Analysis of contrast-enhanced medical images.

Early detection of human organ diseases is of great importance for the accurate diagnosis and institution of appropriate therapies. This can potentially prevent progression to end-stage disease by detecting precursors that evaluate organ functionality. In addition, it also assists the clinicians for therapy evaluation, tracking diseases progression, and surgery operations. Advances in functional and contrast-enhanced (CE) medical images enabled accurate noninvasive evaluation of organ functionality due to their ability to provide superior anatomical and functional information about the tissue-of-interest. The main objective of this dissertation is to develop a computer-aided diagnostic (CAD) system for analyzing complex data from CE magnetic resonance imaging (MRI). The developed CAD system has been tested in three case studies: (i) early detection of acute renal transplant rejection, (ii) evaluation of myocardial perfusion in patients with ischemic heart disease after heart attack; and (iii), early detection of prostate cancer. However, developing a noninvasive CAD system for the analysis of CE medical images is subject to multiple challenges, including, but are not limited to, image noise and inhomogeneity, nonlinear signal intensity changes of the images over the time course of data acquisition, appearances and shape changes (deformations) of the organ-of-interest during data acquisition, determination of the best features (indexes) that describe the perfusion of a contrast agent (CA) into the tissue. To address these challenges, this dissertation focuses on building new mathematical models and learning techniques that facilitate accurate analysis of CAs perfusion in living organs and include: (i) accurate mathematical models for the segmentation of the object-of-interest, which integrate object shape and appearance features in terms of pixel/voxel-wise image intensities and their spatial interactions; (ii) motion correction techniques that combine both global and local models, which exploit geometric features, rather than image intensities to avoid problems associated with nonlinear intensity variations of the CE images; (iii) fusion of multiple features using the genetic algorithm. The proposed techniques have been integrated into CAD systems that have been tested in, but not limited to, three clinical studies. First, a noninvasive CAD system is proposed for the early and accurate diagnosis of acute renal transplant rejection using dynamic contrast-enhanced MRI (DCE-MRI). Acute rejection–the immunological response of the human immune system to a foreign kidney–is the most sever cause of renal dysfunction among other diagnostic possibilities, including acute tubular necrosis and immune drug toxicity. In the U.S., approximately 17,736 renal transplants are performed annually, and given the limited number of donors, transplanted kidney salvage is an important medical concern. Thus far, biopsy remains the gold standard for the assessment of renal transplant dysfunction, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The diagnostic results of the proposed CAD system, based on the analysis of 50 independent in-vivo cases were 96% with a 95% confidence interval. These results clearly demonstrate the promise of the proposed image-based diagnostic CAD system as a supplement to the current technologies, such as nuclear imaging and ultrasonography, to determine the type of kidney dysfunction. Second, a comprehensive CAD system is developed for the characterization of myocardial perfusion and clinical status in heart failure and novel myoregeneration therapy using cardiac first-pass MRI (FP-MRI). Heart failure is considered the most important cause of morbidity and mortality in cardiovascular disease, which affects approximately 6 million U.S. patients annually. Ischemic heart disease is considered the most common underlying cause of heart failure. Therefore, the detection of the heart failure in its earliest forms is essential to prevent its relentless progression to premature death. While current medical studies focus on detecting pathological tissue and assessing contractile function of the diseased heart, this dissertation address the key issue of the effects of the myoregeneration therapy on the associated blood nutrient supply. Quantitative and qualitative assessment in a cohort of 24 perfusion data sets demonstrated the ability of the proposed framework to reveal regional perfusion improvements with therapy, and transmural perfusion differences across the myocardial wall; thus, it can aid in follow-up on treatment for patients undergoing the myoregeneration therapy. Finally, an image-based CAD system for early detection of prostate cancer using DCE-MRI is introduced. Prostate cancer is the most frequently diagnosed malignancy among men and remains the second leading cause of cancer-related death in the USA with more than 238,000 new cases and a mortality rate of about 30,000 in 2013. Therefore, early diagnosis of prostate cancer can improve the effectiveness of treatment and increase the patient’s chance of survival. Currently, needle biopsy is the gold standard for the diagnosis of prostate cancer. However, it is an invasive procedure with high costs and potential morbidity rates. Additionally, it has a higher possibility of producing false positive diagnosis due to relatively small needle biopsy samples. Application of the proposed CAD yield promising results in a cohort of 30 patients that would, in the near future, represent a supplement of the current technologies to determine prostate cancer type. The developed techniques have been compared to the state-of-the-art methods and demonstrated higher accuracy as shown in this dissertation. The proposed models (higher-order spatial interaction models, shape models, motion correction models, and perfusion analysis models) can be used in many of today’s CAD applications for early detection of a variety of diseases and medical conditions, and are expected to notably amplify the accuracy of CAD decisions based on the automated analysis of CE images

