Towards ultra-high resolution 3D reconstruction of a whole rat brain from 3D-PLI data

3D reconstruction of the fiber connectivity of the rat brain at microscopic scale enables gaining detailed insight about the complex structural organization of the brain. We introduce a new method for registration and 3D reconstruction of high- and ultra-high resolution (64 $\mu$m and 1.3 $\mu$m pixel size) histological images of a Wistar rat brain acquired by 3D polarized light imaging (3D-PLI). Our method exploits multi-scale and multi-modal 3D-PLI data up to cellular resolution. We propose a new feature transform-based similarity measure and a weighted regularization scheme for accurate and robust non-rigid registration. To transform the 1.3 $\mu$m ultra-high resolution data to the reference blockface images a feature-based registration method followed by a non-rigid registration is proposed. Our approach has been successfully applied to 278 histological sections of a rat brain and the performance has been quantitatively evaluated using manually placed landmarks by an expert.Comment: 9 pages, Accepted at 2nd International Workshop on Connectomics in NeuroImaging (CNI), MICCAI'201

Local interpolation schemes for landmark-based image registration: a comparison

In this paper we focus, from a mathematical point of view, on properties and performances of some local interpolation schemes for landmark-based image registration. Precisely, we consider modified Shepard's interpolants, Wendland's functions, and Lobachevsky splines. They are quite unlike each other, but all of them are compactly supported and enjoy interesting theoretical and computational properties. In particular, we point out some unusual forms of the considered functions. Finally, detailed numerical comparisons are given, considering also Gaussians and thin plate splines, which are really globally supported but widely used in applications

Automatic Image Segmentation of Healthy and Atelectatic Lungs in Computed Tomography

Computed tomography (CT) has become a standard in pulmonary imaging which allows the analysis of diseases like lung nodules, emphysema and embolism. The improved spatial and temporal resolution involves a dramatic increase in the amount of data that has to be stored and processed. This has motivated the development of computer aided diagnostics (CAD) systems that have released the physician from the tedious task of manually delineating the boundary of the structures of interest from such a large number of images, a pre-processing step known as image segmentation. Apart from being impractical, the manual segmentation is prone to high intra and inter observer subjectiveness. Automatic segmentation of the lungs with atelectasis poses a challenge because in CT images they have similar texture and gray level as the surrounding tissue. Consequently, the available graphical information is not sufficient to distinguish the boundary of the lung. The present work aims to close the existing gap left by the segmentation of atelectatic lungs in volume CT data. A-priori knowledge of anatomical information plays a key role in the achievement of this goal

Development of acquisition system and algorithms for registration towards modeling displacement and deformation of the contour on the digital image

