Performance Overhead of Haxe Programming Language for Cross-Platform Game Development

Video game industry has become the largest entertainment based industry, surpassing both the film and the music industry in terms of revenue. Costs of game development are rising with a number of platforms one has to support. In today’s competitive industry, it is necessary to support as many platforms as possible to remain profitable. One way to cut down on time spent on porting the game to other platforms, is to use cross-platform programming languages and development frameworks. Even though such frameworks allow drastic reduction of development time spent on making sure games work on all intended platforms, they are not without cost. The cost in this case is mainly in reduced performance, compared to games developed in their native development environments. This paper evaluates performance overhead of a relatively new programming language (less than a decade old) called Haxe, which is built especially for cross-platform development. We have implemented the same game in both its native environment and in the Haxe programming language, from which the game is cross-compiled to run in the native environment. The authors tested developed games on three different hardware configurations, with three different complexity settings, and the results show that even though performance overhead of cross-compilation is not insignificant, the overall reduction in development time attained by developing in Haxe presents a viable option for cross-platform game development, with positive aspects outweighing the negatives

Performance Evaluation of Virtualization Tools in Multi-Threaded Applications

In the last decade, virtualization technologies have become very popular. Virtualization enables a user to run multiple operating systems on the same computer concurrently, while providing a degree of isolation between OS instances. Even though virtualization is mostly used on servers, its popularity on desktop also rises, where it is mostly used in cross-platform development and execution of software available to other platforms. Since both of these use cases are performance intensive, the goal of this paper is to evaluate the performance of a couple of the most popular desktop virtualization tools on the market, i.e., VMWare Player and Oracle VirtualBox. Benchmarks used in this paper evaluate the performance of the tools in both CPU intensive and GPU intensive applications, with special emphasis placed on the performance of multi-threaded applications

Evaluation Framework for Computer Vision-Based Guidance of the Visually Impaired

Visually impaired persons have significant problems in their everyday movement. Therefore, some of our previous work involves computer vision in developing assistance systems for guiding the visually impaired in critical situations. Some of those situations includes crosswalks on road crossings and stairs in indoor and outdoor environment. This paper presents an evaluation framework for computer vision-based guiding of the visually impaired persons in such critical situations. Presented framework includes the interface for labeling and storing referent human decisions for guiding directions and compares them to computer vision-based decisions. Since strict evaluation methodology in this research field is not clearly defined and due to the specifics of the transfer of information to visually impaired persons, evaluation criterion for specific simplified guiding instructions is proposed.Comment: Technical paper published at 64th International Symposium ELMAR-2022, ISBN: 978-1-6654-7002-

Segmentatie en analyse van het linker hartoor in cardiovasculaire CT-afbeeldingen

Cardiovascular diseases are the main cause of death both in Europe and globally. Predominantly the elderly population suffers from cardiovascular diseases, especially in the developed countries, while at the same time the world population is getting older. Globally, number of people above 60 is estimated to more than double in thirty years from now. Thus, any improvements in the methods for diagnosis, treatment and prevention of cardiovascular diseases will significantly increase the quality of life and reduce the cost of treatment. Atrial fibrillation is a cardiovascular disease which mostly affects the elderly population and it drastically increases the risk of stroke. The disease is caused when the disorganized electrical signals in the upper heart chambers overwhelm the normal electrical signals propagating through the electrical pathways in the heart. This chaotic electrical activity causes asynchronous contractions and the heart beats outside of the regular sinus rhythm. The asynchronous contractions impede the exchange of blood through the chambers, preventing the complete filling and emptying of the chambers. The blood pools in the chambers, enabling the formation of thrombi. When the thrombi become dislodged and enter the blood circulation (becoming thromboemboli), they can cause stroke. Estimates show that over 90% of strokes caused by cardiovascular diseases are caused by the thromboemboli formed in the left atrial appendage (LAA), small pouch-like structure protruding from the left atrium. A novel percutaneous procedure called the left atrial appendage occlusion has recently been approved for the reduction of the risk of stroke in patients suffering from atrial fibrillation. During the procedure a device called the occluder is placed in the neck of the left atrial appendage, effectively closing it off from the rest of the heart and stopping the blood flow through the LAA. Several occluder device types are available on the market from different manufacturers. Each occluder device type comes in several predefined sizes. Physicians choose a device of the correct size according to each patient’s anatomy. Physicians have to be able to determine the accurate anatomical measurement in order to be able to properly size the device. Advancements in the development of medical imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), have enabled the acquisition of detailed three-dimensional images of the patients cardiovascular anatomy. Physicians can determine detailed anatomical characteristics of patients’ cardiovascular anatomy from such three-dimensional images. The images can be used for pre-procedural planning of the procedures, reducing the time spent on administering the procedure and reducing the complication rate of the procedure. For example, even though percutaneous LAA occlusion can be administered without the prior CT scan, reports have noted a decrease in total time required for the administration as well as a decrease in the complications during the procedure if the preprocedural CT has been administered. Additionally, the patients prefer the pre-procedural CT scan to the pre-procedural transesophageal echocardiography (TEE), despite the increased irradiation during the imaging. Currently, physicians perform the pre-procedural planning with CT in two main ways: either (1) they measure the patients anatomy directly in 2D slices, or (2) they analyse the 3D model of the LAA. Direct analysis of the 2D slices, even when using the multi-planar reconstrution (MPR), is subjective and error-prone. Certain characteristics of the LAA can be determined differently depending on the plane of the reconstruction, while determining them from the 3D visualization of the LAA is less error-prone and less subjective. Thus, accurate 3D segmentation methods of the LAA are very important for pre-procedural planning. This thesis is focused on the segmentation and the analysis in the cardiovascular CT images in order to reduce the time physicians spend on the pre-procedural planning of the LAA occlusion procedure. The final goal of the thesis is to present the methods which will enable the physicians to – with minimal interaction – determine the feasibility of the procedure for the patient, segment the LAA and determine the location for the placement of the device. The main scientific contributions of this thesis are the three novel methods for the LAA segmentation and analysis, which could improve the preprocedural planning of the occlusion. All presented methods require minimal interaction, as the physician only has to select two parameters in the input CT image: a single pixel (seed point) marking the location of the appendage in one of the slices and a single parameter (threshold) value. Both parameters are intuitive to trained medical users. One of the most important scientific contributions of this