Dr Silvia Pani

About 1.7 million new cases of breast cancer were estimated by the World Health Organization (WHO) in 2012, accounting for 23 percent of all female cancers. In the UK 33 percent of women aged 50 and above were diagnosed in the same year, thus positioning the UK as the 6th highest in breast cancer amongst the European countries. The national Screening programme in the UK has been focused on the procedure of early detection and to improve prognosis by timely intervention to extend the life span of patients. To this end, the National Health Service Breast Screening Programme (NHSBSP) employs 2-D planar mammography because it is considered to be the gold standard technique for early breast cancer detection worldwide. Breast tomosynthesis has shown great promise as an alternative method for removing the intrinsic overlying clutter seen in conventional 2D imaging. However, preliminary work in breast CT has provided a number of compelling aspects that motivates the work featured in this thesis. These advantages include removal of the need to mechanically compress the breast which is a source of screening non-attendances, and that it provides unique cross sectional images that removes almost all the overlying clutter seen in 2D. This renders lesions more visible and hence aids in early detection of malignancy. However work in Breast CT to date has been focused on using scaled down versions of standard clinical CT systems. By contrast, this thesis proposes using a photon counting approach. The work of this thesis focuses on investigating photoncounting detector technology and comparing it to conventional CT in terms of contrast visualization. Results presented from simulation work developed in this thesis has demonstrated the ability of photoncounting detector technology to utilize data in polychromatic beam where contrast are seen to decrease with increasing photon energy and compared to the conventional CT approach which is the standard clinical CT system.

I-ImaS (Intelligent Imaging Sensors) is a European project which has designed and developed a new adaptive X-ray imaging system using on-line exposure control, to create locally optimized images. The I-ImaS system allows for real-time image analysis during acquisition, thus enabling real-time exposure adjustment. This adaptive imaging system has the potential of creating images with optimal information within a given dose constraint and to acquire optimally exposed images of objects with variable density during one scan. In this paper we present the control system and results from initial tests on mammographic and encephalographic images. Furthermore, algorithms for visualization of the resulting images, consisting of unevenly exposed image regions, are developed and tested. The preliminary results show that the same image quality can be achieved at 30-70% lower dose using the I-ImaS system compared to conventional mammography systems. © Springer-Verlag Berlin Heidelberg 2007.

The detection limit of invasive carcinoma by standard prone scintimammography appears to be >= 1 cm diameter. Since it is desirable to detect lesions at very earliest stages of growth (0.8 cm or less), the development of prototype scintimammographic systems with improved imaging performances is a primary goal. In this paper we propose a dedicated high resolution breast imaging scanner for SPECT around the Vertical Axis Of Rotation (VAOR) with the breast in prone position. The rotating detector module consists of a compact position sensitive photomultiplier tube (PS-PMTHamamatsu R7600-00-C8 coupled to a CsI(Tl) scintillating array. The compactness is the peculiarity of this detector module to allow the lodging in the breast interspace, to work close to the chest wall and to minimize the tumor to collimator front distance. A preliminary study was performed by a breast phantom and 5 inches small FOV gamma camera with an actual rotation radius of 6.5 cm. Images were reconstructed using a filtered back projection implementation. Tumor SNR from planar images shown very low values; on the contrary reconstructed images strongly enhanced the contrast of a tumor 1 cm sized. A further enhancement was obtained by the compact detector module that was able to achieve higher SNR values for tumor less 1 cm sized).

Conventional K-edge subtraction imaging is based around the acquisition of two separate images at energies respectively below and above the K-edge of a contrast agent. This implies increased patient dose with respect to a conventional procedure and potentially incorrect image registration due to patient motion. © 2012 IEEE.

Contrast-enhanced digital mammography (CEDM) is an alternative to conventional X-ray mammography for imaging dense breasts. However, conventional approaches to CEDM require a double exposure of the patient, implying higher dose and risk of incorrect image registration due to motion artifacts. A novel approach is presented, based on hyperspectral imaging, where a detector combining positional and high-resolution spectral information (in this case based on Cadmium Telluride) is used. This allows simultaneous acquisition of the two images required for CEDM. The approach was tested on a custom breast-equivalent phantom containing iodinated contrast agent (Niopam 150®). Two algorithms were used to obtain images of the contrast agent distribution: K-edge subtraction (KES), providing images of the distribution of the contrast agent with the background structures removed, and a dual-energy (DE) algorithm, providing an iodine-equivalent image and a water-equivalent image. The high energy resolution of the detector allowed the selection of two close-by energies, maximising the signal in KES images and enhancing the visibility of details with low surface concentration of contrast agent. DE performed consistently better than KES in terms of contrast-to-noise ratio of the details; moreover, it allowed a correct reconstruction of the surface concentration of the contrast agent in the iodine image. Comparison with CEDM with a conventional detector proved the superior performance of hyperspectral CEDM in terms of the image quality/dose trade-off.

