Evaluation of room-temperature semiconductor detectors for ultrahigh resolution pet imaging

The evaluation of a room-temperature semiconductor detector for ultrahigh resolution positron emission tomography (PET) imaging is presented. The approach is based on the use of a CdTe semiconductor detector. The detector is a 2mm thick cadmium telluride (CdTe) detector with a pixel pitch of 350μm x 350μm; it is bump bonded to an energy-resolved photo-counting (ERPC) readout applied-specific integrated circuit (ASIC). It can be demonstrated that this configuration yields depth-of-interaction (DOI) information. Two ways of extracting DOI information are presented. A prototype PET system based on this detector has been developed. The corresponding system calibration algorithm is presented for the PET system, which considers the DOI information. The validity of the two proposed methods of extracting DOI information has been studied by doing the following experiment. The measurements were made by using a Co-57 point source with an active spherical area of diameter 0.25mm. The beam entered the sensor at an angle of ~48.8 degrees to the surface; results showed that the beam passed through 5 pixels before exiting the bottom of the sensor. The validity of these two methods of extracting DOI information was further demonstrated by development of a related PET system calibration algorithm. Future work will address image reconstruction based on results from this PET system calibration algorithm

Design of a low-dose, stationary, tomographic Molecular Breast Imaging system using 3D position sensitive CZT detectors

Molecular Breast Imaging (MBI) has been shown to have high sensitivity for lesion detection, particularly in patients with dense breasts where conventional mammography is limited. However, relatively high radiation dose and long imaging time are limiting factors. Most current MBI systems are based on planar imaging. Improved performance can be achieved using tomographic techniques, which normally involve detector motion. Our goal is to develop a low-dose stationary tomographic MBI system with similar or better performance in terms of lesion detection compared to planar MBI. The proposed system utilizes two opposing CZT detectors with high intrinsic resolution and depth of interaction (DOI) capability, combined with densely packed multi-pinhole collimators. This leads to improved efficiency and adequate angular sampling, but also to significant multiplexing (MX), which can result in artefacts. We have developed de-MX algorithms that take advantage of the DOI information. We have performed both analytic and Monte Carlo simulations to demonstrate the feasibility, optimize the design and investigate the expected performance of the proposed system. Lesion detectability was preserved with reduction of acquisition time (or radiation dose) by a factor of 2 compared to planar images at the lowest reported dose. The first prototype is under evaluation at Kromek

Relative Merits of 3D Visualization for the Detection of Subtle Lung Nodules

A new imaging modality called bi-plane correlation imaging (BCI) was examined to determine the merits of using BCI with stereoscopic visualization to detect subtle lung nodules. In the first aim of this project, the optimal geometry for conventional projection imaging applications was assessed using a theoretical model to develop generic results for MTF, NNPS, eDQE. The theoretical model was tested with a clinical system using two magnifications and two anthropomorphic chest phantoms to assess the modalities of single view CXR and stereo/BCI. Results indicated that magnification can potentially improve the signal and noise performance of digital images. Results also demonstrated that a cross over point occurs in the spatial frequency above and below which the effects of magnification differ indicating that there are task dependent tradeoffs associated with magnification. Results indicated that magnification can potentially improve the detection performance primarily due to the air gap which reduced scatter by 30-40%. For both anthropomorphic phantoms, at iso-dose, eDQE(0) for stereo/BCI was ~100 times higher than that for CXR. Magnification at iso-dose improved eDQE(0) by ~10 times for BCI. Increasing the dose did not improve results. The findings indicated that stereo/BCI with magnification may improve detection of subtle lung nodules compared to single view CXR. With quantitative results in place, a pilot clinical trial was constructed. Human subject data was acquired with a BCI acquisition system. Subjects were imaged in the PA position as well as two oblique angles. Realistic simulated lesions were added to a subset of subjects determined to be nodule free. A BCI CAD algorithm was also applied. In randomized readings, radiologists read the cases according to viewing protocol. For the radiologist trainees, the AUC of lesion detection was seen to improve by 2.8% (p < 0.05) for stereoscopic viewing after monoscopic viewing compared to monoscopic viewing only. A 13% decrease in false positives was observed. Stereo/BCI as an adjunct modality was beneficial. However, the full potential of stereo/BCI as a replacement modality for single view chest x-ray may be realized with improved observer training, clinically relevant stereoscopic displays, and more challenging detection tasks.Doctor of Philosoph

