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

Automatic Spatiotemporal Analysis of Cardiac Image Series

RÉSUMÉ À ce jour, les maladies cardiovasculaires demeurent au premier rang des principales causes de décès en Amérique du Nord. Chez l’adulte et au sein de populations de plus en plus jeunes, la soi-disant épidémie d’obésité entraînée par certaines habitudes de vie tels que la mauvaise alimentation, le manque d’exercice et le tabagisme est lourde de conséquences pour les personnes affectées, mais aussi sur le système de santé. La principale cause de morbidité et de mortalité chez ces patients est l’athérosclérose, une accumulation de plaque à l’intérieur des vaisseaux sanguins à hautes pressions telles que les artères coronaires. Les lésions athérosclérotiques peuvent entraîner l’ischémie en bloquant la circulation sanguine et/ou en provoquant une thrombose. Cela mène souvent à de graves conséquences telles qu’un infarctus. Outre les problèmes liés à la sténose, les parois artérielles des régions criblées de plaque augmentent la rigidité des parois vasculaires, ce qui peut aggraver la condition du patient. Dans la population pédiatrique, la pathologie cardiovasculaire acquise la plus fréquente est la maladie de Kawasaki. Il s’agit d’une vasculite aigüe pouvant affecter l’intégrité structurale des parois des artères coronaires et mener à la formation d’anévrismes. Dans certains cas, ceux-ci entravent l’hémodynamie artérielle en engendrant une perfusion myocardique insuffisante et en activant la formation de thromboses. Le diagnostic de ces deux maladies coronariennes sont traditionnellement effectués à l’aide d’angiographies par fluoroscopie. Pendant ces examens paracliniques, plusieurs centaines de projections radiographiques sont acquises en séries suite à l’infusion artérielle d’un agent de contraste. Ces images révèlent la lumière des vaisseaux sanguins et la présence de lésions potentiellement pathologiques, s’il y a lieu. Parce que les séries acquises contiennent de l’information très dynamique en termes de mouvement du patient volontaire et involontaire (ex. battements cardiaques, respiration et déplacement d’organes), le clinicien base généralement son interprétation sur une seule image angiographique où des mesures géométriques sont effectuées manuellement ou semi-automatiquement par un technicien en radiologie. Bien que l’angiographie par fluoroscopie soit fréquemment utilisé partout dans le monde et souvent considéré comme l’outil de diagnostic “gold-standard” pour de nombreuses maladies vasculaires, la nature bidimensionnelle de cette modalité d’imagerie est malheureusement très limitante en termes de spécification géométrique des différentes régions pathologiques. En effet, la structure tridimensionnelle des sténoses et des anévrismes ne peut pas être pleinement appréciée en 2D car les caractéristiques observées varient selon la configuration angulaire de l’imageur. De plus, la présence de lésions affectant les artères coronaires peut ne pas refléter la véritable santé du myocarde, car des mécanismes compensatoires naturels (ex. vaisseaux----------ABSTRACT Cardiovascular disease continues to be the leading cause of death in North America. In adult and, alarmingly, ever younger populations, the so-called obesity epidemic largely driven by lifestyle factors that include poor diet, lack of exercise and smoking, incurs enormous stresses on the healthcare system. The primary cause of serious morbidity and mortality for these patients is atherosclerosis, the build up of plaque inside high pressure vessels like the coronary arteries. These lesions can lead to ischemic disease and may progress to precarious blood flow blockage or thrombosis, often with infarction or other severe consequences. Besides the stenosis-related outcomes, the arterial walls of plaque-ridden regions manifest increased stiffness, which may exacerbate negative patient prognosis. In pediatric populations, the most prevalent acquired cardiovascular pathology is Kawasaki disease. This acute vasculitis may affect the structural integrity of coronary artery walls and progress to aneurysmal lesions. These can hinder the blood flow’s hemodynamics, leading to inadequate downstream perfusion, and may activate thrombus formation which may lead to precarious prognosis. Diagnosing these two prominent coronary artery diseases is traditionally performed using fluoroscopic angiography. Several hundred serial x-ray projections are acquired during selective arterial infusion of a radiodense contrast agent, which reveals the vessels’ luminal area and possible pathological lesions. The acquired series contain highly dynamic information on voluntary and involuntary patient movement: respiration, organ displacement and heartbeat, for example. Current clinical analysis is largely limited to a single angiographic image where geometrical measures will be performed manually or semi-automatically by a radiological technician. Although widely used around the world and generally considered the gold-standard diagnosis tool for many vascular diseases, the two-dimensional nature of this imaging modality is limiting in terms of specifying the geometry of various pathological regions. Indeed, the 3D structures of stenotic or aneurysmal lesions may not be fully appreciated in 2D because their observable features are dependent on the angular configuration of the imaging gantry. Furthermore, the presence of lesions in the coronary arteries may not reflect the true health of the myocardium, as natural compensatory mechanisms may obviate the need for further intervention. In light of this, cardiac magnetic resonance perfusion imaging is increasingly gaining attention and clinical implementation, as it offers a direct assessment of myocardial tissue viability following infarction or suspected coronary artery disease. This type of modality is plagued, however, by motion similar to that present in fluoroscopic imaging. This issue predisposes clinicians to laborious manual intervention in order to align anatomical structures in sequential perfusion frames, thus hindering automation o

