Activity profiling for minimally invasive surgery

Imperial Users onl

Doctor of Philosophy

dissertationFibrillation is defined as turbulent cardiac electrical activity and results in the inability of the myocardium to contract. When fibrillation occurs in the ventricles, it is known as ventricular fibrillation (VF). The consequence of VF is sudden death unless treated immediately. Fibrillation can also occur in the atria and is known as atrial fibrillation (AF). The consequences of atrial fibrillation (AF) are less immediate; however, it leads to increased risk of stroke. Despite the impact of fibrillatory arrhythmias, there are many gaps in our mechanistic knowledge of these arrhythmias. The purpose of this dissertation is to study through several projects how different cardiac substrates help initiate and/or sustain fibrillation. The first project examined several properties of the ventricular conduction system during VF. The conduction system coordinates excitation and consequently coordinates the contraction of the ventricles. Despite the conduction system's unique structure, its role in VF remains unclear. We examined the proximal conduction system and found that it develops a more rapid activation rate than the ventricular myocardium during prolonged VF, and may be driving the arrhythmia. The second and third projects examined the effects of fibrosis on electrical conduction to initiate and/or sustain AF. Despite fibrosis being associated with AF, it is still unknown whether it is a byproduct of an underlying heart disease and does not in itself promote AF, or if it affects the organization of conduction during fibrillation to promote AF. In the second project we studied the effect of fibrosis on conduction following different types of triggers. We found that fibrosis causes transverse conduction slowing following premature stimulation, which makes AF more likely to initiate. As AF persists, single episodes of AF last longer before the patient transitions into normal sinus rhythm, and in some cases AF can become permanent. The third project examined why some patients may never transition from AF to normal sinus rhythm. Specifically, this project found that regions of dense fibrosis anchor high-frequency activation that may be driving the arrhythmia. These studies showed that fibrosis causes conduction changes that make AF more likely to initiate and to be sustained

Investigation of Neonatal Pulmonary Structure and Function via Proton and Hyperpolarized Gas Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a modality that utilizes the phenomenon of nuclear magnetic resonance (NMR) to yield tomographic images of the body. Proton (1H) MRI has historically been successful in soft tissues but has suffered in the lung due to a variety of technical challenges, such as the low proton-density, rapid T2* relaxation time of the lung parenchymal tissue, and inherent physiological motion in the chest. Recent developments in radial ultrashort echo time (UTE) MRI have in part overcome these issues. In addition, there has been much progress in techniques for hyperpolarization of noble gases (3He and 129Xe) out of thermal equilibrium via spin exchange optical pumping, which can greatly enhance the gas NMR signal such that it is detectable within the airspaces of the lung on MRI. The lung is a unique organ due to its complex structural and functional dynamics, and its early development through the neonatal (newborn) period is not yet well understood in normal or abnormal conditions. Pulmonary morbidities are relatively common in infants and are present in a majority of patients admitted to the neonatal intensive care unit, often stemming from preterm birth and/or congenital defects. Current clinical lung imaging in these patients is typically limited to chest x-ray radiography, which does not provide tomographic information and so has lowered sensitivity. More rarely, x-ray computed tomography (CT) is used but exposes infants to ionizing radiation and typically requires sedation, both of which pose increased risks to pediatric patients. Thus the opportunity is ripe for application of novel pulmonary MRI techniques to the infant population. However, MR imaging of very small pulmonary structure and microstructure requires fundamental changes in the imaging theory of both 1H UTE MRI and hyperpolarized gas diffusion MRI. Furthermore, such young patients are often non-compliant, yielding a need for new and innovative techniques for monitoring respiratory and bulk motion. This dissertation describes methodology development and provides experimental results in both 1H UTE MRI and hyperpolarized 3He and 129Xe gas diffusion MRI, with investigation into the structure and function of infant lungs at both the macrostructural and microstructural level. In particular, anisotropically restricted gas diffusion within infant alveolar microstructure is investigated as a measurement of airspace size and geometry. Additionally, the phenomenon of respiratory and bulk motion-tracking via modulation of the k-space center\u27s magnitude and phase is explored and applied via UTE MRI in various neonatal pulmonary conditions to extract imaging-based metrics of diagnostic value. Further, the proton-density regime of pulmonary UTE MRI is validated in translational applications. These techniques are applied in infants with various pulmonary conditions, including patients diagnosed with bronchopulmonary dysplasia, congenital diaphragmatic hernia, esophageal atresia/tracheoesophageal fistula, tracheomalacia, and no suspected lung disease. In addition, explanted lung specimens from both infants with and without lung disease are examined. Development and implementation of these techniques involves a strong understanding of the physics-based theory of NMR, hyperpolarization, and MR imaging, in addition to foundations in hardware, software, and image analysis techniques. This thesis first outlines the theory and background of NMR, MRI, and pulmonary physiology and development (Part I), then proceeds into the theory, equipment, and imaging experiments for hyperpolarized gas diffusion MRI in infant lung airspaces (Part II), and finally details the theory, data processing methods, and applications of pulmonary UTE MRI in infant patients (Part III). The potential for clinical translation of the neonatal pulmonary MRI methods presented in this dissertation is very high, with the foundations of these techniques firmly rooted in the laws of physics

