간 조영술을 위한 혈관 모델 기반의 국부 적응 2D-3D 정합 알고리즘 기법 연구

학위논문 (박사)-- 서울대학교 대학원 : 전기·컴퓨터공학부, 2017. 2. 신영길.Two-dimensional–three-dimensional (2D–3D) registration between intra-operative 2D digital subtraction angiography (DSA) and pre-operative 3D computed tomography angiography (CTA) can be used for roadmapping purposes. However, through the projection of 3D vessels, incorrect intersections and overlaps between vessels are produced because of the complex vascular structure, which make it difficult to obtain the correct solution of 2D–3D registration. To overcome these problems, we propose a registration method that selects a suitable part of a 3D vascular structure for a given DSA image and finds the optimized solution to the partial 3D structure. The proposed algorithm can reduce the registration errors because it restricts the range of the 3D vascular structure for the registration by using only the relevant 3D vessels with the given DSA. To search for the appropriate 3D partial structure, we first construct a tree model of the 3D vascular structure and divide it into several subtrees in accordance with the connectivity. Then, the best matched subtree with the given DSA image is selected using the results from the coarse registration between each subtree and the vessels in the DSA image. Finally, a fine registration is conducted to minimize the difference between the selected subtree and the vessels of the DSA image. In experimental results obtained using 10 clinical datasets, the average distance errors in the case of the proposed method were 2.34 ± 1.94 mm. The proposed algorithm converges faster and produces more correct results than the conventional method in evaluations on patient datasets.Chapter 1 Introduction 1 1.1 Background 1 1.2 Problem statement 6 1.3 Main contributions 8 1.4 Contents organization 10 Chapter 2 Related Works 12 2.1 Overview 12 2.1.1 Definitions 14 2.1.2 Intensity-based and feature-based registration 17 2.2 Neurovascular applications 19 2.3 Liver applications 22 2.4 Cardiac applications 27 2.4.1 Rigid registration 27 2.4.2 Non-rigid registration 31 Chapter 3 3D Vascular Structure Model 33 3.1 Vessel segmentation 34 3.1.1 Overview 34 3.1.2 Vesselness filter 36 3.1.3 Vessel segmentation 39 3.2 Skeleton extraction 40 3.2.1 Overview 40 3.2.2 Skeleton extraction based on fast marching method 41 3.3 Graph construction 45 3.4 Generation of subtree structures from 3D tree model 46 Chapter 4 Locally Adaptive Registration 52 4.1 2D centerline extraction 53 4.1.1 Extraction from a single DSA image 54 4.1.2 Extraction from angiographic image sequence 55 4.2 Coarse registration for the detection of the best matched subtree 58 4.3 Fine registration with selected 3D subtree 61 Chapter 5 Experimental Results 63 5.1 Materials 63 5.2 Phantom study 65 5.3 Performance evaluation 69 5.3.1 Evaluation for a single DSA image 69 5.3.2 Evaluation for angiographic image sequence 75 5.4 Comparison with other methods 77 5.5 Parameter study 87 Chapter 6 Conclusion 90 Bibliography 92 초록 109Docto

3D-3D Deformable Registration and Deep Learning Segmentation based Neck Diseases Analysis in MRI