work is the method for the centerline detection through the appendage. The detected centerline stretches from the seed point in the appendage to the center of the left atrium. The proposed method detects a centerline in the 3D image by tracking the voxels with the largest radius of the maximum inscribed spheres. The detected centerline is used as an input to the two subsequent methods: the LAA segmentation method and the LAA orifice localization method. However, the reason for the centerline detection is not only to use it as an input in the subsequent methods. The detected centerline allows us to determine the length of the appendage, which is an important parameter for the sizing of the device and an exclusion criteria for a certain types of devices (the ratio of the width and the length of the appendage determines the exclusion criterion for the Watchman and LARIAT devices). Currently the length is determined by a direct measurement in the transesophageal echocardiography (TEE) imaging during the procedure, by a direct measurement in CT slices using the MPR, and finally by specialized software where the physician manually selects the points on the centerline. Our proposed method detects the centerline using only one seed point. Finally, the length of the appendage is calculated from the detected centerline. The second key contribution of this work is the method for the segmentation of the left atrial appendage based on the detected centerline. Left atrial appendage segmentation methods are proving to be increasingly clinically important because they enable the use of different techniques for the pre-procedural planning. One of the most important appendage characteristics is the type of the morphology, which is an exclusion criterion for the procedure in certain types of morphologies. The morphology can be simply determined visually by the physician from the 3D model of the LAA. Determining the morphology type from the 2D slices is error-prone, since the appendage looks differently depending on the angle of the MPR reconstruction. Additionally, accurate segmentation allows for the simple determination of the volume of the appendage, which is another factor in determining the risk of stroke. Finally, proliferation of the 3D printing in the pre-procedural planning, combined with the availability of the accurate LAA segmentation methods, allows the physicians to 3D print the model of the heart and the appendage and correctly determine the correct size of the device prior to the procedure. The proposed segmentation method gradually grows the region marked by the detected centerline and accurately extracts the region containing the LAA and most of the left atrium from an initial mask image created by thresholding the input image. The extraction of the appendage together with the left atrium (LA) area around the appendage allows better understanding of the appendage in the context of the surrounding atrial anatomy (e.g. position and direction of the appendage and proximity to blood vessels). The main advantage of the proposed method is the robustness to the selected threshold value and to the leaks occurring in the mask image. Currently, to the best of our knowledge, very few LAA segmentation methods are available on the market, while the standard region growing methods used in the interactive segmentation software are not robust to leaks after thresholding. The third major scientific contribution of the thesis is the method for the localization of the LAA ostium which uses the detected centerline to determine the plane in 3D space delineating the left atrium from the appendage in the segmentation result from the previous method. The shape of the LAA ostium, determined in the segmented image by intersection with the delineation plane, is an important factor in choosing the type of the device used for the occlusion. Certain types of ostia also indicate a greater risk of peri-device leakage of the blood. Currently, the ostium shape is determined visually in the 2D slices using the double oblique view – MPR centered in the neck of the appendage. By using the proposed method, the physician does not have to modify the MPR planes manually, as the ostium plane is determined by the intersection of the segmented LAA and the determined delineation plane. The ostium shape directly indicates the sizing of the device to be used for the procedure. All three proposed methods are validated against the ground truth segmentations manually created by two medical experts (a radiologist and a cardiosurgeon). The methods achieve large overlap coefficients against the ground truth segmentations. Finally, we have developed an application which enables the physician to visualize the LAA from the input image and easily calculate the required parameters for the procedure. Our work in this area resulted in two published papers in journals in the Science Citation Index and appeared in proceedings of four international conferences.Kardiovaskularne bolesti su glavni uzroˇcnik smrti u Europskoj uniji te jedan od glavnih uzroˇcnika smrti globalno. Nadalje, kardiovaskularne bolesti primarno pogad¯aju stariju populaciju, pogotovo u zemljama razvijenog svijeta. Brojne projekcije pokazuju kako ´ce se populacija svijeta starija od 60 godina (osobe tre´ce životne dobi) do sredine stolje´ca udvostruˇciti. Samim time pove´cat ´ce se i negativan utjecaj kardiovaskularnih bolesti na globalno stanovništvo. Kvalitetne metode dijagnosticiranja, lijeˇcenja i prevencije kardiovaskularnih bolesti mogu znaˇcajno pove´cati kvalitetu života osoba tre´ce životne dobi i smanjiti troškove lijeˇcenja. Fibrilacija atrija je kardiovaskularna bolest koja drastiˇcno pove´cava rizik od moždanog udara, a posebno pogad¯a upravo stariju populaciju te se smatra kako je odgovorna za oko petinu moždanih udara. Fibrilacija atrija je kardiovaskularna bolest koja nastaje zbog poreme´caja u elektriˇcnim putevima u srcu, kada zbog kaotiˇcnih elektriˇcnih signala srce kuca van regularnog sinusnog ritma. Zbog asinkronih kontrakcija koje se odvijaju van regularnog srˇcanog ritma, dolazi do nepotpune izmjene krvi pri prolasku kroz srce. Zbog zadržavanja krvi u pretklijetkama može nastati tromb. Ukoliko se takav tromb otkine dolazi do tromboembolizma te ulaskom takvog tromboembolija u krvotok može nastati moždani udar. Procjenjuje se kako preko 90% tromboembolija koji izazovu moždani udar nastaje u aurikulu lijeve srˇcane pretklijetke (engl. left atrial appendage (LAA)), maloj vre´castoj strukturi koja izlazi iz lijeve pretklijetke. Radi smanjenja rizika od moždanog udara kod pacijenata koji pate od fibrilacije atrija uvedena je nova neinvazivna procedura – perkutana okluzija lijevog srˇcanog aurikula. Ovom procedurom postavlja se ured¯aj u aurikul lijeve srcˇane pretklijetke koji c´e zatvoriti aurikul i tako zaustaviti protok krvi kroz njega. Postoji nekoliko proizvod¯acˇa okludera, ured¯aja kojima se provodi zatvaranje (okluzija) LAA, a svaki proizvod¯acˇ nudi svoj tip ured¯aja u više varijanti razlicˇitih dimenzija. Svakom pacijentu tijekom provod¯enja procedure odabire se ured¯aj ˇcije dimenzije odgovaraju anatomiji tog pacijenta. Za odabir toˇcne dimenzije okludera potrebno je poznavati anatomiju lijevog atrija te detaljne anatomske karakteristike aurikula. Napretkom u razvoju medicinskih modaliteta snimanja, kao što je kompjuterizirana tomografija (CT) ili magnetska rezonanca (MRI), mogu´ce je dobiti detaljne trodimenzionalne snimke kardiovaskularne anatomije pacijenta. Detaljne anatomske karakteristike aurikula pojedixix nog pacijenta mogu se odrediti iz takvih trodimenzionalnih snimaka. Pred-operativno planiranje provedbe okluzije pomo´cu CT snimki pacijenta može znaˇcajno ubrzati provedbu same procedure, kao i omogu ´citi rano prepoznavanje pacijenata kod kojih provedba okluzije nije mogu´ca. Trenutno se preoperativno planiranje pomo´cu CT snimaka provodi na dva osnovna naˇcin: mjerenjem anatomskih dimenzija direktno u 2D presjecima u CT snimci te analizom 3D modela LAA. Direktna analiza LAA korištenjem 2D presjeka, ˇcak i ako se koristi više-ravninska rekonstrukcija (engl. MPR) je subjektivna i podložna pogrešci. Odred¯ene znacˇajke aurikula je puno lakše odrediti iz 3D modela te je postojanje metoda koje mogu odrediti preciznu segmentaciju aurikula vrlo bitno za planiranje provedbe okluzije. Ova disertacija se fokusira na segmentaciju i analizu kardiovaskularnih CT snimaka kako bi omogu´cili lijeˇcnicima lakše planiranje provedbe okluzije LAA. Konaˇcni cilj metoda predstavljenih u ovoj disertaciji je, uz minimalnu interakciju