Fast strain mapping in abdominal aortic aneurysm wall reveals heterogeneous patterns

Abdominal aortic aneurysm patients are regularly monitored to assess aneurysm development and risk of rupture. A preventive surgical procedure is recommended when the maximum aortic antero-posterior diameter, periodically assessed on two-dimensional abdominal ultrasound scans, reaches 5.5 mm. Although the maximum diameter criterion has limited ability to predict aneurysm rupture, no clinically relevant tool that could complement the current guidelines has emerged so far. In vivo cyclic strains in the aneurysm wall are related to the wall response to blood pressure pulse, and therefore, they can be linked to wall mechanical properties, which in turn contribute to determining the risk of rupture. This work aimed to enable biomechanical estimations in the aneurysm wall by providing a fast and semi-automatic method to post-process dynamic clinical ultrasound sequences and by mapping the cross-sectional strains on the B-mode image. Specifically, the Sparse Demons algorithm was employed to track the wall motion throughout multiple cardiac cycles. Then, the cyclic strains were mapped by means of radial basis function interpolation and differentiation. We applied our method to two-dimensional sequences from eight patients. The automatic part of the analysis took under 1.5 min per cardiac cycle. The tracking method was validated against simulated ultrasound sequences, and a maximum root mean square error of 0.22 mm was found. The strain was calculated both with our method and with the established finite-element method, and a very good agreement was found, with mean differences of one order of magnitude smaller than the image spatial resolution. Most patients exhibited a strain pattern that suggests interaction with the spine. To conclude, our method is a promising tool for investigating abdominal aortic aneurysm wall biomechanics as it can provide a fast and accurate measurement of the cyclic wall strains from clinical ultrasound sequences

Feature based estimation of myocardial motion from tagged MR images

In the past few years we witnessed an increase in mortality due to cancer relative to mortality due to cardiovascular diseases. In 2008, the Netherlands Statistics Agency reports that 33.900 people died of cancer against 33.100 deaths due to cardiovascular diseases, making cancer the number one cause of death in the Netherlands [33]. Even if the rate of people affected by heart diseases is continually rising, they "simply don’t die of it", according to the research director Prof. Mat Daemen of research institute CARIM of the University of Maastricht [50]. The reason for this is the early diagnosis, and the treatment of people with identified risk factors for diseases like ischemic heart disease, hypertrophic cardiomyopathy, thoracic aortic disease, pericardial (sac around the heart) disease, cardiac tumors, pulmonary artery disease, valvular disease, and congenital heart disease before and after surgical repair. Cardiac imaging plays a crucial role in the early diagnosis, since it allows the accurate investigation of a large amount of imaging data in a small amount of time. Moreover, cardiac imaging reduces costs of inpatient care, as has been shown in recent studies [77]. With this in mind, in this work we have provided several tools with the aim to help the investigation of the cardiac motion. In chapters 2 and 3 we have explored a novel variational optic flow methodology based on multi-scale feature points to extract cardiac motion from tagged MR images. Compared to constant brightness methods, this new approach exhibits several advantages. Although the intensity of critical points is also influenced by fading, critical points do retain their characteristic even in the presence of intensity changes, such as in MR imaging. In an experiment in section 5.4 we have applied this optic flow approach directly on tagged MR images. A visual inspection confirmed that the extracted motion fields realistically depicted the cardiac wall motion. The method exploits also the advantages from the multiscale framework. Because sparse velocity formulas 2.9, 3.7, 6.21, and 7.5 provide a number of equations equal to the number of unknowns, the method does not suffer from the aperture problem in retrieving velocities associated to the critical points. In chapters 2 and 3 we have moreover introduced a smoothness component of the optic flow equation described by means of covariant derivatives. This is a novelty in the optic flow literature. Many variational optic flow methods present a smoothness component that penalizes for changes from global assumptions such as isotropic or anisotropic smoothness. In the smoothness term proposed deviations from a predefined motion model are penalized. Moreover, the proposed optic flow equation has been decomposed in rotation-free and divergence-free components. This decomposition allows independent tuning of the two components during the vector field reconstruction. The experiments and the Table of errors provided in 3.8 showed that the combination of the smoothness term, influenced by a predefined motion model, and the Helmholtz decomposition in the optic flow equation reduces the average angular error substantially (20%-25%) with respect to a similar technique that employs only standard derivatives in the smoothness term. In section 5.3 we extracted the motion field of a phantom of which we know the ground truth of and compared the performance of this optic flow method with the performance of other optic flow methods well known in the literature, such as the Horn and Schunck [76] approach, the Lucas and Kanade [111] technique and the tuple image multi-scale optic flow constraint equation of Van Assen et al. [163]. Tests showed that the proposed optic flow methodology provides the smallest average angular error (AAE = 3.84 degrees) and L2 norm = 0.1. In this work we employed the Helmholtz decomposition also to study the cardiac behavior, since the vector field decomposition allows to investigate cardiac contraction and cardiac rotation independently. In chapter 4 we carried out an analysis of cardiac motion of ten volunteers and one patient where we estimated the kinetic energy for the different components. This decomposition is useful since it allows to visualize and quantify the contributions of each single vector field component to the heart beat. Local measurements of the kinetic energy have also been used to detect areas of the cardiac walls with little movement. Experiments on a patient and a comparison between a late enhancement cardiac image and an illustration of the cardiac kinetic energy on a bull’s eye plot illustrated that a correspondence between an infarcted area and an area with very small kinetic energy exists. With the aim to extend in the future the proposed optic flow equation to a 3D approach, in chapter 6 we investigated the 3D winding number approach as a tool to locate critical points in volume images. We simplified the mathematics involved with respect to a previous work [150] and we provided several examples and applications such as cardiac motion estimation from 3-dimensional tagged images, follicle and neuronal cell counting. Finally in chapter 7 we continued our investigation on volume tagged MR images, by retrieving the cardiac motion field using a 3-dimensional and simple version of the proposed optic flow equation based on standard derivatives. We showed that the retrieved motion fields display the contracting and rotating behavior of the cardiac muscle. We moreover extracted the through-plane component, which provides a realistic illustration of the vector field and is missed by 2-dimensional approaches

