Data registration and fusion for cardiac applications

The registration and fusion of information from multiple cardiac image modalities such as magnetic resonance imaging (MRI), X-ray computed tomography (CT), positron emission tomography (PET) and single photon emission computed tomography (SPECT) has been of increasing interest to the medical community as tools for furthering physiological understanding and for diagnostic of ischemic heart diseases. Ischemic heart diseases and their consequence, myocardial infarct, are the leading cause of mortality in industrial countries. In cardiac image registration and data fusion, the combination of structural information from MR images and functional information from PET and SPECT is of special interest in the estimation of myocardial function and viability. Cardiac image registration is a more complex problem than brain image registration. The non-rigid motion of the heart and the thorax structures introduce additional difficulties in registration. In this thesis the goal was develop methods for cardiac data registration and fusion. A rigid registration method was developed to register cardiac MR and PET images. The method was based on the registration of the segmented thorax structures from MR and PET transmission images. The thorax structures were segmented from images using deformable models. A MR short axis registration with PET emission image was also derived. The rigid registration method was evaluated using simulated images and clinical MR and PET images from ten patients with multivessel coronary artery diseases. Also an elastic registration method was developed to register intra-patient cardiac MR and PET images and inter-patient head MR images. In the elastic registration method, a combination of mutual information, gradient information and smoothness of transformation was used to guide the deformation of one image towards another image. An approach for the creation of 3-D functional maps of the heart was also developed. An individualized anatomical heart model was extracted from the MR images. A rigid registration of anatomical MR images and PET metabolic images was carried out using surface based registration, and the registration of MR images with magnetocardiography (MCG) data using external markers. The method resulted in a 3-D anatomical and functional model of the heart that included structural information from the MRI and functional information from the PET and MCG. Different error sources in the registration method of the MR images and MCG data was also evaluated in this thesis. The results of the rigid MR-PET registration method were also used in the comparison of multimodality MR imaging methods to PET.reviewe

Computer image registration techniques applied to nuclear medicine images

Modern medicine has been using imaging as a fundamental tool in a wide range of applications. Consequently, the interest in automated registration of images from either the same or different modalities has increased. In this chapter, computer techniques of image registration are reviewed, and cover both their classification and the main steps involved. Moreover, the more common geometrical transforms, optimization and interpolation algorithms are described and discussed. The clinical applications examined emphases nuclear medicine

MRI-Based Attenuation Correction in Emission Computed Tomography

The hybridization of magnetic resonance imaging (MRI) with positron emission tomography (PET) or single photon emission computed tomography (SPECT) enables the collection of an assortment of biological data in spatial and temporal register. However, both PET and SPECT are subject to photon attenuation, a process that degrades image quality and precludes quantification. To correct for the effects of attenuation, the spatial distribution of linear attenuation coefficients (μ-coefficients) within and about the patient must be available. Unfortunately, extracting μ-coefficients from MRI is non-trivial. In this thesis, I explore the problem of MRI-based attenuation correction (AC) in emission tomography. In particular, I began by asking whether MRI-based AC would be more reliable in PET or in SPECT. To this end, I implemented an MRI-based AC algorithm relying on image segmentation and applied it to phantom and canine emission data. The subsequent analysis revealed that MRI-based AC performed better in SPECT than PET, which is interesting since AC is more challenging in SPECT than PET. Given this result, I endeavoured to improve MRI-based AC in PET. One problem that required addressing was that the lungs yield very little signal in MRI, making it difficult to infer their μ-coefficients. By using a pulse sequence capable of visualizing lung parenchyma, I established a linear relationship between MRI signal and the lungs’ μ-coefficients. I showed that applying this mapping on a voxel-by-voxel basis improved quantification in PET reconstructions compared to conventional MRI-based AC techniques. Finally, I envisaged that a framework for MRI-based AC methods would potentiate further improvements. Accordingly, I identified three ways an MRI can be converted to μ-coefficients: 1) segmentation, wherein the MRI is divided into tissue types and each is assigned an μ-coefficient, 2) registration, wherein a template of μ-coefficients is aligned with the MRI, and 3) mapping, wherein a function maps MRI voxels to μ-coefficients. I constructed an algorithm for each method and catalogued their strengths and weaknesses. I concluded that a combination of approaches is desirable for MRI-based AC. Specifically, segmentation is appropriate for air, fat, and water, mapping is appropriate for lung, and registration is appropriate for bone

