Accurate geometry reconstruction of vascular structures using implicit splines

3-D visualization of blood vessel from standard medical datasets (e.g. CT or MRI) play an important role in many clinical situations, including the diagnosis of vessel stenosis, virtual angioscopy, vascular surgery planning and computer aided vascular surgery. However, unlike other human organs, the vasculature system is a very complex network of vessel, which makes it a very challenging task to perform its 3-D visualization. Conventional techniques of medical volume data visualization are in general not well-suited for the above-mentioned tasks. This problem can be solved by reconstructing vascular geometry. Although various methods have been proposed for reconstructing vascular structures, most of these approaches are model-based, and are usually too ideal to correctly represent the actual variation presented by the cross-sections of a vascular structure. In addition, the underlying shape is usually expressed as polygonal meshes or in parametric forms, which is very inconvenient for implementing ramification of branching. As a result, the reconstructed geometries are not suitable for computer aided diagnosis and computer guided minimally invasive vascular surgery. In this research, we develop a set of techniques associated with the geometry reconstruction of vasculatures, including segmentation, modelling, reconstruction, exploration and rendering of vascular structures. The reconstructed geometry can not only help to greatly enhance the visual quality of 3-D vascular structures, but also provide an actual geometric representation of vasculatures, which can provide various benefits. The key findings of this research are as follows: 1. A localized hybrid level-set method of segmentation has been developed to extract the vascular structures from 3-D medical datasets. 2. A skeleton-based implicit modelling technique has been proposed and applied to the reconstruction of vasculatures, which can achieve an accurate geometric reconstruction of the vascular structures as implicit surfaces in an analytical form. 3. An accelerating technique using modern GPU (Graphics Processing Unit) is devised and applied to rendering the implicitly represented vasculatures. 4. The implicitly modelled vasculature is investigated for the application of virtual angioscopy

Coronary Artery Segmentation and Motion Modelling

Conventional coronary artery bypass surgery requires invasive sternotomy and the use of a cardiopulmonary bypass, which leads to long recovery period and has high infectious potential. Totally endoscopic coronary artery bypass (TECAB) surgery based on image guided robotic surgical approaches have been developed to allow the clinicians to conduct the bypass surgery off-pump with only three pin holes incisions in the chest cavity, through which two robotic arms and one stereo endoscopic camera are inserted. However, the restricted field of view of the stereo endoscopic images leads to possible vessel misidentification and coronary artery mis-localization. This results in 20-30% conversion rates from TECAB surgery to the conventional approach. We have constructed patient-specific 3D + time coronary artery and left ventricle motion models from preoperative 4D Computed Tomography Angiography (CTA) scans. Through temporally and spatially aligning this model with the intraoperative endoscopic views of the patient's beating heart, this work assists the surgeon to identify and locate the correct coronaries during the TECAB precedures. Thus this work has the prospect of reducing the conversion rate from TECAB to conventional coronary bypass procedures. This thesis mainly focus on designing segmentation and motion tracking methods of the coronary arteries in order to build pre-operative patient-specific motion models. Various vessel centreline extraction and lumen segmentation algorithms are presented, including intensity based approaches, geometric model matching method and morphology-based method. A probabilistic atlas of the coronary arteries is formed from a group of subjects to facilitate the vascular segmentation and registration procedures. Non-rigid registration framework based on a free-form deformation model and multi-level multi-channel large deformation diffeomorphic metric mapping are proposed to track the coronary motion. The methods are applied to 4D CTA images acquired from various groups of patients and quantitatively evaluated

Analysis of Subchondral Bone and Microvessels Using a Novel Vascular Perfusion Contrast Agent and Optimized Dual-Energy Computed Tomography

