An x-ray fluorescence imaging system for gold nanoparticle detection.

Gold nanoparticles (GNPs) may be used as a contrast agent to identify tumour location and can be modified to target and image specific tumour biological parameters. There are currently no imaging systems in the literature that have sufficient sensitivity to GNP concentration and distribution measurement at sufficient tissue depth for use in in vivo and in vitro studies. We have demonstrated that high detecting sensitivity of GNPs can be achieved using x-ray fluorescence; furthermore this technique enables greater depth imaging in comparison to optical modalities. Two x-ray fluorescence systems were developed and used to image a range of GNP imaging phantoms. The first system consisted of a 10 mm(2) silicon drift detector coupled to a slightly focusing polycapillary optic which allowed 2D energy resolved imaging in step and scan mode. The system has sensitivity to GNP concentrations as low as 1 ppm. GNP concentrations different by a factor of 5 could be resolved, offering potential to distinguish tumour from non-tumour. The second system was designed to avoid slow step and scan image acquisition; the feasibility of excitation of the whole specimen with a wide beam and detection of the fluorescent x-rays with a pixellated controlled drift energy resolving detector without scanning was investigated. A parallel polycapillary optic coupled to the detector was successfully used to ascertain the position where fluorescence was emitted. The tissue penetration of the technique was demonstrated to be sufficient for near-surface small-animal studies, and for imaging 3D in vitro cellular constructs. Previous work demonstrates strong potential for both imaging systems to form quantitative images of GNP concentration.

Mammography equipment performance, image quality and mean glandular dose in Malta.

In this first Maltese national mammography survey, the effectiveness of direct digital (DR) mammography in breast cancer screening has been confirmed. Patient data were made available from three clinics out of the participating nine. A dose survey of mean glandular dose (MGD) calculated for 759 patients examined in the state-owned mammography facilities was performed. An MGD national diagnostic reference level was set at 1.87 mGy for patients with breast compression thicknesses (BCT) between 5.0 and 7.0 cm. This range was selected since patient data were retrieved from three clinics only and the results showed that other international BCT reference levels may be unsuitable for the Maltese population. In fact, the overall average BCT was 5.75 ± 1.4 cm. The survey results have shown that the technical standard of mammographic equipment in the Malta National Breast Screening Programme is on a par with other countries, including its Western European counterparts.

A study to determine the differences between the displayed dose values for two full-field digitalmammography units and values calculated using a range of Monte-Carlo-based techniques:a phantom study.

Modern full-field digital mammography (FFDM) units display the mean glandular dose (MGD) and the entrance or incident air kerma (K) to the breast following each exposure. Information on how these values are calculated is limited and knowing how displayed MGD values compare and correlate to conventional Monte-Carlo-based methods is useful. From measurements done on polymethyl methacrylate (PMMA) phantoms, it has been shown that displayed and calculated MGD values are similar for thin to medium thicknesses and appear to differ with larger PMMA thicknesses. As a result, a multiple linear regression analysis on the data was performed to generate models by which displayed MGD values on the two FFDM units included in the study may be converted to the Monte-Carlo values calculated by conventional methods. These models should be a useful tool for medical physicists requiring MGD data from FFDM units included in this paper and should reduce the survey time spent on dose calculations.

A quantitative x-ray detection system for gold nanoparticle tumour biomarkers.

X-ray fluorescence techniques have proven beneficial for identifying and quantifying trace elements in biological tissues. A novel approach is being developed that employs x-ray fluorescence with an aim to locate heavy nanoparticles, such as gold, which are embedded into tissues. Such nanoparticles can be functionalized to act as markers for tumour characteristics to map the disease state, with the future aim of imaging them to inform cancer therapy regimes. The uptake of functionalized nanoparticles by cancer cells will also enable detection of small clusters of infiltrating cancer cells which are currently missed by commonly used imaging modalities. The novel system, consisting of an energy-resolving silicon drift detector with high spectral resolution, shows potential in both quantification of and sensitivity to nanoparticle concentrations typically found in tumours. A series of synchrotron measurements are presented; a linear relationship between fluorescence intensity and gold nanoparticle (GNP) concentration was found down to 0.005 mgAu ml(-1), the detection limit of the system. Successful use of a bench-top source, suitable for possible future clinical use, is also demonstrated, and found not to degrade the detection limit or accuracy of the GNP concentration measurement. The achieved system sensitivity suggests possible future clinical usefulness in measuring tumour uptake in vivo, particularly in shallow tumour sites and small animals, in ex vivo tissue and in 3D in vitro research samples.

The use of a figure-of-merit (FOM) for optimisation in digital mammography: a literature review.

