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

Probabilistic partial volume modelling of biomedical tomographic image data

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Atlas-based segmentation and classification of magnetic resonance brain images

A wide range of different image modalities can be found today in medical imaging. These modalities allow the physician to obtain a non-invasive view of the internal organs of the human body, such as the brain. All these three dimensional images are of extreme importance in several domains of medicine, for example, to detect pathologies, follow the evolution of these pathologies, prepare and realize surgical planning with, or without, the help of robot systems or for statistical studies. Among all the medical image modalities, Magnetic Resonance (MR) imaging has become of great interest in many research areas due to its great spatial and contrast image resolution. It is therefore perfectly suited for anatomic visualization of the human body such as deep structures and tissues of the brain. Medical image analysis is a complex task because medical images usually involve a large amount of data and they sometimes present some undesirable artifacts, as for instance the noise. However, the use of a priori knowledge in the analysis of these images can greatly simplify this task. This prior information is usually represented by the reference images or atlases. Modern brain atlases are derived from high resolution cryosections or in vivo images, single subject-based or population-based, and they provide detailed images that may be interactively and easily examined in their digital format in computer assisted diagnosis or intervention. Then, in order to efficiently combine all this information, a battery of registration techniques is emerging based on transformations that bring two medical images into voxel-to-voxel correspondence. One of the main aims of this thesis is to outline the importance of including prior knowledge in the medical image analysis framework and the indispensable role of registration techniques in this task. In order to do that, several applications using atlas information are presented. First, the atlas-based segmentation in normal anatomy is shown as it is a key application of medical image analysis using prior knowledge. It consists of registering the brain images derived from different subjects and modalities within the atlas coordinate system to improve the localization and delineation of the structures of interest. However, the use of an atlas can be problematic in some particular cases where some structures, for instance a tumor or a sulcus, exists in the subject and not in the atlas. In order to solve this limitation of the atlases, a new atlas-based segmentation method for pathological brains is proposed in this thesis as well as a validation method to assess this new approach. Results show that deep structures of the brain can still be efficiently segmented using an anatomic atlas even if they are largely deformed because of a lesion. The importance of including a priori knowledge is also presented in the application of brain tissue classification. The prior information represented by the tissue templates can be included in a brain tissue segmentation approach thanks to the registration techniques. This is another important issue presented in this thesis and it is analyzed through a comparative study of several non-supervised classification techniques. These methods are selected to represent the whole range of prior information that can be used in the classification process: the image intensity, the local spatial model, and the anatomical priors. Results show that the registration between the subject and the tissue templates allows the use of prior information but the accuracy of both the prior information and the registration highly influence the performance of the classification techniques. Another aim of this thesis is to present the concept of dynamic medical image analysis, in which the prior knowledge and the registration techniques are also of main importance. Actually, many medical image applications have the objective of statically analyzing one single image, as for instance in the case of atlas-based segmentation or brain tissue classification. But in other cases the implicit idea of changes detection is present. Intuitively, since the human body is changing continuously, we would like to do the image analysis from a dynamic point of view by detecting these changes, and by comparing them afterwards with templates to know if they are normal. The need of such approaches is even more evident in the case of many brain pathologies such as tumors, multiple sclerosis or degenerative diseases. In these cases, the key point is not only to detect but also to quantify and even characterize the evolving pathology. The evaluation of lesion variations over time can be very useful, for instance in the pharmaceutical research and clinical follow up. Of course, a sequence of images is needed in order to do such an analysis. Two approaches dealing with the idea of change detection are proposed as the last (but not least) issue presented in this work. The first one consists of performing a static analysis of each image forming the data set and, then, of comparing them. The second one consists of analyzing the non-rigid transformation between the sequence images instead of the images itself. Finally, both static and dynamic approaches are illustrated with a potential application: the cortical degeneration study is done using brain tissue segmentation, and the study of multiple sclerosis lesion evolution is performed by non-rigid deformation analysis. In conclusion, the importance of including a priori information encoded in the brain atlases in medical image analysis has been put in evidence with a wide range of possible applications. In the same way, the key role of registration techniques is shown not only as an efficient way to combine all the medical image modalities but also as a main element in the dynamic medical image analysis