Osteoarthritis (OA), is a chronic debilitating disease that affects millions of individuals and is characterized by the degeneration of joint subchondral bone and cartilage. These tissue degenerations manifest as joint pain, limited range of joint motion, and overall diminished quality of life. Currently, the exact mechanism(s) and cause(s) by which OA initiates and progresses remain unknown. The multi-factorial complex nature of OA (i.e. age, diabetes, obesity, and prior injuries have all been shown to play a role in OA) contributes to the current lack of a cure or effective long-term treatment for OA. One re-emerging and interesting hypothesis revolves around the delicate homeostatic microvascular environment around the cartilage – an avascular tissue. The absence of blood vessels within cartilage stresses the importance of nutrient and oxygen delivery from the neighbouring synovium and subchondral bone. Currently, the effects of changes in the subchondral bone microvessel density on cartilage health remain unknown due to the difficulties in simultaneously studying dense bone and the associated small microvessels. Computed tomography (CT) is widely used in the diagnosis of OA, as the use of x-rays provide detailed images of the bone degeneration associated with OA. However, the study of microvessels using CT has been exceptionally difficult due to their small (\u3c 10 µm) size, lack of contrast from neighbouring soft tissues, and proximity to dense bone. The purpose of this thesis was to develop a novel dual-energy micro-computed tomography (DECT) compatible vascular perfusion contrast agent and the associated instrumentation to optimize DECT on pre-clinical, cone-beam micro-CT scanners. The combination of these two techniques would facilitate the simultaneous visualization and quantification of subchondral bone and microvessels within the bone underlining the cartilage (i.e. distal femoral epiphysis and proximal tibial epiphysis) of rats that have undergone an OA-induced surgery. Results gained from this study will further provide information into the role that microvessels may play in OA

