Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Automated Quantification of Atherosclerosis in CTA of Carotid Arteries

How is the human body built and how does it function? What are the causes of disease, and where is disease located? Throughout the history of mankind these questions were answered by the use of invasive methods that included the “opening” of the human body, mainly cadavers. Thanks to these invasive techniques the first precise and complete anatomy works started to appear in the 16th century. The most influential works were published by Leonardo da Vinci and the anatomist and physician Andreas Vesalius. The discovery of X-rays in 1895, and their use for medical applications, introduced a new era, in which non-invasive imaging of the functioning human body became feasible. Nowadays, medical imaging includes many different imaging modalities, such as X-ray, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), nuclear and optical imaging, and has become an indispensable diagnostic tool for a wide range of applications. Initially, the application of medical imaging focused on the visualization of anatomy and on the detection and localization of disease. However, with the development of different modalities it has evolved into a much more versatile tool providing important information on e.g. physiology and organ function, biochemistry and metabolism using nuclear imaging (mainly positron emission tomography (PET) imaging), molecular and processes on the molecular and cellular level using molecular imaging techniques

Medical Image Analysis: Progress over two decades and the challenges ahead

International audienceThe analysis of medical images has been woven into the fabric of the pattern analysis and machine intelligence (PAMI) community since the earliest days of these Transactions. Initially, the efforts in this area were seen as applying pattern analysis and computer vision techniques to another interesting dataset. However, over the last two to three decades, the unique nature of the problems presented within this area of study have led to the development of a new discipline in its own right. Examples of these include: the types of image information that are acquired, the fully three-dimensional image data, the nonrigid nature of object motion and deformation, and the statistical variation of both the underlying normal and abnormal ground truth. In this paper, we look at progress in the field over the last 20 years and suggest some of the challenges that remain for the years to come

Vascular Segmentation Algorithms for Generating 3D Atherosclerotic Measurements

Atherosclerosis manifests as plaques within large arteries of the body and remains as a leading cause of mortality and morbidity in the world. Major cardiovascular events may occur in patients without known preexisting symptoms, thus it is important to monitor progression and regression of the plaque burden in the arteries for evaluating patient\u27s response to therapy. In this dissertation, our main focus is quantification of plaque burden from the carotid and femoral arteries, which are major sites for plaque formation, and are straight forward to image noninvasively due to their superficial location. Recently, 3D measurements of plaque burden have shown to be more sensitive to the changes of plaque burden than one-/two-dimensional measurements. However, despite the advancements of 3D noninvasive imaging technology with rapid acquisition capabilities, and the high sensitivity of the 3D plaque measurements of plaque burden, they are still not widely used due to the inordinate amount of time and effort required to delineate artery walls plus plaque boundaries to obtain 3D measurements from the images. Therefore, the objective of this dissertation is developing novel semi-automated segmentation methods to alleviate measurement burden from the observer for segmentation of the outer wall and lumen boundaries from: (1) 3D carotid ultrasound (US) images, (2) 3D carotid black-blood magnetic resonance (MR) images, and (3) 3D femoral black-blood MR images. Segmentation of the carotid lumen and outer wall from 3DUS images is a challenging task due to low image contrast, for which no method has been previously reported. Initially, we developed a 2D slice-wise segmentation algorithm based on the level set method, which was then extended to 3D. The 3D algorithm required fewer user interactions than manual delineation and the 2D method. The algorithm reduced user time by ≈79% (1.72 vs. 8.3 min) compared to manual segmentation for generating 3D-based measurements with high accuracy (Dice similarity coefficient (DSC)\u3e90%). Secondly, we developed a novel 3D multi-region segmentation algorithm, which simultaneously delineates both the carotid lumen and outer wall surfaces from MR images by evolving two coupled surfaces using a convex max-flow-based technique. The algorithm required user interaction only on a single transverse slice of the 3D image for generating 3D surfaces of the lumen and outer wall. The algorithm was parallelized using graphics processing units (GPU) to increase computational speed, thus reducing user time by 93% (0.78 vs. 12 min) compared to manual segmentation. Moreover, the algorithm yielded high accuracy (DSC \u3e 90%) and high precision (intra-observer CV \u3c 5.6% and inter-observer CV \u3c 6.6%). Finally, we developed and validated an algorithm based on convex max-flow formulation to segment the femoral arteries that enforces a tubular shape prior and an inter-surface consistency of the outer wall and lumen to maintain a minimum separation distance between the two surfaces. The algorithm required the observer to choose only about 11 points on its medial axis of the artery to yield the 3D surfaces of the lumen and outer wall, which reduced the operator time by 97% (1.8 vs. 70-80 min) compared to manual segmentation. Furthermore, the proposed algorithm reported DSC greater than 85% and small intra-observer variability (CV ≈ 6.69%). In conclusion, the development of robust semi-automated algorithms for generating 3D measurements of plaque burden may accelerate translation of 3D measurements to clinical trials and subsequently to clinical care