Although X-ray mammography is the gold standard technique for breast cancer detection, it suffers from limitations due to tissue superposition which could either obscure or mimic a breast lesion. Dedicated breast computed-tomography (BrCT) represents an alternative technology with the potential to overcome these limitations. However, this technology is still under investigation in order to study and improve certain parameters (e.g. dose, scattered radiation, etc.). In this work, an image simulation framework is proposed to generate realistic BrCT images and spectral imaging analysis is explored to enhance the contrast of breast lesions. Results illustrated an improvement in contrast between 5 and 10% when the final image is reconstructed using X-ray photons with energies between 21 and 30 keV, in comparison with the reconstructed image from the polychromatic energy spectrum recorded within the image receptor. © 2013 IEEE.

X-ray diffraction (XRD) imaging appears as an alternative to conventional (transmission) imaging for characterization of breast tissue. The diffraction pattern of a material depends upon its arrangement at the sub-molecular level, which is altered as cancer progresses. For this reason the diffraction patterns of normal and neoplastic tissue have a detectable difference, unlike their X-ray attenuation coefficients, which underpin conventional imaging. This paper presents key studies in the field of single-point characterization of breast tissue using XRD. It then describes the development of XRD imaging and the main approaches used. Existing studies in the field of XRD imaging of breast tissue, both in the Computed Tomography modality, allowing cross-sectional images of an object, and in the planar geometry, are compared. Finally, future developments, including the adaptation to breast tissue analysis of patented diffraction imaging techniques and technologies, are discussed. © 2012 Bentham Science Publishers.

This project uses the combination of a spectroscopic detector and a monochromator to produce scatter free images for use in mammography. Reducing scatter is vital in mammography, where typical structures have either low contrast or small dimensions. The typical method to reduce scatter is the anti-scatter grid, which has the drawback of absorbing a fraction of the primary beam as well as scattered radiation. An increase in the dose is then required in order to compensate. Compton-scattered X-rays have lower energy than the primary beam. When using a monochromatic beam and a spectroscopic detector the scattered beam will appear at lower energies than the primary beam in the detected spectrum. Therefore if the spectrum of the detected X-rays is available, the scattered component can be windowed out of the spectrum, essentially producing a scatter free image. The monochromator used in this study is made from a Highly Orientated Pyrolytic Graphite (HOPG) crystal with a mosaic spread of 0.4°±0.1°. The detector is a pixellated spectroscopic detector that is made from a 2 cm x 2 cm x 0.1 cm CdTe crystal with a pixel pitch of 250 μm and an energy resolution of 0.8 keV at 59.5 keV. This work presents the characterisation of the monochromator and initial imaging data. The work shows a contrast increase of 20% with the removal of the low energy Compton scattered X-rays. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Recently the application of small imagers in nuclear medicine is growing, particularly in scintimammography. In this paper we propose the use of the Hamamatsu R7600-C8 Position Sensitive Photomultiplier Tube (PSPMT) for detection image optimization in scintimammography through the evaluation of image performances of detector pixellation and its interaction with a collimator lattice . To this aim, a number of CsI(Tl) scintillating arrays with different pixel size and thickness were coupled to the same PSPMT. Considering the very high intrinsic spatial resolution, a look up table was realized to correct accurately the gain non uniformities. The results show an overall energy resolution FWHM, from flood field irradiation source, in close agreement with the individual crystal response and an uniformity response within ± 10%. Finally an analysis of tumor signal to noise ratio (SNR) as a function of detection pixellation was performed, utilizing a breast phantom. Tumor SNR values are highest for 5 mm thick CsI(Tl) arrays but shown slight differences with pixel size. The best tumor SNR value for 6 cm breast thick was obtained with 1.5 × 1.5 mm2 crystal pixel size. The collimator used was a low energy all purpose, parallel hole collimator with 22 mm length, 1.5 mm hexagonal hole, 0.2 mm Pb septa, currently utilized in scintimammography.