lijeˇcnika, segmentirati LAA i predložiti lokaciju za postavljanje okludera. Predstavljena su tri izvorna znanstvena doprinosa – nove metode raˇcunalne obrade CT snimki – ˇcija primjena može olakšati i ubrzati proces planiranja provedbe okluzije. Sve predstavljene metode zahtijevaju samo dva ulazna podatka od lijeˇcnika: postavljanje u ulaznu CT snimku jedne poˇcetne toˇcke (engl. seed point) unutar aurikula te odabir vrijednosti jednog parametra (intenzitet praga) za tu snimku. Oba parametra su intuitivna obuˇcenim medicinskim korisnicima. Prvi znanstveni doprinos je metoda za odred¯ivanje centralne linije kroz aurikul, od poˇcetne odabrane toˇcke do centra lijeve pretklijetke. Predložena metoda traži put u 3D slici od poˇcetne toˇcke prate´ci voksele duž središta LAA dok ne dod¯e do centra lijeve pretklijetke. Odred¯ena centralna linija se koristi kao ulaz u naredne korake – metodu za segmentaciju te metodu za odred¯ivanje lokacije ostiuma LAA. Ipak, bitno je napomenuti kako je centralna odred¯ena centralna linija sama po sebi bitan rezultat za odred¯ivanje moguc´nosti provod¯enja okluzije. Na primjer, duljina centralne linije predstavlja duljinu LAA, a duljina LAA u odnosu na širinu je indikacija za korištenje Watchman i LARIAT okluder ured¯aja. Trenutno se duljina LAA odred¯uje mjerenjem u prikazu transesofagealne ehokardiografije (engl. TEE) tijekom provod¯enja same procedure, direktnim mjerenjem u 2D presjecima CT snimke nakon odred¯ivanja pogodnog kuta za MPR, te konacˇno specijaliziranim softverom koji omoguc´uje rucˇno odred¯ivanje centralne linije postavljanjem više toˇcaka u 2D presjeke. Naša predložena metoda omogu´cuje detekciju centralne linije iz samo jedne pocˇetne tocˇke. Iz odred¯ene centralne linije možemo jednostavno izraˇcunati i prikazati lijeˇcniku duljinu LAA, što c´e pomoc´i lijecˇniku planiranje provod¯enja procedure okluzije. Drugi znanstveni doprinos ove disertacije je metoda za segmentaciju aurikula lijeve srˇcane pretklijetke bazirana na detektiranoj centralnoj liniji. Segmentacija LAA je vjerojatno najbitniji rezultat predloženih metoda, omgu´cuju´ci razliˇcite primjene u planiranju provedbe procedure okluzije. Med¯u najbitnijim znacˇajkama aurikula koje je moguc´e direktno odrediti vizualizacijom segmentacije je tip morfologije aurikula, koji utjeˇce na mogu´cnost provedbe procedure. Postoji ˇcetiri razliˇcita tipa morfologije, a svaki od njih indicira razliˇcit rizik od pojave moždanog udara. U razliˇcitim kutevima MPR rekonstrukcije LAA izgleda kao da ima drugaˇciji tip morfologije, dok je iz 3D modela puno lakše toˇcno odrediti tip morfologije. Nadalje, iz precizne segmentacije mogu ´ce je odrediti i volumen aurikula u odnosu na volumen lijevog atrija, velicˇinu koja takod¯er ukazuje na rizik od moždanog udara. Posljednjih godina, popularizacijom 3D printanja za predoperativno planiranje, precizne metode segmentacije su posebno dobile na važnosti. Iz precizne segmentacije LAA mogu´ce je isprintati 3D model u stvarnoj veliˇcini, na kojem se može uživo isprobati odabrana veliˇcina okludera s obzirom na anatomiju pacijenta. Predložena metoda za segmentaciju vrši segmentaciju iterativnim rastom regije odred¯ene detektiranom centralnom linijom. Metoda iz binarne maske (odred¯ene pomoc´u vrijednosti praga koju je postavio korisnik) izdvaja regiju koja sadrži LAA i ve´cinu lijeve pretklijetke. Izdvajanjem i podruˇcja pretklijetke u okolici aurikula lijeˇcniku omogu ´cujemo bolje razumijevanje anatomije aurikula u kontekstu lokalne anatomije pretklijetke (npr. poziciju i smjer aurikula u zidu atrija, blizinu plu´cnih vena i sliˇcno). Glavna odlika metode je robusnost na odabranu vrijednost praga i na curenje (engl. leaks) koje se pojavljuje u maskiranoj slici. Trenutno na tržištu postoji vrlo malen broj metoda za segmentaciju LAA, dok standardne metode rasta regije koje se koriste za interaktivnu segmentaciju ˇcesto nisu robusne na curenje. Tre´ci znanstveni doprinos ovog rada predstavlja metoda za lokalizaciju ostiuma LAA koja korištenjem odred¯ene centralne linije i segmentiranog aurikula odred¯uje ravninu presjeka koja odvaja aurikul od pretklijetke. Oblik presjeka LAA u podruˇcju ostiuma, koji se dobije presjekom segmentiranog aurikula i odred¯ene ravnine presjeka, definira oblik ostiuma LAA. Oblik ostiuma takod¯er indicira koji je tip ured¯aja moguc´e koristiti za provod¯enje okluzije. Trenutno se oblik ostiuma odred¯uje vizualno iz odgovarajuc´eg 2D presjeka nakon prilagodbe prikaza presjeka korištenjem MPR (double oblique prikaz centriran u ostium LAA). Korištenjem predložene metode lijeˇcnik ne mora ruˇcno prilagod¯avati MPR rekonstrukciju, vec´ se ona odred¯uje automatski iz presjeka segmentiranog LAA i odred¯ene ravnine presjeka. Oblik ostiuma takod¯er odred¯uje maksimalni i minimalni promjer ostiuma, koji direktno utjecˇu na velicˇinu ured¯aja za okluziju koji c´e se koristiti za provedbu okluzije. Sve tri predstavljene metode validirane su na ground-truth segmentacijama koje su ruˇcno kreirala dva medicinska struˇcnjaka (radiolog i kardiokirurg) te postižu visoke koeficijente poklapanja s ruˇcnim segmentacijama. Konaˇcno, razvili smo i aplikaciju koja korištenjem navedenih metoda omoguc´uje lijecˇniku lakše planiranje provod¯enja okluzije. Rezultati dobiveni tijekom istraživaˇckog rada u podruˇcju obrade kardiovaskularnih snimaka, osim što su rezultirali ovom disertacijom, objavljeni su i u dva rada u ˇcasopisima indeksiranim u Science Citation Index te cˇetiri rada na med¯unarodnim znanstvenim konferencijama.Hart- en vaatziekten zijn de belangrijkste doodsoorzaak in de Europese Unie en zelfs wereldwijd. Hart- en vaatziekten treffen voornamelijk de oudere bevolking, vooral in ontwikkelde landen waar de vergrijzing meer en meer voelbaar wordt. Het aantal bejaarden (60 jaar en ouder) zal naar schatting rond het midden van de eeuw verdrievoudigd zijn. Daarom zal elke verbetering in diagnose, behandeling en preventie van hart- en vaatziekten de levenskwaliteit van ouderen aanzienlijk verbeteren en behandelingskosten verlagen. Atriale fibrillatie is een cardiovasculaire aandoening die vooral de oudere bevolking treft en het risico op een beroerte drastisch verhoogt. De ziekte manifesteert zich wanneer de normale elektrische signalen die zich voortplanten door de elektrische paden in het hart worden overweldigd. Als gevolg van die chaotische elektrische signalen slaat het hart dan buiten het normale sinusritme. Asynchrone contracties belemmeren vervolgens de uitwisseling van bloed doorheen de hartkamers, waardoor het vullen en ledigen van de kamers wordt voorkomen. Het bloed verzamelt zich in de kamers, waardoor de vorming van trombi mogelijk wordt. De trombi kunnen losraken en in de bloedsomloop terechtkomen (waardoor trombo-embolie ontstaat). Dergelijke trombo-embolieën veroorzaken vaak een beroerte. Schattingen tonen aan dat meer dan 90beroertes veroorzaakt door hart- en vaatziekten wordt veroorzaakt door de trombo-embolie gevormd in het linker hartoor (LAA), een klein buidelachtig aanhangsel dat uitsteekt uit het linker atrium. Recent is een nieuwe percutane procedure, genaamd occlusie van het linker atrium, goedgekeurd voor het verminderen van het risico op een beroerte bij patiënten die lijden aan atriale fibrillatie. Tijdens de procedure wordt een apparaat, de occluder, geplaatst in de nek van het linker hartoor, waardoor die effectief wordt afgesloten van de rest van het hart en de bloedstroom door de LAA wordt gestopt. Verschillende occluder-apparaten, van verschillende fabrikanten, zijn momenteel op de markt. Elk occluderapparaat wordt geleverd in verschillende grootten. Artsen kiezen een occluder van de geschikte grootte volgens de anatomie van de patiënt. Artsen moeten in staat zijn om via een correcte anatomische meting te bepalen welke occluder het best geschikt is. Vooruitgang in medische beeldvorming, zoals computertomografie (CT) of magnetische resonantiebeeldvorming (MRI), heb

Segmentatie en analyse van het linker hartoor in cardiovasculaire CT-afbeeldingen

