Rapid Segmentation Techniques for Cardiac and Neuroimage Analysis

Recent technological advances in medical imaging have allowed for the quick acquisition of highly resolved data to aid in diagnosis and characterization of diseases or to guide interventions. In order to to be integrated into a clinical work flow, accurate and robust methods of analysis must be developed which manage this increase in data. Recent improvements in in- expensive commercially available graphics hardware and General-Purpose Programming on Graphics Processing Units (GPGPU) have allowed for many large scale data analysis problems to be addressed in meaningful time and will continue to as parallel computing technology improves. In this thesis we propose methods to tackle two clinically relevant image segmentation problems: a user-guided segmentation of myocardial scar from Late-Enhancement Magnetic Resonance Images (LE-MRI) and a multi-atlas segmentation pipeline to automatically segment and partition brain tissue from multi-channel MRI. Both methods are based on recent advances in computer vision, in particular max-flow optimization that aims at solving the segmentation problem in continuous space. This allows for (approximately) globally optimal solvers to be employed in multi-region segmentation problems, without the particular drawbacks of their discrete counterparts, graph cuts, which typically present with metrication artefacts. Max-flow solvers are generally able to produce robust results, but are known for being computationally expensive, especially with large datasets, such as volume images. Additionally, we propose two new deformable registration methods based on Gauss-Newton optimization and smooth the resulting deformation fields via total-variation regularization to guarantee the problem is mathematically well-posed. We compare the performance of these two methods against four highly ranked and well-known deformable registration methods on four publicly available databases and are able to demonstrate a highly accurate performance with low run times. The best performing variant is subsequently used in a multi-atlas segmentation pipeline for the segmentation of brain tissue and facilitates fast run times for this computationally expensive approach. All proposed methods are implemented using GPGPU for a substantial increase in computational performance and so facilitate deployment into clinical work flows. We evaluate all proposed algorithms in terms of run times, accuracy, repeatability and errors arising from user interactions and we demonstrate that these methods are able to outperform established methods. The presented approaches demonstrate high performance in comparison with established methods in terms of accuracy and repeatability while largely reducing run times due to the employment of GPU hardware

Unsupervised image registration towards enhancing performance and explainability in cardiac and brain image analysis

Magnetic Resonance Imaging (MRI) typically recruits multiple sequences (defined here as “modalities”). As each modality is designed to offer different anatomical and functional clinical information, there are evident disparities in the imaging content across modalities. Inter- and intra-modality affine and non-rigid image registration is an essential medical image analysis process in clinical imaging, as for example before imaging biomarkers need to be derived and clinically evaluated across different MRI modalities, time phases and slices. Although commonly needed in real clinical scenarios, affine and non-rigid image registration is not extensively investigated using a single unsupervised model architecture. In our work, we present an unsupervised deep learning registration methodology that can accurately model affine and non-rigid transformations, simultaneously. Moreover, inverse-consistency is a fundamental inter-modality registration property that is not considered in deep learning registration algorithms. To address inverse consistency, our methodology performs bi-directional cross-modality image synthesis to learn modality-invariant latent representations, and involves two factorised transformation networks (one per each encoder-decoder channel) and an inverse-consistency loss to learn topology-preserving anatomical transformations. Overall, our model (named “FIRE”) shows improved performances against the reference standard baseline method (i.e., Symmetric Normalization implemented using the ANTs toolbox) on multi-modality brain 2D and 3D MRI and intra-modality cardiac 4D MRI data experiments. We focus on explaining model-data components to enhance model explainability in medical image registration. On computational time experiments, we show that the FIRE model performs on a memory-saving mode, as it can inherently learn topology-preserving image registration directly in the training phase. We therefore demonstrate an efficient and versatile registration technique that can have merit in multi-modal image registrations in the clinical setting