Cardiac image computing for myocardial infarction patients

Cardiovascular diseases (CVDs), which are a prime cause of global mortality, are disorders that affect the heart and blood vessels' functioning. CVDs may cause consequent complications, due to occlusion in a blood vessel and present as impaired cardiac wall functioning (myocardium). Identifying such impairment (infarction) of the myocardium is of great clinical interest, as it can reveal the nature of altered cardiac topography (ventricular remodelling) to aid the associated intervention decisions. With recent advances in cardiac imaging, such as Magnetic Resonance (MR) imaging, the visualisation and identification of infarcted myocardium has been routinely and effectively used in clinical practice. Diagnosing infarcted myocardium is achieved clinically through the late gadolinium enhancement (LGE) test, which acquires MR images after injecting a gadolinium-based contrast agent (GBCA). Due to the increased accuracy and reproducibility, LGE has emerged as the gold-standard MR imaging test in identifying myocardial infarction. However, clinical studies have reported gadolinium deposition concerns in different body organs and adverse outcomes in patients with advanced kidney failure, over time. Such incidents have motivated researchers to look into the development of both accurate as well as safe diagnostic tools. Emerging research on identifying infarcted myocardium utilises myocardial strain to safely identify infarcted myocardium, which has been addressed in the presented study. For example, myocardial strain represents the shortening or lengthening of the myocardium. If the myocardium is infarcted, then the corresponding strain values differ compared to the healthy myocardium. This finding can be identified and utilised for clinical applications. The research presented in this thesis aims to identify infarcted myocardium accurately and safely by using myocardial strain (shortening or lengthening of the myocardium). To achieve the aforementioned aim, the research methodology is divided into six objectives. The initial objectives relate to the development of a novel myocardial tracking method. The middle objectives relate to the development of clinical application methods, and the final objectives concern the validation of the developed methods through clinical studies and associated datasets. The research presented in this thesis has addressed the following research question: Research question 1: How can a 2D myocardial tracking and strain calculation method be developed using the 2D local weighted mean function and structural deformation within the myocardium? Research question 2: How can a 3D myocardial tracking and strain calculation method be developed using the 3D local weighted mean function to calculate 3D myocardial strain? Research question 3: How can 2D circumferential strain of the myocardium be used in identifying infarcted left ventricular segments for the diagnosis of myocardial infarction patients? In literature, myocardial tracking and strain calculation methods have limited extension to 3D and dependency on tissue material properties. Moreover, additional limitations, such as limited inclusion of structural deformation details within the myocardium, are found in the literature. Therefore, methods are likely to become subjective or numerically unstable during computation. Moreover, the inclusion of myocardial details with grid-tagging MRI, for structural deformation within the myocardium, is more realistic compared to cine MRI.   The aforementioned limitations are overcome by proposing a novel Hierarchical Template Matching method, which performs non-rigid image registration among grid-tagging MR images of a cardiac cycle. This is achieved by employing a local weighted mean transformation function. The proposed non-rigid image registration method does not require the use of tissue material properties. Grid-tagging MRI is used to capture wall function within the myocardium, and the local weighted mean function is used for numerical stability. The performance of the developed methods is evaluated with multiple error measures and with a benchmark framework. This benchmark framework has provided an open-access 3D dataset, a set of validation methods, and results of four leading methods for comparison. Validation methods include qualitative and quantitative methods. The qualitative assessment of outcomes and verified ground truth for the quantitative evaluation of results are followed from the benchmark framework paper (Tobon-Gomez, Craene, Mcleod, et al., 2013). 2D HTM method has reported the root mean square error of point tracking in left ventricular slices, which are the basal slice 0.31±0.07 mm, the upper mid-ventricular slice 0.37±0.06 mm, the mid-ventricular slice 0.41±0.05 mm, and the apical slice 0.32±0.08 mm. The mid-ventricular slice has a significantly higher 4% (P=0.05) mean root mean square error compared to the other slices. However, the other slices do not have a significant difference among them. Compared to the benchmark free form deformation method, HTM has a mean error of 0.35±0.05 mm, which is 17% (P=0.07, CI:[-0.01,0.35]) reduced to the free form deformation method. Our technical method has shown the 3D extension of HTM and a method without using material properties, which is advantageous compared to the methods which are limited to 2D or dependent on material properties. Moreover, the 3D HTM has demonstrated the use of 3D local weighted mean function in 3D myocardial tracking. While comparing to the benchmark methods, it was found that the median tracking error of 3D HTM is comparable to benchmark methods and has very few outliers compared to them. The clinical results are validated with LGE imaging. The quantitative error measure is the area under the curve (AUC) of sensitivity vs 1-specificity curve of the receiver operating characteristic (ROC) test. The achieved AUC value in detecting infarcted segments in basal, mid-ventricular, and apical slices are 0.85, 0.82, and 0.87, respectively. Calculating AUC with 95% confidence level, the confidence intervals of lower and upper mean AUC values in basal, mid-ventricular and apical slices are [0.80, 0.89], [0.74, 0.85], and [0.78, 0.91], respectively. Overall, considering the detections of LGE imaging as the base, our method has an accuracy of AUC 0.73 (P=0.05) in identifying infarcted left ventricular segments. The developed methods have shown, systematically, a promising approach in identifying infarcted left ventricular segments by image processing method and without using GBCA-based LGE imaging.

