Sensitivity correction of images obtained with the prototype Clear-PEM in pre-clinical environment

Dissertation presented at Faculdade de Ciências e Tecnologia Universidade Nova de Lisboa to obtain a Master Degree in Biomedical EngineeringNuclear medicine has, when compared to anatomical imaging techniques, the great advantage of identifying the metabolic activity of the cells, hence becoming a great option for tumour identification. A new technology in this area is Positron Emission Mammography (PEM) that follows the same physical basics of Positron Emission Tomography (PET). The Clear-PEM project, a Portuguese research project, uses this technology and, in alternative to the whole-body exam, only the breast is examined, using two detector plates that rotate around the breast to detect radiation. The prototype has the ability to perform a complementary exam of the axillary region. This scanner is designed to detect small lesions or tumours in early stages, with high resolution and high sensitivity. After the acquisition, the data undergoes a process of reconstruction and corrections. It is our job to study which parameters should be adjusted in order to get the best contrast between lesions and the breast background, as well as meeting the high resolution standards we set to achieve. This work consisted in the correction of some characteristics that might influence image quality. The first correction made was the elimination of the presence of the gaps between the detector crystals’ effects, resulting in the enhancement of the image Signal-to-Noise Ratio (SNR). By varying the energy window of the image acquisitions, it was possible to minimize the effect of scattered photons, and varying the timing window minimized the effect of random coincidences

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

Reconstrução de Imagem em SPECT utilizando um colimador convergente e detectores de imagem pixelizados

Dissertação para obtenção do Grau de Mestre em Engenharia BiomédicaO desenvolvimento de sistemas dedicados com elevada resolução espacial e sensibilidade são cruciais no contexto da detecção, diagnóstico e acompanhamento da evolução do cancro da mama. O scanner Clear-PEM, desenvolvido pelo consórcio português PET-mamografia, é um sistema de imagem funcional com base na tecnologia utilizada em PET que permite detectar precocemente tumores da mama. No âmbito deste projecto pretende-se estudar a possibilidade de detecção de lesões na região do arco costal, pois estas não produzem um sinal detectável em PEM para a geometria de aquisição de imagem existente e são clinicamente relevantes dado corresponderem a zonas de tumores primários e de metastização frequente (junto à axila) do cancro da mama. A utilização do scanner Clear-PEM em modo SPECT utilizando um colimador convergente com um campo de visão que inclua estas regiões assume-se como uma solução viável para este estudo, sendo o objectivo deste trabalho desenvolver algoritmos de reconstrução para este sistema e obter uma resolução espacial de cerca de 2,5 mm. As imagens de fantomas, adquiridas com a plataforma GATE, foram reconstruídas recorrendo ao algoritmo OSEM. Após a reconstrução foram analisadas características como homogeneidade, contraste, razão sinal-ruído e resolução espacial. Os resultados obtidos neste trabalho permitiram concluir que foi possível reconstruir a região acima das cabeças detectoras com a resolução pretendida. Além disso, também permitiu constatar que se conseguem obter bons resultados com um fantoma da mama com um rácio lesão-fundo de 1:10. Neste trabalho também se verificou que por a órbitra de aquisição não verificar a condição de Tuy, surgiu alguma distorção nas imagens pelo que o trabalho futuro deve passar pela adição de uma órbita de aquisição ao sistema ou pela adopção de uma trajectória helicoidal. Após o verificar destas condições, seria interessante aplicar a correcção da atenuação de forma a se poder avançar para estudos clínicos

X-ray space technology transfer for improved mammography screening

openBreast imaging using monochromatic X-rays promises lower dose and better image quality relative to conventional approaches. Currently, the broad-energy spectrum emitted by an x-ray tube is degrading performance due to beam hardening, i.e., low energy X-rays are predominantly absorbed by the tissue, increasing dose, while high energy X-rays pass through the tissue unattenuated, decreasing image contrast. It has been proposed that the use of coated mirrors capable of mono-chromatic x-ray hard spectra have the capability of reducing ionizing radiation exposure while also improving image quality during x-ray medical screening procedures. This research study is centered around screening for breast cancer using Digital Mammography (DM) technique. We present a simplified prototype system developed at DTU Space and implemented to validate proposed designs. The experimental setup consists of a source up to 40 keV, a high resolution roto-translation mechanical support and an advanced high resolution (55 micron), energy-sensitive Si detector with quantum efficiency (20% @22 keV). For testing, phantom objects will be used as samples, allowing for a real-world realistic assessment of the use of space technology for breast screening. In this work, experimental measurements of absorbed dose reduction and contrast-to-noise ratio are reported