Automatic Spatiotemporal Analysis of Cardiac Image Series

RÉSUMÉ À ce jour, les maladies cardiovasculaires demeurent au premier rang des principales causes de décès en Amérique du Nord. Chez l’adulte et au sein de populations de plus en plus jeunes, la soi-disant épidémie d’obésité entraînée par certaines habitudes de vie tels que la mauvaise alimentation, le manque d’exercice et le tabagisme est lourde de conséquences pour les personnes affectées, mais aussi sur le système de santé. La principale cause de morbidité et de mortalité chez ces patients est l’athérosclérose, une accumulation de plaque à l’intérieur des vaisseaux sanguins à hautes pressions telles que les artères coronaires. Les lésions athérosclérotiques peuvent entraîner l’ischémie en bloquant la circulation sanguine et/ou en provoquant une thrombose. Cela mène souvent à de graves conséquences telles qu’un infarctus. Outre les problèmes liés à la sténose, les parois artérielles des régions criblées de plaque augmentent la rigidité des parois vasculaires, ce qui peut aggraver la condition du patient. Dans la population pédiatrique, la pathologie cardiovasculaire acquise la plus fréquente est la maladie de Kawasaki. Il s’agit d’une vasculite aigüe pouvant affecter l’intégrité structurale des parois des artères coronaires et mener à la formation d’anévrismes. Dans certains cas, ceux-ci entravent l’hémodynamie artérielle en engendrant une perfusion myocardique insuffisante et en activant la formation de thromboses. Le diagnostic de ces deux maladies coronariennes sont traditionnellement effectués à l’aide d’angiographies par fluoroscopie. Pendant ces examens paracliniques, plusieurs centaines de projections radiographiques sont acquises en séries suite à l’infusion artérielle d’un agent de contraste. Ces images révèlent la lumière des vaisseaux sanguins et la présence de lésions potentiellement pathologiques, s’il y a lieu. Parce que les séries acquises contiennent de l’information très dynamique en termes de mouvement du patient volontaire et involontaire (ex. battements cardiaques, respiration et déplacement d’organes), le clinicien base généralement son interprétation sur une seule image angiographique où des mesures géométriques sont effectuées manuellement ou semi-automatiquement par un technicien en radiologie. Bien que l’angiographie par fluoroscopie soit fréquemment utilisé partout dans le monde et souvent considéré comme l’outil de diagnostic “gold-standard” pour de nombreuses maladies vasculaires, la nature bidimensionnelle de cette modalité d’imagerie est malheureusement très limitante en termes de spécification géométrique des différentes régions pathologiques. En effet, la structure tridimensionnelle des sténoses et des anévrismes ne peut pas être pleinement appréciée en 2D car les caractéristiques observées varient selon la configuration angulaire de l’imageur. De plus, la présence de lésions affectant les artères coronaires peut ne pas refléter la véritable santé du myocarde, car des mécanismes compensatoires naturels (ex. vaisseaux----------ABSTRACT Cardiovascular disease continues to be the leading cause of death in North America. In adult and, alarmingly, ever younger populations, the so-called obesity epidemic largely driven by lifestyle factors that include poor diet, lack of exercise and smoking, incurs enormous stresses on the healthcare system. The primary cause of serious morbidity and mortality for these patients is atherosclerosis, the build up of plaque inside high pressure vessels like the coronary arteries. These lesions can lead to ischemic disease and may progress to precarious blood flow blockage or thrombosis, often with infarction or other severe consequences. Besides the stenosis-related outcomes, the arterial walls of plaque-ridden regions manifest increased stiffness, which may exacerbate negative patient prognosis. In pediatric populations, the most prevalent acquired cardiovascular pathology is Kawasaki disease. This acute vasculitis may affect the structural integrity of coronary artery walls and progress to aneurysmal lesions. These can hinder the blood flow’s hemodynamics, leading to inadequate downstream perfusion, and may activate thrombus formation which may lead to precarious prognosis. Diagnosing these two prominent coronary artery diseases is traditionally performed using fluoroscopic angiography. Several hundred serial x-ray projections are acquired during selective arterial infusion of a radiodense contrast agent, which reveals the vessels’ luminal area and possible pathological lesions. The acquired series contain highly dynamic information on voluntary and involuntary patient movement: respiration, organ displacement and heartbeat, for example. Current clinical analysis is largely limited to a single angiographic image where geometrical measures will be performed manually or semi-automatically by a radiological technician. Although widely used around the world and generally considered the gold-standard diagnosis tool for many vascular diseases, the two-dimensional nature of this imaging modality is limiting in terms of specifying the geometry of various pathological regions. Indeed, the 3D structures of stenotic or aneurysmal lesions may not be fully appreciated in 2D because their observable features are dependent on the angular configuration of the imaging gantry. Furthermore, the presence of lesions in the coronary arteries may not reflect the true health of the myocardium, as natural compensatory mechanisms may obviate the need for further intervention. In light of this, cardiac magnetic resonance perfusion imaging is increasingly gaining attention and clinical implementation, as it offers a direct assessment of myocardial tissue viability following infarction or suspected coronary artery disease. This type of modality is plagued, however, by motion similar to that present in fluoroscopic imaging. This issue predisposes clinicians to laborious manual intervention in order to align anatomical structures in sequential perfusion frames, thus hindering automation o