The use of image quality parameters in digital mammography such as contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and detective quantum efficiency (DQE) has been widespread, with the intention of detector evaluation and/or quantitative evaluation of the system performance. These parameters are useful in ensuring adequate system performance when tests are done against international standards or guidelines. Parameters like CNR are relative quantities that lie within a range that is manufacturer and system dependent. The use of a figure-of-merit (FOM) is a relatively new concept as a tool in digital mammography permitting quantitative assessment in terms of image quality and patient dose. This review summarises the available evidence for the use and applicability of an FOM in digital mammography.

Performance evaluation of a pixellated Ge Compton camera.

An ongoing project is being carried out to develop a high purity germanium (HPGe) Compton camera for medical applications. The Compton camera offers many potential advantages over the conventional gamma camera. The camera reported in this paper comprises two pixellated germanium detector planes housed 9.6 cm apart in the same vacuum housing. The camera has 177 pixels, 152 in the scatter detector and 25 in the absorption detector. The pixels are 4 × 4 mm(2) with a thickness of 4 mm in the scatter detector and 10 mm in the absorption detector. Images have been taken for a variety of test objects including point sources, a ring source and a Perspex phantom. The measured angular resolution is 9.4° ± 0.4° for a 662 keV gamma-ray source at 3 cm. Due to the limited number of readout modules a multiple-view technique was used to image the source distributions from different angles and simulate the pixel arrangement in the full camera.

Characterization study of an intensified complementary metal-oxide-semiconductor active pixel sensor.

An intensified CMOS active pixel sensor (APS) has been constructed for operation in low-light-level applications: a high-gain, fast-light decay image intensifier has been coupled via a fiber optic stud to a prototype "VANILLA" APS, developed by the UK based MI3 consortium. The sensor is capable of high frame rates and sparse readout. This paper presents a study of the performance parameters of the intensified VANILLA APS system over a range of image intensifier gain levels when uniformly illuminated with 520 nm green light. Mean-variance analysis shows the APS saturating around 3050 Digital Units (DU), with the maximum variance increasing with increasing image intensifier gain. The system's quantum efficiency varies in an exponential manner from 260 at an intensifier gain of 7.45 × 10(3) to 1.6 at a gain of 3.93 × 10(1). The usable dynamic range of the system is 60 dB for intensifier gains below 1.8 × 10(3), dropping to around 40 dB at high gains. The conclusion is that the system shows suitability for the desired application.

An elastically compressible phantom material with mechanical and x-ray attenuation properties equivalent to breast tissue.

We have developed a novel phantom material: a solution of polyvinyl alcohol (PVAL) in ethanol and water, freeze-thawed to produce a solid yet elastically compressible gel. The x-ray attenuation and mechanical properties of these gels are compared with published measurements of breast tissue. Gels with PVAL concentrations from 5 to 20% w/v were produced. The linear x-ray attenuation coefficients of these gels range from 0.76 to 0.86 cm(-1) at 17.5 keV, increasing with PVAL concentration. These values are very similar to the published values of breast tissue at this energy, 0.8-0.9 cm(-1). Under compression cancerous breast tissue is approximately ten times stiffer than healthy breast tissue. The Young's moduli of the gels increase with PVAL concentration. Varying the PVAL concentration from 7.5 to 20% w/v produces gels with Young's moduli from 20 to 220 kPa at 15% strain. These values are characteristic of normal and cancerous breast tissue, respectively.

Assessing the validity of modulation transfer function evaluation techniques with application to small area and scanned digital detectors.

A novel prototype step and shoot x-ray system, the intelligent imaging system (I-Imas), has been developed in the UCL Radiation Physics laboratories. The system uses collimators to split the beam into two: the first, "scout" beam, strongly attenuated, identifies regions of interest in the image. This information is then fed back to the system so that the intensity of the second beam is modulated to optimize the dose distribution--i.e., "interesting" regions of the sample receive a higher dose, whereas other regions receive a lower one. Such systems may be capable of improved diagnostic capability at the same overall patient dose levels as typical when using large area digital plates. This acquisition mode means that large overall images are obtained by aligning many smaller images. This paper investigates the effects that this acquisition modality has on the overall spatial resolution of the system. We review different modulation transfer function (MTF) evaluation techniques and those shown to be optimal are used in the investigation of two considerations key to such a system: (i) whether there is a minimum size sensor whose MTF can accurately be determined using these techniques and (ii) whether the MTF of the large overall image differs significantly from those of the many constituent images. As the use of step and shoot systems is becoming more and more widespread, both are important considerations. We found that, for a fixed pixel pitch, the MTF is determined marginally less accurately the smaller the sensor area, with the perceived resolution varying by up to 0.1 lp/mm. It was also found that use of such a step and shoot technique does cause a very small overall degradation in resolution. The resolution of overall images was calculated to be 0.1 lp/mm lower than that of the individual images acquired.