A versatile imaging system for in vivo small animal research

In vivo small animal imaging has become an essential technique for molecular biology studies. However, requirements of spatial resolution, sensitivity and image quality are quite challenging for the development of small-animal imaging systems. The capabilities of the system are also significant for carrying out small animal imaging in a wide range of biological studies. The goal of this dissertation is to develop a high-performance imaging system that can readily meet a wide range of requirements for a variety of small animal imaging applications. Several achievements have been made in order to fulfill this goal.;To supplement our system for parallel-hole single photon emission computed tomography (SPECT) based upon a 110 mm diameter circular detector, we have developed novel compact gamma cameras suitable for imaging an entire mouse. These gamma cameras facilitate multi-head (\u3e2) parallel-hole SPECT with the mouse in close proximity to the detector face in order to preserve spatial resolution. Each compact gamma cameras incorporates pixellated Nal(Tl) scintillators and a pair of Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMTs). Two types of copper-beryllium parallel-hole collimators have been designed. These provide high-sensitivity imaging of I-125 or excellent spatial resolution over a range of object-detector distances. Both phantom and animal studies have demonstrated that these gamma cameras perform well for planar scintigraphy and parallel-hole SPECT of mice.;To further address the resolution limitations in parallel-hole SPECT and the sensitivity and limited field of view of single-pinhole SPECT, we have developed novel multipinhole helical SPECT based upon a 110 mm diameter circular detector equipped with a pixellated Nal(Tl) scintillator array. A brass collimator has been designed and produced containing five 1 mm diameter pinholes. Results obtained in SPECT studies of various phantoms show an enlarged field of view, very good resolution and improved sensitivity using this new imaging technique.;These studies in small-animal imaging have been applied to in vivo biological studies related to human health issues including studies of the thyroid and breast cancer. A re-evaluation study of potassium iodide blocking efficiency in radioiodine uptake in mice suggests that the FDA-recommended human dose of stable potassium iodide may not be sufficient to effectively protect the thyroid from radioiodine contamination. Another recent study has demonstrated that multipinhole helical SPECT can resolve the fine structure of the mouse thyroid using a relatively low dose (200 muCi). Another preclinical study has focused on breast tumor imaging using a compact gamma camera and an endogenous reporter gene. In that ongoing study, mammary tumors are imaged at different stages. Preliminary results indicate different functional patterns in the uptake of radiotracers and their potential relationship with other tumor parameters such as tumor size.;In summary, we have developed a versatile imaging system suitable for in vivo small animal research as evidenced by a variety of applications. The modular construction of this system will allow expansion and further development as new needs and new opportunities arise