A non-invasive image based system for early diagnosis of prostate cancer.

Prostate cancer is the second most fatal cancer experienced by American males. The average American male has a 16.15% chance of developing prostate cancer, which is 8.38% higher than lung cancer, the second most likely cancer. The current in-vitro techniques that are based on analyzing a patients blood and urine have several limitations concerning their accuracy. In addition, the prostate Specific Antigen (PSA) blood-based test, has a high chance of false positive diagnosis, ranging from 28%-58%. Yet, biopsy remains the gold standard for the assessment of prostate cancer, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The major limitation of the relatively small needle biopsy samples is the higher possibility of producing false positive diagnosis. Moreover, the visual inspection system (e.g., Gleason grading system) is not quantitative technique and different observers may classify a sample differently, leading to discrepancies in the diagnosis. As reported in the literature that the early detection of prostate cancer is a crucial step for decreasing prostate cancer related deaths. Thus, there is an urgent need for developing objective, non-invasive image based technology for early detection of prostate cancer. The objective of this dissertation is to develop a computer vision methodology, later translated into a clinically usable software tool, which can improve sensitivity and specificity of early prostate cancer diagnosis based on the well-known hypothesis that malignant tumors are will connected with the blood vessels than the benign tumors. Therefore, using either Diffusion Weighted Magnetic Resonance imaging (DW-MRI) or Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), we will be able to interrelate the amount of blood in the detected prostate tumors by estimating either the Apparent Diffusion Coefficient (ADC) in the prostate with the malignancy of the prostate tumor or perfusion parameters. We intend to validate this hypothesis by demonstrating that automatic segmentation of the prostate from either DW-MRI or DCE-MRI after handling its local motion, provides discriminatory features for early prostate cancer diagnosis. The proposed CAD system consists of three majors components, the first two of which constitute new research contributions to a challenging computer vision problem. The three main components are: (1) A novel Shape-based segmentation approach to segment the prostate from either low contrast DW-MRI or DCE-MRI data; (2) A novel iso-contours-based non-rigid registration approach to ensure that we have voxel-on-voxel matches of all data which may be more difficult due to gross patient motion, transmitted respiratory effects, and intrinsic and transmitted pulsatile effects; and (3) Probabilistic models for the estimated diffusion and perfusion features for both malignant and benign tumors. Our results showed a 98% classification accuracy using Leave-One-Subject-Out (LOSO) approach based on the estimated ADC for 30 patients (12 patients diagnosed as malignant; 18 diagnosed as benign). These results show the promise of the proposed image-based diagnostic technique as a supplement to current technologies for diagnosing prostate cancer