A Monte-Carlo model was developed to simulate the response of a pixelated hyperspectral CZT X-ray detector. The first part of the simulation was carried out using Geant4, to obtain a list of energy depositions inside the CZT crystal. The second part of the simulation used charge transport equations to calculate the size of the electron charge cloud, as it drifts under the electric field to be read out. Experimentally acquired data from an Am-241 source with the HEXITEC detector were compared to simulated data, and good agreement was found. The model was used to investigate the energy dependence of fluorescence and charge sharing effects. Firstly, the probability of producing an escaped fluorescence photon was quantified as a function of primary photon energy. As expected, at primary photon energies just above the K-edge of Cd, there is a greater chance of producing an escaped fluorescence photon, and this probability decreases as the primary photon energy increases. Secondly, the probability of an event being shared across multiple pixels as a function of primary photon energy was quantified. It was found that as the primary photon energy is increased, there is a greater chance of producing an event shared across multiple pixels. The detector response to a Bremsstrahlung spectrum was simulated. Using previous results, fluorescence and charge sharing effects were corrected for, giving a corrected spectrum in good agreement with the input spectrum.

X-ray detectors are critical to healthcare diagnostics, cancer therapy and homeland security, with many potential uses limited by system cost and/or detector dimensions. Current X-ray detector sensitivities are limited by the bulk X-ray attenuation of the materials and consequently necessitate thick crystals (~ 1 mm – 1 cm), resulting in rigid structure, high operational voltages and high cost. Here we present a disruptive, flexible, low cost, broad-band, and high sensitivity direct X-ray transduction technology produced by embedding high atomic number bismuth oxide nanoparticles in an organic bulk heterojunction. These hybrid detectors demonstrate sensitivities of 1712 µC mGy-1 cm-3 for “soft” X-rays and ~30 and 58 µC mGy-1 cm-3 under 6 and 15 MV “hard” X-rays generated from a medical linear accelerator; strongly competing with the current solid state detectors, all achieved at low bias voltages (-10 V) and low power, enabling detector operation powered by coin cell batteries.

Sensors Technology Series Editor-in-Chief's Preface vii Preface ix 1 Biomedical Sensors: Temperature Sensor ... G. Kim Prisk 4 Biomedical Sensors of Ionizing Radiation 129 Robert Speller, Alessandro Olivo, Silvia Pani, and Gary Royle 5 ...

Compton scattering is one of the main causes of image degradation in X-ray imaging. This is particularly noticeable in mammography where details of interest feature low contrast in comparison to the surrounding tissue. This work shows the feasibility of obtaining scatter-free images by using a quasi-monochromatic X-ray beam and a pixellated spectroscopic detector. This work presents characterisation of the imaging system and quantitative imaging data of a low contrast test object. An improvement in contrast by 8% was observed compared to images obtained including scattered radiation. Comparison with a conventional setup showed an increase in the image quality factor when scatter has been removed.

The scattering properties of breast tissue have been suggested as a diagnostic tool in the early detection of breast cancer. To aid in the development of a clinical imaging system based upon these properties, a series of breast tissue samples have been subjected to diffraction microCT using the SYRMEP beamline at Elettra, Italy. Using 18 keV photons, both transmission and diffraction CT data sets were collected using a specially designed microCT system. This system was based around a finely collimated, x-ray sensitive L3Vision CCD camera and a simple rotary stage controlled using Lab View software. The images were reconstructed using routines developed in IDL. This paper presents both transmission and diffraction CT images of three samples. The samples were excised breast tissue sections known to contain either tumour, normal tissue adjacent to the tumour or a mixture of each. The results demonstrate that diffraction microCT can be used to evaluate the structure of breast tissue tumours. Registration of the transmission and diffraction CT images demonstrated that both techniques showed the same principle features in the sample and allowed the main components to be identified. However, the diffraction images demonstrated an average increase in image contrast over the transmission images. Further improvements in the collimator design used in the experiments will need to be made if detailed structure is to be seen.