Centralna tema ovog rada je primena sistema za akviziciju slike u cilju procene i modelovanja deformacija i pomeranja objekata koji su snimljeni. Glavna metoda koja je pri tom korišćena je metoda registracije slika. Sam postupak registracije podrazumeva skup algoritama i metoda kojim se vrši pronalaženje transformacije koja preslikava prostor jedne slike u prostor druge. Ukoliko se radi o slikama istog objekta u različitim položajima ili konfiguracijama moguće je odrediti pomeranja i deformacije željene tačke poznavanjem ove transformacije. U radu su opisani već postojeći algoritmi, sa svojim najznačajnijim svojstvima. Na bazi ovih osobina razvijen je metod registracije baziran na rešavanju Laplasove jednačine za elektrostatičko polje. Ovakav pristup je moguć zahvaljujući činjenici da gradijent deformacija odgovara linijama elektrostatičkog polja, koje je dobijeno rešavanjem Laplasove jednačine i zadovoljava sva bitna svojstva koja treba da ima registraciona transformacija. Ove osobine se odnose na glatkost polja deformacije, postojanje inverzne funkcije i zabranu ukrštanja linija polja. Sam postupak rešavanja navedene jednačine i određivanje tražene transformaicje sproveden je primenom metode konačnih elemenata pri čemu je korišćena formulacija minimuma energija sistema. Jedna od inspiracija za rad na metodama registracije slike bio je i problem procene mehaničkih karakteristika tkiva aorte sa aneurizmom. U radu je opisana realizacija i način rada sistema koji je iskorišćen za karakterizaciju mehaničkih svojstava aorte, koji kao izlazne podatke daje informaciju o pomeranjima skupa tačaka tkiva kao i o vrednostima pritiska fluida koji izaziva ta pomeranja. Deformacije su procenjene primenom metoda segmentacije slike i izdvajanja ivica nakon čega je primenjen metod registracije slike kojom je određena deformacija tačaka tkiva u određenim vremenskim trenucima. Na osnovu ovih vrednosti primenom genetskog algoritma određena je vrednost Jangovog modula tkiva pri čemu je korišćen mehanički model deformacije tkiva. Analiza hoda upotrebom slika hoda je takođe jedan od izazova kada je u pitanju neinvazivna dijagnostika i praćenje stanja dijagnostifiko- vanih kao i zdravih subjekata. U ovom radu je prikazan postupak određivanja mehaničkog naprezanja hrskavice primenom slika snimljenih kamerom i vrednostima sile normalne reakcije podloge koja nastaje tokom hoda. Za procenu deformacija hrskavice korišćeni su algoritmi registracije slike između slika dobijenih sa kamere i slika dobijenih kompjuterizovanom tomografijom. Postupkom optimizacije procenjeni su i mehanički parametri hrskavice (Jangov modul i Poasonov koeficijent).The main aim of this thesis is the application of image acquisition system for the purpose of assessing and modeling the deformation and displacement of the objects acquired in digital images. The technique used in the study is method of image registration. The procedure of the registration includes a set of algorithms and methods which performs the assessment of transformation that maps the space of one image to another one. If there are images of the same object in different positions or configurations it is possible to determine the displacement and deformation of the desired point of understanding this transformation. The thesis describes the existing algorithms, along with their most important properties. The novel algorithms for image registration is developed based of solving the Laplace equation for electrostatic field. This approach is possible due to the fact that the transformation which corresponds to the deformation gradient field lines of the electrostatic field, which is obtained by solving the Laplace equation satisfies all essential features that should have the registration transformation. These properties are related to the smoothness of the deformation field, the existence of an inverse function of the prohibition of crossing the line field. The procedure for solving the above equation and determining the required transformation was conducted using finite element method with use of a formulation of minimum energy of the system. The motivation for this thesis was consideration problem of evaluation mechanical properties of tissues affected aortic aneurysm. The paper describes the implementation and operation of the system that was used to characterize the mechanical properties of the aorta, which as output data provides information about a set of deformation points on the tissue surface as well as the values of applied fluid pressure. Strains at the certain moment of time were estimated using the image segmentation method and edges extraction, and finally image registration is applied. Using strain values in the mechanical model of tissue, and genetic algorithm as optimization technique, the Young's modulus is assessment. Gait analysis based on the images data is also one of the challenges in non-invasive diagnosis and monitoring of both diagnosed patients and healthy subjects.. This thesis presents a method for determining the mechanical stress of the cartilage using the camera image, and the values of the normal ground reaction force, which is generated during the walk, for assessment of cartilage deformation algorithms were used image registration of images obtained from the camera and the images obtained by computed tomography. Mechanical parameters of cartilage (Young's modulus and Poisson's ratio) are evaluated in the optimization process