Doctor of Philosophy

dissertationImage-based biomechanics, particularly numerical modeling using subject-specific data obtained via imaging, has proven useful for elucidating several biomechanical processes, such as prediction of deformation due to external loads, applicable to both normal function and pathophysiology of various organs. As the field evolves towards applications that stretch the limits of imaging hardware and acquisition time, the information traditionally expected as input for numerical routines often becomes incomplete or ambiguous, and requires specific acquisition and processing strategies to ensure physical accuracy and compatibility with predictive mathematical modeling. These strategies, often derivatives or specializations of traditional mechanics, effectively extend the nominal capability of medical imaging hardware providing subject-specific information coupled with the option of using the results for predictive numerical simulations. This research deals with the development of tools for extracting mechanical measurements from a finite set of imaging data and finite element analysis in the context of constructing structural atlases of the heart, understanding the biomechanics of the venous vasculature, and right ventricular failure. The tools include: (1) application of Hyperelastic Warping image registration to displacement-encoded MRI for reconstructing absolute displacement fields, (2) combination of imaging and a material parameter identification approach to measure morphology, deformation, and mechanical properties of vascular tissue, and (3) extrapolation of diffusion tensor MRI acquired at a single time point for the prediction the structural changes across the cardiac cycle with mechanical simulations. Selected tools were then applied to evaluate structural changes in a reversible animal model for right ventricular failure due to pressure overload

Clinical quantitative cardiac imaging for the assessment of myocardial ischaemia

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality

A novel MRA-based framework for the detection of changes in cerebrovascular blood pressure.

Background: High blood pressure (HBP) affects 75 million adults and is the primary or contributing cause of mortality in 410,000 adults each year in the United States. Chronic HBP leads to cerebrovascular changes and is a significant contributor for strokes, dementia, and cognitive impairment. Non-invasive measurement of changes in cerebral vasculature and blood pressure (BP) may enable physicians to optimally treat HBP patients. This manuscript describes a method to non-invasively quantify changes in cerebral vasculature and BP using Magnetic Resonance Angiography (MRA) imaging. Methods: MRA images and BP measurements were obtained from patients (n=15, M=8, F=7, Age= 49.2 ± 7.3 years) over a span of 700 days. A novel segmentation algorithm was developed to identify brain vasculature from surrounding tissue. The data was processed to calculate the vascular probability distribution function (PDF); a measure of the vascular diameters in the brain. The initial (day 0) PDF and final (day 700) PDF were used to correlate the changes in cerebral vasculature and BP. Correlation was determined by a mixed effects linear model analysis. Results: The segmentation algorithm had a 99.9% specificity and 99.7% sensitivity in identifying and delineating cerebral vasculature. The PDFs had a statistically significant correlation to BP changes below the circle of Willis (p-value = 0.0007), but not significant (p-value = 0.53) above the circle of Willis, due to smaller blood vessels. Conclusion: Changes in cerebral vasculature and pressure can be non-invasively obtained through MRA image analysis, which may be a useful tool for clinicians to optimize medical management of HBP

Computer Aided Analysis of Late Gadolinium Enhanced Cardiac MRI

Ph.DDOCTOR OF PHILOSOPH

Analysis of cardiac motion using MRI and nonrigid image registration

Imperial Users onl