Learning a Generative Motion Model from Image Sequences based on a Latent Motion Matrix

We propose to learn a probabilistic motion model from a sequence of images for spatio-temporal registration. Our model encodes motion in a low-dimensional probabilistic space - the motion matrix - which enables various motion analysis tasks such as simulation and interpolation of realistic motion patterns allowing for faster data acquisition and data augmentation. More precisely, the motion matrix allows to transport the recovered motion from one subject to another simulating for example a pathological motion in a healthy subject without the need for inter-subject registration. The method is based on a conditional latent variable model that is trained using amortized variational inference. This unsupervised generative model follows a novel multivariate Gaussian process prior and is applied within a temporal convolutional network which leads to a diffeomorphic motion model. Temporal consistency and generalizability is further improved by applying a temporal dropout training scheme. Applied to cardiac cine-MRI sequences, we show improved registration accuracy and spatio-temporally smoother deformations compared to three state-of-the-art registration algorithms. Besides, we demonstrate the model's applicability for motion analysis, simulation and super-resolution by an improved motion reconstruction from sequences with missing frames compared to linear and cubic interpolation.Comment: accepted at IEEE TM

Role of deep learning techniques in non-invasive diagnosis of human diseases.

Machine learning, a sub-discipline in the domain of artificial intelligence, concentrates on algorithms able to learn and/or adapt their structure (e.g., parameters) based on a set of observed data. The adaptation is performed by optimizing over a cost function. Machine learning obtained a great attention in the biomedical community because it offers a promise for improving sensitivity and/or specificity of detection and diagnosis of diseases. It also can increase objectivity of the decision making, decrease the time and effort on health care professionals during the process of disease detection and diagnosis. The potential impact of machine learning is greater than ever due to the increase in medical data being acquired, the presence of novel modalities being developed and the complexity of medical data. In all of these scenarios, machine learning can come up with new tools for interpreting the complex datasets that confront clinicians. Much of the excitement for the application of machine learning to biomedical research comes from the development of deep learning which is modeled after computation in the brain. Deep learning can help in attaining insights that would be impossible to obtain through manual analysis. Deep learning algorithms and in particular convolutional neural networks are different from traditional machine learning approaches. Deep learning algorithms are known by their ability to learn complex representations to enhance pattern recognition from raw data. On the other hand, traditional machine learning requires human engineering and domain expertise to design feature extractors and structure data. With increasing demands upon current radiologists, there are growing needs for automating the diagnosis. This is a concern that deep learning is able to address. In this dissertation, we present four different successful applications of deep learning for diseases diagnosis. All the work presented in the dissertation utilizes medical images. In the first application, we introduce a deep-learning based computer-aided diagnostic system for the early detection of acute renal transplant rejection. The system is based on the fusion of both imaging markers (apparent diffusion coefficients derived from diffusion-weighted magnetic resonance imaging) and clinical biomarkers (creatinine clearance and serum plasma creatinine). The fused data is then used as an input to train and test a convolutional neural network based classifier. The proposed system is tested on scans collected from 56 subjects from geographically diverse populations and different scanner types/image collection protocols. The overall accuracy of the proposed system is 92.9% with 93.3% sensitivity and 92.3% specificity in distinguishing non-rejected kidney transplants from rejected ones. In the second application, we propose a novel deep learning approach for the automated segmentation and quantification of the LV from cardiac cine MR images. We aimed at achieving lower errors for the estimated heart parameters compared to the previous studies by proposing a novel deep learning segmentation method. Using fully convolutional neural networks, we proposed novel methods for the extraction of a region of interest that contains the left ventricle, and the segmentation of the left ventricle. Following myocardial segmentation, functional and mass parameters of the left ventricle