Preliminary images from an adaptive imaging system.

I-ImaS (Intelligent Imaging Sensors) is a European project aiming to produce real-time adaptive X-ray imaging systems using Monolithic Active Pixel Sensors (MAPS) to create images with maximum diagnostic information within given dose constraints. Initial systems concentrate on mammography and cephalography. In our system, the exposure in each image region is optimised and the beam intensity is a function of tissue thickness and attenuation, and also of local physical and statistical parameters in the image. Using a linear array of detectors, the system will perform on-line analysis of the image during the scan, followed by optimisation of the X-ray intensity to obtain the maximum diagnostic information from the region of interest while minimising exposure of diagnostically less important regions. This paper presents preliminary images obtained with a small area CMOS detector developed for this application. Wedge systems were used to modulate the beam intensity during breast and dental imaging using suitable X-ray spectra. The sensitive imaging area of the sensor is 512 x 32 pixels 32 x 32 microm(2) in size. The sensors' X-ray sensitivity was increased by coupling to a structured CsI(Tl) scintillator. In order to develop the I-ImaS prototype, the on-line data analysis and data acquisition control are based on custom-developed electronics using multiple FPGAs. Images of both breast tissues and jaw samples were acquired and different exposure optimisation algorithms applied. Results are very promising since the average dose has been reduced to around 60% of the dose delivered by conventional imaging systems without decrease in the visibility of details.

Correlation of energy dispersive diffraction signatures and microCT of small breast tissue samples with pathological analysis.

Identification of specific tissue types in conventional mammographic examinations is extremely limited. However, the use of x-ray diffraction effects during imaging has the potential to characterize the tissue types present due to the fact that each tissue type produces its own unique diffraction signature. Nevertheless, the analysis and categorization of these diffraction signatures by tissue type can be hampered by the inhomogeneous nature of breast tissue, leading to categorization errors where several types are present. This work aims to reduce sample categorization errors by combining spectral diffraction signature collection with sample imaging, giving more detailed data on the composition of each sample. Diffraction microCT was carried out on 19 unfixed breast tissue samples using an energy resolving translate-rotate CT system. High-resolution transmission microCT images were also recorded for comparison and sample composition analysis. Following imaging, the samples were subjected to histopathological analysis. Reconstructing on various momentum transfer regions allows different tissue types to be identified in the diffraction images. Results show a correlation between measured x-ray diffraction images and stained histopathological tissue sections. X-ray diffraction signatures generated from the measured data were categorized and analysed, with a t-test indicating that they have the potential for use in tissue type identification.

X-ray scatter signatures for normal and neoplastic breast tissues.

Measurements of breast tissue scattering properties have been made in an energy dispersive x-ray diffraction system over the momentum transfer range of 0.70 to 3.50 nm(-1). One hundred samples of excised tissue have been used. Results from the diffraction system have been compared with the histological analysis for each individual sample. It has been found that tissue types can be characterized on the basis of the shape of the scatter spectrum and on its relative intensity. The shapes are significantly different between tissue types in the range 1.0 to 1.8 nm(-1) and suggest that if particular values of momentum transfer are monitored, a discriminating signal could be obtained. Analysis of the maximum intensity in the signature also reveals a change of up to a factor of 2 between adipose and fat-free tissues.

Quantitative x-ray diffraction analysis of bone and marrow volumes in excised femoral head samples.

The aim of this paper is to apply the technique of quantitative x-ray diffraction analysis (QXDA) to trabecular bone tissue to demonstrate that quantitative data of the ratio of bone and marrow volumes within the trabecular region can be obtained. Apparatus has been constructed for measuring energy dispersive x-ray diffraction spectra of human femoral head samples in the diagnostic x-ray energy range. Individual diffraction peaks due to bone and marrow tissue were identified in the measured spectra. The relative intensities of the two peaks within the spectra quantify the relative proportions of the two components, and so the bone to marrow peak ratio is proposed as a parameter which is capable of providing information on the osteoporotic state of trabecular tissue. Preliminary results indicate a significant correlation between this method and the bone density measurement techniques of quantitative computed tomography and Compton scatter densitometry. Results have shown that the use of a synthetically prepared calibration curve can enable absolute measurement of bone or marrow volumes.

Tissue characterization using low angle x-ray scattering.

Diffraction studies of polyenergetic x-ray beams at low angles can be used to investigate tissues. Recent evidence on molecular form factors indicates that unique "fingerprints" exist for materials in the form of scattering information at angles between 0° and 10°. We have measured low angle scattering information in the form of energy spectra using a tungsten target x-ray source. It is shown that for certain scattering angles these spectra are highly structured, where this structure can be related to tissue type. We propose that these measurements will be diagnostic for various conditions such as osteoporosis or gall stone disease.