Application of engineering methodologies to address patient-specific clinical questions in congenital heart disease

The recent advances in medical imaging and in computer technologies have improved the prediction capabilities of biomechanical models. In order to replicate physiological, pathological or surgically corrected portions of the cardiovascular system, several engineering methodologies and their combinations can be adopted. Specifically, in this thesis, 3D reconstructions of patient-specific implanted devices and cardiovascular anatomies have been realised using both volumetric and biplanar visualisation methods, such as CT, MR, 4D-MR Flow and fluoroscopy. Finite Element techniques have been used to computationally deploy cardiovascular endoprosthesis, such as stents and percutaneous pulmonary valve devices, under patient-specific boundary conditions. To analyse pressure and velocity fields occurring in patient-specific vessel anatomies under patient-specific conditions, Lumped Parameter Networks and Computational Fluid Dynamics simulations have been employed. The above mentioned engineering tools have been here applied to address three clinical topics: 1 - Percutaneous pulmonary valve implantation (PPVI) Nowadays, more than 5,000 patients with pulmonary valve dysfunctions have been treated successfully with a percutaneous device, consisting in a bovine jugular venous valve sewn inside a balloon expandable stent. However, 25% of the treated patients experienced stent fracture. Using a novel methodological patient-specific approach that combines 3D reconstructions of the implanted stent from patients’ biplane fluoroscopy images and FE analyses, I carried out a risk stratification for stent fracture prediction. 2 - Transposition of the Great Arteries (TGA) Patients born with the congenital heart defect TGA need a surgical correction, which however, is associated with long term complications: the enlargement of the aortic root, and the development of a unilateral pulmonary stenosis. These may originate a complex hemodynamics that I tried to investigate by using patient-specific LPN and CFD models. 3 - Aortic Coarctation (CoA) Finally, combinations of FE and CFD-LPN models have been used to plan treatment in a patient with CoA and aberrant right subclavian

Automatic 3D Reconstruction of Coronary Artery Centerlines from Monoplane X-ray Angiogram Images

We present a new method for the fully automatic 3D reconstruction of the coronary artery centerlines, using two X-ray angiogram projection images from a single rotating monoplane acquisition system. During the first stage, the input images are smoothed using curve evolution techniques. Next, a simple yet efficient multiscale method, based on the information of the Hessian matrix, for the enhancement of the vascular structure is introduced. Hysteresis thresholding using different image quantiles, is used to threshold the arteries. This stage is followed by a thinning procedure to extract the centerlines. The resulting skeleton image is then pruned using morphological and pattern recognition techniques to remove non-vessel like structures. Finally, edge-based stereo correspondence is solved using a parallel evolutionary optimization method based on f symbiosis. The detected 2D centerlines combined with disparity map information allow the reconstruction of the 3D vessel centerlines. The proposed method has been evaluated on patient data sets for evaluation purposes

3D reconstruction of coronary arteries from angiographic sequences for interventional assistance

Introduction -- Review of literature -- Research hypothesis and objectives -- Methodology -- Results and discussion -- Conclusion and future perspectives

Mesh-Derived Image Partition for 3D-2D Registration in Image-Guided Interventions