Peter Josef Ell : discurs llegit a la cerimònia d'investidura celebrada a l'aula magna de Casa Convalescència el dia 5 d'abril de l'any 2005

Peter Josef Ell , nascut el 7 de maig de 1944, és professor de Medicina Nuclear a la Universitat de Londres des de 1987, director del Institute of Nuclear Medicine, UCL, des de 1986, Honorary Consultant Physician del Middlesex Hospital des de 1976, i Clinical Director del UCLH NHS Trust des de 2001. El professor Ell és una de les figures més rellevants del món en l'àrea de la medicina nuclear i del diagnòstic per la imatge. La seva formació, variada i europeista, inclou una llicenciatura en Medicina per la Universitat de Lisboa, un màster en Ciències per la Universitat de Londres i un doctorat per la Universitat de Berna. No solament parla diverses llengües, sinó que ha integrat les cultures portuguesa, alemanya i anglesa. És director del Institute of Nuclear Medicine del UCL, un dels serveis més grans d'Anglaterra en l'especialitat, i catedràtic de Medicina Nuclear en aquest mateix centre. És autor de més de cinc-centes publicacions científiques, moltes d'elles en les revistes de més factor d'impacte (Lancet, JCO, JACC, etc.), i és editor/autor de dotze llibres de text, i de múltiples comunicacions i presentacions a congressos. Ha estat convidat a pronunciar nombroses conferències arreu del món. La seva multiculturalitat li ha permès de tenir un paper central en la creació i formació de la Societat Europea de Medicina Nuclear (EANM), de la qual va ser autor de molts dels documents fundacionals, i de la qual ha estat president entre 1994 i 1996. Ha estat quinze anys redactor en cap del European Journal of Nuclear Medicine and Molecular Imaging, revista que, sota la seva direcció, s'ha consolidat com una de les més importants del món en aquesta àrea científica.Nomenament 10/11/2004. A proposta de Facultat de Medicina. Investidura 05/05/2005. Padrí: Ignasi Carri

Developing advanced mathematical models for detecting abnormalities in 2D/3D medical structures.

