Investigation and Validation of Imaging Techniques for Mitral Valve Disease Diagnosis and Intervention

Mitral Valve Disease (MVD) describes a variety of pathologies that result in regurgitation of blood during the systolic phase of the cardiac cycle. Decisions in valvular disease management rely heavily on non-invasive imaging. Transesophageal echocardiography (TEE) is widely recognized as the key evaluation technique where backflow of high velocity blood can be visualized under Doppler. In most cases, TEE imaging is adequate for identifying mitral valve pathology, though the modality is often limited from signal dropout, artifacts and a restricted field of view. Quantitative analysis is an integral part of the overall assessment of valve morphology and gives objective evidence for both classification and guiding intervention of regurgitation. In addition, patient-specific models derived from diagnostic TEE images allow clinicians to gain insight into uniquely intricate anatomy prior to surgery. However, the heavy reliance on TEE segmentation for diagnosis and modelling has necessitated an evaluation of the accuracy of the oft-used mitral valve imaging modality. Dynamic cardiac 4D-Computed Tomography (4D-CT) is emerging as a valuable tool for diagnosis, quantification and assessment of cardiac diseases. This modality has the potential to provide a high quality rendering of the mitral valve and subvalvular apparatus, to provide a more complete picture of the underlying morphology. However, application of dynamic CT to mitral valve imaging is especially challenging due to the large and rapid motion of the valve leaflets. It is therefore necessary to investigate the accuracy and level of precision by which dynamic CT captures mitral valve motion throughout the cardiac cycle. To do this, we design and construct a silicone and bovine quasi-static mitral valve phantom which can simulate a range of ECG-gated heart rates and reproduce physiologic valve motion over the cardiac cycle. In this study, we discovered that the dynamic CT accurately captures the underlying valve movement, but with a higher prevalence of image artifacts as leaflet and chordae motion increases due to elevated heart rates. In a subsequent study, we acquire simultaneous CT and TEE images of both a silicone mitral valve phantom and an iodine-stained bovine mitral valve. We propose a pipeline to use CT as the ground truth to study the relationship between TEE intensities and the underlying valve morphology. Preliminary results demonstrate that with an optimized threshold selection based solely on TEE pixel intensities, only 40\% of pixels are correctly classified as part of the valve. In addition, we have shown that emphasizing the centre-line rather than the boundaries of high intensity TEE image regions provides a better representation and segmentation of the valve morphology. This work has the potential to inform and augment the use of TEE for diagnosis and modelling of the mitral valve in the clinical workflow for MVD

A Patient-Specific Cardiac Phantom for Training and Pre-Procedure Surgical Planning

Minimally invasive cardiac procedures requiring a transseptal puncture are becoming increasingly common. For cases of complex or diseased anatomy, clinicians may benefit from using a patient-specific cardiac phantom for training, surgical planning, and the validation of devices or techniques. An imaging compatible cardiac phantom was developed to simulate a MitraClip ® procedure. The phantom contained a patient-specific cardiac model manufactured using tissue mimicking materials. To evaluate accuracy, the patient-specific model was imaged using CT, segmented, and the resulting point cloud data set was compared using absolute distance to the original patient data. The phantom was validated using a MitraClip ® device to ensure anatomical features and tools are identifiable under image guidance. Patient-specific cardiac phantoms may allow for surgical complications to be accounted for in pre-operative planning. The information gained by clinicians involved in planning and performing the procedure should lead to shorter procedural times and better outcomes for patients