RÉSUMÉ Les interventions guidées par images effectuées sous modalité 2D bénéficient de la superposition d'images 3D prises en stage préopératoire. La technologie nécessaire pour cette superposition est le recalage 3D-2D, qui consiste à trouver la position et l'orientation de l'image préopératoire 3D par rapport aux images intraopératoires 2D. Une intégration adéquate d'un algorithme de recalage à un processus chirurgical a le potentiel d'avoir un impact positif sur l'issue de la chirurgie et la durée de l'intervention. Cependant, beaucoup de chirurgies sont effectuées sans l'assistance du recalage, car aucune des solutions actuelles n’est applicable dans leur contexte clinique spécifique. Pour remédier à cette situation, cette thèse porte sur la recherche de solutions pratiques applicables à des interventions guidées par images spécifiques. La première chirurgie étudiée est l'ablation par cathéter pour fibrillation atriale/auriculaire (AC pour FA) effectuée sous fluoroscopie rayons X, une procédure électrophysiologique traitant l'arythmie cardiaque. Dans cette chirurgie, une image volumétrique (soit résonance magnétique (RM) ou tomodensitométrie (TDM)) est prise avant l'opération pour définir l'anatomie de l'atrium gauche (AG) et des veines pulmonaires (VP)s. Un maillage segmenté de ce volume est ensuite utilisé pour offrir un support visuel intraopératoire lors du placement du cathéter d'ablation via sa superposition aux images fluoroscopiques. Cependant, les solutions de recalage actuelles sont trop lentes et requièrent des interventions manuelles, ce qui est problématique quand un recalage intraopératoire est nécessaire pour permettre de pallier aux mouvements du patient. Aussi, les solutions automatiques actuelles qui recalent les images 3D et 2D directement, sans passer par l'identification manuelle de points ficudiaux, ne sont pas assez précises pour être cliniquement utilisables. De plus, les solutions qui n'utilisent pas la cartographie électromagnétique ne fonctionnent pas avec les modalités RM/fluoroscopie rayons X. Ceci est un problème, car nous visons les interventions de AC pour FA qui utilisent la modalité RM sans la cartographie électromagnétique. Il y a deux défis principaux pour arriver à une solution utile cliniquement. Premièrement, résoudre le difficile problème du recalage RM/fluoroscopie complexifié dans le cas de AC pour FA à cause de la correspondance partielle entre les modalités au niveau des VPs. Deuxièmement, de faire ce recalage assez rapidement pour permettre une mise à jour intraopératoire en temps réel dans les cas où le patient bouge pendant l'opération. Afin de remédier à cette situation, nous introduisons une nouvelle méthode de recalage basée sur la partition d'image dérivée d'un maillage (recalage PIDM). Cette méthode utilise les projections d'un maillage segmenté de la modalité 3D pour inférer une segmentation des images fluoroscopiques 2D. Ceci est beaucoup plus rapide que de faire des projections volumétriques et, puisque le maillage peut être segmenté d'une image RM ou TDM sans distinction, la même procédure est valide pour les deux modalités. La justesse du recalage est évaluée par des mesures de similarité qui comparent les propriétés statistiques des zones segmentées et incorporent l'information de profondeur des maillages afin de tenir compte de la correspondance partielle au niveau des VPs. Nous validons l'algorithme de recalage PIDM sur des interventions chirurgicales de AC pour FA provenant de 7 patients différents. Quatre mesures de similarité basées sur le principe de la partition à partir du maillage sont introduites et mises à l'épreuve sur 1400 cas biplans chacune. La précision, la portée et la robustesse de la solution sont évaluées en calculant la distribution de l'erreur (distance de projection) en fonction de la justesse de la pose initiale pour chacun des 5600 recalages. La précision est également évaluée de manière visuelle, en superposant les résultats du recalage et les valeurs-vérité sur les images fluoroscopiques. Pour donner une juste appréciation de la performance attendue de notre algorithme, les exemples visuels sont tirés de cas représentant l'erreur moyenne ainsi que d'un écart-type au-dessus et en dessous. Afin d'évaluer l'extension du recalage PIDM à d'autres types de chirurgies, celui-ci est appliqué à des cas de sclérothérapie de malformation veineuse (SdMV). Ce type de chirurgie est particulièrement délicat à recaler car la malformation peut être présente sur toutes les parties du corps, ce qui offre peu de prévisibilité sur les propriétés des images médicales à recaler d'un patient à l'autre. De plus, cette chirurgie est effectuée en imagerie monoplan et les données ne sont pas accompagnées de méta-information permettant la calibration géométrique du système. Nous démontrons que le recalage PIDM est applicable aux cas de SdMV, mais doit être modifié pour être applicable à la grande variété de parties du corps où les malformations veineuses peuvent être présentes. Le protocole développé pour les chirurgies de AC pour FA peut être utilisé dans les cas où une embolisation ou une démarcation intérieure/extérieure d'une partie du corps est proéminente, mais il est nécessaire d'intégrer l'information de gradients dans les mesures de similarité pour recaler les organes où les os sont prédominants.