Whiplash, cervical dystonia (CD), neck pain and work-related upper limb disorder (WRULD) are the most common diseases in the cervical region. Headaches, stiffness, sensory disturbance to the legs and arms, optical problems, aching in the back and shoulder, and auditory and visual problems are common symptoms seen in patients with these diseases. CD patients may also suffer tormenting spasticity in some neck muscles, with the symptoms possibly being acute and persisting for a long time, sometimes a lifetime. Whiplash-associated disorders (WADs) may occur due to sudden forward and backward movements of the head and neck occurring during a sporting activity or vehicle or domestic accident. These diseases affect private industries, insurance companies and governments, with the socio-economic costs significantly related to work absences, long-term sick leave, early disability and disability support pensions, health care expenses, reduced productivity and insurance claims. Therefore, diagnosing and treating neck-related diseases are important issues in clinical practice. The reason for these afflictions resulting from accident is the impairment of the cervical muscles which undergo atrophy or pseudo-hypertrophy due to fat infiltrating into them. These morphological changes have to be determined by identifying and quantifying their bio-markers before applying any medical intervention. Volumetric studies of neck muscles are reliable indicators of the proper treatments to apply. Radiation therapy, chemotherapy, injection of a toxin or surgery could be possible ways of treating these diseases. However, the dosages required should be precise because the neck region contains some sensitive organs, such as nerves, blood vessels and the trachea and spinal cord. Image registration and deep learning-based segmentation can help to determine appropriate treatments by analyzing the neck muscles. However, this is a challenging task for medical images due to complexities such as many muscles crossing multiple joints and attaching to many bones. Also, their shapes and sizes vary greatly across populations whereas their cross-sectional areas (CSAs) do not change in proportion to the heights and weights of individuals, with their sizes varying more significantly between males and females than ages. Therefore, the neck's anatomical variabilities are much greater than those of other parts of the human body. Some other challenges which make analyzing neck muscles very difficult are their compactness, similar gray-level appearances, intra-muscular fat, sliding due to cardiac and respiratory motions, false boundaries created by intramuscular fat, low resolution and contrast in medical images, noise, inhomogeneity and background clutter with the same composition and intensity. Furthermore, a patient's mode, position and neck movements during the capture of an image create variability. However, very little significant research work has been conducted on analyzing neck muscles. Although previous image registration efforts form a strong basis for many medical applications, none can satisfy the requirements of all of them because of the challenges associated with their implementation and low accuracy which could be due to anatomical complexities and variabilities or the artefacts of imaging devices. In existing methods, multi-resolution- and heuristic-based methods are popular. However, the above issues cause conventional multi-resolution-based registration methods to be trapped in local minima due to their low degrees of freedom in their geometrical transforms. Although heuristic-based methods are good at handling large mismatches, they require pre-segmentation and are computationally expensive. Also, current deformable methods often face statistical instability problems and many local optima when dealing with small mismatches. On the other hand, deep learning-based methods have achieved significant success over the last few years. Although a deeper network can learn more complex features and yields better performances, its depth cannot be increased as this would cause the gradient to vanish during training and result in training difficulties. Recently, researchers have focused on attention mechanisms for deep learning but current attention models face a challenge in the case of an application with compact and similar small multiple classes, large variability, low contrast and noise. The focus of this dissertation is on the design of 3D-3D image registration approaches as well as deep learning-based semantic segmentation methods for analyzing neck muscles. In the first part of this thesis, a novel object-constrained hierarchical registration framework for aligning inter-subject neck muscles is proposed. Firstly, to handle large-scale local minima, it uses a coarse registration technique which optimizes a new edge position difference (EPD) similarity measure to align large mismatches. Also, a new transformation based on the discrete periodic spline wavelet (DPSW), affine and free-form-deformation (FFD) transformations are exploited. Secondly, to avoid the monotonous nature of using transformations in multiple stages, affine registration technique, which uses a double-pushing system by changing the edges in the EPD and switching the transformation's resolutions, is designed to align small mismatches. The EPD helps in both the coarse and fine techniques to implement object-constrained registration via controlling edges which is not possible using traditional similarity measures. Experiments are performed on clinical 3D magnetic resonance imaging (MRI) scans of the neck, with the results showing that the EPD is more effective than the mutual information (MI) and the sum of squared difference (SSD) measures in terms of the volumetric dice similarity coefficient (DSC). Also, the proposed method is compared with two state-of-the-art approaches with ablation studies of inter-subject deformable registration and achieves better accuracy, robustness and consistency. However, as this method is computationally complex and has a problem handling large-scale anatomical variabilities, another 3D-3D registration framework with two novel contributions is proposed in the second part of this thesis. Firstly, a two-stage heuristic search optimization technique for handling large mismatches,which uses a minimal user hypothesis regarding these mismatches and is computationally fast, is introduced. It brings a moving image hierarchically closer to a fixed one using MI and EPD similarity measures in the coarse and fine stages, respectively, while the images do not require pre-segmentation as is necessary in traditional heuristic optimization-based techniques. Secondly, a region of interest (ROI) EPD-based registration framework for handling small mismatches using salient anatomical information (AI), in which a convex objective function is formed through a unique shape created from the desired objects in the ROI, is proposed. It is compared with two state-of-the-art methods on a neck dataset, with the results showing that it is superior in terms of accuracy and is computationally fast. In the last part of this thesis, an evaluation study of recent U-Net-based convolutional neural networks (CNNs) is performed on a neck dataset. It comprises 6 recent models, the U-Net, U-Net with a conditional random field (CRF-Unet), attention U-Net (A-Unet), nested U-Net or U-Net++, multi-feature pyramid (MFP)-Unet and recurrent residual U-Net (R2Unet) and 4 with more comprehensive modifications, the multi-scale U-Net (MS-Unet), parallel multi-scale U-Net (PMSUnet), recurrent residual attention U-Net (R2A-Unet) and R2A-Unet++ in neck muscles segmentation, with analyses of the numerical results indicating that the R2Unet architecture achieves the best accuracy. Also, two deep learning-based semantic segmentation approaches are proposed. In the first, a new two-stage U-Net++ (TS-UNet++) uses two different types of deep CNNs (DCNNs) rather than one similar to the traditional multi-stage method, with the U-Net++ in the first stage and the U-Net in the second. More convolutional blocks are added after the input and before the output layers of the multi-stage approach to better extract the low- and high-level features. A new concatenation-based fusion structure, which is incorporated in the architecture to allow deep supervision, helps to increase the depth of the network without accelerating the gradient-vanishing problem. Then, more convolutional layers are added after each concatenation of the fusion structure to extract more representative features. The proposed network is compared with the U-Net, U-Net++ and two-stage U-Net (TS-UNet) on the neck dataset, with the results indicating that it outperforms the others. In the second approach, an explicit attention method, in which the attention is performed through a ROI evolved from ground truth via dilation, is proposed. It does not require any additional CNN, as does a cascaded approach, to localize the ROI. Attention in a CNN is sensitive with respect to the area of the ROI. This dilated ROI is more capable of capturing relevant regions and suppressing irrelevant ones than a bounding box and region-level coarse annotation, and is used during training of any CNN. Coarse annotation, which does not require any detailed pixel wise delineation that can be performed by any novice person, is used during testing. This proposed ROI-based attention method, which can handle compact and similar small multiple classes with objects with large variabilities, is compared with the automatic A-Unet and U-Net, and performs best