Purpose: To define a method and investigate how the adjustment of scan parameters affected the image quality and Hounsfield units (HUs) on a CT scanner used for radiotherapy treatment planning. A lack of similar investigations in the literature may be a contributing factor in the apparent reluctance to optimise radiotherapy CT protocols. Method: A Catphan phantom was used to assess how image quality on a Toshiba Aquilion LB scanner changed with scan parameters. Acquisition and reconstruction field-of-view (FOV), collimation, image slice thickness, effective mAs per rotation and reconstruction algorithm were varied. Changes were assessed for HUs of different materials, high contrast spatial resolution (HCSR), contrast-noise ratio (CNR), HU uniformity, scan direction low contrast and CT dose-index. Results: CNR and HCSR varied most with reconstruction algorithm, reconstruction FOV and effective mAs. Collimation, but not image slice width, had a significant effect on CT dose-index with narrower collimation giving higher doses. Dose increased with effective mAs. Highest HU differences were seen when changing reconstruction algorithm: 56 HU for densities close to water and 117 HU for bone-like materials. Acquisition FOV affected the HUs but reconstruction FOV and effective mAs did not. Conclusions: All the scan parameters investigated affected the image quality metrics. Reconstruction algorithm, reconstruction FOV, collimation and effective mAs were most important. Reconstruction algorithm and acquisition FOV had significant effect on HU. The methodology is applicable to radiotherapy CT scanners when investigating image quality optimisation, prior to assessing the impact of scan protocol changes on clinical CT images and treatment plans.

In mammography, the reduction of scattered X-rays is vital due to the low contrast or small dimension of the details that are searched for. The typical method of doing so in current conventional mammography is the anti-scatter grid. The disadvantage of this method is the absorption of a proportion of the primary beam and therefore an increase in dose is required to compensate for the loss of counts. An alternative method is proposed, using quasi-monochromatic beams and a pixellated spectroscopic detector. As Compton-scattered X-rays lose energy in the scattering process, they are detected at a lower energy in the spectrum. Therefore the spectrum can be windowed around the monochromatic energy peak, removing the scattered Xrays from the image. The work presented here shows contrast improvement of up to 50 % and contrast to noise ratio improvements of around 20 % for scatter free imaging in comparison to full spectrum imaging. Contrast improvements of around 45 % were found when comparing scatter free images to conventional polychromatic imaging for both the low contrast test object and the Rachel anthropomorphic breast phantom.

We have developed a pixellated high energy X-ray detector instrument to be used in a variety of imaging applications. The instrument consists of either a Cadmium Zinc Telluride or Cadmium Telluride (Cd(Zn)Te) detector bump-bonded to a large area ASIC and packaged with a high performance data acquisition system. The 80 by 80 pixels each of 250 μm by 250 μm give better than 1 keV FWHM energy resolution at 59.5 keV and 1.5 keV FWHM at 141 keV, at the same time providing a high speed imaging performance. This system uses a relatively simple wire-bonded interconnection scheme but this is being upgraded to allow multiple modules to be used with very small dead space. The readout system and the novel interconnect technology is described and how the system is performing in several target applications

The I-Imas (Intelligent Imaging Sensors) is an EU project whose objective is to design and develop intelligent imaging sensors and evaluate their use within an adaptive medical imaging system specifically tailored to Mammography and Dental Radiology. The system will employ an in line scanning technology approach and proposes the use of CMOS active pixels sensors. The I-Imas sensor will have the capability of processing the data on every pixel and be able to dynamically respond in real time to changing conditions during imaging recording. The result will be to minimise the radiation exposure to areas of low diagnostic information content while extracting the highest diagnostic information from region of high interest. The first phase of the I-Imas project deals with the characterisation of the key features in a medical image that carry the highest content of diagnostic information. With this objective in mind an End-Users Survey has been carried out. We have been distributed a questionnaire to experts in the field of mammography and dental radiology (the dental radiology results will be presented elsewhere): medical physicists, radiologists, radiographers and dentists. From this survey we have collected information about the most useful specifications to be implemented in the I-Imas imaging system. This paper discusses the results from the End-Users survey and considers design implications for the I-Imas sensors. © 2004 IEEE.

This paper illustrates the effectiveness of a new multi-slice CT system to study the trabecular bone tissue. The system is capable of acquiring 3D images of 5600×5600×52 voxels on specimens up to 130 mm with a spatial resolution of 22.5 micrometers. This new detector is coupled to a CCD intensified camera (EBCCD) and was patented by the University of Bologna. The CT acquisitions were performed with an experimental setup at Elettra facilities at beamline SYRMEP. The reconstructed images were sections containing the femoral head, femoral neck and trochantere. The used spatial resolution allows to visualize also thin trabeculae, which typically lie in a range below 100 microns. The morphometric trabecular characterization parameters as BV/TV, Tb.Th, Tb.Sp, Tb.N were calculated over three regions of interest. The local variations in trabecular and cortical structure of the examined bone are clearly visible at a level not obtainable with medical CT scanners. The quality of the reconstructed cross sections images confirm that this investigation technique is an advanced tool for high resolution three-dimensional imaging of bone structure. © 2004 IEEE.