복부 CT에서 간과 혈관 분할 기법

학위논문(박사)--서울대학교 대학원 :공과대학 컴퓨터공학부,2020. 2. 신영길.복부 전산화 단층 촬영 (CT) 영상에서 정확한 간 및 혈관 분할은 체적 측정, 치료 계획 수립 및 추가적인 증강 현실 기반 수술 가이드와 같은 컴퓨터 진단 보조 시스템을 구축하는데 필수적인 요소이다. 최근 들어 컨볼루셔널 인공 신경망 (CNN) 형태의 딥 러닝이 많이 적용되면서 의료 영상 분할의 성능이 향상되고 있지만, 실제 임상에 적용할 수 있는 높은 일반화 성능을 제공하기는 여전히 어렵다. 또한 물체의 경계는 전통적으로 영상 분할에서 매우 중요한 요소로 이용되었지만, CT 영상에서 간의 불분명한 경계를 추출하기가 어렵기 때문에 현대 CNN에서는 이를 사용하지 않고 있다. 간 혈관 분할 작업의 경우, 복잡한 혈관 영상으로부터 학습 데이터를 만들기 어렵기 때문에 딥 러닝을 적용하기가 어렵다. 또한 얇은 혈관 부분의 영상 밝기 대비가 약하여 원본 영상에서 식별하기가 매우 어렵다. 본 논문에서는 위 언급한 문제들을 해결하기 위해 일반화 성능이 향상된 CNN과 얇은 혈관을 포함하는 복잡한 간 혈관을 정확하게 분할하는 알고리즘을 제안한다. 간 분할 작업에서 우수한 일반화 성능을 갖는 CNN을 구축하기 위해, 내부적으로 간 모양을 추정하는 부분이 포함된 자동 컨텍스트 알고리즘을 제안한다. 또한, CNN을 사용한 학습에 경계선의 개념이 새롭게 제안된다. 모호한 경계부가 포함되어 있어 전체 경계 영역을 CNN에 훈련하는 것은 매우 어렵기 때문에 반복되는 학습 과정에서 인공 신경망이 스스로 예측한 확률에서 부정확하게 추정된 부분적 경계만을 사용하여 인공 신경망을 학습한다. 실험적 결과를 통해 제안된 CNN이 다른 최신 기법들보다 정확도가 우수하다는 것을 보인다. 또한, 제안된 CNN의 일반화 성능을 검증하기 위해 다양한 실험을 수행한다. 간 혈관 분할에서는 간 내부의 관심 영역을 지정하기 위해 앞서 획득한 간 영역을 활용한다. 정확한 간 혈관 분할을 위해 혈관 후보 점들을 추출하여 사용하는 알고리즘을 제안한다. 확실한 후보 점들을 얻기 위해, 삼차원 영상의 차원을 먼저 최대 강도 투영 기법을 통해 이차원으로 낮춘다. 이차원 영상에서는 복잡한 혈관의 구조가 보다 단순화될 수 있다. 이어서, 이차원 영상에서 혈관 분할을 수행하고 혈관 픽셀들은 원래의 삼차원 공간상으로 역 투영된다. 마지막으로, 전체 혈관의 분할을 위해 원본 영상과 혈관 후보 점들을 모두 사용하는 새로운 레벨 셋 기반 알고리즘을 제안한다. 제안된 알고리즘은 복잡한 구조가 단순화되고 얇은 혈관이 더 잘 보이는 이차원 영상에서 얻은 후보 점들을 사용하기 때문에 얇은 혈관 분할에서 높은 정확도를 보인다. 실험적 결과에 의하면 제안된 알고리즘은 잘못된 영역의 추출 없이 다른 레벨 셋 기반 알고리즘들보다 우수한 성능을 보인다. 제안된 알고리즘은 간과 혈관을 분할하는 새로운 방법을 제시한다. 제안된 자동 컨텍스트 구조는 사람이 디자인한 학습 과정이 일반화 성능을 크게 향상할 수 있다는 것을 보인다. 그리고 제안된 경계선 학습 기법으로 CNN을 사용한 영상 분할의 성능을 향상할 수 있음을 내포한다. 간 혈관의 분할은 이차원 최대 강도 투영 기반 이미지로부터 획득된 혈관 후보 점들을 통해 얇은 혈관들이 성공적으로 분할될 수 있음을 보인다. 본 논문에서 제안된 알고리즘은 간의 해부학적 분석과 자동화된 컴퓨터 진단 보조 시스템을 구축하는 데 매우 중요한 기술이다.Accurate liver and its vessel segmentation on abdominal computed tomography (CT) images is one of the most important prerequisites for computer-aided diagnosis (CAD) systems such as volumetric measurement, treatment planning, and further augmented reality-based surgical guide. In recent years, the application of deep learning in the form of convolutional neural network (CNN) has improved the performance of medical image segmentation, but it is difficult to provide high generalization performance for the actual clinical practice. Furthermore, although the contour features are an important factor in the image segmentation problem, they are hard to be employed on CNN due to many unclear boundaries on the image. In case of a liver vessel segmentation, a deep learning approach is impractical because it is difficult to obtain training data from complex vessel images. Furthermore, thin vessels are hard to be identified in the original image due to weak intensity contrasts and noise. In this dissertation, a CNN with high generalization performance and a contour learning scheme is first proposed for liver segmentation. Secondly, a liver vessel segmentation algorithm is presented that accurately segments even thin vessels. To build a CNN with high generalization performance, the auto-context algorithm is employed. The auto-context algorithm goes through two pipelines: the first predicts the overall area of a liver and the second predicts the final liver using the first prediction as a prior. This process improves generalization performance because the network internally estimates shape-prior. In addition to the auto-context, a contour learning method is proposed that uses only sparse contours rather than the entire contour. Sparse contours are obtained and trained by using only the mispredicted part of the network's final prediction. Experimental studies show that the proposed network is superior in accuracy to other modern networks. Multiple N-fold tests are also performed to verify the generalization performance. An algorithm for accurate liver vessel segmentation is also proposed by introducing vessel candidate points. To obtain confident vessel candidates, the 3D image is first reduced to 2D through maximum intensity projection. Subsequently, vessel segmentation is performed from the 2D images and the segmented pixels are back-projected into the original 3D space. Finally, a new level set function is proposed that utilizes both the original image and vessel candidate points. The proposed algorithm can segment thin vessels with high accuracy by mainly using vessel candidate points. The reliability of the points can be higher through robust segmentation in the projected 2D images where complex structures are simplified and thin vessels are more visible. Experimental results show that the proposed algorithm is superior to other active contour models. The proposed algorithms present a new method of segmenting the liver and its vessels. The auto-context algorithm shows that a human-designed curriculum (i.e., shape-prior learning) can improve generalization performance. The proposed contour learning technique can increase the accuracy of a CNN for image segmentation by focusing on its failures, represented by sparse contours. The vessel segmentation shows that minor vessel branches can be successfully segmented through vessel candidate points obtained by reducing the image dimension. The algorithms presented in this dissertation can be employed for later analysis of liver anatomy that requires accurate segmentation techniques.Chapter 1 Introduction 1 1.1 Background and motivation 1 1.2 Problem statement 3 1.3 Main contributions 6 1.4 Contents and organization 9 Chapter 2 Related Works 10 2.1 Overview 10 2.2 Convolutional neural networks 11 2.2.1 Architectures of convolutional neural networks 11 2.2.2 Convolutional neural networks in medical image segmentation 21 2.3 Liver and vessel segmentation 37 2.3.1 Classical methods for liver segmentation 37 2.3.2 Vascular image segmentation 40 2.3.3 Active contour models 46 2.3.4 Vessel topology-based active contour model 54 2.4 Motivation 60 Chapter 3 Liver Segmentation via Auto-Context Neural Network with Self-Supervised Contour Attention 62 3.1 Overview 62 3.2 Single-pass auto-context neural network 65 3.2.1 Skip-attention module 66 3.2.2 V-transition module 69 3.2.3 Liver-prior inference and auto-context 70 3.2.4 Understanding the network 74 3.3 Self-supervising contour attention 75 3.4 Learning the network 81 3.4.1 Overall loss function 81 3.4.2 Data augmentation 81 3.5 Experimental Results 83 3.5.1 Overview 83 3.5.2 Data configurations and target of comparison 84 3.5.3 Evaluation metric 85 3.5.4 Accuracy evaluation 87 3.5.5 Ablation study 93 3.5.6 Performance of generalization 110 3.5.7 Results from ground-truth variations 114 3.6 Discussion 116 Chapter 4 Liver Vessel Segmentation via Active Contour Model with Dense Vessel Candidates 119 4.1 Overview 119 4.2 Dense vessel candidates 124 4.2.1 Maximum intensity slab images 125 4.2.2 Segmentation of 2D vessel candidates and back-projection 130 4.3 Clustering of dense vessel candidates 135 4.3.1 Virtual gradient-assisted regional ACM 136 4.3.2 Localized regional ACM 142 4.4 Experimental results 145 4.4.1 Overview 145 4.4.2 Data configurations and environment 146 4.4.3 2D segmentation 146 4.4.4 ACM comparisons 149 4.4.5 Evaluation of bifurcation points 154 4.4.6 Computational performance 159 4.4.7 Ablation study 160 4.4.8 Parameter study 162 4.5 Application to portal vein analysis 164 4.6 Discussion 168 Chapter 5 Conclusion and Future Works 170 Bibliography 172 초록 197Docto

