Fusion and Analysis of Multidimensional Medical Image Data

Analýza medicínských obrazů je předmětem základního výzkumu již řadu let. Za tu dobu bylo v této oblasti publikováno mnoho výzkumných prací zabývajících se dílčími částmi jako je rekonstrukce obrazů, restaurace, segmentace, klasifikace, registrace (lícování) a fúze. Kromě obecného úvodu, pojednává tato disertační práce o dvou medicínsky orientovaných tématech, jež byla formulována ve spolupráci s Philips Netherland BV, divizí Philips Healthcare. První téma je zaměřeno na oblast zpracování obrazů subtrakční angiografie dolních končetin člověka získaných pomocí výpočetní X-Ray tomografie (CT). Subtrakční angiografie je obvykle využívaná při podezření na periferní cévní onemocnění (PAOD) nebo při akutním poškození dolních končetin jako jsou fraktury apod. Současné komerční metody nejsou dostatečně spolehlivé už v předzpracování, jako je například odstranění pacientského stolu, pokrývky, dlahy, apod. Spolehlivost a přesnost identifikace cév v subtrahovaných datech vedoucích v blízkosti kostí je v důsledku Partial Volume artefaktu rovněž nízká. Automatické odstranění kalcifikací nebo detekce malých cév doplňujících nezbytnou informaci o náhradním zásobení dolních končetin krví v případě přerušení hlavních zásobujících cév v současné době rovněž nesplňují kritéria pro plně automatické zpracování. Proto hlavním cílem týkající se tohoto tématu bylo vyvinout automatický systém, který by mohl současné nedostatky v CTSA vyšetření odstranit. Druhé téma je orientováno na identifikaci patologických změn na páteři člověka v CT obrazech se zaměřením na osteolytické a osteoblastické léze u jednotlivých obratlů. Tyto změny obvykle nastávají v důsledků postižení metastazujícím procesem rakovinového onemocnění. Pro detekci patologických změn je pak potřeba identifikace a segmentace jednotlivých obratlů. Přesnost analýzy jednotlivých lézí však závisí rovněž na správné identifikaci těla a zadních segmentů u jednotlivých obratlů a na segmentaci trabekulárního centra obratlů, tj. odstranění kortikální kosti. Během léčby mohou být pacienti skenováni vícekrát, obvykle s několika-mesíčním odstupem. Hodnocení případného vývoje již detekovaných patologických změn pak logicky vychází ze správné detekce patologií v jednotlivých obratlech korespondujících si v jednotlivých akvizicích. Jelikož jsou příslušné obratle v jednotlivých akvizicích obvykle na různé pozici, jejich fúze, vedoucí k analýze časového vývoje detekovaných patologií, je komplikovaná. Požadovaným výsledkem v tomto tématu je vytvoření komplexního systému pro detekci patologických změn v páteři, především osteoblastických a osteolytických lézí. Takový systém tedy musí umožnovat jak segmentaci jednotlivých obratlů, jejich automatické rozdělení na hlavní části a odstranění kortikální kosti, tak také detekci patologických změn a jejich hodnocení. Ačkoliv je tato disertační práce v obou výše zmíněných tématech primárně zaměřena na experimentální část zpracování medicínských obrazů, zabývá se všemi nezbytnými kroky, jako je předzpracování, registrace, dodatečné zpracování a hodnocení výsledků, vedoucími k možné aplikovatelnosti obou systému v klinické praxi. Jelikož oba systémy byly řešeny v rámci týmové spolupráce jako celek, u obou témat jsou pro některé konkrétní kroky uvedeny odkazy na doktorskou práci Miloše Malínského.Analysis of medical images has been subject of basic research for many years. Many research papers have been published in the field related to image analysis and focused on partial aspects such as reconstruction, restoration, segmentation and classification, registration (spatial alignment) and fusion. Besides the introduction of related general concepts used in medical image processing, this thesis deals with two specific medical problems formulated in cooperation with Philips Netherland BV, Philips Healthcare division. The first topic is focused on subtraction angiography in patients’ lower legs utilizing image data from X-Ray computed tomography (CT). CT subtraction angiography (CTSA) is typically used for indication of the Peripheral Artery Occlusive Disease (PAOD) and for examination of acute injuries of lower legs such as acute fractures, etc. Current methods in clinical praxis are not sufficient regarding the pre-processing such as masking of patient desk, cover, splint, etc. The subtraction of blood vessels adjacent to neighboring bones in lower legs is of low accuracy due to the Partial Volume artifact. Masking of calcifications and detection of tiny blood vessels complementing necessary information about the alternative blood supply in lower legs in case of obstruction in main arteries is also not reliable for fully automated process presently. Therefore, the main aim regarding this topic was to develop an automated framework that could overcome current shortcomings in CTSA examination. The second topic is oriented on the identification and evaluation of pathologic changes in human spine, focusing on osteolytic and osteoblastic lesions in individual vertebrae in CT images. Such changes occur typically as a consequence of metastasizing process of cancerous disease. For the detection of pathologic changes, an identification and segmentation of individual vertebrae is necessary. Moreover, the analysis of individual lesions in vertebrae depends also on correct identification of vertebral body and posterior segments of each vertebra, and on segmentation of their trabecular centers. Patients are typically examined more than once during their therapy. Then, the evaluation of possible tumorous progression is based on accurate detection of pathologies in individual vertebrae in the base-line and corresponding follow-up images. Since the corresponding vertebrae are in mutually different positions in the follow-up images, their fusion leading to the analysis of the lesion progression is complicated. The main aim regarding this topic is to develop a complex framework for detection of pathologic lesions on spine, with the main focus on osteoblastic and osteolystic lesions. Such system has to provide not only reliable segmentation of individual vertebrae and detection of their main regions but also the masking of their cortical bone, detection of their pathologic changes and their evaluation. Although this dissertation thesis is primarily oriented at the experimental part of medical image processing considering both the above mentioned topics, it deals with all necessary processing steps, i.e. preprocessing, image registration, post-processing and evaluation of results, leading to the future use of both frameworks in clinical practice. Since both frameworks were developed in a team, there are some chapters referring to the dissertation thesis of Milos Malinsky.