A detectable difference in x-ray diffraction data of healthy and diseased breast tissues has been observed This information can be used to generate images with a higher contrast than that of conventional transmission mammography. A diffraction enhanced breast imaging (DEBI) system that simultaneously combines transmission and diffraction breast images is currently being developed. This paper presents the imaging system requirements for a clinical DEBI system. The DEBI imaging system employs a phosphor coated L3Vision CCD camera. The DEBI principle has been assessed at the SYRMEP synchrotron beamline (Elettra, Trieste) and with a purpose built mammographic x-ray imaging unit Diffraction enhanced images have been obtained of realistic breast tissue phantoms, consisting of 4cm thick slabs of excised breast tissue containing embedded carcinomas. The images were obtained at pre-determined momentum transfer values, allowing some tissue characterization to be achieved during imaging, as well as optimizing image contrast. This paper presents the current state of the project The spatial resolution of the diffraction images have been studied using test phantoms and suggestions are made for the collimation systems necessary for a clinical system. A correction procedure applied to the diffraction images is also presented.

Semiconducting polymer X-radiation detectors are a completely new family of low-cost radiation detectors with potential application as beam monitors or dosimeters. These detectors are easy to process, mechanically flexible, relatively inexpensive, and able to cover large areas. However, their x-ray photocurrents are typically low as, being composed of elements of low atomic number (Z), they attenuate x-rays weakly. Here, the addition of high-Z nanoparticles is used to increase the x-ray attenuation without sacrificing the attractive properties of the host polymer. Two types of nanoparticles (NPs) are compared: metallic tantalum and electrically insulating bismuth oxide. The detection sensitivity of 5 µm thick semiconducting poly([9,9-dioctylfluorenyl-2,7-diyl]-co-bithiophene) diodes containing tantalum NPs is four times greater than that for the analogous NP-free devices; it is approximately double that of diodes containing an equal volume of bismuth oxide NPs. The x-ray induced photocurrent output of the diodes increases with an increased concentration of NPs. However, contrary to the results of theoretical x-ray attenuation calculations, the experimental current output is higher for the lower-Z tantalum diodes than the bismuth oxide diodes, at the same concentration of NP loading. This result is likely due to the higher tantalum NP electrical conductivity, which increases charge transport through the semiconducting polymer, leading to increased diode conductivity.

Simultaneous dual-tracer brain imaging has the potential to shorten patient pathways in the diagnosis of neurodegenerative diseases, but the poor spectral resolution of conventional gamma cameras limits the utility of this technique. Solid state detectors offer improved capability to distinguish between two radioisotopes, but the technology has yet to be fully evaluated in the field of scintigraphic neuroimaging. We present imaging results for a new small-pixel CdTe detector in simultaneous dual-radioisotope scintigraphy of a brain phantom containing Tc-99m and I-123. Quantitative comparison is made with images of the same phantom obtained using a conventional gamma camera. We show that the CdTe detector offers improved scatter rejection and greatly reduced cross-talk between the energy windows. In addition, the new detector is able to resolve low-energy fluorescence x-rays from the source, which could be incorporated into SPECT reconstruction algorithms. Details of the planned development of the detector into a clinical demonstrator are discussed. © 2012 IEEE.

Graphene-based carbon sponges can be used in different applications in a large number of fields including microelectronics, energy harvesting and storage, antimicrobial activity and environmental remediation. The functionality and scope of their applications can be broadened considerably by the introduction of metallic nanoparticles into the carbon matrix during preparation or post-synthesis. Here, we report on the use of X-ray micro-computed tomography (CT) as a method of imaging graphene sponges after the uptake of metal (silver and iron) nanoparticles. The technique can be used to visualize the inner structure of the graphene sponge in 3D in a non-destructive fashion by providing information on the nanoparticles deposited on the sponge surfaces, both internal and external. Other deposited materials can be imaged in a similar manner providing they return a high enough contrast to the carbon microstructure, which is facilitated by the low atomic mass of carbon.