Multimodal breast imaging: Registration, visualization, and image synthesis

The benefit of registration and fusion of functional images with anatomical images is well appreciated in the advent of combined positron emission tomography and x-ray computed tomography scanners (PET/CT). This is especially true in breast cancer imaging, where modalities such as high-resolution and dynamic contrast-enhanced magnetic resonance imaging (MRI) and F-18-FDG positron emission tomography (PET) have steadily gained acceptance in addition to x-ray mammography, the primary detection tool. The increased interest in combined PET/MRI images has facilitated the demand for appropriate registration and fusion algorithms. A new approach to MRI-to-PET non-rigid breast image registration was developed and evaluated based on the location of a small number of fiducial skin markers (FSMs) visible in both modalities. The observed FSM displacement vectors between MRI and PET, distributed piecewise linearly over the breast volume, produce a deformed Finite-Element mesh that reasonably approximates non-rigid deformation of the breast tissue between the MRI and PET scans. The method does not require a biomechanical breast tissue model, and is robust and fast. The method was evaluated both qualitatively and quantitatively on patients and a deformable breast phantom. The procedure yields quality images with average target registration error (TRE) below 4 mm. The importance of appropriately jointly displaying (i.e. fusing) the registered images has often been neglected and underestimated. A combined MRI/PET image has the benefits of directly showing the spatial relationships between the two modalities, increasing the sensitivity, specificity, and accuracy of diagnosis. Additional information on morphology and on dynamic behavior of the suspicious lesion can be provided, allowing more accurate lesion localization including mapping of hyper- and hypo-metabolic regions as well as better lesion-boundary definition, improving accuracy when grading the breast cancer and assessing the need for biopsy. Eight promising fusion-for-visualization techniques were evaluated by radiologists from University Hospital, in Syracuse, NY. Preliminary results indicate that the radiologists were better able to perform a series of tasks when reading the fused PET/MRI data sets using color tables generated by a newly developed genetic algorithm, as compared to other commonly used schemes. The lack of a known ground truth hinders the development and evaluation of new algorithms for tasks such as registration and classification. A preliminary mesh-based breast phantom containing 12 distinct tissue classes along with tissue properties necessary for the simulation of dynamic positron emission tomography scans was created. The phantom contains multiple components which can be separately manipulated, utilizing geometric transformations, to represent populations or a single individual being imaged in multiple positions. This phantom will support future multimodal breast imaging work

Implementação de algoritmos de reconstrução de imagens de tomossíntese utilizando processamento paralelo em GPU