Intravascular Ultrasound

Intravascular ultrasound (IVUS) is a cardiovascular imaging technology using a specially designed catheter with a miniaturized ultrasound probe for the assessment of vascular anatomy with detailed visualization of arterial layers. Over the past two decades, this technology has developed into an indispensable tool for research and clinical practice in cardiovascular medicine, offering the opportunity to gather diagnostic information about the process of atherosclerosis in vivo, and to directly observe the effects of various interventions on the plaque and arterial wall. This book aims to give a comprehensive overview of this rapidly evolving technique from basic principles and instrumentation to research and clinical applications with future perspectives

International Union of Angiology (IUA) consensus paper on imaging strategies in atherosclerotic carotid artery imaging: From basic strategies to advanced approaches

Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases. Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%–20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries). While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques

Clinical advances in cardiovascular magnetic resonace imaging and angiography

Cardiovascular magnetic resonance imaging is an important noninvasive imaging modality for the diagnosis, clinical work‐up and treatment planning in patients suspected for a wide range of cardiovascular pathology. CMR imaging is accurate and reliable, and provides invaluable information to evaluate the cardiovascular system without the need of ionizing radiation. The studies described in this thesis evaluate new CMR imaging techniques in clinical practice and explore the prognostic value of new CMR imaging biomarkers in patients with symptomatic peripheral arterial occlusive disease. New advances and innovations in MR imaging technology improve and further expand the clinical applications of cardiovascular imaging in daily clinical practice. In this thesis, a new, fast free‐breathing 2D delayed‐enhancement MRI sequence is validated and demonstrated to be a reliable tool for detecting myocardial infarction. Furthermore, new technical developments allow single‐injection, three‐station, moving‐table MRA protocol at 3Tesla with similar diagnostic performance when compared to 1.5Tesla. Additionally, submillimeter isotropic voxel acquisition in the lower legs at 1.5Tesla improves the diagnostic accuracy and depicts more open infragenual arterial segments.Additionally, it is demonstrated that new MRI biomarkers as distal aortic pulse wave velocity statistically significantly correlate with stenosis severity in symptomatic patients with peripheral arterial occlusive disease. Finally, we showed that CMR derived biomarkers relating to stenosis severity, aortic stiffness and left ventricular function play a role in prognosis of outcome in patients with symptomatic PAOD. In the future, incorporation of the described new MRI biomarkers in the clinical workup of peripheral arterial occlusive disease may play an important role for full vascular risk assessment and ultimately, patients may benefit in clinical practice.LUMC / Geneeskunde Repositoriu