----------ABSTRACT Image-guided interventions conducted under a 2D modality benefit from the overlay of relevant 3D information from the preoperative stage. The enabling technology for this overlay is 3D-2D registration: the process of finding the spatial pose of a 3D preoperative image in relation to 2D intraoperative images. The successful integration of a registration solution to a surgery has the potential for significant positive impact in terms of likelihood of treatment success and intervention duration. However, many surgeries are routinely done without the assistance of registration because no current solution is practical in their clinical context. In order to remedy these issues, we focus on producing practical, targeted registration solutions to assist image-guided interventions. The first surgery we address is catheter ablation for atrial fibrillation (CA for AF), an electrophysiology procedure to treat heart arrhythmia conducted under X-ray fluoroscopy. In this surgery, a 3D image, either magnetic resonance (MR) or computed tomography (CT), is taken preoperatively to define the anatomy of the left atrium (LA) and pulmonary veins (PV)s. A mesh, segmented from the 3D image, is subsequently used to help positioning the ablation catheter via its overlay on the intraoperative fluoroscopic images. Current clinical registration solutions for CA for AF are slow and often require extensive manual manipulations such as the identification of fiducial points, which is problematic when intraoperative updates of the 3D image's pose are required because of patient movement. The automatic solutions are currently not precise enough to be used clinically. Also, the solutions which do not involve electroanatomic mapping are not suitable for MR/fluoroscopy registration. This is problematic since we target CA for AF interventions where the 3D modality is MR and electroanatomic mapping is not used. There are two principal challenges to overcome in order to provide a clinically useful registration algorithm. First, solving the notoriously hard MR to X-ray fluoroscopy registration problem which is further complicated in cases of CA for AF because of the partial match between modalities at the level of the PVs. Second, solving the registration quickly enough to allow for intraoperative updates required due to the patient's movement. We introduce a new registration methodology based on mesh-derived image partition (MDIP) which uses projections of a mesh segmented from the 3D image in order to infer a segmentation of the 2D X-ray fluoroscopy images. This is orders of magnitude faster than producing volumetric projections and, since the mesh can be segmented from either MR or CT, the same procedure is valid for both modalities. The fitness of the registration is evaluated by custom-built similarity measures that compare the statistical properties of the segmented zones and incorporates mask-depth information to account for the partial match at the level of the PVs. We validate the MDIP algorithm on 7 cases of patients undergoing CA for AF surgery. Four MDIP-based similarity measures are introduced; each one is validated on 1400 biplane registrations. The precision, range, speed and robustness of the solution is assessed by calculating the distribution of projection distance error in function of the correctness of the initial pose for all 5600 biplane registrations. The precision is also evaluated visually by overlaying the ground-truths with results from the registration algorithm. To give a fair appraisal of the expected behavior, the examples are taken from cases exemplifying the average error measured as well as one standard deviation above and under. The registration algorithm is also applied to cases of sclerotherapy for venous malformation (SfVM) in order to assess its portability to other type of surgeries. SfVM are especially challenging because the malformation can be present on any body part, which offers little predictability on the properties of the medical images from one patient to another. Our dataset is sampled from monoplane surgeries and did not come with metadata allowing a geometrical calibration of the system. We demonstrate that MDIP-based registration is applicable to cases of monoplane SfVM, but that modifications are required in order to account for the wide variety of body parts where VMs are common. The protocol developed for CA for AF surgeries can be used for embolizations or when the interior/exterior border of the organ is prominent, but gradient information has to be taken into account by the similarity measures in order to properly register cases where bones are predominant