The role of tumour vasculature in fluid flow and drug transport in solid tumours

The aberrance of the vasculature in tumours has been linked to increased aggressiveness and poor drug delivery in tumours. Complexities in the microarchitecture of tumour vasculature occurring on microscopic scales can affect fluid flow and drug transport making it difficult to predict tumour response to treatment. Given this, mathematical models can play an important role in understanding the various aspects of the tumour vasculature that can promote invasiveness and limit drug delivery. In this work, computational models are developed to investigate the effect of tumour vasculature on fluid flow and drug distribution and novel imaging methods are assessed for their ability to characterise the tumour vasculature in whole human tumours. A mathematical angiogenesis model is used to generate microscopic details including individual vessel properties on a whole vascular network scale which are coupled with a fluid flow and drug transport model. The interstitial fluid pressure (IFP) in the tumour model was found to be elevated with increased heterogeneity caused by the presence of a necrotic core and heterogenous vessel permeability. Subtle changes to the network on a microscopic scale significantly influenced fluid flow in the tumour vessels and tissue. Delivery of doxorubicin to tumours was found to be highly dependent on the properties of tumour vasculature and blood flow, where regions with excessive branching and vessel tortuosity had reduced drug concentrations due to poor blood flow. Hence, the vascular density was not found to be the main factor in the accumulation of the drug within the tissue space and it’s uptake by cancer cells. An interplay between treatment strategy including dose and administration mode and properties of the vasculature was found by evaluating the spatial intracellular concentration. The fluid flow and drug transport models showed the significant effect of incorporating the microscopic properties of the tumour vasculature which can influence fluid flow and drug distribution on a macroscopic scale. The imaging methods assessed in this work shows that Optical projection tomography combined with fluorescent Immunohistochemistry labelling methods can be used to extract angiogenesis related parameters in whole human tumours. Additionally, the method was able to extract clean network topologies that show promise in application to understanding fluid flow and drug transport in real tumours.Open Acces