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

Efficient dense non-rigid registration using the free-form deformation framework

Medical image registration consists of finding spatial correspondences between two images or more. It is a powerful tool which is commonly used in various medical image processing tasks. Even though medical image registration has been an active topic of research for the last two decades, significant challenges in the field remain to be solved. This thesis addresses some of these challenges through extensions to the Free-Form Deformation (FFD) registration framework, which is one of the most widely used and well-established non-rigid registration algorithm. Medical image registration is a computationally expensive task because of the high degrees of freedom of the non-rigid transformations. In this work, the FFD algorithm has been re-factored to enable fast processing, while maintaining the accuracy of the results. In addition, parallel computing paradigms have been employed to provide near real-time image registration capabilities. Further modifications have been performed to improve the registration robustness to artifacts such as tissues non-uniformity. The plausibility of the generated deformation field has been improved through the use of bio-mechanical models based regularization. Additionally, diffeomorphic extensions to the algorithm were also developed. The work presented in this thesis has been extensively validated using brain magnetic resonance imaging of patients diagnosed with dementia or patients undergoing brain resection. It has also been applied to lung X-ray computed tomography and imaging of small animals. Alongside with this thesis an open-source package, NiftyReg, has been developed to release the presented work to the medical imaging community

Joint segmentation and discontinuity-preserving deformable registration: Application to cardiac cine-MR images

Medical image registration is a challenging task involving the estimation of spatial transformations to establish anatomical correspondence between pairs or groups of images. Recently, deep learning-based image registration methods have been widely explored, and demonstrated to enable fast and accurate image registration in a variety of applications. However, most deep learning-based registration methods assume that the deformation fields are smooth and continuous everywhere in the image domain, which is not always true, especially when registering images whose fields of view contain discontinuities at tissue/organ boundaries. In such scenarios, enforcing smooth, globally continuous deformation fields leads to incorrect/implausible registration results. We propose a novel discontinuity-preserving image registration method to tackle this challenge, which ensures globally discontinuous and locally smooth deformation fields, leading to more accurate and realistic registration results. The proposed method leverages the complementary nature of image segmentation and registration and enables joint segmentation and pair-wise registration of images. A co-attention block is proposed in the segmentation component of the network to learn the structural correlations in the input images, while a discontinuity-preserving registration strategy is employed in the registration component of the network to ensure plausibility in the estimated deformation fields at tissue/organ interfaces. We evaluate our method on the task of intra-subject spatio-temporal image registration using large-scale cinematic cardiac magnetic resonance image sequences, and demonstrate that our method achieves significant improvements over the state-of-the-art for medical image registration, and produces high-quality segmentation masks for the regions of interest

Efficient convolution-based pairwise elastic image registration on three multimodal similarity metrics

Producción CientíficaThis paper proposes a complete convolutional formulation for 2D multimodal pairwise image registration problems based on free-form deformations. We have reformulated in terms of discrete 1D convolutions the evaluation of spatial transformations, the regularization term, and their gradients for three different multimodal registration metrics, namely, normalized cross correlation, mutual information, and normalized mutual information. A sufficient condition on the metric gradient is provided for further extension to other metrics. The proposed approach has been tested, as a proof of concept, on contrast-enhanced first-pass perfusion cardiac magnetic resonance images. Execution times have been compared with the corresponding execution times of the classical tensor product formulation, both on CPU and GPU. The speed-up achieved by using convolutions instead of tensor products depends on the image size and the number of control points considered, the larger those magnitudes, the greater the execution time reduction. Furthermore, the speed-up will be more significant when gradient operations constitute the major bottleneck in the optimization process.Ministerio de Economía, Industria y Competitividad (grants TEC2017-82408-R and PID2020-115339RB-I00)ESAOTE Ltd (grant 18IQBM