Advanced Algorithms for 3D Medical Image Data Fusion in Specific Medical Problems

Fúze obrazu je dnes jednou z nejběžnějších avšak stále velmi diskutovanou oblastí v lékařském zobrazování a hraje důležitou roli ve všech oblastech lékařské péče jako je diagnóza, léčba a chirurgie. V této dizertační práci jsou představeny tři projekty, které jsou velmi úzce spojeny s oblastí fúze medicínských dat. První projekt pojednává o 3D CT subtrakční angiografii dolních končetin. V práci je využito kombinace kontrastních a nekontrastních dat pro získání kompletního cévního stromu. Druhý projekt se zabývá fúzí DTI a T1 váhovaných MRI dat mozku. Cílem tohoto projektu je zkombinovat stukturální a funkční informace, které umožňují zlepšit znalosti konektivity v mozkové tkáni. Třetí projekt se zabývá metastázemi v CT časových datech páteře. Tento projekt je zaměřen na studium vývoje metastáz uvnitř obratlů ve fúzované časové řadě snímků. Tato dizertační práce představuje novou metodologii pro klasifikaci těchto metastáz. Všechny projekty zmíněné v této dizertační práci byly řešeny v rámci pracovní skupiny zabývající se analýzou lékařských dat, kterou vedl pan Prof. Jiří Jan. Tato dizertační práce obsahuje registrační část prvního a klasifikační část třetího projektu. Druhý projekt je představen kompletně. Další část prvního a třetího projektu, obsahující specifické předzpracování dat, jsou obsaženy v disertační práci mého kolegy Ing. Romana Petera.Image fusion is one of today´s most common and still challenging tasks in medical imaging and it plays crucial role in all areas of medical care such as diagnosis, treatment and surgery. Three projects crucially dependent on image fusion are introduced in this thesis. The first project deals with the 3D CT subtraction angiography of lower limbs. It combines pre-contrast and contrast enhanced data to extract the blood vessel tree. The second project fuses the DTI and T1-weighted MRI brain data. The aim of this project is to combine the brain structural and functional information that purvey improved knowledge about intrinsic brain connectivity. The third project deals with the time series of CT spine data where the metastases occur. In this project the progression of metastases within the vertebrae is studied based on fusion of the successive elements of the image series. This thesis introduces new methodology of classifying metastatic tissue. All the projects mentioned in this thesis have been solved by the medical image analysis group led by Prof. Jiří Jan. This dissertation concerns primarily the registration part of the first project and the classification part of the third project. The second project is described completely. The other parts of the first and third project, including the specific preprocessing of the data, are introduced in detail in the dissertation thesis of my colleague Roman Peter, M.Sc.

Characterization of Carotid Plaques with Ultrasound Non-Invasive Vascular Elastography (NIVE) : Feasibility and Correlation with High-Resolution Magnetic Resonance Imaging