Quantitative imaging in cardiovascular CT angiography

In de afgelopen decennia is computertomografie (CT) een prominente niet-invasieve modaliteit om hart- en vaatziekten te evalueren geworden. Dit proefschrift heeft als doel de rol van CT in de therapeutische behandeling van coronaire hartziekte (CAD) en klepaandoeningen te onderzoeken.De relatie tussen kransslagadergeometrie (statisch en dynamisch) en aanwezigheid en omvang van CAD met CT werd onderzocht. De resultaten suggereren dat de statische geometrie van de kransslagader significant gerelateerd is aan de aanwezigheid van plaque en stenose. Er was echter geen verband tussen dynamische verandering van de coronaire arterie-geometrie en de ernst van CAD. Een algoritme om de invloed van intraluminair contrastmiddel op niet-verkalkte atherosclerotische plaque Hounsfield-Unit-waarden te corrigeren werd gepresenteerd en gevalideerd met behulp van fantomen.Diagnose en operatieplanning kunnen cruciale gevolgen hebben voor de klinische uitkomst van chirurgische ingrepen. In dit proefschrift wordt beschreven dat halfautomatische softwareprogramma’s het kwantificeren van het aortaklepgebied betere reproduceerbare resultaten toonden in vergelijking met handmatige metingen, en vergelijkbare resultaten met de huidige gouden standaard, de echocardiografie. Een systematische review over het dynamische gedrag van de aorta-annulus toont aan dat de vorm van de aorta-annulus tijdens de hartcyclus verandert, wat impliceert dat er bij het bepalen van een prothese rekening moet worden gehouden met meerdere fasen. Een andere review beschrijft het gebruik van 3D-printen in de chirurgische planning samen met andere toepassingen voor de behandeling van hartklepaandoeningen.CT is de belangrijkste beeldvormingsmodaliteit in deze onderzoeken, die gericht waren op de therapeutische behandeling van hart- en vaatziekten, van vroege risicobepaling tot diagnose en chirurgische planning.In the recent decades computed tomography (CT) has emerged as a dominant non-invasive modality to evaluate cardiovascular diseases. This thesis aimed to explore the role of CT in the therapeutic management of coronary artery disease (CAD) and valvular diseases.The relationship between both static and dynamic coronary artery geometry and presence and extent of CAD using CT was investigated. The results suggest that the static coronary artery geometry is significantly related to presence of plaque and significant stenosis. However, there were no such relationship between dynamic change of coronary artery geometry and severity of CAD. As part of this thesis an algorithm to correct the influence of lumen contrast enhancement on non-calcified atherosclerotic plaque Hounsfield-Unit values was presented. The algorithm was validated using phantoms. The diagnosis and surgical planning may have crucial impact on clinical outcome. Semi-automatic software for aortic valve area quantification presented in this thesis was proven to be more repeatable and similar to gold standard echocardiography in comparison to manual measurements. The systematic review regarding the dynamic behavior of aortic annulus revealed that aortic annulus geometry changes throughout the cardiac cycle which implies that multiple phases should be taken into account for prosthesis sizing. Another review in this thesis discusses the use of 3D printing in the surgical planning along with other applications for the treatment of valvular diseases.CT is the main imaging modality in these studies which were focused on the therapeutic management of cardiovascular diseases from early risk determination to diagnosis and surgical planning

Standardized evaluation methodology and reference database for evaluating coronary artery centerline extraction algorithms

Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: 1) a method is described to create a consensus centerline with multiple observers, 2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, 3) a database containing thirty-two cardiac CTA datasets with corresponding reference standard is described and made available, and 4) thirteen coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms

Natural ventilation design attributes application effect on, indoor natural ventilation performance of a double storey, single unit residential building

In establishing a good indoor thermal condition, air movement is one of the important parameter to be considered to provide indoor fresh air for occupants. Due to the public awareness on environment impact, people has been increasingly attentive to passive design in achieving good condition of indoor building ventilation. Throughout case studies, significant building attributes were found giving effect on building indoor natural ventilation performance. The studies were categorized under vernacular houses, contemporary houses with vernacular element and contemporary houses. The indoor air movement of every each spaces in the houses were compared with the outdoor air movement surrounding the houses to indicate the space’s indoor natural ventilation performance. Analysis found the wind catcher element appears to be the most significant attribute to contribute most to indoor natural ventilation. Wide opening was also found to be significant especially those with louvers. Whereas it is also interesting to find indoor layout design is also significantly giving impact on the performance. The finding indicates that a good indoor natural ventilation is not only dictated by having proper openings at proper location of a building, but also on how the incoming air movement is managed throughout the interior spaces by proper layout. Understanding on the air pressure distribution caused by indoor windward and leeward side is important in directing the air flow to desired spaces in producing an overall good indoor natural ventilation performance