Microscope Embedded Neurosurgical Training and Intraoperative System

In the recent years, neurosurgery has been strongly influenced by new technologies. Computer Aided Surgery (CAS) offers several benefits for patients\u27 safety but fine techniques targeted to obtain minimally invasive and traumatic treatments are required, since intra-operative false movements can be devastating, resulting in patients deaths. The precision of the surgical gesture is related both to accuracy of the available technological instruments and surgeon\u27s experience. In this frame, medical training is particularly important. From a technological point of view, the use of Virtual Reality (VR) for surgeon training and Augmented Reality (AR) for intra-operative treatments offer the best results. In addition, traditional techniques for training in surgery include the use of animals, phantoms and cadavers. The main limitation of these approaches is that live tissue has different properties from dead tissue and that animal anatomy is significantly different from the human. From the medical point of view, Low-Grade Gliomas (LGGs) are intrinsic brain tumours that typically occur in younger adults. The objective of related treatment is to remove as much of the tumour as possible while minimizing damage to the healthy brain. Pathological tissue may closely resemble normal brain parenchyma when looked at through the neurosurgical microscope. The tactile appreciation of the different consistency of the tumour compared to normal brain requires considerable experience on the part of the neurosurgeon and it is a vital point. The first part of this PhD thesis presents a system for realistic simulation (visual and haptic) of the spatula palpation of the LGG. This is the first prototype of a training system using VR, haptics and a real microscope for neurosurgery. This architecture can be also adapted for intra-operative purposes. In this instance, a surgeon needs the basic setup for the Image Guided Therapy (IGT) interventions: microscope, monitors and navigated surgical instruments. The same virtual environment can be AR rendered onto the microscope optics. The objective is to enhance the surgeon\u27s ability for a better intra-operative orientation by giving him a three-dimensional view and other information necessary for a safe navigation inside the patient. The last considerations have served as motivation for the second part of this work which has been devoted to improving a prototype of an AR stereoscopic microscope for neurosurgical interventions, developed in our institute in a previous work. A completely new software has been developed in order to reuse the microscope hardware, enhancing both rendering performances and usability. Since both AR and VR share the same platform, the system can be referred to as Mixed Reality System for neurosurgery. All the components are open source or at least based on a GPL license

A New Image Quantitative Method for Diagnosis and Therapeutic Response

abstract: Accurate quantitative information of tumor/lesion volume plays a critical role in diagnosis and treatment assessment. The current clinical practice emphasizes on efficiency, but sacrifices accuracy (bias and precision). In the other hand, many computational algorithms focus on improving the accuracy, but are often time consuming and cumbersome to use. Not to mention that most of them lack validation studies on real clinical data. All of these hinder the translation of these advanced methods from benchside to bedside. In this dissertation, I present a user interactive image application to rapidly extract accurate quantitative information of abnormalities (tumor/lesion) from multi-spectral medical images, such as measuring brain tumor volume from MRI. This is enabled by a GPU level set method, an intelligent algorithm to learn image features from user inputs, and a simple and intuitive graphical user interface with 2D/3D visualization. In addition, a comprehensive workflow is presented to validate image quantitative methods for clinical studies. This application has been evaluated and validated in multiple cases, including quantifying healthy brain white matter volume from MRI and brain lesion volume from CT or MRI. The evaluation studies show that this application has been able to achieve comparable results to the state-of-the-art computer algorithms. More importantly, the retrospective validation study on measuring intracerebral hemorrhage volume from CT scans demonstrates that not only the measurement attributes are superior to the current practice method in terms of bias and precision but also it is achieved without a significant delay in acquisition time. In other words, it could be useful to the clinical trials and clinical practice, especially when intervention and prognostication rely upon accurate baseline lesion volume or upon detecting change in serial lesion volumetric measurements. Obviously, this application is useful to biomedical research areas which desire an accurate quantitative information of anatomies from medical images. In addition, the morphological information is retained also. This is useful to researches which require an accurate delineation of anatomic structures, such as surgery simulation and planning.Dissertation/ThesisDoctoral Dissertation Biomedical Informatics 201