Cardiovascular diseases are the main cause of death both in Europe and globally. Predominantly the elderly population suffers from cardiovascular diseases, especially in the developed countries, while at the same time the world population is getting older. Globally, number of people above 60 is estimated to more than double in thirty years from now. Thus, any improvements in the methods for diagnosis, treatment and prevention of cardiovascular diseases will significantly increase the quality of life and reduce the cost of treatment. Atrial fibrillation is a cardiovascular disease which mostly affects the elderly population and it drastically increases the risk of stroke. The disease is caused when the disorganized electrical signals in the upper heart chambers overwhelm the normal electrical signals propagating through the electrical pathways in the heart. This chaotic electrical activity causes asynchronous contractions and the heart beats outside of the regular sinus rhythm. The asynchronous contractions impede the exchange of blood through the chambers, preventing the complete filling and emptying of the chambers. The blood pools in the chambers, enabling the formation of thrombi. When the thrombi become dislodged and enter the blood circulation (becoming thromboemboli), they can cause stroke. Estimates show that over 90% of strokes caused by cardiovascular diseases are caused by the thromboemboli formed in the left atrial appendage (LAA), small pouch-like structure protruding from the left atrium. A novel percutaneous procedure called the left atrial appendage occlusion has recently been approved for the reduction of the risk of stroke in patients suffering from atrial fibrillation. During the procedure a device called the occluder is placed in the neck of the left atrial appendage, effectively closing it off from the rest of the heart and stopping the blood flow through the LAA. Several occluder device types are available on the market from different manufacturers. Each occluder device type comes in several predefined sizes. Physicians choose a device of the correct size according to each patient’s anatomy. Physicians have to be able to determine the accurate anatomical measurement in order to be able to properly size the device. Advancements in the development of medical imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), have enabled the acquisition of detailed three-dimensional images of the patients cardiovascular anatomy. Physicians can determine detailed anatomical characteristics of patients’ cardiovascular anatomy from such three-dimensional images. The images can be used for pre-procedural planning of the procedures, reducing the time spent on administering the procedure and reducing the complication rate of the procedure. For example, even though percutaneous LAA occlusion can be administered without the prior CT scan, reports have noted a decrease in total time required for the administration as well as a decrease in the complications during the procedure if the preprocedural CT has been administered. Additionally, the patients prefer the pre-procedural CT scan to the pre-procedural transesophageal echocardiography (TEE), despite the increased irradiation during the imaging. Currently, physicians perform the pre-procedural planning with CT in two main ways: either (1) they measure the patients anatomy directly in 2D slices, or (2) they analyse the 3D model of the LAA. Direct analysis of the 2D slices, even when using the multi-planar reconstrution (MPR), is subjective and error-prone. Certain characteristics of the LAA can be determined differently depending on the plane of the reconstruction, while determining them from the 3D visualization of the LAA is less error-prone and less subjective. Thus, accurate 3D segmentation methods of the LAA are very important for pre-procedural planning. This thesis is focused on the segmentation and the analysis in the cardiovascular CT images in order to reduce the time physicians spend on the pre-procedural planning of the LAA occlusion procedure. The final goal of the thesis is to present the methods which will enable the physicians to – with minimal interaction – determine the feasibility of the procedure for the patient, segment the LAA and determine the location for the placement of the device. The main scientific contributions of this thesis are the three novel methods for the LAA segmentation and analysis, which could improve the preprocedural planning of the occlusion. All presented methods require minimal interaction, as the physician only has to select two parameters in the input CT image: a single pixel (seed point) marking the location of the appendage in one of the slices and a single parameter (threshold) value. Both parameters are intuitive to trained medical users. One of the most important scientific contributions of this work is the method for the centerline detection through the appendage. The detected centerline stretches from the seed point in the appendage to the center of the left atrium. The proposed method detects a centerline in the 3D image by tracking the voxels with the largest radius of the maximum inscribed spheres. The detected centerline is used as an input to the two subsequent methods: the LAA segmentation method and the LAA orifice localization method. However, the reason for the centerline detection is not only to use it as an input in the subsequent methods. The detected centerline allows us to determine the length of the appendage, which is an important parameter for the sizing of the device and an exclusion criteria for a certain types of devices (the ratio of the width and the length of the appendage determines the exclusion criterion for the Watchman and LARIAT devices). Currently the length is determined by a direct measurement in the transesophageal echocardiography (TEE) imaging during the procedure, by a direct measurement in CT slices using the MPR, and finally by specialized software where the physician manually selects the points on the centerline. Our proposed method detects the centerline using only one seed point. Finally, the length of the appendage is calculated from the detected centerline. The second key contribution of this work is the method for the segmentation of the left atrial appendage based on the detected centerline. Left atrial appendage segmentation methods are proving to be increasingly clinically important because they enable the use of different techniques for the pre-procedural planning. One of the most important appendage characteristics is the type of the morphology, which is an exclusion criterion for the procedure in certain types of morphologies. The morphology can be simply determined visually by the physician from the 3D model of the LAA. Determining the morphology type from the 2D slices is error-prone, since the appendage looks differently depending on the angle of the MPR reconstruction. Additionally, accurate segmentation allows for the simple determination of the volume of the appendage, which is another factor in determining the risk of stroke. Finally, proliferation of the 3D printing in the pre-procedural planning, combined with the availability of the accurate LAA segmentation methods, allows the physicians to 3D print the model of the heart and the appendage and correctly determine the correct size of the device prior to the procedure. The proposed segmentation method gradually grows the region marked by the detected centerline and accurately extracts the region containing the LAA and most of the left atrium from an initial mask image created by thresholding the input image. The extraction of the appendage together with the left atrium (LA) area around the appendage allows better understanding of the appendage in the context of the surrounding atrial anatomy (e.g. position and direction of the appendage and proximity to blood vessels). The main advantage of the proposed method is the robustness to the selected threshold value and to the leaks occurring in the mask image. Currently, to the best of our knowledge, very few LAA segmentation methods are available on the market, while the standard region growing methods used in the interactive segmentation software are not robust to leaks after thresholding. The third major scientific contribution of the thesis is the method for the localization of the LAA ostium which uses the detected centerline to determine the plane in 3D space delineating the left atrium from the appendage in the segmentation result from the previous method. The shape of the LAA ostium, determined in the segmented image by intersection with the delineation plane, is an important factor in choosing the type of the device used for the occlusion. Certain types of ostia also indicate a greater risk of peri-device leakage of the blood. Currently, the ostium shape is determined visually in the 2D slices using the double oblique view – MPR centered in the neck of the appendage. By using the proposed method, the physician does not have to modify the MPR planes manually, as the ostium plane is determined by the intersection of the segmented