Quantitative imaging in cardiovascular CT angiography

In de afgelopen decennia is computertomografie (CT) een prominente niet-invasieve modaliteit om hart- en vaatziekten te evalueren geworden. Dit proefschrift heeft als doel de rol van CT in de therapeutische behandeling van coronaire hartziekte (CAD) en klepaandoeningen te onderzoeken.De relatie tussen kransslagadergeometrie (statisch en dynamisch) en aanwezigheid en omvang van CAD met CT werd onderzocht. De resultaten suggereren dat de statische geometrie van de kransslagader significant gerelateerd is aan de aanwezigheid van plaque en stenose. Er was echter geen verband tussen dynamische verandering van de coronaire arterie-geometrie en de ernst van CAD. Een algoritme om de invloed van intraluminair contrastmiddel op niet-verkalkte atherosclerotische plaque Hounsfield-Unit-waarden te corrigeren werd gepresenteerd en gevalideerd met behulp van fantomen.Diagnose en operatieplanning kunnen cruciale gevolgen hebben voor de klinische uitkomst van chirurgische ingrepen. In dit proefschrift wordt beschreven dat halfautomatische softwareprogramma’s het kwantificeren van het aortaklepgebied betere reproduceerbare resultaten toonden in vergelijking met handmatige metingen, en vergelijkbare resultaten met de huidige gouden standaard, de echocardiografie. Een systematische review over het dynamische gedrag van de aorta-annulus toont aan dat de vorm van de aorta-annulus tijdens de hartcyclus verandert, wat impliceert dat er bij het bepalen van een prothese rekening moet worden gehouden met meerdere fasen. Een andere review beschrijft het gebruik van 3D-printen in de chirurgische planning samen met andere toepassingen voor de behandeling van hartklepaandoeningen.CT is de belangrijkste beeldvormingsmodaliteit in deze onderzoeken, die gericht waren op de therapeutische behandeling van hart- en vaatziekten, van vroege risicobepaling tot diagnose en chirurgische planning.In the recent decades computed tomography (CT) has emerged as a dominant non-invasive modality to evaluate cardiovascular diseases. This thesis aimed to explore the role of CT in the therapeutic management of coronary artery disease (CAD) and valvular diseases.The relationship between both static and dynamic coronary artery geometry and presence and extent of CAD using CT was investigated. The results suggest that the static coronary artery geometry is significantly related to presence of plaque and significant stenosis. However, there were no such relationship between dynamic change of coronary artery geometry and severity of CAD. As part of this thesis an algorithm to correct the influence of lumen contrast enhancement on non-calcified atherosclerotic plaque Hounsfield-Unit values was presented. The algorithm was validated using phantoms. The diagnosis and surgical planning may have crucial impact on clinical outcome. Semi-automatic software for aortic valve area quantification presented in this thesis was proven to be more repeatable and similar to gold standard echocardiography in comparison to manual measurements. The systematic review regarding the dynamic behavior of aortic annulus revealed that aortic annulus geometry changes throughout the cardiac cycle which implies that multiple phases should be taken into account for prosthesis sizing. Another review in this thesis discusses the use of 3D printing in the surgical planning along with other applications for the treatment of valvular diseases.CT is the main imaging modality in these studies which were focused on the therapeutic management of cardiovascular diseases from early risk determination to diagnosis and surgical planning

Entering a new era of surgical training : developing 3-dimensional print models for hands-on surgical training and its introduction into the congenital cardiac surgical curriculum

Congenital heart surgery is a technically challenging subspecialty of cardiothoracic surgery. This is due to a combination of factors including the rarity and variety of pathology and the small patient size. This coupled with the increasing public scrutiny and the expectation of excellent patient outcomes for even the most complex pathologies has led to limitations for surgical trainees to develop their surgical competencies in an efficient manner. Simulation has been used successfully to develop technical skills in other surgical specialities but is limited in congenital heart surgery. The objectives of this work were to develop and integrate hands-on simulation methods into the training of congenital heart surgeons using anatomically accurate 3D-printed heart models and to use validated, objective assessment methods to measure performance. The simulation programme was successfully developed and integrated into the regular training of congenital heart surgeons. The objective assessments demonstrated that there was an improvement in procedural performance and time across multiple complex procedures following deliberate practice and rehearsal. Furthermore, surgeons who had participated in the programme retained their technical skills following a prolonged delay supporting the value of simulation. Overall, there is value in the incorporation of hands-on simulation training into congenital heart surgery and it has the potential to be integrated into training programmes globally