Functional and Biomechanical Effects of the Edge-to-Edge Repair in the Setting of Mitral Regurgitation: Consolidated Knowledge and Novel Tools to Gain Insight into Its Percutaneous Implementation

Mitral regurgitation is the most prevalent heart valve disease in the western population. When severe, it requires surgical treatment, repair being the preferred option. The edge-to-edge repair technique treats mitral regurgitation by suturing the leaflets together and creating a double-orifice valve. Due to its relative simplicity and versatility, it has become progressively more widespread. Recently, its percutaneous version has become feasible, and has raised interest thanks to the positive results of the Mitraclip(\uae) device. Edge-to-edge features and evolution have stimulated debate and multidisciplinary research by both clinicians and engineers. After providing an overview of representative studies in the field, here we propose a novel computational approach to the most recent percutaneous evolution of the edge-to-edge technique. Image-based structural finite element models of three mitral valves affected by posterior prolapse were derived from cine-cardiac magnetic resonance imaging. The models accounted for the patient-specific 3D geometry of the valve, including leaflet compound curvature pattern, patient-specific motion of annulus and papillary muscles, and hyperelastic and anisotropic mechanical properties of tissues. The biomechanics of the three valves throughout the entire cardiac cycle was simulated before and after Mitraclip(\uae) implantation, assessing the biomechanical impact of the procedure. For all three simulated MVs, Mitraclip(\uae) implantation significantly improved systolic leaflets coaptation, without inducing major alterations in systolic peak stresses. Diastolic orifice area was decreased, by up to 58.9%, and leaflets diastolic stresses became comparable, although lower, to systolic ones. Despite established knowledge on the edge-to-edge surgical repair, latest technological advances make its percutanoues implementation a challenging field of research. The modeling approach herein proposed may be expanded to analyze clinical scenarios that are currently critical for Mitraclip(\uae) implantation, helping the search for possible solutions

Reconstruction of coronary arteries from X-ray angiography: A review.

Despite continuous progress in X-ray angiography systems, X-ray coronary angiography is fundamentally limited by its 2D representation of moving coronary arterial trees, which can negatively impact assessment of coronary artery disease and guidance of percutaneous coronary intervention. To provide clinicians with 3D/3D+time information of coronary arteries, methods computing reconstructions of coronary arteries from X-ray angiography are required. Because of several aspects (e.g. cardiac and respiratory motion, type of X-ray system), reconstruction from X-ray coronary angiography has led to vast amount of research and it still remains as a challenging and dynamic research area. In this paper, we review the state-of-the-art approaches on reconstruction of high-contrast coronary arteries from X-ray angiography. We mainly focus on the theoretical features in model-based (modelling) and tomographic reconstruction of coronary arteries, and discuss the evaluation strategies. We also discuss the potential role of reconstructions in clinical decision making and interventional guidance, and highlight areas for future research

VALIDATION OF COMPUTATIONAL FLUID DYNAMIC SIMULATIONS OF MEMBRANE ARTIFICIAL LUNGS WITH X-RAY IMAGING

The functional performance of membrane oxygenators is directly related to the perfusion dynamics of blood flow through the fiber bundle. Non-uniform flow and design characteristics can limit gas exchange efficiency and influence susceptibility of thrombus development in the fiber membrane. Computational fluid dynamics (CFD) is a powerful tool for predicting properties of the flow field based on prescribed geometrical domains and boundary conditions. Validation of numerical results in membrane oxygenators has been predominantly based on experimental pressure measurements with little emphasis placed on confirmation of the velocity fields due to opacity of the fiber membrane and limitations of optical velocimetric methods. A novel approach was developed using biplane X-ray digital subtraction angiography to visualize flow through a commercial membrane artificial lung at 1–4.5 L/min. Permeability based on the coefficients of the Ergun equation, α and β, were experimentally determined to be 180 and 2.4, respectively, and the equivalent spherical diameter was shown to be approximately equal to the outer fiber diameter. For all flow rates tested, biplane image projections revealed non-uniform radial perfusion through the annular fiber bundle, yet without flow bias due to the axisymmetric position of the outlet. At 1 L/min, approximately 78.2% of the outward velocity component was in the radial (horizontal) plane verses 92.0% at 4.5 L/min. The CFD studies were unable to predict the non-radial component of the outward perfusion. Two-dimensional velocity fields were generated from the radiographs using a cross-correlation tracking algorithm and compared with analogous image planes from the CFD simulations. Velocities in the non-porous regions differed by an average of 11% versus the experimental values, but simulated velocities in the fiber bundle were on average 44% lower than experimental. A corrective factor reduced the average error differences in the porous medium to 6%. Finally, biplane image pairs were reconstructed to show 3-D transient perfusion through the device. The methods developed from this research provide tools for more accurate assessments of fluid flow through membrane oxygenators. By identifying non-invasive techniques to allow direct analysis of numerical and experimental velocity fields, researchers can better evaluate device performance of new prototype designs