Development of registration methods for cardiovascular anatomy and function using advanced 3T MRI, 320-slice CT and PET imaging

Different medical imaging modalities provide complementary anatomical and functional information. One increasingly important use of such information is in the clinical management of cardiovascular disease. Multi-modality data is helping improve diagnosis accuracy, and individualize treatment. The Clinical Research Imaging Centre at the University of Edinburgh, has been involved in a number of cardiovascular clinical trials using longitudinal computed tomography (CT) and multi-parametric magnetic resonance (MR) imaging. The critical image processing technique that combines the information from all these different datasets is known as image registration, which is the topic of this thesis. Image registration, especially multi-modality and multi-parametric registration, remains a challenging field in medical image analysis. The new registration methods described in this work were all developed in response to genuine challenges in on-going clinical studies. These methods have been evaluated using data from these studies. In order to gain an insight into the building blocks of image registration methods, the thesis begins with a comprehensive literature review of state-of-the-art algorithms. This is followed by a description of the first registration method I developed to help track inflammation in aortic abdominal aneurysms. It registers multi-modality and multi-parametric images, with new contrast agents. The registration framework uses a semi-automatically generated region of interest around the aorta. The aorta is aligned based on a combination of the centres of the regions of interest and intensity matching. The method achieved sub-voxel accuracy. The second clinical study involved cardiac data. The first framework failed to register many of these datasets, because the cardiac data suffers from a common artefact of magnetic resonance images, namely intensity inhomogeneity. Thus I developed a new preprocessing technique that is able to correct the artefacts in the functional data using data from the anatomical scans. The registration framework, with this preprocessing step and new particle swarm optimizer, achieved significantly improved registration results on the cardiac data, and was validated quantitatively using neuro images from a clinical study of neonates. Although on average the new framework achieved accurate results, when processing data corrupted by severe artefacts and noise, premature convergence of the optimizer is still a common problem. To overcome this, I invented a new optimization method, that achieves more robust convergence by encoding prior knowledge of registration. The registration results from this new registration-oriented optimizer are more accurate than other general-purpose particle swarm optimization methods commonly applied to registration problems. In summary, this thesis describes a series of novel developments to an image registration framework, aimed to improve accuracy, robustness and speed. The resulting registration framework was applied to, and validated by, different types of images taken from several ongoing clinical trials. In the future, this framework could be extended to include more diverse transformation models, aided by new machine learning techniques. It may also be applied to the registration of other types and modalities of imaging data