Additive manufacturing of mitral annuloplasty devices

Mitral valve annuloplasty is a common surgical procedure performed on thousands of patients each year across the world. A less invasive and more successful method of resolving mitral valve regurgitation, repair surgeries now outnumber replacement of the mitral valve in its entirety. As a result, a range of supportive annuloplasty ring devices for maintaining the surgical repair are now available for lifelong implantation. However, these devices underserve some populations leading to replacement surgeries, and rely on assumptions made on the natural, healthy anatomy of the mitral valve. Additive manufacturing (AM) has, for the last few decades, become increasingly adopted into the medical industry. With applications ranging from educational aids to surgical instruments and long-term implantable devices, this field is rapidly expanding and encompassing a greater breadth of medical specialities. In particular, the manufacturing of patient-specific products with reasonable cost and high fidelity is a key area of development for medical applications of additive manufacturing methods. Significant research has already been undertaken in the fields of orthopaedics, regenerative medicine, and pharmaceuticals, producing long-term implantable metal devices, complex polymer scaffolds, and novel drug delivery methods. Personalized annuloplasty rings could lead to greater surgery success rates enabling greater repair longevity, reduced reoperation rates, and reduced risk of future valve replacement. This project aimed to investigate the suitability of the AM technique, selective laser melting (SLM), to create annuloplasty rings tailored to each patient. To achieve this goal, this research focussed first on comparing the existing design assumptions applied to commercial annuloplasty devices against human anatomy using cadaveric dissection and measurement. These studies concluded that whilst the assumed 3:4 ratio applied in annuloplasty design was a good average across a population, the ratio was inconsistent between subjects and could lead to difficulties in sizing devices appropriately for an individual patient. Following this, methods of design and manufacturing were investigated, comparing various tools available in commercial medical-CAD software, Materialise Mimics®. The commonly applied “thresholding” method of isolating structures from patient scan data was found to be insufficient for isolation of soft tissue structures such as the mitral valve annulus from the surrounding cardiac tissue due to the similarity in densities reducing contrast on the scan. A method of single-point design using insertion points of the valve leaflets throughout the scan was shown to be sufficient to reproduce a mitral annular structure, which was then manufactured in the Ti6Al4V alloy, which has been shown to be biocompatible in some orthopaedic applications, using SLM. Post-processing techniques appropriate for the specific application of this device into the cardiovascular system were also investigated. The novel electrolyte jet machining process was employed to moderate surface unevenness caused by inherent properties of the powder bed SLM process, such as stepping or loose powder particles. This process was tested with a range of parameter sets producing varying topographies and therefore applied to different needs of the annuloplasty device. Firstly, the process was applied for reduction of coagulation on the surface of Ti6Al4V alloy samples, and then for amplification of fibroblastic cell growth. The primary parameter sets were found to produce a small reduction in platelet adhesion when compared against as-built SLM surfaces, however failed to reduce the platelet activity to that found on conventionally manufactured Ti6Al4V samples. The secondary parameter sets did not produce any improvement in fibroblastic proliferation in short term studies, however SLM samples were found to be significantly more favourable to fibroblast growth than conventionally manufactured surfaces of the same material grade. Finally, future avenues for work are discussed, including next steps for each of the three areas investigated in this thesis and a view to the future of novel annuloplasty devices as a whole. Recommendations for other applications of electrolyte jet machining are provided, including the potential for anti-biofouling surface processing given the lack of cell survivability found in these studies. Further design recommendations are considered, from computational modelling of the valve through to structured surgical prediction integrated with design of the annuloplasty device

Measuring aortic annulus size using a soft robotic balloon catheter

Transcatheter aortic valve implantation (TAVI) is a minimally invasive surgical technique to treat aortic heart valve diseases. According to current clinical guidelines, the implanted prosthetic valve replacing the native one is selected based on pre-operative size assessment of the aortic annulus through different imaging techniques. That very often leads to suboptimal device selection resulting in major complications, such as aortic regurgitation and atrioventricular blocks. In this work, we propose a new, intra-operative approach to determine the diameter of the aortic annulus exploiting intra-balloon pressure and volume (p-v) data, acquired from a robotised valvuloplasty balloon catheter. This strategy, combined with current imaging-based sizing methods, would allow to obtain more accurate measurements and check whether the implantation region has changed as a consequence of the valvuloplasty procedure. That would improve TAVI device selection, potentially reducing the occurrence of the aforementioned complications. Two robotic inflation devices, capable of collecting real-time intra-balloon p-v data, were designed and interfaced with a commercially available valvuloplasty balloon catheter. A sizing algorithm that can precisely estimate the annular diameter from acquired p-v data was also implemented. The algorithm relies on a mathematical model of the balloon free inflation and an iterative method based on linear regression. Two different mathematical models of the balloon free inflation, one analytical and one numerical, were developed and compared in terms of sizing accuracy. In vitro tests were performed on idealised aortic phantoms. Experimental results show that pressure-volume data can be used to determine annular diameters bigger than the unstretched diameter of the balloon catheter. This conclusion applies to both rigid and compliant phantoms characterised by a rigidity greater than 100 kPa/%. For these cases, the proposed approach exhibited good precision (maximum average error 1.972%) and good repeatability (maximum standard deviation ±0.263 mm)