LAA and the determined delineation plane. The ostium shape directly indicates the sizing of the device to be used for the procedure. All three proposed methods are validated against the ground truth segmentations manually created by two medical experts (a radiologist and a cardiosurgeon). The methods achieve large overlap coefficients against the ground truth segmentations. Finally, we have developed an application which enables the physician to visualize the LAA from the input image and easily calculate the required parameters for the procedure. Our work in this area resulted in two published papers in journals in the Science Citation Index and appeared in proceedings of four international conferences.Kardiovaskularne bolesti su glavni uzroˇcnik smrti u Europskoj uniji te jedan od glavnih uzroˇcnika smrti globalno. Nadalje, kardiovaskularne bolesti primarno pogad¯aju stariju populaciju, pogotovo u zemljama razvijenog svijeta. Brojne projekcije pokazuju kako ´ce se populacija svijeta starija od 60 godina (osobe tre´ce životne dobi) do sredine stolje´ca udvostruˇciti. Samim time pove´cat ´ce se i negativan utjecaj kardiovaskularnih bolesti na globalno stanovništvo. Kvalitetne metode dijagnosticiranja, lijeˇcenja i prevencije kardiovaskularnih bolesti mogu znaˇcajno pove´cati kvalitetu života osoba tre´ce životne dobi i smanjiti troškove lijeˇcenja. Fibrilacija atrija je kardiovaskularna bolest koja drastiˇcno pove´cava rizik od moždanog udara, a posebno pogad¯a upravo stariju populaciju te se smatra kako je odgovorna za oko petinu moždanih udara. Fibrilacija atrija je kardiovaskularna bolest koja nastaje zbog poreme´caja u elektriˇcnim putevima u srcu, kada zbog kaotiˇcnih elektriˇcnih signala srce kuca van regularnog sinusnog ritma. Zbog asinkronih kontrakcija koje se odvijaju van regularnog srˇcanog ritma, dolazi do nepotpune izmjene krvi pri prolasku kroz srce. Zbog zadržavanja krvi u pretklijetkama može nastati tromb. Ukoliko se takav tromb otkine dolazi do tromboembolizma te ulaskom takvog tromboembolija u krvotok može nastati moždani udar. Procjenjuje se kako preko 90% tromboembolija koji izazovu moždani udar nastaje u aurikulu lijeve srˇcane pretklijetke (engl. left atrial appendage (LAA)), maloj vre´castoj strukturi koja izlazi iz lijeve pretklijetke. Radi smanjenja rizika od moždanog udara kod pacijenata koji pate od fibrilacije atrija uvedena je nova neinvazivna procedura – perkutana okluzija lijevog srˇcanog aurikula. Ovom procedurom postavlja se ured¯aj u aurikul lijeve srcˇane pretklijetke koji c´e zatvoriti aurikul i tako zaustaviti protok krvi kroz njega. Postoji nekoliko proizvod¯acˇa okludera, ured¯aja kojima se provodi zatvaranje (okluzija) LAA, a svaki proizvod¯acˇ nudi svoj tip ured¯aja u više varijanti razlicˇitih dimenzija. Svakom pacijentu tijekom provod¯enja procedure odabire se ured¯aj ˇcije dimenzije odgovaraju anatomiji tog pacijenta. Za odabir toˇcne dimenzije okludera potrebno je poznavati anatomiju lijevog atrija te detaljne anatomske karakteristike aurikula. Napretkom u razvoju medicinskih modaliteta snimanja, kao što je kompjuterizirana tomografija (CT) ili magnetska rezonanca (MRI), mogu´ce je dobiti detaljne trodimenzionalne snimke kardiovaskularne anatomije pacijenta. Detaljne anatomske karakteristike aurikula pojedixix nog pacijenta mogu se odrediti iz takvih trodimenzionalnih snimaka. Pred-operativno planiranje provedbe okluzije pomo´cu CT snimki pacijenta može znaˇcajno ubrzati provedbu same procedure, kao i omogu ´citi rano prepoznavanje pacijenata kod kojih provedba okluzije nije mogu´ca. Trenutno se preoperativno planiranje pomo´cu CT snimaka provodi na dva osnovna naˇcin: mjerenjem anatomskih dimenzija direktno u 2D presjecima u CT snimci te analizom 3D modela LAA. Direktna analiza LAA korištenjem 2D presjeka, ˇcak i ako se koristi više-ravninska rekonstrukcija (engl. MPR) je subjektivna i podložna pogrešci. Odred¯ene znacˇajke aurikula je puno lakše odrediti iz 3D modela te je postojanje metoda koje mogu odrediti preciznu segmentaciju aurikula vrlo bitno za planiranje provedbe okluzije. Ova disertacija se fokusira na segmentaciju i analizu kardiovaskularnih CT snimaka kako bi omogu´cili lijeˇcnicima lakše planiranje provedbe okluzije LAA. Konaˇcni cilj metoda predstavljenih u ovoj disertaciji je, uz minimalnu interakciju lijeˇcnika, segmentirati LAA i predložiti lokaciju za postavljanje okludera. Predstavljena su tri izvorna znanstvena doprinosa – nove metode raˇcunalne obrade CT snimki – ˇcija primjena može olakšati i ubrzati proces planiranja provedbe okluzije. Sve predstavljene metode zahtijevaju samo dva ulazna podatka od lijeˇcnika: postavljanje u ulaznu CT snimku jedne poˇcetne toˇcke (engl. seed point) unutar aurikula te odabir vrijednosti jednog parametra (intenzitet praga) za tu snimku. Oba parametra su intuitivna obuˇcenim medicinskim korisnicima. Prvi znanstveni doprinos je metoda za odred¯ivanje centralne linije kroz aurikul, od poˇcetne odabrane toˇcke do centra lijeve pretklijetke. Predložena metoda traži put u 3D slici od poˇcetne toˇcke prate´ci voksele duž središta LAA dok ne dod¯e do centra lijeve pretklijetke. Odred¯ena centralna linija se koristi kao ulaz u naredne korake – metodu za segmentaciju te metodu za odred¯ivanje lokacije ostiuma LAA. Ipak, bitno je napomenuti kako je centralna odred¯ena centralna linija sama po sebi bitan rezultat za odred¯ivanje moguc´nosti provod¯enja okluzije. Na primjer, duljina centralne linije predstavlja duljinu LAA, a duljina LAA u odnosu na širinu je indikacija za korištenje Watchman i LARIAT okluder ured¯aja. Trenutno se duljina LAA odred¯uje mjerenjem u prikazu transesofagealne ehokardiografije (engl. TEE) tijekom provod¯enja same procedure, direktnim mjerenjem u 2D presjecima CT snimke nakon odred¯ivanja pogodnog kuta za MPR, te konacˇno specijaliziranim softverom koji omoguc´uje rucˇno odred¯ivanje centralne linije postavljanjem više toˇcaka u 2D presjeke. Naša predložena metoda omogu´cuje detekciju centralne linije iz samo jedne pocˇetne tocˇke. Iz odred¯ene centralne linije možemo jednostavno izraˇcunati i prikazati lijeˇcniku duljinu LAA, što c´e pomoc´i lijecˇniku planiranje provod¯enja procedure okluzije. Drugi znanstveni doprinos ove disertacije je metoda za segmentaciju aurikula lijeve srˇcane pretklijetke bazirana na detektiranoj centralnoj liniji. Segmentacija LAA je vjerojatno najbitniji rezultat predloženih metoda, omgu´cuju´ci razliˇcite primjene u planiranju provedbe procedure okluzije. Med¯u najbitnijim znacˇajkama aurikula koje je moguc´e direktno odrediti vizualizacijom segmentacije je tip morfologije aurikula, koji utjeˇce na mogu´cnost provedbe procedure. Postoji ˇcetiri razliˇcita tipa morfologije, a svaki od njih indicira razliˇcit rizik od pojave moždanog udara. U razliˇcitim kutevima MPR rekonstrukcije LAA izgleda kao da ima drugaˇciji tip morfologije, dok je iz 3D modela puno lakše toˇcno odrediti tip morfologije. Nadalje, iz precizne segmentacije mogu ´ce je odrediti i volumen aurikula u odnosu na volumen lijevog atrija, velicˇinu koja takod¯er ukazuje na rizik od moždanog udara. Posljednjih godina, popularizacijom 3D printanja za predoperativno planiranje, precizne metode segmentacije su posebno dobile na važnosti. Iz precizne segmentacije LAA mogu´ce je isprintati 3D model u stvarnoj veliˇcini, na kojem se može uživo isprobati odabrana veliˇcina okludera s obzirom na anatomiju pacijenta. Predložena metoda za segmentaciju vrši segmentaciju iterativnim rastom regije odred¯ene detektiranom centralnom linijom. Metoda iz binarne maske (odred¯ene pomoc´u vrijednosti praga koju je postavio korisnik) izdvaja regiju koja sadrži LAA i ve´cinu lijeve pretklijetke. Izdvajanjem i podruˇcja pretklijetke u okolici aurikula lijeˇcniku omogu ´cujemo bolje razumijevanje anatomije aurikula u kontekstu lokalne anatomije pretklijetke (npr. poziciju i smjer aurikula u zidu atrija, blizinu plu´cnih vena i sliˇcno). Glavna odlika metode je robusnost na odabranu vrijednost praga i na curenje (engl. leaks) koje se pojavljuje u maskiranoj slici. Trenutno na tržištu postoji vrlo malen broj metoda za segmentaciju LAA, dok standardne metode rasta regije koje se koriste za interaktivnu segmentaciju ˇcesto nisu robusne na curenje. Tre´ci znanstveni doprinos ovog rada predstavlja metoda za lokalizaciju ostiuma LAA koja korištenjem odred¯ene centralne linije i segmentiranog aurikula odred¯uje ravninu presjeka koja odvaja aurikul od pretklijetke. Oblik presjeka LAA u podruˇcju ostiuma, koji se dobije presjekom segmentiranog aurikula i odred¯ene ravnine presjeka, definira