GATE Model of a SPECT-CT equipment for breast cancer diagnosis

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Radiações em Diagnóstico e Terapia)Universidade de Lisboa, Faculdade de Ciências, 2016Dedicated imaging systems for breast cancer imaging have been comprehensively studied over the past decade. However, since they comprise only one imaging modality these systems are only able to provide either anatomical or functional information of the object of interest. The aim of this work was to simulate and evaluate the implementation of a dedicated system that would be able to extract information regarding both systems in order to provide a complementary diagnostic tool which could be used in inconclusive diagnosis cases. The proposed solution was to develop two dedicated systems. A dedicated breast computed tomography (DBCT) system that would provide anatomical information and a dedicated single photon emission mammography (SPEM), using convergent collimators, that would retrieve functional information. To create a computer model of this multimodality system, Monte Carlo (MC) simulations were conducted with Geant4 Application for Emission Tomography (GATE) using a simple breast cylindrical phantom with 35 mm radius and 150 mm height, which had 5 mm radius spherical masses composed of aluminum inside it. For DBCT, the MC simulations were acquired with a PaxScan A® 2520D/CL Amorphous Silicon Digital X-Ray Imager with total dimensions of 192x242x4 mm and 0.508x0.508x4 mm pixels, over 16 projections covering 180º of the phantom, extended to 360º exploiting its cylindrical symmetry. Inside the phantom were placed 5 tumour masses equidistantly along two axis with a tumour mass at the center. For SPECT, the MC simulations were performed using a dual-head SPECT scanner designed by Dr. Ricardo Capote with 64.0x151.2x188.5 mm as dimensions with pixelated LYSO crystals of 20x2x2 mm and convergent collimators with the same phantom, but with the same 5 mm radius tumour masses placed solely in the x axis. The MC simulations were conducted in a computer cluster with 4 executions machines. The projections resultant of the simulations were reconstructed using different algorithms. For DBCT it was used an analytical method of filtered backprojection (FBP) and for SPEM it was used an iterative maximum likelihood expectation maximization (MLEM) algorithm. To validate the results two non-absolut metrics were calculated to make a relative evaluation of the image quality results. These metrics were only applied to DBCT, since the results obtained for SPEM were not as expected. Contrast and contrast to noise ratio demonstrated that the image quality degrades from the center to the periphery of the DBCT detector. In conclusion, the acquired results demonstrated the feasibility of breast dedicated systems to, especially for the DBCT system, which yielded the best results, but further development need to be pursued in order to take the most potential of the developed systems which have potential for being used in future studies with more complex and realistic conditions and voxelised phantoms.O cancro da mama é o tipo de cancro mais diagnosticado nas mulheres, precedido apenas em termos de incidência estatística pelo cancro da pele. No que diz respeito ao número de mortes, o cancro da mama encontra-se também entre os mais importantes relativamente às mulheres, sendo secundado apenas pelo cancro do pulmão em mortalidade. A deteção precoce de neoplasias na mama ganha assim um papel fundamental de forma a garantir o sucesso do tratamento, melhorando as taxas de sobrevivência daqueles aos quais são diagnosticadas neoplasias mamárias. É nessa deteção que a imagiologia médica se apresenta atualmente como essencial. Não apenas no tremendo esforço nas últimas décadas por melhorar as modalidades imagiológicas já implementadas clinicamente, mas também pelo desenvolvimento de novas que possam adicionar nova informação relevante, especialmente quando perante casos em que o exame médico utilizado não é conclusivo. Atualmente, a mamografia por raios X é a técnica imagiológica utilizada em prática clínica corrente em rastreios de cancro da mama, rastreios esses que permitem um diagnóstico mais precoce, tendo contribuído nas últimas décadas para um aumento muito significativo das taxas de sobrevivência. No entanto, esta técnica apresenta diversas limitações que podem condicionar o correto diagnóstico dos doentes. Sendo uma técnica que fornece essencialmente informação anatómica e a duas dimensões, apesar de esta oferecer um elevado nível de sensibilidade, a sua especificidade é menor. Isto pode levar a uma menor capacidade de discernir entre lesão benigna e maligna, resultado principalmente da não incorporação de informação metabólica relativa às massas tumorais, bem como, da possibilidade da não identificação de neoplasias, resultado da sobreposição de planos sempre inerente a uma técnica imagiológica apenas a duas dimensões. Desta forma, torna-se necessário recorrer a outras técnicas que providenciem informação adicional sobre as neoplasias detetadas, mas também que possibilitem a visualização a três dimensões, evitando ao máximo procedimentos invasivos desnecessários, tais como biopsias. Sistemas dedicados para examinar a mama, tirando partido da cada vez maior miniaturização dos componentes eletrónicos essenciais para o desenvolvimento de novos detetores, que possibilitem a aquisição a três dimensões, com uma menor dose de radiação ionizante, surgem com grande expressão em todo o trabalho de investigação realizado no desenvolvimento na área da imagiologia médica. Este incide não só no sentido de restringir ao