Additive manufacturing of mitral annuloplasty devices

Mitral valve annuloplasty is a common surgical procedure performed on thousands of patients each year across the world. A less invasive and more successful method of resolving mitral valve regurgitation, repair surgeries now outnumber replacement of the mitral valve in its entirety. As a result, a range of supportive annuloplasty ring devices for maintaining the surgical repair are now available for lifelong implantation. However, these devices underserve some populations leading to replacement surgeries, and rely on assumptions made on the natural, healthy anatomy of the mitral valve. Additive manufacturing (AM) has, for the last few decades, become increasingly adopted into the medical industry. With applications ranging from educational aids to surgical instruments and long-term implantable devices, this field is rapidly expanding and encompassing a greater breadth of medical specialities. In particular, the manufacturing of patient-specific products with reasonable cost and high fidelity is a key area of development for medical applications of additive manufacturing methods. Significant research has already been undertaken in the fields of orthopaedics, regenerative medicine, and pharmaceuticals, producing long-term implantable metal devices, complex polymer scaffolds, and novel drug delivery methods. Personalized annuloplasty rings could lead to greater surgery success rates enabling greater repair longevity, reduced reoperation rates, and reduced risk of future valve replacement. This project aimed to investigate the suitability of the AM technique, selective laser melting (SLM), to create annuloplasty rings tailored to each patient. To achieve this goal, this research focussed first on comparing the existing design assumptions applied to commercial annuloplasty devices against human anatomy using cadaveric dissection and measurement. These studies concluded that whilst the assumed 3:4 ratio applied in annuloplasty design was a good average across a population, the ratio was inconsistent between subjects and could lead to difficulties in sizing devices appropriately for an individual patient. Following this, methods of design and manufacturing were investigated, comparing various tools available in commercial medical-CAD software, Materialise Mimics®. The commonly applied “thresholding” method of isolating structures from patient scan data was found to be insufficient for isolation of soft tissue structures such as the mitral valve annulus from the surrounding cardiac tissue due to the similarity in densities reducing contrast on the scan. A method of single-point design using insertion points of the valve leaflets throughout the scan was shown to be sufficient to reproduce a mitral annular structure, which was then manufactured in the Ti6Al4V alloy, which has been shown to be biocompatible in some orthopaedic applications, using SLM. Post-processing techniques appropriate for the specific application of this device into the cardiovascular system were also investigated. The novel electrolyte jet machining process was employed to moderate surface unevenness caused by inherent properties of the powder bed SLM process, such as stepping or loose powder particles. This process was tested with a range of parameter sets producing varying topographies and therefore applied to different needs of the annuloplasty device. Firstly, the process was applied for reduction of coagulation on the surface of Ti6Al4V alloy samples, and then for amplification of fibroblastic cell growth. The primary parameter sets were found to produce a small reduction in platelet adhesion when compared against as-built SLM surfaces, however failed to reduce the platelet activity to that found on conventionally manufactured Ti6Al4V samples. The secondary parameter sets did not produce any improvement in fibroblastic proliferation in short term studies, however SLM samples were found to be significantly more favourable to fibroblast growth than conventionally manufactured surfaces of the same material grade. Finally, future avenues for work are discussed, including next steps for each of the three areas investigated in this thesis and a view to the future of novel annuloplasty devices as a whole. Recommendations for other applications of electrolyte jet machining are provided, including the potential for anti-biofouling surface processing given the lack of cell survivability found in these studies. Further design recommendations are considered, from computational modelling of the valve through to structured surgical prediction integrated with design of the annuloplasty device