oblik ostiuma LAA. Oblik ostiuma takod¯er indicira koji je tip ured¯aja moguc´e koristiti za provod¯enje okluzije. Trenutno se oblik ostiuma odred¯uje vizualno iz odgovarajuc´eg 2D presjeka nakon prilagodbe prikaza presjeka korištenjem MPR (double oblique prikaz centriran u ostium LAA). Korištenjem predložene metode lijeˇcnik ne mora ruˇcno prilagod¯avati MPR rekonstrukciju, vec´ se ona odred¯uje automatski iz presjeka segmentiranog LAA i odred¯ene ravnine presjeka. Oblik ostiuma takod¯er odred¯uje maksimalni i minimalni promjer ostiuma, koji direktno utjecˇu na velicˇinu ured¯aja za okluziju koji c´e se koristiti za provedbu okluzije. Sve tri predstavljene metode validirane su na ground-truth segmentacijama koje su ruˇcno kreirala dva medicinska struˇcnjaka (radiolog i kardiokirurg) te postižu visoke koeficijente poklapanja s ruˇcnim segmentacijama. Konaˇcno, razvili smo i aplikaciju koja korištenjem navedenih metoda omoguc´uje lijecˇniku lakše planiranje provod¯enja okluzije. Rezultati dobiveni tijekom istraživaˇckog rada u podruˇcju obrade kardiovaskularnih snimaka, osim što su rezultirali ovom disertacijom, objavljeni su i u dva rada u ˇcasopisima indeksiranim u Science Citation Index te cˇetiri rada na med¯unarodnim znanstvenim konferencijama.Hart- en vaatziekten zijn de belangrijkste doodsoorzaak in de Europese Unie en zelfs wereldwijd. Hart- en vaatziekten treffen voornamelijk de oudere bevolking, vooral in ontwikkelde landen waar de vergrijzing meer en meer voelbaar wordt. Het aantal bejaarden (60 jaar en ouder) zal naar schatting rond het midden van de eeuw verdrievoudigd zijn. Daarom zal elke verbetering in diagnose, behandeling en preventie van hart- en vaatziekten de levenskwaliteit van ouderen aanzienlijk verbeteren en behandelingskosten verlagen. Atriale fibrillatie is een cardiovasculaire aandoening die vooral de oudere bevolking treft en het risico op een beroerte drastisch verhoogt. De ziekte manifesteert zich wanneer de normale elektrische signalen die zich voortplanten door de elektrische paden in het hart worden overweldigd. Als gevolg van die chaotische elektrische signalen slaat het hart dan buiten het normale sinusritme. Asynchrone contracties belemmeren vervolgens de uitwisseling van bloed doorheen de hartkamers, waardoor het vullen en ledigen van de kamers wordt voorkomen. Het bloed verzamelt zich in de kamers, waardoor de vorming van trombi mogelijk wordt. De trombi kunnen losraken en in de bloedsomloop terechtkomen (waardoor trombo-embolie ontstaat). Dergelijke trombo-embolieën veroorzaken vaak een beroerte. Schattingen tonen aan dat meer dan 90beroertes veroorzaakt door hart- en vaatziekten wordt veroorzaakt door de trombo-embolie gevormd in het linker hartoor (LAA), een klein buidelachtig aanhangsel dat uitsteekt uit het linker atrium. Recent is een nieuwe percutane procedure, genaamd occlusie van het linker atrium, goedgekeurd voor het verminderen van het risico op een beroerte bij patiënten die lijden aan atriale fibrillatie. Tijdens de procedure wordt een apparaat, de occluder, geplaatst in de nek van het linker hartoor, waardoor die effectief wordt afgesloten van de rest van het hart en de bloedstroom door de LAA wordt gestopt. Verschillende occluder-apparaten, van verschillende fabrikanten, zijn momenteel op de markt. Elk occluderapparaat wordt geleverd in verschillende grootten. Artsen kiezen een occluder van de geschikte grootte volgens de anatomie van de patiënt. Artsen moeten in staat zijn om via een correcte anatomische meting te bepalen welke occluder het best geschikt is. Vooruitgang in medische beeldvorming, zoals computertomografie (CT) of magnetische resonantiebeeldvorming (MRI), heb

Segmentatie en analyse van het linker hartoor in cardiovasculaire CT-afbeeldingen

Cardiovascular diseases are the main cause of death both in Europe and globally. Predominantly the elderly population suffers from cardiovascular diseases, especially in the developed countries, while at the same time the world population is getting older. Globally, number of people above 60 is estimated to more than double in thirty years from now. Thus, any improvements in the methods for diagnosis, treatment and prevention of cardiovascular diseases will significantly increase the quality of life and reduce the cost of treatment. Atrial fibrillation is a cardiovascular disease which mostly affects the elderly population and it drastically increases the risk of stroke. The disease is caused when the disorganized electrical signals in the upper heart chambers overwhelm the normal electrical signals propagating through the electrical pathways in the heart. This chaotic electrical activity causes asynchronous contractions and the heart beats outside of the regular sinus rhythm. The asynchronous contractions impede the exchange of blood through the chambers, preventing the complete filling and emptying of the chambers. The blood pools in the chambers, enabling the formation of thrombi. When the thrombi become dislodged and enter the blood circulation (becoming thromboemboli), they can cause stroke. Estimates show that over 90% of strokes caused by cardiovascular diseases are caused by the thromboemboli formed in the left atrial appendage (LAA), small pouch-like structure protruding from the left atrium. A novel percutaneous procedure called the left atrial appendage occlusion has recently been approved for the reduction of the risk of stroke in patients suffering from atrial fibrillation. During the procedure a device called the occluder is placed in the neck of the left atrial appendage, effectively closing it off from the rest of the heart and stopping the blood flow through the LAA. Several occluder device types are available on the market from different manufacturers. Each occluder device type comes in several predefined sizes. Physicians choose a device of the correct size according to each patient’s anatomy. Physicians have to be able to determine the accurate anatomical measurement in order to be able to properly size the device. Advancements in the development of medical imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), have enabled the acquisition of detailed three-dimensional images of the patients cardiovascular anatomy. Physicians can determine detailed anatomical characteristics of patients’ cardiovascular anatomy from such three-dimensional images. The images can be used for pre-procedural planning of the procedures, reducing the time spent on administering the procedure and reducing the complication rate of the procedure. For example, even though percutaneous LAA occlusion can be administered without the prior CT scan, reports have noted a decrease in total time required for the administration as well as a decrease in the complications during the procedure if the preprocedural CT has been administered. Additionally, the patients prefer the pre-procedural CT scan to the pre-procedural transesophageal echocardiography (TEE), despite the increased irradiation during the imaging. Currently, physicians perform the pre-procedural planning with CT in two main ways: either (1) they measure the patients anatomy directly in 2D slices, or (2) they analyse the 3D model of the LAA. Direct analysis of the 2D slices, even when using the multi-planar reconstrution (MPR), is subjective and error-prone. Certain characteristics of the LAA can be determined differently depending on the plane of the reconstruction, while determining them from the 3D visualization of the LAA is less error-prone and less subjective. Thus, accurate 3D segmentation methods of the LAA are very important for pre-procedural planning. This thesis is focused on the segmentation and the analysis in the cardiovascular CT images in order to reduce the time physicians spend on the pre-procedural planning of the LAA occlusion procedure. The final goal of the thesis is to present the methods which will enable the physicians to – with minimal interaction – determine the feasibility of the procedure for the patient, segment the LAA and determine the location for the placement of the device. The main scientific contributions of this thesis are the three novel methods for the LAA segmentation and analysis, which could improve the preprocedural planning of the occlusion. All presented methods require minimal interaction, as the physician only has to select two parameters in the input CT image: a single pixel (seed point) marking the location of the appendage in one of the slices and a single parameter (threshold) value. Both parameters are intuitive to trained medical users. One