Multi-modality cardiac image computing: a survey

Multi-modality cardiac imaging plays a key role in the management of patients with cardiovascular diseases. It allows a combination of complementary anatomical, morphological and functional information, increases diagnosis accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. Fully-automated processing and quantitative analysis of multi-modality cardiac images could have a direct impact on clinical research and evidence-based patient management. However, these require overcoming significant challenges including inter-modality misalignment and finding optimal methods to integrate information from different modalities. This paper aims to provide a comprehensive review of multi-modality imaging in cardiology, the computing methods, the validation strategies, the related clinical workflows and future perspectives. For the computing methodologies, we have a favored focus on the three tasks, i.e., registration, fusion and segmentation, which generally involve multi-modality imaging data, either combining information from different modalities or transferring information across modalities. The review highlights that multi-modality cardiac imaging data has the potential of wide applicability in the clinic, such as trans-aortic valve implantation guidance, myocardial viability assessment, and catheter ablation therapy and its patient selection. Nevertheless, many challenges remain unsolved, such as missing modality, modality selection, combination of imaging and non-imaging data, and uniform analysis and representation of different modalities. There is also work to do in defining how the well-developed techniques fit in clinical workflows and how much additional and relevant information they introduce. These problems are likely to continue to be an active field of research and the questions to be answered in the future

Multimodal image analysis of the human brain

Gedurende de laatste decennia heeft de snelle ontwikkeling van multi-modale en niet-invasieve hersenbeeldvorming technologieën een revolutie teweeg gebracht in de mogelijkheid om de structuur en functionaliteit van de hersens te bestuderen. Er is grote vooruitgang geboekt in het beoordelen van hersenschade door gebruik te maken van Magnetic Reconance Imaging (MRI), terwijl Elektroencefalografie (EEG) beschouwd wordt als de gouden standaard voor diagnose van neurologische afwijkingen. In deze thesis focussen we op de ontwikkeling van nieuwe technieken voor multi-modale beeldanalyse van het menselijke brein, waaronder MRI segmentatie en EEG bronlokalisatie. Hierdoor voegen we theorie en praktijk samen waarbij we focussen op twee medische applicaties: (1) automatische 3D MRI segmentatie van de volwassen hersens en (2) multi-modale EEG-MRI data analyse van de hersens van een pasgeborene met perinatale hersenschade. We besteden veel aandacht aan de verbetering en ontwikkeling van nieuwe methoden voor accurate en ruisrobuuste beeldsegmentatie, dewelke daarna succesvol gebruikt worden voor de segmentatie van hersens in MRI van zowel volwassen als pasgeborenen. Daarenboven ontwikkelden we een geïntegreerd multi-modaal methode voor de EEG bronlokalisatie in de hersenen van een pasgeborene. Deze lokalisatie wordt gebruikt voor de vergelijkende studie tussen een EEG aanval bij pasgeborenen en acute perinatale hersenletsels zichtbaar in MRI

Bayesian generative learning of brain and spinal cord templates from neuroimaging datasets

In the field of neuroimaging, Bayesian modelling techniques have been largely adopted and recognised as powerful tools for the purpose of extracting quantitative anatomical and functional information from medical scans. Nevertheless the potential of Bayesian inference has not yet been fully exploited, as many available tools rely on point estimation techniques, such as maximum likelihood estimation, rather than on full Bayesian inference. The aim of this thesis is to explore the value of approximate learning schemes, for instance variational Bayes, to perform inference from brain and spinal cord MRI data. The applications that will be explored in this work mainly concern image segmentation and atlas construction, with a particular emphasis on the problem of shape and intensity prior learning, from large training data sets of structural MR scans. The resulting computational tools are intended to enable integrated brain and spinal cord morphometric analyses, as opposed to the approach that is most commonly adopted in neuroimaging, which consists in optimising separate tools for brain and spine morphometrics

Development and application of quantitative image analysis for preclinical MRI research