máximo a zona sobre a qual incide a radiação, mas também no sentido de dar novas ferramentas de diagnóstico para casos onde este é mais difícil, sobretudo quando relativo a mamas de maior densidade. Nesse sentido, e como forma de obter informação complementar, a tomografia computorizada (TC) por raios X – que fornece informação anatómica tridimensional – e a tomografia computorizada por emissão de fotão único (TCEFU), que ao ser aplicada em específico ao exame da mama toma o nome de mamografia por emissão de fotão único (MEFU) – que providencia informação funcional tridimensional – são duas modalidades que podem ser utilizadas em sistemas dedicados, como forma de meio de diagnóstico complementar, combatendo assim as limitações inerentes à mamografia. Nesta dissertaçãio, é apresentada uma solução que, por meio da incorporação de dois sistemas dedicados das modalidades acima mencionadas, tem como objetivo a implementação através de simulações de Monte Carlo (MC), com recurso ao programa Geant4 Application for Emission Tomography (GATE) que possui a sua própria linguagem macro dedicada para desenvolvimento de simulações de MC. Este programa, pela incorporação de outros programas externos a si (CLHEP, ROOT, for GEometry ANd Tracking (Geant4)), permite projetar simulações complexas, combinando a vantagem da utilização do Geant4 - com os seus processos físicos bem validados e geometria sofisticada - com funcionalidades próprias para tomografia de emissão. Uma vez que o GATE utiliza uma linguagem própria, a necessidade de uma programação de outra forma exaustiva em C++ é eliminada, necessidade essa que seria uma realidade caso fosse usado o Geant4 diretamente. Utilizando um fantoma cilíndrico com 35 mm de raio e 150 mm de altura, com composição semelhante a tecido mamário, foram realizadas simulações para ambas as modalidades, onde foram colocadas massas tumorais compostas por alumínio, ao longo de várias posições no mesmo eixo, de forma a avaliar a qualidade da imagem conseguida através da aquisição por parte destes equipamentos. A simulação de TC foi efetuada colocando no interior do fantoma 5 massas tumorais com 5 mm de raio equidistantes entre si ao longo do eixo do e do , resultando numa disposição em L. A aquisição foi adquirida em 16 projeções de 10 s a 180o do cilindro, totalizando um tempo total de 160 s. De forma a englobar 360o em torno do fantoma as projeções obtidas foram posteriormente espelhadas e incorporados no resultado final, aproveitando a simetria simétrica do mesmo. A disposição em L permitiu assim verificar a qualidade da imagem reconstruída relativamente a dois tipos de distância em relação ao centro do detetor de 192x242x4 mm, compostos por pixéis quadrangulares de dimensões 0.508x0.508x4 mm. Para o MEFU foi utilizado o detetor desenvolvido pelo Dr. Ricardo Capote, utilizando os mesmos parâmetros de aquisição utilizados no trabalho desenvolvido pelo Dr. Ricardo Capote, composto por duas câmaras gama de 64x151.2x188.5 mm, constituídos por cristais pixelizados de LYSO, sendo que cada um tinha 20x2x2 mm. De forma a direcionar a radiação gama a detetar estas câmaras utilizavam também colimadores convergentes. Tal como no trabalho do Dr. Ricardo Capote foram feitas simulações com 64 projeções por câmara ao longo de uma órbita circular, totalizando 10 minutos de duração de exame. No entanto, ao contrário do que aconteceu para a modalidade de TC, apenas se realizaram simulações onde foram inseridas no interior massas tumorais que variavam a sua posição relativa, apenas em uma coordenada. Os ficheiros finais da TC foram posteriormente processados com recurso a um ficheiro de C++, utilizando comandos próprios do programa ROOT, de forma a extrair as projeções da imagem, sendo posteriormente feita a sua reconstrução tridimensional utilizando o algoritmo analítico Filtered BackProjection (FBP), implementado no MATLAB®. De forma similar, os resultados da MEFU foram tratados por um ficheiro .C que extraía as contagens nos detetores a partir do ficheiro resultado das simulações, sendo estes posteriormente reconstruídos tridimensionalmente com recurso ao algoritmo iterativo Maximum Likelihood Expectation Maximization (MLEM). Após ser feita a reconstrução de ambas as modalidades, os resultados foram validados por meio da utilização de métricas não-absolutas relativas apenas para a TC, nomeadamente o contraste e o rácio entre o contraste e o ruído. Os resultados obtidos demonstraram uma degradação da imagem do centro do detetor para a periferia, degradação essa que seria o expectável tendo em conta a geometria de toda a simulação. Desta forma, foram implementados ambos sistemas com a visualização de um fantoma cilíndrico simples. As métricas utilizadas para avaliação na TC comprovaram a sua viabilidade. No entanto, o desenvolvimento destes sistemas, teve como principal objetivo permitir a possibilidade de ser realizada uma futura implementação que incorporasse as duas modalidades, dando assim dois tipos de informação complementares no mesmo exame. De modo a que o modelo pudesse ser utilizado em ocasiões futuras, e até como ponto de referência para a utilização do próprio GATE em qualquer projeto, a metodologia empregue foi descrita exaustivamente. Espera-se que o modelo elaborado no decorrer deste trabalho, apesar dos resultados de MEFU não terem sido os melhores, possa servir como ponto de partida para novos estudos. Estudos futuros poderão incorporar algoritmos mais complexos de reconstrução, ou ainda efetuar a adaptação das simulações de MC para utilização computação em GPU, utilizando fantomas voxelizados, podendo assim diminuir drasticamente o tempo de computação das simulações