Atlas based image reconstruction for diffuse optical imaging of the human brain

Diffuse Optical Tomography (DOT) has been applied to imaging functional activations in the adult brain. Registered-atlas models are acceptable alternative forward models for the subject-specific models. In this work, different landmark-based rigid registration methods are quantitatively evaluated and compared in geometrical accuracy of the registration result, accuracy of light propagation approximation and recovery accuracy of the brain activations based on the whole head and localized head regions. The most suitable registration methods are selected based on accuracy and efficiency and they vary based on region of interest. For example, the most suitable registration method for recovery of whole cortex activation is the registration method based on 19 landmarks from the EEG 10/20 system and non-iterative Point to Point algorithms (EEG19nP2P registration). Efficiency of the recovery process is another popular research area in DOT. In this work, a modified generation approach of the light propagation approximation is designed based on a reduced sensitivity matrix and parallelisation process. It improves the storage efficiency by >1000% and time efficiency by ~400%. Based on this approach, the brain activation recovery of DOT can be processed on a normal laptop without large memory requirements within 45 minutes which is more suitable for a portable system

Entwicklung von Regularisierungsverfahren und zusammengesetzten Ähnlichkeitsmaßen für die multimodale Bildregistrierung in der medizinischen Physik

Ziel dieser Arbeit ist die Untersuchung und Weiterentwicklung von Ähnlichkeitsmaßen zur Registrierung von multimodalen medizinischen Bilddaten wie sie zum Beispiel in der Planung und Diagnose von klinischen Eingriffen zum Einsatz kommen. Hierbei wird zunächst eine Methode mit einem anisotropen Regularisierungsterm zur elastischen Registrierung von EPI-Daten vorgestellt, der speziell für das zu Grunde liegende Problem entwickelt wurde und dadurch genauere Registrierungsergebnisse ermöglicht. Außerdem werden anhand von rigiden Problemstellungen zwei Konzepte zur Registrierung entwickelt, bei denen zwei Maße zur Messung der Ähnlichkeit kombiniert werden. Durch die vorgestellte Linearkombination zweier Maße, die auf verschiedenen Bildmerkmalen beruhen, wird ein Ähnlichkeitsmaß erzeugt, das vielseitiger einsetzbar ist als die einzelnen Maße. Durch das in dieser Arbeit entwickelte Konzept einer Homotopie von Ähnlichkeitsmaßen, bei dem die Maße durch eine dynamische Gewichtungsfunktion verknüpft werden, lassen sich dagegen die Stärken zweier Maße kombinieren, die diese in unterschiedlichen Phasen der Optimierung aufweisen. Im hier präsentierten Fall kann somit eine kürzere Laufzeit und eine erhöhte Robustheit gegenüber Fehlregistrierungen bei gleicher Genauigkeit erzielt werden. Für die Evaluation der elastischen Registrierungsmethoden wird in dieser Arbeit zusätzlich ein neues Maß entwickelt und diskutiert, das durch eine automatische und damit objektive Auswertung der Registrierungsergebnisse einen Vergleich der Ergebnisse verschiedener Methoden ermöglicht