Detecting abnormalities in two-dimensional (2D) and three-dimensional (3D) medical structures is among the most interesting and challenging research areas in the medical imaging field. Obtaining the desired accurate automated quantification of abnormalities in medical structures is still very challenging. This is due to a large and constantly growing number of different objects of interest and associated abnormalities, large variations of their appearances and shapes in images, different medical imaging modalities, and associated changes of signal homogeneity and noise for each object. The main objective of this dissertation is to address these problems and to provide proper mathematical models and techniques that are capable of analyzing low and high resolution medical data and providing an accurate, automated analysis of the abnormalities in medical structures in terms of their area/volume, shape, and associated abnormal functionality. This dissertation presents different preliminary mathematical models and techniques that are applied in three case studies: (i) detecting abnormal tissue in the left ventricle (LV) wall of the heart from delayed contrast-enhanced cardiac magnetic resonance images (MRI), (ii) detecting local cardiac diseases based on estimating the functional strain metric from cardiac cine MRI, and (iii) identifying the abnormalities in the corpus callosum (CC) brain structure—the largest fiber bundle that connects the two hemispheres in the brain—for subjects that suffer from developmental brain disorders. For detecting the abnormal tissue in the heart, a graph-cut mathematical optimization model with a cost function that accounts for the object’s visual appearance and shape is used to segment the the inner cavity. The model is further integrated with a geometric model (i.e., a fast marching level set model) to segment the outer border of the myocardial wall (the LV). Then the abnormal tissue in the myocardium wall (also called dead tissue, pathological tissue, or infarct area) is identified based on a joint Markov-Gibbs random field (MGRF) model of the image and its region (segmentation) map that accounts for the pixel intensities and the spatial interactions between the pixels. Experiments with real in-vivo data and comparative results with ground truth (identified by a radiologist) and other approaches showed that the proposed framework can accurately detect the pathological tissue and can provide useful metrics for radiologists and clinicians. To estimate the strain from cardiac cine MRI, a novel method based on tracking the LV wall geometry is proposed. To achieve this goal, a partial differential equation (PDE) method is applied to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. The main advantage of the proposed tracking method over traditional texture-based methods is its ability to track the movement and rotation of the LV wall based on tracking the geometric features of the inner, mid-, and outer walls of the LV. This overcomes noise sources that come from scanner and heart motion. To identify the abnormalities in the CC from brain MRI, the CCs are aligned using a rigid registration model and are segmented using a shape-appearance model. Then, they are mapped to a simple unified space for analysis. This work introduces a novel cylindrical mapping model, which is conformal (i.e., one to one transformation and bijective), that enables accurate 3D shape analysis of the CC in the cylindrical domain. The framework can detect abnormalities in all divisions of the CC (i.e., splenium, rostrum, genu and body). In addition, it offers a whole 3D analysis of the CC abnormalities instead of only area-based analysis as done by previous groups. The initial classification results based on the centerline length and CC thickness suggest that the proposed CC shape analysis is a promising supplement to the current techniques for diagnosing dyslexia. The proposed techniques in this dissertation have been successfully tested on complex synthetic and MR images and can be used to advantage in many of today’s clinical applications of computer-assisted medical diagnostics and intervention

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

State of the Art of Level Set Methods in Segmentation and Registration of Medical Imaging Modalities

Segmentation of medical images is an important step in various applications such as visualization, quantitative analysis and image-guided surgery. Numerous segmentation methods have been developed in the past two decades for extraction of organ contours on medical images. Low-level segmentation methods, such as pixel-based clustering, region growing, and filter-based edge detection, require additional pre-processing and post-processing as well as considerable amounts of expert intervention or information of the objects of interest. Furthermore the subsequent analysis of segmented objects is hampered by the primitive, pixel or voxel level representations from those region-based segmentation. Deformable models, on the other hand, provide an explicit representation of the boundary and the shape of the object. They combine several desirable features such as inherent connectivity and smoothness, which counteract noise and boundary irregularities, as well as the ability to incorporate knowledge about the object of interest. However, parametric deformable models have two main limitations. First, in situations where the initial model and desired object boundary differ greatly in size and shape, the model must be re-parameterized dynamically to faithfully recover the object boundary. The second limitation is that it has difficulty dealing with topological adaptation such as splitting or merging model parts, a useful property for recovering either multiple objects or objects with unknown topology. This difficulty is caused by the fact that a new parameterization must be constructed whenever topology change occurs, which requires sophisticated schemes. Level set deformable models, also referred to as geometric deformable models, provide an elegant solution to address the primary limitations of parametric deformable models. These methods have drawn a great deal of attention since their introduction in 1988. Advantages of the contour implicit formulation of the deformable model over parametric formulation include: (1) no parameterization of the contour, (2) topological flexibility, (3) good numerical stability, (4) straightforward extension of the 2D formulation to n-D. Recent reviews on the subject include papers from Suri. In this chapter we give a general overview of the level set segmentation methods with emphasize on new frameworks recently introduced in the context of medical imaging problems. We then introduce novel approaches that aim at combining segmentation and registration in a level set formulation. Finally we review a selective set of clinical works with detailed validation of the level set methods for several clinical applications

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)