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Validation of 3\u27-deoxy-3\u27-[18F]-fluorothymidine positron emission tomography for image-guidance in biologically adaptive radiotherapy

Accelerated tumor cell repopulation during radiation therapy is one of the leading causes for low survival rates of head-and-neck cancer patients. The therapeutic effectiveness of radiotherapy could be improved by selectively targeting proliferating tumor subvolumes with higher doses of radiation. Positron emission tomography (PET) imaging with 3´-deoxy-3´-[18F]-fluorothymidine (FLT) has shown great potential as a non-invasive approach to characterizing the proliferation status of tumors. This thesis focuses on histopathological validation of FLT PET imaging specifically for image-guidance applications in biologically adaptive radiotherapy. The lack of experimental data supporting the use of FLT PET imaging for radiotherapy guidance is addressed by developing a novel methodology for histopathological validation of PET imaging. Using this new approach, the spatial concordance between the intratumoral pattern of FLT uptake and the spatial distribution of cell proliferation is demonstrated in animal tumors. First, a two-dimensional analysis is conducted comparing the microscopic FLT uptake as imaged with autoradiography and the distribution of active cell proliferation markers imaged with immunofluorescent microscopy. It was observed that when tumors present a pattern of cell proliferation that is highly dispersed throughout the tumor, even high-resolution imaging modalities such as autoradiography could not accurately determine the extent and spatial distribution of proliferative tumor subvolumes. While microscopic spatial coincidence between high FLT uptake regions and actively proliferative subvolumes was demonstrated in tumors with highly compartmentalized/aggregated features of cell proliferation, there were no conclusive results across the entire set of utilized tumor specimens. This emphasized the need for addressing the limited resolution of FLT PET when imaging microscopic patterns of cell proliferation. This issue was emphasized in the second part of the thesis where the spatial concordance between volumes segmented on FLT simulated FLT PET images and the three dimensional spatial distribution of cell proliferation markers was analyzed

COMPUTER AIDED SYSTEM FOR BREAST CANCER DIAGNOSIS USING CURVELET TRANSFORM

Breast cancer is a leading cause of death among women worldwide. Early detection is the key for improving breast cancer prognosis. Digital mammography remains one of the most suitable tools for early detection of breast cancer. Hence, there are strong needs for the development of computer aided diagnosis (CAD) systems which have the capability to help radiologists in decision making. The main goal is to increase the diagnostic accuracy rate. In this thesis we developed a computer aided system for the diagnosis and detection of breast cancer using curvelet transform. Curvelet is a multiscale transform which possess directionality and anisotropy, and it breaks some inherent limitations of wavelet in representing edges in images. We started this study by developing a diagnosis system. Five feature extraction methods were developed with curvelet and wavelet coefficients to differentiate between different breast cancer classes. The results with curvelet and wavelet were compared. The experimental results show a high performance of the proposed methods and classification accuracy rate achieved 97.30%. The thesis then provides an automatic system for breast cancer detection. An automatic thresholding algorithm was used to separate the area composed of the breast and the pectoral muscle from the background of the image. Subsequently, a region growing algorithm was used to locate the pectoral muscle and suppress it from the breast. Then, the work concentrates on the segmentation of region of interest (ROI). Two methods are suggested to accomplish the segmentation stage: an adaptive thresholding method and a pattern matching method. Once the ROI has been identified, an automatic cropping is performed to extract it from the original mammogram. Subsequently, the suggested feature extraction methods were applied to the segmented ROIs. Finally, the K-Nearest Neighbor (KNN) and Support Vector Machine (SVM) classifiers were used to determine whether the region is abnormal or normal. At this level, the study focuses on two abnormality types (mammographic masses and architectural distortion). Experimental results show that the introduced methods have very high detection accuracies. The effectiveness of the proposed methods has been tested with Mammographic Image Analysis Society (MIAS) dataset. Throughout the thesis all proposed methods and algorithms have been applied with both curvelet and wavelet for comparison and statistical tests were also performed. The overall results show that curvelet transform performs better than wavelet and the difference is statistically significant