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Radiações em Diagnóstico e Terapia)Universidade de Lisboa, Faculdade de Ciências, 2016O cancro da mama é o tipo de cancro com maior incidência no género feminino, sendo considerado um dos maiores e mais importantes problemas de saúde pública à escala global. A mamografia é a técnica de imagem médica referência para o rastreio e diagnóstico do cancro da mama, no entanto tem associada algumas limitações bem conhecidas: elevada taxa de falsos-negativos (até 66% em mulheres sintomáticas) e falsos-positivos (até 60%). Estes dados estão sobretudo relacionados com o efeito da sobreposição de tecidos na imagem e têm vindo a gerar grande controvérsia na comunidade médica e científica, no que diz respeito ao uso da mamografia como técnica de rastreio, principalmente em mulheres mais jovens (< 50 anos). A DBT (Digital Breast Tomosynthesis) é uma técnica radiológica tridimensional que produz uma pilha de imagens paralelas que representam as várias profundidades do tecido mamário, reduzindo assim o efeito de sobreposição. Existe actualmente evidência da redução das taxas de falsos negativos e de falsos positivos associados à utilização da DBT como técnica de rastreio, quando comparadas às da mamografia digital (FFDM - Full-Field Digital Mammography), sobretudo em mulheres com tecido mamário mais denso. As imagens são reconstruídas a partir de projecções bidimensionais recorrendo a algoritmos computacionais. Estes algoritmos têm um papel fundamental no processo de reconstrução, sobretudo em contexto clínico, uma vez que há a necessidade de implementar um processo que seja simultaneamente preciso e rápido. Actualmente os algoritmos mais utilizados para reconstruir imagens DBT em ambiente clínico são os analíticos, por apresentarem rapidez e simplicidade de execução. Os algoritmos iterativos têm, no entanto, demonstrado produzir imagens de melhor qualidade. O seu uso clínico é actualmente rejeitado devido ao seu elevado tempo de reconstrução e exigência computacional. As capacidades computacionais das unidades de processamento gráfico (GPU – Graphical Processing Units), nomeadamente a capacidade de cálculo paralelo intensivo, foram já utilizadas por vários grupos de investigação para a optimização destes algoritmos iterativos. Um destes estudos foi desenvolvido no Instituto de Biofísica e Engenharia Biomédica (IBEB), na Faculdade de Ciências da Universidade de Lisboa, e consiste na implementação heterogénea (CPU+GPU) do processo de reconstrução de imagens DBT com algoritmos iterativos. Na GPU é executada um dos blocos mais exigentes de todo o algoritmo (o cálculo da matriz de sistema), por intermédio da linguagem de programação CUDA (Compute Unified Device Architecture). Esta implementação apresenta, no entanto, algumas falhas, que se reflectem em ligeiras alterações nas imagens, quando comparadas com as imagens reconstruídas pelo processo puramente sequencial (CPU). O trabalho realizado na presente dissertação visa a correcção destas falhas, de modo a eliminar as diferenças observadas nas imagens reconstruídas, e a aplicação da abordagem heterogénea a outros blocos do algoritmo, de forma a optimizar ainda mais o processo de reconstrução.Breast cancer is the most prevalent type of cancer in women, considered one of the largest and most relevant public health problems worldwide. Mammography is the state-of-the-art medical imaging technique for screening and diagnosis of breast cancer, but has some limitations: high rates of both false-positive and false-negative (up to 66 % and up to 60 %, respectively). This is mainly a result of the overlapping-tissue effect, a fact that has been generating great controversy in the medical-scientific community regarding the use of mammography as a screening technique, especially in younger women (< 50 years).DBT (Digital Breast Tomosynthesis) is a three-dimensional x-ray technique that produces a parallel stack of images representing various depths of the breast volume, thereby reducing the overlapping effect. This technique has shown a reduction in false-negative and false-positive rates, when compared with FFMD (Full-Field Digital Mammography), especially in dense breasts. Images are reconstructed from two-dimensional projections using computer algorithms. These algorithms have a central role in the reconstruction process, especially in clinical context, since it is desirable to implement a process both accurate and fast. Currently the most popular algorithms in clinical setting are analytical, because of their fast and simple execution process. However, iterative algorithms have shown to produce better quality images. The problem is they require a lot of computational capability and thus take more time to reconstruct, making them unattractive to clinical implementation. The computational capabilities of GPUs (Graphical Processing Units), namely intensive parallel computing, have been used by several research groups to optimize these iterative algorithms. One of these studies was developed at the Institute of Biophysics and Biomedical Engineering (IBEB), here at the Faculty of Sciences, and consists of heterogeneous implementation (CPU + GPU) of the DBT image reconstruction process with iterative algorithms. The GPU executes one of the heaviest blocks of the entire reconstruction process (the system matrix calculation), using CUDA (Compute Unified Device Architecture). Still, this implementation has some flaws, which are reflected in slight differences between the reconstructed images and the original ones (images reconstructed by the purely sequential process). My work aims at correcting these flaws in order to eliminate the image errors. Moreover, I intend to generalize this heterogeneous approach to another algorithm blocks, in order to further optimize the reconstruction process

Minimização do ruído em imagens de mamografia por emissão de positrões através da optimização do tempo de aquisição e do tamanho de voxel

