Automatic Affine and Elastic Registration Strategies for Multi-dimensional Medical Images

Medical images have been used increasingly for diagnosis, treatment planning, monitoring disease processes, and other medical applications. A large variety of medical imaging modalities exists including CT, X-ray, MRI, Ultrasound, etc. Frequently a group of images need to be compared to one another and/or combined for research or cumulative purposes. In many medical studies, multiple images are acquired from subjects at different times or with different imaging modalities. Misalignment inevitably occurs, causing anatomical and/or functional feature shifts within the images. Computerized image registration (alignment) approaches can offer automatic and accurate image alignments without extensive user involvement and provide tools for visualizing combined images. This dissertation focuses on providing automatic image registration strategies. After a through review of existing image registration techniques, we identified two registration strategies that enhance the current field: (1) an automated rigid body and affine registration using voxel similarity measurements based on a sequential hybrid genetic algorithm, and (2) an automated deformable registration approach based upon a linear elastic finite element formulation. Both methods streamlined the registration process. They are completely automatic and require no user intervention. The proposed registration strategies were evaluated with numerous 2D and 3D MR images with a variety of tissue structures, orientations and dimensions. Multiple registration pathways were provided with guidelines for their applications. The sequential genetic algorithm mimics the pathway of an expert manually doing registration. Experiments demonstrated that the sequential genetic algorithm registration provides high alignment accuracy and is reliable for brain tissues. It avoids local minima/maxima traps of conventional optimization techniques, and does not require any preprocessing such as threshold, smoothing, segmentation, or definition of base points or edges. The elastic model was shown to be highly effective to accurately align areas of interest that are automatically extracted from the images, such as brains. Using a finite element method to get the displacement of each element node by applying a boundary mapping, this method provides an accurate image registration with excellent boundary alignment of each pair of slices and consequently align the entire volume automatically. This dissertation presented numerous volume alignments. Surface geometries were created directly from the aligned segmented images using the Multiple Material Marching Cubes algorithm. Using the proposed registration strategies, multiple subjects were aligned to a standard MRI reference, which is aligned to a segmented reference atlas. Consequently, multiple subjects are aligned to the segmented atlas and a full fMRI analysis is possible

A new approach for the in-vivo characterization of the biomechanical behavior of the breast and the cornea

The characterization of the mechanical behavior of soft living tissues is a big challenge in Biomechanics. The difficulty arises from both the access to the tissues and the manipulation in order to know their physical properties. Currently, the biomechanical characterization of the organs is mainly performed by testing ex-vivo samples or by means of indentation tests. In the first case, the obtained behavior does not represent the real behavior of the organ. In the second case, it is only a representation of the mechanical response of the indented areas. The purpose of the research reported in this thesis is the development of a methodology to in-vivo characterize the biomechanical behavior of two different organs: the breast and the cornea. The proposed methodology avoids invasive measurements to obtain the mechanical response of the organs and is able to completely characterize of the biomechanical behavior of them. The research reported in this thesis describes a methodology to in-vivo characterize the biomechanical behavior of the breast and the cornea. The estimation of the elastic constants of the constitutive equations that define the mechanical behavior of these organs is performed using an iterative search algorithm which optimizes these parameters. The search is based on the iterative variation of the elastic constants of the model in order to increase the similarity between a simulated deformation of the organ and the real one. The similarity is measured by means of a volumetric similarity function which combines overlap-based coefficients and distance-based coefficients. Due to the number of parameters to be characterized as well as the non-convergences that the solution may present in some regions, genetic heuristics were chosen to drive the search algorithm. In the case of the breast, the elastic constants of an anisotropic hyperelastic neo-Hookean model proposed to simulate the compression of the breast during an MRI-guided biopsy were estimated. Results from this analysis showed that the proposed algorithm accurately found the elastic constants of the proposed model, providing an average relative error below 10%. The methodology was validated using breast software phantoms. Nevertheless, this methodology can be easily transferred into its use with real breasts. In the case of the cornea, the elastic constants of a hyperelastic second-order Ogden model were estimated for 24 corneas corresponding to 12 patients. The finite element method was applied in order to simulate the deformation of the human corneas due to non-contact tonometry. The iterative search was applied in order to estimate the elastic constants of the model which approximates the most the simulated deformation to the real one. Results showed that these constants can be estimated with an error of about 5%. After the results obtained for both organs, it can be concluded that the iterative search methodology presented in this thesis allows the \textit{in-vivo} estimation the patient-specific elastic constants of the constitutive biomechanical models that govern the biomechanical behavior of these two organs.Lago Ángel, MÁ. (2014). A new approach for the in-vivo characterization of the biomechanical behavior of the breast and the cornea [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/44116TESI

Medical imaging analysis with artificial neural networks

Given that neural networks have been widely reported in the research community of medical imaging, we provide a focused literature survey on recent neural network developments in computer-aided diagnosis, medical image segmentation and edge detection towards visual content analysis, and medical image registration for its pre-processing and post-processing, with the aims of increasing awareness of how neural networks can be applied to these areas and to provide a foundation for further research and practical development. Representative techniques and algorithms are explained in detail to provide inspiring examples illustrating: (i) how a known neural network with fixed structure and training procedure could be applied to resolve a medical imaging problem; (ii) how medical images could be analysed, processed, and characterised by neural networks; and (iii) how neural networks could be expanded further to resolve problems relevant to medical imaging. In the concluding section, a highlight of comparisons among many neural network applications is included to provide a global view on computational intelligence with neural networks in medical imaging