Segmentierung medizinischer Bilddaten und bildgestützte intraoperative Navigation

Die Entwicklung von Algorithmen zur automatischen oder semi-automatischen Verarbeitung von medizinischen Bilddaten hat in den letzten Jahren mehr und mehr an Bedeutung gewonnen. Das liegt zum einen an den immer besser werdenden medizinischen Aufnahmemodalitäten, die den menschlichen Körper immer feiner virtuell abbilden können. Zum anderen liegt dies an der verbesserten Computerhardware, die eine algorithmische Verarbeitung der teilweise im Gigabyte-Bereich liegenden Datenmengen in einer vernünftigen Zeit erlaubt. Das Ziel dieser Habilitationsschrift ist die Entwicklung und Evaluation von Algorithmen für die medizinische Bildverarbeitung. Insgesamt besteht die Habilitationsschrift aus einer Reihe von Publikationen, die in drei übergreifende Themenbereiche gegliedert sind: -Segmentierung medizinischer Bilddaten anhand von vorlagenbasierten Algorithmen -Experimentelle Evaluation quelloffener Segmentierungsmethoden unter medizinischen Einsatzbedingungen -Navigation zur Unterstützung intraoperativer Therapien Im Bereich Segmentierung medizinischer Bilddaten anhand von vorlagenbasierten Algorithmen wurden verschiedene graphbasierte Algorithmen in 2D und 3D entwickelt, die einen gerichteten Graphen mittels einer Vorlage aufbauen. Dazu gehört die Bildung eines Algorithmus zur Segmentierung von Wirbeln in 2D und 3D. In 2D wird eine rechteckige und in 3D eine würfelförmige Vorlage genutzt, um den Graphen aufzubauen und das Segmentierungsergebnis zu berechnen. Außerdem wird eine graphbasierte Segmentierung von Prostatadrüsen durch eine Kugelvorlage zur automatischen Bestimmung der Grenzen zwischen Prostatadrüsen und umliegenden Organen vorgestellt. Auf den vorlagenbasierten Algorithmen aufbauend, wurde ein interaktiver Segmentierungsalgorithmus, der einem Benutzer in Echtzeit das Segmentierungsergebnis anzeigt, konzipiert und implementiert. Der Algorithmus nutzt zur Segmentierung die verschiedenen Vorlagen, benötigt allerdings nur einen Saatpunkt des Benutzers. In einem weiteren Ansatz kann der Benutzer die Segmentierung interaktiv durch zusätzliche Saatpunkte verfeinern. Dadurch wird es möglich, eine semi-automatische Segmentierung auch in schwierigen Fällen zu einem zufriedenstellenden Ergebnis zu führen. Im Bereich Evaluation quelloffener Segmentierungsmethoden unter medizinischen Einsatzbedingungen wurden verschiedene frei verfügbare Segmentierungsalgorithmen anhand von Patientendaten aus der klinischen Routine getestet. Dazu gehörte die Evaluierung der semi-automatischen Segmentierung von Hirntumoren, zum Beispiel Hypophysenadenomen und Glioblastomen, mit der frei verfügbaren Open Source-Plattform 3D Slicer. Dadurch konnte gezeigt werden, wie eine rein manuelle Schicht-für-Schicht-Vermessung des Tumorvolumens in der Praxis unterstützt und beschleunigt werden kann. Weiterhin wurde die Segmentierung von Sprachbahnen in medizinischen Aufnahmen von Hirntumorpatienten auf verschiedenen Plattformen evaluiert. Im Bereich Navigation zur Unterstützung intraoperativer Therapien wurden Softwaremodule zum Begleiten von intra-operativen Eingriffen in verschiedenen Phasen einer Behandlung (Therapieplanung, Durchführung, Kontrolle) entwickelt. Dazu gehört die erstmalige Integration des OpenIGTLink-Netzwerkprotokolls in die medizinische Prototyping-Plattform MeVisLab, die anhand eines NDI-Navigationssystems evaluiert wurde. Außerdem wurde hier ebenfalls zum ersten Mal die Konzeption und Implementierung eines medizinischen Software-Prototypen zur Unterstützung der intraoperativen gynäkologischen Brachytherapie vorgestellt. Der Software-Prototyp enthielt auch ein Modul zur erweiterten Visualisierung bei der MR-gestützten interstitiellen gynäkologischen Brachytherapie, welches unter anderem die Registrierung eines gynäkologischen Brachytherapie-Instruments in einen intraoperativen Datensatz einer Patientin ermöglichte. Die einzelnen Module führten zur Vorstellung eines umfassenden bildgestützten Systems für die gynäkologische Brachytherapie in einem multimodalen Operationssaal. Dieses System deckt die prä-, intra- und postoperative Behandlungsphase bei einer interstitiellen gynäkologischen Brachytherapie ab