are estimated. Automated Cardiac Diagnosis Challenge dataset was used to validate our framework, which gave better segmentation, accurate estimation of cardiac parameters, and produced less error compared to other methods applied on the same dataset. Furthermore, we showed that our segmentation approach generalizes well across different datasets by testing its performance on a locally acquired dataset. In the third application, we propose a novel deep learning approach for automated quantification of strain from cardiac cine MR images of mice. For strain analysis, we developed a Laplace-based approach 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. Following tracking, the strain estimation is performed using the Lagrangian-based approach. This new automated system for strain analysis was validated by comparing the outcome of these analysis with the tagged MR images from the same mice. There were no significant differences between the strain data obtained from our algorithm using cine compared to tagged MR imaging. In the fourth application, we demonstrate how a deep learning approach can be utilized for the automated classification of kidney histopathological images. Our approach can classify four classes: the fat, the parenchyma, the clear cell renal cell carcinoma, and the unusual cancer which has been discovered recently, called clear cell papillary renal cell carcinoma. Our framework consists of three convolutional neural networks and the whole-slide kidney images were divided into patches with three different sizes to be inputted to the networks. Our approach can provide patch-wise and pixel-wise classification. Our approach classified the four classes accurately and surpassed other state-of-the-art methods such as ResNet (pixel accuracy: 0.89 Resnet18, 0.93 proposed). In conclusion, the results of our proposed systems demonstrate the potential of deep learning for the efficient, reproducible, fast, and affordable disease diagnosis

Dynamic Image Processing for Guidance of Off-pump Beating Heart Mitral Valve Repair

Compared to conventional open heart procedures, minimally invasive off-pump beating heart mitral valve repair aims to deliver equivalent treatment for mitral regurgitation with reduced trauma and side effects. However, minimally invasive approaches are often limited by the lack of a direct view to surgical targets and/or tools, a challenge that is compounded by potential movement of the target during the cardiac cycle. For this reason, sophisticated image guidance systems are required in achieving procedural efficiency and therapeutic success. The development of such guidance systems is associated with many challenges. For example, the system should be able to provide high quality visualization of both cardiac anatomy and motion, as well as augmenting it with virtual models of tracked tools and targets. It should have the capability of integrating pre-operative images to the intra-operative scenario through registration techniques. The computation speed must be sufficiently fast to capture the rapid cardiac motion. Meanwhile, the system should be cost effective and easily integrated into standard clinical workflow. This thesis develops image processing techniques to address these challenges, aiming to achieve a safe and efficient guidance system for off-pump beating heart mitral valve repair. These techniques can be divided into two categories, using 3D and 2D image data respectively. When 3D images are accessible, a rapid multi-modal registration approach is proposed to link the pre-operative CT images to the intra-operative ultrasound images. The ultrasound images are used to display the real time cardiac motion, enhanced by CT data serving as high quality 3D context with annotated features. I also developed a method to generate synthetic dynamic CT images, aiming to replace real dynamic CT data in such a guidance system to reduce the radiation dose applied to the patients. When only 2D images are available, an approach is developed to track the feature of interest, i.e. the mitral annulus, based on bi-plane ultrasound images and a magnetic tracking system. The concept of modern GPU-based parallel computing is employed in most of these approaches to accelerate the computation in order to capture the rapid cardiac motion with desired accuracy. Validation experiments were performed on phantom, animal and human data. The overall accuracy of registration and feature tracking with respect to the mitral annulus was about 2-3mm with computation time of 60-400ms per frame, sufficient for one update per cardiac cycle. It was also demonstrated in the results that the synthetic CT images can provide very similar anatomical representations and registration accuracy compared to that of the real dynamic CT images. These results suggest that the approaches developed in the thesis have good potential for a safer and more effective guidance system for off-pump beating heart mitral valve repair