Computer aided detection in mammography

Tese de mestrado integrado. Engenharia Electrotécnica e de Computadores. Faculdade de Engenharia. Universidade do Porto. 201

Computer-aided detection and diagnosis of breast cancer in 2D and 3D medical imaging through multifractal analysis

This Thesis describes the research work performed in the scope of a doctoral research program and presents its conclusions and contributions. The research activities were carried on in the industry with Siemens S.A. Healthcare Sector, in integration with a research team. Siemens S.A. Healthcare Sector is one of the world biggest suppliers of products, services and complete solutions in the medical sector. The company offers a wide selection of diagnostic and therapeutic equipment and information systems. Siemens products for medical imaging and in vivo diagnostics include: ultrasound, computer tomography, mammography, digital breast tomosynthesis, magnetic resonance, equipment to angiography and coronary angiography, nuclear imaging, and many others. Siemens has a vast experience in Healthcare and at the beginning of this project it was strategically interested in solutions to improve the detection of Breast Cancer, to increase its competitiveness in the sector. The company owns several patents related with self-similarity analysis, which formed the background of this Thesis. Furthermore, Siemens intended to explore commercially the computer- aided automatic detection and diagnosis eld for portfolio integration. Therefore, with the high knowledge acquired by University of Beira Interior in this area together with this Thesis, will allow Siemens to apply the most recent scienti c progress in the detection of the breast cancer, and it is foreseeable that together we can develop a new technology with high potential. The project resulted in the submission of two invention disclosures for evaluation in Siemens A.G., two articles published in peer-reviewed journals indexed in ISI Science Citation Index, two other articles submitted in peer-reviewed journals, and several international conference papers. This work on computer-aided-diagnosis in breast led to innovative software and novel processes of research and development, for which the project received the Siemens Innovation Award in 2012. It was very rewarding to carry on such technological and innovative project in a socially sensitive area as Breast Cancer.No cancro da mama a deteção precoce e o diagnóstico correto são de extrema importância na prescrição terapêutica e caz e e ciente, que potencie o aumento da taxa de sobrevivência à doença. A teoria multifractal foi inicialmente introduzida no contexto da análise de sinal e a sua utilidade foi demonstrada na descrição de comportamentos siológicos de bio-sinais e até na deteção e predição de patologias. Nesta Tese, três métodos multifractais foram estendidos para imagens bi-dimensionais (2D) e comparados na deteção de microcalci cações em mamogramas. Um destes métodos foi também adaptado para a classi cação de massas da mama, em cortes transversais 2D obtidos por ressonância magnética (RM) de mama, em grupos de massas provavelmente benignas e com suspeição de malignidade. Um novo método de análise multifractal usando a lacunaridade tri-dimensional (3D) foi proposto para classi cação de massas da mama em imagens volumétricas 3D de RM de mama. A análise multifractal revelou diferenças na complexidade subjacente às localizações das microcalci cações em relação aos tecidos normais, permitindo uma boa exatidão da sua deteção em mamogramas. Adicionalmente, foram extraídas por análise multifractal características dos tecidos que permitiram identi car os casos tipicamente recomendados para biópsia em imagens 2D de RM de mama. A análise multifractal 3D foi e caz na classi cação de lesões mamárias benignas e malignas em imagens 3D de RM de mama. Este método foi mais exato para esta classi cação do que o método 2D ou o método padrão de análise de contraste cinético tumoral. Em conclusão, a análise multifractal fornece informação útil para deteção auxiliada por computador em mamogra a e diagnóstico auxiliado por computador em imagens 2D e 3D de RM de mama, tendo o potencial de complementar a interpretação dos radiologistas

Biomedical Image Processing and Classification

Biomedical image processing is an interdisciplinary field involving a variety of disciplines, e.g., electronics, computer science, physics, mathematics, physiology, and medicine. Several imaging techniques have been developed, providing many approaches to the study of the human body. Biomedical image processing is finding an increasing number of important applications in, for example, the study of the internal structure or function of an organ and the diagnosis or treatment of a disease. If associated with classification methods, it can support the development of computer-aided diagnosis (CAD) systems, which could help medical doctors in refining their clinical picture

