficiency at 530 nm. Two different structured CsI:Tl phosphors with thickness 95 and 115 microm, respectively, have been optically coupled via a fiber optic plate to the array resulting in two different system configurations. The sensitivity of the two different system configurations was 43 and 47 electrons per x-ray incident on the sensor. The MTF at 10% of the two different system configurations was 9.5 and 9 cycles/mm with detective quantum efficiency of 0.45 and 0.48, respectively, close to zero frequency at approximately 0.44 microC/kg (1.72 mR) detector entrance exposure. The detector was quantum limited at low spatial frequencies and its performance was comparable with high resolution a: Si and charge coupled device based x-ray imagers. The detector also demonstrates almost an order of magnitude lower noise than active matrix flat panel imagers. The results suggest that CMOS active pixel sensors when coupled to structured CsI:Tl can be used for conventional and advanced digital mammography due to their low noise, high resolution performance.

A CMOS active pixel sensor system for laboratory- based x-ray diffraction studies of biological tissue.

X-ray diffraction studies give material-specific information about biological tissue. Ideally, a large area, low noise, wide dynamic range digital x-ray detector is required for laboratory-based x-ray diffraction studies. The goal of this work is to introduce a novel imaging technology, the CMOS active pixel sensor (APS) that has the potential to fulfil all these requirements, and demonstrate its feasibility for coherent scatter imaging. A prototype CMOS APS has been included in an x-ray diffraction demonstration system. An industrial x-ray source with appropriate beam filtration is used to perform angle dispersive x-ray diffraction (ADXRD). Optimization of the experimental set-up is detailed including collimator options and detector operating parameters. Scatter signatures are measured for 11 different materials, covering three medical applications: breast cancer diagnosis, kidney stone identification and bone mineral density calculations. Scatter signatures are also recorded for three mixed samples of known composition. Results are verified using two independent models for predicting the APS scatter signature: (1) a linear systems model of the APS and (2) a linear superposition integral combining known monochromatic scatter signatures with the input polychromatic spectrum used in this case. Cross validation of experimental, modelled and literature results proves that APS are able to record biologically relevant scatter signatures. Coherent scatter signatures are sensitive to multiple materials present in a sample and provide a means to quantify composition. In the future, production of a bespoke APS imager for x-ray diffraction studies could enable simultaneous collection of the transmitted beam and scattered radiation in a laboratory-based coherent scatter system, making clinical transfer of the technique attainable.

Signal and noise transfer properties of CMOS based active pixel flat panel imager coupled to structured CsI:Tl

Complementary metal-oxide-semiconductors (CMOS) active pixel sensors can be optically coupled to CsI:Tl phosphors forming a indirect active pixel flat panel imager (APFPI) for high performance medical imaging. The aim of this work is to determine the x-ray imaging capabilities of CMOS-based APFPI and study the signal and noise transfer properties of CsI:Tl phosphors. Three different CsI:Tl phosphors from two different vendors have been used to produce three system configurations. The performance of each system configuration has been studied in terms of the modulation transfer function (MTF), noise power spectra, and detective quantum efficiency (DQE) in the mammographic energy range. A simple method to determine quantum limited systems in this energy range is also presented. In addition, with aid of monochromatic synchrotron radiation, the effect of iodine characteristic x-rays of the CsI:Tl on the MTF has been determined. A Monte Carlo simulation of the signal transfer properties of the imager is also presented in order to study the stages that degrade the spatial resolution of our current system. The effect of using substrate patterning during the growth of CsI:Tl columnar structure was also studied, along with the effect of CsI:Tl fixed pattern noise due to local variations in the scintillation light. CsI:Tl fixed pattern noise appears to limit the performance of our current system configurations. All the system configurations are quantum limited at 0.23 microC/kg with two of them having DQE (0) equal to 0.57. Active pixel flat panel imagers are shown to be digital x-ray imagers with almost constant DQE throughout a significant part of their dynamic range and in particular at very low exposures.

Quantitative contrast-enhanced mammography for contrast medium kinetics studies

Quantitative contrast-enhanced mammography, based on a dual-energy approach, aims to extract quantitative and temporal information of the tumour enhancement after administration of iodinated vascular contrast media. Simulations using analytical expressions and optimization of critical parameters essential for the development of quantitative contrast-enhanced mammography are presented. The procedure has been experimentally evaluated using a tissue-equivalent phantom and an amorphous silicon active matrix flat panel imager. The x-ray beams were produced by a tungsten target tube and spectrally shaped using readily available materials. Measurement of iodine projected thickness in mg cm(-2) has been performed. The effect of beam hardening does not introduce nonlinearities in the measurement of iodine projected thickness for values of thicknesses found in clinical investigations. However, scattered radiation introduces significant deviations from slope equal to unity when compared with the actual iodine projected thickness. Scatter correction before the analysis of the dual-energy images provides accurate iodine projected thickness measurements. At 10% of the exposure used in clinical mammography, signal-to-noise ratios in excess of 5 were achieved for iodine projected thicknesses less than 3 mg cm(-2) within a 4 cm thick phantom. For the extraction of temporal information, a limited number of low-dose images were used with the phantom incorporating a flow of iodinated contrast medium. The results suggest that spatial and temporal information of iodinated contrast media can be used to indirectly measure the tumour microvessel density and determine its uptake and washout from breast tumours. The proposed method can significantly improve tumour detection in dense breasts. Its application to perform in situ x-ray biopsy and assessment of the oncolytic effect of anticancer agents is foreseeable.

Optical and x-ray characterization of two novel CMOS image sensors

A UK consortium (MI3) has been founded to develop advanced CMOS pixel designs for scientific applications. Vanilla, a 520x520 array of 25&mgr;m pixels benefits from flushed reset circuitry for low noise and random pixel access for region of interest (ROI) readout. OPIC, a 64x72 test structure array of 30&mgr;m digital pixels has thresholding capabilities for sparse readout at 3,700fps. Characterization is performed with both optical illumination and x-ray exposure via a scintillator. Vanilla exhibits 34±3e- read noise, interactive quantum efficiency of 54% at 500nm and can read a 6x6 ROI at 24,395fps. OPIC has 46±3e- read noise and a wide dynamic range of 65dB due to high full well capacity. Based on these characterization studies, Vanilla could be utilized in applications where demands include high spectral response and high speed region of interest readout while OPIC could be used for high speed, high dynamic range imaging.

Dual energy contrast enhanced breast imaging optimization using contrast to noise ratio

The properties of dual energy contrast enhanced breast imaging have been analyzed by imaging a 4 cm breast equivalent phantom consisting of adipose and glandular equivalent plastics. This phantom had superimposed another thin plastic which incorporated a 2 mm deep cylinder filled with iodinated contrast media. The iodine projected thicknesses used for this study was 3 mg/cm2. Low and high energy spectra that straddle the iodine K-edge were used. Critical parameters such as the energy spectra and exposure are discussed, along with post processing by means of nonlinear energy dependent function. The dual energy image was evaluated using the relative contrast to noise ratio of a 2.5 mm x 2.5 mm region of the image at the different iodine concentrations incorporating different breast composition with respect to the noniodinated areas. Optimum results were achieved when the low and high-energy images were used in such a way that relative contrast to noise ratio of the iodine with respect to the background tissue was maximum. A figure of merit suggests that higher noise levels can be tolerated at the benefit of lower exposure. Contrast media kinetics of a phantom incorporating a water flow of 20.4 ml/min through the plastic cylinder suggests that time domain imaging could be performed with this approach. The results suggest that optimization of dual energy contrast enhanced mammography has the potential to lead to the development of perfusion digital mammography.