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia BiomédicaAs principais etapas na gestão do cancro são o diagnóstico, estádio em que se encontra e avaliação e monitorização do tratamento. A Medicina Nuclear desempenha um importante papel em todos eles. De entre os procedimentos de diagnóstico e terapêutica, esta técnica é a única que oferece a possibilidade de analisar quantitativamente o comportamento dos tecidos, in vivo. A Medicina Nuclear utiliza moléculas biológicas marcadas radioactivamente, denominadas de radiofármacos (radionuclido + fármaco), para estudar os mecanismos moleculares e fisiológicos presentes, tendo por isso uma enorme importância em Oncologia. A Tomografia por Emissão de Positrões (PET, Positron Emission Tomography) é uma técnica de imagem de Medicina Nuclear que fornece informação acerca da distribuição de um radiofármaco, previamente injectado no corpo do paciente. A tecnologia PET dedicada à imagiologia da mama denomina-se Mamografia por Emissão de Positrões (PEM, Positron Emission Mammography). Actualmente, existem vários projectos em desenvolvimento no âmbito desta técnica, sendo o projecto Clear-PEM, a decorrer em Portugal, um deles. Após a aquisição dos dados do paciente, estes têm de ser reconstruídos e corrigidos para originar a imagem final utilizada em ambiente clínico. Este trabalho consiste no estudo de alguns dos parâmetros que influenciam a quantificação dessa imagem. Com a finalidade de determinar qual o tamanho de voxel que permite um melhor equilíbrio entre a resolução espacial e a Razão Sinal – Ruído nas imagens foram reconstruídas, com diferentes tamanhos de voxel, imagens de um fantoma que simula várias lesões numa mama e de fontes pontuais de radiação. Após análise de diversos tamanhos de voxel, chegou-se à conclusão que a melhor opção a utilizar no futuro corresponde a dimensões de 2,0x2,0x1,3 mm3. Por outro lado, para compensar a baixa estatística por voxel, foram também avaliados diferentes tempos de aquisição. Isto porque, tempos de aquisição muito longos podem levar a diferenças significativas de actividade medida nos tecidos, entre a primeira e a última aquisição do exame, que devem ser corrigidas. Deste modo, foi estudada a viabilidade da aplicação destas correcções. Com base nestas análises, a qualidade das imagens reconstruídas foi melhorada, aumentando o potencial de detecção de lesões de dimensões muito reduzidas com este equipamento. Seria interessante, de futuro, estudar o efeito da variação do tamanho de voxel na direcção axial e implementar um método que permita compensar as diferenças de actividade entre os diferentes eventos registados para cada aquisição de um exame, quando assim se justificar

Enhancing the image quality of digital breast tomosynthesis

A novel imaging technology, digital breast tomosynthesis (DBT), is a technique that overcomes the tissue superposition limitation of conventional mammography by acquiring a limited number of X-ray projections from a narrow angular range, and combining these projections to reconstruct a pseudo-3D image. The emergence of DBT as a potential replacement or adjunct to mammographic screening mandates that solutions be found to two of its major limitations, namely X-ray scatter and mono-energetic reconstruction methods. A multi-faceted software-based approach to enhance the image quality of DBT imaging has the potential to increase the sensitivity and specificity of breast cancer detection and diagnosis. A scatter correction (SC) algorithm and a spectral reconstruction (SR) algorithm are both ready for implementation and clinical evaluation in a DBT system and exhibit the potential to improve image quality. A principal component analysis (PCA) based model of breast shape and a PCA model of X-ray scatter optimize the SC algorithm for the clinical realm. In addition, a comprehensive dosimetric characterization of a FDA approved DBT system has also been performed, and the feasibility of a new dual-spectrum, single-acquisition DBT imaging technique has also been evaluated.Ph.D

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

A dual modality, DCE-MRI and x-ray, physical phantom for quantitative evaluation of breast imaging protocols

The current clinical standard for breast cancer screening is mammography. However, this technique has a low sensitivity which results in missed cancers. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has recently emerged as a promising technique for breast cancer diagnosis and has been reported as being superior to mammography for screening of high-risk women and evaluation of extent of disease. At the same time, low and variable specificity has been documented in the literature as well as a rising number of mastectomies possibly due to the increasing use of DCE-MRI. In this study, we developed and characterized a dual-modality, x-ray and DCE-MRI, anthropomorphic breast phantom for the quantitative assessment of breast imaging protocols. X-ray properties of the phantom were quantitatively compared with patient data, including attenuation coefficients, which matched human values to within the measurement error, and tissue structure using spatial covariance matrices of image data, which were found to be similar in size to patient data. Simulations of the phantom scatter-to-primary ratio (SPR) were produced and experimentally validated then compared with published SPR predictions for homogeneous phantoms. SPR values were as high as 85% in some areas and were heavily influenced by the heterogeneous tissue structure. MRI properties of the phantom, T1 and T2 relaxation values and tissue structure, were also quantitatively compared with patient data and found to match within two error bars. Finally, a dynamic lesion that mimics lesion border shape and washout curve shape was included in the phantom. High spatial and temporal resolution x-ray measurements of the washout curve shape were performed to determine the true contrast agent concentration as a function of time. DCE-MRI phantom measurements using a clinical imaging protocol were compared against the x-ray truth measurements. MRI signal intensity curves were shown to be less specific to lesion type than the x-ray derived contrast agent concentration curves. This phantom allows, for the first time, for quantitative evaluation of and direct comparisons between x-ray and MRI breast imaging modalities in the context of lesion detection and characterization