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

Complexity Reduction in Image-Based Breast Cancer Care

The diversity of malignancies of the breast requires personalized diagnostic and therapeutic decision making in a complex situation. This thesis contributes in three clinical areas: (1) For clinical diagnostic image evaluation, computer-aided detection and diagnosis of mass and non-mass lesions in breast MRI is developed. 4D texture features characterize mass lesions. For non-mass lesions, a combined detection/characterisation method utilizes the bilateral symmetry of the breast s contrast agent uptake. (2) To improve clinical workflows, a breast MRI reading paradigm is proposed, exemplified by a breast MRI reading workstation prototype. Instead of mouse and keyboard, it is operated using multi-touch gestures. The concept is extended to mammography screening, introducing efficient navigation aids. (3) Contributions to finite element modeling of breast tissue deformations tackle two clinical problems: surgery planning and the prediction of the breast deformation in a MRI biopsy device

Registration and analysis of dynamic magnetic resonance image series

Cystic fibrosis (CF) is an autosomal-recessive inherited metabolic disorder that affects all organs in the human body. Patients affected with CF suffer particularly from chronic inflammation and obstruction of the airways. Through early detection, continuous monitoring methods, and new treatments, the life expectancy of patients with CF has been increased drastically in the last decades. However, continuous monitoring of the disease progression is essential for a successful treatment. The current state-of-the-art method for lung disease detection and monitoring is computed tomography (CT) or X-ray. These techniques are ill-suited for the monitoring of disease progressions because of the ionizing radiation the patient is exposed during the examination. Through the development of new magnetic resonance imaging (MRI) sequences and evaluation methods, MRI is able to measure physiological changes in the lungs. The process to create physiological maps, i.e. ventilation and perfusion maps, of the lungs using MRI can be split up into three parts: MR-acquisition, image registration, and image analysis. In this work, we present different methods for the image registration part and the image analysis part. We developed a graph-based registration method for 2D dynamic MR image series of the lungs in order to overcome the problem of sliding motion at organ boundaries. Furthermore, we developed a human-inspired learning-based registration method. Here, the registration is defined as a sequence of local transformations. The sequence-based approach combines the advantage of dense transformation models, i.e. large space of transformations, and the advantage of interpolating transformation models, i.e. smooth local transformations. We also developed a general registration framework called Autograd Image Registration Laboratory (AIRLab), which performs automatic calculation of the gradients for the registration process. This allows rapid prototyping and an easy implementation of existing registration algorithms. For the image analysis part, we developed a deep-learning approach based on gated recurrent units that are able to calculate ventilation maps with less than a third of the number of images of the current method. Automatic defect detection in the estimated MRI ventilation and perfusion maps is essential for the clinical routine to automatically evaluate the treatment progression. We developed a weakly supervised method that is able to infer a pixel-wise defect segmentation by using only a continuous global label during training. In this case, we directly use the lung clearance index (LCI) as a global weak label, without any further manual annotations. The LCI is a global measure to describe ventilation inhomogeneities of the lungs and is obtained by a multiple breath washout test

Semiautomated Multimodal Breast Image Registration

Consideration of information from multiple modalities has been shown to have increased diagnostic power in breast imaging. As a result, new techniques such as microwave imaging continue to be developed. Interpreting these novel image modalities is a challenge, requiring comparison to established techniques such as the gold standard X-ray mammography. However, due to the highly deformable nature of breast tissues, comparison of 3D and 2D modalities is a challenge. To enable this comparison, a registration technique was developed to map features from 2D mammograms to locations in the 3D image space. This technique was developed and tested using magnetic resonance (MR) images as a reference 3D modality, as MR breast imaging is an established technique in clinical practice. The algorithm was validated using a numerical phantom then successfully tested on twenty-four image pairs. Dice's coefficient was used to measure the external goodness of fit, resulting in an excellent overall average of 0.94. Internal agreement was evaluated by examining internal features in consultation with a radiologist, and subjective assessment concludes that reasonable alignment was achieved

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

Modified mass-spring system for physically based deformation modeling

Mass-spring systems are considered the simplest and most intuitive of all deformable models. They are computationally efficient, and can handle large deformations with ease. But they suffer several intrinsic limitations. In this book a modified mass-spring system for physically based deformation modeling that addresses the limitations and solves them elegantly is presented. Several implementations in modeling breast mechanics, heart mechanics and for elastic images registration are presented

Modified mass-spring system for physically based deformation modeling

Mass-spring systems are considered the simplest and most intuitive of all deformable models. They are computationally efficient, and can handle large deformations with ease. But they suffer several intrinsic limitations. In this book a modified mass-spring system for physically based deformation modeling that addresses the limitations and solves them elegantly is presented. Several implementations in modeling breast mechanics, heart mechanics and for elastic images registration are presented