The aim of this thesis is to develop quantitative analysis methods to validate MRI and improve the detection of tumour infiltration. The major components include a description of the development the quantitative methods to better validate imaging biomarkers and detect of infiltration of tumour cells into normal tissue, which were then applied to a mouse model of glioblastoma invasion. To do this, a new histology model, called Stacked In-plane Histology (SIH), was developed to allow a quantitative analysis of MRI. Validating imaging biomarkers for glioblastoma infiltration Cancer can be defined as a disease in which a group of abnormal cells grow uncontrollably, often with fatal outcomes. According to (Cancer research UK, 2019), there are more than 363,000 new cancer cases in the UK every year, an increase from the 990 cases reported daily in 2014-2016, with only half of all patients recovering. Glioblastoma (GB) is the most frequent and malignant form of primary brain tumours with a very poor prognosis. Even with the development of modern diagnostic strategies and new therapies, the five-year survival rate is just 5%, with the median survival time only 14 months. Unfortunately, glioblastoma can affect patients at any age, including young children, but has a peak occurrence between the ages of 65 and 75 years. The standard treatment for GB consists of surgical resection, followed by radiotherapy and chemotherapy. However, the infiltration of GB cells into healthy adjacent brain tissue is a major obstacle for successful treatment, making complete removal of a tumour by surgery a difficult task, with the potential for tumour recurrence. Magnetic Resonance Imaging (MRI) is a non-invasive, multipurpose imaging tool used for the diagnosis and monitoring of cancerous tumours. It can provide morphological, physiological, and metabolic information about the tumour. Currently, MRI is the standard diagnostic tool for GB before the pathological examination of tissue from surgical resection or biopsy specimens. The standard MRI sequences used for diagnosis of GB include T2-Weighted (T2W), T1-Weighted (T1W), Fluid-Attenuated Inversion Recovery (FLAIR), and Contrast Enhance T1 gadolinium (CE-T1) scans. These conventional scans are used to localize the tumour, in addition to associated oedema and necrosis. Although these scans can identify the bulk of the tumour, it is known that they do not detect regions infiltrated by GB cells. The MRI signal depends upon many physical parameters including water content, local structure, tumbling rates, diffusion, and hypoxia (Dominietto, 2014). There has been considerable interest in identifying whether such biologically indirect image contrasts can be used as non-invasive imaging biomarkers, either for normal biological functions, pathogenic processes or pharmacological responses to therapeutic interventions (Atkinson et al., 2001). In fact, when new MRI methods are proposed as imaging biomarkers of particular diseases, it is crucial that they are validated against histopathology. In humans, such validation is limited to a biopsy, which is the gold standard of diagnosis for most types of cancer. Some types of biopsies can take an image-guided approach using MRI, Computed Tomography (CT) or Ultrasound (US). However, a biopsy may miss the most malignant region of the tumour and is difficult to repeat. Biomarker validation can be performed in preclinical disease models, where the animal can be terminated immediately after imaging for histological analysis. Here, in principle, co-registration of the biomarker images with the histopathology would allow for direct validation. However, in practice, most preclinical validation studies have been limited to using simple visual comparisons to assess the correlation between the imaging biomarker and underlying histopathology. First objective (Chapter 5): Histopathology is the gold standard for assessing non-invasive imaging biomarkers, with most validation approaches involving a qualitative visual inspection. To allow a more quantitative analysis, previous studies have attempted to co-register MRI with histology. However, these studies have focused on developing better algorithms to deal with the distortions common in histology sections. By contrast, we have taken an approach to improve the quality of the histological processing and analysis, for example, by taking into account the imaging slice orientation and thickness. Multiple histology sections were cut in the MR imaging plane to produce a Stacked In-plane Histology (SIH) map. This approach, which is applied to the next two objectives, creates a histopathology map which can be used as the gold standard to quantitatively validate imaging biomarkers. Second objective (Chapter 6): Glioblastoma is the most malignant form of primary brain tumour and recurrence following treatment is common. Non-invasive MR imaging is an important component of brain tumour diagnosis and treatment planning. Unfortunately, clinic MRI (T1W, T2W, CE-T1, and FLAIR) fails to detect regions of glioblastoma cell infiltration beyond the solid tumour region identified by contrast enhanced T1 scans. However, advanced MRI techniques such as Arterial Spin Labelling (ASL) could provide us with extra information (perfusion) which may allow better detection of infiltration. In order to assess whether local perfusion perturbation could provide a useful biomarker for glioblastoma cell infiltration, we quantitatively analysed the correlation between perfusion MRI (ASL) and stacked in-plane histology. This work used a mouse model of glioblastoma that mimics the infiltrative behaviour found in human patients. The results demonstrate the ability of perfusion imaging to probe regions of low tumour cell infiltration, while confirming the sensitivity limitations of clinic imaging modalities. Third objective (Chapter 7): It is widely hypothesised that Multiparametric MRI (mpMRI), can extract more information than is obtained from the constituent individual MR images, by reconstructing a single map that contains complementary information. Using the MRI and histology dataset from objective 2, we used a multi-regression algorithm to reconstruct a single map which was highly correlated (r>0.6) with histology. The results are promising, showing that mpMRI can better predict the whole tumour region, including the region of tumour cell infiltration

Multimodal Image Fusion and Its Applications.

Image fusion integrates different modality images to provide comprehensive information of the image content, increasing interpretation capabilities and producing more reliable results. There are several advantages of combining multi-modal images, including improving geometric corrections, complementing data for improved classification, and enhancing features for analysis...etc. This thesis develops the image fusion idea in the context of two domains: material microscopy and biomedical imaging. The proposed methods include image modeling, image indexing, image segmentation, and image registration. The common theme behind all proposed methods is the use of complementary information from multi-modal images to achieve better registration, feature extraction, and detection performances. In material microscopy, we propose an anomaly-driven image fusion framework to perform the task of material microscopy image analysis and anomaly detection. This framework is based on a probabilistic model that enables us to index, process and characterize the data with systematic and well-developed statistical tools. In biomedical imaging, we focus on the multi-modal registration problem for functional MRI (fMRI) brain images which improves the performance of brain activation detection.PhDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120701/1/yuhuic_1.pd