Automatic Spatiotemporal Analysis of Cardiac Image Series

RÉSUMÉ À ce jour, les maladies cardiovasculaires demeurent au premier rang des principales causes de décès en Amérique du Nord. Chez l’adulte et au sein de populations de plus en plus jeunes, la soi-disant épidémie d’obésité entraînée par certaines habitudes de vie tels que la mauvaise alimentation, le manque d’exercice et le tabagisme est lourde de conséquences pour les personnes affectées, mais aussi sur le système de santé. La principale cause de morbidité et de mortalité chez ces patients est l’athérosclérose, une accumulation de plaque à l’intérieur des vaisseaux sanguins à hautes pressions telles que les artères coronaires. Les lésions athérosclérotiques peuvent entraîner l’ischémie en bloquant la circulation sanguine et/ou en provoquant une thrombose. Cela mène souvent à de graves conséquences telles qu’un infarctus. Outre les problèmes liés à la sténose, les parois artérielles des régions criblées de plaque augmentent la rigidité des parois vasculaires, ce qui peut aggraver la condition du patient. Dans la population pédiatrique, la pathologie cardiovasculaire acquise la plus fréquente est la maladie de Kawasaki. Il s’agit d’une vasculite aigüe pouvant affecter l’intégrité structurale des parois des artères coronaires et mener à la formation d’anévrismes. Dans certains cas, ceux-ci entravent l’hémodynamie artérielle en engendrant une perfusion myocardique insuffisante et en activant la formation de thromboses. Le diagnostic de ces deux maladies coronariennes sont traditionnellement effectués à l’aide d’angiographies par fluoroscopie. Pendant ces examens paracliniques, plusieurs centaines de projections radiographiques sont acquises en séries suite à l’infusion artérielle d’un agent de contraste. Ces images révèlent la lumière des vaisseaux sanguins et la présence de lésions potentiellement pathologiques, s’il y a lieu. Parce que les séries acquises contiennent de l’information très dynamique en termes de mouvement du patient volontaire et involontaire (ex. battements cardiaques, respiration et déplacement d’organes), le clinicien base généralement son interprétation sur une seule image angiographique où des mesures géométriques sont effectuées manuellement ou semi-automatiquement par un technicien en radiologie. Bien que l’angiographie par fluoroscopie soit fréquemment utilisé partout dans le monde et souvent considéré comme l’outil de diagnostic “gold-standard” pour de nombreuses maladies vasculaires, la nature bidimensionnelle de cette modalité d’imagerie est malheureusement très limitante en termes de spécification géométrique des différentes régions pathologiques. En effet, la structure tridimensionnelle des sténoses et des anévrismes ne peut pas être pleinement appréciée en 2D car les caractéristiques observées varient selon la configuration angulaire de l’imageur. De plus, la présence de lésions affectant les artères coronaires peut ne pas refléter la véritable santé du myocarde, car des mécanismes compensatoires naturels (ex. vaisseaux----------ABSTRACT Cardiovascular disease continues to be the leading cause of death in North America. In adult and, alarmingly, ever younger populations, the so-called obesity epidemic largely driven by lifestyle factors that include poor diet, lack of exercise and smoking, incurs enormous stresses on the healthcare system. The primary cause of serious morbidity and mortality for these patients is atherosclerosis, the build up of plaque inside high pressure vessels like the coronary arteries. These lesions can lead to ischemic disease and may progress to precarious blood flow blockage or thrombosis, often with infarction or other severe consequences. Besides the stenosis-related outcomes, the arterial walls of plaque-ridden regions manifest increased stiffness, which may exacerbate negative patient prognosis. In pediatric populations, the most prevalent acquired cardiovascular pathology is Kawasaki disease. This acute vasculitis may affect the structural integrity of coronary artery walls and progress to aneurysmal lesions. These can hinder the blood flow’s hemodynamics, leading to inadequate downstream perfusion, and may activate thrombus formation which may lead to precarious prognosis. Diagnosing these two prominent coronary artery diseases is traditionally performed using fluoroscopic angiography. Several hundred serial x-ray projections are acquired during selective arterial infusion of a radiodense contrast agent, which reveals the vessels’ luminal area and possible pathological lesions. The acquired series contain highly dynamic information on voluntary and involuntary patient movement: respiration, organ displacement and heartbeat, for example. Current clinical analysis is largely limited to a single angiographic image where geometrical measures will be performed manually or semi-automatically by a radiological technician. Although widely used around the world and generally considered the gold-standard diagnosis tool for many vascular diseases, the two-dimensional nature of this imaging modality is limiting in terms of specifying the geometry of various pathological regions. Indeed, the 3D structures of stenotic or aneurysmal lesions may not be fully appreciated in 2D because their observable features are dependent on the angular configuration of the imaging gantry. Furthermore, the presence of lesions in the coronary arteries may not reflect the true health of the myocardium, as natural compensatory mechanisms may obviate the need for further intervention. In light of this, cardiac magnetic resonance perfusion imaging is increasingly gaining attention and clinical implementation, as it offers a direct assessment of myocardial tissue viability following infarction or suspected coronary artery disease. This type of modality is plagued, however, by motion similar to that present in fluoroscopic imaging. This issue predisposes clinicians to laborious manual intervention in order to align anatomical structures in sequential perfusion frames, thus hindering automation o

Modelling and verification of doses delivered to deformable moving targets in radiotherapy