X-RAY SPECTRAL ANALYSIS IN X-RAY FLUORESCENCE IMAGING FOR BREAST CANCER DETECTION

The knowledge of X-ray spectrum plays a major role in exploiting and optimizing the X-ray utilizations, especially in biomedical application fields. Over the past decades, extensive research efforts have been made in better characterizing the X-ray spectral features in experimental and simulation studies. The objectives of this dissertation are to investigate the applications of X-ray spectral measurement and analysis in X-ray fluorescence (XRF) and micro-computed tomography (micro-CT) imaging modalities, to facilitate the development of new imaging modalities or to optimize the imaging performance of currently available imaging systems. The structure and primary discoveries of this dissertation are as follows: after a brief introduction of the objectives of this dissertation in Chapter 1, Chapter 2 gives a comprehensive background including electromagnetic properties, various applications, and different generation mechanisms of X-rays and their interactions with matter, X-ray spectral measurement and analysis methods, XRF principles and applications for cancer detection, and micro-CT system. Considering relatively high fluorescence production probability and sufficient penetrability of gold Kα fluorescence signals, Chapter 3 establishes a theoretical model of a gold nanoparticle (GNP) K-shell XRF imaging prototype consisting of a pencil-beam X-ray for excitation and a single collimated spectrometer for XRF detection. Then, the optimal energy windows of 66.99±0.56keV and 68.80±0.56keV for two gold Kα fluorescence peaks are determined in Chapter 4. Also, the linear interpolation method for background estimation under the Kα fluorescence peaks is suggested in this chapter. Chapters 5 and 6 propose a novel XRF based imaging modality, X-ray fluorescence mapping (XFM) for the purpose of breast cancer detection, especially emphasizing on the detection of breast tumor located posteriorly, close to the chest wall musculature. The mapping results in these two chapters match well with the known spatial distributions and different GNP concentrations in 2D/3D reconstructions. Chapter 7 presents a method for determining the modulation transfer function (MTF) in XRF imaging modality, evaluating and improving the imaging performance of XFM. Moreover, this dissertation also investigates the importance of X-ray spectral measurement and analysis in a rotating gantry based micro-CT system. A practical alignment method for X-ray spectral measurement is first proposed using 3D printing technology in Chapter 8. With the measured results and corresponding spectral analysis, Chapter 9 further evaluates the impact of spectral filtrations on image quality indicators such as CT number uniformity, noise, and contrast to noise ratio (CNR) in the micro-CT system using a mouse phantom comprising 11 rods for modeling lung, muscle, adipose, and bones (various densities). With a baseline of identical entrance exposure to the imaged mouse phantom, the CNRs are degraded with improved beam quality for bone with high density and soft tissue, while are enhanced for bone with low density, lung, and muscle. Finally, Chapter 10 summarizes the whole dissertation and prospects the future research directions