of the most important scientific contributions of this work is the method for the centerline detection through the appendage. The detected centerline stretches from the seed point in the appendage to the center of the left atrium. The proposed method detects a centerline in the 3D image by tracking the voxels with the largest radius of the maximum inscribed spheres. The detected centerline is used as an input to the two subsequent methods: the LAA segmentation method and the LAA orifice localization method. However, the reason for the centerline detection is not only to use it as an input in the subsequent methods. The detected centerline allows us to determine the length of the appendage, which is an important parameter for the sizing of the device and an exclusion criteria for a certain types of devices (the ratio of the width and the length of the appendage determines the exclusion criterion for the Watchman and LARIAT devices). Currently the length is determined by a direct measurement in the transesophageal echocardiography (TEE) imaging during the procedure, by a direct measurement in CT slices using the MPR, and finally by specialized software where the physician manually selects the points on the centerline. Our proposed method detects the centerline using only one seed point. Finally, the length of the appendage is calculated from the detected centerline. The second key contribution of this work is the method for the segmentation of the left atrial appendage based on the detected centerline. Left atrial appendage segmentation methods are proving to be increasingly clinically important because they enable the use of different techniques for the pre-procedural planning. One of the most important appendage characteristics is the type of the morphology, which is an exclusion criterion for the procedure in certain types of morphologies. The morphology can be simply determined visually by the physician from the 3D model of the LAA. Determining the morphology type from the 2D slices is error-prone, since the appendage looks differently depending on the angle of the MPR reconstruction. Additionally, accurate segmentation allows for the simple determination of the volume of the appendage, which is another factor in determining the risk of stroke. Finally, proliferation of the 3D printing in the pre-procedural planning, combined with the availability of the accurate LAA segmentation methods, allows the physicians to 3D print the model of the heart and the appendage and correctly determine the correct size of the device prior to the procedure. The proposed segmentation method gradually grows the region marked by the detected centerline and accurately extracts the region containing the LAA and most of the left atrium from an initial mask image created by thresholding the input image. The extraction of the appendage together with the left atrium (LA) area around the appendage allows better understanding of the appendage in the context of the surrounding atrial anatomy (e.g. position and direction of the appendage and proximity to blood vessels). The main advantage of the proposed method is the robustness to the selected threshold value and to the leaks occurring in the mask image. Currently, to the best of our knowledge, very few LAA segmentation methods are available on the market, while the standard region growing methods used in the interactive segmentation software are not robust to leaks after thresholding. The third major scientific contribution of the thesis is the method for the localization of the LAA ostium which uses the detected centerline to determine the plane in 3D space delineating the left atrium from the appendage in the segmentation result from the previous method. The shape of the LAA ostium, determined in the segmented image by intersection with the delineation plane, is an important factor in choosing the type of the device used for the occlusion. Certain types of ostia also indicate a greater risk of peri-device leakage of the blood. Currently, the ostium shape is determined visually in the 2D slices using the double oblique view – MPR centered in the neck of the appendage. By using the proposed method, the physician does not have to modify the MPR planes manually, as the ostium plane is determined by the intersection of the segmented LAA and the determined delineation plane. The ostium shape directly indicates the sizing of the device to be used for the procedure. All three proposed methods are validated against the ground truth segmentations manually created by two medical experts (a radiologist and a cardiosurgeon). The methods achieve large overlap coefficients against the ground truth segmentations. Finally, we have developed an application which enables the physician to visualize the LAA from the input image and easily calculate the required parameters for the procedure. Our work in this area resulted in two published papers in journals in the Science Citation Index and appeared in proceedings of four international conferences.Kardiovaskularne bolesti su glavni uzroˇcnik smrti u Europskoj uniji te jedan od glavnih uzroˇcnika smrti globalno. Nadalje, kardiovaskularne bolesti primarno pogad¯aju stariju populaciju, pogotovo u zemljama razvijenog svijeta. Brojne projekcije pokazuju kako ´ce se populacija svijeta starija od 60 godina (osobe tre´ce životne dobi) do sredine stolje´ca udvostruˇciti. Samim time pove´cat ´ce se i negativan utjecaj kardiovaskularnih bolesti na globalno stanovništvo. Kvalitetne metode dijagnosticiranja, lijeˇcenja i prevencije kardiovaskularnih bolesti mogu znaˇcajno pove´cati kvalitetu života osoba tre´ce životne dobi i smanjiti troškove lijeˇcenja. Fibrilacija atrija je kardiovaskularna bolest koja drastiˇcno pove´cava rizik od moždanog udara, a posebno pogad¯a upravo stariju populaciju te se smatra kako je odgovorna za oko petinu moždanih udara. Fibrilacija atrija je kardiovaskularna bolest koja nastaje zbog poreme´caja u elektriˇcnim putevima u srcu, kada zbog kaotiˇcnih elektriˇcnih signala srce kuca van regularnog sinusnog ritma. Zbog asinkronih kontrakcija koje se odvijaju van regularnog srˇcanog ritma, dolazi do nepotpune izmjene krvi pri prolasku kroz srce. Zbog zadržavanja krvi u pretklijetkama može nastati tromb. Ukoliko se takav tromb otkine dolazi do tromboembolizma te ulaskom takvog tromboembolija u krvotok može nastati moždani udar. Procjenjuje se kako preko 90% tromboembolija koji izazovu moždani udar nastaje u aurikulu lijeve srˇcane pretklijetke (engl. left atrial appendage (LAA)), maloj vre´castoj strukturi koja izlazi iz lijeve pretklijetke. Radi smanjenja rizika od moždanog udara kod pacijenata koji pate od fibrilacije atrija uvedena je nova neinvazivna procedura – perkutana okluzija lijevog srˇcanog aurikula. Ovom procedurom postavlja se ured¯aj u aurikul lijeve srcˇane pretklijetke koji c´e zatvoriti aurikul i tako zaustaviti protok krvi kroz njega. Postoji nekoliko proizvod¯acˇa okludera, ured¯aja kojima se provodi zatvaranje (okluzija) LAA, a svaki proizvod¯acˇ nudi svoj tip ured¯aja u više varijanti razlicˇitih dimenzija. Svakom pacijentu tijekom provod¯enja procedure odabire se ured¯aj ˇcije dimenzije odgovaraju anatomiji tog pacijenta. Za odabir toˇcne dimenzije okludera potrebno je poznavati anatomiju lijevog atrija te detaljne anatomske karakteristike aurikula. Napretkom u razvoju medicinskih modaliteta snimanja, kao što je kompjuterizirana tomografija (CT) ili magnetska rezonanca (MRI), mogu´ce je dobiti detaljne trodimenzionalne snimke kardiovaskularne anatomije pacijenta. Detaljne anatomske karakteristike aurikula pojedixix nog pacijenta mogu se odrediti iz takvih trodimenzionalnih snimaka. Pred-operativno planiranje provedbe okluzije pomo´cu CT snimki pacijenta može znaˇcajno ubrzati provedbu same procedure, kao i omogu ´citi rano prepoznavanje pacijenata kod kojih provedba okluzije nije mogu´ca. Trenutno se preoperativno planiranje pomo´cu CT snimaka provodi na dva osnovna naˇcin: mjerenjem anatomskih dimenzija direktno u 2D presjecima u CT snimci te analizom 3D modela LAA. Direktna analiza LAA korištenjem 2D presjeka, ˇcak i ako se koristi više-ravninska rekonstrukcija (engl. MPR) je subjektivna i podložna pogrešci. Odred¯ene znacˇajke aurikula je puno lakše odrediti iz 3D modela te je postojanje metoda koje mogu odrediti preciznu segmentaciju aurikula vrlo bitno za planiranje provedbe okluzije. Ova disertacija se fokusira na segmentaciju i analizu kardiovaskularnih CT snimaka kako bi omogu´cili lijeˇcnicima lakše planiranje provedbe okluzije LAA. Konaˇcni cilj metoda