During the last two decades, advanced treatment techniques have been developed in radiotherapy to achieve more conformal beam targeting of cancerous lesions. The advent of these techniques, such as intensity modulated radiotherapy (IMRT), volumetric modulated arc radiothreapy (VMAT), Tomotherapy etc., allows more precise localisation of higher doses to complex-shaped target volumes, thereby sparing more healthy tissue. In this context, motion management is a critical issue in contemporary radiotherapy (RT). That anatomic structures move during respiration is well known and much research is presently being devoted to strategies to contend with organ motion. However, moving structures are typically regarded as rigid bodies. The fact that many structures deform as a result of motion makes their resultant dose distributions difficult to measure and calculate, and has not been fully accounted for. The potential for ineffective treatments that do not take into account motion and anatomic deformation is self-evident. This thesis addresses the pressing need to investigate dose distributions in targets that deform during and/or between treatments, to ensure robust calculations for dose accumulation and delivery, thus providing the most positive outcomes for patients. This involves the direct measurement of complex and re-distributed dose in deforming objects (an experimental model), as well as calculations of the deformed dose distribution (a mathematical model). The comparison thereof aims to validate the dose deformation technique, thereby to apply the method to a clinical example such as liver stereotactic body radiotherapy. To facilitate four-dimensional deformable dosimetry for both external beam radiotherapy and brachytherapy, methodologies for three-dimensional deformed dose measurements were developed and employed using radiosensitive polymer gel combined with a cone beam optical computed tomography (CT) scanner. This includes the development of a novel prototype deformable target volume using a tissue-equivalent, deformable gel dosimetric phantom, dubbed “defgel”. This can reproducibly simulate targets subject to a range of mass- and density-conserving deformations representative of those observable in anatomical targets. This novel tool was characterised in terms of its suitability for the measurement of dose in deforming geometries. It was demonstrated that planned doses could be delivered to the deformable gel dosimeter in the presence of different deformations and complex spatial re-distributions of dose in all three dimensions could be quantified. For estimating the cumulative dose in different deformed states, deformable image registration (DIR) algorithms were implemented to ‘morph’ a dose distribution calculated by a treatment planning system. To investigate the performance of DIR and dose-warping technique, two key studies were undertaken. The first was to systematically assess the accuracy of a range of different DIR algorithms available in the public domain and quantitatively examine, in particular, low-contrast regions, where accuracy had not previously been established. This work investigates DIR algorithms in 3D via a systematic evaluation process using defgel suitable for verification of mass- and density-conserving deformations. The second study was a full three-dimensional experimental validation of the dose-warping technique using the evaluated DIR algorithm and comparing it to directly measured deformed dose distributions from defgel. It was shown that the dose-warping can be accurate, i.e. over 95% passing rate of 3D-gamma analysis with 3%/3mm criteria for given extents of deformation up to 20 mm For the application of evaluating patient treatment planning involving tumour motion/deformation, two key studies were undertaken in the context of liver stereotactic body radiotherapy. The first was a 4D evaluation of conventional 3D treatment planning, combined with 4D computed tomography, in order to investigate the extent of dosimetric differences between conventional 3D-static and path-integrated 4D-cumulative dose calculation. This study showed that the 3D planning approach overestimated doses to targets by ≤ 9% and underestimated dose to normal liver by ≤ 8%, compared to the 4D methodology. The second study was to assess a consequent reduction of healthy tissue sparing, which may increase risk for surrounding healthy tissues. Estimates for normal tissue complications probabilities (NTCP) based on the two dose calculation schemes are provided. While all NTCP were low for the employed fractionation scheme, analysis of common alternative schemes suggests potentially larger uncertainties exist in the estimation of NTCP for healthy liver and that substantial differences in these values may exist across the different fractionation schemes. These bodies of work have shown the potential to quantify such issues of under- and/or over-dosages which are quite patient dependent in RT. Studies presented in this work consolidate gel dosimetry, image guidance, DIR, dose-warping and consequent dose accumulation calculation to investigate the dosimetric impact and make more accurate evaluation of conventional 3D treatment plans. While liver stereotactic body radiotherapy (SBRT) was primarily concerned for immediate clinical application, the findings of this thesis are also applicable to other organs with various RT techniques. Most importantly, however, it is hoped that the outcomes of this thesis will help to improve treatment plan accuracy. By considering both computation and measurement, it is also hoped that this work will open new windows for future work and hence provide building blocks to further enhance the benefit of radiotherapy treatment