L’accident vasculaire cérébral (AVC) est une cause principale de décès et de morbidité dans le monde; une bonne partie des AVC est causée par la plaque d’athérosclérose carotidienne. La prévention de l’AVC chez les patients ayant une plaque carotidienne demeure controversée, vu les risques et bénéfices ambigus associés au traitement chirurgical ou médical. Plusieurs méthodes d’imagerie ont été développées afin d’étudier la plaque vulnérable (dont le risque est élevé), mais aucune n’est suffisamment validée ou accessible pour permettre une utilisation comme outil de dépistage. L’élastographie non-invasive vasculaire (NIVE) est une technique nouvelle qui cartographie les déformations (élasticité) de la plaque afin de détecter les plaque vulnérables; cette technique n’est pas encore validée cliniquement. Le but de ce projet est d’évaluer la capacité de NIVE de caractériser la composition de la plaque et sa vulnérabilité in vivo chez des patients ayant des plaques sévères carotidiennes, en utilisant comme étalon de référence, l’imagerie par résonance magnétique (IRM) à haute-résolution. Afin de poursuivre cette étude, une connaissance accrue de l’AVC, l’athérosclérose, la plaque vulnérable, ainsi que des techniques actuelles d’imagerie de la plaque carotidienne, est requise. Trente-et-un sujets ont été examinés par NIVE par ultrasonographie et IRM à haute-résolution. Sur 31 plaques, 9 étaient symptomatiques, 17 contenaient des lipides, et 7 étaient vulnérables selon l’IRM. Les déformations étaient significativement plus petites chez les plaques contenant des lipides, avec une sensibilité élevée et une spécificité modérée. Une association quadratique entre la déformation et la quantité de lipide a été trouvée. Les déformations ne pouvaient pas distinguer les plaques vulnérables ou symptomatiques. En conclusion, NIVE par ultrasonographie est faisable chez des patients ayant des sténoses carotidiennes significatives et peut détecter la présence d’un coeur lipidique. Des études supplémentaires de progression de la plaque avec NIVE sont requises afin d’identifier les plaques vulnérables.Stroke is a leading cause of death and morbidity worldwide, and a significant proportion of strokes are caused by carotid atherosclerotic plaque rupture. Prevention of stroke in patients with carotid plaque poses a significant challenge to physicians, as risks and benefits of surgical or medical treatments remain equivocal. Many imaging techniques have been developed to identify and study vulnerable (high-risk) atherosclerotic plaques, but none is sufficiently validated or accessible for population screening. Non-invasive vascular elastography (NIVE) is a novel ultrasonic technique that maps carotid plaque strain (elasticity) characteristics to detect its vulnerability; it has not been clinically validated yet. The goal of this project is to evaluate the ability of ultrasound NIVE strain analysis to characterize carotid plaque composition and vulnerability in vivo in patients with significant plaque burden, as determined by the reference standard, high resolution MRI. To undertake this study, a thorough understanding of stroke, atherosclerosis, vulnerable plaque, and current non-invasive carotid plaque imaging techniques is required. Thirty-one subjects underwent NIVE and high-resolution MRI of internal carotid arteries. Of 31 plaques, 9 were symptomatic, 17 contained lipid and 7 were vulnerable on MRI. Strains were significantly lower in plaques containing a lipid core compared to those without lipid, with high sensitivity and moderate specificity. A quadratic fit was found between strain and lipid content. Strains did not discriminate symptomatic patients or vulnerable plaques. In conclusion, ultrasound NIVE is feasible in patients with significant carotid stenosis and can detect the presence of a lipid core. Further studies of plaque progression with NIVE are required to identify vulnerable plaques

Imaging Atherosclerosis.

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.J.M.T. is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). M.D is supported by the British Heart Foundation (FS/14/78/31020). N.R.E. is supported by a research training fellowship from the Dunhill Medical Trust (RTF44/0114). A.J.B. is supported by the British Heart Foundation. J.H.F.R. is part-supported by the HEFCE, the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust.This is the final version of the article. It first appeared from the American Heart Association via http://dx.doi.org/10.1161/CIRCRESAHA.115.30624

Optimizing Non-Invasive Detection of Coronary Artery Disease and Effects of Advanced Interventional Techniques for Patients with Stable Coronary Artery Disease:It is All about Myocardial Perfusion

The aim of this thesis was to (1) further optimize non-invasive detection of hemodynamically significant coronary artery disease (CAD) with coronary computed tomography angiography (CCTA) and myocardial perfusion imaging (MPI) and to examine (2) the effect of implantation of the bioresorbable vascular scaffold (BVS) and (3) chronic total occlusion percutaneous coronary intervention (CTO PCI). Part I showed that angiographic characteristics such as volumetric measures as well as morphological aspects of atherosclerosis as assessed by CCTA are of interest when considering the hemodynamic consequences of atherosclerosis. These findings add to luminal stenosis grading alone and aid in increasing the diagnostic accuracy of CCTA to predict hemodynamically significant CAD determined by invasive FFR. The main results of Part II indicate that implantation of the BVS is feasible however no benefit with regard to myocardial perfusion is observed during hyperemia or cold pressor testing. These findings do not support the use of BVS instead of metallic DES, especially since large randomized trials have illustrated that there is an increased risk in scaffold thrombosis during the first three years. Still, long-term outcome (>3 years) has yet to become available. The results of the studies in Part III indicate that the vast majority of patients with a CTO have significantly impaired myocardial perfusion with great effect of successful CTO PCI on recovery of myocardial perfusion and decrease of ischemic burden. Patient selection for CTO PCI should be based on expected patient benefit rather than lesion complexity