Automatic BIRAD scoring of breast cancer mammograms

A computer aided diagnosis system (CAD) is developed to fully characterize and classify mass to benign and malignancy and to predict BIRAD (Breast Imaging Reporting and Data system) scores using mammographic image data. The CAD includes a preprocessing step to de-noise mammograms. This is followed by an active counter segmentation to deforms an initial curve, annotated by a radiologist, to separate and define the boundary of a mass from background. A feature extraction scheme wasthen used to fully characterize a mass by extraction of the most relevant features that have a large impact on the outcome of a patient biopsy. For this thirty-five medical and mathematical features based on intensity, shape and texture associated to the mass were extracted. Several feature selection schemes were then applied to select the most dominant features for use in next step, classification. Finally, a hierarchical classification schemes were applied on those subset of features to firstly classify mass to benign (mass with BIRAD score 2) and malignant mass (mass with BIRAD score over 4), and secondly to sub classify mass with BIRAD score over 4 to three classes (BIRAD with score 4a,4b,4c). Accuracy of segmentation performance were evaluated by calculating the degree of overlapping between the active counter segmentation and the manual segmentation, and the result was 98.5%. Also reproducibility of active counter 3 using different manual initialization of algorithm by three radiologists were assessed and result was 99.5%. Classification performance was evaluated using one hundred sixty masses (80 masses with BRAD score 2 and 80 mass with BIRAD score over4). The best result for classification of data to benign and malignance was found using a combination of sequential forward floating feature (SFFS) selection and a boosted tree hybrid classifier with Ada boost ensemble method, decision tree learner type and 100 learners’ regression tree classifier, achieving 100% sensitivity and specificity in hold out method, 99.4% in cross validation method and 98.62 % average accuracy in cross validation method. For further sub classification of eighty malignance data with BIRAD score of over 4 (30 mass with BIRAD score 4a,30 masses with BIRAD score 4b and 20 masses with BIRAD score 4c), the best result achieved using the boosted tree with ensemble method bag, decision tree learner type with 200 learners Classification, achieving 100% sensitivity and specificity in hold out method, 98.8% accuracy and 98.41% average accuracy for ten times run in cross validation method. Beside those 160 masses (BIRAD score 2 and over 4) 13 masses with BIRAD score 3 were gathered. Which means patient is recommended to be tested in another medical imaging technique and also is recommended to do follow-up in six months. The CAD system was trained with mass with BIRAD score 2 and over 4 also 4 it was further tested using 13 masses with a BIRAD score of 3 and the CAD results are shown to agree with the radiologist’s classification after confirming in six months follow up. The present results demonstrate high sensitivity and specificity of the proposed CAD system compared to prior research. The present research is therefore intended to make contributions to the field by proposing a novel CAD system, consists of series of well-selected image processing algorithms, to firstly classify mass to benign or malignancy, secondly sub classify BIRAD 4 to three groups and finally to interpret BIRAD 3 to BIRAD 2 without a need of follow up study

Evaluation of automated organ segmentation for total-body PET-CT

The ability to diagnose rapidly and accurately and treat patients is substantially facilitated by medical images. Radiologists' visual assessment of medical images is crucial to their study. Segmenting images for diagnostic purposes is a crucial step in the medical imaging process. The purpose of medical image segmentation is to locate and isolate ‘Regions of Interest’ (ROI) within a medical image. Several medical uses rely on this procedure, including diagnosis, patient management, and medical study. Medical image segmentation has applications beyond just diagnosis and treatment planning. Quantitative information from medical images can be extracted by image segmentation and employed in the research of new diagnostic and treatment procedures. In addition, image segmentation is a critical procedure in several programs for image processing, including image fusion and registration. In order to construct a single, high-resolution, high-contrast image of an item or organ from several images, a process called "image registration" is used. A more complete picture of the patient's anatomy can be obtained through image fusion, which entails integrating numerous images from different modalities such as computed tomography (CT) and Magnetic resonance imaging (MRI). Once images are obtained using imaging technologies, they go through post-processing procedures before being analyzed. One of the primary and essential steps in post-processing is image segmentation, which involves dividing the images into parts and utilizing only the relevant sections for analysis. This project explores various imaging technologies and tools that can be utilized for image segmentation. Many open-source imaging tools are available for segmenting medical images across various applications. The objective of this study is to use the Jaccard index to evaluate the degree of similarity between the segmentations produced by various medical image visualization and analysis programs