Système d'endoscopie basé sur la tomographie par cohérence optique dédié à l'étude des cordes vocales pédiatriques et des pathologies associées

RÉSUMÉ Le larynx est responsable de la phonation, et son bon fonctionnement est essentiel pour assurer une respiration et une déglutition adéquates. Le développement de cette structure anatomique engendre une série de changement physiologique et morphologique. Au courant de sa vie, de 1 à 9% de la population sera affectée par une pathologie laryngée, dont un grand nombre affecte spécifiquement la population pédiatrique. Les enfants affectés par ces pathologies laryngées sont particulièrement susceptibles de développer des problèmes additionnels de nature médicale, académique et psychosociale. Bien que plusieurs recherches aient été effectuées pour comprendre le développement des cordes vocales et les pathologies laryngées, plusieurs questions restent encore sans réponse. Le cycle de développement de cette microstructure anatomique est incompris, principalement à cause des méthodes actuelles de dépistage qui demeurent invasives. Par conséquent, les traitements thérapeutiques ou chirurgicaux sont peu adaptés à la clientèle pédiatrique et certains résultats sont sous-optimaux. Cette problématique illustre un besoin urgent pour un système d’imagerie non invasif dédié à l’observation des cordes vocales en pédiatrie. La conception et la validation d’un outil clinique pour l’imagerie intraopératoire des cordes vocales comportent de nombreux défis. L’hypothèse principale de cette thèse repose sur la possibilité de caractériser les cordes vocales pédiatriques de façon minimalement invasive. L’innovation est en grande partie attribuée à la conception et à la réalisation d’un système d’imagerie ainsi que d’une méthode permettant l’étude systématique des zones du larynx d’où émergent les pathologies. Cette thèse vise à développer un outil et une méthode menant à une compréhension plus approfondie de la maturation de cette microstructure La tomographie par cohérence optique (ou OCT, de l’anglais « Optical Coherence Tomography») est une technologie d’imagerie laser utilisée depuis quelques années en ophtalmologie,et récemment en cardiologie. Elle permet d’obtenir des coupes transversales (en profondeur) avec une résolution de l’ordre de quelques microns. Cette technique permettrait donc d’imager les structures anatomiques des cordes vocales pédiatriques, jusqu’ici inaccessibles étant donné la nature invasive de la biopsie. Ayant identifié l’OCT comme une modalité d’imagerie optique potentielle pour l’analyse des cordes vocales et des structures avoisinantes du larynx, l’objectif est de définir et de caractériser de façon optique la microstructure des cordes vocales.----------ABSTRACT The larynx is responsible for phonation, and its proper functioning is essential to breathing and swallowing. The development of this anatomical structure creates a series of physiological and morphological changes. In one’s lifetime, 1 to 9 % of the population will be affected by a laryngeal pathology, many of which specifically affecting the pediatric population. Children afflicted by laryngeal pathologies are particularly likely to develop additional medical, academic and psycho-social issues. Although several research studies have been conducted to understand the development of the vocal folds and laryngeal lesions, several questions remain unanswered. The development cycle of this anatomical microstructure is poorly understood, which is mainly due of current lack of noninvasive evaluation tools. This results in therapeutic or surgical treatments not being perfectly adapted to the pediatric clientele and some results are thus suboptimal. This issue illustrates the urgent need for non-invasive Imaging system dedicated to the observation of the vocal folds in the pediatric population. The design and validation of a clinical tool for intraoperative imaging of the vocal folds have many challenges. The main hypothesis of this thesis related to the noninvasive characterization of pediatric vocal folds. The innovation is largely attributed to the design and implementation of an imaging system and a method for the systematic study of the larynx, especially in areas from where diseases originate. This thesis aims at developing a tool and a method leading to a deeper understanding of the maturation of this icrostructure. Optical coherence tomography (OCT) is an optical imaging technology adopted in ophthalmology and recently in cardiology. It provides cross sectional (in depth) images with a resolution of a few microns. This technique allows imaging of anatomical structures of the pediatric vocal folds, without the negative consequences associated with biopsy. Having identified OCT as a potential optical imaging method for the analysis of the vocal folds and surrounding structures of the larynx, the objective is to define and characterize the microstructure of vocal folds. A validation is initially performed using an ex vivo study of different cadaveric specimens, animals and humans. These specimens were analyzed using OCT to identify elements associated with stages of maturation of the vocal folds. A systematic comparison of optical coherence tomography with histology was carried out to identify specific characteristics of each population. These encouraging results have enabled the development of an OCT system coupled to a handheld probe adapted for intraoperative imaging of the pediatric vocal fold

Colorectal Cancer

Colorectal cancer is one of the commonest cancers affecting individuals across the world. An improvement in survival has been attributed to multidisciplinary management, better diagnostics, improved surgical options for the primary and metastatic disease and advances in adjuvant therapy. In this book, international experts share their experience and knowledge on these different aspects in the management of colorectal cancer. An in depth analysis of screening for colorectal cancer, detailed evaluation of diagnostic modalities in staging colorectal cancer, recent advances in adjuvant therapy and principles and trends in the surgical management of colorectal cancer is provided. This will certainly prove to be an interesting and informative read for any clinician involved in the management of patients with colorectal cancer

Cancer Nanomedicine

This special issue brings together cutting edge research and insightful commentary on the currentl state of the Cancer Nanomedicine field