192 research outputs found
Progression of coronary artery disease in patients with end stage renal disease
Coronary artery disease is highly prevalent in the end stage renal disease population. For the general population, there are guidelines for managing coronary artery disease, however there are no clear consensus guidelines for patients with end stage renal disease. Renal transplantation is superior to dialysis in terms of both patient survival and quality of life. A significant proportion of potential renal transplant candidates are at high risk of coronary artery disease; they need to be scrutinized and aggressively treated for risk factors in order to maintain the graft and survival benefit that has been created by organ donation. In addition, clinicians also need to consider the risk of cardiovascular disease for dialysis patients not undergoing transplantation.
In terms of pathophysiological processes, there is growing evidence of a varied and significant effect of chemokines on cardiovascular disease; of particular interest are MCP-1, CCL15 and CCL18. There also exists established data demonstrating that the non-invasive investigation of measuring carotid intimal media thickness appears to be predictive of cardiovascular mortality in patients with end stage renal disease. Whilst coronary angiography is considered the gold standard investigation for diagnosing and treating coronary artery disease, it is an invasive procedure and therefore not without complication and is an expensive resource.
This work examines the effect of elective coronary angiography on glomerular filtration rate in patients with advanced chronic kidney disease and has demonstrated that coronary angiography performed in a timely fashion did not accelerate the decline in renal function. In addition this work examines the cardiac survival of potential transplant patients undergoing coronary angiography and intervention and has demonstrated that a thorough approach to diagnosing and intervening on angiographically significant coronary artery disease was associated with a low incidence of cardiac mortality and morbidity. Finally, this work has demonstrated higher chemokine levels in patients with progressive coronary artery disease compared to patients without progressive coronary artery disease, and shows that a significant proportion of patients with normal coronary angiograms at initial screening have no evidence of angiographically progressive disease over a 3 year period.
These results can be applied when performing cardiac risk stratification in an end stage renal failure population. In addition this work provides some evidence to support chemokines as appealing targets for novel therapies in the future
Automatic Spatiotemporal Analysis of Cardiac Image Series
RÉSUMÉ
Ă€ 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
Automatic Spatiotemporal Analysis of Cardiac Image Series
RÉSUMÉ
Ă€ 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
Biomedical Image Processing and Classification
Biomedical image processing is an interdisciplinary field involving a variety of disciplines, e.g., electronics, computer science, physics, mathematics, physiology, and medicine. Several imaging techniques have been developed, providing many approaches to the study of the human body. Biomedical image processing is finding an increasing number of important applications in, for example, the study of the internal structure or function of an organ and the diagnosis or treatment of a disease. If associated with classification methods, it can support the development of computer-aided diagnosis (CAD) systems, which could help medical doctors in refining their clinical picture
Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Transplantation in Advanced Neovascular Age-Related Macular Degeneration
Age-related macular degeneration (AMD) remains one of the leading causes of permanent vision impairment worldwide. It is a disorder of the central retina that manifests with irreversible cell loss, primarily affecting the retinal pigment epithelium (RPE) and subsequently the retina and choroid, leading to blindness through atrophy or neovascularization and exudation. Current treatments are only able to suppress the progression of the early and moderate neovascular AMD, mainly by controlling leakage and haemorrhage, while there is no established therapy for the atrophic type or the advanced neovascular type. RPE transplantation strategies have been attempted with promising outcomes; however, their operational complexity combined with the large patients’ volume has underlined the need for more accessible cell sources and a more feasible surgical paradigm. This thesis aims to examine the feasibility, safety and efficacy of transplantation of a human Embryonic Stem Cell (hESC)-derived RPE sheet in patients with severe neovascular (n) AMD. A fully differentiated hESC-RPE monolayer on a coated synthetic basement membrane (BM) has been bioengineered ex vivo and, using a purpose-designed surgical tool, has been implanted in the subretinal space of two patients with nAMD and acute vision decline. Systemic immunosuppression was administered during the peri- operative periods, while only local, intra-ocular steroids were given for the longer term. The patients were followed-up in a prospective study to assess the safety, and the structural and functional outcomes of this strategy for two years post-operatively. Both subjects demonstrated good safety outcome with no signs of local or distal tumorigenicity or uncontrolled proliferation from the implanted cells. Both showed reconstruction of the RPE-BM complex sufficient to support the retinal structure and the rescue and preservation of the photoreceptors, during the study period. Furthermore, both patients showed significant gain in their visual function, in terms of fixation, retinal light sensitivity, visual acuity and reading speed, maintained for two years. Most importantly, in both cases there was a clear co-localisation of the structural support, provided by the transplant, with the areas of functional improvement. The work in this thesis provides proof that the reconstruction of the RPE using hESC on synthetic BM can rescue and preserve the retinal structure and function over the long term, in severe neovascular AMD
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