predstavljenih u ovoj disertaciji je, uz minimalnu interakciju lijeˇcnika, segmentirati LAA i predložiti lokaciju za postavljanje okludera. Predstavljena su tri izvorna znanstvena doprinosa – nove metode raˇcunalne obrade CT snimki – ˇcija primjena može olakšati i ubrzati proces planiranja provedbe okluzije. Sve predstavljene metode zahtijevaju samo dva ulazna podatka od lijeˇcnika: postavljanje u ulaznu CT snimku jedne poˇcetne toˇcke (engl. seed point) unutar aurikula te odabir vrijednosti jednog parametra (intenzitet praga) za tu snimku. Oba parametra su intuitivna obuˇcenim medicinskim korisnicima. Prvi znanstveni doprinos je metoda za odred¯ivanje centralne linije kroz aurikul, od poˇcetne odabrane toˇcke do centra lijeve pretklijetke. Predložena metoda traži put u 3D slici od poˇcetne toˇcke prate´ci voksele duž središta LAA dok ne dod¯e do centra lijeve pretklijetke. Odred¯ena centralna linija se koristi kao ulaz u naredne korake – metodu za segmentaciju te metodu za odred¯ivanje lokacije ostiuma LAA. Ipak, bitno je napomenuti kako je centralna odred¯ena centralna linija sama po sebi bitan rezultat za odred¯ivanje moguc´nosti provod¯enja okluzije. Na primjer, duljina centralne linije predstavlja duljinu LAA, a duljina LAA u odnosu na širinu je indikacija za korištenje Watchman i LARIAT okluder ured¯aja. Trenutno se duljina LAA odred¯uje mjerenjem u prikazu transesofagealne ehokardiografije (engl. TEE) tijekom provod¯enja same procedure, direktnim mjerenjem u 2D presjecima CT snimke nakon odred¯ivanja pogodnog kuta za MPR, te konacˇno specijaliziranim softverom koji omoguc´uje rucˇno odred¯ivanje centralne linije postavljanjem više toˇcaka u 2D presjeke. Naša predložena metoda omogu´cuje detekciju centralne linije iz samo jedne pocˇetne tocˇke. Iz odred¯ene centralne linije možemo jednostavno izraˇcunati i prikazati lijeˇcniku duljinu LAA, što c´e pomoc´i lijecˇniku planiranje provod¯enja procedure okluzije. Drugi znanstveni doprinos ove disertacije je metoda za segmentaciju aurikula lijeve srˇcane pretklijetke bazirana na detektiranoj centralnoj liniji. Segmentacija LAA je vjerojatno najbitniji rezultat predloženih metoda, omgu´cuju´ci razliˇcite primjene u planiranju provedbe procedure okluzije. Med¯u najbitnijim znacˇajkama aurikula koje je moguc´e direktno odrediti vizualizacijom segmentacije je tip morfologije aurikula, koji utjeˇce na mogu´cnost provedbe procedure. Postoji ˇcetiri razliˇcita tipa morfologije, a svaki od njih indicira razliˇcit rizik od pojave moždanog udara. U razliˇcitim kutevima MPR rekonstrukcije LAA izgleda kao da ima drugaˇciji tip morfologije, dok je iz 3D modela puno lakše toˇcno odrediti tip morfologije. Nadalje, iz precizne segmentacije mogu ´ce je odrediti i volumen aurikula u odnosu na volumen lijevog atrija, velicˇinu koja takod¯er ukazuje na rizik od moždanog udara. Posljednjih godina, popularizacijom 3D printanja za predoperativno planiranje, precizne metode segmentacije su posebno dobile na važnosti. Iz precizne segmentacije LAA mogu´ce je isprintati 3D model u stvarnoj veliˇcini, na kojem se može uživo isprobati odabrana veliˇcina okludera s obzirom na anatomiju pacijenta. Predložena metoda za segmentaciju vrši segmentaciju iterativnim rastom regije odred¯ene detektiranom centralnom linijom. Metoda iz binarne maske (odred¯ene pomoc´u vrijednosti praga koju je postavio korisnik) izdvaja regiju koja sadrži LAA i ve´cinu lijeve pretklijetke. Izdvajanjem i podruˇcja pretklijetke u okolici aurikula lijeˇcniku omogu ´cujemo bolje razumijevanje anatomije aurikula u kontekstu lokalne anatomije pretklijetke (npr. poziciju i smjer aurikula u zidu atrija, blizinu plu´cnih vena i sliˇcno). Glavna odlika metode je robusnost na odabranu vrijednost praga i na curenje (engl. leaks) koje se pojavljuje u maskiranoj slici. Trenutno na tržištu postoji vrlo malen broj metoda za segmentaciju LAA, dok standardne metode rasta regije koje se koriste za interaktivnu segmentaciju ˇcesto nisu robusne na curenje. Tre´ci znanstveni doprinos ovog rada predstavlja metoda za lokalizaciju ostiuma LAA koja korištenjem odred¯ene centralne linije i segmentiranog aurikula odred¯uje ravninu presjeka koja odvaja aurikul od pretklijetke. Oblik presjeka LAA u podruˇcju ostiuma, koji se dobije presjekom segmentiranog aurikula i odred¯ene ravnine presjeka, definira oblik ostiuma LAA. Oblik ostiuma takod¯er indicira koji je tip ured¯aja moguc´e koristiti za provod¯enje okluzije. Trenutno se oblik ostiuma odred¯uje vizualno iz odgovarajuc´eg 2D presjeka nakon prilagodbe prikaza presjeka korištenjem MPR (double oblique prikaz centriran u ostium LAA). Korištenjem predložene metode lijeˇcnik ne mora ruˇcno prilagod¯avati MPR rekonstrukciju, vec´ se ona odred¯uje automatski iz presjeka segmentiranog LAA i odred¯ene ravnine presjeka. Oblik ostiuma takod¯er odred¯uje maksimalni i minimalni promjer ostiuma, koji direktno utjecˇu na velicˇinu ured¯aja za okluziju koji c´e se koristiti za provedbu okluzije. Sve tri predstavljene metode validirane su na ground-truth segmentacijama koje su ruˇcno kreirala dva medicinska struˇcnjaka (radiolog i kardiokirurg) te postižu visoke koeficijente poklapanja s ruˇcnim segmentacijama. Konaˇcno, razvili smo i aplikaciju koja korištenjem navedenih metoda omoguc´uje lijecˇniku lakše planiranje provod¯enja okluzije. Rezultati dobiveni tijekom istraživaˇckog rada u podruˇcju obrade kardiovaskularnih snimaka, osim što su rezultirali ovom disertacijom, objavljeni su i u dva rada u ˇcasopisima indeksiranim u Science Citation Index te cˇetiri rada na med¯unarodnim znanstvenim konferencijama.Hart- en vaatziekten zijn de belangrijkste doodsoorzaak in de Europese Unie en zelfs wereldwijd. Hart- en vaatziekten treffen voornamelijk de oudere bevolking, vooral in ontwikkelde landen waar de vergrijzing meer en meer voelbaar wordt. Het aantal bejaarden (60 jaar en ouder) zal naar schatting rond het midden van de eeuw verdrievoudigd zijn. Daarom zal elke verbetering in diagnose, behandeling en preventie van hart- en vaatziekten de levenskwaliteit van ouderen aanzienlijk verbeteren en behandelingskosten verlagen. Atriale fibrillatie is een cardiovasculaire aandoening die vooral de oudere bevolking treft en het risico op een beroerte drastisch verhoogt. De ziekte manifesteert zich wanneer de normale elektrische signalen die zich voortplanten door de elektrische paden in het hart worden overweldigd. Als gevolg van die chaotische elektrische signalen slaat het hart dan buiten het normale sinusritme. Asynchrone contracties belemmeren vervolgens de uitwisseling van bloed doorheen de hartkamers, waardoor het vullen en ledigen van de kamers wordt voorkomen. Het bloed verzamelt zich in de kamers, waardoor de vorming van trombi mogelijk wordt. De trombi kunnen losraken en in de bloedsomloop terechtkomen (waardoor trombo-embolie ontstaat). Dergelijke trombo-embolieën veroorzaken vaak een beroerte. Schattingen tonen aan dat meer dan 90beroertes veroorzaakt door hart- en vaatziekten wordt veroorzaakt door de trombo-embolie gevormd in het linker hartoor (LAA), een klein buidelachtig aanhangsel dat uitsteekt uit het linker atrium. Recent is een nieuwe percutane procedure, genaamd occlusie van het linker atrium, goedgekeurd voor het verminderen van het risico op een beroerte bij patiënten die lijden aan atriale fibrillatie. Tijdens de procedure wordt een apparaat, de occluder, geplaatst in de nek van het linker hartoor, waardoor die effectief wordt afgesloten van de rest van het hart en de bloedstroom door de LAA wordt gestopt. Verschillende occluder-apparaten, van verschillende fabrikanten, zijn momenteel op de markt. Elk occluderapparaat wordt geleverd in verschillende grootten. Artsen kiezen een occluder van de geschikte grootte volgens de anatomie van de patiënt. Artsen moeten in staat zijn om via een correcte anatomische meting te bepalen welke occluder het best geschikt is. Vooruitgang in medische beeldvorming, zoals computertomografie (CT) of magnetische resonantiebeeldvorming (MRI), heb

Image segmentation using active contour models and partial differential equations

This article displays benefits of image segmentation for purpose of 3D reconstruction. Medical images and in this case CT slices are being reconstructed in 3D space for better medical investigation. It is relatively hard to use raw images for 3D reconstruction, so certain areas are being singled out using active contour models. Partial Differential Equations (PDEs), as non-linear diffusion, are used for image denoising because CT images have large gradiental areas that need to be evened out