Evaluation of the UCL Compton camera imaging performance

This thesis presents the imaging performance of the University College London (UCL) High Purity Germanium (HPGe) Compton camera. This work is a part of an ongoing project to develop a Compton camera for medical applications. The Compton camera offers many potential advantages over other imaging modalities used in nuclear medicine. These advantages include a wide field of view, the ability to reconstruct 3D images without tomography, and the fact that the camera can have a portable lightweight design due to absence of heavy collimation. The camera was constructed by ORTEC and the readout electronics used are based on GRT4 electronics boards (Daresbury, UK). The camera 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 4x4 mm2. The imaging performance with different gamma-ray source energies was evaluated experimentally and compared to the theoretical estimations. Images have been taken for a variety of test objects including point, ring source and Perspex cylindrical phantom. The measured angular resolution is 7.8° ± 0.4 for 662 keV gamma-ray source at 5 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. In principle, the Compton camera potentially has high sensitivity but this is not recognized in practice due to the limited maximum count rate. Although there are a number of limitations in the current prototype camera some potentially useful qualities have been demonstrated and distributed sources have been imaged. The key limitations in the current prototype are acquisition time, processing time and image viii reconstruction. However, techniques are available to significantly improve and overcome these limitations. This thesis presents the current state of the Compton camera performance along with a demonstration of its strengths and limitations as a potential candidate for nuclear medicine imaging

Evaluation of a diffraction-enhanced imaging (DEI) prototype and exploration of novel applications for clinical implementation of DEI

Conventional mammographic image contrast is derived from x-ray absorption, resulting in breast structure visualization due to density gradients that attenuate radiation without distinction between transmitted, scattered, or refracted x-rays. Diffraction-enhanced imaging (DEI) allows for increased contrast with decreased radiation dose compared to conventional mammographic imaging due to monochromatic x-rays, its unique refraction-based contrast mechanism, and excellent scatter rejection. Although laboratory breast imaging studies have demonstrated excellent breast imaging, important clinical translation and application studies are needed before the DEI system can be established as a useful breast imaging modality. This dissertation focuses on several important studies toward the development of a clinical DEI system. First, contrast-enhanced DEI was explored using commercially available contrast agents. Phantoms were imaged at a range of x-ray energies and relevant contrast agent concentrations. Second, we performed a reader study to determine if superior DEI contrast mechanisms preserve image quality as tissue thickness increases. Breast specimens were imaged at several thicknesses, and radiologist perception of lesion visibility was recorded. Lastly, a prototype DEI system utilizing an x-ray tube source was evaluated through a reader study. Breast tissue specimens were imaged on the traditional and prototype DEI systems, and expert radiologists evaluated image quality and pathology correlation. This dissertation will demonstrate proof-of-principle for contrast-enhanced DEI, establishing the feasibility of contrast-enhanced DEI using commercially available contrast agents. Further, it will show that DEI might be able to reduce breast compression, and thus the perception of pain during mammography, without significantly decreasing breast lesion visibility. Finally, this research shows the successful implementation of a DEI prototype, displaying breast features with approximately statistically equivalent visibility to the traditional DEI system. Together, this research is an important step toward the clinical translation of DEI, a technology with the potential to facilitate early breast cancer detection and diagnosis